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Sample records for vhl disease families

  1. Von Hippel-Lindau disease (vHL)

    DEFF Research Database (Denmark)

    Binderup, Marie Louise Mølgaard; Bisgaard, Søs Marie Luise; Harbud, Vibeke

    2013-01-01

    These clinical guidelines outline the criteria and recommendations for diagnostic and genetic work-up of families suspected of von Hippel-Lindau disease (vHL), as well as recommendations for prophylactic surveillance for vHL patients. The guideline has been composed by the Danish Coordination Group...... for vHL which is comprised of Danish doctors and specialists interested in vHL. The recommendations are based on longstanding clinical experience, Danish original research, and extensive review of the international literature. vHL is a hereditary multi-tumour disease caused by germline mutations...... cell carcinoma), the adrenal glands (pheochromocytoma), the pancreas, as well as in other organs. As many different organs can be affected, several medical specialities often take part in both diagnosis and treatment of manifestations. vHL should be suspected in individuals with a family history...

  2. Von Hippel-Lindau disease (vHL)

    DEFF Research Database (Denmark)

    Binderup, Marie Louise Mølgaard; Bisgaard, Søs Marie Luise; Harbud, Vibeke

    2013-01-01

    These clinical guidelines outline the criteria and recommendations for diagnostic and genetic work-up of families suspected of von Hippel-Lindau disease (vHL), as well as recommendations for prophylactic surveillance for vHL patients. The guideline has been composed by the Danish Coordination Group...... for vHL which is comprised of Danish doctors and specialists interested in vHL. The recommendations are based on longstanding clinical experience, Danish original research, and extensive review of the international literature. vHL is a hereditary multi-tumour disease caused by germline mutations...... of the disease, and/or in individuals with a vHL-associated manifestation; i.e. a hemangioblastoma in the retina or the central nervous system, familial or bilateral pheochromocytomas, familial, multiple, or early onset renal cell carcinomas, and in individuals with an endolymphatic sac tumour in the inner ear...

  3. VHL Manifestations

    Science.gov (United States)

    ... Us Website References Search Patients / What is VHL? / Manifestations People who have VHL disease may experience tumors ... very important to check regularly for possible VHL manifestations throughout a person’s lifetime. Most of these VHL ...

  4. [Prenatal exclusion of von Hippel-Lindau syndrome in a Mexican family carrying a novel VHL gene mutation].

    Science.gov (United States)

    Chacón-Camacho, Oscar Francisco; Benitez-Granados, Jesús; Zenteno, Juan Carlos

    2014-03-01

    von Hippel-Lindau (VHL) disease is an autosomal dominant and familial multisystemic syndrome that is caused by the inactivation of the VHL gene and it is characterized by diverse types of high vasculated tumours of benign and malign nature. In this work we describe the clinical characteristics and the prenatal diagnosis of a woman with VHL. Describe the first exclusion prenatal case by DNA analysis of the VHL syndrome in Latinoamerican population. Analysis of a Mexican familial pedigree showed 5 affected subjects with VHL on 3 consecutive generations. The proband was a 7 weeks pregnancy woman who was referred to our service for familiar and personal history of this disease. Maternal DNA was obtained from peripheral blood leukocytes, while fetal DNA was isolated from amniotic liquid cells on the 15th week. The maternal and fetal DNA analysis were done by the Polymerase Chain reaction (PCR) and the direct nucleotide sequence of the VHL gene. A novel mutation (c. 161_168 dup GGAGGCCG) in the VHL gene was identified in maternal DNA. Fetal DNA analysis indicated that the fetus inherited the wild-type allele from the mother. A novel VHL gene mutation was identified in a familial case of the disease, expanding the mutational spectrum in this disorder. The molecular prenatal testing in the affected woman at 15 weeks of gestation, demonstrated that the fetus did nor inherited the mutated allele. To the best of our knowledge, this is the first example of prenatal-molecular exclusion on VHL syndrome in Latinoamerica population.

  5. Von Hippel-Lindau disease (vHL)

    DEFF Research Database (Denmark)

    Binderup, Marie Louise Mølgaard; Bisgaard, Søs Marie Luise; Harbud, Vibeke

    2013-01-01

    cell carcinoma), the adrenal glands (pheochromocytoma), the pancreas, as well as in other organs. As many different organs can be affected, several medical specialities often take part in both diagnosis and treatment of manifestations. vHL should be suspected in individuals with a family history...

  6. Differences in regulation of tight junctions and cell morphology between VHL mutations from disease subtypes

    Directory of Open Access Journals (Sweden)

    Isanova Bella

    2009-07-01

    Full Text Available Abstract Background In von Hippel-Lindau (VHL disease, germline mutations in the VHL tumor suppressor gene cause clear cell renal carcinomas, hemangioblastomas, and pheochromocytomas. The VHL gene product is part of an ubiquitin E3 ligase complex and hypoxia-inducible factor alpha (HIF-α is a key substrate, although additional VHL functions have been described. A genotype-phenotype relationship exists in VHL disease such that specific VHL mutations elicit certain subsets of these tumors. Here, we examine VHL genotype-phenotype correlations at the cellular level, focusing on the regulation of tight junctions and cell morphology. Methods Wild-type and various mutant VHL proteins representing VHL disease subtypes were stably expressed in 3 VHL-negative renal carcinoma cell lines. Using these cell lines, the roles of various VHL-associated cellular functions in regulation of cell morphology were investigated. Results As a whole, type 1 mutants varied greatly from type 2 mutants, demonstrating high levels of HIF-2α, cyclin D1 and α5 integrin, lower p27 levels, and a spindly, fibroblastic cellular appearance. Type 2 mutations demonstrated an epithelial morphology similar to wild-type VHL in the majority of the renal cell lines used. Knockdown of p27 in cells with wild-type VHL led to perturbations of both epithelial morphology and ZO-1 localization to tight junctions. ZO-1 localization correlated well with VHL disease subtypes, with greater mislocalization observed for genotypes associated with a higher risk of renal carcinoma. HIF-2α knockdown in 786-O partially restored ZO-1 localization, but did not restore an epithelial morphology. Conclusion VHL has both HIF-α dependent and HIF-α independent functions in regulating tight junctions and cell morphology that likely impact the clinical phenotypes seen in VHL disease.

  7. Prevalence, birth incidence, and penetrance of von Hippel-Lindau disease (vHL) in Denmark

    DEFF Research Database (Denmark)

    Binderup, Marie Louise Mølgaard; Galanakis, Michael Carter Bisgaard; Budtz-Jørgensen, Esben

    2017-01-01

    . We further used national health registers to identify individuals who fulfilled the clinical diagnostic vHL criteria based on their registered diagnostic codes, but had not been diagnosed with vHL. We also assessed the medical histories of first-degree relatives to identify familial cases. This study...

  8. Surveillance in von Hippel-Lindau disease (vHL)

    DEFF Research Database (Denmark)

    Poulsen, Marie Louise Mølgaard; Budtz-Jørgensen, E; Bisgaard, M L

    2010-01-01

    54 living vHL-mutation carriers, risks of intercurrent manifestations in-between surveillance examinations were determined and clinical consequences of surveillance findings evaluated. Current recommendations of annual ophthalmic and abdominal examinations corresponded to acceptably low intercurrent...... for the patient. Also, pre-symptomatic surveillance increased cumulative incidence of clinical vHL diagnosis from 46% to 72% and from 89% to 94% by age 30 and 50 years, respectively. The present results promote optimization of surveillance, expectantly improving clinical vHL outcomes....

  9. Von Hippel-Lindau disease (vHL)

    DEFF Research Database (Denmark)

    Binderup, Marie Louise Mølgaard; Bisgaard, Søs Marie Luise; Harbud, Vibeke

    2013-01-01

    in the VHL gene. vHL is inherited in an autosomal dominant manner. Predisposed individuals are advised to undergo prophylactic examinations, as they are at lifelong risk of developing multiple cysts and tumours, especially in the cerebellum, the spinal cord, the retina (hemangioblastomas), the kidneys (renal...... are recommended to start in infancy with annual paediatric examinations and ophthalmoscopy until the age of five years. From five to 14 years, annual plasma-metanephrine and plasma-normetanephrine tests, as well as annual hearing examinations are added. Also, an MRI (Magnetic Resonance Imaging) examination....../MRI of the abdomen, e) annual plasma-metanephrine, plasma-normetanephrine, and plasma-chromogranin A tests, and f) annual hearing examination at a department of audiology. It is advised that one doctor takes on the responsibility of coordination of and referral to the many examinations, and the communication...

  10. Hypoxia-inducible factor-2α stabilizes the von Hippel-Lindau (VHL) disease suppressor, Myb-related protein 2.

    Science.gov (United States)

    Okumura, Fumihiko; Joo-Okumura, Akiko; Nakatsukasa, Kunio; Kamura, Takumi

    2017-01-01

    Ubiquitin ligase von Hippel-Lindau tumor suppressor (pVHL) negatively regulates protein levels of hypoxia-inducible factor-α (HIF-α). Loss of pVHL causes HIF-α accumulation, which contributes to the pathogenesis of von Hippel-Lindau (VHL) disease. In contrast, v-Myb avian myeloblastosis viral oncogene homolog-like 2 (MYBL2; B-Myb), a transcription factor, prevents VHL pathogenesis by regulating gene expression of HIF-independent pathways. Both HIF-α and B-Myb are targets of pVHL-mediated polyubiquitination and proteasomal degradation. Here, we show that knockdown of HIF-2α induces downregulation of B-Myb in 786-O cells, which are deficient in pVHL, and this downregulation is prevented by proteasome inhibition. In the presence of pVHL and under hypoxia-like conditions, B-Myb and HIF-2α are both upregulated, and the upregulation of B-Myb requires expression of HIF-2α. We also show that HIF-2α and B-Myb interact in the nucleus, and this interaction is mediated by the central region of HIF-2α and the C-terminal region of B-Myb. These data indicate that oncogenic HIF-2α stabilizes B-Myb to suppress VHL pathogenesis.

  11. Rare presentation of familial paraganglioma without evidence of mutation in the SDH, RET and VHL genes: towards further genetic heterogeneity.

    Science.gov (United States)

    Persu, Alexandre; Amyere, Mustapha; Gutierrez-Roelens, Ilse; Rustin, Pierre; Sempoux, Christine; Lecouvet, Frédéric E; Van Beers, Bernard E; Horsmans, Yves; De Plaen, Jean-François; MarcHamoir; Vikkula, Miikka

    2009-01-01

    Mutations in genes encoding succinate dehydrogenase and its anchoring subunits (SDH genes) are at the origin of hereditary head and neck paraganglioma (PGL) and a subset of apparently sporadic pheochromocytoma. We describe a family including three patients harbouring bilateral head and neck PGL diagnosed before 25 years of age. Multiple hypervascular hepatic lesions were subsequently discovered in two of them. In both, liver biopsy confirmed the diagnosis of PGL. In addition, in one patient, MRI disclosed multiple target-like lesions of the spine, highly suggestive of metastatic PGL. Family history was compatible with autosomal dominant inheritance with possible maternal imprinting. Combined single-strand conformation polymorphism and heteroduplex analysis followed by sequencing did not show any mutation of the coding parts of SDHB, SDHC, SDHD, RET or VHL genes. Screening of copy number alterations and loss of heterozygosity in the three affected family members showed no deletion or amplification of the SDH, RET and VHL genes. Furthermore, succinate dehydrogenase activity measured in a liver PGL sample was not significantly decreased in the affected patient as compared with controls, underscoring the exclusion of the SDH genes. To our knowledge, this is the first reported family of hereditary head and neck PGL with metastatic dissemination in the liver and the spine. A large body of evidence supports the absence of mutations in SDH, RET and VHL genes, which suggests the existence of a yet unknown gene at the origin of this particular form of familial PGL.

  12. Identification of 3 novel VHL germ-line mutations in Danish VHL patients

    DEFF Research Database (Denmark)

    Dandanell, Mette; Friis-Hansen, Lennart Jan; Sunde, Lone

    2012-01-01

    von Hippel-Lindau (VHL) disease is a hereditary cancer syndrome in which the patients develop retinal and central nervous system hemangioblastomas, pheochromocytomas and clear-cell renal tumors. The autosomal dominant disease is caused by mutations in the VHL gene.......von Hippel-Lindau (VHL) disease is a hereditary cancer syndrome in which the patients develop retinal and central nervous system hemangioblastomas, pheochromocytomas and clear-cell renal tumors. The autosomal dominant disease is caused by mutations in the VHL gene....

  13. Parallel Regulation of von Hippel-Lindau Disease by pVHL-Mediated Degradation of B-Myb and Hypoxia-Inducible Factor α

    Science.gov (United States)

    Uematsu, Keiji; Byrne, Stuart D.; Hirano, Mie; Joo-Okumura, Akiko; Nishikimi, Akihiko; Shuin, Taro; Fukui, Yoshinori; Nakatsukasa, Kunio

    2016-01-01

    pVHL, the protein product of the von Hippel-Lindau (VHL) tumor suppressor gene, is a ubiquitin ligase that targets hypoxia-inducible factor α (HIF-α) for proteasomal degradation. Although HIF-α activation is necessary for VHL disease pathogenesis, constitutive activation of HIF-α alone did not induce renal clear cell carcinomas and pheochromocytomas in mice, suggesting the involvement of an HIF-α-independent pathway in VHL pathogenesis. Here, we show that the transcription factor B-Myb is a pVHL substrate that is degraded via the ubiquitin-proteasome pathway and that vascular endothelial growth factor (VEGF)- and/or platelet-derived growth factor (PDGF)-dependent tyrosine 15 phosphorylation of B-Myb prevents its degradation. Mice injected with B-Myb knockdown 786-O cells developed dramatically larger tumors than those bearing control cell tumors. Microarray screening of B-Myb-regulated genes showed that the expression of HIF-α-dependent genes was not affected by B-Myb knockdown, indicating that B-Myb prevents HIF-α-dependent tumorigenesis through an HIF-α-independent pathway. These data indicate that the regulation of B-Myb by pVHL plays a critical role in VHL disease. PMID:27090638

  14. A patient with bilateral pheochromocytoma as part of a Von Hippel-Lindau (VHL syndrome type 2C

    Directory of Open Access Journals (Sweden)

    Rinkes Inne

    2007-10-01

    Full Text Available Abstract Background Von Hippel-Lindau (VHL disease is an autosomal dominant inherited disease. It is relatively recent that type 2C was identified as a separate group solely presenting with pheochromocytomas. As an illustration, an interesting case is presented of a pregnant woman with refractory hypertension. It proved to be the first manifestation of bilateral pheochromocytomas. The family history may indicate the diagnosis, but only identification of a germ line mutation in the DNA of a patient will confirm carriership. Case presentation A 27 year pregnant patient with intra uterine growth retardation presented with hypertension and pre-eclampsia. Magnetic resonance imaging revealed bilateral adrenal pheochromocytoma. She underwent laparoscopic adrenelectomy and a missense mutation (Gly93Ser in exon 1 of the VHL gene on chromosome 3 (p25 – p26 was shown in the patient, her father and her daughter confirming the diagnosis of VHL. Conclusion In almost all VHL families molecular genetic analysis of DNA will demonstrate an inherited mutation. Because of the involvement in several organs, periodic clinical evaluation should take place in a well coordinated, multidisciplinary setting. VHL disease can be classified into several subtypes. VHL type 2C patients present with pheochromocytomas without evidence of haemangioblastomas in the central nervous system and/or retina and a low risk of renal cell carcinoma. Therefore, in such families, periodic clinical screening can be focussed on pheochromocytomas.

  15. Playing Tag with HIF: The VHL Story

    Directory of Open Access Journals (Sweden)

    Sherri K. Leung

    2002-01-01

    Full Text Available Inactivation of the von Hippel-Lindau (VHL tumour suppressor gene product pVHL is the cause of inherited VHL disease and is associated with sporadic kidney cancer. pVHL is found in a multiprotein complex with elongins B/C, Cul2, and Rbx1 forming an E3 ubiquitin ligase complex called VEC. This modular enzyme targets the α subunits of hypoxia-inducible factor (HIF for ubiquitin-mediated destruction. Consequently, tumour cells lacking functional pVHL overproduce the products of HIF-target genes such as vascular endothelial growth factor (VEGF, which promotes angiogenesis. This likely accounts for the hypervascular nature of VHL-associated neoplasms. Although pVHL has been linked to the cell-cycle, differentiation, and the regulation of extracellular matrix assembly, microenvironment pH, and tissue invasiveness, this review will focus on the recent insights into the molecular mechanisms governing the E3 ubiquitin ligase function of VEC.

  16. Novel homozygous VHL mutation in exon 2 is associated with congenital polycythemia but not with cancer.

    Science.gov (United States)

    Lanikova, Lucie; Lorenzo, Felipe; Yang, Chunzhang; Vankayalapati, Hari; Drachtman, Richard; Divoky, Vladimir; Prchal, Josef T

    2013-05-09

    Germline von Hippel-Lindau (VHL) gene mutations underlie dominantly inherited familial VHL tumor syndrome comprising a predisposition for renal cell carcinoma, pheochromocytoma/paraganglioma, cerebral hemangioblastoma, and endolymphatic sac tumors. However, recessively inherited congenital polycythemia, exemplified by Chuvash polycythemia, has been associated with 2 separate 3' VHL gene mutations in exon 3. It was proposed that different positions of loss-of-function VHL mutations are associated with VHL syndrome cancer predisposition and only C-terminal domain-encoding VHL mutations would cause polycythemia. However, now we describe a new homozygous VHL exon 2 mutation of the VHL gene:(c.413C>T):P138L, which is associated in the affected homozygote with congenital polycythemia but not in her, or her-heterozygous relatives, with cancer or other VHL syndrome tumors. We show that VHL(P138L) has perturbed interaction with hypoxia-inducible transcription factor (HIF)1α. Further, VHL(P138L) protein has decreased stability in vitro. Similarly to what was reported in Chuvash polycythemia and some other instances of HIFs upregulation, VHL(P138L) erythroid progenitors are hypersensitive to erythropoietin. Interestingly, the level of RUNX1/AML1 and NF-E2 transcripts that are specifically upregulated in acquired polycythemia vera were also upregulated in VHL(P138L) granulocytes.

  17. Potential value of EUS in pancreatic surveillance of VHL patients

    NARCIS (Netherlands)

    van Asselt, Sophie Josephien; Brouwers, Adrienne H; van Dullemen, Hendrik M; van der Jagt, Eric J; Bongaerts, Alfons H; Koopmans, Klaas P; Kema, Ido; Zonnenberg, Bernard A; Timmers, Henri Jlm; de Herder, Wouter; Sluiter, Wim; de Vries, Elisabeth G E; Links, T P

    Background: Patients with von Hippel-Lindau (VHL) disease are prone to develop pancreatic neuroendocrine tumors (pNETs). However, the best imaging technique for early detection of pNETs in VHL is currently unknown. In a head-to-head comparison, we evaluated endoscopic ultrasound (EUS) and

  18. Survival and causes of death in patients with von Hippel-Lindau disease

    DEFF Research Database (Denmark)

    Binderup, Marie Louise Mølgaard; Jensen, Annette Møller; Budtz-Jørgensen, Esben

    2017-01-01

    . Surveillance is especially beneficial for truncating mutation carriers, who have the greatest RCC and central nervous system (CNS) hemangioblastoma risk.  Conclusions: vHL survival has improved over time and has become closer to that of siblings without vHL and the general population. Even though the risk of v......Background: Historically, the survival of patients with von Hippel-Lindau disease (vHL) has been poorer than that of the general population. We aimed to determine whether the survival of VHL mutation carriers and their risk of vHL-related death has changed over time and how it has been affected...... by sex, genotype and surveillance attendance.  Methods: In a retrospective cohort study, we included all known Danish vHL families with a VHL mutation. We assessed the survival and causes of death for 143 VHL mutation carriers using Cox regression models and compared vHL survival with that of 137...

  19. Clinical and molecular features of familial and sporadic cases of von Hippel-Lindau disease from Mexico.

    Science.gov (United States)

    Chacon-Camacho, Oscar F; Rodriguez-Dennen, Fernando; Camacho-Molina, Alejandra; Rasmussen, Astrid; Alonso-Vilatela, Elisa; Zenteno, Juan C

    2010-04-01

    von Hippel-Lindau disease (VHL) is an uncommon autosomal dominant condition predisposing to the development of tumours in a variety of body organs and caused by germline mutations in VHL, a tumour suppressor gene located on 3p. Up to 60% of VHL patients show ocular involvement with retinal hemangioblastoma being the most common observed lesion. In this study, we describe the clinical and genetic characteristics of two familial and one apparently non-familial case of VHL ascertained at our institution. Clinical evaluation included ophthalmologic examination and imaging exams for tumours identification; molecular analysis consisted of PCR amplification of the complete VHL gene coding sequence (three exons) and automated nucleotide sequencing. A total of eight affected subjects were demonstrated to carry a causative mutation in VHL. Affected subjects from family #1 had a c.245G > C change, predicting a p.R82P substitution, affected individuals from family #2 were shown to have a c.266T > C change, leading to a p.L89P missense substitution, whereas the apparently non-familial case had a c.298-299insA mutation. One subject from family #2 was a non-penetrant carrier. No ocular anomalies were found in two adult affected subjects carrying the p.L89P mutation. Considerable interfamilial and intrafamilial clinical variability as well as one instance of non penetrance were recorded in these VHL disease cases. Three different mutations were demonstrated, including the c.298-299insA one base insertion, which has been previously described in two unrelated families from our country. Although additional studies are needed, our data suggest that this insertion could be a 'founder' mutation.

  20. Dicty_cDB: VHL444 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available library) VHL444 (Link to dictyBase) - - - Contig-U15033-1 VHL444P (Link to Original site) VHL444F 595 VHL444Z...VHL444Z 674 VHL444P 1249 - - Show VHL444 Library VH (Link to library) Clone ID VHL444 (Link to dictyBase)...tsukuba.ac.jp/CSM/VH/VHL4-B/VHL444Q.Seq.d/ Representative seq. ID VHL444P (Link to Original site) Representative...Representative DNA sequence >VHL444 (VHL444Q) /CSM/VH/VHL4-B/VHL444Q.Seq.d/ CACTGTTGGCCTACTGGTATAGTTACA...significant alignments: (bits) Value VHL444 (VHL444Q) /CSM/VH/VHL4-B/VHL444Q.Seq.d/ 2420 0.0 VHN389 (VHN389Q)

  1. Von Hippel-Lindau (VHL inactivation in sporadic clear cell renal cancer: associations with germline VHL polymorphisms and etiologic risk factors.

    Directory of Open Access Journals (Sweden)

    Lee E Moore

    2011-10-01

    Full Text Available Renal tumor heterogeneity studies have utilized the von Hippel-Lindau VHL gene to classify disease into molecularly defined subtypes to examine associations with etiologic risk factors and prognosis. The aim of this study was to provide a comprehensive analysis of VHL inactivation in clear cell renal tumors (ccRCC and to evaluate relationships between VHL inactivation subgroups with renal cancer risk factors and VHL germline single nucleotide polymorphisms (SNPs. VHL genetic and epigenetic inactivation was examined among 507 sporadic RCC/470 ccRCC cases using endonuclease scanning and using bisulfite treatment and Sanger sequencing across 11 CpG sites within the VHL promoter. Case-only multivariate analyses were conducted to identify associations between alteration subtypes and risk factors. VHL inactivation, either through sequence alterations or promoter methylation in tumor DNA, was observed among 86.6% of ccRCC cases. Germline VHL SNPs and a haplotype were associated with promoter hypermethylation in tumor tissue (OR = 6.10; 95% CI: 2.28-16.35, p = 3.76E-4, p-global = 8E-5. Risk of having genetic VHL inactivation was inversely associated with smoking due to a higher proportion of wild-type ccRCC tumors [former: OR = 0.70 (0.20-1.31 and current: OR = 0.56 (0.32-0.99; P-trend = 0.04]. Alteration prevalence did not differ by histopathologic characteristics or occupational exposure to trichloroethylene. ccRCC cases with particular VHL germline polymorphisms were more likely to have VHL inactivation through promoter hypermethylation than through sequence alterations in tumor DNA, suggesting that the presence of these SNPs may represent an example of facilitated epigenetic variation (an inherited propensity towards epigenetic variation in renal tissue. A proportion of tumors from current smokers lacked VHL alterations and may represent a biologically distinct clinical entity from inactivated cases.

  2. Uptake of genetic testing and long-term tumor surveillance in von Hippel-Lindau disease

    OpenAIRE

    Chávez Mireya; Rodríguez Yaneth; Sosa Ana-Luisa; Yescas Petra; Familiar Itziar; De Biase Irene; Ochoa Adriana; Alonso Elisa; Rasmussen Astrid; López-López Marisol; Bidichandani Sanjay I

    2010-01-01

    Abstract Background von Hippel-Lindau (VHL) disease is a hereditary cancer syndrome caused by germline mutations in the VHL gene. Patients have significant morbidity and mortality secondary to vascular tumors. Disease management is centered on tumor surveillance that allows early detection and treatment. Presymptomatic genetic testing is therefore recommended, including in at-risk children. Methods We tested 17 families (n = 109 individuals) for VHL mutations including 43 children under the a...

  3. VHL type 2B mutations retain VBC complex form and function.

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    Kathryn E Hacker

    Full Text Available von Hippel-Lindau disease is characterized by a spectrum of hypervascular tumors, including renal cell carcinoma, hemangioblastoma, and pheochromocytoma, which occur with VHL genotype-specific differences in penetrance. VHL loss causes a failure to regulate the hypoxia inducible factors (HIF-1alpha and HIF-2alpha, resulting in accumulation of both factors to high levels. Although HIF dysregulation is critical to VHL disease-associated renal tumorigenesis, increasing evidence points toward gradations of HIF dysregulation contributing to the degree of predisposition to renal cell carcinoma and other manifestations of the disease.This investigation examined the ability of disease-specific VHL missense mutations to support the assembly of the VBC complex and to promote the ubiquitylation of HIF. Our interaction analysis supported previous observations that VHL Type 2B mutations disrupt the interaction between pVHL and Elongin C but maintain partial regulation of HIF. We additionally demonstrated that Type 2B mutant pVHL forms a remnant VBC complex containing the active members ROC1 and Cullin-2 which retains the ability to ubiquitylate HIF-1alpha.Our results suggest that subtypes of VHL mutations support an intermediate level of HIF regulation via a remnant VBC complex. These findings provide a mechanism for the graded HIF dysregulation and genetic predisposition for cancer development in VHL disease.

  4. Difference in CXCR4 expression between sporadic and VHL-related hemangioblastoma

    NARCIS (Netherlands)

    Kruizinga, Roeliene C; van Marion, Denise M S; den Dunnen, Wilfred F A; de Groot, Jan C; Hoving, Eelco W; Oosting, Sjoukje F; Timmer-Bosscha, Hetty; Derks, Rosalie P H; Cornelissen, Chantal; van der Luijt, Rob B; Links, Thera P; de Vries, Elisabeth G E; Walenkamp, Annemiek M E

    2016-01-01

    Central nervous system hemangioblastomas occur sporadically and in patients with von Hippel-Lindau (VHL) disease due to a VHL germline mutation. This mutation leads to enhanced transcription of chemokine receptor 4 (CXCR4), its ligand (CXCL12) and vascular endothelial growth factor A (VEGFA). We

  5. Psychosocial impact of Von Hippel-Lindau disease : levels and sources of distress

    NARCIS (Netherlands)

    Lammens, C. R. M.; Bleiker, E. M. A.; Verhoef, S.; Hes, F. J.; Ausems, M. G. E. M.; Majoor-Krakauer, D.; Sijmons, R. H.; van der Luijt, R. B.; van den Ouweland, A. M. W.; Van Os, Tam; Hoogerbrugge, N.; Garcia, E. B. Gomez; Dommering, C. J.; Gundy, C. M.; Aaronson, N. K.

    Von Hippel-Lindau disease (VHL) is a hereditary tumor susceptibility syndrome, characterized by an increased risk of developing multiple benign and malignant tumors at various sites and ages with limited preventive options. This study evaluates the prevalence of distress among VHL family members and

  6. The phenotype of polycythemia due to Croatian homozygous VHL (571C>G:H191D) mutation is different from that of Chuvash polycythemia (VHL 598C>T:R200W).

    Science.gov (United States)

    Tomasic, Nikica Ljubas; Piterkova, Lucie; Huff, Chad; Bilic, Ernest; Yoon, Donghoon; Miasnikova, Galina Y; Sergueeva, Adelina I; Niu, Xiaomei; Nekhai, Sergei; Gordeuk, Victor; Prchal, Josef T

    2013-04-01

    Mutations of VHL (a negative regulator of hypoxia-inducible factors) have position-dependent distinct cancer phenotypes. Only two known inherited homozygous VHL mutations exist and they cause polycythemia: Chuvash R200W and Croatian H191D. We report a second polycythemic Croatian H191D homozygote distantly related to the first propositus. Three generations of both families were genotyped for analysis of shared ancestry. Biochemical and molecular tests were performed to better define their phenotypes, with an emphasis on a comparison with Chuvash polycythemia. The VHL H191D mutation did not segregate in the family defined by the known common ancestors of the two subjects, suggesting a high prevalence in Croatians, but haplotype analysis indicated an undocumented common ancestor ∼six generations ago as the founder of this mutation. We show that erythropoietin levels in homozygous VHL H191D individuals are higher than in VHL R200W patients of similar ages, and their native erythroid progenitors, unlike Chuvash R200W, are not hypersensitive to erythropoietin. This observation contrasts with a report suggesting that polycythemia in VHL R200W and H191D homozygotes is due to the loss of JAK2 regulation from VHL R200W and H191D binding to SOCS1. In conclusion, our studies further define the hematologic phenotype of VHL H191D and provide additional evidence for phenotypic heterogeneity associated with the positional effects of VHL mutations.

  7. Endemic polycythemia in Russia: mutation in the VHL gene.

    Science.gov (United States)

    Ang, Sonny O; Chen, Hua; Gordeuk, Victor R; Sergueeva, Adelina I; Polyakova, Lydia A; Miasnikova, Galina Y; Kralovics, Robert; Stockton, David W; Prchal, Josef T

    2002-01-01

    Chuvash polycythemia (CP) is an autosomal recessive condition that is endemic in the Russian mid-Volga River region of Chuvashia. We previously found that CP patients may have increased serum erythropoietin (EPO) levels, ruled out linkage to both the EPO and EPO receptor (EPOR) gene loci, and hypothesized that the defect may lie in the oxygen homeostasis pathway. We now report a study of five multiplex Chuvash families which confirms that CP is associated with significant elevations of serum EPO levels and rules out a location for the CP gene on chromosome 11 as had been reported by other investigators or a mutation of the HIF-1 alpha gene. Using a genome-wide screen, we localized a region on chromosome 3 with a LOD score >2. After sequencing three candidate genes, we identified a C to T transition at nucleotide 598 (an R200W mutation) in the von Hippel-Lindau (VHL) gene. The VHL protein (pVHL) downregulates the alpha subunit of hypoxia-inducible factor 1 (HIF-1 alpha), the main regulator of hypoxia adaptation, by targeting the protein for degradation. In the simplest scenario, disruption of pVHL function causes a failure to degrade HIF-1 alpha resulting in accumulation of HIF-1 alpha, upregulation of downstream target genes such as EPO, and the clinical manifestation of polycythemia. These findings strongly suggest that CP is a congenital disorder of oxygen homeostasis.

  8. Preimplantation genetic diagnosis of Von Hippel-Lindau disease cancer syndrome by combined mutation and segregation analysis

    Directory of Open Access Journals (Sweden)

    Denilce R. Sumita

    2007-03-01

    Full Text Available Von Hippel-Lindau (VHL disease is an autosomal dominant cancer syndrome, associated with the development of tumors and cysts in multiple organ systems, whose expression and age of onset are highly variable. The VHL disease tumor suppressor gene (VHL maps to 3p25-p26 and mutations ranging from a single base change to large deletions have been detected in patients with VHL disease. We developed a single cell PCR protocol for preimplantation genetic diagnosis (PGD of VHL disease to select unaffected embryos on the basis of the detection of the specific mutation and segregation analysis of polymorphic linked markers. Multiplex-nested PCR using single buccal cells of an affected individual were performed in order to test the accuracy and reliability of this single-cell protocol. For each locus tested, amplification efficiency was 83% to 87% and allelic drop-out rates ranged from 12% to 8%. Three VHL disease PGD cycles were performed on cells from a couple with paternal transmission of a 436delC mutation in exon 2 of the VHL gene, leading to the identification of three unaffected embryos. Independent of the mutation present, this general PGD protocol for the diagnosis of VHL disease can be used in families informative for either the D3S1038 or D3S1317 microsatellite markers.

  9. Through the looking glass: an exploratory study of the lived experiences and unmet needs of families affected by Von Hippel-Lindau disease.

    Science.gov (United States)

    Kasparian, Nadine A; Rutstein, Alison; Sansom-Daly, Ursula M; Mireskandari, Shab; Tyler, Janet; Duffy, Jessica; Tucker, Katherine M

    2015-01-01

    Despite well-established protocols for the medical management of Von Hippel-Lindau disease (VHL), families affected by this rare tumour syndrome continue to face numerous psychological, social, and practical challenges. To our knowledge, this is one of the first qualitative studies to explore the psychosocial difficulties experienced by families affected by VHL. A semi-structured interview was developed to explore patients' and carers' experiences of VHL along several life domains, including: self-identity and self-esteem, interpersonal relationships, education and career opportunities, family communication, physical health and emotional well-being, and supportive care needs. Quantitative measures were also used to examine the prevalence of anxiety, depression, and disease-specific distress in this sample. Participants were recruited via the Hereditary Cancer Clinic at the Prince of Wales Hospital in Sydney, Australia. A total of 23 individual telephone interviews were conducted (15 patients, 8 carers), yielding a response rate of 75%. A diverse range of experiences were reported, including: sustained uncertainty about future tumour development, frustration regarding the need for lifelong medical screening, strained family relationships, difficulties communicating with others about VHL, perceived social isolation and limited career opportunities, financial and care-giving burdens, complex decisions in relation to childbearing, and difficulties accessing expert medical and psychosocial care. Participants also provided examples of psychological growth and resilience, and voiced support for continued efforts to improve supportive care services. More sophisticated systems for connecting VHL patients and their families with holistic, empathic, and person-centred medical and psychosocial care are urgently needed.

  10. Dicty_cDB: VHL663 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available VH (Link to library) VHL663 (Link to dictyBase) - - - Contig-U15767-1 VHL663P (Link... to Original site) VHL663F 574 VHL663Z 702 VHL663P 1256 - - Show VHL663 Library VH (Link to library) Clone ID VHL663 (Link to dict...yBase) Atlas ID - NBRP ID - dictyBase ID - Link to Contig Contig-U15767-1 Original site URL http://dict...WPDGFKYFFVDNQAGDSESAKSGKNLPIQRDIELNWNGEAYEYSNSNYFPINGQG FNDVSYPV--- ---SYATGKCEPDSSLCNDNNICTIDICVHEGILDGLPQG...ik rqelvgqmvlsifl*itklviqnlpnlvkifqfkeiss*igmekhmniviqitsqltdkv smm*aiq--- ---SYATGKCEPDSSLCNDNNICTIDICVHEGI

  11. Dicty_cDB: VHL434 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available VH (Link to library) VHL434 (Link to dictyBase) - - - Contig-U16336-1 VHL434P (Link... to Original site) VHL434F 546 VHL434Z 778 VHL434P 1304 - - Show VHL434 Library VH (Link to library) Clone ID VHL434 (Link to dict...yBase) Atlas ID - NBRP ID - dictyBase ID - Link to Contig Contig-U16336-1 Original site URL http://dict...EVMSCNKFSSKRIGYLAASQSFNEGTDVIVLATHQIRKDFLS SNQSEAYLALNCLSNICTTDLARELANDILTLLSTQKTHILKRAITVLYKIFLRYPES-- - --...GFDISWASFKIVEVMSCNKFSSKRIGYLAASQSFNEGTDVIVLATHQIRKDFLS SNQSEAYLALNCLSNICTTDLARELANDILTLLSTQKTHILKRAITVLYKIFL

  12. [Familial hypoalphalipoproteinemia. Vergani's disease].

    Science.gov (United States)

    Dioguardi, N

    1983-11-16

    Deficiencies of lipoproteins occur as genetic disorders or may be presenting features of underlying disease. Familial high density lipoprotein (HDL), or alpha-lipoprotein, deficiency so far described includes Tangier disease, Lecithin: cholesterol acyltransferase (LCAT) deficiency, A-I Variants syndrome and Fish-eye disease. In 1981 Vergani described a familial aggregation of low HDL-cholesterol (less than 33 mg/dl) and Apo A (about 50% of normal levels) in the presence of normal VLDL and LDL-cholesterol. LCAT and lipoprotein lipase activities, both extrahepatic and hepatic, were normal. By zonal ultracentrifugation HDL2 subclass was found to be reduced. HDL apoproteins, examined by isoelectric focusing in polyacrylamide gel, were qualitatively normal. No disorders to which low levels of HDL might be secondary (e.g., overweight, cigarette smoking, nephropathy, liver disease) are present in the affected members. The underlying biochemical defect is unknown but probably involves altered synthesis or catabolism of HDL. Familial hypo-alpha-lipoproteinemia is accompanied by a high prevalence of premature myocardial infarction and sudden death. The genetic analysis of the disorder is consistent with autosomal inheritance. The criteria for the definition of familial hypo-alpha-lipoproteinemia are, therefore, as follows: 1) low HDL-cholesterol level in the presence of normal VLDL and LDL-cholesterol levels; 2) absence of diseases or factors to which hypo-alpha-lipoproteinemia might be secondary; 3) presence of a similar lipoprotein pattern in a first degree relative.

  13. Pregnancy-related hemangioblastoma progression and complications in von Hippel-Lindau disease.

    NARCIS (Netherlands)

    Frantzen, C.; Kruizinga, R.C.; Asselt, S.J. van; Zonnenberg, B.A.; Lenders, J.W.M.; Herder, W.W. de; Walenkamp, A.M.; Giles, R.H.; Hes, F.J.; Sluiter, W.J.; Pampus, M.G. van; Links, T.P.

    2012-01-01

    OBJECTIVE: We studied the reciprocal effect of pregnancy and von Hippel-Lindau (VHL) disease by analyzing the influence of pregnancy on VHL disease-related lesions and VHL disease on pregnancy outcome. METHODS: Medical charts and imaging reports from the VHL disease expertise centers in the

  14. Identification of the Lipodepsipeptide MDN-0066, a Novel Inhibitor of VHL/HIF Pathway Produced by a New Pseudomonas Species.

    Directory of Open Access Journals (Sweden)

    Bastien Cautain

    Full Text Available Throughout recent history, metabolites of microbial origin have had an extraordinary impact on the welfare of humanity. In fact, natural products have largely been--and still are--considered an exceedingly valuable platform for the discovery of new drugs against diverse pathologies. Such value is partly due to their higher complexity and chemical diversity as compared to those of synthetic and combinatorial compounds. Mutations in the Von Hippel-Lindau (vhl gene are responsible for VHL disease, congenital polycythemia, and are found in many sporadic tumor types. The primary cause of morbidity and mortality for these patients arises from progression of Renal Cell Carcinoma (RCC or end-stage renal disease. Inactivation of the Von Hippel-Lindau (vhl tumor suppressor gene arises in the majority of Renal Cell Carcinoma (RCC as well as in other types of cancer and is associated with a high degree of vascularization and poor prognosis. Loss of pVHL function thus represents a pathognomonic molecular defect for therapeutic exploitation. In this study, renal carcinoma cell lines with naturally occurring vhl mutations (RCC4 VA and their genetically matched wild-type vhl (RCC4 VHL counterparts were seeded onto 96-well plates and treated with a collection of 1,040 organic extracts obtained from 130 bacterial strains belonging to at least 25 genera of the phyla Actinobacteria, Firmicutes, Proteobacteria and Bacteroidetes. This strategy allowed us to identify several extracts obtained from bacterial strain F-278,770T, the type strain of the recently proposed new species Pseudomonas granadensis, showing biological activities not associated with previously known bioactive metabolites. The fractionation and structural elucidation of one of these extracts led to the discovery of a new lipodepsipeptide (MDN-0066 with specific toxicity in pVHL deficient cells that is not detectable in cells with pVHL expression rescue. This specific toxicity is associated with

  15. Identification of the Lipodepsipeptide MDN-0066, a Novel Inhibitor of VHL/HIF Pathway Produced by a New Pseudomonas Species.

    Science.gov (United States)

    Cautain, Bastien; de Pedro, Nuria; Schulz, Christian; Pascual, Javier; Sousa, Thiciana da S; Martin, Jesús; Pérez-Victoria, Ignacio; Asensio, Francisco; González, Ignacio; Bills, Gerald F; Reyes, Fernando; Genilloud, Olga; Vicente, Francisca

    2015-01-01

    Throughout recent history, metabolites of microbial origin have had an extraordinary impact on the welfare of humanity. In fact, natural products have largely been--and still are--considered an exceedingly valuable platform for the discovery of new drugs against diverse pathologies. Such value is partly due to their higher complexity and chemical diversity as compared to those of synthetic and combinatorial compounds. Mutations in the Von Hippel-Lindau (vhl) gene are responsible for VHL disease, congenital polycythemia, and are found in many sporadic tumor types. The primary cause of morbidity and mortality for these patients arises from progression of Renal Cell Carcinoma (RCC) or end-stage renal disease. Inactivation of the Von Hippel-Lindau (vhl) tumor suppressor gene arises in the majority of Renal Cell Carcinoma (RCC) as well as in other types of cancer and is associated with a high degree of vascularization and poor prognosis. Loss of pVHL function thus represents a pathognomonic molecular defect for therapeutic exploitation. In this study, renal carcinoma cell lines with naturally occurring vhl mutations (RCC4 VA) and their genetically matched wild-type vhl (RCC4 VHL) counterparts were seeded onto 96-well plates and treated with a collection of 1,040 organic extracts obtained from 130 bacterial strains belonging to at least 25 genera of the phyla Actinobacteria, Firmicutes, Proteobacteria and Bacteroidetes. This strategy allowed us to identify several extracts obtained from bacterial strain F-278,770T, the type strain of the recently proposed new species Pseudomonas granadensis, showing biological activities not associated with previously known bioactive metabolites. The fractionation and structural elucidation of one of these extracts led to the discovery of a new lipodepsipeptide (MDN-0066) with specific toxicity in pVHL deficient cells that is not detectable in cells with pVHL expression rescue. This specific toxicity is associated with apoptosis

  16. Ga-68 Somatostatin Receptor PET/CT in von Hippel-Lindau Disease

    Energy Technology Data Exchange (ETDEWEB)

    Oh, Jong-Ryool; Min, Jung-Joon [Chonnam National Univ. Hwasun Hospital, Hwasun (Korea, Republic of); Kulkarui, Harshad; Carreras, Cecilia; Schalch, Georg; Baum, Richard P. [Nuclear Medicine and Center for PET/CT, Zentralk Bad Berka, Bad Verka (Germany)

    2012-06-15

    Von Hippel-Lindau (VHL) disease is a dominantly inherited familial cancer syndrome with a variety of benign and malignant tumors such as retinal and central nervous system hemangioblastomas, endolymphatic sac tumors, renalcysts and tumors, pancreatic cysts and tumors, pheochromo-cytomas, and epididymal cystadenomas. Cross-sectional mo-dalities (computed tomography and magnetic resonance imaging) as well as ultrasound play a major role in the initial evaluation and follow-up of the various manifestations of VHL disease. Ga-68-labeled somatostatin receptor analogs already have a significant role in the diagnosis, staging, and therapy management of neuroendocrine neoplasms and neural crest tumors. Herein, we report a case presenting a variety of malignancies in VHL and showing the usefulness of Ga-68 somatostatin receptor PET/CT as a one-stop-shop imaging modality in the management of VHL disease.

  17. Homology modeling and molecular dynamics simulation of the HIF2α degradation-related HIF2α-VHL complex.

    Science.gov (United States)

    Dong, Xiaotian; Su, Xiaoru; Yu, Jiong; Liu, Jingqi; Shi, Xiaowei; Pan, Qiaoling; Yang, Jinfeng; Chen, Jiajia; Li, Lanjuan; Cao, Hongcui

    2017-01-01

    R)-pVHL mutants on the basis of RMSD, DSSP, binding free energy, and hydrogen bonding. The experimental data indicate that the stability of the structural model of the HIF2α-pVHL complex is higher than that of the mutants, consistently with clinical observations. The structural model of the HIF2α-pVHL complex presented in this study enhances understanding of how HIF2α is captured by pVHL. Moreover, the important contact amino acids that we identified may be useful in the development of drugs to treat HIF2a-related diseases. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. LOSS OF JAK2 REGULATION VIA VHL-SOCS1 E3 UBIQUITIN HETEROCOMPLEX UNDERLIES CHUVASH POLYCYTHEMIA

    Science.gov (United States)

    Russell, Ryan C.; Sufan, Roxana I.; Zhou, Bing; Heir, Pardeep; Bunda, Severa; Sybingco, Stephanie S.; Greer, Samantha N.; Roche, Olga; Heathcote, Samuel A.; Chow, Vinca W.K.; Boba, Lukasz M.; Richmond, Terri D.; Hickey, Michele M.; Barber, Dwayne L.; Cheresh, David A.; Simon, M. Celeste; Irwin, Meredith S.; Kim, William Y.; Ohh, Michael

    2011-01-01

    SUMMARY Chuvash polycythemia (CP) is a rare congenital form of polycythemia caused by homozygous R200W and H191D mutations in the von Hippel-Lindau (VHL) gene whose gene product is the principal negative regulator of hypoxia-inducible factor. However, the molecular mechanisms underlying some of the hallmark features of CP such as hypersensitivity to erythropoietin are unclear. Here, we show that VHL directly binds suppressor of cytokine signalling 1 (SOCS1) to form a heterodimeric E3 ligase that targets phosphorylated (p)JAK2 for ubiquitin-mediated destruction. In contrast, CP-associated VHL mutants have altered affinity for SOCS1 and fail to engage and degrade pJAK2. Systemic administration of a highly selective JAK2 inhibitor, TG101209, reverses the disease phenotype in vhlR200W/R200W knock-in mice, a model that faithfully recapitulates human CP. These results reveal VHL as a SOCS1-cooperative negative regulator of JAK2 and provide compelling biochemical and preclinical evidence for JAK2- targeted therapy in CP patients. PMID:21685897

  19. Loss of JAK2 regulation via a heterodimeric VHL-SOCS1 E3 ubiquitin ligase underlies Chuvash polycythemia.

    Science.gov (United States)

    Russell, Ryan C; Sufan, Roxana I; Zhou, Bing; Heir, Pardeep; Bunda, Severa; Sybingco, Stephanie S; Greer, Samantha N; Roche, Olga; Heathcote, Samuel A; Chow, Vinca W K; Boba, Lukasz M; Richmond, Terri D; Hickey, Michele M; Barber, Dwayne L; Cheresh, David A; Simon, M Celeste; Irwin, Meredith S; Kim, William Y; Ohh, Michael

    2011-06-19

    Chuvash polycythemia is a rare congenital form of polycythemia caused by homozygous R200W and H191D mutations in the VHL (von Hippel-Lindau) gene, whose gene product is the principal negative regulator of hypoxia-inducible factor. However, the molecular mechanisms underlying some of the hallmark abnormalities of Chuvash polycythemia, such as hypersensitivity to erythropoietin, are unclear. Here we show that VHL directly binds suppressor of cytokine signaling 1 (SOCS1) to form a heterodimeric E3 ligase that targets phosphorylated JAK2 (pJAK2) for ubiquitin-mediated destruction. In contrast, Chuvash polycythemia-associated VHL mutants have altered affinity for SOCS1 and do not engage with and degrade pJAK2. Systemic administration of a highly selective JAK2 inhibitor, TG101209, reversed the disease phenotype in Vhl(R200W/R200W) knock-in mice, an experimental model that recapitulates human Chuvash polycythemia. These results show that VHL is a SOCS1-cooperative negative regulator of JAK2 and provide biochemical and preclinical support for JAK2-targeted therapy in individuals with Chuvash polycythemia.

  20. Von Hippel-Lindau Disease (VHL)

    Science.gov (United States)

    ... ALS) Information Page NINDS Anencephaly Information Page NINDS Angelman Syndrome Information Page NINDS Antiphospholipid Syndrome Information Page ... ALS) Information Page NINDS Anencephaly Information Page NINDS Angelman Syndrome Information Page NINDS Antiphospholipid Syndrome Information Page ...

  1. Familial pheochromocytoma associated with a novel mutation in the von Hippel-Lindau gene

    Energy Technology Data Exchange (ETDEWEB)

    Gross, D.J.; Avishai, N.; Meiner, V.; Abeliovich, D.; Filon, D. [Hadassah Univ. Hospital and the Hebrew Univ.-Hadassah Medical School, Jerusalem (Israel)] [and others

    1996-01-01

    We report a three generation, 25 member kindred with familial pheochromocytoma. Seven subjects of generations I and II had pheochromocytoma, in five of the seven, the tumors were bilateral, and in two of the seven, the tumors were both adrenal and extraadrenal. One patient also had a carotid body chemodectoma, and one patient had a malignant adrenal tumor and abdominal paraganglioma. In the patient with the chemodectoma, a cerebellar hemagioblastoma became manifest 25 yr after his initial diagnosis with pheochromocytoma, leading only then to a clinical diagnosis of von Hippel-Lindau disease (VHL). A mutational analysis of the VHL gene revealed a novel nucleotide 709 G{r_arrow}T transversion present in all affected subjects and in four presymptomatic children. In familial pheochromocytoma the diagnosis of VHL should be considered, even when the formal criteria for diagnosis of the syndrome are lacking. 16 refs., 2 figs.

  2. Pathological and Clinical Features and Management of Central Nervous System Hemangioblastomas in von Hippel-Lindau Disease

    Directory of Open Access Journals (Sweden)

    Hiroshi Kanno

    2014-08-01

    Full Text Available Central nervous system (CNS hemangioblastoma is the most common manifestation of von Hippel-Lindau (VHL disease. It is found in 70-80% of VHL patients. Hemangioblastoma is a rare form of benign vascular tumor of the CNS, accounting for 2.0% of CNS tumors. It can occur sporadically or as a familial syndrome. CNS hemangioblastomas are typically located in the posterior fossa and the spinal cord. VHL patients usually develop a CNS hemangioblastoma at an early age. Therefore, they require a special routine for diagnosis, treatment and follow-up. The surgical management of symptomatic tumors depends on many factors such as symptom, location, multiplicity, and progression of the tumor. The management of asymptomatic tumors in VHL patients is controversial since CNS hemangioblastomas grow with intermittent quiescent and rapid-growth phases. Preoperative embolization of large solid hemangioblastomas prevents perioperative hemorrhage but is not necessary in every case. Radiotherapy should be reserved for inoperable tumors. Because of complexities of VHL, a better understanding of the pathological and clinical features of hemangioblastoma in VHL is essential for its proper management.

  3. Small activating RNA induced expression of VHL gene in renal cell carcinoma.

    Science.gov (United States)

    Kang, Moo Rim; Park, Ki Hwan; Lee, Chang Woo; Lee, Myeong Youl; Han, Sang-Bae; Li, Long-Cheng; Kang, Jong Soon

    2018-02-06

    Recent studies have reported that chemically synthesized double-stranded RNAs (dsRNAs), also known as small activating RNA (saRNAs), can specifically induce gene expression by targeting promoter sequences by a mechanism termed RNA activation (RNAa). In the present study, we designed 4 candidate saRNAs targeting the Von Hippel-Lindau (VHL) gene promoter. Among these saRNAs, dsVHL-821 significantly inhibited cell growth by up-regulating VHL at both the mRNA and protein levels in renal cell carcinoma 769-P cells. Functional analysis showed that dsVHL-821 induced apoptosis by increasing p53, decreasing Bcl-xL, activating caspase 3/7 and poly-ADP-ribose polymerase in a dose-dependent manner. Chromatin immunoprecipitation analysis revealed that dsVHL-821 increased the enrichment of Ago2 and RNA polymerase II at the dsVHL-821 target site. In addition, Ago2 depletion significantly suppressed dsVHL-821-induced up-regulation of VHL gene expression and related effects. Single transfection of dsVHL-821 caused long-lasting (14 days) VHL up-regulation. Furthermore, the activation of VHL by dsVHL-821 was accompanied by an increase in dimethylation of histone 3 at lysine 4 (H3K4me2) and acetylation of histone 4 (H4ac) and a decrease in dimethylation of histone 3 at lysine 9 (H3K9me2) and lysine 27 (H3K27me2) in the dsVHL-821 target region. Taken together, these results demonstrate that dsVHL-821, a novel saRNA for VHL, induces the expression of the VHL gene by epigenetic changes, leading to inhibition of cell growth and induction of apoptosis, and suggest that targeted activation of VHL by dsVHL-821 may be explored as a novel treatment of renal cell carcinoma. Copyright © 2018 Elsevier Ltd. All rights reserved.

  4. A case of von Hippel-Lindau disease with exudative maculopathy

    Directory of Open Access Journals (Sweden)

    Basel T Ba′arah

    2009-01-01

    Full Text Available Von Hippel-Lindau (VHL disease is a rare multisystem familial tumor syndrome of autosomal dominant inheritance. Hallmark lesions include retinal, cerebellum and spinal cord hemangioblastomas, renal cell carcinomas, adrenal pheochromocytomas, angiomatous or cystic lesions of the kidneys, pancreas, and epididymis. We report a case of VHL disease in a 26-year-old patient who presented with exudative macular edema. Ocular and systemic studies revealed the presence of retinal and central nervous system hemangioblastomas, adrenal pheochromocytoma, multiple pancreatic, and kidney cysts. The retinal angiomas were successfully treated with argon laser photocoagulation and cryotherapy.

  5. Management Strategies and Outcomes for VHL-related Craniospinal Hemangioblastomas

    Directory of Open Access Journals (Sweden)

    Christ Ordookhanian

    2017-08-01

    Full Text Available Hemangioblastomas are rare and benign tumors accounting for less than 2% of all central nervous system (CNS tumors. The vast majority of hemangioblastomas occur sporadically, whereas a small number of cases, especially in younger patients, are associated with Von Hippel–Lindau (VHL syndrome. It is thought that loss of tumor suppressor function of the VHL gene results in stabilization of hypoxia-inducible factor alpha with downstream activation of cellular proliferative and angiogenic genes that promote tumorigenesis. VHL-related hemangioblastomas predominantly occur in the cerebellum and spine. Lesions are often diagnosed on contrast-enhanced craniospinal MRIs, and the diagnosis of VHL occurs through assessment for germline VHL mutations. Surgical resection remains the primary treatment modality for symptomatic or worrisome lesions, with excellent local control rates and neurological outcomes. Stereotactic radiotherapy can be employed in patients who are deemed high risk for surgery, have multiple lesions, or have non-resectable lesions. Given the tendency for development of either new or multiple lesions, close radiographic surveillance is often recommended for asymptomatic lesions.

  6. Role of VEGFA, CXCR4 and VHL mutation in tumour behaviour

    NARCIS (Netherlands)

    Kruizinga, Roeliene

    2014-01-01

    De ziekte van Von Hippel Lindau (VHL) is een zeldzaam kankersyndroom. Patiënten met deze ziekte krijgen zowel goedaardige als kwaadaardige tumoren in verschillende organen. VHL-patiënten hebben een niet goed werkend VHL-eiwit waardoor er meer CXCR4, een chemokine receptor, en VEGFA, een

  7. Role of VHL, HIF1A and SDH on the expression of miR-210: Implications for tumoral pseudo-hypoxic fate.

    Science.gov (United States)

    Merlo, Anna; Bernardo-Castiñeira, Cristóbal; Sáenz-de-Santa-María, Inés; Pitiot, Ana S; Balbín, Milagros; Astudillo, Aurora; Valdés, Nuria; Scola, Bartolomé; Del Toro, Raquel; Méndez-Ferrer, Simón; Piruat, José I; Suarez, Carlos; Chiara, María-Dolores

    2017-01-24

    The hypoxia-inducible factor 1α (HIF-1α) and its microRNA target, miR-210, are candidate tumor-drivers of metabolic reprogramming in cancer. Neuroendocrine neoplasms such as paragangliomas (PGLs) are particularly appealing for understanding the cancer metabolic adjustments because of their associations with deregulations of metabolic enzymes, such as succinate dehydrogenase (SDH), and the von Hippel Lindau (VHL) gene involved in HIF-1α stabilization. However, the role of miR-210 in the pathogenesis of SDH-related tumors remains an unmet challenge. Herein is described an in vivo genetic analysis of the role of VHL, HIF1A and SDH on miR-210 by using knockout murine models, siRNA gene silencing, and analyses of human tumors. HIF-1α knockout abolished hypoxia-induced miR-210 expression in vivo but did not alter its constitutive expression in paraganglia. Normoxic miR-210 levels substantially increased by complete, but not partial, VHL silencing in paraganglia of knockout VHL-mice and by over-expression of p76del-mutated pVHL. Similarly, VHL-mutated PGLs, not those with decreased VHL-gene/mRNA dosage, over-expressed miR-210 and accumulate HIF-1α in most tumor cells. Ablation of SDH activity in SDHD-null cell lines or reduction of the SDHD or SDHB protein levels elicited by siRNA-induced gene silencing did not induce miR-210 whereas the presence of SDH mutations in PGLs and tumor-derived cell lines was associated with mild increase of miR-210 and the presence of a heterogeneous, HIF-1α-positive and HIF-1α-negative, tumor cell population. Thus, activation of HIF-1α is likely an early event in VHL-defective PGLs directly linked to VHL mutations, but it is a late event favored but not directly triggered by SDHx mutations. This combined analysis provides insights into the mechanisms of HIF-1α/miR-210 regulation in normal and tumor tissues potentially useful for understanding the pathogenesis of cancer and other diseases sharing similar underpinnings.

  8. Kidney Tumor in a von Hippel-Lindau (VHL) Patient With Intensely Increased Activity on 68Ga-DOTA-TATE PET/CT.

    Science.gov (United States)

    Papadakis, Georgios Z; Millo, Corina; Sadowski, Samira M; Bagci, Ulas; Patronas, Nicholas J

    2016-12-01

    Renal and pancreatic cysts and tumors are the most common visceral manifestations of von Hippel-Lindau (VHL) disease, a heritable multisystem cancer syndrome characterized by development of a variety of malignant and benign tumors. We report a case of a VHL patient with multiple renal cystic and complex cystic/solid lesions. The patient underwent Ga-DOTA-TATE-PET/CT showing intensely increased activity by a solid lesion which demonstrated enhancement on both CT and MRI scans, raising high suspicion for malignancy. The presented case indicates application of SSTR-imaging using Ga-DOTA-conjugated peptides in VHL-patients and emphasizes the need for cautious interpretation of renal parenchyma Ga-DOTATATE activity.

  9. [Longitudinal study of three families with familial Parkinson's disease].

    Science.gov (United States)

    Baltasar-Rodríguez, Luz Margarita; Millán-Guerrero, Rebeca O; Aceves-Themsel, Roberto; Isais-Millán, Sara; Delgado-Enciso, Iván

    2006-01-01

    Familial Parkinson's is a variant of Parkinson's disease (PD) transmitted generationally with an early onset. Describe the clinical disease characteristics and its 18 year evolution among families in Colima presenting familial PD. We determined disease diagnosis, evolution and hereditary pattern. The UPDRS system was used to follow the longitudinal course of the disease. Descriptive statistics were carried out using means and percentages. Three families were studied, with a total of 51 subjects aged 29 +/- 22 years spanning 4 generations. Thirty-seven percent of studied subjects displayed familial PD, with disease onset at 24 +/- 9 years of age. The highest UPDRS value was 175. Disease transmission with a dominant autosomic heredity pattern was shown. One hundred percent of first and second generation members from family number 1 displayed the disease. The three families displayed early onset PD and rapid progression, coinciding with described characteristics of type 1 familial Parkinsonism (PARK1). This disease is caused by the Ala53Thr mutation of the alpha-synuclein gene.

  10. SOMATIC MUTATIONS OF THE VON HIPPEL-LINDAU DISEASE TUMOR-SUPPRESSOR GENE IN NONFAMILIAL CLEAR-CELL RENAL-CARCINOMA

    NARCIS (Netherlands)

    FOSTER, K; PROWSE, A; van den Berg, Anke; FLEMING, S; HULSBEEK, MMF; CROSSEY, PA; RICHARDS, FM; CAIRNS, P; FERGUSONSMITH, MA; BUYS, CHCM; MAHER, ER

    1994-01-01

    Loss of heterozygosity (LOH) studies have suggested that somatic mutations of a tumour suppressor gene or genes on chromosome 3p are a critical event in the pathogenesis of non-familial renal cell carcinoma (RCC). Germline mutations of the von Hippel - Lindau (VHL) disease gene predispose to early

  11. Phospholamban Is Downregulated by pVHL-Mediated Degradation through Oxidative Stress in Failing Heart

    Directory of Open Access Journals (Sweden)

    Shunichi Yokoe

    2017-10-01

    Full Text Available The E3 ubiquitin ligase, von Hippel–Lindau (VHL, regulates protein expression by polyubiquitination. Although the protein VHL (pVHL was reported to be involved in the heart function, the underlying mechanism is unclear. Here, we show that pVHL was upregulated in hearts from two types of genetically dilated cardiomyopathy (DCM mice models. In comparison with the wild-type mouse, both DCM mice models showed a significant reduction in the expression of phospholamban (PLN, a potent inhibitor of sarco(endoplasmic reticulum Ca2+-ATPase, and enhanced interaction between pVHL and PLN. To clarify whether pVHL is involved in PLN degradation in failing hearts, we used carbonylcyanide m-chlorophenylhydrazone (CCCP, a mitochondrial membrane potential (MMP-lowering reagent, to mimic the heart failure condition in PLN-expressing HEK293 cells and found that CCCP treatment resulted in PLN degradation and increased interaction between PLN and pVHL. However, these effects were reversed with the addition of N-acetyl-l-cysteine. Furthermore, the co-transfection of VHL and PLN in HEK293 cells decreased PLN expression under oxidative stress, whereas knockdown of VHL increased PLN expression both under normal and oxidative stress conditions. Together, we propose that oxidative stress upregulates pVHL expression to induce PLN degradation in failing hearts.

  12. Fabry Disease in Families With Hypertrophic Cardiomyopathy

    DEFF Research Database (Denmark)

    Adalsteinsdottir, Berglind; Palsson, Runolfur; Desnick, Robert J

    2017-01-01

    BACKGROUND: The screening of Icelandic patients clinically diagnosed with hypertrophic cardiomyopathy resulted in identification of 8 individuals from 2 families with X-linked Fabry disease (FD) caused by GLA(α-galactosidase A gene) mutations encoding p.D322E (family A) or p.I232T (family B...

  13. Familial risk of inflammatory bowel disease

    DEFF Research Database (Denmark)

    Moller, Frederik Trier; Andersen, Vibeke; Wohlfahrt, Jan

    2015-01-01

    OBJECTIVES: Estimates of familial risk of inflammatory bowel diseases (IBDs), Crohn's disease (CD), and ulcerative colitis (UC) are needed for counseling of patients and could be used to target future prevention. We aimed to provide comprehensive population-based estimates of familial risk of IBD...

  14. ERK5/BMK1 Is a Novel Target of the Tumor Suppressor VHL: Implication in Clear Cell Renal Carcinoma12

    Science.gov (United States)

    Arias-González, Laura; Moreno-Gimeno, Inmaculada; del Campo, Antonio Rubio; Serrano-Oviedo, Leticia; Valero, María Llanos; Esparís-Ogando, Azucena; de la Cruz-Morcillo, Miguel Ángel; Melgar-Rojas, Pedro; García-Cano, Jesús; Cimas, Francisco José; Hidalgo, María José Ruiz; Prado, Alfonso; Callejas-Valera, Juan Luis; Nam-Cha, Syong Hyun; Giménez-Bachs, José Miguel; Salinas-Sánchez, Antonio S; Pandiella, Atanasio; del Peso, Luis; Sánchez-Prieto, Ricardo

    2013-01-01

    Extracellular signal-regulated kinase 5 (ERK5), also known as big mitogen-activated protein kinase (MAPK) 1, is implicated in a wide range of biologic processes, which include proliferation or vascularization. Here, we show that ERK5 is degraded through the ubiquitin-proteasome system, in a process mediated by the tumor suppressor von Hippel-Lindau (VHL) gene, through a prolyl hydroxylation-dependent mechanism. Our conclusions derive from transient transfection assays in Cos7 cells, as well as the study of endogenous ERK5 in different experimental systems such as MCF7, HMEC, or Caki-2 cell lines. In fact, the specific knockdown of ERK5 in pVHL-negative cell lines promotes a decrease in proliferation and migration, supporting the role of this MAPK in cellular transformation. Furthermore, in a short series of fresh samples from human clear cell renal cell carcinoma, high levels of ERK5 correlate with more aggressive and metastatic stages of the disease. Therefore, our results provide new biochemical data suggesting that ERK5 is a novel target of the tumor suppressor VHL, opening a new field of research on the role of ERK5 in renal carcinomas. PMID:23730213

  15. ERK5/BMK1 Is a Novel Target of the Tumor Suppressor VHL: Implication in Clear Cell Renal Carcinoma

    Directory of Open Access Journals (Sweden)

    Laura Arias-González

    2013-06-01

    Full Text Available Extracellular signal-regulated kinase 5 (ERK5, also known as big mitogen-activated protein kinase (MAPK 1, is implicated in a wide range of biologic processes, which include proliferation or vascularization. Here, we show that ERK5 is degraded through the ubiquitin-proteasome system, in a process mediated by the tumor suppressor von Hippel-Lindau (VHL gene, through a prolyl hydroxylation-dependent mechanism. Our conclusions derive from transient transfection assays in Cos7 cells, as well as the study of endogenous ERK5 in different experimental systems such as MCF7, HMEC, or Caki-2 cell lines. In fact, the specific knockdown of ERK5 in pVHL-negative cell lines promotes a decrease in proliferation and migration, supporting the role of this MAPK in cellular transformation. Furthermore, in a short series of fresh samples from human clear cell renal cell carcinoma, high levels of ERK5 correlate with more aggressive and metastatic stages of the disease. Therefore, our results provide new biochemical data suggesting that ERK5 is a novel target of the tumor suppressor VHL, opening a new field of research on the role of ERK5 in renal carcinomas.

  16. Genetics Home Reference: familial erythrocytosis

    Science.gov (United States)

    ... mutations in the EPOR , VHL , EGLN1 , or EPAS1 gene. Researchers define four types of familial erythrocytosis , ECYT1 through ECYT4, based on which of these genes is altered. The EPOR gene provides instructions for ...

  17. Autism and Autoimmune Disease: A Family Study

    Science.gov (United States)

    Money, John; And Others

    1971-01-01

    Described in a family in which the youngest boy has early infantile autism, Addison's disease, and moniliasis and two older boys have autoimmune disease with hypoparathyroidism, Addison's disease, moniliasis, and either alopecia totalis or diabetes mellitus, while the oldest boy and parents are symptom free. (KW)

  18. Uptake of genetic testing and long-term tumor surveillance in von Hippel-Lindau disease

    Directory of Open Access Journals (Sweden)

    Chávez Mireya

    2010-01-01

    Full Text Available Abstract Background von Hippel-Lindau (VHL disease is a hereditary cancer syndrome caused by germline mutations in the VHL gene. Patients have significant morbidity and mortality secondary to vascular tumors. Disease management is centered on tumor surveillance that allows early detection and treatment. Presymptomatic genetic testing is therefore recommended, including in at-risk children. Methods We tested 17 families (n = 109 individuals for VHL mutations including 43 children under the age of 18. Personalized genetic counseling was provided pre and post-test and the individuals undergoing presymptomatic testing filled out questionnaires gathering socio-demographic, psychological and psychiatric data. Mutation analysis was performed by direct sequencing of the VHL gene. Mutation-carriers were screened for VHL disease-related tumors and were offered follow-up annual examinations. Results Mutations were identified in 36 patients, 17 of whom were asymptomatic. In the initial screening, we identified at least one tumor in five of 17 previously asymptomatic individuals. At the end of five years, only 38.9% of the mutation-carriers continued participating in our tumor surveillance program. During this time, 14 mutation carriers developed a total of 32 new tumors, three of whom died of complications. Gender, education, income, marital status and religiosity were not found to be associated with adherence to the surveillance protocol. Follow-up adherence was also independent of pre-test depression, severity of disease, or number of affected family members. The only statistically significant predictor of adherence was being symptomatic at the time of testing (OR = 5; 95% CI 1.2 - 20.3; p = 0.02. Pre-test anxiety was more commonly observed in patients that discontinued follow-up (64.7% vs. 35.3%; p = 0.01. Conclusions The high initial uptake rate of genetic testing for VHL disease, including in minors, allowed the discontinuation of unnecessary screening

  19. The VHL-dependent regulation of microRNAs in renal cancer

    Directory of Open Access Journals (Sweden)

    Rawlings Lesley H

    2010-10-01

    Full Text Available Abstract Background The commonest histological type of renal cancer, clear cell renal cell carcinoma (cc RCC, is associated with genetic and epigenetic changes in the von Hippel-Lindau (VHL tumour suppressor. VHL inactivation leads to induction of hypoxia-inducible factors (HIFs and a hypoxic pattern of gene expression. Differential levels of specific microRNAs (miRNAs are observed in several tumours when compared to normal tissue. Given the central role of VHL in renal cancer formation, we examined the VHL-dependent regulation of miRNAs in renal cancer. Methods VHL-dependent miRNA expression in cc RCC was determined by microarray analysis of renal cell line RCC4 with mutated VHL (RCC4-VHL and reintroduced wild-type VHL (RCC4 + VHL. Five miRNAs highly upregulated in RCC4 + VHL and five miRNAs highly downregulated in RCC4 + VHL were studied further, in addition to miR-210, which is regulated by the HIF-VHL system. miRNA expression was also measured in 31 cc RCC tumours compared to adjacent normal tissue. Results A significant increase in miR-210, miR-155 and miR-21 expression was observed in the tumour tissue. miR-210 levels also showed a correlation with a HIF-regulated mRNA, carbonic anhydrase IX (CAIX, and with VHL mutation or promoter methylation. An inverse correlation was observed between miR-210 expression and patient survival, and a putative target of miR-210, iron-sulfur cluster assembly protein (ISCU1/2, shows reciprocal levels of mRNA expression in the tumours. Conclusions We have identified VHL-regulated miRNAs and found that for some the regulation is HIF-dependent and for others it is HIF-independent. This pattern of regulation was also seen in renal cancer tissue for several of these miRNAs (miR-210, miR-155, let-7i and members of the miR-17-92 cluster when compared with normal tissue. miR-210 showed marked increases in expression in renal cancer and levels correlated with patient survival. The inverse correlation between miR-210

  20. Heart disease, family history and physical activity.

    Science.gov (United States)

    Chen, J; Millar, W J

    2001-08-01

    This article examines the association of family history of heart disease and leisure-time physical activity with incident heart disease. The data are from the 1994/95, 1996/97 and 1998/99 longitudinal household components of Statistics Canada's National Population Health Survey. This study is based on information provided by 9,255 respondents aged 20 or older who reported that, in 1994/95, they were free of diagnosed heart disease and in good health. Multiple logistic regression was used to estimate the association of family history and physical activity with a new diagnosis of heart disease, while controlling for age, sex, educational attainment, smoking, high blood pressure, diabetes, and body mass index. When family history and other risk factors were taken into account, people who, in 1994/95, engaged in regular physical activity at a moderate level or beyond had lower odds of receiving a new diagnosis of heart disease than did sedentary individuals. People with a family history of heart disease who regularly participated in at least moderate physical activity had lower odds of developing heart disease than did their sedentary counterparts.

  1. Early-onset familial Alzheimer's disease (EOFAD).

    Science.gov (United States)

    Wu, Liyong; Rosa-Neto, Pedro; Hsiung, Ging-Yuek R; Sadovnick, A Dessa; Masellis, Mario; Black, Sandra E; Jia, Jianping; Gauthier, Serge

    2012-07-01

    Early-onset familial Alzheimer's disease (EOFAD) is a condition characterized by early onset dementia (age at onset family history for dementia. To date, 230 mutations in presenilin (PS1, PS2) and amyloid precursor protein (APP) genes have been identified in EOFAD. The mutations within these three genes (PS1/PS2/APP) affect a common pathogenic pathway in APP synthesis and proteolysis, which lead to excessive production of amyloid β. Compared with sporadic Alzheimer's disease (AD), EOFAD has some distinctive features including early age at onset, positive familial history, a variety of non-cognitive neurological symptoms and signs, and a more aggressive course. There is marked phenotypic heterogeneity among different mutations of EOFAD. Studies in presymptomatic mutation carriers reveal biomarkers abnormalities. EOFAD diagnosis is based on clinical and family history, neurological symptoms and examination, biomarker features, as well as genotyping in some cases. New therapeutic agents targeting amyloid formation may benefit EOFAD individuals.

  2. Familial occurrence of inflammatory bowel disease

    DEFF Research Database (Denmark)

    Orholm, M; Munkholm, P; Langholz, E

    1991-01-01

    BACKGROUND AND METHODS: We assessed the familial occurrence of inflammatory bowel disease in Copenhagen County, where there has been a long-term interest in the epidemiology of such disorders. In 1987 we interviewed 662 patients in whom inflammatory bowel disease had been diagnosed before 1979......, asking whether their first- and second-degree relatives had this disorder. Ninety-six percent of the patients (504 with ulcerative colitis and 133 with Crohn's disease) provided adequate information. RESULTS: As compared with the general population, the first-degree relatives of the 637 patients...... with ulcerative colitis or Crohn's disease had a 10-fold increase in the risk of having the same disease as the patients, after standardization for age and sex. The risk of having the other of the two diseases was also increased, but less so, and the increase in the risk of having Crohn's disease...

  3. Family physician perspectives on primary immunodeficiency diseases

    Directory of Open Access Journals (Sweden)

    Jordan eOrange

    2016-03-01

    Full Text Available Primary immunodeficiency diseases (PID include over 250 diverse disorders. The current study assessed management of PID by family practice physicians. The American Academy of Allergy, Asthma, and Immunology Primary Immunodeficiency Committee and the Immune Deficiency Foundation conducted an incentivized mail survey of family practice physician members of the American Medical Association and the American Osteopathic Association in direct patient care. Responses were compared with subspecialist immunologist responses from a similar survey. Surveys were returned by 528 (of 4500 surveys mailed family practice physicians, of whom 44% reported following ≥1 patient with a PID. Selective immunoglobulin A (IgA, deficiency (21%, and chronic granulomatous disease (11% were most common and were followed by significantly more subspecialist immunologists (P<.0001. Use of intravenously administered Ig, and live viral vaccinations across PID was significantly different (P<.0001. Few family practice physicians were aware of professional guidelines for diagnosis and management of PID (4% vs. 79% of subspecialist immunologists, P<.0001. Family practice physicians will likely encounter patients with a PID diagnoses during their career. Differences in how family practice physicians and subspecialist immunologists manage patients with PID underscore areas where improved educational and training initiatives may benefit patient care.

  4. VHL genetic alteration in CCRCC does not determine de-regulation of HIF, CAIX, hnRNP A2/B1 and osteopontin.

    LENUS (Irish Health Repository)

    Nyhan, Michelle J

    2012-01-31

    BACKGROUND: von Hippel-Lindau (VHL) tumour suppressor gene inactivation is associated with clear cell renal cell carcinoma (CCRCC) development. The VHL protein (pVHL) has been proposed to regulate the expression of several proteins including Hypoxia Inducible Factor-alpha (HIF-alpha), carbonic anhydrase (CA)IX, heterogeneous nuclear ribonucleoprotein (hnRNP) A2\\/B1 and osteopontin. pVHL has been characterized in vitro, however, clinical studies are limited. We evaluated the impact of VHL genetic alterations on the expression of several pVHL protein targets in paired normal and tumor tissue. METHODS: The VHL gene was sequenced in 23 CCRCC patients and VHL transcript levels were evaluated by real-time RT-PCR. Expression of pVHL\\'s protein targets were determined by Western blotting in 17 paired patient samples. RESULTS: VHL genetic alterations were identified in 43.5% (10\\/23) of CCRCCs. HIF-1alpha, HIF-2alpha and CAIX were up-regulated in 88.2% (15\\/17), 100% (17\\/17) and 88.2% (15\\/17) of tumors respectively and their expression is independent of VHL status. hnRNP A2\\/B1 and osteopontin expression was variable in CCRCCs and had no association with VHL genetic status. CONCLUSION: As expression of these proposed pVHL targets can be achieved independently of VHL mutation (and possibly by hypoxia alone), these data suggests that other pVHL targets may be more crucial in renal carcinogenesis.

  5. Diseases of herbs from Apiaceae family

    Directory of Open Access Journals (Sweden)

    Ewa Dorota Zalewska

    2013-04-01

    Full Text Available The largest participation in causing the disease of herbal plants have fungi. Studies on their occurrence on plants of the family Apiaceae are conducted in the Lublin region since 2001. The observations of plant healthiness are carried out directly on the plantations. Plants with symptoms of disease are studied in the laboratory. Identification of the fungi is performed based on etiological symptoms and on the base of fungal cultures isolated from plants. Among the many species of fungi obtained from diseased plants to the particularly harmful belong: Septoria carvi, Colletotrichum gloeosporioidesand C. dematium, Sclerotinia sclerotiorum, Passalora puncta(Cercosporidium punctum and Erysiphe umbelliferarum.

  6. Duplication of the VHL and IRAK2 genes in a patient with mental retardation/multiple congenital anomalies, epilepsy and ectomorphic habitus.

    Science.gov (United States)

    Chabchoub, E; Michils, G; Vermeesch, J R; De Cock, P; Lagae, L; Fryns, J P

    2010-01-01

    Partial 3p duplications are very rare. Often they are reported in translocations involving other chromosomes, whereas deletions encompassing the VHL gene in 3p25.3 predispose to Van-Hippel Lindau syndrome. We report here a paternally-inherited microduplication of 3p25.3 detected by array comparative genomic hybridisation (aCGH) in a 17 year-old male patient presenting with mental retardation and multiple congenital anomalies (MR/MCA), epilepsy and ectomorphic habitus. He has no tumour and there is no history of familial cancer. We refined the duplication by Multiplex Ligation-dependent Probe Amplification (MLPA) to a 251 kb region encompassing the VHL and IRAK2 genes. The duplication is likely to be causal. Interestingly, duplication of IRAK2 can cause epilepsy. Disruption of the GHRL gene can explain the ectomorphic habitus. To our knowledge, this is the smallest 3p duplication encompassing the VHL region. Its prognosis is unknown and a long-term follow-up is essential for an early diagnosis of malignancy.

  7. Familial risk of inflammatory bowel disease

    DEFF Research Database (Denmark)

    Trier Møller, Frederik; Andersen, Vibeke; Jess, Tine

    2014-01-01

    Background The inflammatory bowel diseases (IBD) – ulcerative colitis (UC) and Crohn’s disease (CD) - are caused by complex gene-environment interactions. This study provides updated familial aggregation patterns in a large population-based Danish IBD cohort. Methods: Our cohort study was based.......92(5.28-9.06) 2.62(1.63-4.23) 1.15(0.29-4.62) One CD relative 2.57(2.28-2.90) 1.51(1.22-1.86) 1.47(1.00-2.17) One UC relative 4.09(3.81-4.38) 1.85(1.60-2.13) 1.51(1.07-2.13) Conclusion: This large-scale population-based study provides updated numbers of familial aggregation of IBD. Familial exposure to CD...... in the entire population. Individuals receiving at least 2 diagnoses of IBD during the time period (n=45,780) were identified using the Danish National Registry of Patients. Risk of IBD in family members to individuals with IBD was assessed by Poisson regression analysis. Results: The overall proportion...

  8. Family aggregation of cardiovascular disease mortality

    DEFF Research Database (Denmark)

    Silventoinen, Karri; Hjelmborg, Jacob; Möller, Sören

    2017-01-01

    Background: Familial factors play an important role in the variation of risk factors of cardiovascular diseases (CVD), but less is known about how they affect the risk of death from CVD. We estimated familial aggregation of CVD mortality for twins offering the maximum level of risk due to genetic...... and other familial factors. Methods: Altogether, 132 771 twin individuals, including 65 196 complete pairs from Denmark, Finland and Sweden born in 1958 or earlier, participated in this study. During the register-based follow-up, 11 641 deaths occurred from coronary heart disease (CHD), including 6280......: In the analyses pooling men and women, the RRR for monozygotic twins was 1.49 (95% CI 1.40-1.57) for CHD and 1.81 for any stroke (95% CI 1.54-2.09). The highest RRR was found for haemorrhagic stroke (3.53 95% CI 2.01-5.04). For dizygotic twins, the RRRs were generally lower. Conclusions: Family aggregation...

  9. Src family kinases in chronic kidney disease.

    Science.gov (United States)

    Wang, Jun; Zhuang, Shougang

    2017-09-01

    Src family kinases (SFKs) belong to nonreceptor protein tyrosine kinases and have been implicated in the regulation of numerous cellular processes, including cell proliferation, differentiation, migration and invasion, and angiogenesis. The role and mechanisms of SFKs in tumorgenesis have been extensively investigated, and some SFK inhibitors are currently under clinical trials for tumor treatment. Recent studies have also demonstrated the importance of SFKs in regulating the development of various fibrosis-related chronic diseases (e.g., idiopathic pulmonary fibrosis, liver fibrosis, renal fibrosis, and systemic sclerosis). In this article, we summarize the roles of SFKs in various chronic kidney diseases, including glomerulonephritis, diabetic nephropathy, human immunodeficiency virus-associated nephropathy, autosomal dominant form of polycystic kidney disease, and obesity-associated kidney disease, and discuss the mechanisms involved. Copyright © 2017 the American Physiological Society.

  10. Tay Sachs and Related Storage Diseases: Family Planning

    Science.gov (United States)

    Schneiderman, Gerald; And Others

    1978-01-01

    Based on interviews with 24 families, the article discusses family planning and the choices available to those families in which a child has previously died from Tay-Sachs or related lipid storage diseases. (IM)

  11. Absence of consensus in diagnostic criteria for familial neurodegenerative diseases.

    LENUS (Irish Health Repository)

    Byrne, Susan

    2012-04-01

    A small proportion of cases seen in neurodegenerative conditions such as amyotrophic lateral sclerosis (ALS), Parkinson\\'s disease and Alzheimer disease are familial. These familial cases are usually clinically indistinguishable from sporadic cases. Identifying familial cases is important both in terms of clinical guidance for family members and for gene discovery.

  12. Multiple Components of the VHL Tumor Suppressor Complex Are Frequently Affected by DNA Copy Number Loss in Pheochromocytoma

    Directory of Open Access Journals (Sweden)

    David A. Rowbotham

    2014-01-01

    Full Text Available Pheochromocytomas (PCC are rare tumors that arise in chromaffin tissue of the adrenal gland. PCC are frequently inherited through predisposing mutations in genes such as the von Hippel-Lindau (VHL tumor suppressor. VHL is part of the VHL elongin BC protein complex that also includes CUL2/5, TCEB1, TCEB2, and RBX1; in normoxic conditions this complex targets hypoxia-inducible factor 1 alpha (HIF1A for degradation, thus preventing a hypoxic response. VHL inactivation by genetic mechanisms, such as mutation and loss of heterozygosity, inhibits HIF1A degradation, even in the presence of oxygen, and induces a pseudohypoxic response. However, the described <10% VHL mutation rate cannot account for the high frequency of hypoxic response observed. Indeed, little is known about genetic mechanisms disrupting other complex component genes. Here, we show that, in a panel of 171 PCC tumors, 59.6% harbored gene copy number loss (CNL of at least one complex component. CNL significantly reduced gene expression and was associated with enrichment of gene targets controlled by HIF1. Interestingly, we show that VHL-related renal clear cell carcinoma harbored disruption of VHL alone. Our results indicate that VHL elongin BC protein complex components other than VHL could be important for PCC tumorigenesis and merit further investigation.

  13. Pancreatic cyst development: insights from von Hippel-Lindau disease

    Directory of Open Access Journals (Sweden)

    van Asselt Sophie J

    2013-02-01

    Full Text Available Abstract Pancreatic cysts are a heterogeneous group of lesions, which can be benign or malignant. Due to improved imaging techniques, physicians are more often confronted with pancreatic cysts. Little is known about the origin of pancreatic cysts in general. Von Hippel-Lindau (VHL disease is an atypical ciliopathy and inherited tumor syndrome, caused by a mutation in the VHL tumor suppressor gene encoding the VHL protein (pVHL. VHL patients are prone to develop cysts and neuroendocrine tumors in the pancreas in addition to several other benign and malignant neoplasms. Remarkably, pancreatic cysts occur in approximately 70% of VHL patients, making it the only hereditary tumor syndrome with such a discernible expression of pancreatic cysts. Cellular loss of pVHL due to biallelic mutation can model pancreatic cystogenesis in other organisms, suggesting a causal relationship. Here, we give a comprehensive overview of various pVHL functions, focusing on those that can potentially explain pancreatic cyst development in VHL disease. Based on preclinical studies, cilia loss in ductal cells is probably an important early event in pancreatic cyst development.

  14. Characterization of endolymphatic sac tumors and von Hippel-Lindau disease in the International Endolymphatic Sac Tumor Registry.

    Science.gov (United States)

    Bausch, Birke; Wellner, Ulrich; Peyre, Mathieu; Boedeker, Carsten C; Hes, Frederik J; Anglani, Mariagiulia; de Campos, Jose M; Kanno, Hiroshi; Maher, Eamonn R; Krauss, Tobias; Sansó, Gabriela; Barontini, Marta; Letizia, Claudio; Hader, Claudia; Schiavi, Francesca; Zanoletti, Elisabetta; Suárez, Carlos; Offergeld, Christian; Malinoc, Angelica; Zschiedrich, Stefan; Glasker, Sven; Bobin, Serge; Sterkers, Olivier; Ba Huy, Patrice Tran; Giraud, Sophie; Links, Thera; Eng, Charis; Opocher, Giuseppe; Richard, Stephane; Neumann, Hartmut P H

    2016-04-01

    Endolymphatic sac tumors (ELSTs) are, with a prevalence of up to 16%, a component of von Hippel-Lindau (VHL) disease. Data from international registries regarding heritable fraction and characteristics, germline VHL mutation frequency, and prevalence are lacking. Systematic registration of ELSTs from international centers of otorhinolaryngology and from multidisciplinary VHL centers' registries was performed. Molecular genetic analyses of the VHL gene were offered to all patients. Our population-based registry comprised 93 patients with ELST and 1789 patients with VHL. The prevalence of VHL germline mutations in apparently sporadic ELSTs was 39%. The prevalence of ELSTs in patients with VHL was 3.6%. ELST was the initial manifestation in 32% of patients with VHL-ELST. Prevalence of ELST in VHL disease is much lower compared to the literature. VHL-associated ELSTs can be the first presentation of the syndrome and mimic sporadic tumors, thus emphasizing the need of molecular testing in all presentations of ELST. © 2015 Wiley Periodicals, Inc. Head Neck 38: 673-679, 2016. © 2015 Wiley Periodicals, Inc.

  15. Caregiver roles in families affected by Huntington's disease

    DEFF Research Database (Denmark)

    Røthing, Merete; Malterud, Kirsti; Frich, Jan C

    2013-01-01

    AIM: The objective of this study was to explore family caregivers' experiences with the impact of Huntington's disease (HD) on the family structure and roles in the family. METHODOLOGY: We interviewed 15 family caregivers in families affected by HD, based on a semi-structured interview guide....... The participants were recruited through hospital departments and a lay organisation for HD in Norway. Data from the interviews were analysed with systematic text condensation. RESULTS: Huntington's disease could have a substantial impact on the family system, the shape of roles among family members......: Huntington's disease has a major impact on family systems. Caregiver roles are shaped by impairments in the affected family member and corresponding dynamic adoption and change in roles within the family. Making assessments of the family structure and roles, professionals may understand more about how...

  16. Pathology of the Nervous System in Von Hippel-Lindau Disease

    Directory of Open Access Journals (Sweden)

    Alexander O. Vortmeyer

    2015-06-01

    Full Text Available Von Hippel-Lindau (VHL disease is a tumor syndrome that frequently involves the central nervous system (CNS. It is caused by germline mutation of the VHL gene. Subsequent VHL inactivation in selected cells is followed by numerous well-characterized molecular consequences, in particular, activation and stabilization of hypoxia-inducible factors HIF1 and HIF2. The link between VHL gene inactivation and tumorigenesis remains poorly understood. Hemangioblastomas are the most common manifestation in the CNS; however, CNS invasion by VHL disease-associated endolymphatic sac tumors or metastatic renal cancer also occur, and their differentiation from primary hemangioblastoma may be challenging. Finally, in this review, we present recent morphologic insights on the developmental concept of VHL tumorigenesis which is best explained by pathologic persistence of temporary embryonic progenitor cells. 

  17. Anesthesia experience along with familial Mediterranean fever and celiac disease

    Directory of Open Access Journals (Sweden)

    Mehmet Sargın

    2014-03-01

    Full Text Available (Anesthetic management in patient with Familial Mediterranean Fever and Celiac Disease Familial Mediterranean Fever is an autosomal recessive transmitted disease which often seen at Mediterranean origin society and it goes by deterioration at inflammation control. Celiac disease is a proximal small intestine disease which develops gluten intolerance by autoimmune mechanism in sensitive people. Association of Familial Mediterranean Fever and Celiac disease is a rare situation. In this article we present our anesthesia experience on a bilateral septic arthritis case who also have Familial Mediterranean Fever and Celiac disease association.

  18. Familial systemic autoimmune rheumatic disease in Nigerians: a ...

    African Journals Online (AJOL)

    SARDs occasionally run in families - among mothers and daughters, among siblings. Such clustering has however not been documented among black Africans. We present four Nigerian families with clustering of systemic autoimmune rheumatic disease. Keywords: Systemic autoimmune disease, Familial clustering, ...

  19. VHL and HIF-1α: gene variations and prognosis in early-stage clear cell renal cell carcinoma.

    Science.gov (United States)

    Lessi, Francesca; Mazzanti, Chiara Maria; Tomei, Sara; Di Cristofano, Claudio; Minervini, Andrea; Menicagli, Michele; Apollo, Alessandro; Masieri, Lorenzo; Collecchi, Paola; Minervini, Riccardo; Carini, Marco; Bevilacqua, Generoso

    2014-03-01

    Von Hipple-Lindau gene (VHL) inactivation represents the most frequent abnormality in clear cell renal cell carcinoma (ccRCC). Hypoxia-inducible factor-1α (HIF-1α) expression is regulated by O2 level. In normal O2 conditions, VHL binds HIF-1α and allows HIF-1α proteasomal degradation. A single-nucleotide polymorphism (SNP) has been found located in the oxygen-dependent degradation domain at codon 582 (C1772T, rs11549465, Pro582Ser). In hypoxia, VHL/HIF-1α interaction is abolished and HIF-1α activates target genes in the nucleus. This study analyzes the impact of genetic alterations and protein expression of VHL and the C1772T SNP of HIF-1α gene (HIF-1α) on prognosis in early-stage ccRCC (pT1a, pT1b, and pT2). Mutational analysis of the entire VHL sequence and the genotyping of HIF-1α C1772T SNP were performed together with VHL promoter methylation analysis and loss of heterozygosis (LOH) analysis at (3p25) locus. Data obtained were correlated with VHL and HIF-1α protein expression and with tumor-specific survival (TSS). VHL mutations, methylation status, and LOH were detected in 51, 11, and 12% of cases, respectively. Our results support the association between biallelic alterations and/or VHL silencing with a worse TSS. Moreover, we found a significant association between the HIF-1α C1772C genotype and a worse TSS. The same association was found when testing the presence of HIF-1α protein in the nucleus. Our results highlight the role of VHL/HIF-1α pathway in RCC and support the molecular heterogeneity of early-stage ccRCC. More important, we show the involvement of HIF-1α C1772T SNP in ccRCC progression.

  20. Familial Renal Cancer: Molecular Genetics and Surgical Management

    Directory of Open Access Journals (Sweden)

    Glen W. Barrisford

    2011-01-01

    Full Text Available Familial renal cancer (FRC is a heterogeneous disorder comprised of a variety of subtypes. Each subtype is known to have unique histologic features, genetic alterations, and response to therapy. Through the study of families affected by hereditary forms of kidney cancer, insights into the genetic basis of this disease have been identified. This has resulted in the elucidation of a number of kidney cancer gene pathways. Study of these pathways has led to the development of novel targeted molecular treatments for patients affected by systemic disease. As a result, the treatments for families affected by von Hippel-Lindau (VHL, hereditary papillary renal carcinoma (HPRC, hereditary leiomyomatosis renal cell carcinoma (HLRCC, and Birt-Hogg-Dubé (BHD are rapidly changing. We review the genetics and contemporary surgical management of familial forms of kidney cancer.

  1. Chronic illness and family: impact of schizophrenia and Crohn's disease on the family quality of life.

    Science.gov (United States)

    Loga, Slobodan; Sošić, Bojan; Kulenović, Alma Džubur; Svraka, Emira; Bosankić, Nina; Kučukalić, Abdulah; Cemalović, Omer; Hadžić, Alma

    2012-12-01

    Quality of life assessments are increasingly present in health research. Chronic and progressive illness of a family member unavoidably affects quality of life of a family as a whole. The goals of this study were to gain insight into the family burden of chronic disorders, especially possible differences in family quality of life (FQOL) in families that have members suffering from either schizophrenia or Crohn's disease, and families in which none of the members have chronic somatic or mental illness, as well as to pilot an instrument for this purpose. The sample consisted of 53 families with a member suffering from schizophrenia, 50 families with a member suffering from Crohn's disease, and 45 families with no identifiable chronic illnesses. An informant from each family underwent a structured face to face interview, using a questionnaire specially adapted from Family Quality of Life Survey, an instrument widely used to assess FQOL in families with members with disabilities, and which addresses nine areas of family life. In the domain of health, both groups of families with chronic illnesses believe they have significantly different conditions when compared to members of the Control group. In the Crohn's disease group, families had a great deal more of challenges in accessing healthcare services; and see themselves at a disadvantage when compared to both other groups in the domain of finances. Control group offered lowest rating in the domain of support from others. Overall measures of FQOL show significant variation among the three groups, Crohn's disease group offering lowest ratings, followed by families of mental health service users. Overall, FQOL seems to be lower in families that have members diagnosed with Crohn's disease than in families with members suffering from schizophrenia. Illness-specific studies are required, as well as instruments with stronger psychometric properties and studies of determinants of FQOL. Qualitative approach should be emphasised

  2. Familial graves' disease among three black africa families, case ...

    African Journals Online (AJOL)

    In the African setting with improvement in iodine supplementation by iodization of salt and drinking water; Graves disease may become more prominent as the main aetiology of thyrotoxicosis as toxic nodular goitre used to rank side by side in the causation of thyrotoxicosis. A report of Graves disease is being made among ...

  3. Family history assessment: impact on disease risk perceptions.

    Science.gov (United States)

    Wang, Catharine; Sen, Ananda; Ruffin, Mack T; Nease, Donald E; Gramling, Robert; Acheson, Louise S; O'Neill, Suzanne M; Rubinstein, Wendy S

    2012-10-01

    Family Healthware™, a tool developed by the CDC, is a self-administered web-based family history tool that assesses familial risk for six diseases (coronary heart disease; stroke; diabetes; and colon, breast, and ovarian cancers) and provides personalized prevention messages based on risk. The Family Healthware Impact Trial (FHITr) set out to examine the clinical utility of presenting personalized preventive messages tailored to family history risk for improving health behaviors. The purpose of this study was to examine the impact of Family Healthware on modifying disease risk perceptions, particularly among those who initially underestimated their risk for certain diseases. A total of 3786 patients were enrolled in a cluster-randomized trial to evaluate the clinical utility of Family Healthware. Participants were recruited from 41 primary care practices among 13 states between 2005 and 2007. Perceived risk for each disease was assessed at baseline and 6-month follow-up using a single-item comparative risk question. Analyses were completed in March 2012. Compared to controls, Family Healthware increased risk perceptions among those who underestimated their risk for heart disease (15% vs 9%, prisk perceptions. Family Healthware was effective at increasing disease risk perceptions, particularly for metabolic conditions, among those who underestimated their risk. Results from this study also demonstrate the relatively resistant nature of risk perceptions. This study is registered at clinicaltrials.govNCT00164658. Copyright © 2012 American Journal of Preventive Medicine. All rights reserved.

  4. Dock protein family in brain development and neurological disease.

    Science.gov (United States)

    Shi, Lei

    2013-11-01

    The family of dedicator of cytokinesis (Dock), a protein family that belongs to the atypical Rho guanine nucleotide exchange factors (GEFs) for Rac and/or Cdc42 GTPases, plays pivotal roles in various processes of brain development. To date, 11 members of Docks have been identified in the mammalian system. Emerging evidence has suggested that members of the Dock family are associated with several neurodegenerative and neuropsychiatric diseases, including Alzheimer disease and autism spectrum disorders. This review summarizes recent advances on the understanding of the roles of the Dock protein family in normal and diseased processes in the nervous system. Furthermore, interacting proteins and the molecular regulation of Docks are discussed.

  5. A familial concurrence of schizophrenia and Gaucher's disease

    Directory of Open Access Journals (Sweden)

    Siomos Konstantinos E

    2007-12-01

    Full Text Available Abstract Background Gaucher's disease (GD is the most frequently encountered lysosomal storage disease. Here, we describe and discuss the observed concurrence of schizophrenia and Gaucher's disease in two siblings. Methods Presentation of a family with two siblings with Gaucher's disease. Results In a six-member family, the first son suffers from schizophrenia, while the third and fourth sons suffer from the Gaucher's disease (type 1 non-neuronopathic. The parents and the second son do not suffer from either illness. Conclusion The concurrence of schizophrenia and Gaucher's disease in the same family is an unusual phenomenon. The literature regarding this coincidence is limited, despite the fact that patients with Gaucher's disease have one or two mutated alleles, considered to be a risk factor leading to conditions such as Dementia, Parkinson's disease and schizophrenia.

  6. Childhood interstitial lung disease: family experiences

    OpenAIRE

    Gilbert, C.; Bush, A; Cunningham, S.

    2015-01-01

    Aims: To present experiences of UK families of children diagnosed with ILD, to inform clinical practice and service development. Methods: Thirty seven such families completed an anonymous web-based survey between February and March 2014. Results: Median time from first symptoms to diagnosis was 25 weeks. Most reported that they were happy with the overall management of their child. Areas highlighted for development included improved communication especially the need for written information; p...

  7. Heritability and familial aggregation of diverticular disease

    DEFF Research Database (Denmark)

    Strate, Lisa L; Erichsen, Rune; Baron, John A

    2013-01-01

    Little is known about the role of heritable factors in diverticular disease. We evaluated the contribution of heritable factors to the development of diverticular disease diagnosed at a hospitalization or outpatient visit.......Little is known about the role of heritable factors in diverticular disease. We evaluated the contribution of heritable factors to the development of diverticular disease diagnosed at a hospitalization or outpatient visit....

  8. Coeliac disease | Badenhorst | South African Family Practice

    African Journals Online (AJOL)

    Coeliac disease is an autoimmune enteropathy triggered by the ingestion of gluten-containing cereals, such as wheat, rye and barley. It is estimated to occur in one per cent of people of European ancestry, and in 0.3% of black Africans. Coeliac disease has a strong genetic component as nearly all patients with the disease ...

  9. Development of synchronous VHL syndrome tumors reveals contingencies and constraints to tumor evolution

    DEFF Research Database (Denmark)

    Fisher, Rosalie; Horswell, Stuart; Rowan, Andrew

    2014-01-01

    with a germline VHL mutation. We report that tumors arising in this context are clonally independent and harbour distinct secondary events exemplified by loss of chromosome 3p, despite an identical genetic background and tissue microenvironment. We propose that divergent mutational and copy number anomalies......Background : Genomic analysis of multi-focal renal cell carcinomas from an individual with a germline VHL mutation offers a unique opportunity to study tumor evolution. Results : We perform whole exome sequencing on four clear cell renal cell carcinomas removed from both kidneys of a patient...... are contingent upon the nature of 3p loss of heterozygosity occurring early in tumorigenesis. However, despite distinct 3p events, genomic, proteomic and immunohistochemical analyses reveal evidence for convergence upon the PI3K-AKT-mTOR signaling pathway. Four germline tumors in this young patient...

  10. Chemokine receptor CXCR4 downregulated by von Hippel-Lindau tumour suppressor pVHL

    DEFF Research Database (Denmark)

    Staller, Peter; Sulitkova, Jitka; Lisztwan, Joanna

    2003-01-01

    Organ-specific metastasis is governed, in part, by interactions between chemokine receptors on cancer cells and matching chemokines in target organs. For example, malignant breast cancer cells express the chemokine receptor CXCR4 and commonly metastasize to organs that are an abundant source...... regulates CXCR4 expression owing to its capacity to target hypoxia-inducible factor (HIF) for degradation under normoxic conditions. This process is suppressed under hypoxic conditions, resulting in HIF-dependent CXCR4 activation. An analysis of clear cell renal carcinoma that manifests mutation of the VHL...... gene in most cases revealed an association of strong CXCR4 expression with poor tumour-specific survival. These results suggest a mechanism for CXCR4 activation during tumour cell evolution and imply that VHL inactivation acquired by incipient tumour cells early in tumorigenesis confers not only...

  11. Celiac is a social disease: family challenges and strategies.

    Science.gov (United States)

    Bacigalupe, Gonzalo; Plocha, Aleksandra

    2015-03-01

    Celiac disease is the most common autoimmune inherited disorder in the United States, affecting approximately 1% of the population. Little research exists on the impact of family processes on adherence to a gluten-free diet (GFD), the only treatment for celiac disease. The objective of this qualitative study was to examine the barriers that families with a celiac child face and the strategies they use to adhere to the recommended diet. In-depth interviews were conducted with 10 families with a child between the ages of 6 and 12 diagnosed with celiac disease. Grounded theory and narrative analysis were used to analyze interview transcripts. Social isolation and misunderstandings about celiac disease and the GFD emerged as the most significant barriers to diet adherence including the reproduction of traditional gender relations among parents. Diet adherence facilitators included various types of institutional and societal support and idiosyncratic family arrangements. Successful diet adherence strategies used by families included planning ahead and taking their own food to social functions. Family processes play a critical role in GFD adherence. Implications for health care clinicians working with families with a child with celiac disease are discussed. (PsycINFO Database Record (c) 2015 APA, all rights reserved).

  12. Familial risk assessment for early-onset coronary heart disease.

    Science.gov (United States)

    Scheuner, Maren T; Whitworth, William C; McGruder, Henraya; Yoon, Paula W; Khoury, Muin J

    2006-08-01

    We examined the performance of a familial risk assessment method that stratifies risk for early-onset coronary heart disease by considering the number of relatives with coronary disease, degree of relationship, lineage, and age at diagnosis. By using data from the HealthStyles 2003 survey, we assessed the associations between familial risk and early-onset coronary heart disease, diabetes, hypercholesterolemia, hypertension, and obesity. By using area under the curve statistics, we evaluated the discriminatory ability of various risk assessment models. Of 4,035 respondents, 60% were female and 72% were white, with a mean age of 48.8 years. After adjustment for demographics, strong and moderate risk were significantly associated with approximately a five- and twofold risk of early-onset coronary disease, respectively. After adjustment for demographics and personal history of cardiovascular disease, strong familial risk was also significantly associated with diabetes, hypercholesterolemia, hypertension, and obesity. A risk assessment model that included familial risk, demographics, and personal history of diabetes, hypercholesterolemia, hypertension, and obesity was most optimal with an area under the curve statistic of 87.2% Familial risk assessment can stratify risk for early-onset coronary heart disease. Several conditions associated with increased familial risk can be prevented. These results have important implications for risk assessment and risk-reducing interventions.

  13. VHL negatively regulates SARS coronavirus replication by modulating nsp16 ubiquitination and stability.

    Science.gov (United States)

    Yu, Xiao; Chen, Shuliang; Hou, Panpan; Wang, Min; Chen, Yu; Guo, Deyin

    2015-04-03

    Eukaryotic cellular and most viral RNAs carry a 5'-terminal cap structure, a 5'-5' triphosphate linkage between the 5' end of the RNA and a guanosine nucleotide (cap-0). SARS coronavirus (SARS-CoV) nonstructural protein nsp16 functions as a methyltransferase, to methylate mRNA cap-0 structure at the ribose 2'-O position of the first nucleotide to form cap-1 structures. However, whether there is interplay between nsp16 and host proteins was not yet clear. In this report, we identified several potential cellular nsp16-interacting proteins from a human thymus cDNA library by yeast two-hybrid screening. VHL, one of these proteins, was proven to interact with nsp16 both in vitro and in vivo. Further studies showed that VHL can inhibit SARS-CoV replication by regulating nsp16 ubiquitination and promoting its degradation. Our results have revealed the role of cellular VHL in the regulation of SARS-CoV replication. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Vhl deletion in osteoblasts boosts cellular glycolysis and improves global glucose metabolism.

    Science.gov (United States)

    Dirckx, Naomi; Tower, Robert J; Mercken, Evi M; Vangoitsenhoven, Roman; Moreau-Triby, Caroline; Breugelmans, Tom; Nefyodova, Elena; Cardoen, Ruben; Mathieu, Chantal; Van der Schueren, Bart; Confavreux, Cyrille B; Clemens, Thomas L; Maes, Christa

    2018-02-12

    The skeleton has emerged as an important regulator of systemic glucose homeostasis, with osteocalcin and insulin representing prime mediators of the interplay between bone and energy metabolism. However, genetic evidence indicates that osteoblasts can influence global energy metabolism through additional, as yet unknown, mechanisms. Here, we report that constitutive or postnatally induced deletion of the hypoxia signaling pathway component von Hippel-Lindau (VHL) in skeletal osteolineage cells of mice led to high bone mass as well as hypoglycemia and increased glucose tolerance, not accounted for by osteocalcin or insulin. In vitro and in vivo data indicated that Vhl-deficient osteoblasts displayed massively increased glucose uptake and glycolysis associated with upregulated HIF-target gene expression, resembling the Warburg effect that typifies cancer cells. Overall, the glucose consumption by the skeleton was increased in the mutant mice, as revealed by 18F-FDG radioactive tracer experiments. Moreover, the glycemia levels correlated inversely with the level of skeletal glucose uptake, and pharmacological treatment with the glycolysis inhibitor dichloroacetate (DCA), which restored glucose metabolism in Vhl-deficient osteogenic cells in vitro, prevented the development of the systemic metabolic phenotype in the mutant mice. Altogether, these findings reveal a novel link between cellular glucose metabolism in osteoblasts and whole-body glucose homeostasis, controlled by local hypoxia signaling in the skeleton.

  15. Elevated homocysteine, glutathione and cysteinylglycine concentrations in patients homozygous for the Chuvash polycythemia VHL mutation

    Science.gov (United States)

    Sergueeva, Adelina I.; Miasnikova, Galina Y.; Okhotin, Daniel J.; Levina, Alla A.; Debebe, Zufan; Ammosova, Tatiana; Niu, Xiaomei; Romanova, Elena A.; Nekhai, Sergei; DiBello, Patricia M.; Jacobsen, Donald W.; Prchal, Josef T.; Gordeuk, Victor R.

    2010-01-01

    In Chuvash polycythemia, homozygous von Hippel-Lindau (VHL) 598C>T leads to increased hypoxia inducible factor-1α and 2α, thromboses and lower systemic blood pressures. Circulating homocysteine, glutathione, γ-glutamyltransferase and cysteinylglycine concentrations were higher in 34 VHL598C>T homozygotes than in 37 normal controls and cysteine was lower. Multivariate analysis showed elevated homocysteine independently associated with higher mean systemic blood pressures and elevated glutathione was associated with lower pressures to a similar degree. Among VHL598C>T homozygotes, homocysteine was elevated with low and normal folate concentrations, consistent with a possible defect in the remethylation pathway. The elevated glutathione and γ-glutamyltranserase levels correlated positively with cysteinylglycine, consistent with possible upregulation of a glutathione synthetic enzyme and γ-glutamyltransferase. Cysteinylglycine correlated inversely with cysteine, consistent with possible reduced cysteinyldipeptidase activity. We conclude that up-regulated hypoxia-sensing may influence multiple steps in thiol metabolism. The effects of the resultant elevated levels of homocysteine and glutathione on systemic blood pressure may largely balance each other out. PMID:18223282

  16. Crystal Structure of the Cul2-Rbx1-EloBC-VHL Ubiquitin Ligase Complex.

    Science.gov (United States)

    Cardote, Teresa A F; Gadd, Morgan S; Ciulli, Alessio

    2017-06-06

    Cullin RING E3 ubiquitin ligases (CRLs) function in the ubiquitin proteasome system to catalyze the transfer of ubiquitin from E2 conjugating enzymes to specific substrate proteins. CRLs are large dynamic complexes and attractive drug targets for the development of small-molecule inhibitors and chemical inducers of protein degradation. The atomic details of whole CRL assembly and interactions that dictate subunit specificity remain elusive. Here we present the crystal structure of a pentameric CRL2VHL complex, composed of Cul2, Rbx1, Elongin B, Elongin C, and pVHL. The structure traps a closed state of full-length Cul2 and a new pose of Rbx1 in a trajectory from closed to open conformation. We characterize hotspots and binding thermodynamics at the interface between Cul2 and pVHL-EloBC and identify mutations that contribute toward a selectivity switch for Cul2 versus Cul5 recognition. Our findings provide structural and biophysical insights into the whole Cul2 complex that could aid future drug targeting. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  17. Characterization of endolymphatic sac tumors and von Hippel-Lindau disease in the International Endolymphatic Sac Tumor Registry

    NARCIS (Netherlands)

    Bausch, Birke; Wellner, Ulrich; Peyre, Mathieu; Boedeker, Carsten C.; Hes, Frederik J.; Anglani, Mariagiulia; de Campos, Jose M.; Kanno, Hiroshi; Maher, Eamonn R.; Krauss, Tobias; Sanso, Gabriela; Barontini, Marta; Letizia, Claudio; Hader, Claudia; Schiavi, Francesca; Zanoletti, Elisabetta; Suarez, Carlos; Offergeld, Christian; Malinoc, Angelica; Zschiedrich, Stefan; Glasker, Sven; Bobin, Serge; Sterkers, Olivier; Huy, Patrice Tran Ba; Giraud, Sophie; Links, Thera; Eng, Charis; Opocher, Giuseppe; Richard, Stephane; Neumann, Hartmut P. H.

    Background. Endolymphatic sac tumors (ELSTs) are, with a prevalence of up to 16%, a component of von Hippel-Lindau (VHL) disease. Data from international registries regarding heritable fraction and characteristics, germline VHL mutation frequency, and prevalence are lacking. Methods. Systematic

  18. BEHСET'S DISEASE: ETHNOS AND FAMILIAL AGGREGATION

    Directory of Open Access Journals (Sweden)

    Z. S. Alekberova

    2016-01-01

    Full Text Available Familial aggregation (repeated cases of the disease in the families of probands is considered as an argument in favor of the genetic nature of Behсet's disease (BD. The results of a survey of 180 patients with BD in three ethnic groups indicated that there were repeated cases of recurrent aphthous stomatitis (RAS in 54 (30% families: more commonly among Dagestanis (n =32, less commonly in Chechens (n = 12 and Russians (10. Thus, the relatives of the RAS proband should be included in a group at risk for BD.

  19. Family caregivers' views on coordination of care in Huntington's disease

    DEFF Research Database (Denmark)

    Røthing, Merete; Malterud, Kirsti; Frich, Jan C

    2015-01-01

    's illness may be unpredictable or not well understood by some of those involved in the treatment and care. AIM: The aim of this study was to explore the experiences and expectations of family caregivers for persons with Huntington's disease concerning collaboration with healthcare professionals. METHODS......: To shed light on collaboration from the perspectives of family caregivers, we conducted an explorative, qualitative interview study with 15 adult participants experienced from caring for family members in all stages of Huntington's disease. Data were analysed with systematic text condensation, a cross...

  20. Lifestyle, family history, and risk of idiopathic Parkinson disease

    DEFF Research Database (Denmark)

    Kenborg, Line; Lassen, Christina F.; Ritz, Beate

    2015-01-01

    The relationship between Parkinson disease (PD) and smoking has been examined in several studies, but little is known about smoking in conjunction with other behaviors and a family history of PD. Using unconditional logistic regression analysis, we studied individual and joint associations...... with smoking, the odds ratios were lower than those for each one alone. Compared with never smokers with no family history of PD, never smokers who did have a family history had an odds ratio of 2.81 (95% confidence interval: 1.91, 4.13); for smokers with a family history, the odds ratio was 1.60 (95...

  1. Prevalence of Chronic Kidney Disease in a Nigerian Family Practice ...

    African Journals Online (AJOL)

    Background: Chronic kidney disease (CKD) is a global public health problem, with a greater burden and prohibitive cost of care particularly in developing countries. This study determined the prevalence of chronic kidney disease and identified its associated risk factors in patients attending the Family Practice Clinic, Wesley ...

  2. Type 2 Gaucher's disease in a Malian family

    African Journals Online (AJOL)

    Summary. Gaucher's disease is a recessive autosomal disorder caused by an inherited. deficiency of betaglucocerebrosidase. We report here the case of an 8 month old child, fourth in a family of four children, who presents the neuropathic form of the disease. The dosages of betaglucosidase activity using C14 techniques ...

  3. Wolman disease in patients with familial hemophagocytic ...

    African Journals Online (AJOL)

    Solaf Elsayed

    2015-09-26

    Sep 26, 2015 ... The pregnancy was uncomplicated and he was deliv- ered by CS with a birth weight of 3.5 kg. His condition started at the age of 2.5 months when the ... Wolman disease, severe anemia and thrombocytopenia, increased ferritin and both foamy histiocytes and hemophago- cytic cells in bone marrow [8].

  4. [Update in family medicine: Periodontal disease].

    Science.gov (United States)

    López Silva, M C; Diz-Iglesias, P; Seoane-Romero, J M; Quintas, V; Méndez-Brea, F; Varela-Centelles, P

    2017-03-01

    About 85-94% of the Spanish adults older than 35 experience gum problems, and about 15-30% suffer from periodontitis, being severe in up to 5-11% of them. Unlike other inflammatory conditions, periodontal disease rarely causes discomfort, or limits life or causes functional limitations until its advanced stages, when clinical signs and symptoms arise (gingival recession, pathological teeth migration, or mobility). Lack of knowledge about the disease, together with the idea that tooth loss is linked to ageing, frequently results in a late diagnosis, requiring extensive treatments with a worse prognosis. At Primary Care level, there is series of drugs have been related to periodontal disease (anticonvulsants, immunosuppressive drugs, and calcium channel blockers) as secondary effects, which vary as regards their frequency and severity depending of the amount of accumulated plaque. Stress and depression have also been reported to alter the immune response and to increase the inflammatory response as well as periodontal susceptibility. Certain systemic conditions, such as diabetes mellitus, cardiovascular disorders, respiratory diseases, as well as low-weight pre-term birth, have also been linked to periodontitis. Copyright © 2016 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.

  5. Interdisciplinary psychosocial care for families with inherited cardiovascular diseases.

    Science.gov (United States)

    Caleshu, Colleen; Kasparian, Nadine A; Edwards, Katharine S; Yeates, Laura; Semsarian, Christopher; Perez, Marco; Ashley, Euan; Turner, Christian J; Knowles, Joshua W; Ingles, Jodie

    2016-10-01

    Inherited cardiovascular diseases pose unique and complex psychosocial challenges for families, including coming to terms with life-long cardiac disease, risk of sudden death, grief related to the sudden death of a loved one, activity restrictions, and inheritance risk to other family members. Psychosocial factors impact not only mental health but also physical health and cooperation with clinical recommendations. We describe an interdisciplinary approach to the care of families with inherited cardiovascular disease, in which psychological care provided by specialized cardiac genetic counselors, nurses, and psychologists is embedded within the cardiovascular care team. We report illustrative cases and the supporting literature to demonstrate common scenarios, as well as practical guidance for clinicians working in the inherited cardiovascular disease setting. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Familial periodontal disease in the Cayo Santiago rhesus macaques.

    Science.gov (United States)

    Gonzalez, Octavio A; Orraca, Luis; Kensler, Terry B; Gonzalez-Martinez, Janis; Maldonado, Elizabeth; Ebersole, Jeffrey L

    2016-01-01

    Substantial ongoing research continues to explore the contribution of genetics and environment to the onset, extent and severity of periodontal disease(s). Existing evidence supports that periodontal disease appears to have an increased prevalence in family units with a member having aggressive periodontitis. We have been using the nonhuman primate as a model of periodontal disease for over 25 years with these species demonstrating naturally occurring periodontal disease that increases with age. This report details our findings from evaluation of periodontal disease in skulls from 97 animals (5-31 years of age) derived from the skeletons of the rhesus monkeys (Macaca mulatta) on Cayo Santiago. Periodontal disease was evaluated by determining the distance from the base of the alveolar bone defect to the cemento-enamel junction on 1st/2nd premolars and 1st/2nd molars from all four quadrants. The results demonstrated an increasing extent and severity of periodontitis with aging across the population of animals beyond only compensatory eruption. Importantly, irrespective of age, extensive heterogeneity in disease expression was observed among the animals. Linking these variations to multi-generational matriarchal family units supported familial susceptibility of periodontitis. As the current generations of animals that are descendants from these matrilines are alive, studies can be conducted to explore an array of underlying factors that could account for susceptibility or resistance to periodontal disease. © 2016 Wiley Periodicals, Inc.

  7. Exploring family communication about sickle cell disease in adolescence.

    Science.gov (United States)

    Graff, J Carolyn; Hankins, Jane; Graves, Rebecca J; Robitaille, Kimberly Y; Roberts, Ruth; Cejda, Katherine; Hardy, Belinda T; Johnson, Margery; Porter, Jerlym S

    2012-01-01

    Sickle cell disease (SCD) is a lifelong disorder that involves progressive organ damage and requires ongoing medical attention to prevent and treat episodic acute complications. Children with SCD need ongoing monitoring and extra attention that may be stressful to family members. Communication within families can help resolve family stress and may be associated with medical follow-up and management of SCD. Focus groups were conducted with 12 African American families to explore the communication that occurred within and outside of the family from the perspectives of adolescents with SCD, siblings, and parents. Factors that influence family communication were explored. The extended family was an important social network and resource to adolescents, siblings, and parents. Family member knowledge of SCD was an important factor that influenced communication about SCD; adolescents and parents communicated more easily than siblings and also reported having more knowledge of SCD than siblings. Future research focusing on the knowledge of immediate and extended family members and their recognition of their contribution to the child with SCD is recommended.

  8. Building resilience in families with pediatric chronic diseases

    Directory of Open Access Journals (Sweden)

    Claudia Grau Rubio

    2013-07-01

    Full Text Available This article describes the different approaches that can be applied to the study of the concept of family resilience in the context of pediatric disease and their implications for clinical practice and education. It also describes the general principles that should govern this practice and the specific activities of the professional of health systems, educational and social. The resilience is essential to maintain a good quality of life of the sick and the family as a whole.

  9. Examination of Huntington's disease in a Chinese family.

    Science.gov (United States)

    Yu, Mingxia; Li, Xiaogai; Wu, Sanyun; Shen, Ji; Tu, Jiancheng

    2014-02-15

    We report brain imaging and genetic diagnosis in a family from Wuhan, China, with a history of Huntington's disease. Among 17 family members across three generations, four patients (II2, II6, III5, and III9) show typical Huntington's disease, involuntary dance-like movements. Magnetic resonance imaging found lateral ventricular atrophy in three members (II2, II6, and III5). Moreover, genetic analysis identified abnormally amplified CAG sequence repeats (> 40) in two members (III5 and III9). Among borderline cases, with clinical symptoms and brain imaging features of Huntington's disease, two cases were identified (II2 and II6), but shown by mutation analysis for CAG expansions in the important transcript 15 gene, to be non-Huntington's disease. Our findings suggest that clinical diagnosis of Huntington's disease requires a combination of clinical symptoms, radiological changes, and genetic diagnosis.

  10. Association of Familial Mediterranean Fever and Crohn’s disease

    Directory of Open Access Journals (Sweden)

    Gökhan Tümgör

    2013-01-01

    Full Text Available Familial Mediterranean fever is an autosomal recessive,short, acute, self-limiting disease characterized by attacksof fever and polyserositis, which is common in countriesaround the Mediterranean. Inflammatory bowel diseaseis a term used to describe Ulcerative colitis and Crohn’sdisease that associated with chronic idiopathic inflammatory.The patient had FMF but she had been well untilapproximately 20 days before admission, when malaise,fever, abdominal pain, right knee and ankle edema developed.She was taking colchicine. The patient diagnosedas Crohn Disease by endoscopy and histopathology. Thiscase report is presented to emphasize the association oftwo diseases.Key words: Familial Mediterranean Fever, inflammatorybowel disease, Crohn’s disease, childhood

  11. Balancing needs as a family caregiver in Huntington's disease

    DEFF Research Database (Denmark)

    Røthing, Merete; Malterud, Kirsti; Frich, Jan C.

    2015-01-01

    Family members in families with severe chronic disease play importantroles in care-giving. In families affected by Huntington’s disease (HD), caregivers encounter practical and emotional challenges and distress.Enduring caregiver burdens may lead to problems and caregivers are inneed of social...... support and health services to deal with challenges. Wewanted to explore coping strategies and behaviour patterns used byfamily caregivers to care for themselves, while caring for a familymember with HD. Participants were recruited from hospitals andcommunity-based healthcare. The sample represents...... various coping strategies, adjusted to the stage and progression ofHD. They tried to regulate information about the disease, balancingconsiderations for protection and disclosure, within and outside thefamily. The participants made efforts to maintain a balance between theirown needs in everyday life...

  12. Familial associations of lymphoma and myeloma with autoimmune diseases

    OpenAIRE

    Hemminki, K; F?rsti, A; Sundquist, K.; Sundquist, J.; Li, X

    2017-01-01

    Many B-cell neoplasms are associated with autoimmune diseases (AIDs) but most evidence is based on a personal rather than a family history of AIDs. Here we calculated risks for non-Hodgkin lymphoma (NHL), Hodgkin lymphoma (HL) and multiple myeloma (MM) when family members were diagnosed with any of 44 different AIDs, or, independently, risk for AIDs when family members were diagnosed with a neoplasm. A total of 64?418 neoplasms and 531?155 AIDs were identified from Swedish nationwide health c...

  13. Aluminium in brain tissue in familial Alzheimer's disease.

    Science.gov (United States)

    Mirza, Ambreen; King, Andrew; Troakes, Claire; Exley, Christopher

    2017-03-01

    The genetic predispositions which describe a diagnosis of familial Alzheimer's disease can be considered as cornerstones of the amyloid cascade hypothesis. Essentially they place the expression and metabolism of the amyloid precursor protein as the main tenet of disease aetiology. However, we do not know the cause of Alzheimer's disease and environmental factors may yet be shown to contribute towards its onset and progression. One such environmental factor is human exposure to aluminium and aluminium has been shown to be present in brain tissue in sporadic Alzheimer's disease. We have made the first ever measurements of aluminium in brain tissue from 12 donors diagnosed with familial Alzheimer's disease. The concentrations of aluminium were extremely high, for example, there were values in excess of 10μg/g tissue dry wt. in 5 of the 12 individuals. Overall, the concentrations were higher than all previous measurements of brain aluminium except cases of known aluminium-induced encephalopathy. We have supported our quantitative analyses using a novel method of aluminium-selective fluorescence microscopy to visualise aluminium in all lobes of every brain investigated. The unique quantitative data and the stunning images of aluminium in familial Alzheimer's disease brain tissue raise the spectre of aluminium's role in this devastating disease. Copyright © 2016 The Authors. Published by Elsevier GmbH.. All rights reserved.

  14. pVHL co-ordinately regulates CXCR4/CXCL12 and MMP2/MMP9 expression in human clear-cell renal cell carcinoma

    DEFF Research Database (Denmark)

    Struckmann, K; Mertz, Kd; Steu, S

    2008-01-01

    Loss of pVHL function, characteristic for clear-cell renal cell carcinoma (ccRCC), causes increased expression of CXCR4 chemokine receptor, which triggers expression of metastasis-associated MMP2/MMP9 in different human cancers. The impact of pVHL on MMP2/MMP9 expression and their relationship...

  15. Familial occurrence of systemic mast cell activation disease.

    Directory of Open Access Journals (Sweden)

    Gerhard J Molderings

    Full Text Available Systemic mast cell activation disease (MCAD comprises disorders characterized by an enhanced release of mast cell mediators accompanied by accumulation of dysfunctional mast cells. Demonstration of familial clustering would be an important step towards defining the genetic contribution to the risk of systemic MCAD. The present study aimed to quantify familial aggregation for MCAD and to investigate the variability of clinical and molecular findings (e.g. somatic mutations in KIT among affected family members in three selected pedigrees. Our data suggest that systemic MCAD pedigrees include more systemic MCAD cases than would be expected by chance, i.e., compared with the prevalence of MCAD in the general population. The prevalence of MCAD suspected by symptom self-report in first-degree relatives of patients with MCAD amounted to approximately 46%, compared to prevalence in the general German population of about 17% (p<0.0001. In three families with a high familial loading of MCAD, the subtype of MCAD and the severity of mediator-related symptoms varied between family members. In addition, genetic alterations detected in KIT were variable, and included mutations at position 816 of the amino acid sequence. In conclusion, our data provide evidence for common familial occurrence of MCAD. Our findings observed in the three pedigrees together with recent reports in the literature suggest that, in familial cases (i.e., in the majority of MCAD, mutated disease-related operator and/or regulator genes could be responsible for the development of somatic mutations in KIT and other proteins important for the regulation of mast cell activity. Accordingly, the immunohistochemically different subtypes of MCAD (i.e. mast cell activation syndrome and systemic mastocytosis should be more accurately regarded as varying presentations of a common generic root process of mast cell dysfunction, than as distinct diseases.

  16. Vhl deletion in renal epithelia causes HIF-1?-dependent, HIF-2?-independent angiogenesis and constitutive diuresis

    OpenAIRE

    Schönenberger, Désirée; Rajski, Michal; Harlander, Sabine; Frew, Ian J

    2016-01-01

    One of the earliest requirements for the formation of a solid tumor is the establishment of an adequate blood supply. Clear cell renal cell carcinomas (ccRCC) are highly vascularized tumors in which the earliest genetic event is most commonly the biallelic inactivation of the VHL tumor suppressor gene, leading to constitutive activation of the HIF-1α and HIF-2α transcription factors, which are known angiogenic factors. However it remains unclear whether either or both HIF-1α or HIF-2α stabili...

  17. The homozygous VHL(D126N) missense mutation is associated with dramatically elevated erythropoietin levels, consequent polycythemia, and early onset severe pulmonary hypertension.

    Science.gov (United States)

    Sarangi, Susmita; Lanikova, Lucie; Kapralova, Katarina; Acharya, Suchitra; Swierczek, Sabina; Lipton, Jeffrey M; Wolfe, Lawrence; Prchal, Josef T

    2014-11-01

    von Hippel-Lindau (VHL) protein is the principal negative regulator of hypoxia sensing mediated by transcription factors. Mutations in exon 3 of the VHL gene lead to Chuvash (VHL(R200W)) and Croatian (VHL(H191D)) polycythemias. Here, we describe an infant of Bangladesh ethnicity with a novel homozygous VHL(D126N) mutation with congenital polycythemia and dramatically elevated erythropoietin (EPO) levels, who developed severe fatal pulmonary hypertension. In contrast to Chuvash polycythemia, erythroid progenitors (BFU-Es) did not reveal a marked EPO hypersensitivity. Further, NF-E2 and RUNX1 transcripts that correlate with BFU-Es EPO hypersensitivity in polycythemic mutations were not elevated. © 2014 Wiley Periodicals, Inc.

  18. Familial Hemophagocytic Lymphohistiocytosis Type 3 with Demyelinating CNS Disease

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2009-02-01

    Full Text Available A case of familial hemophagocytic lymphohistiocytosis type 3 (FHLH3 presenting in a 3-year-old boy with fulminant demyelinating neurological disease is reported by researchers at Kravis Children’s Hospital at Mount Sinai Medical Center, New York.

  19. Schizophrenia as a Brain Disease: Implications for Psychologists and Families.

    Science.gov (United States)

    Johnson, Dale L.

    1989-01-01

    The belief that schizophrenia is a brain disease is the consensus among families of persons with mental illness and is supported by the National Alliance for the Mentally Ill. This article summarizes implications for psychologists from the following standpoints: (1) etiology; (2) vulnerability; (3) treatment; (4) rehabilitation; (5) assessment;…

  20. Microtubular stability affects pVHL-mediated regulation of HIF-1alpha via the p38/MAPK pathway in hypoxic cardiomyocytes.

    Directory of Open Access Journals (Sweden)

    Miao Teng

    Full Text Available BACKGROUND: Our previous research found that structural changes of the microtubule network influence glycolysis in cardiomyocytes by regulating the hypoxia-inducible factor (HIF-1α during the early stages of hypoxia. However, little is known about the underlying regulatory mechanism of the changes of HIF-1α caused by microtubule network alternation. The von Hippel-Lindau tumor suppressor protein (pVHL, as a ubiquitin ligase, is best understood as a negative regulator of HIF-1α. METHODOLOGY/PRINCIPAL FINDINGS: In primary rat cardiomyocytes and H9c2 cardiac cells, microtubule-stabilization was achieved by pretreating with paclitaxel or transfection of microtubule-associated protein 4 (MAP4 overexpression plasmids and microtubule-depolymerization was achieved by pretreating with colchicine or transfection of MAP4 siRNA before hypoxia treatment. Recombinant adenovirus vectors for overexpressing pVHL or silencing of pVHL expression were constructed and transfected in primary rat cardiomyocytes and H9c2 cells. With different microtubule-stabilizing and -depolymerizing treaments, we demonstrated that the protein levels of HIF-1α were down-regulated through overexpression of pVHL and were up-regulated through knockdown of pVHL in hypoxic cardiomyocytes. Importantly, microtubular structure breakdown activated p38/MAPK pathway, accompanied with the upregulation of pVHL. In coincidence, we found that SB203580, a p38/MAPK inhibitor decreased pVHL while MKK6 (Glu overexpression increased pVHL in the microtubule network altered-hypoxic cardiomyocytes and H9c2 cells. CONCLUSIONS/SIGNIFICANCE: This study suggests that pVHL plays an important role in the regulation of HIF-1α caused by the changes of microtubular structure and the p38/MAPK pathway participates in the process of pVHL change following microtubule network alteration in hypoxic cardiomyocytes.

  1. Two childhood pheochromocytoma cases due to von Hippel -Lindau disease, one associated with pancreatic neuroendocrine tumor; a rare manifestation.

    Science.gov (United States)

    Dağdeviren Çakır, Aydilek; Turan, Hande; Aykut, Ayça; Durmaz, Asude; Ercan, Oya; Evliyaoğlu, Olcay

    2017-10-12

    (VHL) disease is an autosomal dominantly inherited disorder characterized by hemangioblastomas of retina and central nervous system (CNS); renal cysts, clear cell carcinoma; PCC; endolymphatic sac tumors; cystadenomas of the epididymis in males, broad ligament of uterus in females; pancreatic cysts, cystadenomas and neuroendocrine tumors. We here report two cases of VHL disease presented with PCC as the first manifestation. Hemangioblastoma of CNS in the first case and PNET in the second case developed during follow- up and led to the diagnosis of VHL disease. Genetic analyses of cases revealed p.Arg161Gln (c.482G>A) and p.Leu129Pro(c.386T>G) heterozygous missense mutation in VHL gene, respectively. In children, PCC may be the only and/or initial manifestation of the disease with delayed manifestations of the syndrome in other organs. PNET is a very rare manifestation of VHL disease. To best of our knowledge, this is the second case in literature, presenting with combination of PNET and bilateral PCC as components of childhood VHL disease. Pediatric patients diagnosed with PCC should be investigated for the genetic causes especially for VHL.

  2. Caffey disease in neonatal period: the importance of the family!

    Science.gov (United States)

    Prior, Ana Rita; Moldovan, Oana; Azevedo, António; Moniz, Carlos

    2012-10-09

    A male newborn was apparently well until his second day of life, when increased irritability and a swelling in his right leg were noted. He was rooming-in with his mother since birth. On examination, a mass on the anterior surface of the right leg was noticed. The mass was firm, elongated, ill-defined, unmovable and painful at palpation. No overlying skin changes were seen. The newborn had a family history of neonatal bone swelling with resolution before the age of 2. Subsequent images showed hyperostosis in the diaphysis of the right tibia. After exclusion of other conditions such as trauma, osteomyelitis and congenital syphilis, the involvement of the tibial diaphysis, sparing the epiphyses and the benign course of the disease in family history, were indicative of Caffey disease. The genetic study confirmed this diagnosis. Caffey disease, although rare, should not be overlooked in the diagnostic approach to childhood bone swelling.

  3. Childhood family psychosocial environment and coronary heart disease risk.

    Science.gov (United States)

    Loucks, Eric B; Almeida, Nisha D; Taylor, Shelley E; Matthews, Karen A

    2011-09-01

    Little is known about whether the childhood family psychosocial environment affects coronary heart disease (CHD). Study objectives were to evaluate associations of childhood family psychosocial environment (termed "risky families"; characterized by cold, unaffectionate interactions, conflict, aggression, neglect, and/or low nurturance) with calculated risk for CHD. Study participants included 3554 participants of the Coronary Artery Risk Development in Young Adults Study, aged 33 to 45 years. Childhood family psychosocial environment was measured using a risky family questionnaire via self-report. Ten-year CHD risk was calculated using the validated Framingham risk algorithm. In a multivariable-adjusted regression analysis adjusted for age, race/ethnicity, and childhood socioeconomic position, a 1-unit (range, 0-21) increase in risky family score was associated with 1.0% (95% confidence interval = 0.4%-1.7%) and 1.0% (95% confidence interval = 0.2%-1.8%) higher CHD risk in women and men, respectively. Multiple mediation analyses suggested significant indirect effects of education, income, depressive symptomatology, and anger-out expression in women and education in men, indicating that these may be mediating mechanisms between childhood psychosocial environment and CHD risk. Of the modifiable Framingham algorithm components, smoking (in women and men) and high-density lipoprotein (in women) were the factors most strongly associated with risky family score. Childhood family psychosocial environment was positively associated with the calculated 10-year CHD risk. Mechanisms may include the potential negative impact of childhood family psychosocial environment on later-life socioeconomic position (e.g., education in men and women) and/or psychosocial functioning (e.g., depression and anger-out expression in women), which may in turn lead to higher CHD risk, particularly through smoking (in men and women) and low level of high-density lipoprotein cholesterol (in women).

  4. Von Hippel-Lindau disease: an evaluation of natural history and functional disability

    Science.gov (United States)

    Feletti, Alberto; Anglani, Mariagiulia; Scarpa, Bruno; Schiavi, Francesca; Boaretto, Francesca; Zovato, Stefania; Taschin, Elisa; Gardi, Mario; Zanoletti, Elisabetta; Piermarocchi, Stefano; Murgia, Alessandra; Pavesi, Giacomo; Opocher, Giuseppe

    2016-01-01

    Background Although many studies have been published about specific lesions characterizing von Hippel-Lindau(VHL) disease, none have dealt with the natural history of the whole disease and the consequent disabilities. We aim to define the comprehensive natural history of VHL disease and to describe the functional disabilities and their impact upon patients' quality of life, thereby tailoring the follow-up schedule accordingly. Methods We performed a prospective analysis on 128 VHL-affected patients beginning in 1996. For each affected organ, we defined intervals between the first and subsequent VHL-related manifestations and compared them with current VHL surveillance protocols. We looked for any association of the number of involved organs with age, sex, type of VHL gene mutation, and functional domain mutation. Ultimately, we assessed the organ-specific disabilities caused by VHL disease. Results Hemangioblastomas show different patterns of progression depending on their location, whereas both renal cysts and carcinomas have similar progression rates. Surgery for pheochromocytoma and CNS hemangioblastoma is performed earlier than for pancreatic or renal cancer. The number of involved organs is associated with age but not with sex, type of VHL gene mutation, or functional domain mutation. A thorough analysis of functional disabilities showed that age is related to the first-appearing functional impairment, but it is not predictive of the final number of disabilities. Conclusions Our study defines the disease progression and provides a comprehensive view of the syndrome over time. We analyzed for the first time the functional disability of VHL patients, assessing the progression for each function. PMID:26763786

  5. Characteristics of scientific production in Special Education in Virtual Health Library (VHL: a bibliometric study

    Directory of Open Access Journals (Sweden)

    Luciana Pizzani

    2010-12-01

    Full Text Available Objective: To characterize, through bibliometric approach, the scientific literature in this Special Education in the databases of the Virtual Health Library (VHL. The VHL is coordinated by BIREME - Specialized Center of the Pan American Health Organization whose objective is to promote the dissemination and use of scientific information in health. Method: The research methodology was performed by observing the following steps: a literature review on education special and bibliometrics, data collection from the site of BIREME about the presence of special education in the databases, organization, processing and bibliometric analysis of data collected using the software MS Excel and Vantage Point. Results: indicators produced allow signal that the predominant language of scientific production was the Portuguese and the majority of records were written individually, the themes addressed were psychology and developmental psychology. Conclusion: These bibliometric indicators characterizing the state of the art of scientific literature in Special Education at the various bases Data Bireme and also showed a field of interconnections between Health Sciences and Special Education.

  6. Alzheimer disease family history impacts resting state functional connectivity.

    Science.gov (United States)

    Wang, Liang; Roe, Catherine M; Snyder, Abraham Z; Brier, Matthew R; Thomas, Jewell B; Xiong, Chengjie; Benzinger, Tammie L; Morris, John C; Ances, Beau M

    2012-10-01

    Offspring whose parents have Alzheimer disease (AD) are at increased risk for developing dementia. Patients with AD typically exhibit disruptions in the default mode network (DMN). The aim of this study was to investigate the effect of a family history of late onset AD on DMN integrity in cognitively normal individuals. In particular, we determined whether a family history effect is detectable in apolipoprotein E (APOE) ε4 allele noncarriers. We studied a cohort of 348 cognitively normal participants with or without family history of late onset AD. DMN integrity was assessed by resting state functional connectivity magnetic resonance imaging. A family history of late onset AD was associated with reduced resting state functional connectivity between particular nodes of the DMN, namely the posterior cingulate and medial temporal cortex. The observed functional connectivity reduction was not attributable to medial temporal structural atrophy. Importantly, we detected a family history effect on DMN functional connectivity in APOE ε4 allele noncarriers. Unknown genetic factors, embodied in a family history of late onset AD, may affect DMN integrity prior to cognitive impairment. Copyright © 2012 American Neurological Association.

  7. Memory binding and white matter integrity in familial Alzheimer's disease.

    Science.gov (United States)

    Parra, Mario A; Saarimäki, Heini; Bastin, Mark E; Londoño, Ana C; Pettit, Lewis; Lopera, Francisco; Della Sala, Sergio; Abrahams, Sharon

    2015-05-01

    Binding information in short-term and long-term memory are functions sensitive to Alzheimer's disease. They have been found to be affected in patients who meet criteria for familial Alzheimer's disease due to the mutation E280A of the PSEN1 gene. However, only short-term memory binding has been found to be affected in asymptomatic carriers of this mutation. The neural correlates of this dissociation are poorly understood. The present study used diffusion tensor magnetic resonance imaging to investigate whether the integrity of white matter structures could offer an account. A sample of 19 patients with familial Alzheimer's disease, 18 asymptomatic carriers and 21 non-carrier controls underwent diffusion tensor magnetic resonance imaging, neuropsychological and memory binding assessment. The short-term memory binding task required participants to detect changes across two consecutive screens displaying arrays of shapes, colours, or shape-colour bindings. The long-term memory binding task was a Paired Associates Learning Test. Performance on these tasks were entered into regression models. Relative to controls, patients with familial Alzheimer's disease performed poorly on both memory binding tasks. Asymptomatic carriers differed from controls only in the short-term memory binding task. White matter integrity explained poor memory binding performance only in patients with familial Alzheimer's disease. White matter water diffusion metrics from the frontal lobe accounted for poor performance on both memory binding tasks. Dissociations were found in the genu of corpus callosum which accounted for short-term memory binding impairments and in the hippocampal part of cingulum bundle which accounted for long-term memory binding deficits. The results indicate that white matter structures in the frontal and temporal lobes are vulnerable to the early stages of familial Alzheimer's disease and their damage is associated with impairments in two memory binding functions known to

  8. Family history of melanoma and Parkinson disease risk.

    Science.gov (United States)

    Gao, X; Simon, K C; Han, J; Schwarzschild, M A; Ascherio, A

    2009-10-20

    Co-occurrence of Parkinson disease (PD) and melanoma has been reported in numerous studies. If this was due to common genetic mechanisms, a positive family history of melanoma would be associated with an excessive PD risk, independent of environmental risk factors for PD. We prospectively examined associations between a family history of melanoma and PD among 157,036 men and women free of PD at baseline (1990 for men and 1982 for women) who participated in 2 ongoing US cohorts: the Health Professional Follow-up Study and the Nurses' Health Study. Information on family history of melanoma in parents or siblings was assessed via questionnaire. Relative risks and 95% confidence intervals were estimated using Cox proportional hazards models and pooled using a fixed-effects model. During 14-20 years follow-up, we identified 616 incident PD cases. A family history of melanoma in a first-degree relative was associated with a higher risk of PD (multivariate relative risk = 1.85; 95% confidence interval: 1.2, 2.8; p = 0.004), after adjusting for smoking, ethnicity, caffeine intake, and other covariates. In contrast, we did not observe significant associations between a family history of colorectal, lung, prostate, or breast cancer and PD risk. Interactions between melanoma family history and age, smoking, or caffeine intake were not significant and subgroup analyses according to these factors generated similar results. Our findings support the notion that melanoma and Parkinson disease (PD) share common genetic components. The genetic determinants of melanoma could therefore be explored as susceptibility candidate genes for PD.

  9. Gaucher disease in a family from Maranhão

    Directory of Open Access Journals (Sweden)

    Samira Shizuko Parreão Oi

    2014-10-01

    Full Text Available Background: Gaucher disease is an inborn, autosomal recessive error of the metabolism which belongs to the group of lysosomal storage disorders. Objective: This work reports on the treatment of Gaucher disease in several members of the same family from the countryside of Maranhão. Methods: This was an observational, retrospective and prospective, descriptive case study about the efficacy of enzyme replacement therapy. Results: The results showed that women were more affected (80% of patients by the disease, age at diagnosis ranged from 24 to 33 years, the predominant ethnicity was mulatto (80% and all cases were classified as type 1. The diagnosis of these patients was performed by measuring the levels of glucocerebrosidase and chitotriosidase enzymes and confirmed by genotyping. All patients suffering from Gaucher disease had low glucocerebrosidase levels. Before replacement therapy, hepatosplenomegaly was the most common clinical manifestation (100% and osteopenia was seen in 80% of the cases. Regarding hematological manifestations, anemia and leukopenia were found in 40% of patients at diagnosis; however the hemoglobin and leukocyte levels were normalized after four years of therapy. Thrombocytopenia, observed in 20% of cases, was normalized after the second year of treatment. Conclusion: In these cases, despite gaps in the treatment as the family resides in the rural region of the state, the patients with Gaucher disease showed satisfactory therapeutic response over time.

  10. Families with familial combined hyperlipidemia and families enriched for coronary artery disease share genetic determinants for the atherogenic lipoprotein phenotype

    Energy Technology Data Exchange (ETDEWEB)

    Allayee, H.; Aouizerat, B.E.; Lusis, A.J. [Univ. of California, Los Angeles, CA (United States); Cantor, R.M.; Lanning, C.D.; Rotter, J.I. [Cedars-Sinai Research Inst., Los Angeles, CA (United States); Dallinga-Thie, G.M. [University Hospital, Utrecht (Netherlands). Dept. of Medicine; Krauss, R.M. [Lawrence Berkeley Lab., CA (United States); Bruin, T.W.A. de [University Hospital, Utrecht (Netherlands). Dept. of Medicine]|[University Hospital, Maastricht (Netherlands). Dept. of Medicine and Endocrinology

    1998-08-01

    Small, dense LDL particles consistently have been associated with hypertriglyceridemia, premature coronary artery disease (CAD), and familial combined hyperlipidemia (FCH). Previously, the authors have observed linkage of LDL particle size with four separate candidate-gene loci in a study of families enriched for CAD. These loci contain the genes for manganese superoxide dismutase (MnSOD), on chromosome 6q; for apolipoprotein AI-CIII-AIV, on chromosome 11q; for cholesteryl ester transfer protein (CETP) and lecithin:cholesterol acyl-transferase (LCAT), on chromosome 16q; and for the LDL receptor (LDLR), on chromosome 19p. The authors have now tested whether these loci also contribute to LDL particle size in families ascertained for FCH. The members of 18 families (481 individuals) were typed for genetic markers at the four loci, and linkage to LDL particle size was assessed by nonparametric sib-pair linkage analysis. The presence of small, dense LDL (pattern B) was much more frequent in the FCH probands than in the spouse controls. Evidence for linkage was observed at the MnSOD (P = .02), CETP/LCAT (P = .03), and apolipoprotein AI0CIII0AIV loci (P = .005) but not at the LDLR locus. The authors conclude that there is a genetically based association between FCH and small, dense LDL and that the genetic determinants for LDL particle size are shared, at least in part, among FCH families and the more general population at risk for CAD.

  11. Family Stress with Chronic Childhood Illness: Cystic Fibrosis, Neuromuscular Disease, and Renal Disease.

    Science.gov (United States)

    Holroyd, Jean; Guthrie, Donald

    1986-01-01

    Parents of children with neuromuscular disease, cystic fibrosis, and renal disease were compared with parents of control subjects matched by age to the clinical cases. The three clinical groups exhibited different patterns of stressful response, consistent with the nature of their illnesses and the requirements for care imposed on the families.…

  12. DnaJ/Hsp40 Family and Parkinson's Disease

    Directory of Open Access Journals (Sweden)

    Takafumi Hasegawa

    2018-01-01

    Full Text Available Parkinson's disease (PD is the second most common devastating neurodegenerative disorder after Alzheimer's disease. The precise molecular and cellular basis underlying PD still remains uncertain; however, accumulating evidence suggests that neuronal cell death is caused by a combination of environmental and genetic factors. Over the previous two decades, more than 20 genes have been identified as the cause of and/or risk for PD. Because sporadic and familial forms of PD have many similarities in clinical and neuropathological features, common molecular pathways, such as aberrant mitochondrial and protein homeostasis, are likely to exist in both conditions. Of the various genes and proteins involved in PD, the versatile DnaJ/Hsp40 co-chaperones have attracted particular attention since several genes encoding this protein family have been successively identified as the cause of the familial forms of PD/Parkinsonism. In this review, we will introduce the current knowledge regarding the integratory and modulatory effect of DnaJ/Hsp40 in various cellular functions and argue how the failure of these proteins may initiate and/or facilitate of the disease.

  13. Three cases of Dowling Degos disease in two families

    Directory of Open Access Journals (Sweden)

    Bhagwat P

    2009-01-01

    Full Text Available Dowling Degos disease is a rare condition inherited as autosomal dominant trait characterized by numerous, asymptomatic, symmetrical, progressive, small, round-pigmented macules over axillae and groins, face, neck, arms and trunk, scattered comedo-like lesions (dark dot follicles and pitted acneiform scars. Histopathology is diagnostic. We are hereby reporting three cases of Dowling Degos disease belonging to two families. Our first and second case belonged to the same family, whereas our third case belonged to different family. In our series, all the patients had onset after puberty. All three cases had reticulate pigmentation over face and/or flexures, black comedones and follicular pits. On histopathological examination of the skin biopsy taken from the lesion over the back, all these patients showed classical histopathological features of Dowling Degos disease. We feel that one should investigate the patient presenting with reticulate pigmentation over the face and flexures with blackish comedone-like lesions, because histopathological features of this condition are unmistakable.

  14. Molecular Basis of Familial and Sporadic Alzheimer's Disease.

    Science.gov (United States)

    Dorszewska, Jolanta; Prendecki, Michal; Oczkowska, Anna; Dezor, Mateusz; Kozubski, Wojciech

    2016-01-01

    Alzheimer's disease (AD) is a multifactorial disease with genetic (70%) and environmental (30%) causes. Among the genetic factors are genes associated with a family history of the disease (familial AD, FAD) and sporadic AD (SAD). The genes: APP (amyloid precursor protein), PSEN1 (Presenilin 1) and PSEN2 (Presenilin 2) are responsible for the presence of FAD. The APOE gene is responsible for the sporadic form of the disease. Other molecular factors related to the immunological cause (TREM2) of the disease are a disorder of the lipid (ABCA1, ABCA7) or biothiol (MTHFD1) metabolism and of the transport of metabolites (BIN1). Currently, it is believed that APOE is a risk factor for both SAD and late-onset FAD. The pathomechanism of AD is most commonly explained as based on the amyloid cascade theory. This theory is related to the FAD, although there are reports indicating the probability of its occurrence in the SAD. It seems that the excessive deposition of β-amyloid (Aβ) peptides and intracellular neurofibrillary tangles of tau protein hyperphosphorylated forms contribute to the damage of both DNA and RNA. Furthermore, it is believed that RNA-interference can affect both the level of pathological proteins (Aβ, tau protein) and the onset and progress of AD. It seems that a complete understanding of both FAD and SAD pathogenesis may contribute to the search for earlier clinical diagnosis and to an understanding of later occurrence of the disease, which may help modify its course and affect more effective therapy of this incurable neurological disease.

  15. A pediatric approach to family history of cardiovascular disease: diagnosis, risk assessment, and management.

    Science.gov (United States)

    Miller, Erin M; Hinton, Robert B

    2014-02-01

    The medical family history is a comprehensive and dynamic record of illnesses and other pertinent health information among family members. Family history is used to facilitate diagnosis, to identify family members at risk for developing a particular disease, and increasingly to manage disease. This article reviews the application of family history to pediatric cardiovascular disease. As more is learned about the genetic basis of cardiovascular disease, the family history will play an increasingly central role in management. Improved understanding of the causes of pediatric cardiovascular disease promises the opportunity to develop new diagnostic and therapeutic strategies. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. Adjustment for misclassification in studies of familial aggregation of disease using routine register data

    DEFF Research Database (Denmark)

    Andersen, Elisabeth Anne Wreford; Andersen, Per Kragh

    2002-01-01

    disease register; EM-algorithm; familial aggregation; misclassification; nested case-control study; regression calibration......disease register; EM-algorithm; familial aggregation; misclassification; nested case-control study; regression calibration...

  17. Haplotype of the angiotensinogen gene is associated with coronary heart disease in familial hypercholesterolemia

    NARCIS (Netherlands)

    van der Net, Jeroen B.; Isaacs, Aaron; Dallinga-Thie, Geesje M.; Kastelein, John J. P.; Defesche, Joep C.; Steyerberg, Ewout W.; Sijbrands, Eric J. G.

    2008-01-01

    OBJECTIVE: Familial hypercholesterolemia is characterized by high plasma low-density lipoprotein cholesterol levels and premature coronary heart disease. Despite the monogenetic origin of familial hypercholesterolemia, the incidence of coronary heart disease varies considerably among patients, which

  18. Psychosocial issues in families affected by maple syrup urine disease.

    Science.gov (United States)

    Packman, Wendy; Henderson, Shelly L; Mehta, Indira; Ronen, Rama; Danner, Dean; Chesterman, Beth; Packman, Seymour

    2007-12-01

    The primary aim of this study was to ascertain the psychosocial issues faced by families affected by maple syrup urine disease (MSUD). The psychosocial adjustment and quality of life of children with MSUD were also described. Participants included 55 families and their children (ages 5 to 18 years) and teachers. Measures included a MSUD Family Survey, the Behavior Assessment System for Children (BASC) and the Pediatric Quality of Life Inventory (PedsQL). Parents reported via the MSUD Family Survey that the greatest sources of stress were financial and emotional. Many parents reported difficulty interacting with the medical staff and with schools. On the BASC, half of the children fell within the average range in psychosocial adjustment, although there were elevations in scales measuring attention, hyperactivity, and learning problems. On the PedsQL, the mean quality of life scores were closer to children with cancer than to a healthy sample. Despite the emotional and financial burden, parents reported that MSUD has also had a positive influence on their lives, leading to a world-view that is more compassionate and caring.

  19. A family study of Charcot-Marie-Tooth disease.

    Science.gov (United States)

    Brooks, A P; Emery, A E

    1982-04-01

    Forty-seven cases of Charcot-Marie-Tooth peripheral neuropathy were seen in 18 families within a defined area, with a disease prevalence of 1 in 16 400. Maximum motor nerve conduction velocity (MNCV) measurement divided off two types of neuropathy (MNCV less than 30 ms-1 and greater than 40 ms-1), but did not distinguish clinically affected from normal in families whose probands had median nerve MNCV greater than 40 ms-1. In the neuronal type of neuropathy ((MNCV greater than 40 ms-1) two genotypes were seen, autosomal dominant (ADN) and autosomal recessive (ARN). Most cases with the demyelinating type (MNCV less than 30 ms-1) had an autosomal dominant genotype (ADD) but one family had possible X linked recessive inheritance (XRD). In one autosomal dominant family a father and son had different electrophysiological types of neuropathy. Peroneal muscle weakness was progressive with age in the ADD genotype and certain patterns of phenotypic features were associated with the major genotypes. Age of onset was not found to be reliable in distinguishing genotypes. Care is needed when counselling isolated male cases because of asymptomatic affected females in the autosomal dominant genotypes, and the possibility of ill defined X linked forms.

  20. Dock-family exchange factors in cell migration and disease.

    Science.gov (United States)

    Gadea, Gilles; Blangy, Anne

    2014-10-01

    Dock family proteins are evolutionary conserved exchange factors for the Rho GTPases Rac and Cdc42. There are 11 Dock proteins in mammals, named Dock1 (or Dock180) to Dock11 that play different cellular functions. In particular, Dock proteins regulate actin cytoskeleton, cell adhesion and migration. Not surprisingly, members of the Dock family have been involved in various pathologies, including cancer and defects in the central nervous and immune systems. This review proposes an update of the recent findings regarding the function of Dock proteins, focusing on their role in the control of cell migration and invasion and the consequences in human diseases. Copyright © 2014 Elsevier GmbH. All rights reserved.

  1. Family history of vascular disease and the risk of cardiovascular events

    NARCIS (Netherlands)

    Weijmans, M.

    2015-01-01

    A positive family history of cardiovascular disease is an established risk factor for the development of cardiovascular disease. In clinical practice, this evident relation between the presence of cardiovascular disease in families and first cardiovascular events has resulted in family history being

  2. Familial Aggregation of Panic Disturbances in Parkinson’s Disease

    OpenAIRE

    Pontone, Gregory M.; Palanci, Justin; Bienvenu, O. Joseph; Liang, Kung-Yee; Nestadt, Gerald; Rabins, Peter V.; Williams, James R.; Marsh, Laura

    2011-01-01

    Panic disorder has an elevated prevalence in Parkinson’s disease (PD). To explore the basis for this co-occurrence, the familial aggregation of panic disorder was examined in patients with PD. Probands and relatives of patients with PD and panic disorder (PD-PANIC; N=20, N=115) and control probands with PD and no active psychiatric illness (PD-NA; N=17, N=108) were interviewed by phone, using a structured interview to determine panic status. Lifetime prevalence of panic and “panic-like” disor...

  3. ALZHEIMER’S DISEASE: THE EXPERIENCE OF ILLNESS FROM THE PERSPECTIVE OF FAMILY CAREGIVERS

    Directory of Open Access Journals (Sweden)

    Thaís Oliveira da Silva

    2017-07-01

    Full Text Available The Alzheimer's disease is characterized by being a degenerative disease that affects the brain, promoting progressive impairment of mental function. The disease progresses to a stage of total dependence, which requires the assistance of health professionals and family caregivers. This study aimed to describe the relationship between the patient and family caregiver; and, to understand how the family caregivers experiences the care.  The methodology adopted was the oral history with the technique of semi-structured interview and content analysis. The themes were: Family Caregivers and patients: initial experience; The discovery of the disease: how it happens; How the family caregiver experiences the disease. The experience of care for patients of Alzheimer's disease requires changes in the family dynamics of caregivers, which require knowledge about the disease, symptoms and evolution.  These changes generate anxiety and despair in family caregivers and adaptation to exercise the care in different situations that are emerging with the disease.

  4. Inactivation of Vhl in Osteochondral Progenitor Cells Causes High Bone Mass Phenotype and Protects Against Age-Related Bone Loss in Adult Mice

    Science.gov (United States)

    Weng, Tujun; Xie, Yangli; Huang, Junlan; Luo, Fengtao; Yi, Lingxian; He, Qifen; Chen, Di; Chen, Lin

    2014-01-01

    Previous studies have shown that disruption of von Hippel–Lindau gene (Vhl) coincides with activation of hypoxia-inducible factor α (HIFα) signaling in bone cells and plays an important role in bone development, homeostasis, and regeneration. It is known that activation of HIF1α signaling in mature osteoblasts is central to the coupling between angiogenesis and bone formation. However, the precise mechanisms responsible for the coupling between skeletal angiogenesis and osteogenesis during bone remodeling are only partially elucidated. To evaluate the role of Vhl in bone homeostasis and the coupling between vascular physiology and bone, we generated mice lacking Vhl in osteochondral progenitor cells (referred to as Vhl cKO mice) at postnatal and adult stages in a tamoxifen-inducible manner and changes in skeletal morphology were assessed by micro–computed tomography (µCT), histology, and bone histomorphometry. We found that mice with inactivation of Vhl in osteochondral progenitor cells at the postnatal stage largely phenocopied that of mice lacking Vhl in mature osteoblasts, developing striking and progressive accumulation of cancellous bone with increased microvascular density and bone formation. These were accompanied with a significant increase in osteoblast proliferation, upregulation of differentiation marker Runx2 and osteocalcin, and elevated expression of vascular endothelial growth factor (VEGF) and phosphorylation of Smad1/5/8. In addition, we found that Vhl deletion in osteochondral progenitor cells in adult bone protects mice from aging-induced bone loss. Our data suggest that the VHL-mediated signaling in osteochondral progenitor cells plays a critical role in bone remodeling at postnatal/adult stages through coupling osteogenesis and angiogenesis. © 2014 American Society for Bone and Mineral Research. PMID:23999831

  5. Familial paragangliomas

    Directory of Open Access Journals (Sweden)

    Lips CJM

    2006-10-01

    Full Text Available Abstract Paragangliomas are rare tumours of the autonomic nervous system and occur in sporadic and hereditary forms. They are usually benign and have a low mortality. However, they cause significant morbidity related to their mass effect. Genetic predisposition can occur within the familial tumour syndromes multiple endocrine neoplasia type 2 (MEN 2, von Hippel-Lindau (VHL and neurofibromatosis type 1 (NF-1, or be due to mutations in genes specific to the development of paraganglioma only. Compared to sporadic forms, familial paragangliomas tend to present at a younger age and at multiple sites. Tumours should be diagnosed and resected as early as possible, as it has been shown that morbidity is related to tumour size. This article gives an overview of the current literature on the origin of the different forms of paragangliomas, DNA diagnosis, as well as biochemical and radiological screening guidelines.

  6. Association of peripheral arterial and cardiovascular diseases in familial hypercholesterolemia.

    Science.gov (United States)

    Pereira, Carolina; Miname, Marcio; Makdisse, Marcia; Kalil Filho, Roberto; Santos, Raul D

    2014-08-01

    Familial hypercholesterolemia (FH) is an autosomal dominant genetic disease characterized by an elevation in the serum levels of total cholesterol and of low-density lipoproteins (LDL- c). Known to be closely related to the atherosclerotic process, FH can determine the development of early obstructive lesions in different arterial beds. In this context, FH has also been proposed to be a risk factor for peripheral arterial disease (PAD). This observational cross-sectional study assessed the association of PAD with other manifestations of cardiovascular disease (CVD), such as coronary artery and cerebrovascular disease, in patients with heterozygous FH. The diagnosis of PAD was established by ankle-brachial index (ABI) values ≤ 0.90. This study assessed 202 patients (35% of men) with heterozygous FH (90.6% with LDL receptor mutations), mean age of 51 ± 14 years and total cholesterol levels of 342 ± 86 mg /dL. The prevalences of PAD and previous CVD were 17% and 28.2 %, respectively. On multivariate analysis, an independent association between CVD and the diagnosis of PAD was observed (OR = 2.50; 95% CI: 1.004 - 6.230; p = 0.049). Systematic screening for PAD by use of ABI is feasible to assess patients with FH, and it might indicate an increased risk for CVD. However, further studies are required to determine the role of ABI as a tool to assess the cardiovascular risk of those patients.

  7. Association of Peripheral Arterial and Cardiovascular Diseases in Familial Hypercholesterolemia

    Directory of Open Access Journals (Sweden)

    Carolina Pereira

    2014-08-01

    Full Text Available Background: Familial hypercholesterolemia (FH is an autosomal dominant genetic disease characterized by an elevation in the serum levels of total cholesterol and of low-density lipoproteins (LDL- c. Known to be closely related to the atherosclerotic process, FH can determine the development of early obstructive lesions in different arterial beds. In this context, FH has also been proposed to be a risk factor for peripheral arterial disease (PAD. Objective: This observational cross-sectional study assessed the association of PAD with other manifestations of cardiovascular disease (CVD, such as coronary artery and cerebrovascular disease, in patients with heterozygous FH. Methods: The diagnosis of PAD was established by ankle-brachial index (ABI values ≤ 0.90. This study assessed 202 patients (35% of men with heterozygous FH (90.6% with LDL receptor mutations, mean age of 51 ± 14 years and total cholesterol levels of 342 ± 86 mg /dL. Results: The prevalences of PAD and previous CVD were 17% and 28.2 %, respectively. On multivariate analysis, an independent association between CVD and the diagnosis of PAD was observed (OR = 2.50; 95% CI: 1.004 - 6.230; p = 0.049. Conclusion: Systematic screening for PAD by use of ABI is feasible to assess patients with FH, and it might indicate an increased risk for CVD. However, further studies are required to determine the role of ABI as a tool to assess the cardiovascular risk of those patients.

  8. Association of Peripheral Arterial and Cardiovascular Diseases in Familial Hypercholesterolemia

    Energy Technology Data Exchange (ETDEWEB)

    Pereira, Carolina [Instituto do Coração HCFMUSP, São Paulo, SP (Brazil); Hospital Israelita Albert Einstein, São Paulo, SP (Brazil); Miname, Marcio [Instituto do Coração HCFMUSP, São Paulo, SP (Brazil); Makdisse, Marcia [Hospital Israelita Albert Einstein, São Paulo, SP (Brazil); Kalil, Roberto Filho [Instituto do Coração HCFMUSP, São Paulo, SP (Brazil); Santos, Raul D., E-mail: rdsf@cardiol.br [Instituto do Coração HCFMUSP, São Paulo, SP (Brazil); Hospital Israelita Albert Einstein, São Paulo, SP (Brazil)

    2014-08-15

    Familial hypercholesterolemia (FH) is an autosomal dominant genetic disease characterized by an elevation in the serum levels of total cholesterol and of low-density lipoproteins (LDL- c). Known to be closely related to the atherosclerotic process, FH can determine the development of early obstructive lesions in different arterial beds. In this context, FH has also been proposed to be a risk factor for peripheral arterial disease (PAD). This observational cross-sectional study assessed the association of PAD with other manifestations of cardiovascular disease (CVD), such as coronary artery and cerebrovascular disease, in patients with heterozygous FH. The diagnosis of PAD was established by ankle-brachial index (ABI) values ≤ 0.90. This study assessed 202 patients (35% of men) with heterozygous FH (90.6% with LDL receptor mutations), mean age of 51 ± 14 years and total cholesterol levels of 342 ± 86 mg /dL. The prevalences of PAD and previous CVD were 17% and 28.2 %, respectively. On multivariate analysis, an independent association between CVD and the diagnosis of PAD was observed (OR = 2.50; 95% CI: 1.004 - 6.230; p = 0.049). Systematic screening for PAD by use of ABI is feasible to assess patients with FH, and it might indicate an increased risk for CVD. However, further studies are required to determine the role of ABI as a tool to assess the cardiovascular risk of those patients.

  9. 68Ga-DOTA-NOC PET/CT detects somatostatin receptors expression in von hippel-lindau cerebellar disease.

    Science.gov (United States)

    Ambrosini, Valentina; Campana, Davide; Allegri, Vincenzo; Opocher, Giuseppe; Fanti, Stefano

    2011-01-01

    A case of Von-Hippel Lindau (VHL) disease has been studied using 68Ga-DOTA-NOC PET/CT. PET/CT demonstrated the presence of somatostatin receptors within 2 focal areas in the cerebellum corresponding to the lesions detected by MRI. Considering the heterogeneous lesions localizations in VHL disease, PET/CT may be a useful imaging modality for diagnosing lesions of central nervous system and neuroendocrine lesions and for direct demonstration of somatostatin receptors for targeted treatment.

  10. Family history of coronary heart disease and markers of subclinical cardiovascular disease: where do we stand?

    Science.gov (United States)

    Pandey, Arvind K; Pandey, Shivda; Blaha, Michael J; Agatston, Arthur; Feldman, Theodore; Ozner, Michael; Santos, Raul D; Budoff, Matthew J; Blumenthal, Roger S; Nasir, Khurram

    2013-06-01

    The goals of this systematic analysis are to determine the association between family history of coronary heart disease (CHD) and markers of subclinical cardiovascular disease as well as to discuss the inclusion of CHD family history in the frequently used coronary risk prediction algorithms. Individuals with a family history of CHD are at high risk for developing atherosclerosis and events related to CHD, regardless of the presence of other coronary risk factors. They form a target population that might benefit from primary prevention strategies; however, family history data is not a part of the frequently used risk prediction algorithms. Medline and PubMed databases were searched for all studies evaluating the relationship between measures of subclinical atherosclerosis and family history of CHD, published till June 2010. Thirty-two studies met the above criteria and were included in this review. Coronary artery calcium, carotid intima thickness, vascular function, and inflammatory markers including C reactive protein, fibrinogen, and D-dimer were used as measures of subclinical atherosclerosis. Studies differed in design, demographic data of the population, techniques and validation of family history information. Most studies established a statistically significant relationship between the above markers and family history of CAD; further, the association was noted to be independent of traditional risk factors. Family history of CAD is associated with markers of subclinical atherosclerosis, and this relationship remains statistically significant after adjusting for traditional risk factors. The above data suggest these individuals should be considered strongly as candidates for assessment of subclinical CVD to further refine risk and treatment goals. Copyright © 2013. Published by Elsevier Ireland Ltd.

  11. Components of family history associated with women's disease perceptions for cancer: A report from the Family Healthware™ Impact Trial

    Science.gov (United States)

    Rubinstein, Wendy S.; O'Neill, Suzanne M.; Rothrock, Nan; Starzyk, Erin J.; Beaumont, Jennifer L.; Acheson, Louise S.; Wang, Catharine; Gramling, Robert; Galliher, James M.; Ruffin, Mack T.

    2014-01-01

    Purpose To determine the specific components of family history and personal characteristics related to disease perceptions about breast, colon, and ovarian cancers. Methods Baseline, cross-sectional data on 2,505 healthy women aged 35–65 years enrolled from 41 primary care practices in the cluster-randomized Family Healthware™ Impact Trial, assessed for detailed family history and perceived risk, perceived severity, worry, and perceived control over getting six common diseases including breast, colon, and ovarian cancers. Results Participants provided family history information on 41,841 total relatives. We found evidence of underreporting of paternal family history and lower perceived breast cancer risk with cancer in the paternal versus maternal lineage. We observed cancer-specific perceived risks and worry for individual family history elements and also found novel “spillover” effects where a family history of one cancer was associated with altered disease perceptions of another. Having a mother with early-onset breast or ovarian cancer was strongly associated with perceived risk of breast cancer. Age, parenthood, and affected lineage were associated with disease perceptions and ran counter to empiric risks. Conclusions Understanding patients' formulation of risk for multiple diseases is important for public health initiatives that seek to inform risk appraisal, influence disease perceptions, or match preventive interventions to existing risk perceptions. PMID:21150785

  12. Identification of Somatic Mutations in the von Hippel–Lindau (VHL Gene in a Patient With Renal Cell Carcinoma

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    Wen-Chung Wang

    2009-11-01

    Full Text Available One of the known causal molecular events in renal cell carcinoma is somatic mutation in the von Hippel–Lindau (VHL gene. Our study describes a 51-year-old Taiwanese man who had bilateral renal cell carcinoma. The patient underwent radical nephrectomy without postoperative chemotherapy or radiotherapy, and is still alive after renal transplantation without tumor recurrence after > 5 years. To clarify his predisposition for bilateral tumors, we performed molecular genetic analysis of the VHL gene in this study. Polymerase chain reaction–single-strand conformation polymorphism and direct sequencing were performed on DNA of blood samples and paraffin-embedded tumor specimens from this patient. DNA from peripheral blood lymphocytes tested negative for germline mutations. However, there were two heterozygous alleles in the promoter and 3′ untranslated regions of this gene. Nonetheless, the DNA from his tumors showed loss of heterozygosity (LOH in these two loci. In addition to the LOH, we identified some different somatic mutations in his tumor tissues: C287T and G460A in the right-sided tumor, and G244A and G390A in the left-sided tumor. The possible roles of these genetic polymorphisms and point mutations in his renal tumorigenesis are discussed. This report provides new insights into renal cell carcinoma that result from VHL gene alterations in Taiwan.

  13. Premature Valvular Heart Disease in Homozygous Familial Hypercholesterolemia

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    Akl C. Fahed

    2017-01-01

    Full Text Available Valvular heart disease frequently occurs as a consequence of premature atherosclerosis in individuals with familial hypercholesterolemia (FH. Studies have primarily focused on aortic valve calcification in heterozygous FH, but there is paucity of data on the incidence of valvular disease in homozygous FH. We performed echocardiographic studies in 33 relatively young patients (mean age: 26 years with homozygous FH (mean LDL of 447 mg/dL, 73% on LDL apheresis to look for subclinical valvulopathy. Twenty-one patients had evidence of valvulopathy of the aortic or mitral valves, while seven subjects showed notable mitral regurgitation. Older patients were more likely to have aortic valve calcification (>21 versus ≤21 years: 59% versus 12.5%; p = 0.01 despite lower LDL levels at the time of the study (385 versus 513 mg/dL; p = 0.016. Patients with valvulopathy were older and had comparable LDL levels and a lower carotid intima-media thickness. Our data suggests that, in homozygous FH patients, valvulopathy (1 is present across a wide age spectrum and LDL levels and (2 is less likely to be influenced by lipid-lowering treatment. Echocardiographic studies that focused on aortic root thickening and stenosis and regurgitation are thus likely an effective modality for serial follow-up of subclinical valvular heart disease.

  14. The IL-17 family cytokines in immunity and disease.

    Science.gov (United States)

    Pappu, Rajita; Ramirez-Carrozzi, Vladimir; Ota, Naruhisa; Ouyang, Wenjun; Hu, Yan

    2010-03-01

    Accumulating evidence suggests that the interleukin (IL)-17 cytokines are major players in the immune response to foreign pathogens. In addition, the pathogeneses of a number of inflammatory diseases have been linked to uncontrolled expression of these cytokine pathways. Genetic and biochemical analyses have elucidated the cellular and molecular events triggered by these proteins during an inflammatory response. While significant efforts have been placed on understanding the functions of IL-17A, IL-17F, and IL-17E, the significance of the other family members, IL-17B-D, in inflammation remains to be determined. This review will focus on the cellular sources, target cell/receptors that are utilized by these cytokines to control pathogenesis, and the therapeutic potential of targeting these pathways to treat inflammatory disorders.

  15. Management of renal cell carcinoma in von Hippel-Lindau disease.

    Science.gov (United States)

    Hes, F J; Slootweg, P J; van Vroonhoven, T J; Hené, R J; Feldberg, M A; Zewald, R A; Ploos van Amstel, J K; Höppener, J W; Pearson, P L; Lips, C J

    1999-01-01

    An evaluation of nephron-sparing surgery (NSS) or radical nephrectomy (RN) for treating renal cell carcinoma (RCC) in patients with von Hippel-Lindau disease (VHL) was carried out. Between 1976 and 1997, 10 patients with RCC from four VHL families, of whom seven were from one family, were studied by clinical and histopathological examination. Before 1991, three patients were treated using RN, and thereafter five patients were treated using NSS. Two patients were not operated on. RCCs in our patients showed a slow growth rate (on average 0.3 cm year-1), and asymptomatic patients presented with tumours of low-grade malignancy. In all patients, tumours were surrounded by a fibrous pseudocapsule. In 5 out of 17 tumours, pseudocapsular invasion was observed, and three of these five tumours broke through the pseudocapsule. To date, these patients have not shown a less favourable outcome than those without pseudocapsular involvement by tumour growth. Multicentricity of RCC was relatively low (4.6 lesions per kidney). In two of the three RN patients, only a single satellite lesion, in the direct vicinity of a RCC, was found in one kidney. Six tumours (1.8-5.5 cm) were enucleated by NSS. During a mean follow-up of 30 months, renal function in these patients was well preserved. In our patients, RCCs grew slowly, were of low grade, had a dense fibrous pseudocapsule and were thus good candidates for NSS.

  16. Maternal inheritance and mitochondrial DNA variants in familial Parkinson's disease

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    Pfeiffer Ronald F

    2010-04-01

    Full Text Available Abstract Background Mitochondrial function is impaired in Parkinson's disease (PD and may contribute to the pathogenesis of PD, but the causes of mitochondrial impairment in PD are unknown. Mitochondrial dysfunction is recapitulated in cell lines expressing mitochondrial DNA (mtDNA from PD patients, implicating mtDNA variants or mutations, though the role of mtDNA variants or mutations in PD risk remains unclear. We investigated the potential contribution of mtDNA variants or mutations to the risk of PD. Methods We examined the possibility of a maternal inheritance bias as well as the association between mitochondrial haplogroups and maternal inheritance and disease risk in a case-control study of 168 multiplex PD families in which the proband and one parent were diagnosed with PD. 2-tailed Fisher Exact Tests and McNemar's tests were used to compare allele frequencies, and a t-test to compare ages of onset. Results The frequency of affected mothers of the proband with PD (83/167, 49.4% was not significantly different from the frequency of affected females of the proband generation (115/259, 44.4% (Odds Ratio 1.22; 95%CI 0.83 - 1.81. After correcting for multiple tests, there were no significant differences in the frequencies of mitochondrial haplogroups or of the 10398G complex I gene polymorphism in PD patients compared to controls, and no significant associations with age of onset of PD. Mitochondrial haplogroup and 10398G polymorphism frequencies were similar in probands having an affected father as compared to probands having an affected mother. Conclusions These data fail to demonstrate a bias towards maternal inheritance in familial PD. Consistent with this, we find no association of common haplogroup-defining mtDNA variants or for the 10398G variant with the risk of PD. However, these data do not exclude a role for mtDNA variants in other populations, and it remains possible that other inherited mitochondrial DNA variants, or somatic m

  17. Clinical Polymorphism of Stargardt Disease in a Large Consanguineous Tunisian Family; Implications for Nosology

    Directory of Open Access Journals (Sweden)

    Leila El Matri

    2013-01-01

    Full Text Available Purpose: To describe the polymorphic expression of Stargardt disease in a large Tunisian family with clinical intra- and interfamilial variation of the condition. Methods: Twelve subjects from two related families with autosomal recessive Stargardt disease were enrolled. A detailed clinical examination including visual acuity and visual field measurement, fundus photography, fluorescein angiography, electroretinography (ERG and color vision testing was performed for all subjects. Results: The youngest child from family A manifested typical Stargardt disease while her two brothers presented with Stargardt disease-fundus flavimaculatus (STGD-FFM and her two sisters demonstrated a peculiar phenotype overlapping Stargardt disease and cone-rod dystrophy; their phenotypic manifestation corresponded well with ERG groups I, II and III, respectively. This uncommon occurrence of an age-related decline in ERG amplitude and worsening of fundus changes is suggestive of a grading pattern in Stargardt disease. Their two cousins in family B, displayed the STGD-FFM phenotype. Despite clinically similar STGD-FFM patterns in both families, age of onset and progression of the phenotype in family B differed from family A. Conclusion: This is the first report on phenotypic variation of Stargardt disease in a large Tunisian family. Regarding phenotype and severity of visual symptoms, family A demonstrated Stargardt disease at various stages of progression. In addition, STGDFFM appeared to be an independent clinical entity in family B. These findings imply that further parameters are required to classify Stargardt′s disease.

  18. Familial polycystic kidney disease in Nigeria: A report of two cases ...

    African Journals Online (AJOL)

    A case of familial polycystic kidney disease is reported. Although isolated cases of adult polycystic kidney disease have been reported in our environment, no case to our knowledge has been reported with a familial link. Polycystic kidney disease is said to be rare in Africans. Although it commonly terminates in chronic renal ...

  19. Association between CD40 C/T1 polymorphism and familial autoimmune thyroid disease

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    A K Pyankova

    2013-09-01

    Full Text Available High prevalence of family cases of autoimmune thyroid diseases (AITD causes requirement of researching this group of patients. The objective of this study is to estimate genotypes and alleles frequencies of CD40 C(1T poly morphism (rs1883832 in Graves` disease and Hashimoto`s disease families at least two firstdegree affected relatives. 70 patients with AITD took part in the study (35 families and 76 control subjects. Results suggested that carrying of CT and TT genotypes of CD40 C(1T polymorphism is associated with the low risk of developing of Graves` disease family cases without any regards to degree relationship. No association between CD40 C(1T polymorphism and Hashimoto`s disease was identified. Carrying of allele C is associated with the high risk of developing of Graves` dis ease family cases odds ratio OR = 2,669, 95% CI, 1,6124,39, but not Hashimoto`s disease family cases.

  20. Genetic basis of kidney cancer: Role of genomics for the development of disease-based therapeutics

    Science.gov (United States)

    Linehan, W. Marston

    2012-01-01

    Kidney cancer is not a single disease; it is made up of a number of different types of cancer, including clear cell, type 1 papillary, type 2 papillary, chromophobe, TFE3, TFEB, and oncocytoma. Sporadic, nonfamilial kidney cancer includes clear cell kidney cancer (75%), type 1 papillary kidney cancer (10%), papillary type 2 kidney cancer (including collecting duct and medullary RCC) (5%), the microphalmia-associated transcription (MiT) family translocation kidney cancers (TFE3, TFEB, and MITF), chromophobe kidney cancer (5%), and oncocytoma (5%). Each has a distinct histology, a different clinical course, responds differently to therapy, and is caused by mutation in a different gene. Genomic studies identifying the genes for kidney cancer, including the VHL, MET, FLCN, fumarate hydratase, succinate dehydrogenase, TSC1, TSC2, and TFE3 genes, have significantly altered the ways in which patients with kidney cancer are managed. While seven FDA-approved agents that target the VHL pathway have been approved for the treatment of patients with advanced kidney cancer, further genomic studies, such as whole genome sequencing, gene expression patterns, and gene copy number, will be required to gain a complete understanding of the genetic basis of kidney cancer and of the kidney cancer gene pathways and, most importantly, to provide the foundation for the development of effective forms of therapy for patients with this disease. PMID:23038766

  1. Genetic screening for a single common LRRK2 mutation in familial Parkinson's disease.

    Science.gov (United States)

    Nichols, William C; Pankratz, Nathan; Hernandez, Dena; Paisán-Ruíz, Coro; Jain, Shushant; Halter, Cheryl A; Michaels, Veronika E; Reed, Terry; Rudolph, Alice; Shults, Clifford W; Singleton, Andrew; Foroud, Tatiana

    Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene cause some forms of autosomal dominant Parkinson's disease. We measured the frequency of a novel mutation (Gly2019 ser) in familial Parkinson's disease by screening genomic DNA of patients and controls. Of 767 affected individuals from 358 multiplex families, 35 (5%) individuals were either heterozygous (34) or homozygous (one) for the mutation, and had typical clinical findings of idiopathic Parkinson's disease. Thus, our results suggest that a single LRRK2 mutation causes Parkinson's disease in 5% of individuals with familial disease. Screening for this mutation should be a component of genetic testing for Parkinson's disease.

  2. ALZHEIMER’S DISEASE: THE EXPERIENCE OF ILLNESS FROM THE PERSPECTIVE OF FAMILY CAREGIVERS

    OpenAIRE

    Thaís Oliveira da Silva; Patrícia Mônica Ribeiro; Maria Regina Martinez

    2017-01-01

    The Alzheimer's disease is characterized by being a degenerative disease that affects the brain, promoting progressive impairment of mental function. The disease progresses to a stage of total dependence, which requires the assistance of health professionals and family caregivers. This study aimed to describe the relationship between the patient and family caregiver; and, to understand how the family caregivers experiences the care.  The methodology adopted was the oral history with the techn...

  3. A consanguineous family with Hirschsprung disease, microcephaly, and mental retardation (Goldberg-Shprintzen syndrome)

    NARCIS (Netherlands)

    Brooks, AS; Breuning, MH; Osinga, J; Van der Smagt, JJ; Catsman, CE; Buys, CHCM; Meijers, C; Hofstra, RMW

    Hirschsprung disease, mental retardation, microcephaly, and specific craniofacial dysmorphism were observed in three children from a large, consanguineous, Moroccan family. A fourth child showed similar clinical features, with the exception of Hirschsprung disease. The association of these

  4. Family Health History Communication Networks of Older Adults: Importance of Social Relationships and Disease Perceptions

    Science.gov (United States)

    Ashida, Sato; Kaphingst, Kimberly A.; Goodman, Melody; Schafer, Ellen J.

    2013-01-01

    Older individuals play a critical role in disseminating family health history (FHH) information that can facilitate disease prevention among younger family members. This study evaluated the characteristics of older adults and their familial networks associated with two types of communication ("have shared" and "intend to share…

  5. Von Hippel-Lindau disease associated with myasthenia gravis not related to thymoma

    Directory of Open Access Journals (Sweden)

    Paolo Pozzato

    2013-04-01

    Full Text Available BACKGROUND Von Hippel-Lindau disease (VHL is a rare autosomal dominant inherited disorder characterized by an increased risk of tumours in a number of locations (eyes, brain, adrenal gland, pancreas, liver, kidneys, or other areas of the body. It is caused by germline mutation in the VHL gene. The VHL gene is a tumour suppressor gene that has been identified on the short arm of chromosome 3. CASE REPORT We report a case of a 60 year-old female with the clinical diagnosis of VHL type 1 (cerebellar haemangioblastoma, pancreatic cysts with subsequent steatorrhoea, and bilateral renal carcinoma who developed weakness and fatigability of skeletal muscles, left lid ptosis, snarling expression and nasal timbre speech. Acetylcholine receptor antibodies were negative in serum, while the electrodiagnostic test demonstrated an alteration of neuromuscolar junction which was consistent with the diagnosis of myasthenia gravis. Contrast-enhanced TC scan of the anterior mediastinum was performed, which excluded thymus enlargement. VHL gene evaluation in this patient identified a new mutation (c279delC9 and polymorphism c291C>G. At present the patient still suffers from ataxia and dysmetria due to cerebellar involvement in VHL, while fatigue and lid ptosis improved after the treatment with oral pyridostigmine 60 mg tid. DISCUSSION AND CONCLUSIONS To our knowledge this is the first report of a case of VHL associated with myasthenia gravis without thymoma. A case of VHL associated with a form of myasthenia gravis related to thymoma has been recently reported. In our case the absence of acetylcholine receptor antibodies may suggest a genetic origin also for the myasthenia gravis.

  6. Retinal hemangioblastoma

    DEFF Research Database (Denmark)

    Binderup, Marie Louise Mølgaard; Stendell, Anne-Sophie; Galanakis, Michael

    2017-01-01

    an asymptomatic first hemangioblastoma (80% vs 20%). Overall, 76% (41 of 54) of the vHL patients had a family history of vHL, while none of the patients without vHL did. Despite the rarity of the disease, on average more than eight new tumours are diagnosed each year due to multiple tumour development in v...

  7. Adrenal Cortex-Sparing Surgery for Bilateral Multiple Pheochromocytomas in a Patient with Von Hippel-Lindau Disease

    Directory of Open Access Journals (Sweden)

    Tarık Esen

    2012-01-01

    Full Text Available Pheochromocytomas can be a part of familial neoplastic syndromes, in which case they tend to be multiple and involve both adrenal glands. Therefore, sparing adrenocortical function represents a major concern while dealing with these hereditary lesions. Herein, we describe the clinical characteristics and the management strategy of a patient with von Hippel-Lindau (VHL disease who had multiple, bilateral pheochromocytomas as well as bilateral renal masses, pancreatic masses, and a paracaval mass. Only a portion of the left adrenal gland has remained in situ after two consecutive open surgeries and a percutaneous radiofrequency ablation which have been performed to treat the various components of this syndrome. No adrenal or extra-adrenal pheochromocytoma recurrences have been detected during a follow-up period of more than 2 years. Pancreatic and adrenal functions were normal throughout the postoperative period and never necessitated any replacement therapy. Adrenal cortex-sparing surgery is a valid option for VHL disease patients who present with synchronous bilateral adrenal pheochromocytomas.

  8. Family history of premature death and risk of early onset cardiovascular disease

    DEFF Research Database (Denmark)

    Ranthe, Mattis Flyvholm; Carstensen, Lisbeth; Oyen, Nina

    2012-01-01

    The purpose of this study was to examine the effect of a family history of premature death, cardiovascular death in particular, on the risk of early cardiovascular disease.......The purpose of this study was to examine the effect of a family history of premature death, cardiovascular death in particular, on the risk of early cardiovascular disease....

  9. Hospital Admissions, Biological Therapy, and Surgery in Familial and Sporadic Cases of Inflammatory Bowel Disease

    DEFF Research Database (Denmark)

    Trier Moller, Frederik; Andersen, Vibeke; Andersson, Mikael

    2015-01-01

    -related hospitalization, biological treatment, and surgery in familial versus sporadic cases of IBD. RESULTS: A total of 27,886 IBD cases, including 1006 IBD-relative pairs, were followed-up for up to 16 years, totaling 164,979 person-years. We observed no difference in risk of hospital admissions between familial...... and sporadic cases of IBD. However, patients with familial CD had significantly higher risk of major surgery than sporadic CD cases after 2 years of disease duration (hazard ratio, 1.62; 95% confidence interval, 1.26-2.07). Also, sensitivity analysis suggested a slightly reduced time from diagnosis to first......BACKGROUND: Easily accessible predictors of disease course in inflammatory bowel disease (IBD) are scarce, and it remains largely unknown whether a family history of IBD predicts the course of Crohn's disease (CD) and ulcerative colitis (UC). We aimed to compare the course of disease in familial...

  10. How do autoimmune diseases cluster in families? A systematic review and meta-analysis

    Science.gov (United States)

    2013-01-01

    Background A primary characteristic of complex genetic diseases is that affected individuals tend to cluster in families (that is, familial aggregation). Aggregation of the same autoimmune condition, also referred to as familial autoimmune disease, has been extensively evaluated. However, aggregation of diverse autoimmune diseases, also known as familial autoimmunity, has been overlooked. Therefore, a systematic review and meta-analysis were performed aimed at gathering evidence about this topic. Methods Familial autoimmunity was investigated in five major autoimmune diseases, namely, rheumatoid arthritis, systemic lupus erythematosus, autoimmune thyroid disease, multiple sclerosis and type 1 diabetes mellitus. Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines were followed. Articles were searched in Pubmed and Embase databases. Results Out of a total of 61 articles, 44 were selected for final analysis. Familial autoimmunity was found in all the autoimmune diseases investigated. Aggregation of autoimmune thyroid disease, followed by systemic lupus erythematosus and rheumatoid arthritis, was the most encountered. Conclusions Familial autoimmunity is a frequently seen condition. Further study of familial autoimmunity will help to decipher the common mechanisms of autoimmunity. PMID:23497011

  11. Opportunities for involving men and families in chronic disease management: a qualitative study from Chiapas, Mexico.

    Science.gov (United States)

    Fort, Meredith P; Castro, Maricruz; Peña, Liz; López Hernández, Sergio Hernán; Arreola Camacho, Gabriel; Ramírez-Zea, Manuel; Martínez, Homero

    2015-10-05

    A healthy lifestyle intervention was implemented in primary care health centers in urban parts of Tuxtla Gutiérrez, Chiapas, Mexico with an aim of reducing cardiovascular disease risk for patients with type 2 diabetes and/or hypertension. During implementation, research questions emerged. Considerably fewer men participated in the intervention than women, and an opportunity was identified to increase the reach of activities aimed at improving disease self-management through strategies involving family members. A qualitative study was conducted to identify strategies to involve men and engage family members in disease management and risk reduction. Nine men with hypertension and/or type 2 diabetes with limited to no participation in disease self-management and health promotion activities, six families in which at least one family member had a diagnosis of one or both conditions, and nine health care providers from four different government health centers were recruited for the study. Participants took part in semi-structured interviews. During interviews with families, genograms and eco-maps were used to diagram family composition and structure, and capture the nature of patients' relationships to the extended family and community resources. Transcripts were coded and a general inductive analytic approach was used to identify themes related to men's limited participation in health promotion activities, family support and barriers to disease management, and health care providers' recommendations. Participants reported barriers to men's participation in chronic disease management and healthy lifestyle education activities that can be grouped into two categories: internal and external factors. Internal factors are those for which they are able to make the decision on their own and external factors are those that are not related solely to their decision to take part or not. Four primary aspects were identified related to families' relationships with disease: different

  12. Familial associations of Alzheimer disease and essential tremor with Parkinson disease.

    Science.gov (United States)

    Costello, S; Bordelon, Y; Bronstein, J; Ritz, B

    2010-06-01

    We constructed a cohort of first-degree relatives of participants in a population-based case-control study of Parkinson disease (PD) and compared the occurrence of Alzheimer disease (AD) and essential tremor (ET) in relatives of PD cases and controls. We relied on proband interviews to assess family history in 372 probands with incident PD confirmed by a movement disorder specialist and 404 controls from three rural California counties. Overall, for the 2980 first-degree relatives of PD cases, the risk of AD was not increased compared with the 2981 relatives of controls. But relatives of younger onset PD cases (familial susceptibility to AD amongst first-degree relatives of younger onset PD cases.

  13. Pheochromocytoma complicated by cyanotic congenital heart disease: a case report.

    Science.gov (United States)

    Yamamoto, Keiko; Namba, Noriyuki; Kubota, Takuo; Usui, Takeshi; Takahashi, Kunihiko; Kitaoka, Taichi; Fujiwara, Makoto; Hori, Yumiko; Kogaki, Shigetoyo; Oue, Takaharu; Morii, Eiichi; Ozono, Keiichi

    2016-04-01

    Coincidental cyanotic congenital heart disease and pheochromocytoma is uncommon, although some cases have been reported. We describe a girl aged 15 yr and 11 mo with pheochromocytoma and tricuspid atresia treated by performing the Fontan surgery. The patient did not have any specific symptoms of syndrome related to pheochromoytoma or a family history of pheochromocytoma. During cardiac catheterization, her blood pressure increased markedly, and an α-blocker was administered. Catecholamine hypersecretion was observed in the blood and urine, and abdominal computed tomography revealed a tumor in the right adrenal gland. Scintigraphy showed marked accumulation of (123)I-metaiodobenzylguanidine in the tumor, which led to a diagnosis of pheochromocytoma. We did not detect any germline mutations in the RET, VHL, SDHB, SDHD, TMEM127, or MAX genes. This patient had experienced mild systemic hypoxia since birth, which may have contributed to the development of pheochromocytoma.

  14. Identification and description of three families with familial Alzheimer disease that segregate variants in the SORL1 gene.

    Science.gov (United States)

    Thonberg, Håkan; Chiang, Huei-Hsin; Lilius, Lena; Forsell, Charlotte; Lindström, Anna-Karin; Johansson, Charlotte; Björkström, Jenny; Thordardottir, Steinunn; Sleegers, Kristel; Van Broeckhoven, Christine; Rönnbäck, Annica; Graff, Caroline

    2017-06-09

    Alzheimer disease (AD) is a progressive neurodegenerative disorder and the most common form of dementia. The majority of AD cases are sporadic, while up to 5% are families with an early onset AD (EOAD). Mutations in one of the three genes: amyloid beta precursor protein (APP), presenilin 1 (PSEN1) or presenilin 2 (PSEN2) can be disease causing. However, most EOAD families do not carry mutations in any of these three genes, and candidate genes, such as the sortilin-related receptor 1 (SORL1), have been suggested to be potentially causative. To identify AD causative variants, we performed whole-exome sequencing on five individuals from a family with EOAD and a missense variant, p.Arg1303Cys (c.3907C > T) was identified in SORL1 which segregated with disease and was further characterized with immunohistochemistry on two post mortem autopsy cases from the same family. In a targeted re-sequencing effort on independent index patients from 35 EOAD-families, a second SORL1 variant, c.3050-2A > G, was found which segregated with the disease in 3 affected and was absent in one unaffected family member. The c.3050-2A > G variant is located two nucleotides upstream of exon 22 and was shown to cause exon 22 skipping, resulting in a deletion of amino acids Gly1017- Glu1074 of SORL1. Furthermore, a third SORL1 variant, c.5195G > C, recently identified in a Swedish case control cohort included in the European Early-Onset Dementia (EU EOD) consortium study, was detected in two affected siblings in a third family with familial EOAD. The finding of three SORL1-variants that segregate with disease in three separate families with EOAD supports the involvement of SORL1 in AD pathology. The cause of these rare monogenic forms of EOAD has proven difficult to find and the use of exome and genome sequencing may be a successful route to target them.

  15. Modeling familial Alzheimer's disease with induced pluripotent stem cells

    National Research Council Canada - National Science Library

    Yagi, Takuya; Ito, Daisuke; Okada, Yohei; Akamatsu, Wado; Nihei, Yoshihiro; Yoshizaki, Takahito; Yamanaka, Shinya; Okano, Hideyuki; Suzuki, Norihiro

    2011-01-01

    ...). Induced pluripotent stem cell (iPSC) technology can be used to model human disorders and provide novel opportunities to study cellular mechanisms and establish therapeutic strategies against various diseases, including neurodegenerative diseases...

  16. Emerging Models for Mobilizing Family Support for Chronic Disease Management: A Structured Review

    Science.gov (United States)

    Rosland, Ann-Marie; Piette, John D.

    2015-01-01

    Objectives We identify recent models for programs aiming to increase effective family support for chronic illness management and self-care among adult patients without significant physical or cognitive disabilities. We then summarize evidence regarding the efficacy for each model identified. Methods Structured review of studies published in medical and psychology databases from 1990 to the present, reference review, general Web searches, and conversations with family intervention experts. Review was limited to studies on conditions that require ongoing self-management, such as diabetes, chronic heart disease, and rheumatologic disease. Results Programs with three separate foci were identified: 1) Programs that guide family members in setting goals for supporting patient self-care behaviors have led to improved implementation of family support roles, but have mixed success improving patient outcomes. 2) Programs that train family in supportive communication techniques, such as prompting patient coping techniques or use of autonomy supportive statements, have successfully improved patient symptom management and health behaviors. 3) Programs that give families tools and infrastructure to assist in monitoring clinical symptoms and medications are being conducted, with no evidence to date on their impact on patient outcomes. Discussion The next generation of programs to improve family support for chronic disease management incorporate a variety of strategies. Future research can define optimal clinical situations for family support programs, the most effective combinations of support strategies, and how best to integrate family support programs into comprehensive models of chronic disease care. PMID:20308347

  17. Alpha-synuclein in familial Alzheimer disease: epitope mapping parallels dementia with Lewy bodies and Parkinson disease.

    Science.gov (United States)

    Lippa, C F; Schmidt, M L; Lee, V M; Trojanowski, J Q

    2001-11-01

    Alpha-synuclein is a major component of Lewy bodies (LBs) in Parkinson disease and dementia with LBs and of glial cytoplasmic inclusions in multiple system atrophy. However, epitope mapping for alpha-synuclein is distinctive in different neurodegenerative diseases. The reasons for this are poorly understood but may reflect fundamental differences in disease mechanisms. To investigate the alpha-synuclein epitope mapping properties of LBs in familial Alzheimer disease. We compared LBs in familial Alzheimer disease with those in synucleinopathies by probing 6 brains of persons with familial Alzheimer disease using a panel of antibodies to epitopes spanning the alpha-synuclein protein. Results were compared with data from brains of persons with Parkinson disease, dementia with LBs, and multiple system atrophy. The brains of persons with familial Alzheimer disease showed consistent staining of LBs with all antibodies, similar to Parkinson disease and dementia with LBs but different from alpha-synuclein aggregates that occurred in multiple system atrophy. These data suggest that the epitope profiles of alpha-synuclein in LBs are similar, regardless of whether the biological trigger is related to synuclein or a different genetic pathway. These findings support the hypothesis that the mechanism of alpha-synuclein aggregation is the same within cell types but distinctive between cell types.

  18. Cystic changes of breast in a family with autosomal dominant polycystic kidney disease.

    Science.gov (United States)

    Maleki, Davood; Ghafari, Ali

    2009-10-01

    Autosomal dominant polycystic kidney disease is associated with cysts in many organs including the liver, pancreas, lungs, spleen, ovaries, testes, thyroid, and uterus. However, there is no report, to our knowledge, of cystic changes of the breast along with this disease. We describe 3 members of a family with multiple bilateral breast cysts in association with autosomal dominant polycystic kidney disease.

  19. Higher prevalence of autoimmune diseases and longer spells of vertigo in patients affected with familial Ménière's disease: A clinical comparison of familial and sporadic Ménière's disease.

    Science.gov (United States)

    Hietikko, Elina; Sorri, Martti; Männikkö, Minna; Kotimäki, Jouko

    2014-06-01

    PURPOSE This study compared clinical features, predisposing factors, and concomitant diseases between sporadic and familial Ménière's disease (MD). METHOD Retrospective chart review and postal questionnaire were used. Participants were 250 definite patients with MD (sporadic, n =149; familial, n = 101) who fulfilled the American Academy of Otorhinolaryngology-Head and Neck Surgery (1995) criteria. RESULTS On average, familial patients were affected 5.6 years earlier than sporadic patients, and they suffered from significantly longer spells of vertigo (p = .007). The prevalence of rheumatoid arthritis (p = .002) and other autoimmune diseases (p = .046) was higher among the familial patients, who also had more migraine (p = .036) and hearing impairment (p = .002) in their families. CONCLUSION The clinical features of familial and sporadic MD are very similar in general, but some differences do exist. Familial MD patients are affected earlier and suffer from longer spells of vertigo.

  20. [Fragility of the social network of families of children with chronic disease].

    Science.gov (United States)

    Araújo, Yana Balduíno; Reichert, Altamira Pereira da Silva; Vasconcelos, Maria Gorete Lucena de; Collet, Neusa

    2013-01-01

    Chronic disease in childhood affects the family social relations. The social network can contribute for a better coping by giving support. This work aims to analyze the fragilities of the social network of families in this condition. It is a qualitative study conducted in a public hospital of Paraíba, from April to June 2011, using genogram, ecomap and semi-structured interview with seven family members of children with chronic disease. The thematic analysis of the results helped to characterize the network and understand the social interactions in the course of the disease and the types of support received. The empirical category (dis)articulation of the social network and the modifications in family routine was built in this process and pointed the diversity of the social network composition, emphasizing that the social support provided by the network is significant, however, not always continuous and suitable with the needs of the families.

  1. Converging approaches to understanding early onset familial Alzheimer disease: A First Nation study.

    Science.gov (United States)

    Cabrera, Laura Y; Beattie, B Lynn; Dwosh, Emily; Illes, Judy

    2015-01-01

    In 2007, a novel pathogenic genetic mutation associated with early onset familial Alzheimer disease was identified in a large First Nation family living in communities across British Columbia, Canada. Building on a community-based participatory study with members of the Nation, we sought to explore the impact and interplay of medicalization with the Nation's knowledge and approaches to wellness in relation to early onset familial Alzheimer disease. We performed a secondary content analysis of focus group discussions and interviews with 48 members of the Nation between 2012 and 2013. The analysis focused specifically on geneticization, medicalization, and traditional knowledge of early onset familial Alzheimer disease, as these themes were prominent in the primary analysis. We found that while biomedical explanations of disease permeate the knowledge and understanding of early onset familial Alzheimer disease, traditional concepts about wellness are upheld simultaneously. The analysis brings the theoretical framework of "two-eyed seeing" to the case of early onset familial Alzheimer disease for which the contributions of different ways of knowing are embraced, and in which traditional and western ways complement each other on the path of maintaining wellness in the face of progressive neurologic disease.

  2. Patients with premature cardiovascular disease and a positive family history for cardiovascular disease are prone to recurrent events

    NARCIS (Netherlands)

    Mulders, Ties A.; Meyer, Zainna; van der Donk, Christel; Kroon, Abraham A.; Ferreira, Isabel; Stehouwer, Coen D. A.; Pinto-Sietsma, Sara-Joan

    2011-01-01

    Background: Premature cardiovascular disease (CVD) is treated in the same way as CVD of advanced age. However, in patients with premature CVD and a family history of CVD, different -possibly genetic-mechanisms may underlie this disease, which current medical treatment is not targeted to. This

  3. Family genetics of Paget’s disease of bone

    OpenAIRE

    Santos, Patrícia Alexandra Silva, 1991-

    2014-01-01

    Tese de mestrado. Biologia (Biologia Humana e Ambiente). Universidade de Lisboa, Faculdade de Ciências, 2014 Paget's disease of bone (PDB) is a systemic disease characterized by increased bone resorption and formation, causing gradual destruction of parts of the skeleton and subsequent reconstruction of a more fragile bone. PDB has an overall incidence of 2% in the population over 55 years. PDB is a complex disease with multiple genes implicated in its pathogenesis, but in its monogenic fo...

  4. Family Stigma and Caregiver Burden in Alzheimer's Disease

    Science.gov (United States)

    Werner, Perla; Mittelman, Mary S.; Goldstein, Dovrat; Heinik, Jeremia

    2012-01-01

    Purpose: The stigma experienced by the family members of an individual with a stigmatized illness is defined by 3 dimensions: caregiver stigma, lay public stigma, and structural stigma. Research in the area of mental illness suggests that caregivers' perception of stigma is associated with increased burden. However, the effect of stigma on…

  5. Relative exchangeable copper: a promising tool for family screening in Wilson disease.

    Science.gov (United States)

    Trocello, Jean-Marc; El Balkhi, Souleiman; Woimant, France; Girardot-Tinant, Nadège; Chappuis, Philippe; Lloyd, Carla; Poupon, Joël

    2014-04-01

    Family screening is a main step for the diagnosis in Wilson disease. This study was undertaken to evaluate the value of relative exchangeable copper for family screening. Data from family screening were collected from the French National Center of Reference for Wilson disease. Subjects who were first- or second-degree relatives of the index case underwent clinical examination and biological parameters. Of 127 subjects examined, copper abnormalities or low ceruloplasminemia were detected in 21 subjects, corresponding to 5 patients with Wilson disease, 14 heterozygous ATP7B carriers and 2 subjects with no ATP7B mutations. Relative exchangeable copper determination significantly discriminates heterozygous ATP7B carriers and subjects with no ATP7B mutations from WD patients with a cutoff of 15%. Exchangeable copper appears to be a promising tool for family screening in Wilson disease. © 2013 International Parkinson and Movement Disorder Society.

  6. Quality of life in Chinese family caregivers for elderly people with chronic diseases

    National Research Council Canada - National Science Library

    Xie, Hui; Cheng, Cheng; Tao, Yisheng; Zhang, Jie; Robert, Delprino; Jia, Jihui; Su, Yonggang

    2016-01-01

    .... Quality of life in family caregivers for elderly people with chronic diseases was evaluated, and the demographic and characteristic factors of both elderly people and their caregivers were explored...

  7. Lyme Disease: Knowledge and Practices of Family Practitioners in Southern Quebec

    Directory of Open Access Journals (Sweden)

    Cécile Ferrouillet

    2015-01-01

    Full Text Available BACKGROUND: Public health authorities in Quebec have responded to the progressive emergence of Lyme disease (LD with surveillance activities and education for family physicians (FPs who are key actors in both vigilance and case management.

  8. Online information as support to the families of children and adolescents with chronic disease.

    Science.gov (United States)

    Mazza, Verônica de Azevedo; Lima, Vanessa Ferreira de; Carvalho, Ana Karoline da Silva; Weissheimer, Gisele; Soares, Larissa Gramazio

    2017-04-20

    To describe the use of online information as support to families of children and adolescents with chronic disease. This is an integrative review conducted in August 2015, with an online search in the following databases: PubMed, Biblioteca Virtual em Saúde, Cumulative Index to Nursing & Allied Health Literature, and Science Direct. Twelve studies were selected from the 293 studies found in the databases. After analysis, the following two categories emerged: Potentialities of the use of online information by families of children and adolescents with chronic disease, and Weaknesses of the use of online information by families of children and adolescents with chronic disease. The internet offers a wide range of information that helps families manage the care of children and adolescents with chronic diseases, but it also has characteristics that need to be analysed.

  9. GVHD (Graft-Versus-Host Disease): A Guide for Patients and Families After Stem Cell Transplant

    Science.gov (United States)

    ... Disease): A guide for patients and families after stem cell transplant The immune system is the body's tool ... and attacking them. When you receive a donor's stem cells (the “graft”), the stem cells recreate the donor's ...

  10. 76 FR 13621 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Family...

    Science.gov (United States)

    2011-03-14

    ... Control Special Emphasis Panel (SEP): Family History and Diamond Blackfan Anemia, DD11- 010, Initial... the Agency for Toxic Substances and Disease Registry. Dated: March 7, 2011. Elaine L. Baker, Director...

  11. Archetypal and new families with Alexander disease and novel mutations in GFAP

    NARCIS (Netherlands)

    Messing, Albee; Li, Rong; Naidu, Sakkubai; Taylor, J. Paul; Silverman, Lital; Flint, Daniel; van der Knaap, Marjo S.; Brenner, Michael

    2012-01-01

    To describe genetic analyses of the 2 most thoroughly studied, historically seminal multigenerational families with Alexander disease described prior to the identification of GFAP as the related gene, as well as 1 newly discovered family. Clinical histories were obtained and DNA was analyzed from

  12. Disease evolution and outcomes in familial AML with germline CEBPA mutations

    DEFF Research Database (Denmark)

    Tawana, Kiran; Wang, Jun; Renneville, Aline

    2015-01-01

    In-depth molecular investigation of familial leukemia has been limited by the rarity of recognized cases. This study examines the genetic events initiating leukemia and details the clinical progression of disease across multiple families harboring germ-line CEBPA mutations. Clinical data were col...

  13. The impact of an infant's severe congenital heart disease on the family: a prospective cohort study.

    Science.gov (United States)

    Werner, Helene; Latal, Beatrice; Valsangiacomo Buechel, Emanuela; Beck, Ingrid; Landolt, Markus A

    2014-01-01

    The aim of this article is to investigate the impact of a child's severe congenital heart disease on the family and to prospectively examine the influence of disease specific and psychosocial factors on the family. A prospective cohort study. Parents of 104 infants who had undergone cardiopulmonary bypass surgery before the age of 12 months for congenital heart disease were included. None. Parents completed the generic Impact on Family scale and a social support questionnaire; a large number of medical data were extracted from the patients' hospital records. Parents most frequently reported that they were thinking about not having more children and living on a "roller coaster." No difference was found in the total Impact on Family scale score between fathers and mothers. The presence of a genetic disorder in the child and lower levels of perceived social support was significantly associated with a greater impact on the family. The impact of an infant's congenital heart disease on the family is determined both by child's medical condition and family's psychosocial factors. Families with poorer social support network may have the greatest need for professional interventions, especially if their child has an underlying genetic disorder. © 2013 Wiley Periodicals, Inc.

  14. Cultural adaptation of the Family Management Measure among families of children and adolescents with chronic diseases

    Directory of Open Access Journals (Sweden)

    Carolliny Rossi de Faria Ichikawa

    2014-01-01

    Full Text Available OBJECTIVES: to perform the cultural adaptation of the Family Management Measure into the Brazilian Portuguese language. METHOD: the method complied with international recommendations for this type of study and was composed of the following steps: translation of the instrument into the Portuguese language; reaching consensus over the translated versions; assessment by an expert committee; back translation; and pretest. RESULTS: these stages enabled us to obtain conceptual, by-item, semantic, idiomatic, and operational equivalences, in addition to content validation. CONCLUSION: the Family Management Measure is adapted to the Brazilian Portuguese language and that version is named Instrumento de Medida de Manejo Familiar.

  15. The eye in systemic disease | Lenake | South African Family Practice

    African Journals Online (AJOL)

    The eye is a unique organ which is often involved in systemic disease. Patients with systemic disease may first present with eye pathology, and patients with known systemic illnesses may need to have their eyes specifically checked for ocular complications. It is thus useful for the physician to be familiar with the ocular ...

  16. Mortality in inherited cardiac diseases: directing care in affected families

    NARCIS (Netherlands)

    Nannenberg, E.A.

    2014-01-01

    Many patients with an inherited cardiac disease face a substantial mortality risk, due to arrhythmias (sudden cardiac death), heart failure or embolic stroke. Knowledge about the mortality of diseases can help doctors and patients to make decisions on (timing of) treatment, screening strategies,

  17. Palliative Care for Patients and Families With Parkinson's Disease

    NARCIS (Netherlands)

    Bouca-Machado, R.; Titova, N.; Chaudhuri, K.R.; Bloem, B.R.; Ferreira, J.J.

    2017-01-01

    Parkinson's disease is the second most common neurodegenerative disease worldwide. There is widespread consensus that Parkinson patients, their carers, and clinicians involved in their care would benefit from a fully integrated, need-based provision of palliative care. However, the concept of

  18. Neuropsychiatric symptoms of the elderly with Alzheimer's disease and the family caregivers' distress

    OpenAIRE

    Luana Baldin Storti; Débora Teles Quintino; Natália Michelato Silva; Luciana Kusumota; Sueli Marques

    2016-01-01

    ABSTRACT Objective: to analyze the relationship between the distress of the family caregiver and the presence of neuropsychiatric symptoms in elderly patients with Alzheimer's disease or mixed dementia. Method: a descriptive, cross-sectional study conducted in the Geriatric and Dementias Clinic of a general tertiary hospital, with 96 elderly people with Alzheimer's disease or mixed dementia and their family caregivers. Questionnaires to characterize the elderly and caregivers, and the Neu...

  19. Rare deleterious mutations are associated with disease in bipolar disorder families.

    Science.gov (United States)

    Rao, A R; Yourshaw, M; Christensen, B; Nelson, S F; Kerner, B

    2017-07-01

    Bipolar disorder (BD) is a common, complex and heritable psychiatric disorder characterized by episodes of severe mood swings. The identification of rare, damaging genomic mutations in families with BD could inform about disease mechanisms and lead to new therapeutic interventions. To determine whether rare, damaging mutations shared identity-by-descent in families with BD could be associated with disease, exome sequencing was performed in multigenerational families of the NIMH BD Family Study followed by in silico functional prediction. Disease association and disease specificity was determined using 5090 exomes from the Sweden-Schizophrenia (SZ) Population-Based Case-Control Exome Sequencing study. We identified 14 rare and likely deleterious mutations in 14 genes that were shared identity-by-descent among affected family members. The variants were associated with BD (Pdisorders including holoprosencephaly and epilepsy. Our results demonstrate that exome sequencing in multigenerational families with BD is effective in identifying rare genomic variants of potential clinical relevance and also disease modifiers related to coexisting medical conditions. Replication of our results and experimental validation are required before disease causation could be assumed.

  20. A family study of asymptomatic small bowel Crohn's disease.

    Science.gov (United States)

    Biancone, Livia; Calabrese, Emma; Petruzziello, Carmelina; Capanna, Alessandra; Zorzi, Francesca; Onali, Sara; Condino, Giovanna; Lolli, Elisabetta; Ciccacci, Cinzia; Borgiani, Paola; Pallone, Francesco

    2014-03-01

    Discrepancies between severity of lesions and symptoms may be observed in Crohn's disease. We prospectively assessed whether Crohn's disease may be diagnosed among asymptomatic relatives of patients, using Small Bowel Contrast Ultrasonography. Diagnosis of asymptomatic Crohn's disease relatives was defined ultrasonographically as: bowel wall thickness >3mm, bowel dilation/stricture, lumen diameter >2.5 cm. Diagnosis was confirmed by ileocolonoscopy. Subjects were also screened for the Leu3020insC mutation. Consent was given by 35 asymptomatic first-degree relatives of 18 Crohn's disease patients. Ultrasonography indicated increased bowel wall thickness (5mm) compatible with ileal Crohn's disease in 1 relative (2.8%), a 42 year-old male. Ileocolonoscopy, histology, and radiology confirmed the diagnosis of stricturing ileal Crohn's disease. Gallbladder stones were detected in 7/35 (20%) relatives and Leu3020insC mutation in 3/35 (8.5%). Small Bowel Contrast Ultrasonography may be a useful tool to diagnose asymptomatic small bowel Crohn's disease among first-degree relatives of patients. Copyright © 2013 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  1. Generalized Vitiligo Associated Autoimmune Diseases in Japanese Patients Their Families

    Directory of Open Access Journals (Sweden)

    Tomohiko Narita

    2011-01-01

    Conclusions: Among Japanese vitiligo patients, there is a subgroup with strong evidence of genetically determined susceptibility to not only vitiligo, but also to autoimmune thyroid disease and other autoimmune disorders.

  2. Patients and families realising their future with chronic obstructive pulmonary disease-A qualitative study.

    Science.gov (United States)

    Bragadottir, Gudrun H; Halldorsdottir, Bryndis S; Ingadottir, Thorbjorg S; Jonsdottir, Helga

    2017-04-05

    To gain insight into the lived experience of learning about having chronic obstructive pulmonary disease for patients and their families. Chronic obstructive pulmonary disease often progresses for years. Adjustment to declining health is gradual, and the disease may have developed considerably when health care is sought and people are diagnosed. Reaching patients at early stages is necessary to delay progression of the disease. Interpretive phenomenology. Data were collected in four family focus group interviews (N = 37) and a subsample of eight family-dyad interviews. Patients were eight men, and 14 women aged 51-68 years. Majority of the patients (n = 19) were at GOLD grades II and III, with three at grade IV. The family members were eight men, and seven women aged 29-73 years. Data were collected between June-November 2012. Five, not mutually exclusive themes, revealed a long and arduous process of learning about and becoming diagnosed with chronic obstructive pulmonary disease and how unaware participants were of the imminent threat that the disease imposes on life. The themes were as follows: burden of shame and self-blame, enclosed in addiction, living in parallel worlds, realising the existence of the disease and a cry for empathy. Learning about and realising the existence of chronic obstructive pulmonary disease and what it entails at present time and in the future was bleak for the participants. The patients tended to put aside the thought of being a person with chronic obstructive pulmonary disease and defer actions that might halter progression of the disease, particularly to quit smoking. Individuals and families need support early in the disease process to realise and accept the existence of chronic obstructive pulmonary disease and particularly to deal with the challenges that nicotine addiction, shame and self-blame present. Increased public awareness about this enormous, but hidden, health problem is necessary. © 2017 John Wiley & Sons Ltd.

  3. Postpolio syndrome. Unusual disease in rural family practice.

    Science.gov (United States)

    Hatcher, L. B.

    1995-01-01

    Postpolio syndrome is a sequela of paralytic poliomyelitis seen in approximately 25% of polio victims. Because the symptoms are nonspecific, it can be difficult to diagnose. Getting information about diagnosis and treatment of unusual conditions in rural and remote regions can be difficult, and physicians sometimes find themselves in the position of being the on-site "expert." Physicians must make difficult decisions with patients and their families about life-giving therapies, advance directives, and the like. Images Figure 1 Figure 2 PMID:7787494

  4. Familial Prion Disease with Alzheimer Disease-Like Tau Pathology and Clinical Phenotype

    Science.gov (United States)

    Jayadev, Suman; Nochlin, David; Poorkaj, Parvoneh; Steinbart, Ellen J.; Mastrianni, James A.; Montine, Thomas J.; Ghetti, Bernardino; Schellenberg, Gerard D.; Bird, Thomas D.; Leverenz, James B.

    2011-01-01

    Objective To describe the Alzheimer disease (AD)-like clinical and pathological features, including marked neurofibrillary tangle (NFT) pathology, of a familial prion disease due to a rare nonsense mutation of the prion gene (PRNP). Methods Longitudinal clinical assessments were available for the proband and her mother. After death, both underwent neuropathological evaluation. PRNP was sequenced after failure to find immunopositive Aβ deposits in the proband and the documentation of prion protein (PrP) immunopositive pathology. Results The proband presented at age 42 years with a 3-year history of progressive short-term memory impairment and depression. Neuropsychological testing found impaired memory performance, with relatively preserved attention and construction. She was diagnosed with AD and died at age 47 years. Neuropathologic evaluation revealed extensive limbic and neocortical NFT formation and neuritic plaques consistent with a Braak stage of VI. The NFTs were immunopositive, with multiple tau antibodies, and electron microscopy revealed paired helical filaments. However, the neuritic plaques were immunonegative for Aβ, whereas immunostaining for PrP was positive. The mother of the proband had a similar presentation, including depression, and had been diagnosed clinically and pathologically as AD. Reevaluation of her brain tissue confirmed similar tau and PrP immunostaining findings. Genetic analysis revealed that both the proband and her mother had a rare PRNP mutation (Q160X) that resulted in the production of truncated PrP. Interpretation We suggest that PRNP mutations that result in a truncation of PrP lead to a prolonged clinical course consistent with a clinical diagnosis of AD and severe AD-like NFTs. PMID:21416485

  5. Familial Alzheimer's disease-associated presenilin-1 alters cerebellar activity and calcium homeostasis

    NARCIS (Netherlands)

    Sepulveda-Falla, Diego; Barrera-Ocampo, Alvaro; Hagel, Christian; Korwitz, Anne; Vinueza-Veloz, Maria Fernanda; Zhou, Kuikui; Schonewille, Martijn; Zhou, Haibo; Velazquez-Perez, Luis; Rodriguez-Labrada, Roberto; Villegas, Andres; Ferrer, Isidro; Lopera, Francisco; Langer, Thomas; De Zeeuw, Chris I; Glatzel, Markus

    2014-01-01

    Familial Alzheimer's disease (FAD) is characterized by autosomal dominant heritability and early disease onset. Mutations in the gene encoding presenilin-1 (PS1) are found in approximately 80% of cases of FAD, with some of these patients presenting cerebellar damage with amyloid plaques and ataxia

  6. Mutations in ABC1 in Tangier disease and familial high-density lipoprotein deficiency

    NARCIS (Netherlands)

    Brooks-Wilson, A.; Marcil, M.; Clee, S. M.; Zhang, L. H.; Roomp, K.; van Dam, M.; Yu, L.; Brewer, C.; Collins, J. A.; Molhuizen, H. O.; Loubser, O.; Ouelette, B. F.; Fichter, K.; Ashbourne-Excoffon, K. J.; Sensen, C. W.; Scherer, S.; Mott, S.; Denis, M.; Martindale, D.; Frohlich, J.; Morgan, K.; Koop, B.; Pimstone, S.; Kastelein, J. J.; Genest, J.; Hayden, M. R.

    1999-01-01

    Genes have a major role in the control of high-density lipoprotein (HDL) cholesterol (HDL-C) levels. Here we have identified two Tangier disease (TD) families, confirmed 9q31 linkage and refined the disease locus to a limited genomic region containing the gene encoding the ATP-binding cassette

  7. Using family history information to promote healthy lifestyles and prevent diseases; A discussion of the evidence

    NARCIS (Netherlands)

    L. Claassen (Liesbeth); L. Henneman (Lidewij); A.C.J.W. Janssens (Cécile); M. Wijdenes-Pijl (Miranda); N. Qureshi (Nadeem); F.M. Walter (Fiona); P.W. Yoon (Paula); D.R.M. Timmermans (Danielle)

    2010-01-01

    textabstractBackground. A family history, reflecting genetic susceptibility as well as shared environmental and behavioral factors, is an important risk factor for common chronic multifactorial diseases such as cardiovascular diseases, type 2 diabetes and many cancers. Discussion. The purpose of the

  8. Type 2 Gaucher\\'s disease in a Malian family | Traoré | African ...

    African Journals Online (AJOL)

    Gaucher's disease is a recessive autosomal disorder caused by an inherited deficiency of betaglucocerebrosidase. We report here the case of an 8 month old child, fourth in a family of four children, who presents the neuropathic form of the disease. The dosages of betaglucosidase activity using C14 techniques have ...

  9. Nigerian family physicians' knowledge of oral diseases and their ...

    African Journals Online (AJOL)

    Oral health knowledge was not satisfactory with 54% and 45.7% of them being able to give a correct description of dental caries and periodontal diseases respectively. Physicians who had practiced for ten years or less had better knowledge than those who had practiced for over fifteen years. This was however not ...

  10. Family history of cardiovascular disease and parental lifestyle behaviors are associated with offspring cardiovascular disease risk markers in childhood.

    Science.gov (United States)

    Silva, Danilo R; Werneck, André O; Collings, Paul J; Fernandes, Rômulo A; Barbosa, Décio S; Ronque, Enio R V; Sardinha, Luís B; Cyrino, Edilson S

    2017-09-10

    Cardiovascular disease risk markers have become more prevalent in childhood. To provide increased understanding of the etiology of this public health issue, we investigated associations between family characteristics with cardiovascular disease risk markers in adolescents from a developing nation. In this cross-sectional study data for fasting glucose, lipoproteins (LDL-C and HDL-C), triglycerides, and total cholesterol were collected from 991 adolescents aged 10-17 who were recruited from public schools in Londrina city, Southern Brazil. Family history of cardiovascular disease and parental engagement in risk behavior (alcohol consumption and tobacco smoking) were collected using a self-reported parental questionnaire. Socioeconomic status, adolescent physical activity (estimated by Baecke questionnaire), self-reported tobacco and alcohol intake, and somatic maturation (age at peak height velocity) were used as covariates. Logistic regression was used for the main analyses. Independent of adolescent lifestyle behaviors, associations (ORadj [95% CI]) were found between: (1) paternal family history of cardiovascular disease with increased likelihood of high adolescent offspring BMI (1.53 [1.01 to 2.32]) and high triglycerides (2.93 [1.04 to 8.27]); (2) maternal family history of cardiovascular disease with heightened odds of high adolescent offspring triglycerides (2.84 [1.02 to 7.91]); (3) maternal cardiovascular disease with higher odds of high fasting glucose (2.16 [1.13 to 4.14]), and (4) maternal smoking with increased odds of high LDL-C (1.78 [1.14 to 2.79]) and high total cholesterol (1.77 [1.01 to 3.10]) in adolescent offspring. Family history of cardiovascular disease and maternal tobacco smoking are related to increased cardiovascular risk in adolescents, potentially independent of their own lifestyle behaviors. © 2017 Wiley Periodicals, Inc.

  11. Assessment of Quality of Life of Family Members of Inpatients with End-Stage Disease.

    Science.gov (United States)

    Bužgová, Radka; Kozáková, Radka; Sikorová, Lucie

    2015-01-01

    An important aim of palliative care is to ensure the highest possible quality of life (QoL) for the family members of patients. We aimed to determine the QoL of family members of hospitalized patients with end-stage disease, as well as differences in QoL based on socio-demographic characteristics and the patient's functional status, psychological distress, and QoL. Study participants were 292 family members of terminally ill patients at University Hospital, Ostrava, Czech Republic. To evaluate family members' QoL, we used the Quality of Life in Life-Threatening Illness--Family Carer Version (QOLLTI-F). We used the Hospital Anxiety and Depression Scale (HADS) and the Karnofsky Performance Status (KPS) Scale to assess patients' functional status and psychological distress. A statistically significant difference was found in QoL evaluation based on family members' socio-demographic characteristics in education, employment, and age. A significantly lower QoL score was observed for patients' life partners in six domains. A correlation was found between patients' poorer functional status and family members' lower QoL. We found lower global QoL in family members of patients with depression. Family support is a cornerstone of palliative care. Palliative care professionals should focus on at-risk family members--the life partners of patients, the unemployed, younger people, and those whose ill loved one has a poor functional status.

  12. Pulmonary artery pressure and iron deficiency in patients with upregulation of hypoxia sensing due to homozygous VHL(R200W) mutation (Chuvash polycythemia).

    Science.gov (United States)

    Sable, Craig A; Aliyu, Zakari Y; Dham, Niti; Nouraie, Mehdi; Sachdev, Vandana; Sidenko, Stanislav; Miasnikova, Galina Y; Polyakova, Lydia A; Sergueeva, Adelina I; Okhotin, Daniel J; Bushuev, Vladimir; Remaley, Alan T; Niu, Xiaomei; Castro, Oswaldo L; Gladwin, Mark T; Kato, Gregory J; Prchal, Josef T; Gordeuk, Victor R

    2012-02-01

    Patients with Chuvash polycythemia, (homozygosity for the R200W mutation in the von Hippel Lindau gene (VHL)), have elevated levels of hypoxia inducible factors HIF-1 and HIF-2, often become iron-deficient secondary to phlebotomy, and have elevated estimated pulmonary artery pressure by echocardiography. The objectives of this study were to provide a comprehensive echocardiographic assessment of cardiovascular physiology and to identify clinical, hematologic and cardiovascular risk factors for elevation of tricuspid regurgitation velocity in children and adults with Chuvash polycythemia. This cross-sectional observational study of 120 adult and pediatric VHL(R200W) homozygotes and 31 controls at outpatient facilities in Chuvashia, Russian Federation included echocardiography assessment of pulmonary artery pressure (tricuspid regurgitation velocity), cardiac volume, and systolic and diastolic function, as well as hematologic and clinical parameters. We determined the prevalence and risk factors for elevation of tricuspid regurgitation velocity in this population and its relationship to phlebotomy. The age-adjusted mean ± SE tricuspid regurgitation velocity was higher in VHL(R200W) homozygotes than controls with normal VHL alleles (2.5±0.03 vs. 2.3±0.05 m/sec, P=0.005). The age-adjusted left ventricular diastolic diameter (4.8±0.05 vs. 4.5±0.09 cm, P=0.005) and left atrial diameter (3.4±0.04 vs. 3.2±0.08 cm, P=0.011) were also greater in the VHL(R200W) homozygotes, consistent with increased blood volume, but the elevation in tricuspid regurgitation velocity persisted after adjustment for these variables. Among VHL(R200W) homozygotes, phlebotomy therapy was associated with lower serum ferritin concentration, and low ferritin independently predicted higher tricuspid regurgitation velocity (standardized beta=0.29; P=0.009). Children and adults with Chuvash polycythemia have higher estimated right ventricular systolic pressure, even after adjustment for

  13. Combined genetic and imaging diagnosis for two large Chinese families affected with Pelizaeus-Merzbacher disease.

    Science.gov (United States)

    Lv, Y; Cao, L H; Pang, H; Lu, L N; Li, J L; Fu, Y; Qi, S L; Luo, Y; Li-Ling, J

    2012-08-06

    Pelizaeus-Merzbacher disease (PMD) is a rare X-linked recessive disorder characterized by nystagmus, impaired motor development, ataxia, and progressive spasticity. Genetically defective or altered levels of proteolipid protein (PLP1) or gap-junction alpha protein 12 gene have been found to be a common cause. Here we report on two large Han Chinese families affected with this disease. The probands of both families had produced sons featuring cerebral palsy that had never been correctly diagnosed. PMD was suspected after careful analysis of family history and clinical features. Three rounds of molecular testing, including RT-PCR, genetics linkage and SRY sequence analyses, in combination with fetal ultrasound and magnetic resonance imaging, confirmed the diagnosis. In Family 1, in addition to two patients, three carriers were identified, including one who was not yet married. Genetic testing indicated that a fetus did not have the disease. A healthy girl was born later. In Family 2, two patients and two carriers were identified, while a fetus was genetically normal. A healthy girl was born later. We concluded that by combining genetic testing and imaging, awareness of the symptoms of PMD and understanding of its molecular biology, there is great benefit for families that are at risk for producing offspring affected with this severe disease.

  14. Anterior Urethral Stricture Disease Negatively Impacts the Quality of Life of Family Members

    Directory of Open Access Journals (Sweden)

    Jonathan R. Weese

    2016-01-01

    Full Text Available Purpose. To quantify the quality of life (QoL distress experienced by immediate family members of patients with urethral stricture via a questionnaire given prior to definitive urethroplasty. The emotional, social, and physical effects of urethral stricture disease on the QoL of family members have not been previously described. Materials and Methods. A questionnaire was administered prospectively to an immediate family member of 51 patients undergoing anterior urethroplasty by a single surgeon (SBB. The survey was comprised of twelve questions that addressed the emotional, social, and physical consequences experienced as a result of their loved one. Results. Of the 51 surveyed family members, most were female (92.2%, lived in the same household (86.3%, and slept in the same room as the patient (70.6%. Respondents experienced sleep disturbances (56.9% and diminished social lives (43.1%. 82.4% felt stressed by the patient’s surgical treatment, and 83.9% (26/31 felt that their intimacy was negatively impacted. Conclusions. Urethral stricture disease has a significant impact on the family members of those affected. These effects may last decades and include sleep disturbance, decreased social interactions, emotional stress, and impaired sexual intimacy. Treatment of urethral stricture disease should attempt to mitigate the impact of the disease on family members as well as the patient.

  15. THE PREVALENCE OF CELIAC DISEASE AMONG PATIENTS WITH FAMILIAL MEDITERRANEAN FEVER

    Directory of Open Access Journals (Sweden)

    Sedat IŞIKAY

    2015-03-01

    Full Text Available Background Familial Mediterranean Fever and celiac disease are both related to auto-inflammation and/or auto-immunity and they share some common clinical features such as abdominal pain, diarrhea, bloating and flatulence. Objectives We aimed to determine the association of these two diseases, if present. Methods Totally 112 patients diagnosed with Familial Mediterranean Fever and 32 cases as healthy control were included in the study. All participants were examined for the evidence of celiac disease, with serum tissue transglutaminase IgA levels (tTG IgA. Results Totally 144 cases, 112 with Familial Mediterranean Fever and 32 healthy control cases were included in the study. tTG IgA positivity was determined in three cases with Familial Mediterranean Fever and in one case in control group. In that aspect there was no significant difference regarding the tTG IgA positivity between groups (P=0.81. Duodenum biopsy was performed to the tTG IgA positive cases and revealed Marsh Type 3b in two Familial Mediterranean Fever cases and Marsh Type 3c in the other one while the biopsy results were of the only tTG IgA positive case in control group was Marsh Type 3b. In HLA evaluation of the celiac cases; HLA DQ2 was present in two celiac cases of the Familial Mediterranean Fever group and in the only celiac case of the control group while HLA DQ8 was present in one celiac case of the Familial Mediterranean Fever group. Conclusions We did not determine an association of Familial Mediterranean Fever with celiac disease. Larger studies with subgroup analysis are warranted to determine the relationship of these two diseases.

  16. Relevance of Chronic Lyme Disease to Family Medicine as a Complex Multidimensional Chronic Disease Construct: A Systematic Review

    Directory of Open Access Journals (Sweden)

    Liesbeth Borgermans

    2014-01-01

    Full Text Available Lyme disease has become a global public health problem and a prototype of an emerging infection. Both treatment-refractory infection and symptoms that are related to Borrelia burgdorferi infection remain subject to controversy. Because of the absence of solid evidence on prevalence, causes, diagnostic criteria, tools and treatment options, the role of autoimmunity to residual or persisting antigens, and the role of a toxin or other bacterial-associated products that are responsible for the symptoms and signs, chronic Lyme disease (CLD remains a relatively poorly understood chronic disease construct. The role and performance of family medicine in the detection, integrative treatment, and follow-up of CLD are not well studied either. The purpose of this paper is to describe insights into the complexity of CLD as a multidimensional chronic disease construct and its relevance to family medicine by means of a systematic literature review.

  17. Familial hyperhomocysteinemia, age and peripheral vascular diseases - an Italian study

    Directory of Open Access Journals (Sweden)

    Sandro Michelini

    2013-01-01

    Full Text Available Hyperhomocysteinemia is a widely recognized, although not yet entirely understood, risk factor for cardiovascular disease. Particularly, the complex relationships between age, hyperhomocysteinemia, predisposing genetic factors and peripheral vascular diseases have not been fully evaluated. Our contribution to this issue is a retrospective analysis of a large series of patients with peripheral arterial, venous and lymphatic disease, and of their blood relatives, with special reference to homocysteine plasma levels, age and methylenetetrahydrofolate reductase (MTHFR polymorphisms. Serum homocysteine was measured in 477 patients (286 males, 191 females, age range 19-78 years with various vascular clinical conditions: postphlebitic syndrome (46 recurrent venous ulcers (78, arterial diseases (101 primary lymphoedema (87, secondary lymphoedema (161 and outlet thoracic syndrome (4, and in 50 normal controls. A MTHFR study for polymorphisms was carried on in the subjects with homocysteine values exceeding 15 mol/L. Serum homocysteine determination and MTHFR polymorphism studies were performed also in 1430 healthy blood related relatives (mainly siblings, descendents and sibling descendents of the subjects with hyperhomocysteinemia and MTHFR polymorphisms. We found MTHFR polymorphisms in 20% of controls and in 69.3%, 69.5% and 53.8% of hyperhomocysteinemic subjects with arterial diseases, postphlebitic syndrome and venous ulcers, respectively. As expected, the percentage of hyperhomocysteinemia in patients with secondary lymphoedema and with thoracic outlet syndrome did not show significant differences compared to the control group. A MTHFR polymorphism was found in 116 out of the 214 hyperhomocysteinemic patients, i.e., in the 54% of the overall patient population with hyperhomocysteinemia (214 patients. Interestingly 750 (52% out of the 1430 blood relatives of the 116 patients with hyperhomocysteinemia and MTHFR polymorphisms showed at least one

  18. Caring for people with early and advanced chronic obstructive pulmonary disease: how do family carers cope?

    Science.gov (United States)

    Figueiredo, Daniela; Gabriel, Raquel; Jácome, Cristina; Marques, Alda

    2014-01-01

    To examine the coping strategies of family carers of people with early and advanced chronic obstructive pulmonary disease and how those relate to their subjective health. Caring for a family member with chronic obstructive pulmonary disease can be a stressful experience. Understanding how carers cope with this is critical for improving outcomes. However, this topic has received little attention in the literature, particularly considering the care-giving experience with early chronic obstructive pulmonary disease. A cross-sectional study with a convenience sample of family carers of people with chronic obstructive pulmonary disease. A structured questionnaire was used to collect data on socio-demographics and care-giving characteristics. Self-rated physical and mental health was measured by two items from the International Classification of Functioning, Disability and Health checklist. Coping strategies were assessed with the Carers' Assessment of Managing Index. Descriptive and inferential analyses were performed. A total of 158 family carers participated: 109 caring for people with early and 49 with advanced chronic obstructive pulmonary disease. The two groups differed significantly on self-rated mental health and on problem-solving, emotional-cognitive and managing stress coping type. Significant correlations between self-rated physical health and problem-solving coping and between self-rated mental health and emotion-cognitive and managing stress coping were found for carers of patients with advanced chronic obstructive pulmonary disease. This study provides a unique insight into family carer coping strategies at different stages of chronic obstructive pulmonary disease. Carers of people with early and advanced chronic obstructive pulmonary disease cope differently with their caring demands. Nevertheless, problem-focused coping strategies were perceived as the most helpful by both groups. The findings are relevant to informing early supportive interventions

  19. Polyphenols as Modulators of Aquaporin Family in Health and Disease

    Directory of Open Access Journals (Sweden)

    Diana Fiorentini

    2015-01-01

    Full Text Available Polyphenols are bioactive molecules widely distributed in fruits, vegetables, cereals, and beverages. Polyphenols in food sources are extensively studied for their role in the maintenance of human health and in the protection against development of chronic/degenerative diseases. Polyphenols act mainly as antioxidant molecules, protecting cell constituents against oxidative damage. The enormous number of polyphenolic compounds leads to huge different mechanisms of action not fully understood. Recently, some evidence is emerging about the role of polyphenols, such as curcumin, pinocembrin, resveratrol, and quercetin, in modulating the activity of some aquaporin (AQP isoforms. AQPs are integral, small hydrophobic water channel proteins, extensively expressed in many organs and tissues, whose major function is to facilitate the transport of water or glycerol over cell plasma membranes. Here we summarize AQP physiological functions and report emerging evidence on the implication of these proteins in a number of pathophysiological processes. In particular, this review offers an overview about the role of AQPs in brain, eye, skin diseases, and metabolic syndrome, focusing on the ability of polyphenols to modulate AQP expression. This original analysis can contribute to elucidating some peculiar effects exerted by polyphenols and can lead to the development of an innovative potential preventive/therapeutic strategy.

  20. [Surgical treatment of a pheocromocytoma bilateral in a 5 year old patient with the von Hippel-Lindau disease].

    Science.gov (United States)

    Blanco, J A; Blanco, D; Alastrue, A; Castellví, A; Isnard, R M; Pintos, G; Mangas, A; Roig, N; Casasa, J M

    2004-01-01

    The disease of Von Hippel Lindau (VHL) is hereditary and causes a predisposition to the development of tumours. Organs such as the cerebellum, the pancreas, the kidney, the suprarenal glands and the retina are more usually affected by this disease. We present the case of a 5-year-old patient who suffers from asiymptomatic high blood pressure. In the family antecedents, it is relevant the case of the father, with pheocromocytoma bilateral, which led us to carry out a genetic study of his two sons. Our patient, the younger; presented a mutation of the VHL gene in the short arm of the chromosome 3. In one of the periodic controls, it could be detected high blood pressure of 160/100 mm. Hg, clinically asymptomatic. The other child did not present a genetic mutation and has no disease. The presence of high catecholamines, the detection of a 3 cm left suprarenal mass through the ecography, the TAC that did not show a right suprarenal pathology and the MBIG scintigraphy confirmed the diagnostic of pheocromocytoma. The RNM showed another 0.8-cm mass which confirmed a pheocromocytoma bilateral. We started the treatment against high blood pressure with fenoxibenzamine and diltiazem, and we controlled this problem. We also prepared the pre-and-post operation anesthetic strategy, which is so important for the surgical success. The operation started by a laparoscopic, we made left adrenalectomy and we had to reconvert to laparotomy to make partial right adrenalectomy. Six months after the operation, the patient is free from symptomatology and follows a treatment with glucocorticoides with smaller and smaller doses. The case is exceptional because it embodies the following characteristics: early diagnostic age, family affectation and discovery of asymptomatic high blood pressure. It needed an appropriate preanesthetic and anesthetic preparation, which gave way to an operation without complications. The postoperation was also stable and presented no complications.

  1. Anxiety and depression in family caregivers of people with Alzheimer disease - The LASER-AD study

    OpenAIRE

    Mahoney, R.; Regan, C.; Katona, C.; Livingston, G

    2005-01-01

    Objective: There are high rates of stress, distress, and psychological illness in family caregivers of people with dementia. Female caregivers and those caring for people with neuropsychiatric symptoms are particularly at risk. The authors report on the prevalence of anxiety and depression in a sample of family caregivers of people with Alzheimer disease (AD) and compare the characteristics of those who did or did not have those conditions. Methods: A group of 153 people with AD and their car...

  2. A Yoga and Compassion Meditation Program Reduces Stress in Familial Caregivers of Alzheimer's Disease Patients

    OpenAIRE

    Danucalov, M. A. D.; Kozasa, E. H.; Ribas, K. T.; Galdur?z, J. C. F.; Garcia, M. C.; Verreschi, I. T. N.; Oliveira, K. C.; Romani de Oliveira, L.; Leite, J. R.

    2013-01-01

    Familial caregivers of patients with Alzheimer's disease exhibit reduced quality of life and increased stress levels. the aim of this study was to investigate the effects of an 8-week yoga and compassion meditation program on the perceived stress, anxiety, depression, and salivary cortisol levels in familial caregivers. A total of 46 volunteers were randomly assigned to participate in a stress-reduction program for a 2-month period (yoga and compassion meditation program-YCMP group) (n = 25) ...

  3. Legg-Calve-Perthes disease in two generations of male family members: a case report.

    Science.gov (United States)

    Al-Omran, Ammar K; Sadat-Ali, Mir

    2013-08-01

    Legg-Calve-Perthes disease (LCPD) is a type of avascular necrosis of the femoral head occurring mainly in male children and causing early osteoarthritis. We report 2 generations of 4 male family members with LCPD-like features and mutation of the COL2A1 gene of the 12q13 chromosome. If LCPD occurs in any family member, we recommend genetic analysis and counselling as well as early radiological screening of related children.

  4. Case of Familial Moyamoya Disease Presenting 10 Years After Initial Negative Magnetic Resonance Screening in Childhood.

    Science.gov (United States)

    Aoyama, Jiro; Nariai, Tadashi; Mukawa, Maki; Inaji, Motoki; Tanaka, Yoji; Maehara, Taketoshi

    2017-09-01

    Both genetic and environmental factors are considered to contribute to the onset of moyamoya disease, but the exact mechanism has not yet been clarified. Furthermore, the typical time course of progression to vessel occlusion has not been established, even in the genetically high-risk population. We present the case of a 21-year-old female with familial history of moyamoya disease. She underwent screening for moyamoya disease 10 years prior, but no abnormalities in magnetic resonance imaging or magnetic resonance angiography were found. She presented to our hospital for transient numbness of the left upper and lower extremities and dysarthria at the age of 21. She was diagnosed with moyamoya disease and underwent bilateral encephaloduroarteriosynangiosis. Gene analysis on the point mutation of RNF213, p.R4810K, was conducted for this patient, her younger sister with moyamoya disease, and their nonsymptomatic parents. A rare variant (p.R4810K) was positive in these sisters and their mother. We show a case of familial moyamoya disease diagnosed 10 years after the magnetic resonance imaging screening in childhood. We must carefully consider when, how, and for whom screening for moyamoya disease should be performed, taking into account familial history of the disease. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. “Essential Tremor” or “the Essential Tremors”: Is This One Disease or a Family of Diseases?

    Science.gov (United States)

    Louis, Elan D.

    2014-01-01

    There is accumulating evidence that entity referred to as “essential tremor” (ET) is not a single disease. It may be a family of diseases better referred to as “the essential tremors”. This review will summarize the following evidence: (1) the presence of etiological heterogeneity, (2) the heterogeneity of findings in postmortem studies, thus suggesting several diseases, (3) recent discussion that age of onset may be an important marker of disease heterogeneity, (4) clinical expansion of the concept of “ET” in recent years to include a broader range of tremor phenomenology, other motor features (gait ataxia), other involuntary movements (dystonia), and non-motor features (cognitive problems, psychiatric problems), some of which could be primary, (5) heterogeneity of pharmacological response profile and clinical progression, (6) association of ET with Parkinson's disease, Alzheimer's disease and possibly progressive supranuclear palsy, with the possibility that some ET patients are more predisposed to develop one of these. PMID:24335621

  6. Chromosome 9p-linked families with frontotemporal dementia associated with motor neuron disease.

    Science.gov (United States)

    Le Ber, I; Camuzat, A; Berger, E; Hannequin, D; Laquerrière, A; Golfier, V; Seilhean, D; Viennet, G; Couratier, P; Verpillat, P; Heath, S; Camu, W; Martinaud, O; Lacomblez, L; Vercelletto, M; Salachas, F; Sellal, F; Didic, M; Thomas-Anterion, C; Puel, M; Michel, B-F; Besse, C; Duyckaerts, C; Meininger, V; Campion, D; Dubois, B; Brice, A

    2009-05-12

    Frontotemporal dementia associated with motor neuron disease (FTD-MND) is a rare neurodegenerative disorder that may be inherited by autosomal dominant trait. No major gene has been identified but a locus was mapped on chromosome 9 (9p21.3-p13.3). Ten French families with FTD-MND were tested for linkage to the 9p21.3-p13.3 region. We report extensive mutation screening in 9p-linked families and their clinical characteristics. We identified six new families with evidence for linkage to the chromosome 9p. Cumulative multipoint LOD score values were positive between markers D9S1121 and D9S301, reaching a peak of 8.0 at marker D9S248. Haplotype reconstruction defined the telomeric boundary at marker AFM218xg11, slightly narrowing the candidate interval. We found no disease-causing mutations by sequencing 29 candidate genes including IFT74 and no copy number variations in the 9p region. The mean age at onset was 57.9 +/- 10.3 years (range, 41-84), with wide heterogeneity within and among families suggesting age-dependant penetrance. The patients presented isolated FTD (32%), isolated MND (29%), or both disorders (39%). The general characteristics of the disease did not differ, except for an older age at onset and shorter disease duration in the 9p-linked compared to nonlinked families. TDP-43-positive neuronal cytoplasmic inclusions were found in cortex and spinal cord in 3 patients. This study increases the number of 9p-linked families now reported and shows that this locus may have a major effect on frontotemporal dementia (FTD) and motor neuron disease (MND). Considering our results, the causative gene might be implicated in at least 60% of the families with FTD-MND disorder.

  7. Coronary artery disease risk in familial combined hyperlipidemia and familial hypertriglyceridemia: a case-control comparison from the National Heart, Lung, and Blood Institute Family Heart Study.

    Science.gov (United States)

    Hopkins, Paul N; Heiss, Gerardo; Ellison, R Curtis; Province, Michael A; Pankow, James S; Eckfeldt, John H; Hunt, Steven C

    2003-08-05

    Conventional wisdom suggests that a diagnosis of familial combined hyperlipidemia (FCHL) carries a substantially greater risk of premature coronary artery disease (CAD) than a diagnosis of familial hypertriglyceridemia (FHTG). However, no population-based studies have critically addressed this issue. FCHL and FHTG were diagnosed in 10.2% and 12.3% of 334 random control families and in 16.7% and 20.5% of 293 families with at least one case of premature CAD. The diagnosis of either FCHL or FHTG in an individual was associated with an odds ratio for CAD of 2.0 (P=0.003 and 0.002, respectively). However, odds ratios for premature CAD associated with both lipid disorders decreased substantially and identically with further adjustment for hypertension, diabetes, and especially HDL cholesterol, triglycerides, or apolipoprotein B. Similar results were found for differences in carotid intima-medial thickness and ankle-brachial index. Metabolic syndrome was identified in 65% of FCHL and 71% of FHTG patients compared with 19% in controls without FCHL or FHTG and was associated with an odds ratio of 3.3 (Phypertriglyceridemia in FHTG is not benign and may warrant a change in epidemiological, genetic, and clinical approaches to these lipid disorders.

  8. Caregiver bodywork: family members' experiences of caring for a person with motor neurone disease.

    Science.gov (United States)

    Ray, Robin A; Street, Annette F

    2006-10-01

    This paper reports a study of how family members caring for people living with motor neurone disease managed the deteriorating body, their own bodywork and the associated emotional labour. People living with the neurodegenerative condition of motor neurone disease face the prospect of dying in 3-5 years from progressive loss of voluntary muscle mass and function, culminating in respiratory failure. Theories concerning the body in illness have been used to illustrate patient perspectives; however, family caregivers' experiences of the body have been neglected. An ethnographic case study was undertaken with 18 primary family caregivers and six peripheral caregivers. Primary caregivers participated over 10 months in three face-to-face, semi-structured interviews which included mapping their support networks using ecomaps. Observational data were also recorded as field notes. Peripheral caregivers were interviewed once during the same time period. The data were generated between 2003 and 2004. Informal caregiving requires engagement in various aspects of bodywork. Three body concepts were identified: the visible body--how the disease affected the patient and caregivers; the dependent body--the resulting care requirements; and the social body--how living with motor neurone disease affected their social support networks. The visible body is a continual reminder of the ravages of the disease, while the dependent body demands physical and emotional care. Social interactions decline over time, depriving family caregivers of the much needed support for sustaining their commitment to the bodywork required in caregiving. The demands of bodywork for family caregivers are increased by the continual presence of emotional labour as they seek to implement the best way to support their relative with motor neurone disease. Nurses and allied healthcare workers need to assess each family situation, asking appropriate questions to establish the most appropriate interventions to

  9. Parental consanguinity and family history of coronary artery disease strongly predict early stenosis.

    Science.gov (United States)

    Youhanna, Sonia; Platt, Daniel E; Rebeiz, Abdallah; Lauridsen, Michael; Deeb, Mary E; Nasrallah, Antoine; Alam, Samir; Puzantian, Houry; Kabbani, Samer; Ghoul, Melanie; Zreik, Tony G; el Bayeh, Hamid; Abchee, Antoine; Zalloua, Pierre

    2010-10-01

    Coronary artery disease (CAD) is a multifactorial disease with acquired and inherited components. We investigated the roles of family history and consanguinity on CAD risk and age at diagnosis in 4284 patients. The compounded impact of diabetes, hyperlipidemia, hypertension, smoking, and BMI, which are known CAD risk factors, on CAD risk and age at diagnosis was also explored. CAD was determined by cardiac catheterization. Logistic regression and stratification were performed to determine the impact of family history and consanguinity on risk and onset of CAD, controlling for diabetes, hyperlipidemia, hypertension, smoking, and BMI. Family history of CAD and gender significantly increased the risk for young age at diagnosis of CAD (pConsanguinity did not promote risk of CAD (p=0.38), but did affect age of disease diagnosis (pconsanguinity were considered as unique risk factors for CAD, compared to 62.8 years for the no-risk-factor patient category (pconsanguinity in the presence of family history lowers the age of disease diagnosis significantly for CAD, emphasizing the role of strong genetic and cultural CAD modifiers. These findings highlight the increased role of genetic determinants of CAD in some population subgroups, and suggest that populations and family structure influence genetic heterogeneity between patients with CAD. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  10. Human Papillomavirus 16 E6 Contributes HIF-1α Induced Warburg Effect by Attenuating the VHL-HIF-1α Interaction

    Directory of Open Access Journals (Sweden)

    Yi Guo

    2014-05-01

    Full Text Available Cervical cancer is still one of the leading causes of cancer deaths in women worldwide, especially in the developing countries. It is a major metabolic character of cancer cells to consume large quantities of glucose and derive more energy by glycolysis even in the presence of adequate oxygen, which is called Warburg effect that can be exaggerated by hypoxia. The high risk subtype HPV16 early oncoprotein E6 contributes host cell immortalization and transformation through interacting with a number of cellular factors. Hypoxia-inducible factor 1α (HIF-1α, a ubiquitously expressed transcriptional regulator involved in induction of numerous genes associated with angiogenesis and tumor growth, is highly increased by HPV E6. HIF-1α is a best-known target of the von Hippel-Lindau tumor suppressor (VHL as an E3 ligase for degradation. In the present work, we found that HPV16 E6 promotes hypoxia induced Warburg effect through hindering the association of HIF-1α and VHL. This disassociation attenuates VHL-mediated HIF-1α ubiquitination and causes HIF-1α accumulation. These results suggest that oncoprotein E6 plays a major role in the regulation of Warburg effect and can be a valuable therapeutic target for HPV-related cancer.

  11. The Impact of Familial Predisposition to Obesity and Cardiovascular Disease on Childhood Obesity

    Science.gov (United States)

    Nielsen, Louise Aas; Nielsen, Tenna Ruest Haarmark; Holm, Jens-Christian

    2015-01-01

    The prevalence of childhood obesity has reached alarming rates world-wide. The aetiology seems to be an interplay between genetic and environmental factors, and a surrogate measure of this complex interaction is suggested as familial predisposition. Familial predisposition to obesity and related cardiovascular disease (CVD) complications constitute the presence of obesity and/or obesity-related complications in primarily blood-related family members. The approaches of its measurement and applicability vary, and the evidence especially of its influence on obesity and obesity treatment in childhood is limited. Studies have linked a familial predisposition of obesity, CVD (hypertension, dyslipidaemia and thromboembolic events), and type 2 diabetes mellitus to BMI as well as other adiposity measures in children, suggesting degrees of familial aggregation of metabolic derangements. A pattern of predispositions arising from mothers, parents or grandparents as being most influential have been found, but further comprehensive studies are needed in order to specify the exact implications of familial predisposition. In the scope of childhood obesity this article reviews the current literature regarding familial predisposition to obesity and obesity-related complications, and how these familial predispositions may impact obesity in the offspring. PMID:26465142

  12. Family history of cardiovascular disease and non-HDL cholesterol in prepubescent non-obese children

    Directory of Open Access Journals (Sweden)

    Maria Wany Louzada Strufaldi

    Full Text Available Summary Objective: To describe the values of non-HDL cholesterol (NHDL-c and the frequency of a family history of early cardiovascular disease (family HCVD in healthy prepubescent children. Analyze the association between NHDL-c and family HCVD, and possible associations with other risk factors for cardiovascular disease (CVD. Method: Cross-sectional study including 269 prepubescent (aged 6-10 years schoolchildren with a normal body mass index (+1SD-2SD. Data collected: Family HCVD; weight and height, waist circumference and systemic blood pressure; lipid profile (total cholesterol TC, HDL-c, triglycerides and LDL-c, NHDL-c calculation (CT-HDL-c, cut-off = 145 mg/dL and insulin resistance (HOMA-IR. Results: High levels were found for NHDL-c in 10 (3.7% of these schoolchildren, and family early HCVD was found in 46 (17.1% of them. There was a weak association between family HCVD and NHDL-c (Cramer’s-V-test = 0.120; p=0.050. Among the children with NHDL-c≥145 mg/dL, 4 (40% have family HCVD. The presence of family HCVD was not associated with the variables being studied. The variables independently associated with NHDL-c ≥ 145 mg/dL were: HOMA-IR (OR=1.7; 95CI 1.1-2.6 and diastolic blood pressure (OR=1.1; 95CI 1.02-1.2. Conclusion: NHDL-c values were associated with blood pressure and insulin resistance. Family HCVD was not associated with other classic risk factors for CVD, even though the frequency found was five times higher than that of high NHDL-c.

  13. Dying with motor neurone disease, what can we learn from family caregivers?

    Science.gov (United States)

    Ray, Robin A; Brown, Janice; Street, Annette F

    2014-08-01

    Increasingly, people with neurodegenerative illness are cared for at home until close to death. Yet, discussing the reality of dying remains a social taboo. To examine the ways, family caregivers of people living with motor neurone disease (MND) experienced the dying of their relative and to identify how health practitioners can better prepare families for end-of-life care. Secondary analysis was undertaken on data sets generated from two longitudinal qualitative studies employing similar data collection and analysis methods. Combining data sets increased participant numbers in a low incidence disease group. Primary studies were undertaken with family caregivers in England and Australia. Interview and observational data were collected mostly in home. Participants who discussed dying and death formed the sample for secondary analysis. Combined data revealed four major themes: planning for end of life, unexpected dying, dignity in the dying body and positive end to MND. Despite short survival predictions, discussions among family members about dying were often sporadic and linked to loss of hope. Effective planning for death assisted caregivers to manage the final degenerative processes of dying. When plans were not effectively communicated or enacted, capacity to preserve personhood was reduced. Returning death and dying to social discourse will raise the level of community awareness and normalize conversations about end-of-life care. Strategies for on-going, effective communication that facilitates advance care planning among patients, their families and practitioners are essential to improve dying and death for people with MND and their family caregivers. © 2012 John Wiley & Sons Ltd.

  14. Elderly patients with Alzheimer’s disease and their family relationships: Caregiver perspectives

    Science.gov (United States)

    Cachioni, Meire; Lima-Silva, Thaís Bento; Ordonez, Tiago Nascimento; Galo-Tiago, Juliana; Alves, Ana Regina; Suzuki, Milena Yuri; Falcão, Deusivania Vieira da Silva

    2011-01-01

    Objective The present study was to investigate the status of the family relationships of elderly patients with Alzheimer’s disease from a caregiver’s perspective. Methods A total of sixteen relatives/caregivers of AD patients were assessed by applying a semi-structured questionnaire about family relationships. Frequency tables containing categorical variables (gender, schooling, personal income and current occupation) were compiled. Descriptive statistics were calculated of continuous variables such as age. Answers to open questions were submitted to Bardin’s content analysis. The data were held on the Epidata program and statistical analysis was performed using the SPSS v.17.0 software package. Results In line with the literature, the family was the main source of caregivers and the typical caregiver profile was female. In contrast to other studies, emotional burnout was not a major complaint in the sample studied. The ties created among family members and the life experience of each individual influences how interviewees cope with AD. Conclusion The family relationships of caregivers of AD patients represent a constant challenge, due to changes in roles within the family structure as well as to disease progression. However, participation in psychological and socio-educational activities run by pioneering institutions in Brazil, act as a mediator of stress in the lives of both caregivers and patients. PMID:29213733

  15. Elderly patients with Alzheimer's disease and their family relationships: Caregiver perspectives

    Directory of Open Access Journals (Sweden)

    Meire Cachioni

    Full Text Available Abstract Objective: The present study was to investigate the status of the family relationships of elderly patients with Alzheimer's disease from a caregiver's perspective. Methods: A total of sixteen relatives/caregivers of AD patients were assessed by applying a semi-structured questionnaire about family relationships. Frequency tables containing categorical variables (gender, schooling, personal income and current occupation were compiled. Descriptive statistics were calculated of continuous variables such as age. Answers to open questions were submitted to Bardin's content analysis. The data were held on the Epidata program and statistical analysis was performed using the SPSS v.17.0 software package. Results: In line with the literature, the family was the main source of caregivers and the typical caregiver profile was female. In contrast to other studies, emotional burnout was not a major complaint in the sample studied. The ties created among family members and the life experience of each individual influences how interviewees cope with AD. Conclusion: The family relationships of caregivers of AD patients represent a constant challenge, due to changes in roles within the family structure as well as to disease progression. However, participation in psychological and socio-educational activities run by pioneering institutions in Brazil, act as a mediator of stress in the lives of both caregivers and patients.

  16. Parenting stress in pediatric IBD: relations with child psychopathology, family functioning, and disease severity.

    Science.gov (United States)

    Gray, Wendy N; Graef, Danielle M; Schuman, Shana S; Janicke, David M; Hommel, Kevin A

    2013-05-01

    Parenting stress in pediatric inflammatory bowel disease (IBD) has been under-examined. Data validating use of the Pediatric Inventory for Parents (PIP), a measure of parenting stress associated with caring for a chronically ill child, in chronic diseases with intermittent, unpredictable disease courses, such as IBD, are needed. This study presents validity data in support of the PIP in pediatric IBD and examines relations between parenting stress and important psychosocial and medical outcomes. Adolescents (N = 130) with IBD and their caregivers across 3 sites completed measures of parenting stress, family functioning, and emotional/behavioral functioning. Disease severity was also assessed for each participant. The PIP demonstrates excellent internal consistency. Parenting stress was significantly higher among those with unhealthy general family functioning and those with children with borderline or clinically elevated internalizing symptoms. Caregiving stress was greater among parents of youth with more active Crohn's disease. Results supported the reliability and validity of the PIP for assessing caregiving stress in pediatric IBD. Routine assessment of parenting stress is recommended, particularly among parents reporting unhealthy family functioning and parents of youth with borderline or clinically elevated internalizing symptoms and more active disease.

  17. [Family and religious traditions present in medical discourses by medical professionals about children with genetic diseases].

    Science.gov (United States)

    Martins, Antilia Januária; Cardoso, Maria Helena Cabral de Almeida; Llerena, Juan Clinton; Moreira, Martha Cristina Nunes

    2012-02-01

    This study explores the influences of cultural traditions rooted in the tone of medical discourse at the Instituto Fernandes Figueira/ Fundação Oswaldo Cruz by physicians regarding children with genetic diseases involving malformations and mental retardation, as well as reflections upon the professional care for these children. Data were collected using oral interviews (in the form of conversational narratives) and were submitted to semiotic analysis. The results pointed to four main cultural traditions present in medical discourse: the norm, the reason, the family and the Jewish-Christian religiosity. This article, however, focuses on the latter two, emphasizing how the notion of the family, mainly the mythification of the mother, can make the child with a genetic disease 'invisible,' in addition to contributing towards womanhood being underestimated when contrasted with motherhood. Such concepts overlap with those brought by the religious traditions and directly influence the medical perceptions towards patients and their families.

  18. Work-Family Conflict Modifies the Association of Smoking and Periodontal Disease.

    Science.gov (United States)

    Brennan, David S; Spencer, A John; Roberts-Thomson, Kaye F

    2017-02-01

    The aims of the study were to assess the association of periodontal loss of attachment with smoking and work-family conflict and assess whether work-family conflict modifies the association of smoking and periodontal disease. A random sample of 45-54 year olds from metropolitan Adelaide, South Australia, was surveyed by mailed self-complete questionnaire during 2004-2005. Oral examinations were performed on persons who responded to the questionnaire, providing an assessment of periodontal status. A total of 879 responded (participation rate = 43.8 %), with n = 709 oral examinations (completion rate = 80.7 %). Prevalence of periodontal loss of attachment (LOA) of 6+ mm was higher (p periodontal disease. Higher levels of work interfering with family were associated with higher levels of periodontal LOA for smokers compared with non-smokers.

  19. Genetic transmission of Alzheimer disease among families in a Dutch population-based study

    NARCIS (Netherlands)

    C.M. van Duijn (Cornelia); L.A. Farrer (Lindsay); L.A. Cupples (Adrienne); A. Hofman (Albert)

    1993-01-01

    textabstractWe evaluated age at onset and transmission patterns of Alzheimer's disease (AD) in families of 198 patients who had onset of symptoms before the age of 65 years and were diagnosed before the age of 70 years. Patients were ascertained in a population based study in The Netherlands. The

  20. Cholesterol efflux regulatory protein, Tangier disease and familial high-density lipoprotein deficiency

    NARCIS (Netherlands)

    Hayden, M. R.; Clee, S. M.; Brooks-Wilson, A.; Genest, J.; Attie, A.; Kastelein, J. J.

    2000-01-01

    Cellular cholesterol efflux, by which cholesterol is transported from peripheral cells to HDL acceptor molecules for transport to the liver, is the first step of reverse cholesterol transport. Two genetic disorders, Tangier disease and some cases of familial HDL deficiency, have defects of cellular

  1. Feasibility of recruiting families into a heart disease prevention program based on dietary patterns

    Science.gov (United States)

    Offspring of parents with a history of cardiovascular disease (CVD) inherit a similar genetic profile and share diet and lifestyle behaviors. This study aimed to evaluate the feasibility of recruiting families at risk of CVD to a dietary prevention program, determine the changes in diet achieved, an...

  2. Longitudinal evaluation and assessment of cardiovascular disease in patients with homozygous familial hypercholesterolemia

    NARCIS (Netherlands)

    Kolansky, Daniel M.; Cuchel, Marina; Clark, Bernard J.; Paridon, Steve; McCrindle, Brian W.; Wiegers, Susan E.; Araujo, Luis; Vohra, Yogesh; Defesche, Joep C.; Wilson, James M.; Rader, Daniel J.

    2008-01-01

    Homozygous familial hypercholesterolemia (hoFH) is caused by mutations in the low-density lipoprotein receptor gene and is characterized by severe hypercholesterolemia from birth and onset of premature cardiovascular disease (CVD) during childhood. The onset and progression of CVD using currently

  3. Genetic determinants of white matter hyperintensities and amyloid angiopathy in familial Alzheimer's disease

    NARCIS (Netherlands)

    Ryan, Natalie S.; Biessels, Geert Jan; Kim, Lois; Nicholas, Jennifer M.; Barber, Philip A.; Walsh, Phoebe; Gami, Priya; Morris, Huw R.; Bastos-Leite, António J.; Schott, Jonathan M.; Beck, Jon; Mead, Simon; Chavez-Gutierrez, Lucia; de Strooper, Bart; Rossor, Martin N.; Revesz, Tamas; Lashley, Tammaryn; Fox, Nick C.

    2015-01-01

    Familial Alzheimer's disease (FAD) treatment trials raise interest in the variable occurrence of cerebral amyloid angiopathy (CAA); an emerging important factor in amyloid-modifying therapy. Previous pathological studies reported particularly severe CAA with postcodon 200 PSEN1 mutations and amyloid

  4. Moral landscapes and everyday life in families with Huntington´s Disease

    DEFF Research Database (Denmark)

    Huniche, Lotte

    2011-01-01

    This article is concerned with understanding moral aspects of everyday life in families with Huntington’s Disease (HD). It draws on findings from an empirical research project in Denmark in 1998e2002 involving multi-sited ethnography to argue that medical genetics provides a particular framework...

  5. CSF studies facilitate DNA diagnosis in familial Alzheimer's disease due to a presenilin-1 mutation

    NARCIS (Netherlands)

    de Bot, Susanne T; Kremer, H P H; Dooijes, Dennis; Verbeek, Marcel M

    2009-01-01

    In sporadic Alzheimer's disease (AD), cerebrospinal fluid (CSF) analysis is becoming increasingly relevant to establish an early diagnosis. We present a case of familial AD due to a presenilin-1 mutation in which CSF studies suggested appropriate DNA diagnostics. A 38 year old Dutch man presented

  6. CSF studies facilitate DNA diagnosis in familial Alzheimer's disease due to a presenilin-1 mutation.

    NARCIS (Netherlands)

    Bot, S.T. de; Kremer, H.P.H.; Dooijes, D.; Verbeek, M.M.

    2009-01-01

    In sporadic Alzheimer's disease (AD), cerebrospinal fluid (CSF) analysis is becoming increasingly relevant to establish an early diagnosis. We present a case of familial AD due to a presenilin-1 mutation in which CSF studies suggested appropriate DNA diagnostics. A 38 year old Dutch man presented

  7. Coronary heart disease risk : family history and gene-environment interaction

    NARCIS (Netherlands)

    Boer, J.M.A.

    1999-01-01

    The first part of this thesis describes research into lifestyle, genetic, and biological factors that may underlie the increased risk for coronary heart disease (CHD) in individuals with a family history of this disorder. The second part of this thesis describes whether levels of plasma

  8. Genomic selection exploits within-family genetic variation for disease resistance in rainbow trout

    Science.gov (United States)

    Flavobacterium psychrophilum is the etiological agent causing bacterial cold water disease (BCWD) in salmonid fish. Previous breeding strategies to reduce losses due to BCWD involve testing and determining phenotypic differences between multiple families of rainbow trout. These results were used to ...

  9. Family physicians and the surgical disease burden in west Africa: a ...

    African Journals Online (AJOL)

    Background: Surgical disease burden is quite high in sub Saharan Africa (SSA), and is complicated by low human resource for health. These factors tend to increase thesurgical Disability Adjusted Life Years (DALYs)in SSA. Increasing the training and deployment of surgically trained generalists like Family Physicians, is a ...

  10. COL4A2 mutation associated with familial porencephaly and small-vessel disease

    Science.gov (United States)

    Verbeek, Elly; Meuwissen, Marije EC; Verheijen, Frans W; Govaert, Paul P; Licht, Daniel J; Kuo, Debbie S; Poulton, Cathryn J; Schot, Rachel; Lequin, Maarten H; Dudink, Jeroen; Halley, Dicky J; de Coo, René IF; den Hollander, Jan C; Oegema, Renske; Gould, Douglas B; Mancini, Grazia MS

    2012-01-01

    Familial porencephaly, leukoencephalopathy and small-vessel disease belong to the spectrum of disorders ascribed to dominant mutations in the gene encoding for type IV collagen alpha-1 (COL4A1). Mice harbouring mutations in either Col4a1 or Col4a2 suffer from porencephaly, hydrocephalus, cerebral and ocular bleeding and developmental defects. We observed porencephaly and white matter lesions in members from two families that lack COL4A1 mutations. We hypothesized that COL4A2 mutations confer genetic predisposition to porencephaly, therefore we sequenced COL4A2 in the family members and characterized clinical, neuroradiological and biochemical phenotypes. Genomic sequencing of COL4A2 identified the heterozygous missense G1389R in exon 44 in one family and the c.3206delC change in exon 34 leading to frame shift and premature stop, in the second family. Fragmentation and duplication of epidermal basement membranes were observed by electron microscopy in a c.3206delC patient skin biopsy, consistent with abnormal collagen IV network. Collagen chain accumulation and endoplasmic reticulum (ER) stress have been proposed as cellular mechanism in COL4A1 mutations. In COL4A2 3206delC fibroblasts we detected increased rates of apoptosis and no signs of ER stress. Mutation phenotypes varied, including porencephaly, white matter lesions, cerebellar and optic nerve hypoplasia and unruptured carotid aneurysm. In the second family however, we found evidence for additional factors contributing to the phenotype. We conclude that dominant COL4A2 mutations are a novel major risk factor for familial cerebrovascular disease, including porencephaly and small-vessel disease with reduced penetrance and variable phenotype, which might also be modified by other contributing factors. PMID:22333902

  11. Family health history communication networks of older adults: importance of social relationships and disease perceptions.

    Science.gov (United States)

    Ashida, Sato; Kaphingst, Kimberly A; Goodman, Melody; Schafer, Ellen J

    2013-10-01

    Older individuals play a critical role in disseminating family health history (FHH) information that can facilitate disease prevention among younger family members. This study evaluated the characteristics of older adults and their familial networks associated with two types of communication (have shared and intend to share new FHH information with family members) to inform public health efforts to facilitate FHH dissemination. Information on 970 social network members enumerated by 99 seniors (aged 57 years and older) at 3 senior centers in Memphis, Tennessee, through face-to-face interviews was analyzed. Participants shared FHH information with 27.5% of the network members; 54.7% of children and 24.4% of siblings. Two-level logistic regression models showed that participants had shared FHH with those to whom they provided emotional support (odds ratio [OR] = 1.836) and felt close to (OR = 1.757). Network-members were more likely to have received FHH from participants with a cancer diagnosis (OR = 2.617) and higher familiarity with (OR = 1.380) and importance of sharing FHH with family (OR = 1.474). Participants intended to share new FHH with those who provide tangible support to (OR = 1.804) and were very close to them (OR = 2.112). Members with whom participants intend to share new FHH were more likely to belong to the network of participants with higher perceived severity if family members encountered heart disease (OR = 1.329). Many first-degree relatives were not informed of FHH. Perceptions about FHH and disease risk as well as quality of social relationships may play roles in whether seniors communicate FHH with their families. Future studies may consider influencing these perceptions and relationships.

  12. Familial occurrence of autoimmune diseases and autoantibodies in a Caucasian population of patients with systemic lupus erythematosus

    NARCIS (Netherlands)

    Corporaal, S.; Bijl, Marc; Kallenberg, Cees

    To determine the prevalence of autoimmune diseases and autoantibodies in relatives of Caucasian patients with systemic lupus erythematosus (SLE) we questioned 118 patients for the prevalence of autoimmune diseases in their relatives. Multicase SLE families were selected for further investigation:

  13. Protocol for a randomized controlled trial testing the impact of feedback on familial risk of chronic diseases on family-level intentions to participate in preventive lifestyle behaviors

    Directory of Open Access Journals (Sweden)

    Carlene J. Wilson

    2016-09-01

    Full Text Available Abstract Background Common disease risk clusters in families due to shared genetics, exposure to environmental risk factors, and because many health behaviours are established and maintained in family environments. This randomised controlled trial will test whether the provision of a family health history (FHH risk assessment tool increases intentions and engagement in health behaviors. Message distribution and collective behavior change within family networks will be mapped using social network analysis. The relative intervention impact will be compared between families from different ethnic backgrounds. Methods One hundred and fifty mothers (50 Anglo-Australian, 50 Italian-Australian, 50 Vietnamese-Australian will be recruited, with four or more other family members across three generations, including a child (aged 10–18 years. Each family is randomly assigned to intervention or control. At baseline and 6-month follow-up, all participants complete surveys to assess dietary and physical activity intentions and behaviors, attitudes towards food, and perceived disease risk. Intervention families receive a visual pedigree detailing their FHH of diabetes, heart disease, breast and bowel cancer, a health education workbook to ascertain members’ disease risk (i.e. average or above average risk, and screening and primary prevention recommendations. After completion of follow-up assessments, controls will receive their pedigree and workbook. The primary hypothesis is that attitudes and lifestyle behaviors will improve more within families exposed to FHH feedback, although the extent of this improvement may vary between families from different ethnic backgrounds. Additionally, the extent of improvement in the treatment group will be moderated by the level of family disease risk, with above-average risk leading to greater improvement. A secondary aim will explore different family members’ roles in message distribution and collective responses to

  14. Burden and associated pathologies in family caregivers of Alzheimer’s disease patients in Spain.

    Directory of Open Access Journals (Sweden)

    Vérez Cotelo N

    2015-06-01

    Full Text Available Objectives: To evaluate the profile of family caregivers of Alzheimer´s disease patients, identify any signs of psychopathology, quantify the level of perceived burden on the caregiver, and determine the caregiver’s relationship with their pharmacist. Methods: A cross-sectional study was conducted at a community pharmacy in Pontevedra, Spain. Demographic variables were collected, and the following questionnaires were administered: the Beck Depression Inventory-II, STAI-Anxiety Questionnaire, Zarit Burden Scale, family APGAR scale, and the Duke-UNC questionnaire. Results: The typical caregiver profile consists of a 55-year old first degree relative (mostly daughters with a primary education who belongs to a functional or mildly dysfunctional family. Nearly one quarter (24% of caregivers had a high perception of burden, with anxiety in 20% of caregivers and symptoms of depression in 20%. Family caregivers usually went to the same pharmacy as the patients (96%, were treated with psychotropic drugs (68%, and interacted with the pharmacist (92%. Conclusion: This study confirmed that psychological distress and burden is present among family caregivers. Care for caregivers should be integrated into patient care as part of a national plan, including grants and subsidies, which will result in better care of Alzheimer's patients. Pharmacists are the most accessible health care professionals and can provide information about Alzheimer's disease management to caregivers to ease the burden of care.

  15. Burden and associated pathologies in family caregivers of Alzheimer's disease patients in Spain.

    Science.gov (United States)

    Cotelo, Natalia Vérez; Rodríguez, N Floro Andrés; Pérez, José A Fornos; Iglesias, J Carlos Andrés; Lago, Marcos Ríos

    2015-01-01

    To evaluate the profile of family caregivers of Alzheimer's disease patients, identify any signs of psychopathology, quantify the level of perceived burden on the caregiver, and determine the caregiver's relationship with their pharmacist. A cross-sectional study was conducted at a community pharmacy in Pontevedra, Spain. Demographic variables were collected, and the following questionnaires were administered: the Beck Depression Inventory-II, STAI-Anxiety Questionnaire, Zarit Burden Scale, family APGAR scale, and the Duke-UNC questionnaire. The typical caregiver profile consists of a 55-year old first degree relative (mostly daughters) with a primary education who belongs to a functional or mildly dysfunctional family. Nearly one quarter (24%) of caregivers had a high perception of burden, with anxiety in 20% of caregivers and symptoms of depression in 20%. Family caregivers usually went to the same pharmacy as the patients (96%), were treated with psychotropic drugs (68%), and interacted with the pharmacist (92%). This study confirmed that psychological distress and burden is present among family caregivers. Care for caregivers should be integrated into patient care as part of a national plan, including grants and subsidies, which will result in better care of Alzheimer's patients. Pharmacists are the most accessible health care professionals and can provide information about Alzheimer's disease management to caregivers to ease the burden of care.

  16. Targeted Screening of Fabry Disease in Male Hemodialysis Patients in Brazil Highlights Importance of Family Screening.

    Science.gov (United States)

    Silva, Cassiano Augusto Braga; Barreto, Fellype Carvalho; Dos Reis, Marlene Antonia; Moura Junior, José Andrade; Cruz, Constança Margarida Sampaio

    2016-01-01

    Fabry disease (FD) is a lysosomal storage disorder caused by enzyme α galactosidase A (α-Gal A) deficiency due to mutations in the galactosidase alpha (GLA) gene. It leads to damage several organs, such as the kidneys, due to progressive accumulation of glycosphingolipids. To estimate the prevalence of FD among male hemodialysis (HD) patients in a northern state of Brazil. Screening was performed using a dried blood spot on filter paper to identify patients with low α-Gal A enzyme activity (≤2.2 µmol/l/h). Those with low enzyme activity underwent genetic analysis of the GLA gene. Family screening was conducted in the index cases. 2,583 male HD patients (age: 52 (18-91 years)) were screened. The α-Gal A assay identified 72 males (2.78%) with low enzyme activity. Genotyping identified 3 patients with GLA mutations: W204X, A368T, both previously reported; and C52F, a novel missense mutation. Only the patient with W204X mutation had classic FD. The prevalence rate was 0.12%. Family screening of the index cases identified 23 family members with the same mutations. The prevalence of FD amongst male HD patients found in the Northern of Brazil was low (0.12%). However, family screening of the 3 index cases identified family members at an early stage of the disease, which may benefit from earlier treatment. © 2016 S. Karger AG, Basel.

  17. Exome sequencing reveals a high genetic heterogeneity on familial Hirschsprung disease

    Science.gov (United States)

    Luzón-Toro, Berta; Gui, Hongsheng; Ruiz-Ferrer, Macarena; Sze-Man Tang, Clara; Fernández, Raquel M.; Sham, Pak-Chung; Torroglosa, Ana; Kwong-Hang Tam, Paul; Espino-Paisán, Laura; Cherny, Stacey S.; Bleda, Marta; Enguix-Riego, María del Valle; Dopazo, Joaquín; Antiñolo, Guillermo; García-Barceló, María-Mercé; Borrego, Salud

    2015-01-01

    Hirschsprung disease (HSCR; OMIM 142623) is a developmental disorder characterized by aganglionosis along variable lengths of the distal gastrointestinal tract, which results in intestinal obstruction. Interactions among known HSCR genes and/or unknown disease susceptibility loci lead to variable severity of phenotype. Neither linkage nor genome-wide association studies have efficiently contributed to completely dissect the genetic pathways underlying this complex genetic disorder. We have performed whole exome sequencing of 16 HSCR patients from 8 unrelated families with SOLID platform. Variants shared by affected relatives were validated by Sanger sequencing. We searched for genes recurrently mutated across families. Only variations in the FAT3 gene were significantly enriched in five families. Within-family analysis identified compound heterozygotes for AHNAK and several genes (N = 23) with heterozygous variants that co-segregated with the phenotype. Network and pathway analyses facilitated the discovery of polygenic inheritance involving FAT3, HSCR known genes and their gene partners. Altogether, our approach has facilitated the detection of more than one damaging variant in biologically plausible genes that could jointly contribute to the phenotype. Our data may contribute to the understanding of the complex interactions that occur during enteric nervous system development and the etiopathology of familial HSCR. PMID:26559152

  18. Abdominal aortic aneurysms do not develop more aggressively among patients with a positive family history of the disease

    DEFF Research Database (Denmark)

    Mejnert Jørgensen, Trine; Wemmelund, Holger; Green, Anders

    Title: Abdominal aortic aneurysms no not develop more aggressively among patients with a positive family history of the disease Authors: Trine M. M. Joergensen, Holger Wemmelund, Anders Green, Jes Lindholt, Kim Houlind. Introduction: It is well known, that a family history of abdominal aortic...... among patients with a positive family history of the disease....... with information on family history of AAA, diameter of AAA throughout follow-up, surgery, ruptures, comorbidity, smoking, and use of medication. Methods: Patients with and without a family history of AAA were compared regarding mean age at diagnosis and surgery, diameter of AAA at diagnosis, risk of surgery...

  19. von Hippel-Lindau disease

    DEFF Research Database (Denmark)

    Binderup, Marie Louise Mølgaard; Gimsing, Steen; Kosteljanetz, Michael

    2013-01-01

    Endolymphatic sac tumours (ELSTs) of the inner ear occur in 16% of patients with the hereditary tumor syndrome von Hippel-Lindau disease (vHL). ELSTs of all sizes can cause irreversible hearing loss which can, however, be prevented through early diagnosis and treatment. We aim to emphasize the ch...... the challenges of prophylactic ELST screening and to explore the role of audiometry in pre-symptomatic ELST screening....

  20. Supporting cystic fibrosis disease management during adolescence: the role of family and friends.

    Science.gov (United States)

    Barker, D H; Driscoll, K A; Modi, A C; Light, M J; Quittner, A L

    2012-07-01

    Successful management of a complex disease, such as cystic fibrosis (CF), requires support from family and friends; however, few studies have examined social support in adolescents with CF. Twenty-four adolescents were interviewed about the support they receive from family and friends. Interviews were transcribed, coded and analysed to determine the types, frequency and perceived supportiveness of specific behaviours. Both family and friends provided treatment-related support to adolescents with CF. Family provided more tangible support and friends provided more relational support. Adolescents also reported that the manner, timing and context of support behaviours influenced their perceptions of the behaviours' supportiveness. A subset of adolescents (17%) chose not to disclose their diagnosis to their friends. The provision of support appears to be distinct from adolescent's perception of support and there may be some behaviours, such as treatment reminders, that are important to disease management but viewed as less supportive by adolescents. Facilitating increased social support holds the promise of improving disease management during adolescents, but more work is need to understand which aspects of support are related to management outcomes. © 2011 Blackwell Publishing Ltd.

  1. [Social support through using ICT for family caregivers regarding people suffering chronic disease].

    Science.gov (United States)

    Barrera-Ortiz, Lucy; Carrillo-González, Gloria M; Chaparro-Díaz, Lorena; Afanador, Natividad P; Sánchez-Herrera, Beatriz

    2011-06-01

    The study was aimed at determining the effectiveness of social support using information and communication technology (ICT) for family caregivers regarding people suffering chronic disease. This descriptive exploratory study involving 144 family caregivers for people suffering from chronic disease was carried out in Bogota during 2008 and 2009. It was carried out in three phases: planning and designing ICT strategies (including a pilot trial and selecting the target population), implementing the ICTs in support of the target population and data analysis regarding implementing the ICTs, with a description of the indicators of structure and process for ICT use and results of ICT use in providing social support. G. Hilbert's Social support in chronic disease inventory (SSCI) was used for measurements, including the following categories: personal interaction, guide, feedback, tangible help and social interaction. ICT-based intervention was effective and proved positive for social support for most family caregivers. While analysing the different categories, the guide, information and instruction and personal interaction received high scores while feedback and social interaction received lower ones. Identifying and designing appropriate ICTs for family caregivers should be continued and supported in different contexts and tools such as internet and on-line social support networks should continue being explored.

  2. Quality of life in Chinese family caregivers for elderly people with chronic diseases.

    Science.gov (United States)

    Xie, Hui; Cheng, Cheng; Tao, Yisheng; Zhang, Jie; Robert, Delprino; Jia, Jihui; Su, Yonggang

    2016-07-06

    Inadequate studies have been conducted in China to examine quality of life in family caregivers. Quality of life in family caregivers for elderly people with chronic diseases was evaluated, and the demographic and characteristic factors of both elderly people and their caregivers were explored. The 36-Item Short Form Health Survey (SF-36) was used to assess health-related quality of life in 407 family caregivers caring for elderly people with chronic diseases in six communities on the Mainland China. The explanatory variables included family caregivers' demographic and other caregiving variables related to eldercare. Descriptive statistics and multiple linear regression analysis were used in the data analysis, performed via SPSS 17.0. Mean SF-36 and physical and mental component scores were 66.14 ± 17.50, 70.06 ± 16.49, and 62.22 ± 18.51, respectively. The scores of caregivers' physical function and bodily pain were significantly higher, while the scores of caregivers' role limitations due to physical problems, general health, vitality, social function, mental health and role limitations due to emotional problems were significantly lower. Caregivers' ages, comorbidity, the perceived effects of caregiving on caregivers' social lives and elderly individuals' ages, marital status and Activities of Daily Living scores were significantly associated with the physical component score. In addition, caregivers' age, the affordability of the elderly person's healthcare expenses, the perceived effects of caregiving on caregivers' social lives, and elderly people's marital status and ADL scores were significantly associated with the mental component score. Family caregivers for elderly people with chronic diseases showed poorer mental and better physical well-being. Factors of both elderly people and their caregivers impact the caregivers' quality of life. These findings highlight the importance of addressing mental health of family caregivers, and of providing

  3. Keeping Things in Balance: Family Experiences of Living With Alzheimer's Disease.

    Science.gov (United States)

    Esandi, Nuria; Nolan, Mike; Alfaro, Cristina; Canga-Armayor, Ana

    2017-06-15

    Historically, research, practice, and policy on Alzheimer's family care has been largely focused on dyadic relationships and the experience of burden and stress, often failing to capture the complex caring dynamics as they unfold over time. This study sought to develop a more nuanced understanding of how people with Alzheimer's disease (AD) and their families are affected by the disease and how they respond to the challenges AD poses. Using constructivist grounded theory, the study explored the experiences of living with AD for native Spanish families residing in Navarra. Data were collected from a series of 26 interviews with seven family units living with early stage AD and further validated with three focus groups with 14 caregivers of people with mid/advanced AD. Data were analyzed to capture the main processes involved and charted how these evolved over time. Keeping things in balance describes the way family works to preserve a balance between caring and their lives before the onset of AD. Three main temporal stages to the experience of early AD, along with their associated processes, were identified: (a) what's going on here and the processes of noticing, suspecting, and confirming; (b) our life is changing underpinned by the processes of watching and redefining; and (c) keeping things together and its associated balancing process. These reinforced the dynamic nature of living with AD over time. This study was novel in its design as it included the person with AD as part of the functioning family unit. The temporal stages and the key social processes identified have the potential to inform the development of "stage-specific" interventions for the support of the whole family at various points in time.

  4. Transmission of infectious diseases from internationally adopted children to their adoptive families.

    Science.gov (United States)

    Sciauvaud, J; Rigal, E; Pascal, J; Nourrisson, C; Poirier, P; Poirier, V; Vidal, M; Mrozek, N; Laurichesse, H; Beytout, J; Labbe, A; Lesens, O

    2014-08-01

    Internationally adopted children may suffer from different pathologies, including infectious diseases contracted in the country of origin. We evaluated the frequency of infectious diseases that may disseminate from adoptees to adoptive families on their arrival in France. All children who attended the clinic for international adoption in Clermont-Ferrand from January 2009 through to December 2011 were eligible for inclusion in the study. Standardized medical records dedicated to international adoption were retrospectively reviewed for demographic data, clinical diagnosis, and biological and radiological results. Data were completed by phone interviews with adoptive families after informed consent. One hundred and forty-two medical records were retrospectively reviewed and 86% of families agreed to be interviewed. One hundred and seventy-one potentially transmissible infections were diagnosed in 142 children, 12% (n = 20) of which were transmitted to adoptive families. Most of these infections were benign and transmission was restricted to the close family. Tinea was diagnosed in 44 adoptees and transmitted in 15 cases. Panton Valentine leukocidin producing methicillin-sensitive S. aureus (MSSA) was transmitted to an adoptive father who required hospitalization for bursitis. Transmission also occurred for CMV (n = 1), hepatitis A (n = 1), giardiasis (n = 1), scabies (n = 1), Moluscum (n = 2) and pediculosis (n = 2). Two cases of chronic hepatitis B and latent tuberculosis were diagnosed without subsequent transmission. In conclusion, infectious diseases are common in internationally adopted children and should be detected shortly after arrival to avoid transmission. © 2013 The Authors Clinical Microbiology and Infection © 2013 European Society of Clinical Microbiology and Infectious Diseases.

  5. The joint impact of family history of myocardial infarction and other risk factors on 12-year coronary heart disease mortality

    NARCIS (Netherlands)

    Boer, J M; Feskens, E.J.; Verschuren, W M Monique; Seidell, J C; Kromhout, D.

    1999-01-01

    We investigated the impact of family history of myocardial infarction on 12-year coronary heart disease mortality. Men and women with a family history had an increased risk for coronary heart disease death, irrespective of other risk factors (RR = 1.58; 95% CI = 1.17-2.13 and RR = 2.12; 95% CI =

  6. Feasibility of Recruiting Families into a Heart Disease Prevention Program Based on Dietary Patterns

    Directory of Open Access Journals (Sweden)

    Tracy L. Schumacher

    2015-08-01

    Full Text Available Offspring of parents with a history of cardiovascular disease (CVD inherit a similar genetic profile and share diet and lifestyle behaviors. This study aimed to evaluate the feasibility of recruiting families at risk of CVD to a dietary prevention program, determine the changes in diet achieved, and program acceptability. Families were recruited into a pilot parallel group randomized controlled trial consisting of a three month evidence-based dietary intervention, based on the Mediterranean and Portfolio diets. Feasibility was assessed by recruitment and retention rates, change in diet by food frequency questionnaire, and program acceptability by qualitative interviews and program evaluation. Twenty one families were enrolled over 16 months, with fourteen families (n = 42 individuals completing the study. Post-program dietary changes in the intervention group included small daily increases in vegetable serves (0.8 ± 1.3 and reduced usage of full-fat milk (−21%, cheese (−12% and meat products (−17%. Qualitative interviews highlighted beneficial changes in food purchasing habits. Future studies need more effective methods of recruitment to engage families in the intervention. Once engaged, families made small incremental improvements in their diets. Evaluation indicated that feedback on diet and CVD risk factors, dietetic counselling and the resources provided were appropriate for a program of this type.

  7. Alzheimer’s disease family history impacts resting state functional connectivity

    Science.gov (United States)

    Wang, Liang; Roe, Catherine M.; Snyder, Abraham Z.; Brier, Matthew R.; Thomas, Jewell B.; Xiong, Chengjie; Benzinger, Tammie L.; Morris, John C.; Ances, Beau M.

    2012-01-01

    Objective Offspring whose parents have Alzheimer’s disease (AD) are at increased risk for developing dementia. Patients with AD typically exhibit disruptions in the default mode network (DMN). The aim of this study was to investigate the effect of a family history of late-onset AD on DMN integrity in cognitively normal individuals. In particular, we determined whether a family history effect is detectable in apolipoprotein E (APOE) ε4 allele non-carriers. Method We studied a cohort of 348 cognitively normal participants with or without family history of late-onset AD. DMN integrity was assessed by resting state functional connectivity magnetic resonance imaging. Results A family history of late-onset AD was associated with reduced resting state functional connectivity between particular nodes of the DMN, namely the posterior cingulate and medial temporal cortex. The observed functional connectivity reduction was not attributable to medial temporal structural atrophy. Importantly, we detected a family history effect on DMN functional connectivity in APOE ε4 allele non-carriers. Interpretation Unknown genetic factors, embodied in a family history of late-onset AD, may affect DMN integrity prior to cognitive impairment. PMID:23109152

  8. Familial aggregation of Alzheimer's disease and related disorders: A collaborative re-analysis of case-control studies

    NARCIS (Netherlands)

    C.M. van Duijn (Cornelia); D.G. Clayton (David); V. Chandra; L. Fratiglioni (Laura); A.B. Graves; A. Heyman; A.F. Jorm; E. Kokmen (Emre); K. Kondo; J.A. Mortimer; W.A. Rocca; S.L. Shalat; H. Soininen; A. Hofman (Albert)

    1991-01-01

    textabstractCase-control studies of Alzheimer's disease were re-analysed to examine the association of Alzheimer's disease with family history in first degree relatives of dementia, Down's syndrome and Parkinson's disease. Overall, the relative risk of Alzheimer's disease for those with at least one

  9. Social support perceived in family caregivers of people with chronic disease

    Directory of Open Access Journals (Sweden)

    Sandra Lucrecia Romero Guevara

    2017-05-01

    Full Text Available Introduction: The increase in chronic diseases has put in evidence the problem between the supply and demand for health services, generating the displacement of care to home and the overload to family caregivers. Objective: To determine the social support perceived by family caregivers of people with chronic disease. Materials and Methods: A transversal study was conducted and the Inventory of Social Support on Chronic Disease of Hilbert instrument was used with 129 family caregivers of people with chronic disease seen in a hospital of third level of attention. Results: The caregivers are primarily women (89.9%. The average score of the scale was of $110.7, standard deviation = 38.1. Significant differences were found in the schooling (p=0.030, socioeconomic status (p=0.013 and the housing to the patient (p=0.010. Conclusion: The caregivers reported to be unhappy with perceived social support and this perception was related to the socio-economic conditions of the people.

  10. Genetic and familial predisposition to rotator cuff disease: a systematic review.

    Science.gov (United States)

    Dabija, Dominique I; Gao, Chan; Edwards, Todd L; Kuhn, John E; Jain, Nitin B

    2017-06-01

    Rotator cuff disease is a common disorder leading to shoulder pain and loss of function. Its etiology in atraumatic cases is uncertain and is likely to extend beyond repetitive microtrauma or overuse. Our objective was to determine whether there is a genetic or familial predisposition to rotator cuff disease. A literature search of PubMed and Embase databases identified 251 citations. After review of the titles, abstracts, and full articles, 7 met our inclusion and exclusion criteria. Four studies assessed familial predisposition to rotator cuff disease. One of these demonstrated that siblings of an individual with a rotator cuff tear were more likely to develop a full-thickness tear and more likely to be symptomatic. A 5-year follow-up showed that the relative risks were increased for the siblings to have a full-thickness tear, for a tear to progress in size, and for being symptomatic. Another study demonstrated that a significantly higher number of individuals with tears had family members with a history of tears or surgery than those without tears did. The other 3 studies investigated whether a genetic predisposition to rotator cuff disease exists and found significant association of haplotypes in DEFB1, FGFR1, FGF3, ESRRB, and FGF10 and 2 single-nucleotide polymorphisms within SAP30BP and SASH1. Prior studies provide preliminary evidence for genetic and familial predisposition to rotator cuff disease. However, there is a lack of large genome-wide studies that can provide more definitive information and guide early detection of individuals at risk, prophylactic rehabilitation, and potential gene therapies and regenerative medicine interventions. Copyright © 2016 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

  11. Screening strategies for colorectal cancer among patients with nonalcoholic fatty liver disease and family history.

    Science.gov (United States)

    Wong, Martin C S; Ching, Jessica Y L; Chan, Victor C W; Lam, Thomas Y T; Luk, Arthur K C; Wong, Sunny H; Ng, Siew C; Wong, Vincent W S; Ng, Simon S M; Wu, Justin C Y; Chan, Francis K L; Sung, Joseph J Y

    2016-02-01

    Patients with nonalcoholic fatty liver disease (NAFLD) and family history of colorectal cancer (CRC) are at higher risks but how they should be screened remains uncertain. Hence, we evaluated the cost-effectiveness of CRC screening among patients with NAFLD and family history by different strategies. A hypothetical population of 100,000 subjects aged 40-75 years receive: (i) yearly fecal immunochemical test (FIT) at 50 years; (ii) flexible sigmoidoscopy (FS) every 5 years at 50 years; (iii) colonoscopy 10 yearly at 50 years; (iv) colonoscopy 10 yearly at 50 years among those with family history/NAFLD and yearly FIT at 50 years among those without; (v) colonoscopy 10 yearly at 40 years among those with family history/NAFLD and yearly FIT at 50 years among those without and (vi) colonoscopy 10 yearly at 40 years among those with family history/NAFLD and colonoscopy 10 yearly at 50 years among those without. The incremental cost-effectiveness ratio (ICER) was studied by Markov modeling. It was found that colonoscopy, FS and FIT reduced incidence of CRC by 49.5, 26.3 and 23.6%, respectively. Using strategies 4, 5 and 6, the corresponding reduction in CRC incidence was 29.9, 30.9 and 69.3% for family history, and 33.2, 34.7 and 69.8% for NAFLD. Compared with no screening, strategies 4 (US$1,018/life-year saved) and 5 (US$7,485) for family history offered the lowest ICER, whilst strategy 4 (US$5,877) for NAFLD was the most cost-effective. These findings were robust when assessed with a wide range of deterministic sensitivity analyses around the base case. These indicated that screening patients with family history or NAFLD by colonoscopy at 50 years was economically favorable. © 2015 UICC.

  12. GATA2 is associated with familial early-onset coronary artery disease.

    Directory of Open Access Journals (Sweden)

    Jessica J Connelly

    2006-08-01

    Full Text Available The transcription factor GATA2 plays an essential role in the establishment and maintenance of adult hematopoiesis. It is expressed in hematopoietic stem cells, as well as the cells that make up the aortic vasculature, namely aortic endothelial cells and smooth muscle cells. We have shown that GATA2 expression is predictive of location within the thoracic aorta; location is suggested to be a surrogate for disease susceptibility. The GATA2 gene maps beneath the Chromosome 3q linkage peak from our family-based sample set (GENECARD study of early-onset coronary artery disease. Given these observations, we investigated the relationship of several known and novel polymorphisms within GATA2 to coronary artery disease. We identified five single nucleotide polymorphisms that were significantly associated with early-onset coronary artery disease in GENECARD. These results were validated by identifying significant association of two of these single nucleotide polymorphisms in an independent case-control sample set that was phenotypically similar to the GENECARD families. These observations identify GATA2 as a novel susceptibility gene for coronary artery disease and suggest that the study of this transcription factor and its downstream targets may uncover a regulatory network important for coronary artery disease inheritance.

  13. Coronary Heart Disease, Peripheral Arterial Disease, and Stroke in Familial Hypercholesterolaemia: Insights From the SAFEHEART Registry (Spanish Familial Hypercholesterolaemia Cohort Study).

    Science.gov (United States)

    Pérez de Isla, Leopoldo; Alonso, Rodrigo; Mata, Nelva; Saltijeral, Adriana; Muñiz, Ovidio; Rubio-Marin, Patricia; Diaz-Diaz, José L; Fuentes, Francisco; de Andrés, Raimundo; Zambón, Daniel; Galiana, Jesús; Piedecausa, Mar; Aguado, Rocio; Mosquera, Daniel; Vidal, José I; Ruiz, Enrique; Manjón, Laura; Mauri, Marta; Padró, Teresa; Miramontes, José P; Mata, Pedro

    2016-09-01

    Heterozygous familial hypercholesterolemia (FH) is the most common premature atherosclerotic cardiovascular disease (ASCVD)-related monogenic disorder, and it is associated with ischemic heart disease. There is limited information whether FH increases the risk of peripheral arterial and cerebrovascular disease. Our aim was to analyze ASCVD prevalence and characteristics in different arterial territories in a large FH population, to compare them with an unaffected control population and to determine which factors are associated to ASCVD. SAFEHEART (Spanish Familial Hypercholesterolaemia Cohort Study) is an ongoing registry of molecularly defined patients with heterozygous FH in Spain. ASCVD in the different arterial territories was analyzed, as well as individual characteristics, genetic variables, and lipid-lowering therapies. The study recruited 4132 subjects (3745 ≥18 years); 2,752 of those enrolled were molecularly diagnosed FH cases. Median age was 44.0 years (45.9% men) and 40 years (46.6% men) in FH patients and unaffected relatives (Pdifferences were found for cerebrovascular events. Age, body mass index, type 2 diabetes mellitus, high blood pressure, previous use of tobacco, and lipoprotein(a) >50 mg/dL were independently associated with ASCVD. The prevalence of ASCVD is higher, and the involvement of the arterial territories is different in FH patients when compared with their unaffected relatives. Age, male sex, increased body mass index, hypertension, type 2 diabetes mellitus, smoking habit, and lipoprotein(a) >50 mg/dL were independently associated to ASCVD. URL: https://www.clinicaltrials.gov. Unique identifier: NCT02693548. © 2016 American Heart Association, Inc.

  14. A yoga and compassion meditation program reduces stress in familial caregivers of Alzheimer's disease patients.

    Science.gov (United States)

    Danucalov, M A D; Kozasa, E H; Ribas, K T; Galduróz, J C F; Garcia, M C; Verreschi, I T N; Oliveira, K C; Romani de Oliveira, L; Leite, J R

    2013-01-01

    Familial caregivers of patients with Alzheimer's disease exhibit reduced quality of life and increased stress levels. The aim of this study was to investigate the effects of an 8-week yoga and compassion meditation program on the perceived stress, anxiety, depression, and salivary cortisol levels in familial caregivers. A total of 46 volunteers were randomly assigned to participate in a stress-reduction program for a 2-month period (yoga and compassion meditation program-YCMP group) (n = 25) or an untreated group for the same period of time (control group) (n = 21). The levels of stress, anxiety, depression, and morning salivary cortisol of the participants were measured before and after intervention. The groups were initially homogeneous; however, after intervention, the groups diverged significantly. The YCMP group exhibited a reduction of the stress (P anxiety (P meditation program may offer an effective intervention for reducing perceived stress, anxiety, depression, and salivary cortisol in familial caregivers.

  15. Patent landscape of neglected tropical diseases: an analysis of worldwide patent families.

    Science.gov (United States)

    Akinsolu, Folahanmi Tomiwa; de Paiva, Vitor Nobre; Souza, Samuel Santos; Varga, Orsolya

    2017-11-14

    "Neglected Tropical Diseases" (NTDs) affect millions of people in Africa, Asia and South America. The two primary ways of strategic interventions are "preventive chemotherapy and transmission control" (PCT), and "innovative and intensified disease management" (IDM). In the last 5 years, phenomenal progress has been achieved. However, it is crucial to intensify research effort into NTDs, because of the emerging drug resistance. According to the World Health Organization (WHO), the term NTDs covers 17 diseases, namely buruli ulcer, Chagas disease, dengue, dracunculiasis, echinococcosis, trematodiasis, human African trypanosomiasis, leishmaniasis, leprosy, lymphatic filariasis, onchocerciasis, rabies, schistosomiasis, soil-transmitted helminthes, taeniasis, trachoma, and yaws. The aim of this study is to map out research and development (R&D) landscape through patent analysis of these identified NTDs. To achieve this, analysis and evaluation have been conducted on patenting trends, current legal status of patent families, priority countries by earliest priority years and their assignee types, technological fields of patent families over time, and original and current patent assignees. Patent families were extracted from Patseer, an international database of patents from over 100 patent issuing authorities worldwide. Evaluation of the patents was carried out using the combination of different search terms related to each identified NTD. In this paper, a total number of 12,350 patent families were analyzed. The main countries with sources of inventions were identified to be the United States (US) and China. The main technological fields covered by NTDs patent landscape are pharmaceuticals, biotechnology, organic fine chemistry, analysis of biological materials, basic materials chemistry, and medical technology. Governmental institutions and universities are the primary original assignees. Among the NTDs, leishmaniasis, dengue, and rabies received the highest number of

  16. Genetic mosaicism of a frameshift mutation in the RET gene in a family with Hirschsprung disease.

    Science.gov (United States)

    Müller, Charlotte M; Haase, Michael G; Kemnitz, Ivonne; Fitze, Guido

    2014-05-10

    Mutations and polymorphisms in the RET gene are a major cause of Hirschsprung disease (HSCR). Theoretically, all true heterozygous patients with a new manifestation of a genetically determined disease must have parents with a genetic mosaicism of some extent. However, no genetic mosaicism has been described for the RET gene in HSCR yet. Therefore, we analyzed families with mutations in the RET gene for genetic mosaicism in the parents of the patients. Blood samples were taken from patients with HSCR and their families/parents to sequence the RET coding region. Among 125 families with HSCR, 33 families with RET mutations were analyzed. In one family, we detected a frameshift mutation due to a loss of one in a row of four cytosines in codon 117/118 of the RET gene (c.352delC) leading to a frameshift mutation in the protein (p.Leu118Cysfs*105) that affected two siblings. In the blood sample of the asymptomatic father we found a genetic mosaicism of this mutation which was confirmed in two independent samples of saliva and hair roots. Quantification of peak-heights and comparison with different mixtures of normal and mutated plasmid DNA suggested that the mutation occurred in the early morula stadium of the founder, between the 4- and 8-cell stages. We conclude that the presence of a RET mutation leading to loss of one functional allele in 20 to 25% of the cells is not sufficient to cause HSCR. The possibility of a mosaicism has to be kept in mind during genetic counseling for inherited diseases. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Family Cohesion: A Study on Caregiving Daughters of Parents With Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    Deusivania Vieira da Silva Falcão

    2016-11-01

    Full Text Available In this regard, investigating these aspects might facilitate the evaluation of family relations and the development of interventions that create, keep, restore, or enhance the skills families need to better deal with the disease. Based on this information, the objective of this chapter is to present and discuss investigative research on family cohesion and hierarchy from the perspective of caregiver daughters of elderly with Alzheimer’s in four situations: before the disease, currently, in conflict, and ideally. 32 women caretakers and their respective parents (6 fathers and 26 mothers diagnosed with possible or probable AD participated in the survey. The instruments used were the Mini-Mental State Examination (MMSE in an Open Interview with a Semi-Structured Script, and the Family System Test (FAST. We observed that before onset of the disease, the caregivers generally perceived themselves to have more hierarchy than their siblings, χ2(2 = 4.92, p < .10. The current situation showed a greater number of caregivers in higher hierarchical positions than their siblings (72%, and a lesser number of siblings than expected in higher hierarchical positions than the caregivers, χ2(2 = 18.32, p < .001. The ideal representation showed that most caregivers did not want themselves or any of their siblings to have more power than the other (66.7%, χ2(2 = 14.89, p < .001. Comparing conflict representations to ideal representations showed that family members demonstrated lower cohesion in conflict situations than in ideal situations, z = -2.86, p < .01.

  18. Cerebrospinal Fluid Biomarkers in Familial Forms of Alzheimer's Disease and Frontotemporal Dementia

    DEFF Research Database (Denmark)

    Rostgaard, Nina; Waldemar, Gunhild; Nielsen, Jørgen Erik

    2015-01-01

    As dementia is a fast-growing health care problem, it is becoming an increasingly urgent need to provide an early diagnosis in order to offer patients the best medical treatment and care. Validated biomarkers which reflect the pathology and disease progression are essential for diagnosis...... and are important when developing new therapies. Today, the core protein biomarkers amyloid-β42, total tau and phosphorylated tau in the cerebrospinal fluid (CSF) are used to diagnose Alzheimer's disease (AD), because these biomarkers have shown to reflect the underlying amyloid and tau pathology. However...... profiles in patients with familial dementias are not clear. This review summarizes CSF biomarker findings from studies on symptomatic and presymptomatic individuals carrying a mutation in one of the genes known to cause early-onset familial AD or FTD. In conclusion, the biomarker profile of inherited AD...

  19. Are the educational differences in incidence of cardiovascular disease explained by underlying familial factors?

    DEFF Research Database (Denmark)

    Madsen, Mia; Andersen, Per Kragh; Gerster, Mette

    2014-01-01

    To isolate the effect of education from the influence of potential underlying factors, we investigated the association of education with the risk of cardiovascular disease (CVD) and ischemic heart disease (IHD) using twin data to adjust for familial factors shared within twins, including genetic...... make-up and childhood environment. The study was based on data from the Danish Twin Registry linked to administrative and heath registers in Statistics Denmark. A total of 11,968 monozygotic and 20,464 dizygotic same sexed twins were followed from 1980 to 2009, including more than 8000 events of CVD....... Unpaired and intra-pair analyses were compared. In the unpaired analyses, an inverse educational gradient in CVD- and IHD risk was observed. This association was not replicated in the intra-pair analyses that control for shared familial factors exploiting that twins share their intrauterine- and childhood...

  20. A Novel Missense Mutation of GATA4 in a Chinese Family with Congenital Heart Disease.

    Science.gov (United States)

    Zhang, Xiaoqing; Wang, Jian; Wang, Bo; Chen, Sun; Fu, Qihua; Sun, Kun

    2016-01-01

    Congenital heart disease (CHD) is the most prevalent type of birth defect in human, with high morbidity in infant. Several genes essential for heart development have been identified. GATA4 is a pivotal transcription factor that can regulate the cardiac development. Many GATA4 mutations have been identified in patients with different types of CHD. In this study, the NKX2-5, HAND1 and GATA4 coding regions were sequenced in a family spanning three generations in which seven patients had CHD. Disease-causing potential variation in this family was evaluated by bioinformatics programs and the transcriptional activity of mutant protein was analyzed by the dual luciferase reporter assay. A novel GATA4 mutation, c.C931T (p.R311W), was identified and co-segregated with the affected patients in this family. The bioinformatics programs predicted this heterozygous mutation to be deleterious and the cross-species alignment of GATA4 sequences showed that the mutation occurred within a highly conserved amino acid. Even though it resided in the nuclear localization signal domain, the mutant protein didn't alter its intracellular distribution. Nevertheless, further luciferase reporter assay demonstrated that the p.R311W mutation reduced the ability of GATA4 to activate its downstream target gene. Our study identified a novel mutation in GATA4 that likely contributed to the CHD in this family. This finding expanded the spectrum of GATA4 mutations and underscored the pathogenic correlation between GATA4 mutations and CHD.

  1. [Study on factors associated with family burden of Alzheimer' s disease].

    Science.gov (United States)

    Zhai, Junwei; Wang, Xiaocheng; Wang, Jingying; Song, Zejing; Yu, Hongmei

    2015-09-01

    To understand the family burden of Alzheimer' s disease (AD) and associated factors. The subjects were 168 caregivers of patients with AD selected from two class 3A hospitals and three communities in Taiyuan through cluster sampling. The data were collected by using the Caregiver Burden Inventory (CBI) and the Family Burden Scale (FBS) of diseases. Path analysis was applied to identify the factors associated with the total score of CBI. T-test and One-way analysis of variance were applied to identify the factors associated with the total score of FBS. Multiple linear regression analysis was applied to identify the factors associated with family burden of AD. The total score of the caregivers' burden was 52.41±17.07. AD patients' cognitive function had direct (standardized β =-0.280, Pfamily burden was 16.23± 9.00. Univariate analysis showed that the sex, age, education level, cognitive function, daily performance, mental status, depression and dementia rating of AD patients might affect the total score of FBS (Paffected the total score of FBS included the sex (standardized β=0.280, Pfamily burden of AD was mainly associated with the cognitive function and daily performance of AD patients. It is necessary to take targeted measures to reduce the caregiver and family burden of AD.

  2. Differences in age at onset and familial aggregation between clinical types of idiopathic Parkinson's disease.

    Science.gov (United States)

    Korchounov, Alexei; Schipper, Hayo I; Preobrazhenskaya, Irina S; Kessler, Kirn R; Yakhno, Nikolay N

    2004-09-01

    Idiopathic Parkinson's disease (PD) can be subdivided by its patterns of motor symptoms into tremor-dominant (TDT), akinetic-rigid (ART), and mixed type (MT). Our objective was to determine whether age at onset and family history are different in these three types. In total, 366 patients with PD were assigned in a standardized approach to one of the three subtypes. Age at onset and family history were obtained in all patients and all presumably affected family members were examined. Mean ages at disease onset were similar in all three groups, but distribution of age at onset was markedly different: monophasic in TDT with a peak around 60 years, biphasic in ART with two peaks, one in the middle of the sixth decade (earlier onset, ART-EO), another during the first half of the seventh decade (later onset, ART-LO), and increasing with age only in MT patients A positive family history was significantly associated only with TDT (odds ratio = 5.7) and ART-EO (odds ratio = 7.8), but not with MT or ART-LO patients. Segregation analysis suggested an autosomal recessive mode of transmission in ART-EO and an autosomal dominant mode of transmission in TDT.

  3. Influences on clinical reasoning in family and psychosocial interventions in nursing practice with patients and their families living with chronic kidney disease.

    Science.gov (United States)

    Thirsk, Lorraine M; Moore, Sarah G; Keyko, Kacey

    2014-09-01

    To explore how Registered Nurses address psychosocial issues for patients and their families living with chronic kidney disease. It is in the scope of registered nursing practice to address the emotional, psychological and relational implications of living with chronic disease through psychosocial and family interventions. Patients living with chronic kidney disease frequently report poor quality of life and numerous psychosocial issues; however, they do not find that these issues are always adequately addressed. This research was hermeneutic inquiry as guided by Gadamer's philosophy of understanding. Family/psychosocial nursing practices are examined from the perspective of self-reports of Registered Nurses working in acute care nephrology units. Interviews with nurses were conducted throughout 2012. Nurses attribute, or explain, patient and family member behaviour in a variety of ways. These explanations may or may not align with actual patient/family reasons for behaviour. Nurses' explanations influence subsequent nursing practice. While there is some evidence of practices that overcome biased attributions of patient behaviour, the cognitive processes by which nurses develop these explanations are more complex than previously reported in nursing literature. Clinical reasoning and subsequent nursing practice are influenced by how nurses explain patients'/families' behaviour. Exploration of this issue with the support of social cognition literature suggests a need for further research with significant implications for nursing education and practice to improve family/psychosocial interventions. © 2014 John Wiley & Sons Ltd.

  4. Airway wall thickening and emphysema show independent familial aggregation in chronic obstructive pulmonary disease

    DEFF Research Database (Denmark)

    Patel, Bipen D; Coxson, Harvey O; Pillai, Sreekumar G

    2008-01-01

    RATIONALE: It is unclear whether airway wall thickening and emphysema make independent contributions to airflow limitation in chronic obstructive pulmonary disease (COPD) and whether these phenotypes cluster within families. OBJECTIVES: To determine whether airway wall thickening and emphysema (1...... the severity of airway wall thickening and emphysema. MEASUREMENTS AND MAIN RESULTS: A total of 3,096 individuals were recruited to the study, of whom 1,159 (519 probands and 640 siblings) had technically adequate high-resolution computed tomography scans without significant non-COPD-related thoracic disease....... Airway wall thickness correlated with pack-years smoked (P chronic bronchitis (P emphysema at -950...

  5. Duration of residence and disease occurrence among refugees and family reunited immigrants

    DEFF Research Database (Denmark)

    Nørredam, Marie Louise; Agyemang, Charles; Hoejbjerg Hansen, Oluf K

    2014-01-01

    Ratios (HRs) were modelled for disease incidence by residence duration since arrival (0-5 years; 0-10 years; 0-18 years) adjusting for age and sex. RESULTS: Compared with Danish-born individuals, refugees and family reunited immigrants had lower HRs of stroke and breast cancer within 5 years after...... of residence on disease occurrence among migrants imply that, when explaining migrants' advantageous health outcomes, the ruling theory of the HME should be used with caution, and other explanatory models should be included....

  6. Burden and associated pathologies in family caregivers of Alzheimer’s disease patients in Spain.

    OpenAIRE

    Vérez Cotelo N; Andrés Rodríguez NF; Fornos Pérez JA; Andrés Iglesias JC; Ríos Lago M.

    2015-01-01

    Objectives: To evaluate the profile of family caregivers of Alzheimer?s disease patients, identify any signs of psychopathology, quantify the level of perceived burden on the caregiver, and determine the caregiver?s relationship with their pharmacist. Methods: A cross-sectional study was conducted at a community pharmacy in Pontevedra, Spain. Demographic variables were collected, and the following questionnaires were administered: the Beck Depression Inventory-II, STAI-Anxiety Questionnaire, ...

  7. Expanding the definition of a positive family history for early-onset coronary heart disease.

    Science.gov (United States)

    Scheuner, Maren T; Whitworth, William C; McGruder, Henraya; Yoon, Paula W; Khoury, Muin J

    2006-08-01

    Assessing familial risk for early-onset coronary heart disease (CHD) is typically limited to first-degree relatives with early-onset CHD. To evaluate the impact of additional family history, we examined the associations between various family history definitions and early-onset CHD. By using the national HealthStyles 2003 survey data, we assessed associations between self-reported family history and personal history of early-onset CHD (diagnosed at or before age 60 years), adjusting for demographics, hypercholesterolemia, hypertension, and obesity. Of 4,035 respondents, 60% were female and 72% were white, with a mean age of 48.8 years; 4.4% had early-onset CHD. In addition to having at least one first-degree relative with early-onset CHD, other significant associations included having at least one first-degree relative with late-onset CHD, at least one second-degree relative with early-onset CHD, and two or more affected second-degree relatives regardless of age of onset of CHD. Early-onset stroke in at least one first-degree relative and, in women, having at least one first-degree relative with diabetes were also significantly associated with early-onset CHD. Family history beyond early-onset CHD in first-degree relatives is significantly associated with prevalent CHD diagnosed at or before age 60 years.

  8. Mutant LRP6 Impairs Endothelial Cell Functions Associated with Familial Normolipidemic Coronary Artery Disease

    Directory of Open Access Journals (Sweden)

    Jian Guo

    2016-07-01

    Full Text Available Mutations in the genes low-density lipoprotein (LDL receptor-related protein-6 (LRP6 and myocyte enhancer factor 2A (MEF2A were reported in families with coronary artery disease (CAD. We intend to determine the mutational spectrum of these genes among hyperlipidemic and normolipidemic CAD families. Forty probands with early-onset CAD were recruited from 19 hyperlipidemic and 21 normolipidemic Chinese families. We sequenced all exons and intron-exon boundaries of LRP6 and MEF2A, and found a novel heterozygous variant in LRP6 from a proband with normolipidemic CAD. This variant led to a substitution of histidine to tyrosine (Y418H in an evolutionarily conserved domain YWTD in exon 6 and was not found in 1025 unrelated healthy individuals. Co-segregated with CAD in the affected family, LRP6Y418H significantly debilitated the Wnt3a-associated signaling pathway, suppressed endothelial cell proliferation and migration, and decreased anti-apoptotic ability. However, it exhibited no influences on low-density lipoprotein cholesterol uptake. Thus, mutation Y418H in LRP6 likely contributes to normolipidemic familial CAD via impairing endothelial cell functions and weakening the Wnt3a signaling pathway.

  9. Family Caregiver's Perception of Alzheimer's disease and caregiving in Chinese culture.

    Science.gov (United States)

    Dai, Baozhen; Mao, Zongfu; Wu, Bei; Mei, Y John; Levkoff, Sue; Wang, Huali

    2015-01-01

    This study examined the perception of Alzheimer's disease (AD) and caregiving among family caregivers of individuals with mild cognitive impairment (MCI) and AD in China. In-depth semistructured interviews were conducted with 46 family caregivers of individuals with cognitive impairment in 2009 in Wuhan and Beijing, China. Participants included 38 spouses, 7 adult children, and 1 sibling, aged between 41 and 85 years old. The findings showed that all family caregivers thought the Chinese terminology of AD laonian chidai, brought discrimination to individuals with cognitive impairment. Caregivers of individuals with AD experienced burden and desired an increase of formal services. Traditional beliefs of respecting elders and caring for extended family members were held among family caregivers of individuals with cognitive impairment, and there was nearly no difference found between caregivers of AD and those of MCI. It implied that traditional culture provided positive influences on caring for elders with cognitive impairment. An alternative term for MCI may contribute to further reducing the discrimination brought by the old Chinese terminology of AD laonian chidai. Development of formal services for elders with cognitive impairment may contribute to reducing caregivers' worries about future caregiving.

  10. Attitude and knowledge of family medicine practitioners towards the association between periodontal disease and obesity.

    Science.gov (United States)

    Akram, Z; Abduljabbar, T; Hanif, A; Khan, A; Vohra, F

    2017-05-01

    To assess the attitude and knowledge of family medicine practitioners (FMPs) towards the association between periodontal disease and obesity. A cross-sectional study was performed and a 13-item survey questionnaire was given to FMPs practicing in 12 different teaching hospitals in Karachi, Pakistan. The questions were aimed at exploring the knowledge of FMP's regarding the association of obesity and periodontal disease and their attitude towards the association of obesity and periodontal disease. Chi-square and Spearman co-efficient were conducted to compare subgroups and correlate factors with the knowledge score of FMPs. A total of 314 questionnaires were completed (response rate = 92%). Median age of participants was 41 years and 57% were females. Almost 61% of FMPs answered all the knowledge questions correctly and 64% reported moderate understanding of the association between periodontal health and obesity. Nearly 73% FMPs inquired from obese patients regarding the periodontal disease and more than half (58%) refer patients to a dentist for evaluation. More than half of FMPs perform periodontal disease screening. Nearly all FMPs considered informing obese patients regarding periodontal disease as one of their roles. FMP's play an important role in the early diagnosis, prevention and treatment of periodontal conditions in obese patients. More than two thirds of FMPs showed good knowledge of the association of obesity and periodontal disease. The attitudes of FMPs towards assessing and referring obese patients at a risk of having periodontal disease were reassuring.

  11. Familial frontotemporal dementia with neuronal intranuclear inclusions is not a polyglutamine expansion disease

    Directory of Open Access Journals (Sweden)

    Neal Scott J

    2006-08-01

    Full Text Available Abstract Background Many cases of frontotemporal dementia (FTD are familial, often with an autosomal dominant pattern of inheritance. Some are due to a mutation in the tau- encoding gene, on chromosome 17, and show an accumulation of abnormal tau in brain tissue (FTDP-17T. Most of the remaining familial cases do not exhibit tau pathology, but display neuropathology similar to patients with dementia and motor neuron disease, characterized by the presence of ubiquitin-immunoreactive (ub-ir, dystrophic neurites and neuronal cytoplasmic inclusions in the neocortex and hippocampus (FTLD-U. Recently, we described a subset of patients with familial FTD with autopsy-proven FTLD-U pathology and with the additional finding of ub-ir neuronal intranuclear inclusions (NII. NII are a characteristic feature of several other neurodegenerative conditions for which the genetic basis is abnormal expansion of a polyglutamine-encoding trinucleotide repeat region. The genetic basis of familial FTLD-U is currently not known, however the presence of NII suggests that a subset of cases may represent a polyglutamine expansion disease. Methods We studied DNA and post mortem brain tissue from 5 affected members of 4 different families with NII and one affected individual with familial FTLD-U without NII. Patient DNA was screened for CAA/CAG trinucleotide expansion in a set of candidate genes identified using a genome-wide computational approach. Genes containing CAA/CAG trinucleotide repeats encoding at least five glutamines were examined (n = 63, including the nine genes currently known to be associated with human disease. CAA/CAG tract sizes were compared with published normal values (where available and with those of healthy controls (n = 94. High-resolution agarose gel electrophoresis was used to measure allele size (number of CAA/CAG repeats. For any alleles estimated to be equal to or larger than the maximum measured in the control population, the CAA/CAG tract

  12. Familial Creutzfeldt-Jakob Disease: Case report and role of genetic counseling in post mortem testing.

    Science.gov (United States)

    Clift, Kristin; Guthrie, Kimberly; Klee, Eric W; Boczek, Nicole; Cousin, Margot; Blackburn, Patrick; Atwal, Paldeep

    2016-11-01

    Here we present a case of an asymptomatic 53-year-old woman who sought genetic testing for Familial Creutzfeldt-Jakob Disease (fCJD) after learning that her mother had fCJD. The patient's mother had a sudden onset of memory problems and rapidly deteriorating mental faculties in her late 70s, which led to difficulties ambulating, progressive non-fluent aphasia, dysphagia and death within ∼1 y of symptom onset. The cause of death was reported as "rapid onset dementia." The patient's family, unhappy with the vague diagnosis, researched prion disorders online and aggressively pursued causation and submitted frozen brain tissue from the mother to the National Prion Disease Surveillance Center, where testing revealed a previously described 5-octapeptide repeat insertion (5-OPRI) in the prion protein gene (PRNP) that is known to cause fCJD. The family had additional questions about the implications of this result and thus independently sought out genetic counseling.  While rare, fCJD is likely underdiagnosed due to clinical heterogeneity, rapid onset, early non-specific symptomatology, and overlap in the differential diagnosis of Alzheimer disease and Lewy body dementias. When fCJD is identified, a multidisciplinary approach to return of results that includes the affected patient's provider, genetics professionals, and mental health professionals is key to the care of the family. We present an example case which discusses the psychosocial issues encountered and the role of genetic counseling in presymptomatic testing for incurable neurodegenerative conditions. Ordering physicians should be aware of the basic issues surrounding presymptomatic genetic testing and identify local genetic counseling resources for their patients.

  13. Clinical outcome of patients with familial hypercholesterolemia and coronary artery disease undergoing partial ileal bypass surgery

    Directory of Open Access Journals (Sweden)

    Jaqueline Scholz Issa

    2000-07-01

    Full Text Available Familial hypercholesterolemia is characterized by high serum levels of total cholesterol and LDL-cholesterol. It may be homozygous or heterozygous. In homozygous patients, LDL-cholesterol levels range from 500 to 1000mg/dL and coronary artery disease is precocious, usually manifesting itself between the 2nd and 3rd decades of life. The diagnosis is often made by the presence of xanthoma tuberosum and tendinous xanthomas that appear between the 1st and 2nd decades of life. The use of high doses of statins or even unusual procedures (apheresis, partial ileal bypass surgery, liver transplantation, gene therapy, or both, is necessary for increasing survival and improving quality of life, because a reduction in cholesterol levels is essential for stabilizing the coronary artery disease and reducing xanthomas. We report our experience with 3 patients with xanthomatous familial hypercholesterolemia and coronary artery disease, who underwent partial ileal bypass surgery. Their follow-up over the years (approximately 8 years showed a mean 30% reduction in total cholesterol, with a significant reduction in the xanthomas and stabilization of the coronary artery disease.

  14. Impact of Environmental and Familial Factors in a Cohort of Pediatric Patients With Inflammatory Bowel Disease.

    Science.gov (United States)

    Strisciuglio, Caterina; Giugliano, Francesca; Martinelli, Massimo; Cenni, Sabrina; Greco, Luigi; Staiano, Annamaria; Miele, Erasmo

    2017-04-01

    The primary role of environment on inflammatory bowel disease (IBD) onset has been recently stressed. We aimed to investigate the effect of environmental factors in an IBD pediatric cohort. A total of 467 subjects (264 IBD and 203 controls) were enrolled. All patients underwent a questionnaire including 5 different groups of environmental risk factors: family history of IBD and autoimmune diseases, perinatal period, home amenities and domestic hygiene, childhood diseases and vaccinations, and diet. In a multivariate model, mother's degree (odds ratio [OR]: 5.5; 2.5-11.6), duration of breast feeding >3rd month (OR: 4.3; 1.6-10.5), father's employment (OR: 3.7; 1.2-8.7), gluten introduction environmental factors are closely linked to IBD onset and may partly explain IBD rise in developed countries.

  15. The interleukin-17 cytokine family: critical players in host defence and inflammatory diseases.

    Science.gov (United States)

    Pappu, Rajita; Ramirez-Carrozzi, Vladimir; Sambandam, Arivazhagan

    2011-09-01

    The interleukin-17 (IL-17) cytokines, IL-17A to IL-17F, are emerging as critical players in host defence responses and inflammatory diseases. Substantial data support the role of these proteins in innate and adaptive immunity. Of these family members, IL-17A, IL-17F and IL-17E have been the best studied. Both IL-17A and IL-17F contribute to the host response to extracellular bacteria and fungi, and IL-17E has been shown to play a role in parasitic infections. In addition, numerous pre-clinical and clinical studies link these proteins to the pathogenesis of inflammatory diseases, and a number of therapeutic programmes targeting these family members are in clinical development. This review will highlight the cellular sources, receptors/target cells, and role in inflammation of these and the less-characterized family members, IL-17B, IL-17C and IL-17D. © 2011 Genentech, Inc. Immunology © 2011 Blackwell Publishing Ltd.

  16. Sleep pattern in Charcot-Marie-Tooth disease type 2: report of family case series.

    Science.gov (United States)

    Souza, Cynthia C; Hirotsu, Camila; Neves, Eduardo L A; Santos, Lidiane C L; Costa, Iandra M P F; Garcez, Catarina A; Nunes, Paula S; Antunes, Adriano

    2015-03-15

    Charcot-Marie-Tooth (CMT) disease is the most prevalent hereditary motor and sensory polyneuropathy, and a condition in which sleep has rarely been studied, particularly in relation to the type 2 (CMT2). Thus, we aimed to characterize the sleep patterns of a family affected by CMT2 disease. Sixteen volunteers with CMT2 from the same multigenerational family agreed to participate in the study (refusal rate = 31%). All participants answered sleep questionnaires and came to the sleep laboratory to perform a diagnostic polysomnography (PSG). Clinical manifestation and severity of the disease were also evaluated. 56% of the sample were male and 44% female, with a mean age of 32 ± 17 years, of normal weight (body mass index 21 ± 3 kg/m(2)); 64% presented moderate to severe CMT2. Regarding subjective sleep, 31% had excessive daytime sleepiness and 75% reported poor sleep quality. The PSG results revealed that CMT2 patients had an increase in stage N3 and a reduction in REM sleep, in addition to a high arousal index. Although 81% of the sample were snorers, only 13% had an apnea-hypopnea index (AHI) > 5. However, a positive correlation was found between the severity of disease and the AHI. Taken together, these data show that CMT2 disease is characterized by important changes in sleep architecture, probably due to sleep fragmentation. Although these alterations may worsen with disease severity, it seems that they are not related to sleep breathing or movement disorders. © 2014 American Academy of Sleep Medicine.

  17. Conveying a probabilistic genetic test result to families with an inherited heart disease.

    Science.gov (United States)

    Ingles, Jodie; Semsarian, Christopher

    2014-06-01

    The evolution of genetic testing in the past few years has been astounding. In a matter of only a few years, we now have comprehensive gene tests comprising vast panels of "cardiac" genes, whole exome sequencing (the entire coding region) and even whole genome sequencing (the entire genome). Making the call as to whether a DNA variant is causative or benign is difficult and the focus of intense research efforts. In most cases, the final answer will not be a simple yes/no outcome but rather a graded continuum of pathogenicity. This allows classification of variants in a more probabilistic way. How we convey this to a patient is the challenge, and certainly shines a spotlight on the important skills of the cardiac genetic counselor. This is an exciting step forward, but the overwhelming complexity of the information generated from these tests means our current practices of conveying genetic information to the family must be carefully considered. Despite the challenges, a genetic diagnosis in a family has great benefit both in reassuring unaffected family members and removing the need for lifetime clinical surveillance. The multidisciplinary specialized clinic model, incorporating genetic counselors, cardiologists and geneticists, provides the ideal framework for ensuring the best possible care for genetic heart disease families. Copyright © 2014 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

  18. Clinical Guidance on Screening Chronic Kidney Disease in Type 2 Diabetic Patients for Family Physicians

    Directory of Open Access Journals (Sweden)

    Seyed Esmaeil Managheb

    2015-10-01

    Full Text Available Incidence of diabetes is increasing in developing countries as well as Iran. Half of the patients are not aware of their disease so screening of diabetes is necessary. Lifestyle changes in society, high-saturated fat diet and decreased physical activity are the factors that influence the growing rate of diabetes in Iran.1 The need for addressing type 2 diabetes has been clarified for family physicians.2 Diabetes is a common disease that is associated with significant morbidity and mortality. It has an asymptomatic stage that may be present for up to several years before diagnosis.3 Diabetes is the leading cause of kidney disease.4 In a study among patients over 45 years with type 2 diabetes, these results were reported: 22% suffered from retinopathy, 7% had impaired vision, 6% had kidney diseases, 9% had clinical symptoms, and 19.1% were at risk for foot ulcers.5 Early treatment of type 2 diabetes can reduce or delay complications.6 Optimal glycemia and BP are important in the prevention of diabetic chronic kidney disease (CKD.4 Therapeutic goals in patients with complications, such as CKD, include maintaining renal function and stopping the trend of renal deterioration.5 Progression of diabetic nephropathy can be slowed through the use of some medications.4 How to screen and manage chronic kidney disease in patients with type 2 diabetes is shown in Figure 1.

  19. Cytogenetic abnormalities in tumors of patients with von Hippel-Lindau disease.

    Science.gov (United States)

    Jordan, D K; Patil, S R; Divelbiss, J E; Vemuganti, S; Headley, C; Waziri, M H; Gurll, N J

    1989-10-15

    Von Hippel-Lindau (VHL) disease is an autosomal dominant disorder that causes the development of benign and malignant tumors in several organ systems. Tumors causing significant morbidity include retinal angioma, cerebellar hemangioblastoma (CH), renal cell carcinoma (RCC), and pheochromocytoma (Pheo). Cytogenetic studies of tumors in VHL patients are rare. Cytogenetic findings in tumors from 12 patients with VHL disease, including four RCCs, three CHs, and five Pheos are presented. Three of the four RCC cases were abnormal. Monosomy 3 or a deletion of 3p was present in all three abnormal cases. Complete or partial trisomy of chromosome 5 was present in two cases. A deletion of 14q, trisomy 7, and a missing Y were each observed in one case. These findings indicate that a deletion of 3p may be a primary cytogenetic change in RCCs associated with VHL disease in addition to playing a role in sporadic RCC. Duplications of 5q and deletions of 14q may be important secondary changes in the progression of the malignant phenotype. No visible cytogenetic abnormalities were observed in the three CHs, or in four of the Pheos. One of the five Pheos was found to exhibit mosaic trisomy 7; its significance is unclear at the present time.

  20. Surveillance and management of upper gastrointestinal disease in Familial Adenomatous Polyposis

    DEFF Research Database (Denmark)

    Gallagher, Michelle C; Phillips, Robin K S; Bülow, Steffen

    2006-01-01

    develop colorectal cancer, but the lifetime risk of upper gastrointestinal cancer is lower, estimated at approximately 5%. Management of the upper gastrointestinal cancer risk is one of the greatest challenges facing clinicians involved in the care of Polyposis families, and with improved survival......Almost all patients affected by Familial Adenomatous polyposis (FAP) will develop foregut as well as hindgut polyps, and following prophylactic colectomy duodenal cancer constitutes one of the leading causes of death in screened populations. Without prophylactic colectomy, FAP patients predictably...... following prophylactic colectomy, the burden of foregut disease (particularly duodenal adenomatosis) will increase. Until recently, the value of upper gastrointestinal surveillance in FAP populations has been contentious, but with improved understanding of the natural history coupled with developments...

  1. Ethnie Differences in Beliefs Regarding Alzheimer Disease Among Dementia Family Caregivers

    Science.gov (United States)

    Gray, Heather L.; Jimenez, Daniel E.; Cucciare, Michael A.; Tong, Hui-Qi; Gallagher-Thompson, Dolores

    2014-01-01

    Objective The purpose of this study was to examine ethnic differences in female dementia family caregivers’ knowledge, attitudes, and beliefs about Alzheimer disease (AD). Methods Baseline data were collected from 215 female caregivers before their participation in various psychoeducational intervention programs. Caregivers were questioned about the epidemiology, etiology, and treatment of AD. Logistic regressions and one-way analysis of variance were conducted to assess ethnic differences. Results Hispanic and Chinese caregivers were more likely to believe that AD is a normal part of aging and that AD can be diagnosed by a blood test than the white group. These beliefs about AD may delay help-seeking activities for these patients and their family caregivers. Conclusion Increased public education about AD is needed in these communities. Results are discussed in terms of barriers to accessing information about AD and ways to improve public informational outreach activities, so that the intended audiences are reached more effectively. PMID:20104051

  2. Ethical issues related to computerised family medical histories in sickle cell disease: Inforare.

    Science.gov (United States)

    Franrenet, Sandra; Duchange, Nathalie; Galactéros, Fréderic; Quantin, Catherine; Cohen, Olivier; Nzouakou, Ruben; Sudraud, Sophie; Hervé, Christian; Moutel, Grégoire

    2010-10-01

    The Inforare project aims to set up a system for the sharing of clinical and familial data, in order to study how genes are related to the severity of sickle cell disease. While the computerisation of clinical records represents a valuable research goal, an ethical framework is necessary to guarantee patients' protection and their rights in this developing field. Issues relating to patient information during the Inforare study were analysed by the steering committee. Several major concerns were discussed by the committee and formalized in the patients' information letter: educating patients to aid the recruitment of family members, rules of confidentiality and the disclosure of aggregate, individual and unexpected research results. This paper presents the main issues addressed.

  3. Neurofilament L gene is not a genetic factor of sporadic and familial Parkinson's disease.

    Science.gov (United States)

    Rahner, Nils; Holzmann, Carsten; Krüger, Rejko; Schöls, Ludger; Berger, Klaus; Riess, Olaf

    2002-09-27

    Mutations in two genes, alpha-synuclein and parkin, have been identified as some rare causes for familial Parkinson's disease (PD). alpha-Synuclein and parkin protein have subsequently been identified in Lewy bodies (LB). To gain further insight into the pathogenesis of PD we investigated the role of neurofilament light (NF-L), another component of LB aggregation. A detailed mutation search of the NF-L gene in 328 sporadic and familial PD patients of German ancestry revealed three silent DNA changes (G163A, C224T, C487T) in three unrelated patients. Analysis of the promoter region of the NF-L gene identified a total of three base pair substitutions defining five haplotypes. Association studies based on these haplotypes revealed no significant differences between PD patients and 344 control individuals. Therefore, NF-L is unlikely to play a major role in the pathogenesis of PD.

  4. Family-centered brief intervention for reducing obesity and cardiovascular disease risk

    DEFF Research Database (Denmark)

    Duncan, Scott; Goodyear-Smith, Felicity; McPhee, Julia

    2016-01-01

    OBJECTIVE: To assess the effects of a family-centered, physical activity and nutrition "brief" intervention (time-limited contact) on body weight and related health outcomes in primary health care patients with an elevated 5-year cardiovascular disease (CVD) risk. METHODS: This study implemented...... hundred and twenty patients aged 35 to 65 years from 16 primary health care clinics in Auckland, New Zealand, participated in the study. Intervention effects on BMI, waist circumference, blood pressure, blood cholesterol, triglycerides, 5-year CVD risk, physical activity, and dietary patterns were...... cholesterol at 4 and 12 months, the total cholesterol to high-density lipoprotein cholesterol ratio at 4 months, 5-year CVD risk at 4 months, and fast food consumption at 12 months. CONCLUSIONS: Our findings show that a family-centered brief intervention targeting physical activity and nutrition can generate...

  5. Surveillance and management of upper gastrointestinal disease in Familial Adenomatous Polyposis

    DEFF Research Database (Denmark)

    Gallagher, Michelle C; Phillips, Robin K S; Bülow, Steffen

    2006-01-01

    Almost all patients affected by Familial Adenomatous polyposis (FAP) will develop foregut as well as hindgut polyps, and following prophylactic colectomy duodenal cancer constitutes one of the leading causes of death in screened populations. Without prophylactic colectomy, FAP patients predictably...... develop colorectal cancer, but the lifetime risk of upper gastrointestinal cancer is lower, estimated at approximately 5%. Management of the upper gastrointestinal cancer risk is one of the greatest challenges facing clinicians involved in the care of Polyposis families, and with improved survival...... following prophylactic colectomy, the burden of foregut disease (particularly duodenal adenomatosis) will increase. Until recently, the value of upper gastrointestinal surveillance in FAP populations has been contentious, but with improved understanding of the natural history coupled with developments...

  6. VHL loss in renal cell carcinoma leads to up-regulation of CUB domain-containing protein 1 to stimulate PKC{delta}-driven migration.

    Science.gov (United States)

    Razorenova, Olga V; Finger, Elizabeth C; Colavitti, Renata; Chernikova, Sophia B; Boiko, Alexander D; Chan, Charles K F; Krieg, Adam; Bedogni, Barbara; LaGory, Edward; Weissman, Irving L; Broome-Powell, Marianne; Giaccia, Amato J

    2011-02-01

    A common genetic mutation found in clear cell renal cell carcinoma (CC-RCC) is the loss of the von Hippel-Lindau (VHL) gene, which results in stabilization of hypoxia-inducible factors (HIFs), and contributes to cancer progression and metastasis. CUB-domain-containing protein 1 (CDCP1) was shown to promote metastasis in scirrhous and lung adenocarcinomas as well as in prostate cancer. In this study, we established a molecular mechanism linking VHL loss to induction of the CDCP1 gene through the HIF-1/2 pathway in renal cancer. Also, we report that Fyn, which forms a complex with CDCP1 and mediates its signaling to PKCδ, is a HIF-1 target gene. Mechanistically, we found that CDCP1 specifically regulates phosphorylation of PKCδ, but not of focal adhesion kinase or Crk-associated substrate. Signal transduction from CDCP1 to PKCδ leads to its activation, increasing migration of CC-RCC. Furthermore, patient survival can be stratified by CDCP1 expression at the cell surface of the tumor. Taken together, our data indicates that CDCP1 protein might serve as a therapeutic target for CC-RCC.

  7. A Novel Missense Mutation of GATA4 in a Chinese Family with Congenital Heart Disease.

    Directory of Open Access Journals (Sweden)

    Xiaoqing Zhang

    Full Text Available Congenital heart disease (CHD is the most prevalent type of birth defect in human, with high morbidity in infant. Several genes essential for heart development have been identified. GATA4 is a pivotal transcription factor that can regulate the cardiac development. Many GATA4 mutations have been identified in patients with different types of CHD.In this study, the NKX2-5, HAND1 and GATA4 coding regions were sequenced in a family spanning three generations in which seven patients had CHD. Disease-causing potential variation in this family was evaluated by bioinformatics programs and the transcriptional activity of mutant protein was analyzed by the dual luciferase reporter assay.A novel GATA4 mutation, c.C931T (p.R311W, was identified and co-segregated with the affected patients in this family. The bioinformatics programs predicted this heterozygous mutation to be deleterious and the cross-species alignment of GATA4 sequences showed that the mutation occurred within a highly conserved amino acid. Even though it resided in the nuclear localization signal domain, the mutant protein didn't alter its intracellular distribution. Nevertheless, further luciferase reporter assay demonstrated that the p.R311W mutation reduced the ability of GATA4 to activate its downstream target gene.Our study identified a novel mutation in GATA4 that likely contributed to the CHD in this family. This finding expanded the spectrum of GATA4 mutations and underscored the pathogenic correlation between GATA4 mutations and CHD.

  8. Vascular risk factors, vascular disease, lipids and lipid targets in patients with familial dysbetalipoproteinemia : A European cross-sectional study

    NARCIS (Netherlands)

    Koopal, C.|info:eu-repo/dai/nl/413754820; Retterstol, K.; Sjouke, B.; Hovingh, G. K.; Ros, E.; de Graaf, J.; Dullaart, R. P. F.; Bertolini, S.; Visseren, F. L. J.|info:eu-repo/dai/nl/166267678

    Background: Familial dysbetalipoproteinemia (FD), also known as type III hyperlipoproteinemia, is a genetic dyslipidemia characterized by elevated very low density lipoprotein (VLDL) and chylomicron remnant particles that confers increased risk of cardiovascular disease (CVD). The objective of this

  9. Cardiovascular Risk Factors and Health Knowledge among Freshman College Students with a Family History of Cardiovascular Disease.

    Science.gov (United States)

    Tamragouri, Ravikiran N.; And Others

    1986-01-01

    This study compared the cardiovascular health knowledge, perception of risk factors, and health behavior of 69 freshmen with a family history of cardiovascular disease with 154 freshmen without this history. Results are discussed. (Author/MT)

  10. Neuropsychiatric symptoms of the elderly with Alzheimer's disease and the family caregivers' distress

    Directory of Open Access Journals (Sweden)

    Luana Baldin Storti

    Full Text Available ABSTRACT Objective: to analyze the relationship between the distress of the family caregiver and the presence of neuropsychiatric symptoms in elderly patients with Alzheimer's disease or mixed dementia. Method: a descriptive, cross-sectional study conducted in the Geriatric and Dementias Clinic of a general tertiary hospital, with 96 elderly people with Alzheimer's disease or mixed dementia and their family caregivers. Questionnaires to characterize the elderly and caregivers, and the Neuropsychiatric Inventory were used. Descriptive statistics and Pearson correlation test were performed. Results: 68.7% of the elderly were women, average age 80.8 years, 56.2% had Alzheimer's disease and 43.7%, mixed dementia. Among caregivers, 90.6% were women, average age 56, 70.8% took care of parents and 64.6% lived with the elderly. There was a strong (r = 0.82 and significant (p <0.01 correlation between the total score on the Neuropsychiatric Inventory and the total score on the Neuropsychiatric Inventory-Distress and strong (r = 0.80 and significant (p <0 01 correlation between the total score on the Neuropsychiatric Inventory Distress and the number of neuropsychiatric symptoms, i.e., the higher the number, frequency and severity of these symptoms in the elderly, the more intense is the caregiver distress. Conclusion: the presence of neuropsychiatric symptoms in the elderly was related to increased distress in caregivers.

  11. Family-based association analysis implicates IL-4 in susceptibility to Kawasaki disease.

    Science.gov (United States)

    Burns, J C; Shimizu, C; Shike, H; Newburger, J W; Sundel, R P; Baker, A L; Matsubara, T; Ishikawa, Y; Brophy, V A; Cheng, S; Grow, M A; Steiner, L L; Kono, N; Cantor, R M

    2005-08-01

    Several compelling lines of evidence suggest an important influence of genetic variation in susceptibility to Kawasaki disease (KD), an acute vasculitis that causes coronary artery aneurysms in children. We performed a family-based genotyping study to test for association between KD and 58 genes involved in cardiovascular disease and inflammation. By analysis of a cohort of 209 KD trios using the transmission disequilibrium test, we documented the asymmetric transmission of five alleles including the interleukin-4 (IL-4) C(-589)T allele (P=0.03). Asymmetric transmission of the IL-4 C(-589)T was replicated in a second, independent cohort of 60 trios (P=0.05, combined P=0.002). Haplotypes of alleles in IL-4, colony-stimulating factor 2 (CSF2), IL-13, and transcription factor 7 (TCF7), all located in the interleukin gene cluster on 5q31, were also asymmetrically transmitted. The reported associations of KD with atopic dermatitis and allergy, elevated serum IgE levels, eosinophilia, and increased circulating numbers of monocyte/macrophages expressing the low-affinity IgE receptor (FCepsilonR2) may be related to effects of IL-4. Thus, the largest family-based genotyping study of KD patients to date suggests that genetic variation in the IL-4 gene, or regions linked to IL-4, plays an important role in KD pathogenesis and disease susceptibility.

  12. Family caregiver's experiences of providing care to patients with End-Stage Renal Disease in South-West Nigeria.

    Science.gov (United States)

    Oyegbile, Yemisi Okikiade; Brysiewicz, Petra

    2017-09-01

    To describe the experiences of family caregivers providing care for patients living with End-Stage Renal Disease in Nigeria BACKGROUND: Family caregiving is where an unpaid volunteer, usually a close family member, attends to the needs of a loved one with a chronic, disabling illness within the home. Much research has been conducted in the area of family caregiving in high-income countries. However, the same cannot be said for many of the low-resource, multicultural African countries. Qualitative descriptive study. This qualitative descriptive study used manifest content analysis to analyse data from semi-structured, individual interviews, with 15 purposively selected family caregivers. Two tertiary institutions providing renal care in South-Western Nigeria: the research setting for this study. Five categories were identified, and these included disconnectedness with self and others, never-ending burden, 'a fool being tossed around', obligation to care and promoting a closer relationship. Experiences associated with the caregiving of patients diagnosed with End-Stage Renal Disease evoked a number of emotions from the family caregivers, and the study revealed that caregiving imposed some burdens that are specific to low-resource countries on participants. Nurses need to engage family caregivers on disease-specific teachings that might promote understanding of the disease process and role expectation. Family caregivers may benefit from social support services. © 2016 John Wiley & Sons Ltd.

  13. Family history of premature coronary heart disease and risk prediction in the EPIC-Norfolk prospective population study

    NARCIS (Netherlands)

    Sivapalaratnam, Suthesh; Boekholdt, S. Matthijs; Trip, Mieke D.; Sandhu, Manjinder S.; Luben, Robert; Kastelein, John J. P.; Wareham, Nicholas J.; Khaw, Kay-Tee

    2010-01-01

    Objective The value of a family history for coronary heart disease (CHD) in addition to established cardiovascular risk factors in predicting an individual's risk of CHD is unclear. In the European Prospective Investigation of Cancer (EPIC)-Norfolk cohort, the authors tested whether adding family

  14. Using Family Health History for Chronic Disease Prevention in the Age of Genomics: Translation to Health Education Practice

    Science.gov (United States)

    Hanson, Carl; Novilla, Lelinneth; Barnes, Michael; De La Cruz, Natalie; Meacham, Aaron

    2007-01-01

    Advances in the field of human genomics have important implications for the prevention of chronic disease. In response to these advancements, public health professionals--including health educators--must become competent in the principles underlying the interface between genomics and the use of family health history. Family health history captures…

  15. Genetic polymorphism of MMP family and coronary disease susceptibility: a meta-analysis.

    Science.gov (United States)

    Li, Min; Shi, Jingpu; Fu, Lingyu; Wang, Hailong; Zhou, Bo; Wu, Xiaomei

    2012-03-01

    The issue that genetic polymorphism of matrix metalloproteinase (MMP) family is in association with coronary disease is controversial. So we did a meta-analysis to clarify it clearly. We made a literature search of PubMed, the Web of Science, and Cochrane Collaboration's database to identify eligible reports. The methodological quality of each included studies was assessed. We calculated the pooled ORs with their 95%CI for each genetic polymorphism in STATA 11 software. Separate analysis was performed to address the consistency of results across the subgroup with different continents. A total of 39 studies were included, with a sample of 42269 individuals. This meta-analysis provided evidence that genetic polymorphism of MMP1-1607 1G/2G, MMP3-Gly45lys, MMP3-376 G/C, MMP3-1171 5A/6A, MMP9-1562 C/T and MMP9-R279Q have a small to medium effect on incidence of coronary disease. There was no evidence that MMP1-519 A/G, MMP1-340 T/C and MMP2-1306 C/T polymorphism could increase risk of coronary disease. Results from subgroup analysis supported a relation between MMP3-1711 5A allele, MMP9-1562 C allele and coronary disease especially in Asian population. The results provide moderate association between the six common genetic polymorphism of matrix metalloproteinase family and coronary disease. However, the challenge for researcher is identifying separate effect on different races. Copyright © 2011 Elsevier B.V. All rights reserved.

  16. Caring for a family member with Alzheimer's disease: coping with caregiver burden post-nursing home placement.

    Science.gov (United States)

    Garity, Joan

    2006-06-01

    Most nursing home research has focused on predictors for placement, the placement decision-making process, or the effects of placement on the nursing home resident. Little research is available on family caregivers' experiences after placing their loved ones in a nursing home. The purpose of this qualitative study was to identify how family caregivers coped with the burden of post-nursing home placement of a family member with Alzheimer's disease (AD). Several factors that positively or negatively affected coping among family caregivers were identified. Family caregivers' interactions with their loved one, other nursing home residents, family and friends, nursing staff, and the nursing home-sponsored support group all contributed positively to their coping with the burden of post-nursing home placement. Factors that decreased family caregivers' coping were role disruption, guilt over placement, and uncertainty about the future.

  17. Alzheimer disease-like clinical phenotype in a family with FTDP-17 caused by a MAPT R406W mutation

    DEFF Research Database (Denmark)

    Lindquist, S.G.; Holm, I.E.; Schwartz, M.

    2008-01-01

    We report clinical, molecular, neuroimaging and neuropathological features of a Danish family with autosomal dominant inherited dementia, a clinical phenotype resembling Alzheimer's disease and a pathogenic mutation (R406W) in the microtubule associated protein tau (MAPT) gene. Pre-symptomatic an......We report clinical, molecular, neuroimaging and neuropathological features of a Danish family with autosomal dominant inherited dementia, a clinical phenotype resembling Alzheimer's disease and a pathogenic mutation (R406W) in the microtubule associated protein tau (MAPT) gene. Pre...

  18. Surgical Treatment of 13-year-old Patient with Coronary Artery Disease and Supravalvular Aortic Stenosis with Familial Hypercholesterolemia

    Directory of Open Access Journals (Sweden)

    Yüksel Atay

    2011-12-01

    Full Text Available Familial hypercholesterolemia is a genetic disorder caused by a mutation in low density lipoprotein (LDL gene. The homozygous type of the disease is rare and causes tendon xanthomas and coronary artery disease during the early years of life. Because of that, some of these patients needs early coronary revascularization. We presented 13-year-old patient who underwent coronary artery bypass graft due to familial hypercholesterolemia and repair of supravalvular aortic stenosis at the same time.

  19. Psychosocial risk in families of infants undergoing surgery for a serious congenital heart disease.

    Science.gov (United States)

    Hearps, Simone J; McCarthy, Maria C; Muscara, Frank; Hearps, Stephen J C; Burke, Kylie; Jones, Bryn; Anderson, Vicki A

    2014-08-01

    The aim of this study was to explore the acute psychosocial risk in families with infants undergoing surgery for a congenital heart disease and, secondarily, to explore the psychosocial impact of antenatal versus post-natal diagnoses. The study sample comprised 39 caregivers (28 mothers) of 29 children diagnosed with a congenital heart disease and requiring surgery within the first 4 weeks of life. Psychosocial risk was measured using the Psychosocial Assessment Tool, which was adapted to include four novel items examining infant risk factors, namely, sleeping, feeding, crying, and bonding difficulties. Parents' psychosocial risk was measured within 4 weeks after their child's surgery and stratified into a three-tiered framework: Universal, Targeted, and Clinical risk. Of the total sample, 61.5% of parents were classified as Universal, that is, at lowest risk; 35.9% as Targeted, and 2.6% as Clinical. The within-family parent total Psychosocial Assessment Tool score correlations were non-significant, and there were no differences between families of infants who received post-natal versus antenatal diagnosis or single ventricle versus biventricular repair. Linear regression found that a higher parent education significantly predicted a lower total Psychosocial Assessment Tool score. Findings indicate that, although the majority of parents adapt to the acute stress of surgery for a serious cardiac illness in their infant, the remaining 38.5% report an increased psychosocial risk associated with higher rates of emotional distress, which may impact on the parental quality of life and capacity for optimal parenting. The distribution of psychosocial risk in parents of children undergoing surgery for a congenital heart disease is consistent with that described for parents of children with other serious paediatric diagnoses.

  20. Management of endolymphatic sac tumors: sporadic cases and von Hippel-Lindau disease.

    Science.gov (United States)

    Nevoux, Jérôme; Nowak, Catherine; Vellin, Jean-François; Lepajolec, Christine; Sterkers, Olivier; Richard, Stéphane; Bobin, Serge

    2014-06-01

    To analyze the difference between the endolymphatic sac tumors (ELSTs) in sporadic cases and in von Hippel-Lindau (VHL) disease. Retrospective case review in a tertiary referral center. Fourteen cases of ELST, occurring since 1998, were reviewed. We analyzed the initial symptoms, characteristics of the tumor, treatment, sequelae, and follow-up for each group. The ELSTs were sporadic in 6 cases and associated with VHL disease in 8 cases. The mean age at the time of the first surgery was 26 years (range, 12-41). All except two of the patients presented with a unilateral tumor. The initial symptoms were hearing loss (n = 9), tinnitus (n = 7), and/or vertigo (n = 5). Hearing loss was more prevalent in the sporadic cases. Preoperative arteriography was performed for 4 patients, with embolization performed for 1 patient. The size of the tumor was significantly larger in the sporadic cases (31.7 mm) than in the cases of VHL disease (19.3 mm). The surgical approach was more extensive in the sporadic cases. The surgeons found 2 types of tumors. Cystic tumors with massive bleeding invading the surrounding structures (the dura mater or jugular bulb) were more common in the sporadic cases. Fibrous tumors that infiltrate the bone and have moderate bleeding were more common in the cases associated with VHL disease.Two patients with small lesions were not operated on but were followed for 6 years without tumor growth. They died of metastasis from gastric and kidney cancer. Four recurrences occurred during the 14 years of follow-up. Four facial palsies and 8 cases of profound deafness were encountered postoperatively. Sporadic tumors are more aggressive than those associated with VHL disease. Complete surgical resection should be the goal of treatment. Preoperative angiography with embolization is recommended. In some cases, embolization may be impossible, and preoperative or postoperative radiotherapy should be discussed.

  1. The Role of Cardiovascular Risk Factors and Stroke in Familial Alzheimer Disease.

    Science.gov (United States)

    Tosto, Giuseppe; Bird, Thomas D; Bennett, David A; Boeve, Bradley F; Brickman, Adam M; Cruchaga, Carlos; Faber, Kelley; Foroud, Tatiana M; Farlow, Martin; Goate, Alison M; Graff-Radford, Neill R; Lantigua, Rafael; Manly, Jennifer; Ottman, Ruth; Rosenberg, Roger; Schaid, Daniel J; Schupf, Nicole; Stern, Yaakov; Sweet, Robert A; Mayeux, Richard

    2016-10-01

    The contribution of cardiovascular disease (CV) and cerebrovascular disease to the risk for late-onset Alzheimer disease (LOAD) has been long debated. Investigations have shown that antecedent CV risk factors increase the risk for LOAD, although other investigations have failed to validate this association. To study the contribution of CV risk factors (type 2 diabetes, hypertension, and heart disease) and the history of stroke to LOAD in a data set of large families multiply affected by LOAD. The National Institute on Aging Late-Onset Alzheimer Disease/National Cell Repository for Alzheimer Disease family study (hereinafter referred to as NIA-LOAD study) is a longitudinal study of families with multiple members affected with LOAD. A multiethnic community-based longitudinal study (Washington Heights-Inwood Columbia Aging Project [WHICAP]) was used to replicate findings. The 6553 participants in the NIA-LOAD study were recruited from 23 US Alzheimer disease centers with ongoing data collection since 2003; the 5972 WHICAP participants were recruited at Columbia University with ongoing data collection since 1992. Data analysis was performed from 2003 to 2015. Generalized mixed logistic regression models tested the association of CV risk factors (primary association) with LOAD. History of stroke was used for the secondary association. A secondary model adjusted for the presence of an apolipoprotein E (APOE) ε4 allele. A genetic risk score, based on common variants associated with LOAD, was used to account for LOAD genetic risk beyond the APOE ε4 effect. Mediation analyses evaluated stroke as a mediating factor between the primary association and LOAD. A total of 6553 NIA-LOAD participants were included in the analyses (4044 women [61.7%]; 2509 men [38.3%]; mean [SD] age, 77.0 [9] years), with 5972 individuals from the WHICAP study included in the replication sample (4072 women [68.2%]; 1900 men [31.8%]; mean [SD] age, 76.5 [7.0] years). Hypertension was associated

  2. Familial Adult-onset Alexander Disease: Clinical and Neuroradiological Findings of Three Cases.

    Science.gov (United States)

    Elmali, Ayşe Deniz; Çetinçelik, Ümran; Işlak, Civan; Uzun Adatepe, Nurten; Karaali Savrun, Feray; Yalçinkaya, Cengiz

    2016-06-01

    The adult-onset Alexander disease (AOAD) dramatically differs from the early onset AD with respect to clinical and neuroradiological findings. Herein we report the detailed clinical and neuroradiological findings of a Turkish family with AOAD. In all three cases, magnetic resonance imaging revealed marked atrophy of the mesencephalon, bulbus, and cervical spinal cord accompanied with signal abnormalities in the same regions along with supratentorial white matter. Basal ganglia were affected in two cases. Molecular genetic analysis revealed heterozygous mutation in the 8th exon of the glial fibrillary acidic protein gene M451I (c.1245G>A), leading to the diagnosis of AOAD in all cases.

  3. Type 1 diabetes mellitus associated with autoimmune thyroid disease, celiac disease and familial Mediterranean fever: case report.

    Science.gov (United States)

    Baş, Firdevs; Kabataş-Eryilmaz, Sema; Günöz, Hülya; Darendeliler, Feyza; Küçükemre, Banu; Bundak, Rüveyde; Saka, Nurçin

    2009-01-01

    It is known that type 1 diabetes mellitus (type 1 DM) may be associated with other autoimmune diseases. Recently, a patient with an association of type 1 DM and familial Mediterranean fever (FMF) was reported in the medical literature. A 10.5-year-old boy was brought to our clinic with complaints of polydipsia, polyuria and weight loss and was diagnosed as diabetic ketoacidosis due to autoimmune type 1 DM. Insulin therapy was started. Elevated thyroid antibodies associated with diffuse goiter and hypothyroidism led to the diagnosis of autoimmune thyroid disease (ATD), and elevated antiendomysial antibodies and abnormal intestinal biopsy findings led to the diagnosis of celiac disease (CD). L-thyroxine therapy and gluten-free diet were initiated accordingly. At the third-year of follow-up, acute attacks of fever, abdominal pain and chest pain developed. Laboratory investigations, which were normal between the attacks, revealed elevated erythrocyte sedimentation rate, fibrinogen, white blood cell count and pleural effusion on chest X-ray during the attacks. Molecular analysis for FMF revealed compound heterozygous M694I and V726A. The patient responded well to colchicine therapy started at a dose of 1.5 mg/day. We present the second patient with type 1 DM associated with FMF who also had ATD and CD.

  4. Availability and quality of coronary heart disease family history in primary care medical records: implications for cardiovascular risk assessment.

    Science.gov (United States)

    Dhiman, Paula; Kai, Joe; Horsfall, Laura; Walters, Kate; Qureshi, Nadeem

    2014-01-01

    The potential to use data on family history of premature disease to assess disease risk is increasingly recognised, particularly in scoring risk for coronary heart disease (CHD). However the quality of family health information in primary care records is unclear. To assess the availability and quality of family history of CHD documented in electronic primary care records. Cross-sectional study. 537 UK family practices contributing to The Health Improvement Network database. Data were obtained from patients aged 20 years or more, registered with their current practice between 1(st) January 1998 and 31(st) December 2008, for at least one year. The availability and quality of recorded CHD family history was assessed using multilevel logistic and ordinal logistic regression respectively. In a cross-section of 1,504,535 patients, 19% had a positive or negative family history of CHD recorded. Multilevel logistic regression showed patients aged 50-59 had higher odds of having their family history recorded compared to those aged 20-29 (OR:1.23 (1.21 to 1.25)), however most deprived patients had lower odds compared to those least deprived (OR: 0.86 (0.85 to 0.88)). Of the 140,058 patients with a positive family history recorded (9% of total cohort), age of onset was available in 45%; with data specifying both age of onset and relative affected available in only 11% of records. Multilevel ordinal logistic regression confirmed no statistical association between the quality of family history recording and age, gender, deprivation and year of registration. Family history of CHD is documented in a small proportion of primary care records; and where positive family history is documented the details are insufficient to assess familial risk or populate cardiovascular risk assessment tools. Data capture needs to be improved particularly for more disadvantaged patients who may be most likely to benefit from CHD risk assessment.

  5. Availability and quality of coronary heart disease family history in primary care medical records: implications for cardiovascular risk assessment.

    Directory of Open Access Journals (Sweden)

    Paula Dhiman

    Full Text Available The potential to use data on family history of premature disease to assess disease risk is increasingly recognised, particularly in scoring risk for coronary heart disease (CHD. However the quality of family health information in primary care records is unclear.To assess the availability and quality of family history of CHD documented in electronic primary care records.Cross-sectional study.537 UK family practices contributing to The Health Improvement Network database.Data were obtained from patients aged 20 years or more, registered with their current practice between 1(st January 1998 and 31(st December 2008, for at least one year. The availability and quality of recorded CHD family history was assessed using multilevel logistic and ordinal logistic regression respectively.In a cross-section of 1,504,535 patients, 19% had a positive or negative family history of CHD recorded. Multilevel logistic regression showed patients aged 50-59 had higher odds of having their family history recorded compared to those aged 20-29 (OR:1.23 (1.21 to 1.25, however most deprived patients had lower odds compared to those least deprived (OR: 0.86 (0.85 to 0.88. Of the 140,058 patients with a positive family history recorded (9% of total cohort, age of onset was available in 45%; with data specifying both age of onset and relative affected available in only 11% of records. Multilevel ordinal logistic regression confirmed no statistical association between the quality of family history recording and age, gender, deprivation and year of registration.Family history of CHD is documented in a small proportion of primary care records; and where positive family history is documented the details are insufficient to assess familial risk or populate cardiovascular risk assessment tools. Data capture needs to be improved particularly for more disadvantaged patients who may be most likely to benefit from CHD risk assessment.

  6. Familial risk for lifestyle-related chronic diseases: can family health history be used as a motivational tool to promote health behaviour in young adults?

    Science.gov (United States)

    Prichard, I; Lee, A; Hutchinson, A D; Wilson, C

    2015-08-01

    Risk for colorectal cancer, breast cancer, heart disease and diabetes has both a familial and a lifestyle component. This quasi-experimental study aimed to determine whether a Family Health History (FHH) assessment and the subsequent provision of risk information would increase young adults' (17-29 years) intentions to modify health behaviours associated with the risk of these chronic diseases (i.e. alcohol consumption, fruit and vegetable intake and physical activity) and to talk to their family about their risk. After baseline measures of current and intended health-related behaviours, participants (n = 116) were randomly allocated to either a FHH assessment or control information. Based on the FHH provided, participants in the FHH condition were then classified as 'above-average risk' or 'average risk'. One week later, participants were provided with tailored health information and completed follow-up measures of intended health-related behaviours and perceived vulnerability. Participants classified as 'above-average risk' had increased perceptions of vulnerability to a chronic disease. Despite this, no group differences were found in intentions to change physical activity or fruit and vegetable consumption. Participants with above-average risk reported greater intentions to decrease the frequency of their alcohol consumption than average risk/control participants. In addition, completing a FHH assessment promoted intended communication with family members about chronic disease risk. FHH assessments may have the greatest value within the family context. SO WHAT? Future research could examine the impact of providing FHH information to different family members as a health promotion strategy.

  7. Copper Inhibits the AlkB Family DNA Repair Enzymes under Wilson's Disease Condition.

    Science.gov (United States)

    Bian, Ke; Chen, Fangyi; Humulock, Zachary T; Tang, Qi; Li, Deyu

    2017-10-16

    Disturbed metabolism of copper ions can cause diseases such as Wilson's disease (WD). In this work, we investigated the inhibitory effect of Cu(II) ion in vitro on the AlkB family DNA repair enzymes, which are members of the Fe(II)/alpha-ketoglutarate-dependent dioxygenase and include human ALKBH2, ALKBH3, and E. coli AlkB proteins. None of the three proteins was significantly inhibited under normal cellular copper concentrations. However, under WD related condition, we observed that the activities of all three enzymes were strongly suppressed (from 95.2 to 100.0%). We also noted the repair efficiency under ds-DNA condition was less susceptible than ss-DNA to the inhibition.

  8. Five cases of a Joseph disease family with non-REM sleep apnea and MRI study

    Energy Technology Data Exchange (ETDEWEB)

    Kitamura, Junichi; Tsuruta, Kazuhito; Yamamura, Yoshinori; Kurihara, Teruyuki; Matsukura, Shigeru

    1987-09-01

    Four male and one female patients of a new Joseph disease family in southern Kyushu are presented. This disorder is inherited by autosomal dominant trait. The clinical symptoms are characterized by bulging eyes, ophthalmoplegia, dysarthria, rigospasticity of the lower limbs, marked dystonia and bradykinesia. In our cases, extrapyramidal symptoms were improved by amantadine and L-dopa therapy. CSF homovanilic acid (HVA) was markedly reduced. Muscle biopsy and electromyographic studies revealed neurogenic changes. MRI revealed mild atrophy of frontal lobe and cerebellum, and marked atrophy of brain stem. These findings were consistent with the clinical manifestations. Our case had central type sleep apnea by sleep EEG and polygraphic studies. This is the first report about sleep apnea and MRI of Joseph disease.

  9. Specific deficit of colour-colour short-term memory binding in sporadic and familial Alzheimer's disease.

    Science.gov (United States)

    Parra, Mario A; Sala, Sergio Della; Abrahams, Sharon; Logie, Robert H; Méndez, Luis Guillermo; Lopera, Francisco

    2011-06-01

    Short-term memory binding of visual features which are processed across different dimensions (shape-colour) is impaired in sporadic Alzheimer's disease, familial Alzheimer's disease, and in asymptomatic carriers of familial Alzheimer's disease. This study investigated whether Alzheimer's disease also impacts on within-dimension binding processes. The study specifically explored whether visual short-term memory binding of features of the same type (colour-colour) is sensitive to Alzheimer's disease. We used a neuropsychological battery and a short-term memory binding task to assess patients with sporadic Alzheimer's disease (Experiment 1), familial Alzheimer's disease (Experiment 2) due to the mutation E280A of the Presenilin-1 gene and asymptomatic carriers of the mutation. The binding task assessed change detection within arrays of unicoloured objects (Colour Only) or bicoloured objects the colours of which had to be remembered separately (Unbound Colours) or together (Bound Colours). Performance on the Bound Colours condition (1) explained the largest proportion of variance between patients (sporadic and familial Alzheimer's disease), (2) combined more sensitivity and specificity for the disease than other more traditional neuropsychological tasks, (3) identified asymptomatic carriers of the mutation even when traditional neuropsychological measures and other measures of short-term memory did not and, (4) contrary to shape-colour binding, correlated with measures of hippocampal functions. Colour-colour binding and shape-colour binding both appear to be sensitive to AD even though they seem to rely on different brain mechanisms. Copyright © 2011 Elsevier Ltd. All rights reserved.

  10. Anxiety and depression in family caregivers of people with Alzheimer disease: the LASER-AD study.

    Science.gov (United States)

    Mahoney, Rachel; Regan, Ciaran; Katona, Cornelius; Livingston, Gill

    2005-09-01

    There are high rates of stress, distress, and psychological illness in family caregivers of people with dementia. Female caregivers and those caring for people with neuropsychiatric symptoms are particularly at risk. The authors report on the prevalence of anxiety and depression in a sample of family caregivers of people with Alzheimer disease (AD) and compare the characteristics of those who did or did not have those conditions. A group of 153 people with AD and their caregivers were interviewed as part of a larger study of AD. In all, 23.5% of caregivers scored at or above caseness level for anxiety, and 10.5%, at levels for depression. Care-recipient (CR) activities of daily living (ADL) impairment, being a caregiver living with the CR, being a female caregiver, reporting a poorer quality of relationship with the CR, and caregivers reporting their health as being poor all predicted anxiety disorder. CR irritability, caregivers reporting poor health, and a poorer quality of relationship with the CR predicted depression. Clinicians should be aware of the high rates of anxiety as well as depressive symptoms in family caregivers of people with AD, especially in female caregivers. CRs and Caregivers' impaired physical health put them at risk for psychological morbidity and should be treated energetically. A poor-quality relationship between the caregiver and the CR predicts both caregiver depression and anxiety. Caregivers living with the CR are much more likely to be anxious than depressed.

  11. A Yoga and Compassion Meditation Program Reduces Stress in Familial Caregivers of Alzheimer's Disease Patients

    Directory of Open Access Journals (Sweden)

    M. A. D. Danucalov

    2013-01-01

    Full Text Available Familial caregivers of patients with Alzheimer's disease exhibit reduced quality of life and increased stress levels. The aim of this study was to investigate the effects of an 8-week yoga and compassion meditation program on the perceived stress, anxiety, depression, and salivary cortisol levels in familial caregivers. A total of 46 volunteers were randomly assigned to participate in a stress-reduction program for a 2-month period (yoga and compassion meditation program—YCMP group (n=25 or an untreated group for the same period of time (control group (n=21. The levels of stress, anxiety, depression, and morning salivary cortisol of the participants were measured before and after intervention. The groups were initially homogeneous; however, after intervention, the groups diverged significantly. The YCMP group exhibited a reduction of the stress (P<0.05, anxiety (P<0.000001, and depression (P<0.00001 levels, as well as a reduction in the concentration of salivary cortisol (P<0.05. Our study suggests that an 8-week yoga and compassion meditation program may offer an effective intervention for reducing perceived stress, anxiety, depression, and salivary cortisol in familial caregivers.

  12. Probing sporadic and familial Alzheimer’s disease using induced pluripotent stem cells

    Science.gov (United States)

    Israel, Mason A.; Yuan, Shauna H.; Bardy, Cedric; Reyna, Sol M.; Mu, Yangling; Herrera, Cheryl; Hefferan, Michael P.; Van Gorp, Sebastiaan; Nazor, Kristopher L.; Boscolo, Francesca S.; Carson, Christian T.; Laurent, Louise C.; Marsala, Martin; Gage, Fred H.; Remes, Anne M.; Koo, Edward H.; Goldstein, Lawrence S. B.

    2012-01-01

    Our understanding of Alzheimer’s disease pathogenesis is currently limited by difficulties in obtaining live neurons from patients and the inability to model the sporadic form of the disease. It may be possible to overcome these challenges by reprogramming primary cells from patients into induced pluripotent stem cells (iPSCs). Here we reprogrammed primary fibroblasts from two patients with familial Alzheimer’s disease, both caused by a duplication of the amyloid-β precursor protein gene1 (APP; termed APPDp), two with sporadic Alzheimer’s disease (termed sAD1, sAD2) and two non-demented control individuals into iPSC lines. Neurons from differentiated cultures were purified with fluorescence-activated cell sorting and characterized. Purified cultures contained more than 90% neurons, clustered with fetal brain messenger RNA samples by microarray criteria, and could form functional synaptic contacts. Virtually all cells exhibited normal electrophysiological activity. Relative to controls, iPSC-derived, purified neurons from the two APPDp patients and patient sAD2 exhibited significantly higher levels of the pathological markers amyloid-β(1–40), phospho-tau(Thr 231) and active glycogen synthase kinase-3β (aGSK-3β). Neurons from APPDp and sAD2 patients also accumulated large RAB5-positive early endosomes compared to controls. Treatment of purified neurons with β-secretase inhibitors, but not γ-secretase inhibitors, caused significant reductions in phospho-Tau(Thr 231) and aGSK-3β levels. These results suggest a direct relationship between APP proteolytic processing, but not amyloid-β, in GSK-3β activation and tau phosphorylation in human neurons. Additionally, we observed that neurons with the genome of one sAD patient exhibited the phenotypes seen in familial Alzheimer’s disease samples. More generally, we demonstrate that iPSC technology can be used to observe phenotypes relevant to Alzheimer’s disease, even though it can take decades for overt

  13. Homozygosity mapping and targeted sanger sequencing reveal genetic defects underlying inherited retinal disease in families from pakistan.

    Directory of Open Access Journals (Sweden)

    Maleeha Maria

    Full Text Available Homozygosity mapping has facilitated the identification of the genetic causes underlying inherited diseases, particularly in consanguineous families with multiple affected individuals. This knowledge has also resulted in a mutation dataset that can be used in a cost and time effective manner to screen frequent population-specific genetic variations associated with diseases such as inherited retinal disease (IRD.We genetically screened 13 families from a cohort of 81 Pakistani IRD families diagnosed with Leber congenital amaurosis (LCA, retinitis pigmentosa (RP, congenital stationary night blindness (CSNB, or cone dystrophy (CD. We employed genome-wide single nucleotide polymorphism (SNP array analysis to identify homozygous regions shared by affected individuals and performed Sanger sequencing of IRD-associated genes located in the sizeable homozygous regions. In addition, based on population specific mutation data we performed targeted Sanger sequencing (TSS of frequent variants in AIPL1, CEP290, CRB1, GUCY2D, LCA5, RPGRIP1 and TULP1, in probands from 28 LCA families.Homozygosity mapping and Sanger sequencing of IRD-associated genes revealed the underlying mutations in 10 families. TSS revealed causative variants in three families. In these 13 families four novel mutations were identified in CNGA1, CNGB1, GUCY2D, and RPGRIP1.Homozygosity mapping and TSS revealed the underlying genetic cause in 13 IRD families, which is useful for genetic counseling as well as therapeutic interventions that are likely to become available in the near future.

  14. Behavioral and Pharmacological Adherence in Pediatric Sickle Cell Disease: Parent-Child Agreement and Family Factors Associated With Adherence.

    Science.gov (United States)

    Klitzman, Page H; Carmody, Julia K; Belkin, Mary H; Janicke, David M

    2017-04-21

    This study aimed to evaluate agreement between children and parents on a measure of behavioral and pharmacological adherence in children with sickle cell disease (SCD), and the associations among family factors (i.e., problem-solving skills, routines, communication) and adherence behaviors. In all, 85 children (aged 8-18 years) with SCD and their parents completed questionnaires assessing individual and family factors. Overall parent-child agreement on an adherence measure was poor, particularly for boys and older children. Greater use of child routines was associated with better overall child-reported adherence. Open family communication was associated with higher overall parent-reported adherence. While further research is needed before definitive conclusions can be drawn, results suggest the need to assess child adherence behaviors via both child and parent reports. Findings also suggest that more daily family routines and open family communication may be protective factors for better disease management.

  15. Atypical MRI features in familial adult onset Alexander disease: case report.

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    Liu, Yonghong; Zhou, Heng; Wang, Huabing; Gong, Xiaoqing; Zhou, Anna; Zhao, Lin; Li, Xindi; Zhang, Xinghu

    2016-11-04

    Alexander disease (AxD) is a rare neurological disease, especially in adults. It shows variable clinical and radiological features. We diagnosed a female with AxD presenting with paroxysmal numbness of the limbs at the onset age of 28-year-old, progressing gradually to spastic paraparesis at age 30. One year later, she had ataxia, bulbar paralysis, bowel and bladder urgency. Her mother had a similar neurological symptoms and died within 2 years after onset (at the age of 47), and her maternal aunt also had similar but mild symptoms at the onset age of 54-year-old. Her brain magnetic resonance imaging (MRI) showed abnormal signals in periventricular white matter with severe atrophy in the medulla oblongata and thoracic spinal cord, and mild atrophy in cervical spinal cord, which is unusual in the adult form of AxD. She and her daughter's glial fibrillary acidic protein (GFAP) gene analysis revealed the same heterozygous missense mutation, c.1246C > T, p.R416W, despite of no neurological symptoms in her daughter. Our case report enriches the understanding of the familial adult AxD. Genetic analysis is necessary when patients have the above mentioned symptoms and signs, MRI findings, especially with family history.

  16. Variable expressivity familial cherubism: woman transmitting cherubism without suffering the disease.

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    Pérez-Sayáns, Mario; Barros-Angueira, Francisco; Suárez-Peñaranda, Jos Ém; García-García, Abel

    2013-11-05

    Cherubism is classified within the group of benign osteo-fibrous lesions. Aside from facial deformities, it may account for major complications. It has been observed that the disease is caused by a mutation in the gene SH3BP2 (SH3-domain binding protein 2), which is located at chromosome 4pl6.3. Here we present two cases of familial cherubism, uncle and nephew, with variable clinical involvement ("Expressivity"), and one case of a woman (sister and mother, respectively), who transmitted cherubism without suffering the disease. In this article we have shown that, in familial cherubism cases, the mutation is inherited through an autosomal dominant transmission. Mutations affecting gene SH3BP2 cause variable clinical involvement (variable expressivity), involvement can be moderate, severe or may result merely in asymptomatic carriers. Since the possibility of transmission reaches 50% of chances, we believe that it is important to develop genetic counseling for both patients and carriers, in order to prevent or minimize new affected offspring. Cherubism; SH3BP2; Expressivity.

  17. Modeling familial Danish dementia in mice supports the concept of the amyloid hypothesis of Alzheimer's disease

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    Coomaraswamy, Janaky; Kilger, Ellen; Wölfing, Heidrun; Schäfer, Claudia; Kaeser, Stephan A.; Wegenast-Braun, Bettina M.; Hefendehl, Jasmin K.; Wolburg, Hartwig; Mazzella, Matthew; Ghiso, Jorge; Goedert, Michel; Akiyama, Haruhiko; Garcia-Sierra, Francisco; Wolfer, David P.; Mathews, Paul M.; Jucker, Mathias

    2010-01-01

    Familial Danish dementia (FDD) is a progressive neurodegenerative disease with cerebral deposition of Dan-amyloid (ADan), neuroinflammation, and neurofibrillary tangles, hallmark characteristics remarkably similar to those in Alzheimer's disease (AD). We have generated transgenic (tg) mouse models of familial Danish dementia that exhibit the age-dependent deposition of ADan throughout the brain with associated amyloid angiopathy, microhemorrhage, neuritic dystrophy, and neuroinflammation. Tg mice are impaired in the Morris water maze and exhibit increased anxiety in the open field. When crossed with TauP301S tg mice, ADan accumulation promotes neurofibrillary lesions, in all aspects similar to the Tau lesions observed in crosses between β-amyloid (Aβ)-depositing tg mice and TauP301S tg mice. Although these observations argue for shared mechanisms of downstream pathophysiology for the sequence-unrelated ADan and Aβ peptides, the lack of codeposition of the two peptides in crosses between ADan- and Aβ-depositing mice points also to distinguishing properties of the peptides. Our results support the concept of the amyloid hypothesis for AD and related dementias, and suggest that different proteins prone to amyloid formation can drive strikingly similar pathogenic pathways in the brain. PMID:20385796

  18. Gene expression of the TGF-beta family in rat brain infected with Borna disease virus.

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    Nishino, Yoshii; Ooishi, Ryo; Kurokawa, Sachiko; Fujino, Kan; Murakami, Masaru; Madarame, Hiroo; Hashimoto, Osamu; Sugiyama, Kazutoshi; Funaba, Masayuki

    2009-01-01

    CRNP5, a variant of Borna disease virus (BDV), has stronger pathogenesis in rats than the related variant CRP3, although only 4 amino acids in the whole genome are different. As a first step to clarify the differential pathogenesis between the variants, the present study focused on examining the expression of the transforming growth factor (TGF)-beta family in the brain of rats infected with BDV. The main results were as follows. (1) BDV infection, irrespective of the variant, up-regulates TGF-beta1 expression in the brain, (2) the expressions of signal receptors for TGF-beta1 are also increased, (3) the expression of brain inhibin/activin betaE is up-regulated by BDV infection, and (4) the expression of brain inhibin/activin betaC tends to be higher in rats exhibiting severe Borna disease. These results indicate that members of the TGF-beta family are involved in neuronal disorders induced by BDV infection in a ligand-dependent manner. In particular, up-regulation of inhibin/activin betaC may be a key event responsible for induction of the stronger pathogenesis of the CRNP5 variant of BDV.

  19. Novel mutations in CRB1 and ABCA4 genes cause Leber congenital amaurosis and Stargardt disease in a Swedish family.

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    Jonsson, Frida; Burstedt, Marie S; Sandgren, Ola; Norberg, Anna; Golovleva, Irina

    2013-11-01

    This study aimed to identify genetic mechanisms underlying severe retinal degeneration in one large family from northern Sweden, members of which presented with early-onset autosomal recessive retinitis pigmentosa and juvenile macular dystrophy. The clinical records of affected family members were analysed retrospectively and ophthalmological and electrophysiological examinations were performed in selected cases. Mutation screening was initially performed with microarrays, interrogating known mutations in the genes associated with recessive retinitis pigmentosa, Leber congenital amaurosis and Stargardt disease. Searching for homozygous regions with putative causative disease genes was done by high-density SNP-array genotyping, followed by segregation analysis of the family members. Two distinct phenotypes of retinal dystrophy, Leber congenital amaurosis and Stargardt disease were present in the family. In the family, four patients with Leber congenital amaurosis were homozygous for a novel c.2557C>T (p.Q853X) mutation in the CRB1 gene, while of two cases with Stargardt disease, one was homozygous for c.5461-10T>C in the ABCA4 gene and another was carrier of the same mutation and a novel ABCA4 mutation c.4773+3A>G. Sequence analysis of the entire ABCA4 gene in patients with Stargardt disease revealed complex alleles with additional sequence variants, which were evaluated by bioinformatics tools. In conclusion, presence of different genetic mechanisms resulting in variable phenotype within the family is not rare and can challenge molecular geneticists, ophthalmologists and genetic counsellors.

  20. [Psychosocial strategies to strengthen the coping with Parkinson's disease: Perspectives from patients, family carers and healthcare professionals].

    Science.gov (United States)

    Navarta-Sánchez, María Victoria; Caparrós, Neus; Ursúa Sesma, María Eugenia; Díaz de Cerio Ayesa, Sara; Riverol, Mario; Portillo, Mari Carmen

    2017-04-01

    To explore the main psychosocial aspects which have influence on the coping with the disease in patients with Parkinson's disease (PD) and their family carers. An exploratory qualitative study which constitutes the second phase of a mixed-methods project. Multicenter study carried out in Navarre in 2014 in collaboration with Primary Care of Navarre Service of Health-Osasunbidea, Clínica Universidad de Navarra and Navarre Association of Parkinson's patients. A total of 21 participants: 9 people with PD, 7 family carers and 5 healthcare professionals. Participants were selected through purposive sampling. Focus groups were conducted until a suitable saturation data was achieved. Transcriptions were analysed by 2 researchers through a content analysis. Three aspects that affected how patients and family carers coped with PD were identified: features of the clinical practice; family environment, and disease's acceptance. Taking account of these findings, some strategies which could foster these aspects from primary healthcare are suggested in order to improve the adjustment to the disease in patients and family carers. The healthcare in people with PD should have an integral approach that tackle the symptoms control in patients and also deal with psychosocial aspects that influence on the coping with the disease, in patients and family carers. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

  1. Effect of psychosocial stressors on patients with Crohn's disease: threatening life experiences and family relations.

    Science.gov (United States)

    Slonim-Nevo, Vered; Sarid, Orly; Friger, Michael; Schwartz, Doron; Chernin, Elena; Shahar, Ilana; Sergienko, Ruslan; Vardi, Hillel; Rosenthal, Alexander; Mushkalo, Alexander; Dizengof, Vitaly; Ben-Yakov, Gil; Abu-Freha, Naim; Munteanu, Daniella; Gaspar, Nava; Eidelman, Leslie; Segal, Arik; Fich, Alexander; Greenberg, Dan; Odes, Shmuel

    2016-09-01

    Threatening life experiences and adverse family relations are major psychosocial stressors affecting mental and physical health in chronic illnesses, but their influence in Crohn's disease (CD) is unclear. We assessed whether these stressors would predict the psychological and medical condition of CD patients. Consecutive adult CD patients completed a series of instruments including demography, Patient Harvey-Bradshaw Index (P-HBI), Short Inflammatory Bowel Disease Questionnaire (SIBDQ), short-form survey instrument (SF-36), brief symptom inventory (BSI), family assessment device (FAD), and list of threatening life experiences (LTE). Associations of FAD and LTE with P-HBI, SIBDQ, SF-36, and BSI were examined by multiple linear and quantile regression analyses. The cohort included 391 patients, mean age 38.38±13.95 years, 59.6% women, with intermediate economic status. The median scores were as follows: P-HBI 4 (2-8), FAD 1.67 (1.3-2.1), LTE 1 (0-3), SF-36 physical health 43.75 (33.7-51.0), SF-36 mental health 42.99 (34.1-51.9), and BSI-Global Severity Index 0.81 (0.4-1.4). The SIBDQ was 47.27±13.9. LTE was associated with increased P-HBI in all quantiles and FAD in the 50% quantile. FAD and LTE were associated with reduced SIBDQ (Pfamily relations were less healthy both physically and mentally. Physicians offering patients sociopsychological therapy should relate to threatening life experiences and family relations.

  2. Genetics, environment, and asthma associated with celiac disease in the extended family of an affected child.

    Science.gov (United States)

    Sigala-Robles, R; Aguayo-Patrón, S V; Calderón de la Barca, A M

    2017-11-18

    Celiac disease (CD) is an autoimmune enteropathy associated with gluten ingestion. In extended families of celiac patients that live in close proximity of one another, shared genetic and environmental factors can predispose them to CD. The aim of this study was to provide evidence about the genetic and environmental factors involved in the development of CD in the extended family of a pediatric patient. The medical history, environmental conditions, and participant weight, height, and peripheral blood samples were evaluated. The HLA-DQ2/DQ8 haplotypes were genotyped through qPCR testing and the IgA anti-gliadin and anti-transglutaminase antibodies were quantified using the ELISA test. Twelve close-living maternal relatives of the index case participated in the study. Eight of them presented with the HLA-DQ2 haplotype, inherited from the grandfather, and 7/12 and 9/12 were positive for IgA anti-gliadin and IgA anti-transglutaminase antibodies, respectively. The main intestinal symptoms stated by the participants were abdominal bloating, excess flatulence, constipation, and gastroesophageal reflux. The most frequent extra-intestinal symptoms were fatigue, stress, and anxiety. In addition, 6/13 participants had bronchial asthma. The extended family living in close proximity of one another shared a genetic predisposition, environmental conditions, and asthma, which could have predisposed them to celiac disease. Copyright © 2017 Asociación Mexicana de Gastroenterología. Publicado por Masson Doyma México S.A. All rights reserved.

  3. Impact of DNA testing for early-onset familial Alzheimer disease and frontotemporal dementia.

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    Steinbart, E J; Smith, C O; Poorkaj, P; Bird, T D

    2001-11-01

    DNA testing of persons at risk for hereditary, degenerative neurologic diseases is relatively new. Only anecdotal reports of such testing in familial Alzheimer disease (FAD) exist, and little is know about the personal and social impact of such testing. In a descriptive, observational study, individuals at 50% risk for autosomal dominant, early-onset FAD or frontotemporal dementia with parkinsonism linked to chromosome 17 underwent DNA testing for the genetic mutations previously identified in affected family members. Individuals were followed up for (1/2) to 3 years and were interviewed regarding attitudes toward the testing process and the impact of the results. Twenty-one (8.4%) of 251 persons at risk for FAD or frontotemporal dementia requested genetic testing. The most common reasons for requesting testing were concern about early symptoms of dementia, financial or family planning, and relief from anxiety. Twelve individuals had positive DNA test results, and 6 of these had early symptoms of dementia; 8 had negative results; and 1 has not yet received results. Of 14 asymptomatic individuals completing testing, 13 believed the testing was beneficial. Two persons reported moderate anxiety and 1 reported moderate depression. As expected, persons with negative test results had happier experiences overall, but even they had to deal with ongoing anxiety and depression. Thus far, there have been no psychiatric hospitalizations, suicide attempts, or denials of insurance. Genetic testing in early-onset FAD and frontotemporal dementia can be completed successfully. Most individuals demonstrate effective coping skills and find the testing to be beneficial, but long-term effects remain unknown.

  4. Expression of REG family genes in human inflammatory bowel diseases and its regulation

    Directory of Open Access Journals (Sweden)

    Chikatsugu Tsuchida

    2017-12-01

    Full Text Available The pathophysiology of inflammatory bowel disease (IBD reflects a balance between mucosal injury and reparative mechanisms. Some regenerating gene (Reg family members have been reported to be expressed in Crohn's disease (CD and ulcerative colitis (UC and to be involved as proliferative mucosal factors in IBD. However, expression of all REG family genes in IBD is still unclear. Here, we analyzed expression of all REG family genes (REG Iα, REG Iβ, REG III, HIP/PAP, and REG IV in biopsy specimens of UC and CD by real-time RT-PCR. REG Iα, REG Iβ, and REG IV genes were overexpressed in CD samples. REG IV gene was also overexpressed in UC samples. We further analyzed the expression mechanisms of REG Iα, REG Iβ, and REG IV genes in human colon cells. The expression of REG Iα was significantly induced by IL-6 or IL-22, and REG Iβ was induced by IL-22. Deletion analyses revealed that three regions (− 220 to − 211, − 179 to − 156, and − 146 to − 130 in REG Iα and the region (− 274 to− 260 in REG Iβ promoter were responsible for the activation by IL-22/IL-6. The promoters contain consensus transcription factor binding sequences for MZF1, RTEF1/TEAD4, and STAT3 in REG Iα, and HLTF/FOXN2F in REG Iβ, respectively. The introduction of siRNAs for MZF1, RTEF1/TEAD4, STAT3, and HLTF/FOXN2F abolished the transcription of REG Iα and REG Iβ. The gene activation mechanisms of REG Iα/REG Iβ may play a role in colon mucosal regeneration in IBD.

  5. Social representation of Alzheimer's disease for family caregivers: stressful and rewarding

    Directory of Open Access Journals (Sweden)

    Aline Duarte Folle

    2016-02-01

    Full Text Available Abstract OBJECTIVE To understand the content of Social Representation (SR of family caregivers of Alzheimer's disease patients. METHOD Interviews were conducted with 26 caregivers and analyzed by the ALCESTE software. RESULTS The SR content was structured in two thematic axes called Daily Life and Care and Medical and Emotional Concepts and Outcomes. The first axis creates images related to the routine of interaction with the sick person, and contains a description of care procedures, experiences, and practices applied every day. The second is composed of subjective and conceptual aspects that make up the social representation of Alzheimer's disease, with meanings related to the emotional, medical, and biological contexts. CONCLUSION Due to the importance of topics related to patients' dependence and the personal and emotional consequences of the disease, overload is the main content of the SR of Alzheimer's disease for caregivers, and the understanding of these SR by health professionals should support the planning of interventions addressing this group of individuals.

  6. Factors associated with chronic diseases among the elderly receiving treatment under the Family Health Strategy.

    Science.gov (United States)

    Pimenta, Fernanda Batista; Pinho, Lucinéia; Silveira, Marise Fagundes; Botelho, Ana Cristina de Carvalho

    2015-08-01

    The profile of a sample population of elderly receiving treatment under the Family Health Strategy in the municipality of Teófilo Otoni, State of Minas Gerais, Brazil, is described, and the factors associated with diseases prevalence examined. Using simple random sampling, 385 elderly were interviewed using Form A and Elderly Form from the Primary Health Care Information System. The majority of the sample (83.1%) self-reported at least one disease, 69.9% had hypertension, and 17.7% had diabetes. Poisson regression analysis showed that the main factors associated with hypertension and other diseases were being non-white, having a low level of education, medication use, dental prosthesis use, and lack of a private health plan. The prevalence of diabetes was greater among women and individuals who depended on other people to live. It can be concluded that this sample population of elderly has a generally low socioeconomic status and are more susceptible to developing diseases, particularly hypertension. Diabetes should be controlled although had relatively low prevalence. It is suggested investments in structuring the health system network to provide adequate care for the elderly and in training health professionals to play an effective role in improving the quality of life of the elderly in Brazil.

  7. Social skills and well-being among family caregivers to patients with Alzheimer’s disease

    Directory of Open Access Journals (Sweden)

    Flávia Araujo de Amorim

    Full Text Available Abstract Background: Caring for a demented relative is frequently associated with burden; yet, a subset of family caregivers may experience it as rewarding. Certain characteristics, including personality factors, may render caregivers more resilient to stress and therefore attenuate the perception of burden and its impact on quality of life. Objective: To determine the association between social skills and well being among family caregivers to patients with dementia. Methods: Forty-one family caregivers to patients with dementia due to Alzheimer's disease (AD were assessed with Social Skills Inventory (SSI-Del-Prette and the Zarit Burden Interview; quality of life was estimated with WHO-QoL-bref questionnaire. Results: We found positive correlations between total SSI scores and the psychological (r = 0.450; p = 0.003 and environmental (r = 0.408; p = 0.008 domains of WHO-QoL-bref. The SSI factor ‘self-control of aggressiveness’ (SSI-F5 was negatively correlated with the magnitude of caregiver burden (r = -0.483; p = 0.001 and positively associated with the psychological domain of WHO-QoL-bref (r = 0.446; p = 0.003. Caregivers with better ‘self-assertion in the expression of positive affect’ (SSI-F2 also had better ‘social relationships’ according to WHO-QoL-bref (r = 0.402; p = 0.009. Discussion: The availability of more sophisticated repertoires of social skills may render family caregivers more resilient to burden, preserving their quality of life while enduring this task.

  8. Pesticide exposure and risk of Parkinson's disease: A family-based case-control study

    Directory of Open Access Journals (Sweden)

    Scott Burton L

    2008-03-01

    Full Text Available Abstract Background Pesticides and correlated lifestyle factors (e.g., exposure to well-water and farming are repeatedly reported risk factors for Parkinson's disease (PD, but few family-based studies have examined these relationships. Methods Using 319 cases and 296 relative and other controls, associations of direct pesticide application, well-water consumption, and farming residences/occupations with PD were examined using generalized estimating equations while controlling for age-at-examination, sex, cigarette smoking, and caffeine consumption. Results Overall, individuals with PD were significantly more likely to report direct pesticide application than their unaffected relatives (odds ratio = 1.61; 95% confidence interval, 1.13–2.29. Frequency, duration, and cumulative exposure were also significantly associated with PD in a dose-response pattern (p ≤ 0.013. Associations of direct pesticide application did not vary by sex but were modified by family history of PD, as significant associations were restricted to individuals with no family history. When classifying pesticides by functional type, both insecticides and herbicides were found to significantly increase risk of PD. Two specific insecticide classes, organochlorines and organophosphorus compounds, were significantly associated with PD. Consuming well-water and living/working on a farm were not associated with PD. Conclusion These data corroborate positive associations of broadly defined pesticide exposure with PD in families, particularly for sporadic PD. These data also implicate a few specific classes of pesticides in PD and thus emphasize the need to consider a more narrow definition of pesticides in future studies.

  9. The interleukin (IL)-1 cytokine family--Balance between agonists and antagonists in inflammatory diseases.

    Science.gov (United States)

    Palomo, Jennifer; Dietrich, Damien; Martin, Praxedis; Palmer, Gaby; Gabay, Cem

    2015-11-01

    The interleukin (IL)-1 family of cytokines comprises 11 members, including 7 pro-inflammatory agonists (IL-1α, IL-1β, IL-18, IL-33, IL-36α, IL-36β, IL-36γ) and 4 defined or putative antagonists (IL-1R antagonist (IL-1Ra), IL-36Ra, IL-37, and IL-38) exerting anti-inflammatory activities. Except for IL-1Ra, IL-1 cytokines do not possess a leader sequence and are secreted via an unconventional pathway. In addition, IL-1β and IL-18 are produced as biologically inert pro-peptides that require cleavage by caspase-1 in their N-terminal region to generate active proteins. N-terminal processing is also required for full activity of IL-36 cytokines. The IL-1 receptor (IL-1R) family comprises 10 members and includes cytokine-specific receptors, co-receptors and inhibitory receptors. The signaling IL-1Rs share a common structure with three extracellular immunoglobulin (Ig) domains and an intracellular Toll-like/IL-1R (TIR) domain. IL-1 cytokines bind to their specific receptor, which leads to the recruitment of a co-receptor and intracellular signaling. IL-1 cytokines induce potent inflammatory responses and their activity is tightly controlled at the level of production, protein processing and maturation, receptor binding and post-receptor signaling by naturally occurring inhibitors. Some of these inhibitors are IL-1 family antagonists, while others are IL-1R family members acting as membrane-bound or soluble decoy receptors. An imbalance between agonist and antagonist levels can lead to exaggerated inflammatory responses. Several genetic modifications or mutations associated with dysregulated IL-1 activity and autoinflammatory disorders were identified in mouse models and in patients. These findings paved the road to the successful use of IL-1 inhibitors in diseases that were previously considered as untreatable. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Genetic variants associated with susceptibility to psychosis in late-onset Alzheimer's disease families.

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    Barral, Sandra; Vardarajan, Badri N; Reyes-Dumeyer, Dolly; Faber, Kelley M; Bird, Thomas D; Tsuang, Debby; Bennett, David A; Rosenberg, Roger; Boeve, Bradley F; Graff-Radford, Neill R; Goate, Alison M; Farlow, Martin; Lantigua, Rafael; Medrano, Martin Z; Wang, Xinbing; Kamboh, M Ilyas; Barmada, Mahmud Muhiedine; Schaid, Daniel J; Foroud, Tatiana M; Weamer, Elise A; Ottman, Ruth; Sweet, Robert A; Mayeux, Richard

    2015-11-01

    Psychotic symptoms are frequent in late-onset Alzheimer's disease (LOAD) patients. Although the risk for psychosis in LOAD is genetically mediated, no genes have been identified. To identify loci potentially containing genetic variants associated with risk of psychosis in LOAD, a total of 263 families from the National Institute of Aging-LOAD cohort were classified into psychotic (LOAD+P, n = 215) and nonpsychotic (LOAD-P, n = 48) families based on the presence/absence of psychosis during the course of LOAD. The LOAD+P families yielded strong evidence of linkage on chromosome 19q13 (two-point [2-pt] ​logarithm of odds [LOD] = 3.8, rs2285513 and multipoint LOD = 2.7, rs541169). Joint linkage and association in 19q13 region detected strong association with rs2945988 (p = 8.7 × 10(-7)). Linkage results for the LOAD-P families yielded nonsignificant 19q13 LOD scores. Several 19q13 single-nucleotide polymorphisms generalized the association of LOAD+P in a Caribbean Hispanic (CH) cohort, and the strongest signal was rs10410711 (pmeta = 5.1 × 10(-5)). A variant located 24 kb upstream of rs10410711 and rs10421862 was strongly associated with LOAD+P (pmeta = 1.0 × 10(-5)) in a meta-analysis of the CH cohort and an additional non-Hispanic Caucasian dataset. Identified variants rs2945988 and rs10421862 affect brain gene expression levels. Our results suggest that genetic variants in genes on 19q13, some of which are involved in brain development and neurodegeneration, may influence the susceptibility to psychosis in LOAD patients. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  11. Mutations in the gene DNAJC5 cause autosomal dominant Kufs disease in a proportion of cases: study of the Parry family and 8 other families.

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    Milen Velinov

    Full Text Available The Neuronal Ceroid Lipofuscinoses (NCL comprise at least nine progressive neurodegenerative genetic disorders. Kufs disease, an adult-onset form of NCL may be recessively or dominantly inherited. Our study aimed to identify genetic mutations associated with autosomal dominant Kufs disease (ADKD.We have studied the family first reported with this phenotype in the 1970s, the Parry family. The proband had progressive psychiatric manifestations, seizures and cognitive decline starting in her mid 20 s. Similarly affected relatives were observed in seven generations. Several of the affected individuals had post-mortem neuropathological brain study confirmatory for NCL disease. We conducted whole exome sequencing of three affected family members and identified a pLeu116del mutation in the gene DNAJC5, which segregated with the disease phenotype. An additional eight unrelated affected individuals with documented autosomal dominant or sporadic inheritance were studied. All had diagnostic confirmation with neuropathological studies of brain tissue. Among them we identified an additional individual with a p.Leu115Arg mutation in DNAJC5. In addition, a pAsn477Ser change in the neighboring gene PRPF6, a gene previously found to be associated with retinitis pigmentosa, segregated with the ADKD phenotype. Interestingly, two individuals of the Parry family did report visual impairment.Our study confirmed the recently reported association of DNAJC5 mutations with ADKD in two out of nine well-defined families. Sequence changes in PRPF6 have not been identified in other unrelated cases. The association of vision impairment with the expected PRPF6 dysfunction remains possible but would need further clinical studies in order to confirm the co-segregation of the visual impairment with this sequence change.

  12. Analysis of copy number variation in Alzheimer's disease: the NIALOAD/ NCRAD Family Study.

    Science.gov (United States)

    Swaminathan, Shanker; Shen, Li; Kim, Sungeun; Inlow, Mark; West, John D; Faber, Kelley M; Foroud, Tatiana; Mayeux, Richard; Saykin, Andrew J

    2012-09-01

    Copy number variants (CNVs) are DNA regions that have gains (duplications) or losses (deletions) of genetic material. CNVs may encompass a single gene or multiple genes and can affect their function. They are hypothesized to play an important role in certain diseases. We previously examined the role of CNVs in late-onset Alzheimer's disease (AD) and mild cognitive impairment (MCI) using participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) study and identified gene regions overlapped by CNVs only in cases (AD and/or MCI) but not in controls. Using a similar approach as ADNI, we investigated the role of CNVs using 794 AD and 196 neurologically evaluated control non-Hispanic Caucasian NIA-LOAD/NCRAD Family Study participants with DNA derived from blood/brain tissue. The controls had no family history of AD and were unrelated to AD participants. CNV calls were generated and analyzed after detailed quality review. 711 AD cases and 171 controls who passed all quality thresholds were included in case/control association analyses, focusing on candidate gene and genome-wide approaches. We identified genes overlapped by CNV calls only in AD cases but not controls. A trend for lower CNV call rate was observed for deletions as well as duplications in cases compared to controls. Gene-based association analyses confirmed previous findings in the ADNI study (ATXN1, HLA-DPB1, RELN, DOPEY2, GSTT1, CHRFAM7A, ERBB4, NRXN1) and identified a new gene (IMMP2L) that may play a role in AD susceptibility. Replication in independent samples as well as further analyses of these gene regions is warranted.

  13. Family clustering of secondary chronic kidney disease with hypertension or diabetes mellitus. A case-control study.

    Science.gov (United States)

    de Almeida, Fernando Antonio; Ciambelli, Giuliano Serafino; Bertoco, André Luz; Jurado, Marcelo Mai; Siqueira, Guilherme Vasconcelos; Bernardo, Eder Augusto; Pavan, Maria Valeria; Gianini, Reinaldo José

    2015-02-01

    In Brazil hypertension and type 2 diabetes mellitus are responsible for 60% of cases of end-stage renal disease in renal replacement therapy. In the United States studies have identified family clustering of chronic kidney disease, predominantly in African-Americans. A single Brazilian study observed family clustering among patients with chronic kidney disease when compared with hospitalized patients with normal renal function. This article aims to assess whether there is family clustering of chronic kidney disease in relatives of individuals in renal replacement therapy caused by hypertension and/or diabetes mellitus. A case-control study with 336 patients in renal replacement therapy with diabetes mellitus or hypertension for at least 5 years (cases) and a control matched sample group of individuals with hypertension or diabetes mellitus and normal renal function (n = 389). Individuals in renal replacement therapy (cases) had a ratio of 2.35 (95% CI 1.42-3.89, p hypertension or diabetes mellitus).

  14. Polygenic risk score predicts prevalence of cardiovascular disease in patients with familial hypercholesterolemia.

    Science.gov (United States)

    Paquette, Martine; Chong, Michael; Thériault, Sébastien; Dufour, Robert; Paré, Guillaume; Baass, Alexis

    Although familial hypercholesterolemia (FH) is a severe monogenic disease, it has been shown that clinical risk factors and common genetic variants can modify cardiovascular disease (CVD) risk. The aim of the study was to evaluate the polygenic contribution to lipid traits and CVD in FH using genetic risk scores (GRSs). Among the 20,434 subjects attending the lipid clinic, we identified and included 725 individuals who carried an FH causing mutation in this retrospective cohort study. We evaluated the association of GRSs for several traits including coronary artery disease (CAD; GRSCAD) as well as plasma concentrations of low-density lipoprotein cholesterol (LDL-C; GRSLDL-C), high-density lipoprotein cholesterol (GRSHDL-C) and triglycerides (GRSTG). A total of 32% (n = 231) of FH subjects presented a CVD event before their first visit. Patients in the highest GRSLDL-C tertile presented an LDL-C 0.4 mmol/L (15.5 mg/dL) higher than the subjects in the lowest tertile (P = .01). The GRSCAD was strongly associated with CVD events (odds ratio 1.80; 95% confidence interval 1.14-2.85; P = .01) even after adjustment for cardiovascular risk factors. Compared with subjects in the first tertile, those in the third GRSCAD tertile had a significantly higher prevalence of events (40.9% vs 24.7%, P < .0001) and a significantly higher number of events (average 0.97 vs 0.57 [P = .0001] events per individual). These results indicate that even in the context of a severe monogenic disease such as FH, common genetic variants can significantly modify the disease phenotype. The use of the 192-SNPs GRSCAD may refine CVD risk prediction in FH patients and this could lead to a more personalized approach to therapy. Copyright © 2017 National Lipid Association. Published by Elsevier Inc. All rights reserved.

  15. Calgary Family Intervention Model Approach ( CFIM ) Prevention of Food Borne Disease and Self Care Agency for Children

    OpenAIRE

    Nurbadriyah, Wiwit Dwi

    2016-01-01

    Food borne disease (FBD) is a disease caused by consumption of contaminated food. The problem is, school aged children are vulnerable Food borne disease because of household food contamination. This indicates the family hygiene as a food handler mainly mother during preparing the food still need to be improved. The study design used pre experiment one group pre and post test design with a sample of 35 respondents namely, 4th grade students with their parents and 5th grade students with their ...

  16. Is autism a member of a family of diseases resulting from genetic/cultural mismatches? Implications for treatment and prevention.

    Science.gov (United States)

    Bilbo, Staci D; Jones, John P; Parker, William

    2012-01-01

    Several lines of evidence support the view that autism is a typical member of a large family of immune-related, noninfectious, chronic diseases associated with postindustrial society. This family of diseases includes a wide range of inflammatory, allergic, and autoimmune diseases and results from consequences of genetic/culture mismatches which profoundly destabilize the immune system. Principle among these consequences is depletion of important components, particularly helminths, from the ecosystem of the human body, the human biome. Autism shares a wide range of features in common with this family of diseases, including the contribution of genetics/epigenetics, the identification of disease-inducing triggers, the apparent role of immunity in pathogenesis, high prevalence, complex etiologies and manifestations, and potentially some aspects of epidemiology. Fortunately, using available resources and technology, modern medicine has the potential to effectively reconstitute the human biome, thus treating or even avoiding altogether the consequences of genetic/cultural mismatches which underpin this entire family of disease. Thus, if indeed autism is an epidemic of postindustrial society associated with immune hypersensitivity, we can expect that the disease is readily preventable.

  17. Cultural adaptation of the Family Management Measure among families of children and adolescents with chronic diseases 1

    Science.gov (United States)

    Ichikawa, Carolliny Rossi de Faria; Bousso, Regina Szylit; Misko, Maira Deguer; Mendes-Castillo, Ana Marcia Chiaradia; Bianchi, Estela Regina Ferraz; Damião, Elaine Buchhorn Cintra

    2014-01-01

    Objectives to perform the cultural adaptation of the Family Management Measure into the Brazilian Portuguese language. Method the method complied with international recommendations for this type of study and was composed of the following steps: translation of the instrument into the Portuguese language; reaching consensus over the translated versions; assessment by an expert committee; back translation; and pretest. Results these stages enabled us to obtain conceptual, by-item, semantic, idiomatic, and operational equivalences, in addition to content validation. Conclusion the Family Management Measure is adapted to the Brazilian Portuguese language and that version is named Instrumento de Medida de Manejo Familiar. PMID:24553711

  18. Complex educational and care (geron)technology for elderly individuals/families experiencing Alzheimer's disease.

    Science.gov (United States)

    Ilha, Silomar; Santos, Silvana Sidney Costa; Backes, Dirce Stein; Barros, Edaiane Joana Lima; Pelzer, Marlene Teda; Costenaro, Regina Gema Santini

    2017-01-01

    To describe the contributions of the Integrated Multidisciplinary Care Group for Caregivers of Individuals with Alzheimer's Disease as an educational and care (geron)technology in the context of Alzheimer's disease in elderly individuals from the perspective of family members/caregivers. Exploratory, descriptive study with a qualitative approach conducted with 13 family members/caregivers of elderly people participating in the support group of a university institution of the state of Rio Grande do Sul, Brazil. Data collected between January and April 2016 through a semi-structured interview were submitted to discursive textual analysis. Family members/caregivers pointed out education and care as contributions of the group; education for care and for the future; exchange, socialization, and development of knowledge through the range of knowledge existing in the Group. The Group contributes as a (geron)technology of care and education for care in which knowledge is built and applied in practice, supporting the experienced disorders and improving the quality of care provided for elderly individuals with Alzheimer's disease. Descrever as contribuições do Grupo de Assistência Multidisciplinar Integrada aos Cuidadores de Pessoas com a Doença de Alzheimer como (geronto)tecnologia cuidativo-educacional no contexto da doença de Alzheimer em pessoas idosas, na perspectiva de familiares/cuidadores. Pesquisa exploratório-descritiva, qualitativa, realizada com 13 familiares/cuidadores de pessoas idosas, participantes do grupo de apoio de uma instituição universitária do Rio Grande do Sul, Brasil. Os dados coletados entre janeiro a abril/2016, com uma entrevista semiestruturada, foram submetidos à análise textual discursiva. Os familiares/cuidadores referiram como contribuições do Grupo a educação e o cuidado; a educação para o cuidado e para o futuro; a troca, socialização e construção do conhecimento por meio dos diversos saberes existentes no Grupo. O

  19. Facial appearance reflects human familial longevity and cardiovascular disease risk in healthy individuals.

    Science.gov (United States)

    Gunn, David A; de Craen, Anton J M; Dick, Joanne L; Tomlin, Cyrena C; van Heemst, Diana; Catt, Sharon D; Griffiths, Tamara; Ogden, Stephanie; Maier, Andrea B; Murray, Peter G; Griffiths, Christopher E M; Slagboom, P Eline; Westendorp, Rudi G J

    2013-02-01

    As facial appearance can be readily quantified and skin tissue easily accessed, they could be valuable tools for determining how biological mechanisms influence tissue degeneration with age and, consequently, human health and lifespan. It is unknown, however, whether appearance reflects disease risk or lifespan independently of factors already known to associate with both health and appearance. In a cross-sectional study, we compared the amount of skin wrinkling on a sun-protected site (upper inner arm) and the facial appearance of 261 offspring (mean age 63.2 y) of nonagenarian siblings with 253 age-matched controls (mean age 62.7 y), all with no reported disease history. We next examined whether any appearance features that significantly associated with familial longevity also associated with the Framingham cardiovascular disease (CVD) risk score. All analyses were adjusted for chronological age, smoking, photodamage, and body mass index. Female and male offspring had reduced upper inner arm skin wrinkling (p = .03 and p appearance and skin wrinkling at a sun-protected site reflect the propensity to reach an extreme old age, and facial appearance reflects the risk of succumbing to CVD independently of chronological age, smoking, photodamage, and BMI.

  20. An Uncommon Association of Familial Partial Lipodystrophy, Dilated Cardiomyopathy, and Conduction System Disease

    Directory of Open Access Journals (Sweden)

    Ragesh Panikkath MD

    2016-07-01

    Full Text Available A 46-year-old African American woman presented with severe respiratory distress requiring intubation and was diagnosed with nonischemic cardiomyopathy. She had the typical phenotype of familial partial lipodystrophy 2 (FPLD2. Sequence analysis of LMNA gene showed a heterozygous missense mutation at exon 8 (c.1444C>T causing amino acid change, p.R482W. She later developed severe coronary artery disease requiring multiple percutaneous coronary interventions and coronary artery bypass surgery. She was later diagnosed with diabetes, primary hyperparathyroidism, and euthyroid multinodular goiter. She had sinus nodal and atrioventricular nodal disease and had an implantable cardioverter defibrillator implantation due to persistent left ventricular dysfunction. The device eroded through the skin few months after implantation and needed a re-implant on the contralateral side. She had atrial flutter requiring ablation. This patient with FPLD2 had most of the reported cardiac complications of FPLD2. This case is presented to improve the awareness of the presentation of this disease among cardiologists and internists.

  1. "Boring" family routines reduce non-communicable diseases: a commentary and call for action.

    Science.gov (United States)

    Rotheram-Borus, Mary Jane; Tomlinson, Mark; Davis, Emily

    2015-01-01

    As global donors shift their efforts from infectious diseases to non-communicable diseases (NCD), it is critical to capitalize on our prior mistakes and successes. Policy makers and public health administrators are often looking for magic bullets: drugs or treatments to eradicate disease. Yet, each potential magic bullet requires consistent, daily implementation and adherence to a new set of habits to actually work. Families' and communities' daily, interlocking routines will be the battlefield on which scientific and technological breakthroughs will be implemented and succeed or not. Currently, there are many evidence-based interventions (EBI) which have been demonstrated to shift specific habits which account for most NCD (eating, drinking, moving, and smoking). Yet, securing sustained uptake of these programs is rare - suggesting different intervention strategies are needed. Structural changes, policy nudges, and partnerships with private enterprise may be able to shift the health behaviors of more citizens faster and at a lower cost than existing EBI. Addressing concurrent risk and protective factors at the community level and intervening to shape new cultural routines may be useful to reduce NCD.

  2. Qualitative changes in human γ-secretase underlie familial Alzheimer’s disease

    Science.gov (United States)

    Szaruga, Maria; Veugelen, Sarah; Benurwar, Manasi; Lismont, Sam; Sepulveda-Falla, Diego; Lleo, Alberto; Ryan, Natalie S.; Lashley, Tammaryn; Fox, Nick C.; Murayama, Shigeo; Gijsen, Harrie

    2015-01-01

    Presenilin (PSEN) pathogenic mutations cause familial Alzheimer’s disease (AD [FAD]) in an autosomal-dominant manner. The extent to which the healthy and diseased alleles influence each other to cause neurodegeneration remains unclear. In this study, we assessed γ-secretase activity in brain samples from 15 nondemented subjects, 22 FAD patients harboring nine different mutations in PSEN1, and 11 sporadic AD (SAD) patients. FAD and control brain samples had similar overall γ-secretase activity levels, and therefore, loss of overall (endopeptidase) γ-secretase function cannot be an essential part of the pathogenic mechanism. In contrast, impaired carboxypeptidase-like activity (γ-secretase dysfunction) is a constant feature in all FAD brains. Significantly, we demonstrate that pharmacological activation of the carboxypeptidase-like γ-secretase activity with γ-secretase modulators alleviates the mutant PSEN pathogenic effects. Most SAD cases display normal endo- and carboxypeptidase-like γ-secretase activities. However and interestingly, a few SAD patient samples display γ-secretase dysfunction, suggesting that γ-secretase may play a role in some SAD cases. In conclusion, our study highlights qualitative shifts in amyloid-β (Aβ) profiles as the common denominator in FAD and supports a model in which the healthy allele contributes with normal Aβ products and the diseased allele generates longer aggregation-prone peptides that act as seeds inducing toxic amyloid conformations. PMID:26481686

  3. Practices of Family Health Professionals Regarding Chronic Disease Control and Prevention Programs

    Directory of Open Access Journals (Sweden)

    Esma Kabasakal

    2017-10-01

    Full Text Available Introduction: Chronic diseases are of the utmost importance, due to their impact on high death rates, excessive increases in health expenses, and sustainability of health services. Further, it is recommended for individuals, and society at large, to decrease exposure to modifiable risk factors, like tobacco use, malnutrition, and lack of physical activity, and to encourage a lifestyle that supports the fight against chronic diseases. The aim of this study was to determine the practices of health professionals in terms of preventing chronic diseases and improving health. Methods: Health professionals from family health centers participated in this survey study. The data collection tool was developed by the researcher, by considering the nationwide health programs applied in Turkey, namely the Tobacco Control Program, Healthy Nutrition and Active Life Program, Turkey Diabetes Prevention and Control Program, and Cancer Control Programs. Results: Those who received training on health promotion had higher rates of involvement in tobacco cessation guidance, directing individuals to smoking cessation centers, giving trainings to cancer patients and others at risk, following up on individuals with a risk of obesity, raising awareness of healthy individuals concerning obesity, and training patients/patient relatives on diabetes. Discussion: The level of training that health professionals offer to patients and their relatives is higher than the level of training given to healthy individuals in all control programs. This inclination is an indicator of a treatment-oriented service approach to health. The capacity of health professionals should be directed more towards preventive medicine and health improving practices.

  4. High incidence of pediatric idiopathic epilepsy is associated with familial and autosomal dominant disease in Eastern Newfoundland.

    Science.gov (United States)

    Mahoney, Krista; Buckley, David; Alam, Muhammed; Penney, Sharon; Young, Terry-Lynn; Parfrey, Patrick; Moore, Susan J

    2012-02-01

    To describe the incidence and epidemiology of pediatric idiopathic epilepsy (IE) in Newfoundland and Labrador. All children in Newfoundland and Labrador aged 0-15 years with IE were ascertained through the provincial neurology clinic at the Janeway Child Health Centre. Family history, medical history and blood samples were obtained from probands and relatives. Two genes, SCN1A and KCNQ2, were screened for mutations by direct sequencing. The mean annual incidence of IE for the population of children living in the Avalon region of Newfoundland from 2000 to 2004 was 107 per 100,000. This rate is approximately three-fold greater than rates reported in other developed countries. Of 117 families with IE eligible for study, 86 (74%) provided detailed pedigree data. Multiple different epilepsy phenotypes were identified. Fifty-five families (64%) had a positive family history. Eight of these had family histories compatible with autosomal dominant (AD) inheritance and these families lived in five different geographic isolates. DNA was obtained from 21 families (79 individuals). The two previously identified mutations in Newfoundland families with epilepsy were sequenced and excluded as pathogenic sites in all but one family which had a mutation in SCN1A. The incidence of IE is high in the Avalon Peninsula of Newfoundland and the rate of familial disease is high throughout the province of Newfoundland and Labrador. The distribution of familial and AD IE in different geographic isolates, together with the clinical heterogeneity of disease suggests substantial genetic heterogeneity. It is likely that other novel mutations will be identified in this population. Copyright © 2011 Elsevier B.V. All rights reserved.

  5. Core elements to understand and improve coping with Parkinson's disease in patients and family carers: A focus group study.

    Science.gov (United States)

    Navarta-Sánchez, M Victoria; Caparrós, Neus; Riverol Fernández, Mario; Díaz De Cerio Ayesa, Sara; Ursúa Sesma, M Eugenia; Portillo, Mari Carmen

    2017-11-01

    The aim of this study were: (1) To explore the meaning that coping with Parkinson's disease has for patients and family carers; (2) To suggest the components of an intervention focused on enhancing their coping with the disease. Adapting to Parkinson's disease involves going through many difficult changes; however, it may improve quality of life in patients and family carers. One of the key aspects for facilitating the psychosocial adjustment to Parkinson's disease is the strengthening of coping skills. A sequential explanatory mixed methods study was carried out. Findings from the qualitative phase are presented. Data were collected in May 2014 through three focus groups: one of people with Parkinson's disease (n = 9), one of family carers (n = 7) and one of healthcare professionals (n = 5). All focus groups were digitally recorded and transcribed verbatim and content analysis was independently carried out by two researchers. The participants coincided in highlighting that coping with Parkinson's disease helped the patient and the family carer in their search for balance; and it implied a transformation in their lives. To aid the process of coping with Parkinson's disease, a multifaceted intervention is proposed. Coping with Parkinson's disease is a complex process for both patients and family carers and it should therefore be considered a standard service in healthcare policies aimed at this group. The proposed intervention constitutes a nursing tool which has great potential to improve the quality of life in Parkinson's disease and in other long-term conditions. © 2017 John Wiley & Sons Ltd.

  6. Linkage studies in Spanish autosomal dominant polycystic kidney disease-type 2 (ADPKD-2) families

    Energy Technology Data Exchange (ETDEWEB)

    San Millan, J.L.; Viribay, M.; Perral, B. [Hospital Ramon y Cajal, Madrid (Spain)] [and others

    1994-09-01

    ADPKD results from mutations in at least two genetically distinct loci. Most of the cases (ADPKD-1) are due to mutations in the locus PKD1, on the short arm of chromosome 16. ADPKD-2 accounts for 15% of ADPKD in Spanish population. Previous linkage studies have localized the gene for ADPKD-2 (PKD2) in the chromosome region 4q13-q23, and the distance between the flanking markers, D4S231 and D4S423/D4S414, was 7 cM. We have analyzed seven unrelated families with ADPKD not linked to PKD1 by using eight microsatellite markers that map within the candidate region. All the families did show linkage to any of the markers for which they were informative. Pairwise linkage analysis revealed that loci D4S414 and D4S423 are tightly linked to the disease with lod scores of 3.12 and 6.50, respectively, at a recombination fraction of 0.00. Multilocus linkage analysis indicates that the most likely location for PKD2 is distal to D4S1542, with odds of 1000:1 over the location proximal to D4S1542. Two recombination events involving PKD2 chromosomes have been identified in our seven families. These results provide a proximal boundary for the PKD2 locus and, considering previous studies, its localization is further refined to a 3 cM interval flanked by markers D4S1542 and D4S414/D4S423.

  7. Bacteriome and Mycobiome Interactions Underscore Microbial Dysbiosis in Familial Crohn’s Disease

    Directory of Open Access Journals (Sweden)

    G. Hoarau

    2016-09-01

    Full Text Available Crohn’s disease (CD results from a complex interplay between host genetic factors and endogenous microbial communities. In the current study, we used Ion Torrent sequencing to characterize the gut bacterial microbiota (bacteriome and fungal community (mycobiome in patients with CD and their nondiseased first-degree relatives (NCDR in 9 familial clusters living in northern France-Belgium and in healthy individuals from 4 families living in the same area (non-CD unrelated [NCDU]. Principal component, diversity, and abundance analyses were conducted, and CD-associated inter- and intrakingdom microbial correlations were determined. Significant microbial interactions were identified and validated using single- and mixed-species biofilms. CD and NCDR groups clustered together in the mycobiome but not in the bacteriome. Microbiotas of familial (CD and NCDR samples were distinct from those of nonfamilial (NCDU samples. The abundance of Serratia marcescens and Escherichia coli was elevated in CD patients, while that of beneficial bacteria was decreased. The abundance of the fungus Candida tropicalis was significantly higher in CD than in NCDR (P = 0.003 samples and positively correlated with levels of anti-Saccharomyces cerevisiae antibodies (ASCA. The abundance of C. tropicalis was positively correlated with S. marcescens and E. coli, suggesting that these organisms interact in the gut. The mass and thickness of triple-species (C. tropicalis plus S. marcescens plus E. coli biofilm were significantly greater than those of single- and double-species biofilms. C. tropicalis biofilms comprised blastospores, while double- and triple-species biofilms were enriched in hyphae. S. marcescens used fimbriae to coaggregate or attach with C. tropicalis/E. coli, while E. coli was closely apposed with C. tropicalis. Specific interkingdom microbial interactions may be key determinants in CD.

  8. Genetic Analyses of a Three Generation Family Segregating Hirschsprung Disease and Iris Heterochromia.

    Directory of Open Access Journals (Sweden)

    Long Cui

    Full Text Available We present the genetic analyses conducted on a three-generation family (14 individuals with three members affected with isolated-Hirschsprung disease (HSCR and one with HSCR and heterochromia iridum (syndromic-HSCR, a phenotype reminiscent of Waardenburg-Shah syndrome (WS4. WS4 is characterized by pigmentary abnormalities of the skin, eyes and/or hair, sensorineural deafness and HSCR. None of the members had sensorineural deafness. The family was screened for copy number variations (CNVs using Illumina-HumanOmni2.5-Beadchip and for coding sequence mutations in WS4 genes (EDN3, EDNRB, or SOX10 and in the main HSCR gene (RET. Confocal microscopy and immunoblotting were used to assess the functional impact of the mutations. A heterozygous A/G transition in EDNRB was identified in 4 affected and 3 unaffected individuals. While in EDNRB isoforms 1 and 2 (cellular receptor the transition results in the abolishment of translation initiation (M1V, in isoform 3 (only in the cytosol the replacement occurs at Met91 (M91V and is predicted benign. Another heterozygous transition (c.-248G/A; -predicted to affect translation efficiency- in the 5'-untranslated region of EDN3 (EDNRB ligand was detected in all affected individuals but not in healthy carriers of the EDNRB mutation. Also, a de novo CNVs encompassing DACH1 was identified in the patient with heterochromia iridum and HSCR Since the EDNRB and EDN3 variants only coexist in affected individuals, HSCR could be due to the joint effect of mutations in genes of the same pathway. Iris heterochromia could be due to an independent genetic event and would account for the additional phenotype within the family.

  9. SLC31 (CTR) Family of Copper Transporters in Health and Disease

    Science.gov (United States)

    Kim, Heejeong; Wu, Xiaobin; Lee, Jaekwon

    2012-01-01

    Copper is a vital mineral for many organisms, yet it is highly toxic as demonstrated by serious health concerns associated with its deficiency or excess accumulation. The SLC31 (CTR) family of copper transporters is a major gateway of copper acquisition in eukaryotes, ranging from yeast to humans. Characterization of the function, modes of action, and regulation of CTR and other molecular factors that functionally cooperate with CTR for copper transport, compartmentalization, incorporation into cuproproteins, and detoxification has revealed that organisms have evolved fascinating mechanisms for tight control of copper metabolism. This research progress further indicates the significance of copper in health and disease and opens avenues for therapeutic control of copper bioavailability and its metabolic pathways. PMID:23506889

  10. Hereditary Sensory Autonomic Neuropathy II, a rare disease in a large Pakistani family.

    Science.gov (United States)

    Arain, Fazal Manzoor; Chand, Prem

    2015-10-01

    Hereditary Sensory Autonomic Neuropathy II (HSAN II) is a rare genetic disorder, characterized by severe loss of pain, temperature and touch sensation. Injuries in these patients can progress to necrosis and shedding of digits and limbs. Here we report two cases of HSAN II belonging to a Pakistani family. Individual 1, a forty five year old man, had complete loss of pain sensation since birth. Self-mutilation and complication of injuries resulted in the shedding of all the digits and right foot and surgical amputation of left leg. Individual 2, a five year old girl,had delay in healing of wounds and self-mutilation. Examination showed a complete lack of pain sensation throughout her body and hyporeflexia. As the genetic cause of HSAN II is unknown, identification of more patients will allow further research on this disease and possibly develop a cure.

  11. Association of coronary heart disease with age-adjusted aortocoronary calcification in patients with familial hypercholesterolaemia

    DEFF Research Database (Denmark)

    Jensen, J M; Gerdes, Lars Ulrik; Jensen, H K

    2000-01-01

    OBJECTIVES: Existing algorithms of risk of coronary heart disease (CHD) do not pertain to patients with familial hypercholesterolaemia (FH), whose arteries have been exposed to hypercholesterolaemia since birth. We studied a cohort of FH patients to compare four diagnostic models of CHD......: traditional risk factors of CHD (age, sex, cholesterol, hypertension, smoking and body mass index), cholesterol year score, and aortic as well as coronary calcium measured by spiral computed tomography (CT). SUBJECTS: We invited 88 individuals with molecularly defined FH of whom 80 (91%) decided...... to participate. RESULTS: Analysis of receiver operating characteristic curves showed that the age-adjusted coronary calcium score was more strongly associated with clinical manifestations of CHD than were traditional risk factors (P

  12. Solute carrier family 2 member 1 is involved in the development of nonalcoholic fatty liver disease

    DEFF Research Database (Denmark)

    Vazquez-Chantada, Mercedes; Gonzalez-Lahera, Aintzane; Martinez-Arranz, Ibon

    2013-01-01

    Susceptibility to develop nonalcoholic fatty liver disease (NAFLD) has genetic bases, but the associated variants are uncertain. The aim of the present study was to identify genetic variants that could help to prognose and further understand the genetics and development of NAFLD. Allele frequencies......)-enriched medium on lipid accumulation in siSLC2A1-THLE2 cells were studied by gene-expression analysis, dihydroethidium staining, BODIPY, and quantification of intracellular triglyceride content, respectively. Several SNPs of SLC2A1 (solute carrier family 2 [facilitated glucose transporter] member 1) showed...... association with NAFLD, but not with T2DM, being the haplotype containing the minor allele of SLC2A1 sequence related to the susceptibility to develop NAFLD. Gene-expression analysis demonstrated a significant down-regulation of SLC2A1 in NAFLD livers. Enrichment functional analyses of transcriptome profiles...

  13. Family Health Strategy professionals' view on the effects of Hansen's disease training

    Directory of Open Access Journals (Sweden)

    Ana Lúcia Alves de Souza

    2015-08-01

    Full Text Available OBJECTIVEEvaluating how professionals of family health teams from three municipalities of Pernambuco perceive and interpret the effects of Hansen's disease training.METHODSA qualitative study using the perspective of Habermas. Six focus groups, totaling 33 nurses and 22 doctors were formed. The guide consisted of: reactions to training, learning, transfer of knowledge and organizational results.RESULTSThere were recurrent positive opinions on instructor performance, course materials, and an alert attitude to the occurrence of cases; the negative points were about lack of practical teaching, a lot of information in a short period of time and little emphasis on basic content. Low perceived self-efficacy and low locus of control, ambiguity, conflict of skills and the lack of support for the learning application. Nurses showed greater dissatisfaction with the organizational support.CONCLUSIONThe low effectiveness of training reveals the need to negotiate structured training from work problematization, considering performance conditions.

  14. Family history of systemic lupus erythematosus and risk of autoimmune disease

    DEFF Research Database (Denmark)

    Ulff-Møller, Constance Jensina; Simonsen, Jacob; Kyvik, Kirsten Ohm

    2017-01-01

    Objective.: To provide population-based estimates of relative risk of SLE and other autoimmune diseases (ADs) in relatives of SLE patients. Methods.: A cohort of 5 237 319 Danish residents identified through the Civil Registration System was coupled to their relatives through the parental link...... diabetes mellitus (HR = 1.23; 95% CI: 1.01, 1.48; n = 106). Risk of other ADs was significantly increased both among SLE-affected first-degree (HR = 2.08; 95% CI: 1.88, 2.31; n = 371) and second- or third-degree relatives (HR = 1.38; 95% CI: 1.23, 1.54; n = 313). Conclusion.: Family history of SLE...

  15. Prevalence of chronic renal disease in adults attended by the family health strategy.

    Science.gov (United States)

    Pereira, Edna Regina Silva; Pereira, Aline de Castro; Andrade, Guilherme Borges de; Naghettini, Alessandra Vitorino; Pinto, Fernanda Karolline Melchior Silva; Batista, Sandro Rodrigues; Marques, Solomar Martins

    2016-03-01

    Chronic Kidney Disease (CKD) is an important Brazilian public health issue that has as main etiologies, arterial hypertension and diabetes mellitus (DM). The precocious diagnosis is important, because it allows the implementation of preventive measures that retard or interrupt the progression to the most advanced stages of the CKD. Identify the prevalence and the associated factors to the CKD among adults served by the Family Health Strategy (FHS). Cross-sectional study with epidemiological, descriptive and observational design, realized with 511 adults older than 20 years, served by the FSH in a region of Goiania. CKD was defined as GFR old, masculine gender, DM and alcohol consume. Therefore, a CKD screening and monitoring is suggested in adults who are served by the FHS.

  16. [Family Health Strategy professionals' view on the effects of Hansen's disease training].

    Science.gov (United States)

    Souza, Ana Lúcia Alves de; Feliciano, Katia Virginia de Oliveira; Mendes, Marina Ferreira de Medeiros

    2015-08-01

    Evaluating how professionals of family health teams from three municipalities of Pernambuco perceive and interpret the effects of Hansen's disease training. A qualitative study using the perspective of Habermas. Six focus groups, totaling 33 nurses and 22 doctors were formed. The guide consisted of: reactions to training, learning, transfer of knowledge and organizational results. There were recurrent positive opinions on instructor performance, course materials, and an alert attitude to the occurrence of cases; the negative points were about lack of practical teaching, a lot of information in a short period of time and little emphasis on basic content. Low perceived self-efficacy and low locus of control, ambiguity, conflict of skills and the lack of support for the learning application. Nurses showed greater dissatisfaction with the organizational support. The low effectiveness of training reveals the need to negotiate structured training from work problematization, considering performance conditions.

  17. Family, Community, and Health System Considerations for Reducing the Burden of Pediatric Sickle Cell Disease in Uganda Through Newborn Screening

    Directory of Open Access Journals (Sweden)

    Nancy S. Green MD

    2016-04-01

    Full Text Available Sickle cell disease (SCD is associated with high mortality for children under 5 years of age in sub-Saharan Africa. Newborn sickle screening program and enhanced capacity for SCD treatment are under development to reduce disease burden in Uganda and elsewhere in the region. Based on an international stakeholder meeting and a family-directed conference on SCD in Kampala in 2015, and interviews with parents, multinational experts, and other key informants, we describe health care, community, and family perspectives in support of these initiatives. Key stakeholder meetings, discussions, and interviews were held to understand perspectives of public health and multinational leadership, patients and families, as well as national progress, resource needs, medical and social barriers to program success, and resources leveraged from HIV/AIDS. Partnering with program leadership, professionals, patients and families, multinational stakeholders, and leveraging resources from existing programs are needed for building successful programs in Uganda and elsewhere in sub-Saharan Africa.

  18. The economic cost of Alzheimer's disease: Family or public health burden?

    Science.gov (United States)

    Castro, Diego M.; Dillon, Carol; Machnicki, Gerardo; Allegri, Ricardo F.

    2010-01-01

    Alzheimer’s disease (AD) patients suffer progressive cognitive, behavioral and functional impairment which result in a heavy burden to patients, families, and the public-health system. AD entails both direct and indirect costs. Indirect costs (such as loss or reduction of income by the patient or family members) are the most important costs in early and community-dwelling AD patients. Direct costs (such as medical treatment or social services) increase when the disorder progresses, and the patient is institutionalized or a formal caregiver is required. Drug therapies represent an increase in direct cost but can reduce some other direct or indirect costs involved. Several studies have projected overall savings to society when using drug therapies and all relevant cost are considered, where results depend on specific patient and care setting characteristics. Dementia should be the focus of analysis when public health policies are being devised. South American countries should strengthen their policy and planning capabilities by gathering more local evidence about the burden of AD and how it can be shaped by treatment options. PMID:29213697

  19. The economic cost of Alzheimer's disease: Family or public-health burden?

    Directory of Open Access Journals (Sweden)

    Diego M. Castro

    Full Text Available Abstract Alzheimer's disease (AD patients suffer progressive cognitive, behavioral and functional impairment which result in a heavy burden to patients, families, and the public-health system. AD entails both direct and indirect costs. Indirect costs (such as loss or reduction of income by the patient or family members are the most important costs in early and community-dwelling AD patients. Direct costs (such as medical treatment or social services increase when the disorder progresses, and the patient is institutionalized or a formal caregiver is required. Drug therapies represent an increase in direct cost but can reduce some other direct or indirect costs involved. Several studies have projected overall savings to society when using drug therapies and all relevant cost are considered, where results depend on specific patient and care setting characteristics. Dementia should be the focus of analysis when public health policies are being devised. South American countries should strengthen their policy and planning capabilities by gathering more local evidence about the burden of AD and how it can be shaped by treatment options.

  20. Modulators of inhibitor of growth (ING) family expression in development and disease.

    Science.gov (United States)

    Maher, Stacey K; Helbing, Caren C

    2009-05-01

    The inhibitor of growth (ING) gene family proteins regulate many critical cellular processes such as cell proliferation and growth, apoptosis, DNA repair, senescence, angiogenesis, and drug resistance. Their transcripts and proteins are differentially expressed in health and disease and there is evidence for developmental regulation. The vast majority of studies have characterized ING levels in the context of cancer. However, relatively little attention has been paid to the expression of ING family members in other contexts. This review summarizes the findings from human and animal model systems that provide insight into the factors influencing the expression of these important proteins. We examine the influence of cell cycle and aging as well as genotoxic stress on ING expression levels and evaluate several emerging areas of inquiry demonstrating that ING gene activity may be modulated by factors such as the p53 tumor suppressor, DNA methylation, and ING proteins themselves with external factors such as hormones, reactive oxygen species, TGFbeta signalling, and other proteins of pathological significance also influencing ING levels. We then briefly discuss the influence of post-translational modification and changes in subcellular localization as it pertains to modulation of ING expression. Understanding how ING expression is modulated represents a vital aspect of effective drug targeting strategies.

  1. Family-centered brief intervention for reducing obesity and cardiovascular disease risk: A randomized controlled trial.

    Science.gov (United States)

    Duncan, Scott; Goodyear-Smith, Felicity; McPhee, Julia; Zinn, Caryn; Grøntved, Anders; Schofield, Grant

    2016-11-01

    To assess the effects of a family-centered, physical activity and nutrition "brief" intervention (time-limited contact) on body weight and related health outcomes in primary health care patients with an elevated 5-year cardiovascular disease (CVD) risk. This study implemented a cluster randomized controlled trial design with two treatment conditions: a CVD risk assessment and one-time consultation ("usual care" control) and a CVD risk assessment and up to five home sessions that aimed to reduce obesity by encouraging physical activity and healthy eating (intervention). Three hundred and twenty patients aged 35 to 65 years from 16 primary health care clinics in Auckland, New Zealand, participated in the study. Intervention effects on BMI, waist circumference, blood pressure, blood cholesterol, triglycerides, 5-year CVD risk, physical activity, and dietary patterns were assessed using generalized linear mixed models. When compared with the control group, the intervention resulted in a significant but relatively modest decrease in BMI between baseline and the 12-month follow-up (-0.633 kg m(-2) , Padj  = 0.048). Significant decreases were also observed for total cholesterol at 4 and 12 months, the total cholesterol to high-density lipoprotein cholesterol ratio at 4 months, 5-year CVD risk at 4 months, and fast food consumption at 12 months. Our findings show that a family-centered brief intervention targeting physical activity and nutrition can generate slightly better obesity-related health outcomes than usual care alone. © 2016 The Obesity Society.

  2. Effect of parental family history of Alzheimer's disease on serial position profiles.

    Science.gov (United States)

    La Rue, Asenath; Hermann, Bruce; Jones, Jana E; Johnson, Sterling; Asthana, Sanjay; Sager, Mark A

    2008-07-01

    An exaggerated recency effect (ie, disproportionate recall of last-presented items) has been consistently observed in the word list learning of patients with Alzheimer's disease (AD). Our study sought to determine whether there were similar alterations in serial position learning among asymptomatic persons at risk for AD as a result of parental family history. Subjects included 623 asymptomatic middle-aged children of patients with AD (median, 53 years) and 157 control participants whose parents survived to at least age 70 without AD or other memory disorders. All participants were administered the Rey Auditory Verbal Learning Test, which requires learning and recall of 15 unrelated nouns. There was no significant difference in total words recalled between the AD children and control groups. However, compared with controls, AD children exhibited a significantly greater tendency to recall words from the end (recency) versus beginning (primacy) of the list. Serial position effects were unrelated to apolipoprotein allele epsilon 4 or depressive symptoms. Asymptomatic persons at risk for AD by virtue of family history do not show a difference in total words recalled compared with controls, but they exhibit a distinctly different serial position curve, suggesting greater reliance on immediate as opposed to episodic memory. This is the same serial position pattern observed in mild AD, seen here in reduced severity. Longitudinal follow-up is planned to determine whether changes in serial position patterns are a meaningful marker for preclinical detection of AD.

  3. Genetic testing in familial and young-onset Alzheimer's disease: mutation spectrum in a Serbian cohort.

    Science.gov (United States)

    Dobricic, Valerija; Stefanova, Elka; Jankovic, Milena; Gurunlian, Nicole; Novakovic, Ivana; Hardy, John; Kostic, Vladimir; Guerreiro, Rita

    2012-07-01

    Alzheimer's disease (AD) is the most common form of dementia. To date, more than 200 mutations in three genes have been identified as cause of early-onset autosomal dominant inherited AD. The aim of this study was to characterize the mutation spectrum and describe genotype-phenotype correlations in Serbian patients with positive family history of AD or/and early-onset AD. We performed a genetic screening for mutations in the coding regions of Presenilins 1 and 2 (PSEN1 and PSEN2), as well as exons 16 and 17 of the Amyloid Precursor Protein gene (APP) in a total of 47 patients from Serbia with a clinical diagnosis of familial and/or early-onset AD (mean age at onset of 60.3 years; range 32-77). We found one novel mutation in PSEN1, one novel variant in PSEN2, and three previously described variants, one in each of the analyzed genes. Interestingly, we identified one patient harboring two heterozygous mutations: one in APP (p.L723P) and one in PSEN1 (p.R108Q). Copyright © 2012 Elsevier Inc. All rights reserved.

  4. Characterization and molecular profiling of PSEN1 familial Alzheimer's disease iPSC-derived neural progenitors.

    Directory of Open Access Journals (Sweden)

    Andrew A Sproul

    Full Text Available Presenilin 1 (PSEN1 encodes the catalytic subunit of γ-secretase, and PSEN1 mutations are the most common cause of early onset familial Alzheimer's disease (FAD. In order to elucidate pathways downstream of PSEN1, we characterized neural progenitor cells (NPCs derived from FAD mutant PSEN1 subjects. Thus, we generated induced pluripotent stem cells (iPSCs from affected and unaffected individuals from two families carrying PSEN1 mutations. PSEN1 mutant fibroblasts, and NPCs produced greater ratios of Aβ42 to Aβ40 relative to their control counterparts, with the elevated ratio even more apparent in PSEN1 NPCs than in fibroblasts. Molecular profiling identified 14 genes differentially-regulated in PSEN1 NPCs relative to control NPCs. Five of these targets showed differential expression in late onset AD/Intermediate AD pathology brains. Therefore, in our PSEN1 iPSC model, we have reconstituted an essential feature in the molecular pathogenesis of FAD, increased generation of Aβ42/40, and have characterized novel expression changes.

  5. Lack of MEF2A Delta7aa mutation in Irish families with early onset ischaemic heart disease, a family based study.

    LENUS (Irish Health Repository)

    Horan, Paul G

    2006-01-01

    BACKGROUND: Ischaemic heart disease (IHD) is a complex disease due to the combination of environmental and genetic factors. Mutations in the MEF2A gene have recently been reported in patients with IHD. In particular, a 21 base pair deletion (Delta7aa) in the MEF2A gene was identified in a family with an autosomal dominant pattern of inheritance of IHD. We investigated this region of the MEF2A gene using an Irish family-based study, where affected individuals had early-onset IHD. METHODS: A total of 1494 individuals from 580 families were included (800 discordant sib-pairs and 64 parent-child trios). The Delta7aa region of the MEF2A gene was investigated based on amplicon size. RESULTS: The Delta7aa mutation was not detected in any individual. Variation in the number of CAG (glutamate) and CCG (proline) residues was detected in a nearby region. However, this was not found to be associated with IHD. CONCLUSION: The Delta7aa mutation was not detected in any individual within the study population and is unlikely to play a significant role in the development of IHD in Ireland. Using family-based tests of association the number of tri-nucleotide repeats in a nearby region of the MEF2A gene was not associated with IHD in our study group.

  6. The mediating effects of family functioning on psychosocial outcomes in healthy siblings of children with sickle cell disease.

    Science.gov (United States)

    Gold, Jeffrey I; Treadwell, Marsha; Weissman, Lina; Vichinsky, Elliott

    2011-12-01

    Children with siblings coping with chronic illness experience stresses and disruptions in daily life as families work together to care for the affected child. Research suggests that children and adolescents with sickle cell disease (SCD) may be at risk for adjustment problems, impaired psychosocial functioning, and reduced quality of life. These potential stressors affect the child with SCD as well as their caregivers and other family members. This study examined the role of family functioning on the psychosocial functioning of healthy siblings of children with SCD. Participants were 65 healthy African-American siblings of children with SCD with a mean age of 11.19 years (range: 7-16) and their primary caregiver. Caregivers completed questionnaires assessing family functioning and child adjustment including demographic surveys, the Family Relations Scale (FRS), and the Child Behavior Checklist (CBCL). Increased number of emergency room visits (β = -0.28, P Family functioning mediated this effect (β = 0.27; P family expressiveness (total score, r = -0.34; P family conflict (total score, r = 0.41; P children with SCD. Awareness of the possible negative psychosocial outcomes of living with a sister or a brother with SCD is important for clinicians. In particular, interventions that focus on family expressiveness, support, and conflict are indicated for this population. Copyright © 2011 Wiley-Liss, Inc.

  7. Serum neurofilament light in familial Alzheimer disease: A marker of early neurodegeneration.

    Science.gov (United States)

    Weston, Philip S J; Poole, Teresa; Ryan, Natalie S; Nair, Akshay; Liang, Yuying; Macpherson, Kirsty; Druyeh, Ronald; Malone, Ian B; Ahsan, R Laila; Pemberton, Hugh; Klimova, Jana; Mead, Simon; Blennow, Kaj; Rossor, Martin N; Schott, Jonathan M; Zetterberg, Henrik; Fox, Nick C

    2017-11-21

    To investigate whether serum neurofilament light (NfL) concentration is increased in familial Alzheimer disease (FAD), both pre and post symptom onset, and whether it is associated with markers of disease stage and severity. We recruited 48 individuals from families with PSEN1 or APP mutations to a cross-sectional study: 18 had symptomatic Alzheimer disease (AD) and 30 were asymptomatic but at 50% risk of carrying a mutation. Serum NfL was measured using an ultrasensitive immunoassay on the single molecule array (Simoa) platform. Cognitive testing and MRI were performed; 33 participants had serial MRI, allowing calculation of atrophy rates. Genetic testing established mutation status. A generalized least squares regression model was used to compare serum NfL among symptomatic mutation carriers, presymptomatic carriers, and noncarriers, adjusting for age and sex. Spearman coefficients assessed associations between serum NfL and (1) estimated years to/from symptom onset (EYO), (2) cognitive measures, and (3) MRI measures of atrophy. Nineteen of the asymptomatic participants were mutation carriers (mean EYO -9.6); 11 were noncarriers. Compared with noncarriers, serum NfL concentration was higher in both symptomatic ( p < 0.0001) and presymptomatic mutation carriers ( p = 0.007). Across all mutation carriers, serum NfL correlated with EYO (ρ = 0.81, p < 0.0001) and multiple cognitive and imaging measures, including Mini-Mental State Examination (ρ = -0.62, p = 0.0001), Clinical Dementia Rating Scale sum of boxes (ρ = 0.79, p < 0.0001), baseline brain volume (ρ = -0.62, p = 0.0002), and whole-brain atrophy rate (ρ = 0.53, p = 0.01). Serum NfL concentration is increased in FAD prior to symptom onset and correlates with measures of disease stage and severity. Serum NfL may thus be a feasible biomarker of early AD-related neurodegeneration. Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

  8. T-box family of transcription factor-TBX5, insights in development and disease.

    Science.gov (United States)

    Zhu, Ting; Qiao, Longwei; Wang, Qian; Mi, Rui; Chen, Jinnan; Lu, Yaojuan; Gu, Junxia; Zheng, Qiping

    2017-01-01

    The T-box gene family refers to a group of transcription factors that share a highly conserved, sequence-specific DNA-binding domain (T-box) containing around 180-amino acids. According to HUGO gene nomenclature committee (HGNC), there are 18 T-box family members. These T-box genes have been implicated essential roles during embryogenesis and cardiac development, given their specific expression pattern in developing mammalian heart for several T-box genes, including TBX5. TBX5 is consisted of three transcriptional variants which cover 9 exons and encode two distinct isoforms that differ in N-terminus. TBX5 is probably the most frequently studied T-box gene over the past decade due to the typical cardiac defects observed in Holt-Oram syndrome (HOS), which is caused by TBX5 mutation. Most of the mutations are within exons 3-7 where locate sequence coding for the T-box domain. Notably, a variety of cardiac defects, as well as abnormalities in limb and other organs have been seen in HOS syndrome with different kinds of TBX5 mutations, suggesting a heterogeneous disease mechanism. We have performed a meta-analysis of TBX5 and found a significant correlation between its single nucleotide polymorphism (SNP) rs3825214 (A to G), and risk of atrial fibrillation and its subtypes, supporting TBX5 as a master transcription factor for cardiac development. In addition, bioinformatics analysis of this SNP identified several TFs that may be affected for their binding affinity with TBX5. Identification and characterization of more TBX5 mutations and SNPs hold promise for therapeutic strategy targeting TBX5 associated developmental abnormalities and diseases.

  9. Evaluation of the Families SHARE workbook: an educational tool outlining disease risk and healthy guidelines to reduce risk of heart disease, diabetes, breast cancer and colorectal cancer.

    Science.gov (United States)

    Koehly, Laura M; Morris, Bronwyn A; Skapinsky, Kaley; Goergen, Andrea; Ludden, Amanda

    2015-11-13

    Common diseases such as heart disease, diabetes, and cancer are etiologically complex with multiple risk factors (e.g., environment, genetic, lifestyle). These risk factors tend to cluster in families, making families an important social context for intervention and lifestyle-focused disease prevention. The Families Sharing Health Assessment and Risk Evaluation (SHARE) workbook was designed as an educational tool outlining family health history based risk of heart disease, type 2 diabetes, breast cancer, and colorectal cancer. The current paper describes the steps taken to develop and evaluate the workbook employing a user-centered design approach. The workbook was developed in four steps, culminating in an evaluation focusing on understanding and usability of the tool. The evaluation was based on two Phases of data collected from a sample of mothers of young children in the Washington, D.C., area. A baseline assessment and follow-up approximately two weeks after receipt of the workbook were conducted, as well as focus groups with participants. The design of the workbook was refined in response to participant feedback from the first evaluation Phase and subsequently re-evaluated with a new sample. After incorporating user-based feedback and revising the workbook, Phase 2 evaluation results indicated that understanding of the workbook components improved for all sections (from 6.26 to 6.81 on a 7-point scale). In addition, 100% of users were able to use the algorithm to assess their disease risk and over 60% used the algorithm to assess family members' disease risk. At follow-up, confidence to increase fruit, vegetable and fiber intake improved significantly, as well. The Families SHARE workbook was developed and evaluated resulting in a family health history tool that is both understandable and usable by key stakeholders. This educational tool will be used in intervention studies assessing the effectiveness of family genomics health educators who use the Families

  10. Aortic Disease in the Young: Genetic Aneurysm Syndromes, Connective Tissue Disorders, and Familial Aortic Aneurysms and Dissections

    Directory of Open Access Journals (Sweden)

    Marcelo Cury

    2013-01-01

    Full Text Available There are many genetic syndromes associated with the aortic aneurysmal disease which include Marfan syndrome (MFS, Ehlers-Danlos syndrome (EDS, Loeys-Dietz syndrome (LDS, familial thoracic aortic aneurysms and dissections (TAAD, bicuspid aortic valve disease (BAV, and autosomal dominant polycystic kidney disease (ADPKD. In the absence of familial history and other clinical findings, the proportion of thoracic and abdominal aortic aneurysms and dissections resulting from a genetic predisposition is still unknown. In this study, we propose the review of the current genetic knowledge in the aortic disease, observing, in the results that the causative genes and molecular pathways involved in the pathophysiology of aortic aneurysm disease remain undiscovered and continue to be an area of intensive research.

  11. Age-Specific Incidence Rates for Dementia and Alzheimer Disease in NIA-LOAD/NCRAD and EFIGA Families

    Science.gov (United States)

    Vardarajan, Badri N.; Faber, Kelley M.; Bird, Thomas D.; Bennett, David A.; Rosenberg, Roger; Boeve, Bradley F.; Graff-Radford, Neill R.; Goate, Alison M.; Farlow, Martin; Sweet, Robert A.; Lantigua, Rafael; Medrano, Martin Z.; Ottman, Ruth; Schaid, Daniel J.; Foroud, Tatiana M.; Mayeux, Richard

    2014-01-01

    IMPORTANCE Late-onset Alzheimer disease (LOAD), defined as onset of symptoms after age 65 years, is the most common form of dementia. Few reports investigate incidence rates in large family-based studies in which the participants were selected for family history of LOAD. OBJECTIVE To determine the incidence rates of dementia and LOAD in unaffected members in the National Institute on Aging Genetics Initiative for Late-Onset Alzheimer Disease/National Cell Repository for Alzheimer Disease (NIA-LOAD/NCRAD) and Estudio Familiar de Influencia Genetica en Alzheimer (EFIGA) family studies. DESIGN, SETTING, AND PARTICIPANTS Families with 2 or more affected siblings who had a clinical or pathological diagnosis of LOAD were recruited as a part of the NIA-LOAD/NCRAD Family Study. A cohort of Caribbean Hispanics with familial LOAD was recruited in a different study at the Taub Institute for Research on Alzheimer’s Disease and the Aging Brain in New York and from clinics in the Dominican Republic as part of the EFIGA study. MAIN OUTCOMES AND MEASURES Age-specific incidence rates of LOAD were estimated in the unaffected family members in the NIA-LOAD/NCRAD and EFIGA data sets. We restricted analyses to families with follow-up and complete phenotype information, including 396 NIA-LOAD/NCRAD and 242 EFIGA families. Among the 943 at-risk family members in the NIA-LOAD/NCRAD families, 126 (13.4%) developed dementia, of whom 109 (86.5%) met criteria for LOAD. Among 683 at-risk family members in the EFIGA families, 174 (25.5%) developed dementia during the study period, of whom 145 (83.3%) had LOAD. RESULTS The annual incidence rates of dementia and LOAD in the NIA-LOAD/NCRAD families per person-year were 0.03 and 0.03, respectively, in participants aged 65 to 74 years; 0.07 and 0.06, respectively, in those aged 75 to 84 years; and 0.08 and 0.07, respectively, in those 85 years or older. Incidence rates in the EFIGA families were slightly higher, at 0.03 and 0.02, 0.06 and 0.05, 0

  12. Human prion disease with a G114V mutation and epidemiological studies in a Chinese family: a case series

    Directory of Open Access Journals (Sweden)

    Ye Jing

    2008-10-01

    Full Text Available Abstract Introduction Transmissible spongiform encephalopathies are a group of neurodegenerative diseases of humans and animals. Genetic Creutzfeldt-Jakob diseases, in which mutations in the PRNP gene predispose to disease by causing the expression of abnormal PrP protein, include familial Creutzfeldt-Jakob disease, Gerstmann-Straussler-Scheinker syndrome and fatal familial insomnia. Case presentation A 47-year-old Han-Chinese woman was hospitalized with a 2-year history of progressive dementia, tiredness, lethargy and mild difficulty in falling asleep. On neurological examination, there was severe apathy, spontaneous myoclonus of the lower limbs, generalized hyperreflexia and bilateral Babinski signs. A missense mutation (T to G was identified at the position of nt 341 in one PRNP allele, leading to a change from glycine (Gly to valine (Val at codon 114. PK-resistant PrPSc was detected in brain tissues by Western blotting and immunohistochemical assays. Information on pedigree was collected notably by interviews with family members. A further four suspected patients in five consecutive generations of the family have been identified. One of them was hospitalized for progressive memory impairment at the age of 32. On examination, he had impairment of memory, calculation and comprehension, mild ataxia of the limbs, tremor and a left Babinski sign. He is still alive. Conclusion This family with G114V inherited prion disease is the first to be described in China and represents the second family worldwide in which this mutation has been identified. Three other suspected cases have been retrospectively identified in this family, and a further case with suggestive clinical manifestations has been shown by gene sequencing to have the causal mutation.

  13. Novel ATPase Cu(2+ transporting beta polypeptide mutations in Chinese families with Wilson's disease.

    Directory of Open Access Journals (Sweden)

    Shaojuan Gu

    Full Text Available Wilson's disease (WD is an autosomal recessive inherited disorder caused by mutations in the ATPase Cu(2+ transporting beta polypeptide gene (ATP7B. The detailed metabolism of copper-induced pathology in WD is still unknown. Gene mutations as well as the possible pathways involved in the ATP7B deficiency were documented. The ATP7B gene was analyzed for mutations in 18 Chinese Han families with WD by direct sequencing. Cell viability and apoptosis analysis of ATP7B small interfering RNA (siRNA-treated human liver carcinoma (HepG2 cells were measured by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT assay and Hoechst 33342 staining. Finally, the expression of B-cell CLL/lymphoma 2 (BCL2, BCL2-associated X protein (BAX, sterol regulatory element binding protein 1 (SREBP1, and minichromosome maintenance protein 7 (MCM7 of ATP7B siRNA-treated cells were tested by real-time polymerase chain reaction (real-time PCR and Western blot analysis. Twenty different mutations including four novel mutations (p.Val145Phe, p.Glu388X, p.Thr498Ser and p.Gly837X in the ATP7B gene were identified in our families. Haplotype analysis revealed that founder effects for four mutations (p.Arg778Leu, p.Pro992Leu, p.Ile1148Thr and p.Ala1295Val existed in these families. Transfection of HepG2 cells with ATP7B siRNA resulted in decreased mRNA expression by 86.3%, 93.1% and 90.8%, and decreased protein levels by 58.5%, 85.5% and 82.1% at 24, 48 and 72 hours, respectively (All P<0.01. In vitro study revealed that the apoptotic, cell cycle and lipid metabolism pathway may be involved in the mechanism of WD. Our results revealed that the genetic cause of 18 Chinese families with WD and ATP7B deficiency-induce apoptosis may result from imbalance in cell cycle and lipid metabolism pathway.

  14. Dimerization of the transmembrane domain of amyloid precursor proteins and familial Alzheimer's disease mutants

    Directory of Open Access Journals (Sweden)

    Fraser Paul E

    2008-01-01

    Full Text Available Abstract Background Amyloid precursor protein (APP is enzymatically cleaved by γ-secretase to form two peptide products, either Aβ40 or the more neurotoxic Aβ42. The Aβ42/40 ratio is increased in many cases of familial Alzheimer's disease (FAD. The transmembrane domain (TM of APP contains the known dimerization motif GXXXA. We have investigated the dimerization of both wild type and FAD mutant APP transmembrane domains. Results Using synthetic peptides derived from the APP-TM domain, we show that this segment is capable of forming stable transmembrane dimers. A model of a dimeric APP-TM domain reveals a putative dimerization interface, and interestingly, majority of FAD mutations in APP are localized to this interface region. We find that FAD-APP mutations destabilize the APP-TM dimer and increase the population of APP peptide monomers. Conclusion The dissociation constants are correlated to both the Aβ42/Aβ40 ratio and the mean age of disease onset in AD patients. We also show that these TM-peptides reduce Aβ production and Aβ42/Aβ40 ratios when added to HEK293 cells overexpressing the Swedish FAD mutation and γ-secretase components, potentially revealing a new class of γ-secretase inhibitors.

  15. HLA Class I and II study in a mestizo family with high incidence of autoimmune disease.

    Science.gov (United States)

    de Sorrentino, Alicia Habegger; Young, Marcela; Marinic, Karina; Motta, Patricia Fabiana; Baruzzo, Carlos

    2013-01-01

    There are many factors that influence the pathogenesis of autoimmune disease of which host genetic factors play an important role. The aim of this study was to investigate the HLA Class I and II genes in a family with a high incidence of AID to establish whether they contribute to the development of these disease. Four of them had been diagnosed with SLE and one with AHA. The patients with SLE showed the presence of HLA-A*02 B*40 DRB1*04:07 DQB1*03:02 haplotype with a high statistical significance. This haplotype was not present in the healthy individuals and in the patient with AHA, although the DRB1*04:07 DQB1*03:02 haplotype (carried by both parents) was found in the AHA patients and one of the healthy individuals. We must consider how HLA Class I in linkage disequilibrium with HLA Class II may be involved in susceptibility or in the development of SLE. An extensive study in this population should be conducted to establish the true participation of the HLA Class I region. Copyright © 2012 Elsevier España, S.L. All rights reserved.

  16. PINK1 and its familial Parkinson's disease-associated mutation regulate brain vascular endothelial inflammation.

    Science.gov (United States)

    Yunfu, Wang; Guangjian, Liu; Ping, Zhong; Yanpeng, Sun; Xiaoxia, Fang; Wei, Hu; Jiang, Yuan; Jingquan, Hu; Songlin, Wang; Hongyan, Zhang; Yong, Liu; Shi, Chen

    2014-05-01

    Parkinson's disease (PD) is a debilitating disorder that affects movement. Inflammation-mediated endothelial dysfunction has been found to be involved in neurodegenerative diseases, including PD. More than 40 PTEN-induced putative kinase 1 (PINK1) mutations have been found in PD patients. The effects of PINK1 in vascular inflammation are as yet unknown. In this study, our findings revealed that PINK1 can be increased by the inflammatory cytokine tumor necrosis factor-α in primary human brain microvascular endothelial cells (HBMECs). We found that wild-type PINK1 prevents expression of the adhesion molecule vascular cell adhesion molecule-1 (VCAM-1), thus inhibiting the attachment of monocytes to brain endothelial cells. However, PINK1G309D, the loss-of-function mutation associated with early-onset familial PD, promotes expression of VCAM-1 and exacerbates attachment of monocytes to brain endothelial cells. Mechanism studies revealed that overexpression of wild-type PINK1 inhibits the VCAM-1 promoter by inhibiting the transcriptional activity of interferon regulatory factor 1 (IRF-1). However, PINK1G309D promotes the VCAM-1 promoter by increasing the transcriptional activity of IRF-1.

  17. [The symptoms in family medicine are not symptoms of disease, they are symptoms of life].

    Science.gov (United States)

    Turabián, José Luis; Pérez Franco, Benjamín; Turabián Fernández, José Luis; Pérez Franco, Benjamin

    2012-04-01

    The symptoms in family medicine are not signs of disease, but "signs of life"; in the consultation "all patient life comes together with him". Every consultation is primarily a biopsicosocial problem: the person perceives a dysfunction or alteration in relation with himself and his context. To do a diagnosis only with physical symptoms, can be a mistake because these do not identify the real problem. The different types of symptoms are "entangled" or chained some in others: the symptoms can be fitted or inevitable; to be expressions of biochemical alterations, symbols for the patient, group context expressions, or kinds of facing the facts; and they depend on the previous psychological patient performance, the severity of the deficit of the psychological function associated with the disease, the residual skills, the adjustment and the confrontation of the functional limitations, the relation doctor-patient, as well as on the influence of the context. Copyright © 2011 Elsevier España, S.L. All rights reserved.

  18. Using linkage analysis to detect gene-gene interaction by stratifying family data on known disease, or disease-associated, alleles.

    Directory of Open Access Journals (Sweden)

    Barbara Corso

    Full Text Available Detecting gene-gene interaction in complex diseases is a major challenge for common disease genetics. Most interaction detection approaches use disease-marker associations and such methods have low power and unknown reliability in real data. We developed and tested a powerful linkage-analysis-based gene-gene interaction detection strategy based on conditioning the family data on a known disease-causing allele or disease-associated marker allele. We computer-generated multipoint linkage data for a disease caused by two epistatically interacting loci (A and B. We examined several two-locus epistatic inheritance models: dominant-dominant, dominant-recessive, recessive-dominant, recessive-recessive. At one of the loci (A, there was a known disease-related allele. We stratified the family data on the presence of this allele, eliminating family members who were without it. This elimination step has the effect of raising the "penetrance" at the second locus (B. We then calculated the lod score at the second locus (B and compared the pre- and post-stratification lod scores at B. A positive difference indicated interaction. We also examined if it was possible to detect interaction with locus B based on a disease-marker association (instead of an identified disease allele at locus A. We also tested whether the presence of genetic heterogeneity would generate false positive evidence of interaction. The power to detect interaction for a known disease allele was 60-90%. The probability of false positives, based on heterogeneity, was low. Decreasing linkage disequilibrium between the disease and marker at locus A decreased the likelihood of detecting interaction. The allele frequency of the associated marker made little difference to the power.

  19. Resilience as a concept for understanding family caregiving of adults with Chronic Obstructive Pulmonary Disease (COPD): an integrative review.

    Science.gov (United States)

    Rosa, Francesca; Bagnasco, Annamaria; Aleo, Giuseppe; Kendall, Sally; Sasso, Loredana

    2017-04-01

    This paper was a report of the synthesis of evidence on examining the origins and definitions of the concept of resilience, investigating its application in chronic illness management and exploring its utility as a means of understanding family caregiving of adults with Chronic Obstructive Pulmonary Disease. Resilience is a concept that is becoming relevant to understanding how individuals and families live with illness, especially long-term conditions. Caregivers of adults with Chronic Obstructive Pulmonary Disease must be able to respond to exacerbations of the condition and may themselves experience cognitive imbalances. Yet, resilience as a way of understanding family caregiving of adults with COPD is little explored. Literature review - integrative review. CINAHL, PubMed, Google Scholar and EBSCO were searched between 1989-2015. The principles of rapid evidence assessment were followed. We identified 376 relevant papers: 20 papers reported the presence of the concept of resilience in family caregivers of chronic diseases patients but only 12 papers reported the presence of the concept of resilience in caregivers of Chronic Obstructive Pulmonary Disease patients and have been included in the synthesis. The term resilience in Chronic Obstructive Pulmonary Disease caregiving is most often understood using a deficit model of health.

  20. A Diffusion Model Analysis of Episodic Recognition in Individuals with a Family History for Alzheimer Disease: The Adult Children Study

    Science.gov (United States)

    Aschenbrenner, Andrew J.; Balota, David A.; Gordon, Brian A.; Ratcliff, Roger; Morris, John C.

    2015-01-01

    Objective A family history of Alzheimer disease (AD) increases the risk of developing AD and can influence the accumulation of well-established AD biomarkers. There is some evidence that family history can influence episodic memory performance even in cognitively normal individuals. We attempted to replicate the effect of family history on episodic memory and used a specific computational model of binary decision making (the diffusion model) to understand precisely how family history influences cognition. Finally, we assessed the sensitivity of model parameters to family history controlling for standard neuropsychological test performance. Method Across two experiments, cognitively healthy participants from the Adult Children Study completed an episodic recognition test consisting of high and low frequency words. The diffusion model was applied to decompose accuracy and reaction time into latent parameters which were analyzed as a function of family history. Results In both experiments, individuals with a family history of AD exhibited lower recognition accuracy and this occurred in the absence of an apolipoprotein E (APOE) ε4 allele. The diffusion model revealed this difference was due to changes in the quality of information accumulation (the drift rate) and not differences in response caution or other model parameters. This difference remained after controlling for several standard neuropsychological tests. Conclusions These results confirm that the presence of a family history of AD confers a subtle cognitive deficit in episodic memory as reflected by decreased drift rate that cannot be attributed to APOE. This measure may serve as a novel cognitive marker of preclinical AD. PMID:26192539

  1. Genome-wide linkage analysis of cardiovascular disease biomarkers in a large, multigenerational family.

    Directory of Open Access Journals (Sweden)

    Daniel Nolan

    Full Text Available Given the importance of cardiovascular disease (CVD to public health and the demonstrated heritability of both disease status and its related risk factors, identifying the genetic variation underlying these susceptibilities is a critical step in understanding the pathogenesis of CVD and informing prevention and treatment strategies. Although one can look for genetic variation underlying susceptibility to CVD per se, it can be difficult to define the disease phenotype for such a qualitative analysis and CVD itself represents a convergence of diverse etiologic pathways. Alternatively, one can study the genetics of intermediate traits that are known risk factors for CVD, which can be measured quantitatively. Using the latter strategy, we have measured 21 cardiovascular-related biomarkers in an extended multigenerational pedigree, the CARRIAGE family (Carolinas Region Interaction of Aging, Genes, and Environment. These biomarkers belong to inflammatory and immune, connective tissue, lipid, and hemostasis pathways. Of these, 18 met our quality control standards. Using the pedigree and biomarker data, we have estimated the broad sense heritability (H2 of each biomarker (ranging from 0.09-0.56. A genome-wide panel of 6,015 SNPs was used subsequently to map these biomarkers as quantitative traits. Four showed noteworthy evidence for linkage in multipoint analysis (LOD score ≥ 2.6: paraoxonase (chromosome 8p11, 21, the chemokine RANTES (22q13.33, matrix metalloproteinase 3 (MMP3, 17p13.3, and granulocyte colony stimulating factor (GCSF, 8q22.1. Identifying the causal variation underlying each linkage score will help to unravel the genetic architecture of these quantitative traits and, by extension, the genetic architecture of cardiovascular risk.

  2. Visual short-term memory binding deficit in familial Alzheimer's disease.

    Science.gov (United States)

    Liang, Yuying; Pertzov, Yoni; Nicholas, Jennifer M; Henley, Susie M D; Crutch, Sebastian; Woodward, Felix; Leung, Kelvin; Fox, Nick C; Husain, Masud

    2016-05-01

    Long-term episodic memory deficits in Alzheimer's disease (AD) are well characterised but, until recently, short-term memory (STM) function has attracted far less attention. We employed a recently-developed, delayed reproduction task which requires participants to reproduce precisely the remembered location of items they had seen only seconds previously. This paradigm provides not only a continuous measure of localization error in memory, but also an index of relational binding by determining the frequency with which an object is misplaced to the location of one of the other items held in memory. Such binding errors in STM have previously been found on this task to be sensitive to medial temporal lobe (MTL) damage in focal lesion cases. Twenty individuals with pathological mutations in presenilin 1 or amyloid precursor protein genes for familial Alzheimer's disease (FAD) were tested together with 62 healthy controls. Participants were assessed using the delayed reproduction memory task, a standard neuropsychological battery and structural MRI. Overall, FAD mutation carriers were worse than controls for object identity as well as in gross localization memory performance. Moreover, they showed greater misbinding of object identity and location than healthy controls. Thus they would often mislocalize a correctly-identified item to the location of one of the other items held in memory. Significantly, asymptomatic gene carriers - who performed similarly to healthy controls on standard neuropsychological tests - had a specific impairment in object-location binding, despite intact memory for object identity and location. Consistent with the hypothesis that the hippocampus is critically involved in relational binding regardless of memory duration, decreased hippocampal volume across FAD participants was significantly associated with deficits in object-location binding but not with recall precision for object identity or localization. Object-location binding may therefore

  3. The family's role as a support network for people living with HIV/AIDS: a review of Brazilian research into the theme.

    Science.gov (United States)

    da Silva, Leonara Maria Souza; Tavares, Jeane Saskya Campos

    2015-04-01

    The study of HIV transmission and the implementation of AIDS prevention actions recognize the importance of social networks in the transmission of the disease, the adherence to treatment and the quality of life of those infected. For this relevance there was a review of articles on social support networks to people living with HIV /AIDS available in the Virtual Health Library (VHL) were published in Brazil between 2002 and 2012. In this study 31 articles were used from journals covering the following áreas: Nursing (n = 15), Psychology (n = 6) and Science Health / Biomedica (n = 6), were included, which some principal authors were affiliated to higher education public institutions (n = 17). In relation to the methodology used, priority wasgiven to conducting: qualitative research (n = 18), cross-sectional studies (n = 19) and studies that involved talking to people living with HIV/AIDS (n = 13). Particular importance was placed on analytic categories related to: adherence to treatment (n = 6), the family (n = 4), vulnerability (n = 3) and support from social networks (n = 5). Within this paper we argue for more investments into studies that focus on the family, carers and their households, as well as deepening the theoretical study of the themes discussed and the use of developed theories for the analysis of Social Networks.

  4. No founder effect in three novel Alzheimer's disease families with APP 717 Val-->Ile mutation. Clerget-darpoux. French Alzheimer's Disease Study Group.

    Science.gov (United States)

    Campion, D; Brice, A; Hannequin, D; Charbonnier, F; Dubois, B; Martin, C; Michon, A; Penet, C; Bellis, M; Calenda, A; Martinez, M; Agid, Y; Clerget-Darpoux, F; Frebourg, T

    1996-08-01

    We sequenced exons 16 and 17 of the APP (amyloid precursor protein) gene in 18 unrelated French Alzheimer's disease (AD) patients. These patients had an onset before the age of 60 and belonged to families with autosomal dominant transmission of the disease. We detected the APP 717 Val-->Ile mutation in three out of 18 (16.6%) families. In these three families, all affected subjects had the APOE 3/3 genotype, but their ages of onset ranged from 38 to 60 years, indicating that factors other than the APOE genotype influence age of onset. Analysis of two polymorphic loci adjacent to the APP gene showed that at least two independent mutational events had occurred within these pedigrees, in spite of their origin in the same region of France.

  5. Influence of Alzheimer disease family history and genetic risk on cognitive performance in healthy middle-aged and older people.

    Science.gov (United States)

    Donix, Markus; Ercoli, Linda M; Siddarth, Prabha; Brown, Jesse A; Martin-Harris, Laurel; Burggren, Alison C; Miller, Karen J; Small, Gary W; Bookheimer, Susan Y

    2012-07-01

    Identification of risk factors for Alzheimer disease (AD) is critical for establishing effective diagnostic and therapeutic strategies. Carrying the ε4 allele of the apolipoprotein E gene (APOE4) and having a family history of the disease are two such factors, with family history risk reflecting additional yet unknown or rarely studied genetic and perhaps nongenetic risks. Our aim was to determine the influence of APOE genotype and family history status on cognitive performance in healthy individuals. Longitudinal study. Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles. Seventy-two cognitively healthy middle-aged and older people (mean age ± SD: 62 ± 9 years). Neuropsychological examinations at baseline and after 2 years. Subjects with a family history of AD had lower baseline scores in processing speed, executive functioning, memory encoding, and delayed memory when compared with those without a family history. The family history risk factor did not influence degree of cognitive decline over time. By contrast, baseline cognitive performance did not vary according to APOE4 carrier status. Non-APOE4 carriers showed improved cognitive performance in the memory domains at follow-up, while performance of APOE4 carriers did not change. Our data highlight the unique contributions of each risk factor to cognitive performance in healthy people. Both factors should be modeled in neuropsychological assessments of people at risk for AD.

  6. "I'm scared of being like mum": The Experience of Adolescents Living in Families with Huntington Disease.

    Science.gov (United States)

    Mand, Cara M; Gillam, Lynn; Duncan, Rony E; Delatycki, Martin B

    2015-01-01

    The debilitating and very visible motor effects of the incurable, progressive, and fatal neurodegenerative condition Huntington disease (HD) are accompanied by more insidious cognitive, behavioural and personality disturbance. The usual age of HD onset exposes children and adolescents to the natural history of the condition as it affects a parent. This group of young people has been largely overlooked in most research, which has concentrated upon the experiences of affected individuals and their partners. This study explores the psychosocial context of young people living in families affected by HD, to better understand their experiences and the specific challenges they face. Ten young people from five unrelated families affected by HD separately participated in semi-structured individual interviews. At the time of interview, nine were less than 18 years of age, and none had requested a predictive genetic test. The young people demonstrated a depth of insight in their descriptions of complex and often painful family circumstances. In addition to the tasks and challenges associated with typical adolescent development, young people from families affected by Huntington disease recognize that they face greater responsibilities and stresses. This study highlights areas of unmet needs for young people living in families affected by HD. Best practice HD care should include consideration of the needs of young people in the family, and offer developmentally appropriate HD education, prospective orientation to genetic services, and psychological and social support.

  7. Increasing Incidence of Crohn's Disease with Familial Clustering in the Kingdom of Bahrain: A 25-Year Population-based Study.

    Science.gov (United States)

    Zayyani, Najah R; Malaty, Hoda M; Graham, David Y

    2017-02-01

    The incidence of Crohn's disease has been increasing in developed countries; whether this trend has extended to countries in Middle East, especially in the Arab world, remains unclear. Our aim was to study the epidemiology, incidence, time trends and clustering of Crohn's disease within the population of the Kingdom of Bahrain. A retrospective case-cohort study was conducted on patients diagnosed with Crohn's disease at Bahrain Specialist Hospital between 1990 and 2015. The diagnosis was based on clinical, radiological, endoscopic, and histological examinations. Five hundred twenty-two cases were eligible for analysis; 14.5% were below the age of 19 with a male-to-female ratio of 1.1:1. The overall incidence was 4.8/100,000 person-years and significantly increased from 5.5/100,000 person-years during the 1990's to 8.0/100,000 person-years during the last study period [incidence rate ratio (IRR) 0.32, 95% CI = 0.26-0.42]. This trend was persistent for adults, children, men and women. There were 129 patients with at least one family member diagnosed with Crohn's disease consisting of 40 families. Three clusters were identified based on first or second degree relationship of the family member. The mean interval for diagnosis between family members was significantly shorter between siblings than second degree relatives; (2.0 ± 1.2 years) versus (5.0 ± 2.8 years), respectively; (P = 0.04). The incidence rate of Crohn's disease in Bahrain is comparable to the U.S.A and has increased for men and women in all age groups. Crohn's disease clusters were common among families and included up to 3 generations consistent with presence of a common source or common genetic factors.

  8. A novel LMX1B mutation in a family with end-stage renal disease of 'unknown cause'.

    Science.gov (United States)

    Edwards, Noel; Rice, Sarah J; Raman, Shreya; Hynes, Ann Marie; Srivastava, Shalabh; Moore, Iain; Al-Hamed, Mohamed; Xu, Yaobo; Santibanez-Koref, Mauro; Thwaites, David T; Gale, Daniel P; Sayer, John A

    2015-02-01

    End-stage renal disease (ESRD) presenting in a familial autosomal dominant pattern points to an underlying monogenic cause. Nail-patella syndrome (NPS) is an autosomal dominant disorder that may lead to ESRD caused by mutations in the transcription factor LMX1B. Renal-limited forms of this disease, termed nail-patella-like renal disease (NPLRD), and LMX1B nephropathy have recently been described. We report a large family, from the North East of England, with seven affected members with varying phenotypes of renal disease, ranging from ESRD at 28 years of age to microscopic haematuria and proteinuria and relatively preserved renal function. In this family, there were no extra-renal manifestations to suggest NPS. Genome-wide linkage studies and inheritance by descent (IBD) suggested disease loci on Chromosome 1 and 9. Whole exome sequencing (WES) analysis identified a novel sequence variant (p.R249Q) in the LMX1B gene in each of the three samples submitted, which was confirmed using Sanger sequencing. The variant segregated with the disease in all affected individuals. In silico modelling revealed that R249 is putatively located in close proximity to the DNA phosphoskeleton, supporting a role for this residue in the interaction between the LMX1B homeodomain and its target DNA. WES and analysis of potential target genes, including CD2AP, NPHS2, COL4A3, COL4A4 and COL4A5, did not reveal any co-inherited pathogenic variants. In conclusion, we confirm a novel LMX1B mutation in a large family with an autosomal dominant pattern of nephropathy. This report confirms that LMX1B mutations may cause a glomerulopathy without extra-renal manifestations. A molecular genetic diagnosis of LMX1B nephropathy thus provides a definitive diagnosis, prevents the need for renal biopsies and allows at risk family members to be screened.

  9. Clinical phenotype and genetic associations in autosomal dominant familial Alzheimer's disease: a case series.

    Science.gov (United States)

    Ryan, Natalie S; Nicholas, Jennifer M; Weston, Philip S J; Liang, Yuying; Lashley, Tammaryn; Guerreiro, Rita; Adamson, Gary; Kenny, Janna; Beck, Jon; Chavez-Gutierrez, Lucia; de Strooper, Bart; Revesz, Tamas; Holton, Janice; Mead, Simon; Rossor, Martin N; Fox, Nick C

    2016-12-01

    The causes of phenotypic heterogeneity in familial Alzheimer's disease with autosomal dominant inheritance are not well understood. We aimed to characterise clinical phenotypes and genetic associations with APP and PSEN1 mutations in symptomatic autosomal dominant familial Alzheimer's disease (ADAD). We retrospectively analysed genotypic and phenotypic data (age at symptom onset, initial cognitive or behavioural symptoms, and presence of myoclonus, seizures, pyramidal signs, extrapyramidal signs, and cerebellar signs) from all individuals with ADAD due to APP or PSEN1 mutations seen at the Dementia Research Centre in London, UK. We examined the frequency of presenting symptoms and additional neurological features, investigated associations with age at symptom onset, APOE genotype, and mutation position, and explored phenotypic differences between APP and PSEN1 mutation carriers. The proportion of individuals presenting with various symptoms was analysed with descriptive statistics, stratified by mutation type. Between July 1, 1987, and Oct 31, 2015, age at onset was recorded for 213 patients (168 with PSEN1 mutations and 45 with APP mutations), with detailed history and neurological examination findings available for 121 (85 with PSEN1 mutations and 36 with APP mutations). We identified 38 different PSEN1 mutations (four novel) and six APP mutations (one novel). Age at onset differed by mutation, with a younger onset for individuals with PSEN1 mutations than for those with APP mutations (mean age 43·6 years [SD 7·2] vs 50·4 years [SD 5·2], respectively, ponset variance was explained by the specific mutation. A cluster of five mutations with particularly early onset (mean age at onset onset and clinical features being influenced by mutation position as well as causative gene. This highlights the importance of considering genetic testing in young patients with dementia and additional neurological features in order to appropriately diagnose and treat their

  10. Long-Term Risk of Atherosclerotic Cardiovascular Disease in US Adults With the Familial Hypercholesterolemia Phenotype.

    Science.gov (United States)

    Perak, Amanda M; Ning, Hongyan; de Ferranti, Sarah D; Gooding, Holly C; Wilkins, John T; Lloyd-Jones, Donald M

    2016-07-05

    Heterozygous familial hypercholesterolemia (FH) affects up to 1 in 200 individuals in the United States, but atherosclerotic cardiovascular disease (ASCVD) outcomes of FH in the general US population have not been described. We therefore sought to evaluate long-term coronary heart disease (CHD) and total ASCVD risks in US adults with an FH phenotype. Using individual pooled data from 6 large US epidemiological cohorts, we stratified participants by low-density lipoprotein cholesterol level at index ages from 20 to 79 years. For the primary analysis, low-density lipoprotein cholesterol levels ≥190 and definition. We used Cox regression models to assess covariate-adjusted associations of the FH phenotype with 30-year hazards for CHD (CHD death or nonfatal myocardial infarction) and total ASCVD (CHD or stroke). We included 68 565 baseline person-examinations; 3850 (5.6%) had the FH phenotype by the primary definition. Follow-up across index ages ranged from 78 985 to 308 378 person-years. After covariate adjustment, the FH phenotype was associated with substantially elevated 30-year CHD risk, with hazard ratios up to 5.0 (95% confidence interval, 1.1-21.7). Across index ages, CHD risk was accelerated in those with the FH phenotype by 10 to 20 years in men and 20 to 30 years in women. Similar patterns of results were found for total ASCVD risk, with hazard ratios up to 4.1 (95% confidence interval, 1.2-13.4). Alternative FH phenotype definitions incorporating family history, more stringent age-based low-density lipoprotein cholesterol thresholds, or alternative lipid fractions decreased the FH phenotype prevalence to as low as 0.2% to 0.4% without materially affecting CHD risk estimates (hazard ratios up to 8.0; 95% confidence interval, 1.0-61.6). In the general US population, the long-term ASCVD burden related to phenotypic FH, defined by low-density lipoprotein cholesterol ≥190 mg/dL, is likely substantial. Our finding of CHD risk acceleration may aid

  11. Hypertrophic cardiomyopathy family with double-heterozygous mutations; does disease severity suggest doubleheterozygosity?

    OpenAIRE

    van Rijsingen, I.A.W.; Hermans-van Ast, J.F.; Arens, Y.H.J.M.; Schalla, S.M.; de Die-Smulders, C.E.M.; van den Wijngaard, A.; Pinto, Y.M.

    2009-01-01

    Background. With the improvement in genetic testing over time, double-heterozygous mutations are more often found by coincidence in families with hypertrophic cardiomyopathy (HCM). Double heterozygosity can be a cause of the wellknown clinical diversity within HCM families.

  12. Cascade Screening in Families with Inherited Cardiac Diseases Driven by Cardiologists

    DEFF Research Database (Denmark)

    Theilade, Juliane; Kanters, Jørgen; Henriksen, Finn Lund

    2013-01-01

    We assessed the outcome of cascade screening of families with congenital long QT syndrome (LQTS) in Danish heart centers.......We assessed the outcome of cascade screening of families with congenital long QT syndrome (LQTS) in Danish heart centers....

  13. Undifferentiated seronegative spondyloarthritis with inflammatory bowel disease and a family history of psoriasis. Sicca syndrome

    Directory of Open Access Journals (Sweden)

    Norma Marigliano

    2013-04-01

    Full Text Available Background: Seronegative spondyloarthritis is characterized by the presence of subcutaneous nodules, asymmetrical peripheral arthritis, sacroileitis with or without spondylitis, and rheumatoid-factor negativity. Other common clinical manifestations include oral ulcers, conjunctivitis, and cutaneous lesions such as psoriasis. Familial aggregation has also been described. According to the 1986 classification, corresponding clinical entities include ankylosing spondylitis, psoriatic arthritis, Reiter’s syndrome, arthritis associated with inflammatory bowel disease (IBD, and undifferentiated spondyloarthritis. The disease is also frequently associated with the HLA B27 antigen. From the clinical point of view, there are often incomplete forms of spondyloarthritis, such as reactive arthritis triggered by asymptomatic infections, psoriatic arthritis without psoriasis itself, initial phases of specific forms of spondyloarthritis or the phase of ankylosing spondylitis characterized by sacroiliac lesions, and all forms that remain undifferentiated for long periods of time. Moreover, there are close relations between arthropathy and IBDs, such as Crohn’s disease, ulcerative colitis, and Whipple’s syndrome. Recently, microscopic inflammatory bowel lesions and psoriatic arthritis have been described. Case report: A 30-year-old man (HLA B27-negative who had been vaccinated against TBC and HBV presented with a 6-year history of recurrent episodes of predominantly left-sided sciatica. The pain was worse at night and during rest. He was suffering from bilateral sacroileitis without spondylitis. Three to five times a day, usually after eating, he passed watery feces containing mucous and small amounts of bright red blood. Colonoscopy revealed pancolitis with histological evidence of chronic inflammation interspersed with areas of acute inflammation, edema, hyperemia, and glandular distortion. One year later, the clinical manifestations and histological

  14. Family history of coronary heart disease is associated with a higher incidence of nonalcoholic fatty liver disease: Central obesity the likely link.

    Science.gov (United States)

    Zhang, Lei; Pu, Kui; Chai, Zhonglin; Dixon, John B

    2007-05-01

    To examine the relationship between family history of coronary heart disease (CHD), hypertension, and diabetes with risk of non-alcoholic fatty liver disease (NAFLD), and the possible interaction between these family histories and metabolic components for NAFLD. The 202 health office workers with no evidence of excessive alcohol drinking or hepatitis B or C virus infection were enrolled in the present study performed from March to June 2004. NAFLD was identified in 68 subjects by abdominal ultrasound. Logistic regression analysis showed that the presence of CHD family history increased the risk of NAFLD by 2.25-fold, 95% CI 1.1-4.1 (P = 0.014), while family history of diabetes or hypertension did not increase the risk. In combination with the presence of a family history of CHD, the effect on odds ratios (ORs) was increased for several metabolic features in predicting the incidence of NAFLD, including increased waist circumference, hypertriglyceridemia, hypertension and the occurrence of the metabolic syndrome. In a logistic regression model, the CHD family history enhances the summary predictive power of baseline clinical variables for NAFLD, but when the occurrence of increased waist circumference and hypertriglyceridemia are considered, the predictive value of a family history of CHD is no longer significant. This study has shown that the CHD family history may be clinically useful and associated with the occurrence of NAFLD, and that the likely link is through central obesity and the metabolic syndrome. © 2007 Asian Oceanian Association for the Study of Obesity . Published by Elsevier Ltd. All rights reserved.

  15. Subjective experiences of an art museum engagement activity for persons with early-stage Alzheimer's disease and their family caregivers.

    Science.gov (United States)

    Flatt, Jason D; Liptak, Amy; Oakley, Mary Ann; Gogan, Jessica; Varner, Tresa; Lingler, Jennifer H

    2015-06-01

    To describe the subjective experiences of older adults with early-stage Alzheimer's disease or related cognitive disorders (ADRDs) and their family caregivers who participated in an art museum engagement activity. Four focus groups were conducted with 10 persons with ADRD and 10 family caregivers following the completion of a 1-time, 3-hour engagement activity. Participants also completed a brief satisfaction survey, and associations were examined using nonparametric statistics. Three key themes were identified: cognitive stimulation, social connections, and self-esteem. In addition, we identified programmatic issues such as activity-specific concerns and program logistics that could help improve future art program offerings. Past experience with art and perceived social cohesion were correlated with participants' overall satisfaction with the program. Efforts aimed at improving the quality of life of those with Alzheimer's disease and their family caregivers should consider the potential role of art museums. © The Author(s) 2014.

  16. Gene-load score of the renin-angiotensin-aldosterone system is associated with coronary heart disease in familial hypercholesterolaemia

    NARCIS (Netherlands)

    J.B. van der Net (Jeroen); J. van Etten (Jeroen); M. Yazdanpanah (Mojgan); G.M. Dallinga-Thie (Geesje); J.J.P. Kastelein (John); J.C. Defesche (Joep); R.P. Koopmans (Richard); E.W. Steyerberg (Ewout); E.J.G. Sijbrands (Eric)

    2008-01-01

    textabstractAims: Familial hypercholesterolaemia (FH) is characterized by premature coronary heart disease (CHD). However, the incidence of CHD varies considerably among FH patients. Genetic variation in the renin-angiotensin-aldosterone system (RAAS) and the adrenalin/noradrenalin system may be of

  17. Alzheimer's Disease and Other Dementias: An Organizational Approach to Identifying and Addressing Practices and Learning Needs of Family Physicians

    Science.gov (United States)

    Allen, Michael; Ferrier, Suzanne; Sargeant, Joan; Loney, Elaine; Bethune, Graeme; Murphy, Gerard

    2005-01-01

    Caring for patients with dementia is complex and demanding. Since family physicians (FPs) provide much of this care, we examined their practices, learning needs, and barriers to care concerning Alzheimer's disease and other dementias. We surveyed 392 (approximately 50%) Nova Scotia FPs and conducted focus groups and interviews with: FPs; staff of…

  18. Stage-matched nutrition guidance for patients at elevated risk for cardiovascular disease: A randomized intervention study in family practice

    NARCIS (Netherlands)

    Veen, van der J.E.; Bakx, J.C.; Hoogen, van den H.; Verheijden, M.W.; Bosch, van den W.; Weel, van C.; Staveren, van W.A.

    2002-01-01

    OBJECTIVE To examine stage-matched nutrition counseling by family physicians and its effect on dietary intake, anthropometry, and serum lipid levels in patients at elevated risk for cardiovascular disease. METHODS In this controlled trial, patients randomized to intervention practices received

  19. Gene-load score of the renin-angiotensin-aldosterone system is associated with coronary heart disease in familial hypercholesterolaemia

    NARCIS (Netherlands)

    van der Net, Jeroen B.; van Etten, Jeroen; Yazdanpanah, Mojgan; Dallinga-Thie, Geesje M.; Kastelein, John J. P.; Defesche, Joep C.; Koopmans, Richard P.; Steyerberg, Ewout W.; Sijbrands, Eric J. G.

    2008-01-01

    AIMS: Familial hypercholesterolaemia (FH) is characterized by premature coronary heart disease (CHD). However, the incidence of CHD varies considerably among FH patients. Genetic variation in the renin-angiotensin-aldosterone system (RAAS) and the adrenalin/noradrenalin system may be of importance

  20. A Dutch family with autosomal recessively inherited lower motor neuron predominant motor neuron disease due to optineurin mutations

    NARCIS (Netherlands)

    Beeldman, Emma; van der Kooi, Anneke J.; de Visser, Marianne; van Maarle, Merel C.; van Ruissen, Fred; Baas, Frank

    2015-01-01

    Approximately 10% of motor neuron disease (MND) patients report a familial predisposition for MND. Autosomal recessively inherited MND is less common and is most often caused by mutations in the superoxide dismutase 1 (SOD1) gene. In 2010, autosomal recessively inherited mutations in the optineurin

  1. Pooling and expanding registries of familial hypercholesterolaemia to assess gaps in care and improve disease management and outcomes

    DEFF Research Database (Denmark)

    Vallejo-Vaz, Antonio J; Akram, Asif; Kondapally Seshasai, Sreenivasa Rao

    2016-01-01

    BACKGROUND: The potential for global collaborations to better inform public health policy regarding major non-communicable diseases has been successfully demonstrated by several large-scale international consortia. However, the true public health impact of familial hypercholesterolaemia (FH), a c...

  2. Homozygosity mapping and targeted sanger sequencing reveal genetic defects underlying inherited retinal disease in families from pakistan

    NARCIS (Netherlands)

    Maria, M.; Ajmal, M.; Azam, M.; Waheed, N.K.; Siddiqui, S.N.; Mustafa, B.; Ayub, H.; Ali, L.; Ahmad, S.; Micheal, S.; Hussain, A.; Shah, S.T.; Ali, S.H.; Ahmed, W.; Khan, Y.M.; Hollander, A.I. den; Haer-Wigman, L.; Collin, R.W.J.; Khan, M.I.; Qamar, R.; Cremers, F.P.M.

    2015-01-01

    BACKGROUND: Homozygosity mapping has facilitated the identification of the genetic causes underlying inherited diseases, particularly in consanguineous families with multiple affected individuals. This knowledge has also resulted in a mutation dataset that can be used in a cost and time effective

  3. Evidence for allelic heterogeneity in familial early-onset Alzheimer's disease

    NARCIS (Netherlands)

    C.M. van Duijn (Cornelia); J. Hardy (John); A.M. Goate (Alison); M.N. Rossor (Martin); A. Vandenberghe (Anton); J-J. Martin (Jean-Jacques); M.J. Mullan; C. van Broeckhoven (Christine); A. Hofman (Albert)

    1991-01-01

    textabstractAge of onset was examined for 139 members of 30 families affected by early-onset AD. Most (77%) of the variance of age of onset derived from differences between rather than within families. The constancy of age of onset within families was also observed in an analysis restricted to

  4. Familial hemophagocytic lymphohistiocytosis: when rare diseases shed light on immune system functioning

    Directory of Open Access Journals (Sweden)

    Elena eSieni

    2014-04-01

    Full Text Available The human immune system depends on the activity of cytotoxic T lymphocytes, Natural Killer cells, and NKT cells in order to fight off a viral infection. Understanding the molecular mechanisms during this process and the role of individual proteins was greatly improved by the study of Familial Hemophagocytic Lymphohistiocytosis (FHL. Since 1999, genetic sequencing is the gold standard to classify patients into different subgroups of FHL. The diagnosis, once based on a clinical constellation of abnormalities, is now strongly supported by the results of a functional flow-cytometry screening, which directs the genetic study. A few additional congenital immune deficiencies can also cause a resembling or even identical clinical picture to FHL. As in many other rare human disorders, the collection and analysis of a relatively large number of cases in registries is crucial to draw a complete picture of the disease. The conduction of prospective therapeutic trials allows investigators to increase the awareness of the disease and to speed up the diagnostic process, but also provides important functional and genetic confirmations. Children with confirmed diagnosis may undergo hematopoietic stem cell transplantation, which is the only cure known to date. Moreover, detailed characterization of these rare patients helped to understand the function of individual proteins within the exocytic machinery of CTL, NK and NKT cells. Moreover, identification of these genotypes also provides valuable information on variant phenotypes, other than FHL, associated with biallelic and monoallelic mutations in the FHL-related genes.In this review we describe how detailed characterization of patients with genetic HLH has resulted in improvement in knowledge regarding contribution of individual proteins to the functional machinery of cytotoxic T-cells and NK cells. The review also details how identification of these genotypes has provided valuable information on variant

  5. Cardiovascular disease in familial hypercholesterolemia: Validation and refinement of the Montreal-FH-SCORE.

    Science.gov (United States)

    Paquette, Martine; Brisson, Diane; Dufour, Robert; Khoury, Étienne; Gaudet, Daniel; Baass, Alexis

    Familial hypercholesterolemia (FH) is a disease characterized by increased low-density lipoprotein cholesterol and premature cardiovascular disease (CVD) but there is marked individuality in the occurrence of CVD events. Recently, the Montreal-FH-SCORE (MFHS) has been shown to stratify CVD frequency in FH subjects, but this score has not yet been validated. The aims of the present study were to conduct an independent external validation of the MFHS in a retrospective cohort of heterozygous FH and to identify additional variables that could significantly improve the prediction of prevalent CVD. The MFHS calculation is based on 5 variables: age, high-density lipoprotein cholesterol, gender, hypertension, and smoking status. This score was validated in a cohort of 718 adult FH using receiver operating characteristic (ROC) curves analysis to determine the discriminatory ability of the MFHS. The performance of the MFHS was compared to a novel Combined-FH-SCORE in 1388 FH. The MFHS had an excellent discrimination for prevalent CVD events in the validation cohort, with an area under the receiver operating characteristic curve of 0.799 (0.766-0.832, P < .0001). Patients with a high MFHS score presented a significant 8.8-fold increased odd of CVD events compared with patients with a low score (95% confidence interval 5.8-13.3, P < .0001). The addition of lipoprotein(a) to the score did not improve the prediction of CVD events (area under the receiver operating characteristic curve 0.823 vs 0.817, P = .11). This study confirmed that the MFHS is a strong predictor of prevalent CVD in FH and that the addition of lipoprotein(a) offers a minor improvement in the discrimination of the score. Copyright © 2017 National Lipid Association. Published by Elsevier Inc. All rights reserved.

  6. Effects of a psychoeducational intervention in family caregivers of people with Alzheimer's disease

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    Cinthia Costa Ponce

    Full Text Available Abstract Psychoeducational activities are a way of promoting help for caregivers of patients with Alzheimer's disease, representing a forum for knowledge sharing, and in which the primary focus is on psychological themes aimed at carers developing coping skills and strategies. Objective: The main objective of this study was to gauge perceptions about care and its impact among family caregivers of patients with AD participating in a psychoeducational group intervention, as well as the possible positive and negative aspects associated with this role. The subjective impact of AD on the lives of these caregivers was assessed on each of the dimensions of the Caregiver Burden Scale using a semi-directed interview on perceptions about care. Methods: This was a prospective study, in which information was collected twice, before and after, psychoeducational intervention. Through the application of the scale, benefits were evident for all dimensions assessed in the instrument (general strain, isolation, disappointment, emotional involvement and environment. Results: The results showed that after the psychoeducational intervention, caregivers felt less burdened by care compared to pre-intervention. Conclusion: These findings confirm that expanded implementation of psychoeducational interventions for caregivers of patients with AD can be beneficial for both caregivers and patients.

  7. Age Effects on Cognitive and Physiological Parameters in Familial Caregivers of Alzheimer's Disease Patients.

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    Márcio Silveira Corrêa

    Full Text Available Older familial caregivers of Alzheimer's disease patients are subjected to stress-related cognitive and psychophysiological dysfunctions that may affect their quality of life and ability to provide care. Younger caregivers have never been properly evaluated. We hypothesized that they would show qualitatively similar cognitive and psychophysiological alterations to those of older caregivers.The cognitive measures of 17 young (31-58 years and 18 old (63-84 years caregivers and of 17 young (37-57 years and 18 old (62-84 years non-caregiver controls were evaluated together with their salivary cortisol and dehydroepiandrosterone (DHEA levels, as measured by radioimmunoassays and ELISA assays of brain-derived neurotrophic factor (BDNF in serum.Although younger caregivers had milder impairments in memory and executive functions than older caregivers, their performances fell to the same or lower levels as those of the healthy older controls. Decreases in DHEA and BDNF levels were correlated with the cognitive dysfunctions observed in the older and younger caregivers, respectively. Cortisol at 10PM increased in both caregiver groups.Younger caregivers were prone to cognitive impairments similar to older caregivers, although the degree and the neuropsychological correlates of the cognitive dysfunctions were somewhat different between the two groups. This work has implications for caregiver and care-recipient health and for research on the neurobiology of stress-related cognitive dysfunctions.

  8. Differential cerebral deposition of IDE and NEP in sporadic and familial Alzheimer’s disease

    Science.gov (United States)

    Dorfman, Verónica Berta; Pasquini, Laura; Riudavets, Miguel; López-Costa, Juan José; Villegas, Andrés; Troncoso, Juan Carlos; Lopera, Francisco; Castaño, Eduardo Miguel; Morelli, Laura

    2011-01-01

    Alzheimer’s disease (AD) is characterized by amyloid β (Aβ) accumulation in the brain and is classified as familial early-onset (FAD) or sporadic late-onset (SAD). Evidences suggest that deficits in the brain expression of insulin degrading enzyme (IDE) and neprilysin (NEP), both proteases involved in amyloid degradation, may promote Aβ deposition in SAD. We studied by immunohistochemistry IDE and NEP cortical expression in SAD and FAD samples carrying the E280A presenilin-1 missense mutation. We showed that IDE, a soluble peptidase, is linked with aggregated Aβ40 isoform while NEP, a membrane-bound protease, negatively correlates with amyloid angiopathy and its expression in the senile plaques is independent of aggregated amyloid and restricted to SAD cases. NEP, but not IDE, is over-expressed in dystrophic neurites, both proteases are immunoreactive in activated astrocytes but not in microglia and IDE was the only one detected in astrocytes of white matter from FAD cases. Collectively, our results support the notion that gross conformational changes involved in the modification from “natively folded-active” to “aggregated-inactive” IDE and NEP may be a relevant pathogenic mechanism in SAD. PMID:19019493

  9. Clinical and molecular findings of chronic granulomatous disease in Oman: family studies.

    Science.gov (United States)

    Al-Zadjali, S; Al-Tamemi, S; Elnour, I; AlKindi, S; Lapoumeroulie, C; Al-Maamari, S; Pathare, A; Dennison, D; Krishnamoorthy, R

    2015-02-01

    Chronic granulomatous disease (CGD), a rare inherited disorder of the innate immune system, results from mutations in any one of the five genes encoding the subunits of the nicotinamide adenine dinucleotide phosphate-oxidase (NADPH) oxidase enzyme, and is characterized by recurrent life-threatening bacterial and fungal infections. Molecular analysis of 14 Omani CGD patients from 10 families, diagnosed to have CGD on clinical (recurrent infections) and biochemical grounds (positive for both the nitroblue tetrazolium (NBT) test and the dihydrorhodamine (DHR-1,2,3 assay), revealed that only one patient had X-linked CGD, with a large deletion involving both the gp91-phox gene (CYBB) and the McLeod gene (XK). The remaining 13 patients were all homozygotes from a previously described c.579G>A (p.Trp193X) mutation in the NCF1 gene on chromosome 7, responsible for autosomal recessive CGD (AR-CGD). Although X-linked CGD is the most common type of CGD disorder in most population groups, AR-CGD is the most prevalent type in Oman. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  10. Genetic testing of children for diseases that have onset in adulthood: the limits of family interests.

    Science.gov (United States)

    Hardart, George E; Chung, Wendy K

    2014-10-01

    Two recent policy statements, one from the American Academy of Pediatrics and one from the American College of Medical Genetics, reach very different conclusions about the question of whether children should be tested for adult-onset genetic conditions. The American Academy of Pediatrics policy begins with the presumption that genetic testing for children should be driven by the best interest of the child. It recognizes the importance of preserving the child's open future, recommending that genetic testing for adult-onset diseases be deferred. The American College of Medical Genetics, by contrast, recommended testing children for at least some adult conditions, although it should be noted they have recently modified this recommendation. They justified this recommendation by arguing that it, in fact, was in the best interests of the child and family to receive this information. In this article, we analyze these 2 different positions and suggest ways that the seeming conflicts between them might be reconciled. Copyright © 2014 by the American Academy of Pediatrics.

  11. Age Effects on Cognitive and Physiological Parameters in Familial Caregivers of Alzheimer's Disease Patients

    Science.gov (United States)

    Corrêa, Márcio Silveira; Giacobbo, Bruno Lima; Vedovelli, Kelem; de Lima, Daiane Borba; Ferrari, Pamela; Argimon, Irani Iracema de Lima; Walz, Julio Cesar

    2016-01-01

    Objectives Older familial caregivers of Alzheimer’s disease patients are subjected to stress-related cognitive and psychophysiological dysfunctions that may affect their quality of life and ability to provide care. Younger caregivers have never been properly evaluated. We hypothesized that they would show qualitatively similar cognitive and psychophysiological alterations to those of older caregivers. Method The cognitive measures of 17 young (31–58 years) and 18 old (63–84 years) caregivers and of 17 young (37–57 years) and 18 old (62–84 years) non-caregiver controls were evaluated together with their salivary cortisol and dehydroepiandrosterone (DHEA) levels, as measured by radioimmunoassays and ELISA assays of brain-derived neurotrophic factor (BDNF) in serum. Results Although younger caregivers had milder impairments in memory and executive functions than older caregivers, their performances fell to the same or lower levels as those of the healthy older controls. Decreases in DHEA and BDNF levels were correlated with the cognitive dysfunctions observed in the older and younger caregivers, respectively. Cortisol at 10PM increased in both caregiver groups. Discussion Younger caregivers were prone to cognitive impairments similar to older caregivers, although the degree and the neuropsychological correlates of the cognitive dysfunctions were somewhat different between the two groups. This work has implications for caregiver and care-recipient health and for research on the neurobiology of stress-related cognitive dysfunctions. PMID:27706235

  12. Callose Synthase Family Genes Involved in the Grapevine Defense Response to Downy Mildew Disease.

    Science.gov (United States)

    Yu, Ying; Jiao, Li; Fu, Shufang; Yin, Ling; Zhang, Yali; Lu, Jiang

    2016-01-01

    The deposition of callose is a common plant defense response to intruding pathogens and part of the plant's innate immunity. In this study, eight grapevine callose synthase (CalS) genes were identified and characterized. To investigate biological function of CalS in grapevine against the infection of Plasmopara viticola, expression patterns of grapevine CalS family genes were analyzed among resistant/susceptible cultivars. After P. viticola infection, expression of CalS1, 3, 7, 8, 9, 10, and 11 were significantly modified among the grapevine cultivars. For example, the expression of CalS1 and CalS10 were greatly increased in downy mildew (DM)-immune Muscadinia rotundifolia 'Carlos' and 'Noble'. Transient expression assay with promoters of the CalS1 and CalS10 genes confirmed that they were regulated by the oomycete pathogen P. viticola. CalS1 promoter activity was also significantly up-regulated by ABA in DM-immune M. rotundifolia 'Noble', but down-regulated in DM-susceptible Vitis vinifera 'Chardonnay'. The CalS1 promoter, however, was also down-regulated by GA in 'Chardonnay', but not affected in 'Noble'. The promoter activity of CalS10 was significantly up-regulated by GA in 'Chardonnay', but not regulated by ABA at all. It is proposed that CalS1 and CalS10 were involved in grapevine defense against DM disease.

  13. Haplotype analysis of the 4p16.3 region in Portuguese families with Huntington's disease.

    Science.gov (United States)

    Ramos, Eliana Marisa; Gillis, Tammy; Mysore, Jayalakshmi S; Lee, Jong-Min; Gögele, Martin; D'Elia, Yuri; Pichler, Irene; Sequeiros, Jorge; Pramstaller, Peter P; Gusella, James F; MacDonald, Marcy E; Alonso, Isabel

    2015-03-01

    Huntington's disease (HD) is a neurodegenerative disorder characterized by involuntary choreic movements, cognitive impairment, and behavioral changes, caused by the expansion of an unstable CAG repeat in HTT. We characterized the genetic diversity of the HD mutation by performing an extensive haplotype analysis of ∼1Mb region flanking HTT in over 300 HD families of Portuguese origin. We observed that haplotype A, marked by HTT delta2642, was enriched in HD chromosomes and carried the two largest expansions reported in the Portuguese population. However, the most frequent HD haplotype B carried one of the largest (+12 CAGs) expansions, which resulted in an allele class change to full penetrance. Despite having a normal CAG distribution skewed to the higher end of the range, these two core haplotypes had similar expanded CAG repeat sizes compared to the other major core haplotypes (C and D) and there was no statistical difference in transmitted repeat instability across haplotypes. We observed a diversity of HTT region haplotypes in both normal and expanded chromosomes, representative of more than one ancestral chromosome underlying HD in Portugal, where multiple independent events on distinct chromosome 4 haplotypes have given rise to expansion into the pathogenic range. © 2015 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Published by Wiley Periodicals, Inc.

  14. Family carers: A role in addressing chronic disease risk behaviours for people with a mental illness?

    Science.gov (United States)

    Bailey, Jacqueline M; Wye, Paula M; Wiggers, John H; Bartlem, Kate M; Bowman, Jennifer A

    2017-09-01

    People with a mental illness experience greater chronic disease morbidity and mortality compared to those without mental illness. Family carers have the potential to promote the health behaviours of those they care for however factors which may influence the extent to which they do so have not been reported. An exploratory study was conducted to investigate carers': 1) promotion of fruit and vegetable consumption, physical activity, quitting smoking, and reducing alcohol consumption; 2) perceptions of their role and ability to promote such behaviours; 3) and the association between carer perceptions and the promotion of such behaviours. A cross-sectional survey was conducted with mental health carers (N = 144, 37.6% response rate) in New South Wales, Australia in 2013. Associations between current promotion of health behaviours and carer perceptions were explored through multivariate regression analysis in 2016. A majority of respondents promoted fruit and vegetable consumption (63.8%), physical activity (60.3%), quitting smoking (56.3%), and reducing alcohol consumption (56.2%) to the person they cared for. A perception that it was 'very important' to have a positive influence on these behaviours was positively related with promotion of each of the four behaviours, with those holding such a view being more likely to promote such behaviours, than those who did not (odds ratio: 9.47-24.13, p mental illness.

  15. Structure and function of the contactin-associated protein family in myelinated axons and their relationship with nerve diseases

    Directory of Open Access Journals (Sweden)

    Yan Zou

    2017-01-01

    Full Text Available The contactin-associated protein (Caspr family participates in nerve excitation and conduction, and neurotransmitter release in myelinated axons. We analyzed the structures and functions of the Caspr family–CNTNAP1 (Caspr1, CNTNAP2 (Caspr2, CNTNAP3 (Caspr3, CNTNAP4 (Caspr4 and CNTNAP5 (Caspr5, Caspr1–5 is not only involved in the formation of myelinated axons, but also participates in maintaining the stability of adjacent connections. Caspr1 participates in the formation, differentiation, and proliferation of neurons and astrocytes, and in motor control and cognitive function. We also analyzed the relationship between the Caspr family and neurodegenerative diseases, multiple sclerosis, and autoimmune encephalitis. However, the effects of Caspr on disease course and prognosis remain poorly understood. The effects of Caspr on disease diagnosis and treatment need further investigation.

  16. Neuropsychiatric symptoms of the elderly with Alzheimer's disease and the family caregivers' distress.

    Science.gov (United States)

    Storti, Luana Baldin; Quintino, Débora Teles; Silva, Natália Michelato; Kusumota, Luciana; Marques, Sueli

    2016-08-15

    to analyze the relationship between the distress of the family caregiver and the presence of neuropsychiatric symptoms in elderly patients with Alzheimer's disease or mixed dementia. a descriptive, cross-sectional study conducted in the Geriatric and Dementias Clinic of a general tertiary hospital, with 96 elderly people with Alzheimer's disease or mixed dementia and their family caregivers. Questionnaires to characterize the elderly and caregivers, and the Neuropsychiatric Inventory were used. Descriptive statistics and Pearson correlation test were performed. 68.7% of the elderly were women, average age 80.8 years, 56.2% had Alzheimer's disease and 43.7%, mixed dementia. Among caregivers, 90.6% were women, average age 56, 70.8% took care of parents and 64.6% lived with the elderly. There was a strong (r = 0.82) and significant (p idosos com doença de Alzheimer ou demência mista. estudo descritivo, transversal, realizado no Ambulatório de Geriatria e Demências de um Hospital Geral Terciário, com 96 idosos com doença de Alzheimer ou demência mista e seus cuidadores familiares. Foram utilizados o questionário para caracterização dos idosos e cuidadores e o Inventário Neuropsiquiátrico. Foram realizadas estatísticas descritivas e o teste de correlação de Pearson. 68,7% dos idosos eram mulheres, média de idade 80,8 anos, 56,2% possuíam doença de Alzheimer e 43,7%, demência mista. Dos cuidadores, 90,6% eram mulheres, média de idade 56 anos, 70,8% cuidavam do pai/mãe e 64,6% moravam com o idoso. Houve correlação forte (r=0,82) e significativa (pidosos maior é o desgaste do cuidador. a presença dos sintomas neuropsiquiátricos nos idosos apresentou relação com maior desgaste nos cuidadores. analizar la relación entre el desgaste del cuidador familiar y la presencia de síntomas neuropsiquiátricos en pacientes ancianos con enfermedad de Alzheimer o demencia mixta. estudio descriptivo, transversal, realizado en la clínica de Geriatría y

  17. Expression and role of the TGF-β family in glial cells infected with Borna disease virus.

    Science.gov (United States)

    Nishino, Yoshii; Murakami, Masaru; Funaba, Masayuki

    2016-02-01

    A previous study revealed that the expression of the Borna disease virus (BDV)-encoding phosphoprotein in glial cells was sufficient to induce neurobehavioral abnormalities resembling Borna disease. To evaluate the involvement of the TGF-β family in BDV-induced changes in cell responses by C6 glial cells, we examined the expression levels of the TGF-β family and effects of inhibiting the TGF-β family pathway in BDV-infected C6 (C6BV) cells. The expression of activin βA and BMP7 was markedly increased in BDV-infected cells. Expression of Smad7, a TGF-β family-inducible gene, was increased by BDV infection, and the expression was decreased by treatment with A-83-01 or LDN-193189, inhibitors of the TGF-β/activin or BMP pathway, respectively. These results suggest autocrine effects of activin A and BMP7 in C6BV cells. IGFBP-3 expression was also induced by BDV infection; it was below the detection limit in C6 cells. The expression level of IGFBP-3 was decreased by LDN-193189 in C6BV cells, suggesting that endogenous BMP activity is responsible for IGFBP-3 gene induction. Our results reveal the regulatory expression of genes related to the TGF-β family, and the role of the enhanced BMP pathway in modulating cell responses in BDV-infected glial cells. Copyright © 2015 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  18. Children with Hepatitis C: The Impact of Disease and Treatment on Patients, Caregivers and Families.

    Science.gov (United States)

    Annunziato, Rachel A; Lee, Samantha G; Galici, Elizabeth; Arnon, Ronen

    Previous research on children with HCV has examined patient psychosocial outcomes but little is known about the impact of HCV and its prolonged treatment, which includes weekly injections and oral medications for 6-12 months, on caregivers and families. The present study aimed to address this gap. Using a case series design (N=10), baseline distress levels of individuals and families as well as changes during HCV treatment were examined. A brief patient, caregiver, and family assessment packet was given before and immediately after treatment, but before the final outcome of treatment was known. During the study period, 10 families at our site began treatment for HCV. Each family was given a battery assessing patient quality of life, (the Pediatric Quality of Life Inventory; PedsQL), caregiver distress related to their child's illness (Impact of Events Scale; IES), and overall family functioning (Family Assessment Device; FAD). At baseline, patients displayed poorer quality of life than population norms, caregiver distress was elevated and family functioning was also in the "stressed" range. After treatment, all parameters worsened. In conclusion, in this case series of patients in treatment for HCV, significant psychosocial distress was noted for individuals and families and this was exacerbated over the course of treatment. Caregivers may benefit from additional support given the implications of HCV and grueling nature of its treatment. Broadly, the impact of continuous intensive treatments on families perhaps should be monitored. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Evidence for major gene inheritance of Alzheimer disease in families of patients with and without Apolipoprotein E {epsilon}4

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    Rao, V.S.; Auerbach, S.A.; Farrer, L.A. [Boston Univ. School of Medicine, MA (United States)] [and others

    1996-09-01

    Apolipoprotein E (APOE) genotype is the single most important determinant to the common form of Alzheimer disease (AD) yet identified. Several studies show that family history of AD is not entirely accounted for by APOE genotype. Also, there is evidence for an interaction between APOE genotype and gender. We carried out a complex segregation analysis in 636 nuclear families of consecutively ascertained and rigorously diagnosed probands in the Multi-Institutional Research in Alzheimer Genetic Epidemiology study in order to derive models of disease transmission which account for the influences of APOE genotype of the proband and gender. In the total group of families, models postulating sporadic occurrence, no major gene effect, random environmental transmission, and Mendelian inheritance were rejected. Transmission of AD in families of probands with at least one {epsilon}4 allele best fit a dominant model. Moreover, single gene inheritance best explained clustering of the disorder in families of probands lacking E4, but a more complex genetic model or multiple genetic models may ultimately account for risk in this group of families. Our results also suggest that susceptibility to AD differs between men and women regardless of the proband`s APOE status. Assuming a dominant model, AD appears to be completely penetrant in women, whereas only 62%-65% of men with predisposing genotypes develop AD. However, parameter estimates from the arbitrary major gene model suggests that AD is expressed dominantly in women and additively in men. These observations, taken together with epidemiologic data, are consistent with the hypothesis of an interaction between genes and other biological factors affecting disease susceptibility. 76 refs., 4 tabs.

  20. A novel mutation in ABCA1 gene causing Tangier Disease in an Italian family with uncommon neurological presentation

    Directory of Open Access Journals (Sweden)

    Marco Ceccanti

    2016-11-01

    Full Text Available Tangier disease is an autosomal recessive disorder characterized by severe reduction in HDL-cholesterol and peripheral lipid storage. We describe a family with c.5094C>A p.Tyr16980* mutation in the ABCA1 gene, clinically characterized by syringomyelic-like anesthesia, demyelinating multineuropathy and reduction in intraepidermal small fibers innervation. In the proband patient, cardiac involvement determined a myocardial infarction; lipid storage was demonstrated in gut, cornea and aortic wall. The reported ABCA1 mutation has never been described before in a Tangier family.

  1. Improving the quality of care for patients with chronic diseases: what research and education in family medicine can contribute.

    Science.gov (United States)

    Wensing, Michel; Kersnik, Janko

    2012-12-01

    The theme of the EGPRN conference in Ljubljana 2012 was 'Quality improvement in the care of chronic disease in family practice: the contribution of education and research.' In this contribution, we summarize our key note lectures and provide reflections on the theme. Many countries have established programmes for training of primary care professionals and quality improvement in family medicine. Research and development has focused on new educational methods, practice accreditation, patient safety in primary care, models of structured chronic care, and tailored improvement. An international academic network of physicians, teachers and researchers in primary care should be nurtured to address the challenges of chronic illness care.

  2. Children with asthma and their families' viewpoints on spiritual and psychological resources in adaptation with the disease.

    Science.gov (United States)

    Alijani Renani, Houshang; Hajinejad, Fatemeh; Idani, Esmaeil; Ravanipour, Maryam

    2014-08-01

    Recognition of the spiritual and psychological needs of children and their families with chronic asthma disease may be helpful in a successful coping with their problems in order to control over the condition. In a qualitative content analysis study, nine children with moderate to severe asthma and 10 parents were studied in order to discover the resources of compatibility of them. The participants were chosen purposefully and they were asked some semi-structure questions about their experiences. The spiritual and psychological experiences of the participants were divided into two main categories as follows: (1) contrive to religious-belief consisting of three sub-categories known as "religious rituals, believe in a divine predestination, and Islamic-based patience," and (2) psycho-intellectual management that includes the five sub-categories of "psycho-intellectual attention, maintaining family's mental peace, reduction in negative burden of disease, satisfaction from optimal treatment, and matching internal desires with disease conditions." It is recommended that heath care providers by reinforcing parent's and children's religious and spiritual backgrounds and according to child's cognitive development at this age provide a suitable foreground through necessary instructions for children and their families in order to spiritual growth and suitable adaptation with disease.

  3. Mutations in SLC29A3, encoding an equilibrative nucleoside transporter ENT3, cause a familial histiocytosis syndrome (Faisalabad histiocytosis and familial Rosai-Dorfman disease.

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    Neil V Morgan

    2010-02-01

    Full Text Available The histiocytoses are a heterogeneous group of disorders characterised by an excessive number of histiocytes. In most cases the pathophysiology is unclear and treatment is nonspecific. Faisalabad histiocytosis (FHC (MIM 602782 has been classed as an autosomal recessively inherited form of histiocytosis with similarities to Rosai-Dorfman disease (RDD (also known as sinus histiocytosis with massive lymphadenopathy (SHML. To elucidate the molecular basis of FHC, we performed autozygosity mapping studies in a large consanguineous family and identified a novel locus at chromosome 10q22.1. Mutation analysis of candidate genes within the target interval identified biallelic germline mutations in SLC29A3 in the FHC kindred and in two families reported to have familial RDD. Analysis of SLC29A3 expression during mouse embryogenesis revealed widespread expression by e14.5 with prominent expression in the central nervous system, eye, inner ear, and epithelial tissues including the gastrointestinal tract. SLC29A3 encodes an intracellular equilibrative nucleoside transporter (hENT3 with affinity for adenosine. Recently germline mutations in SLC29A3 were also described in two rare autosomal recessive disorders with overlapping phenotypes: (a H syndrome (MIM 612391 that is characterised by cutaneous hyperpigmentation and hypertrichosis, hepatomegaly, heart anomalies, hearing loss, and hypogonadism; and (b PHID (pigmented hypertrichosis with insulin-dependent diabetes mellitus syndrome. Our findings suggest that a variety of clinical diagnoses (H and PHID syndromes, FHC, and familial RDD can be included in a new diagnostic category of SLC29A3 spectrum disorder.

  4. Novel protein biomarkers associated with coronary artery disease in statin-treated patients with familial hypercholesterolemia.

    Science.gov (United States)

    Bos, Sven; Phillips, Michael; Watts, Gerald F; Verhoeven, Adrie J M; Sijbrands, Eric J G; Ward, Natalie C

    Familial hypercholesterolemia (FH) is the most common and serious monogenic disorder of lipid metabolism. The incidence of coronary artery disease (CAD) varies among both treated and untreated FH patients. The aim of the study was to utilize proteomics to identify novel protein biomarkers that differentiate genetically confirmed heterozygous patients with FH at high CAD risk from those at low CAD risk. Sixty genetically confirmed FH patients were recruited and stratified into (1) asymptomatic FH with low atherosclerotic burden (FH, n = 20); (2) asymptomatic FH with high atherosclerotic burden (FH + Ca, n = 20); and (3) FH with previously confirmed symptomatic CAD (FH + CAD, n = 20). Six new potential proteins were identified; leucine-rich alpha-2-glycoprotein (LRG1), inter-alpha-trypsin inhibitor heavy chain H3, complement C4-B (C4B), complement C1q subcomponent subunit B (C1QB), monocyte differentiation antigen (CD14), and histidine-rich glycoprotein (HRG). There were significant associations between gender and C4B (Z = 2.31, P = .021), C1QB (Z = 2.49, P = .013), CD14 (Z = 2.17, P = .03), and HRG (Z = 2.14, P = .033). There were significant associations between smoking and LRG1 (χ(2)2 = 6.59, P = .037), CB4 (χ(2)2 = 7.85, P = .02), and HRG (χ(2)2 = 6.11, P = .047). All the peptides were significantly associated with advanced CAD stages, independently of age and smoking. However, the absence of the proteins was the strongest marker. The most accurate association with CAD was HRG (area under the receiver operating characteristic curve = 0.922), whereas LRG1, C4B, and C1QB were also associated with CAD (area under the receiver operating characteristic curve >0.9). For either coronary atherosclerosis or CAD, LRG1, C4B, C1QB, and HRG were relatively well associated. The present study has identified 6 novel protein biomarkers that are associated with more advanced stages of atherosclerotic disease and subsequent coronary events

  5. Family carers: A role in addressing chronic disease risk behaviours for people with a mental illness?

    Directory of Open Access Journals (Sweden)

    Jacqueline M. Bailey

    2017-09-01

    Full Text Available People with a mental illness experience greater chronic disease morbidity and mortality compared to those without mental illness. Family carers have the potential to promote the health behaviours of those they care for however factors which may influence the extent to which they do so have not been reported. An exploratory study was conducted to investigate carers': 1 promotion of fruit and vegetable consumption, physical activity, quitting smoking, and reducing alcohol consumption; 2 perceptions of their role and ability to promote such behaviours; 3 and the association between carer perceptions and the promotion of such behaviours. A cross-sectional survey was conducted with mental health carers (N = 144, 37.6% response rate in New South Wales, Australia in 2013. Associations between current promotion of health behaviours and carer perceptions were explored through multivariate regression analysis in 2016. A majority of respondents promoted fruit and vegetable consumption (63.8%, physical activity (60.3%, quitting smoking (56.3%, and reducing alcohol consumption (56.2% to the person they cared for. A perception that it was ‘very important’ to have a positive influence on these behaviours was positively related with promotion of each of the four behaviours, with those holding such a view being more likely to promote such behaviours, than those who did not (odds ratio: 9.47–24.13, p < 0.001. The majority (56.2%–63.8% of carers reported promoting the health behaviours of those they cared for, demonstrating a need and opportunity to build the capacity of carers to contribute to reducing the health risk behaviours among people with a mental illness.

  6. Primary prevention of cardiovascular diseases: a cost study in family practices

    Directory of Open Access Journals (Sweden)

    Verheij Robert A

    2011-07-01

    Full Text Available Abstract Background Considering the scarcity of health care resources and the high costs associated with cardiovascular diseases, we investigated the spending on cardiovascular primary preventive activities and the prescribing behaviour of primary preventive cardiovascular medication (PPCM in Dutch family practices (FPs. Methods A mixed methods design was used, which consisted of a questionnaire (n = 80 FPs, video recordings of hypertension- or cholesterol-related general practitioner visits (n = 56, and the database of Netherlands Information Network of General Practice (n = 45 FPs; n = 157,137 patients. The questionnaire and video recordings were used to determine the average frequency and time spent on cardiovascular primary preventive activities per FP respectively. Taking into account the annual income and full time equivalents of general practitioners, health care assistants, and practice nurses as well as the practice costs, the total spending on cardiovascular primary preventive activities in Dutch FPs was calculated. The database of Netherlands Information Network of General Practice was used to determine the prescribing behaviour in Dutch FPs by conducting multilevel regression models and adjusting for patient and practice characteristics. Results Total expenditure on cardiovascular primary preventive activities in FPs in 2009 was €38.8 million (€2.35 per capita, of which 47% was spent on blood pressure measurements, 26% on cardiovascular risk profiling, and 11% on lifestyle counselling. Fifteen percent (€11 per capita of all cardiovascular medication prescribed in FPs was a PPCM. FPs differed greatly on prescription of PPCM (odds ratio of 3.1. Conclusions Total costs of cardiovascular primary preventive activities in FPs such as blood pressure measurements and lifestyle counselling are relatively low compared to the costs of PPCM. There is considerable heterogeneity in prescribing behaviour of PPCM between FPs. Further research

  7. Different disease subtypes with distinct clinical expression in familial Mediterranean fever: results of a cluster analysis.

    Science.gov (United States)

    Akar, Servet; Solmaz, Dilek; Kasifoglu, Timucin; Bilge, Sule Yasar; Sari, Ismail; Gumus, Zeynep Zehra; Tunca, Mehmet

    2016-02-01

    The aim of this study was to evaluate whether there are clinical subgroups that may have different prognoses among FMF patients. The cumulative clinical features of a large group of FMF patients [1168 patients, 593 (50.8%) male, mean age 35.3 years (s.d. 12.4)] were studied. To analyse our data and identify groups of FMF patients with similar clinical characteristics, a two-step cluster analysis using log-likelihood distance measures was performed. For clustering the FMF patients, we evaluated the following variables: gender, current age, age at symptom onset, age at diagnosis, presence of major clinical features, variables related with therapy and family history for FMF, renal failure and carriage of M694V. Three distinct groups of FMF patients were identified. Cluster 1 was characterized by a high prevalence of arthritis, pleuritis, erysipelas-like erythema (ELE) and febrile myalgia. The dosage of colchicine and the frequency of amyloidosis were lower in cluster 1. Patients in cluster 2 had an earlier age of disease onset and diagnosis. M694V carriage and amyloidosis prevalence were the highest in cluster 2. This group of patients was using the highest dose of colchicine. Patients in cluster 3 had the lowest prevalence of arthritis, ELE and febrile myalgia. The frequencies of M694V carriage and amyloidosis were lower in cluster 3 than the overall FMF patients. Non-response to colchicine was also slightly lower in cluster 3. Patients with FMF can be clustered into distinct patterns of clinical and genetic manifestations and these patterns may have different prognostic significance. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  8. Prevalence of Cardiovascular Disease Risk Factors in Migrants Participating in the PEP Family Heart Study, Nuremberg.

    Science.gov (United States)

    Haas, Gerda-Maria; Parhofer, Klaus-Georg; Schwandt, Peter

    2010-01-01

    The aim of this study was to assess the prevalence of cardiovascular risk factors in adults and their children from the 3 major groups of migrants participating in the PEP Family Heart Study11 and to compare the cardio-metabolic risk profiles between migrants and German participants. In this community-based cross-sectional study, anthropometric data, blood pressure and lipid profiles of migrants (480 children, 363 adults) from Turkey (TUR), Eastern Europe (EEU) and German immigrants from the former Soviet Union (GFSU) were compared with age and gender adjusted German (GER) residents (3253 children, 2491 adults). The profile of risk factors differed considerably regarding specificity and frequency. The prevalence of ≥3 risk factors was as follows: in GFSU men 62%, women 36%, boys 19% and girls 17%; in TUR men 57%, women 30%, 15% boys and 6% girls; in GER men 48%, women 19%, boys 4% and girls 6%; for EEU men 38%, women 25% and 0% in children. No risk factor was present in GFSU men 13%, women 25%, boys 38% and girls 42%; TUR men 13%, women 28%, boys 27% and girls 22 %; GER men16%, women 45%, boys 46% and girls 41%; EEU men 17%, women 42 %, boys 29% and girls 27%. About 50% of the adults from Turkey and Eastern Europe were current smokers and one third of women and half of men from these two countries were overweight. The implementation of primary care measures for the prevention of cardiovascular disease in migrants is necessary, and it should consider the ethnic differences and the heterogeneous risk profiles.

  9. Prevalence of cardiovascular disease risk factors in migrants participating in the PEP family heart study, Nuremberg

    Directory of Open Access Journals (Sweden)

    Gerda-Maria Haas

    2010-01-01

    Full Text Available Objectives: The aim of this study was to assess the prevalence of cardiovascular risk factors in adults and their children from the 3 major groups of migrants participating in the PEP Family Heart Study [11] and to compare the cardio-metabolic risk profiles between migrants and German participants. Methods: In this community-based cross-sectional study, anthropometric data, blood pressure and lipid profiles of migrants (480 children, 363 adults from Turkey (TUR, Eastern Europe (EEU and German immigrants from the former Soviet Union (GFSU were compared with age and gender adjusted German (GER resi-dents (3253 children, 2491 adults. Results: The profile of risk factors differed considerably regarding specificity and frequency. The prevalence of ≥3 risk factors was as follows: in GFSU men 62%, women 36%, boys 19% and girls 17%; in TUR men 57%, women 30%, 15% boys and 6% girls; in GER men 48%, women 19%, boys 4% and girls 6%; for EEU men 38%, women 25% and 0% in children. No risk factor was present in GFSU men 13%, women 25%, boys 38% and girls 42%; TUR men 13%, women 28%, boys 27% and girls 22 %; GER men16%, women 45%, boys 46% and girls 41%; EEU men 17%, women 42 %, boys 29% and girls 27%. About 50% of the adults from Turkey and Eastern Europe were current smokers and one third of women and half of men from these two countries were over-weight. Conclusions: The implementation of primary care measures for the prevention of cardiovascular disease in migrants is necessary, and it should consider the ethnic differences and the heterogene-ous risk profiles.

  10. Prevalence of Cardiovascular Disease Risk Factors in Migrants Participating in the PEP Family Heart Study, Nuremberg

    Directory of Open Access Journals (Sweden)

    Gerda-Maria Haas

    2010-01-01

    Full Text Available Objectives: The aim of this study was to assess the prevalence of cardiovascularrisk factors in adults and their children from the 3 majorgroups of migrants participating in the PEP Family Heart Study 11 andto compare the cardio-metabolic risk profiles between migrants andGerman participants.Methods: In this community-based cross-sectional study, anthropometricdata, blood pressure and lipid profiles of migrants (480 children,363 adults from Turkey (TUR, Eastern Europe (EEU and Germanimmigrants from the former Soviet Union (GFSU were comparedwith age- and gender adjusted German (GER residents (3253 children,2491 adults.Results: The profile of risk factors differed considerably regardingspecificity and frequency. The prevalence of ≥3 risk factors was asfollows: in GFSU men 62%, women 36%, boys 19% and girls 17%; inTUR men 57%, women 30%, 15% boys and 6% girls; in GER men48%, women 19%, boys 4% and girls 6%; for EEU men 38%, women25% and 0% in children. No risk factor was present in GFSU men13%, women 25%, boys 38% and girls 42%; TUR men 13%, women28%, boys 27% and girls 22 %; GER men16%, women 45%, boys 46%and girls 41%; EEU men 17%, women 42 %, boys 29% and girls 27%.About 50% of the adults from Turkey and Eastern Europe were currentsmokers and one third of women and half of men from these twocountries were overweight.Conclusions: The implementation of primary care measures for theprevention of cardiovascular disease in migrants is necessary, and itshould consider the ethnic differences and the heterogeneous risk profiles

  11. Novel and recurrent NDP gene mutations in familial cases of Norrie disease and X-linked exudative vitreoretinopathy.

    Science.gov (United States)

    Pelcastre, Erika L; Villanueva-Mendoza, Cristina; Zenteno, Juan C

    2010-05-01

    To present the results of molecular analysis of the NDP gene in Mexican families with Norrie disease (ND) and X-linked familial exudative vitreoretinopathy (XL-FEVR). Two unrelated families with ND and two with XL-FEVR were studied. Clinical diagnosis was suspected on the basis of a complete ophthalmologic examination. Molecular methods included DNA isolation from peripheral blood leucocytes, polymerase chain reaction amplification and direct nucleotide sequencing analysis of the complete coding region and exon-intron junctions of NDP. Haplotype analysis using NDP-linked microsatellites markers was performed in both ND families. A novel Norrin missense mutation, p.Arg41Thr, was identified in two apparently unrelated families with ND. Haplotype analysis demonstrated that affected males in these two families shared the same ND-linked haplotype, suggesting a common origin for this novel mutation. The previously reported p.Arg121Trp and p.Arg121Gln Norrin mutations were identified in the two families with XL-FEVR. Our results expand the mutational spectrum in ND. This is the first report of ND resulting from mutation at arginine position 41 of Norrin. Interestingly, mutations at the same residue but resulting in a different missense change were previously described in subjects with XL-FEVR (p.Arg41Lys) or persistent fetal vasculature syndrome (p.Arg41Ser), indicating that the novel p.Arg41Thr change causes a more severe retinal phenotype. Preliminary data suggest a founder effect for the ND p.Arg41Thr mutation in these two Mexican families.

  12. Family history of neurodegenerative and vascular diseases in ALS: a population-based study

    NARCIS (Netherlands)

    Huisman, M.H.; Jong, S.W. de; Verwijs, M.C.; Schelhaas, H.J.; Kooi, A.J. van der; Visser, M. de; Veldink, J.H.; Berg, L.H. van den

    2011-01-01

    OBJECTIVE: To determine whether the frequency of Parkinson disease (PD), dementia, and vascular diseases in relatives of patients with amyotrophic lateral sclerosis (ALS) differs from the frequency of those diseases in relatives of controls, providing further information about the association

  13. A PROgramme of Lifestyle Intervention in Families for Cardiovascular risk reduction (PROLIFIC Study: design and rationale of a family based randomized controlled trial in individuals with family history of premature coronary heart disease

    Directory of Open Access Journals (Sweden)

    Panniyammakal Jeemon

    2017-01-01

    Full Text Available Abstract Background Recognizing patterns of coronary heart disease (CHD risk in families helps to identify and target individuals who may have the most to gain from preventive interventions. The overall goal of the study is to test the effectiveness and sustainability of an integrated care model for managing cardiovascular risk in high risk families. The proposed care model targets the structural and environmental conditions that predispose high risk families to development of CHD through the following interventions: 1 screening for cardiovascular risk factors, 2 providing lifestyle interventions 3 providing a framework for linkage to appropriate primary health care facility, and 4 active follow-up of intervention adherence. Methods Initially, a formative qualitative research component will gather information on understanding of diseases, barriers to care, specific components of the intervention package and feedback on the intervention. Then a cluster randomized controlled trial involving 740 families comprising 1480 participants will be conducted to determine whether the package of interventions (integrated care model is effective in reducing or preventing the progression of CHD risk factors and risk factor clustering in families. The sustainability and scalability of this intervention will be assessed through economic (cost-effectiveness analyses and qualitative evaluation (process outcomes to estimate value and acceptability. Scalability is informed by cost-effectiveness and acceptability of the integrated cardiovascular risk reduction approach. Discussion Knowledge generated from this trial has the potential to significantly affect new programmatic policy and clinical guidelines that will lead to improvements in cardiovascular health in India. Trial registration number NCT02771873, registered in May 2016 ( https://clinicaltrials.gov/ct2/show/results/NCT02771873

  14. Hypertrophic cardiomyopathy family with double-heterozygous mutations; does disease severity suggest doubleheterozygosity?

    NARCIS (Netherlands)

    van Rijsingen, I. A. W.; Hermans-van Ast, J. F.; Arens, Y. H. J. M.; Schalla, S. M.; de Die-Smulders, C. E. M.; van den Wijngaard, A.; Pinto, Y. M.

    2009-01-01

    Background. With the improvement in genetic testing over time, double-heterozygous mutations are more often found by coincidence in families with hypertrophic cardiomyopathy (HCM). Double heterozygosity can be a cause of the wellknown clinical diversity within HCM families.Methods and results. We

  15. Patients' and their family members' experiences of participation in care following an acute exacerbation in chronic obstructive pulmonary disease

    DEFF Research Database (Denmark)

    Andersen, Ingrid Charlotte; Thomsen, Thora Grothe; Bruun, Poul

    2017-01-01

    members were conducted on a Danish hospital ward and twice at the participants' homes. A phenomenological-hermeneutic approach inspired by Ricoeur's theory of interpretation guided the data analysis. RESULTS: Participation in care was perceived as valuable, but could be associated with tensions......AIM AND OBJECTIVES: To explore the experiences of patients with chronic obstructive pulmonary disease (COPD) and their family members relating to both participation in care during hospitalization for an acute exacerbation in COPD, and to the subsequent day-to-day care at home. BACKGROUND: When...... recovering from an exacerbation, the challenges associated with an unpredictable health condition dominate everyday life for patients and can involve their family members. Proper patient and family participation in care during discharge and follow-up can help patients to improve self-management. However...

  16. Subjective Experiences of an Art Museum Engagement Activity for Persons with Early Alzheimer’s disease and their Family Caregivers

    Science.gov (United States)

    Flatt, Jason D.; Liptak, Amy; Oakley, Mary Ann; Gogan, Jessica; Varner, Tresa; Lingler, Jennifer H.

    2014-01-01

    Objective To describe the subjective experiences of older adults with early-stage Alzheimer’s disease or related cognitive disorders (ADRD) and their family caregivers who participated in an art museum engagement activity. Methods Four focus groups were conducted with 10 persons with ADRD and 10 family caregivers following the completion one-time, three hour engagement activity. Participants also completed a brief satisfaction survey, and associations were examined using nonparametric statistics. Results Three key themes were identified: cognitive stimulation, social connections, and a sense of self. In addition, we identified programmatic issues such as activity-specific concerns and program logistics that could help improve future art program offerings. Past experience with art and perceived social cohesion were correlated with participants’ overall satisfaction with the program. Discussion Efforts aimed at improving the quality of life of those with Alzheimer’s and their family caregivers should consider the potential role of art museums. PMID:25216658

  17. A novel presenilin 1 mutation resulting in familial Alzheimer's disease with an onset age of 29 years.

    Science.gov (United States)

    Campion, D; Brice, A; Dumanchin, C; Puel, M; Baulac, M; De La Sayette, V; Hannequin, D; Duyckaerts, C; Michon, A; Martin, C; Moreau, V; Penet, C; Martinez, M; Clerget-Darpoux, F; Agid, Y; Frebourg, T

    1996-07-08

    We have identified a novel Alzheimer's disease family in which affected subjects had a very young age of onset (range 29-35 years). Neuropathological confirmation of the diagnosis was obtained for one patient. Molecular analysis shows that within this family the disease results from a missense mutation at codon 235 of the presenilin 1 (PS-1) gene. Two patients had exhibited generalized tonico-clonic seizures several years before the onset of dementia. Whether this particular clinical feature is a consequence of the PS-1 mutation remains to be established. The Leu235Pro mutation is, to our knowledge, the PS-1 mutation associated with the youngest age of AD onset, which suggests that it has a drastic effect on PS-1 function.

  18. Can family history and cord blood IgE predict sensitization and allergic diseases up to adulthood?

    DEFF Research Database (Denmark)

    Borrits Pagh Nissen, Susanne; Fomsgaard Kjær, Henrik; Høst, Arne

    2015-01-01

    used. RESULTS: A total of 455 infants were included, 188 with CB-IgE ≥0.5 kU/l and 267 with CB-IgE history and elevated CB-IgE were significantly associated to allergic disease until 26 yr. Concerning any allergic...... with high NPV and specificity, but low PPV and sensitivity. CONCLUSION: Although family history and elevated CB-IgE were significantly associated with primarily atopic disease until 26 yr, none of these were strong predictors for subsequent sensitization and allergic symptoms from childhood until early......BACKGROUND: Long-term studies of the predictive value of family history and cord blood IgE level until adulthood are few, and their conclusions have been contradictory. METHODS: Screening of total IgE in 1617 cord blood samples was performed in a Danish birth cohort. All infants with cord blood Ig...

  19. Variable expressivity and genetic heterogeneity involving DPT and SEMA3D genes in autosomal dominant familial Meniere's disease.

    Science.gov (United States)

    Martín-Sierra, Carmen; Gallego-Martinez, Alvaro; Requena, Teresa; Frejo, Lidia; Batuecas-Caletrío, Angel; Lopez-Escamez, Jose A

    2017-02-01

    Autosomal dominant (AD) familial Meniere's disease (FMD) is a rare disorder involving the inner ear defined by sensorineural hearing loss, tinnitus and episodic vertigo. Here, we have identified two novel and rare heterozygous variants in the SEMA3D and DPT genes segregating with the complete phenotype that have variable expressivity in two pedigrees with AD-FMD. A detailed characterization of the phenotype within each family illustrates the clinical heterogeneity in the onset and progression of the disease. We also showed the expression of both genes in the human cochlea and performed in silico analyses of these variants. Three-dimensional protein modelling showed changes in the structure of the protein indicating potential physical interactions. These results confirm a genetic heterogeneity in FMD with incomplete penetrance and variable expressivity.

  20. Family cord blood banking for sickle cell disease: a twenty-year experience in two dedicated public cord blood banks.

    Science.gov (United States)

    Rafii, Hanadi; Bernaudin, Françoise; Rouard, Helene; Vanneaux, Valérie; Ruggeri, Annalisa; Cavazzana, Marina; Gauthereau, Valerie; Stanislas, Aurélie; Benkerrou, Malika; De Montalembert, Mariane; Ferry, Christele; Girot, Robert; Arnaud, Cecile; Kamdem, Annie; Gour, Joelle; Touboul, Claudine; Cras, Audrey; Kuentz, Mathieu; Rieux, Claire; Volt, Fernanda; Cappelli, Barbara; Maio, Karina T; Paviglianiti, Annalisa; Kenzey, Chantal; Larghero, Jerome; Gluckman, Eliane

    2017-06-01

    Efforts to implement family cord blood banking have been developed in the past decades for siblings requiring stem cell transplantation for conditions such as sickle cell disease. However, public banks are faced with challenging decisions about the units to be stored, discarded, or used for other endeavors. We report here 20 years of experience in family cord blood banking for sickle cell disease in two dedicated public banks. Participants were pregnant women who had a previous child diagnosed with homozygous sickle cell disease. Participation was voluntary and free of charge. All mothers underwent mandatory serological screening. Cord blood units were collected in different hospitals, but processed and stored in two public banks. A total of 338 units were stored for 302 families. Median recipient age was six years (11 months-15 years). Median collected volume and total nucleated cell count were 91 mL (range 23-230) and 8.6×108 (range 0.7-75×108), respectively. Microbial contamination was observed in 3.5% (n=12), positive hepatitis B serology in 25% (n=84), and homozygous sickle cell disease in 11% (n=37) of the collections. Forty-four units were HLA-identical to the intended recipient, and 28 units were released for transplantation either alone (n=23) or in combination with the bone marrow from the same donor (n=5), reflecting a utilization rate of 8%. Engraftment rate was 96% with 100% survival. Family cord blood banking yields good quality units for sibling transplantation. More comprehensive banking based on close collaboration among banks, clinical and transplant teams is recommended to optimize the use of these units. Copyright© Ferrata Storti Foundation.

  1. Massively parallel sequencing and targeted exomes in familial kidney disease can diagnose underlying genetic disorders.

    Science.gov (United States)

    Mallett, Andrew J; McCarthy, Hugh J; Ho, Gladys; Holman, Katherine; Farnsworth, Elizabeth; Patel, Chirag; Fletcher, Jeffery T; Mallawaarachchi, Amali; Quinlan, Catherine; Bennetts, Bruce; Alexander, Stephen I

    2017-12-01

    Inherited kidney disease encompasses a broad range of disorders, with both multiple genes contributing to specific phenotypes and single gene defects having multiple clinical presentations. Advances in sequencing capacity may allow a genetic diagnosis for familial renal disease, by testing the increasing number of known causative genes. However, there has been limited translation of research findings of causative genes into clinical settings. Here, we report the results of a national accredited diagnostic genetic service for familial renal disease. An expert multidisciplinary team developed a targeted exomic sequencing approach with ten curated multigene panels (207 genes) and variant assessment individualized to the patient's phenotype. A genetic diagnosis (pathogenic genetic variant[s]) was identified in 58 of 135 families referred in two years. The genetic diagnosis rate was similar between families with a pediatric versus adult proband (46% vs 40%), although significant differences were found in certain panels such as atypical hemolytic uremic syndrome (88% vs 17%). High diagnostic rates were found for Alport syndrome (22 of 27) and tubular disorders (8 of 10), whereas the monogenic diagnostic rate for congenital anomalies of the kidney and urinary tract was one of 13. Quality reporting was aided by a strong clinical renal and genetic multidisciplinary committee review. Importantly, for a diagnostic service, few variants of uncertain significance were found with this targeted, phenotype-based approach. Thus, use of targeted massively parallel sequencing approaches in inherited kidney disease has a significant capacity to diagnose the underlying genetic disorder across most renal phenotypes. Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  2. A missense mutation (p.G274R) in gene ASPA causes Canavan disease in a Pakistani family.

    Science.gov (United States)

    Hussain, Rashida; Daud, Shakeela; Kakar, Naseebullah; Ahmad, Adeel; Baloch, Abdul Hameed; Tareen, Abdul Malik; Kakar, Muhammad Azam; Ahmad, Jamil

    2012-05-01

    Canavan disease (OMIM 271900) is an autosomal recessive lethal neurodegenerative disorder characterized by spongy degeneration of the brain. A highly consanguineous Pakistani family with Canavan disease was enrolled on the basis of diagnosis. All the affected individuals have mental retardation, megalocephaly and degradation of motor skills, poor head control, partial vision loss, weakness of the muscles and raised urinary concentration of N-acetyl aspartic acid in the urine. Blood samples were collected from affected as well as normal siblings and processed for DNA purification. Linkage analysis was performed by typing three short tandem repeat markers D17S1583 (7.19 cM), D17S1828 (10.02 cM) and D17S919 (14.69 cM) for an already-reported gene/locus ASPA at chromosome 17p13.2 causing Canavan disease. During linkage analysis, all the affected individuals were homozygous for short tandem repeat markers while the normal siblings were heterozygous showing co-segregation of the disease. Gene ASPA (NM_000049) was undertaken to sequence for mutation analysis. As a result of sequence analysis, we found missense substitution 740A→G (p.G274R) in exon 6 of gene ASPA. To our knowledge, this is the first report about Canavan disease on a Pakistani family.

  3. Family carers' experiences of receiving the news of a diagnosis of Motor Neurone Disease: A national survey.

    Science.gov (United States)

    Aoun, Samar M; Breen, Lauren J; Oliver, David; Henderson, Robert D; Edis, Robert; O'Connor, Margaret; Howting, Denise; Harris, Rodney; Birks, Carol

    2017-01-15

    Family carers have a central role in the care and support of people with MND and face the challenges of the disease from diagnosis to progression and the multiple losses of MND, but their support needs are often neglected. This study aimed to investigate the experiences of family carers at the time of diagnosis and their satisfaction with receiving the news. An anonymous postal survey was facilitated by all MND Associations in Australia (2014) and 190 family carers completed the questionnaire. The questions centred on the SPIKES protocol for communicating bad news. Two-thirds of family carers rated the skills of their neurologists as above average and were satisfied with the delivery of the diagnosis, in terms of having a significantly longer consultation time, the neurologist being warm and caring, satisfaction with the amount and content of information they received and relevant supports, and a plan for following up support. Conversely those who rated the neurologist's skills as below average commented on the difficulties they encountered and the long term emotional stress engendered by poor communication. The study emphasises previous research that suggested that neurologists may require education and training in communicating the diagnosis and this should include family carers as a vital member in MND care. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Caspase-6 Activation in Familial Alzheimer Disease Brains Carrying Amyloid Precursor Protein, Presenilin I or Presenilin II Mutations

    Science.gov (United States)

    Albrecht, Steffen; Bogdanovic, Nenad; Ghetti, Bernardino; Winblad, Bengt; LeBlanc, Andréa C.

    2010-01-01

    We previously demonstrated the activation of Caspase-6 in the hippocampus and cortex in cases of mild, moderate, severe and very severe Alzheimer disease (AD). To determine whether Caspase-6 is also activated in familial AD, we performed an immunohistochemical analysis of active Caspase-6 and Tau cleaved by Caspase-6 in temporal cortex and hippocampal tissue sections from cases of familial AD. The cases included 5 carrying the amyloid precursor protein K670N, M671L Swedish mutation, 1 carrying the amyloid precursor protein E693G Arctic mutation, 2 each carrying the Presenilin I M146V, F105L, A431E, V261F, Y115C mutations, and 1 with the Presenilin II N141I mutation. Active Caspase-6 immunoreactivity was found in all cases. Caspase-6 immunoreactivity was observed in neuritic plaques or cotton wool plaques in some cases, neuropil threads and neurofibrillary tangles. These results indicate that Caspase-6 is activated in familial forms of AD, as previously observed in sporadic forms. Since sporadic and familial AD cases have similar pathological features, these results support a fundamental role of Caspase-6 in the pathophysiology of both familial and sporadic AD. PMID:19915487

  5. R47H Variant of TREM2 Associated With Alzheimer Disease in a Large Late-Onset Family

    Science.gov (United States)

    Korvatska, Olena; Leverenz, James B.; Jayadev, Suman; McMillan, Pamela; Kurtz, Irina; Guo, Xindi; Rumbaugh, Malia; Matsushita, Mark; Girirajan, Santhosh; Dorschner, Michael O.; Kiianitsa, Kostantin; Yu, Chang-En; Brkanac, Zoran; Garden, Gwenn A.; Raskind, Wendy H.; Bird, Thomas D.

    2016-01-01

    Importance The R47H variant in the triggering receptor expressed on myeloid cells 2 gene (TREM2), a modulator of the immune response of microglia, is a strong genetic risk factor for Alzheimer disease (AD) and possibly other neurodegenerative disorders. Objective To investigate a large family with late-onset AD (LOAD), in which R47H cosegregated with 75% of cases. Design, Setting, and Participants This study includes genetic and pathologic studies of families with LOAD from 1985 to 2014. A total of 131 families with LOAD (751 individuals) were included from the University of Washington Alzheimer Disease Research Center. To identify LOAD genes/risk factors in the LOAD123 family with 21 affected members and 12 autopsies, we sequenced 4 exomes. Candidate variants were tested for cosegregation with the disease. TREM2 R47H was genotyped in an additional 130 families with LOAD. We performed clinical and neuropathological assessments of patients with and without R47H and evaluated the variant's effect on brain pathology, cellular morphology, and expression of microglial markers. Main Outcomes and Measures We assessed the effect of TREM2 genotype on age at onset and disease duration. We compared Braak and Consortium to Establish a Registry for Alzheimer's Disease scores, presence of α-synuclein and TAR DNA-binding protein 43 aggregates, and additional vascular or Parkinson pathology in TREM2 R47H carriers vs noncarriers. Microglial activation was assessed by quantitative immunohistochemistry and morphometry. Results Twelve of 16 patients with AD in the LOAD123 family carried R47H. Eleven patients with dementia had apolipoprotein E 4 (ApoE4) and R47H genotypes. We also found a rare missense variant, D353N, in a nominated AD risk gene, unc-5 homolog C (UNC5C), in 5 affected individuals in the LOAD123 family. R47H carriers demonstrated a shortened disease duration (mean [SD], 6.7 [2.8] vs 11.1 [6.6] years; 2-tailed t test; P = .04) and more frequent α-synucleinopathy. The

  6. Communication and Huntington's Disease: Qualitative Interviews and Focus Groups with Persons with Huntington's Disease, Family Members, and Carers

    Science.gov (United States)

    Hartelius, Lena; Jonsson, Maria; Rickeberg, Anneli; Laakso, Katja

    2010-01-01

    Background: As an effect of the cognitive, emotional and motor symptoms associated with Huntington's disease, communicative interaction is often dramatically changed. No study has previously included the subjective reports on this subject from individuals with Huntington's disease. Aims: To explore the qualitative aspects of how communication is…

  7. Immune regulatory functions of DOCK family proteins in health and disease.

    Science.gov (United States)

    Nishikimi, Akihiko; Kukimoto-Niino, Mutsuko; Yokoyama, Shigeyuki; Fukui, Yoshinori

    2013-09-10

    DOCK proteins constitute a family of evolutionarily conserved guanine nucleotide exchange factors (GEFs) for Rho family of GTPases. Although DOCK family proteins do not contain the Dbl homology domain typically found in GEFs, they mediate the GTP-GDP exchange reaction through DHR-2 domain. Accumulating evidence indicates that the DOCK proteins act as major GEFs in varied biological settings. For example, DOCK2, which is predominantly expressed in hematopoietic cells, regulates migration and activation of leukocytes through Rac activation. On the other hand, it was recently reported that mutations of DOCK8, another member of the DOCK family proteins, cause a combined immunodeficiency syndrome in humans. This article reviews the structure, functions and signaling of DOCK2 and DOCK8, especially focusing on their roles in immune responses. © 2013 Elsevier Inc. All rights reserved.

  8. A mutation at IVS1 + 5 of the von Hippel-Lindau gene resulting in intron retention in transcripts is not pathogenic in a patient with a tongue cancer?: case report

    Directory of Open Access Journals (Sweden)

    Asakawa Takeshi

    2012-03-01

    Full Text Available Abstract Background Von Hippel-Lindau disease (VHL is a dominantly inherited familial cancer syndrome predisposing the patient to a variety of malignant and benign neoplasms, most frequently hemangioblastoma, renal cell carcinoma, pheochromocytoma, and pancreatic tumors. VHL is caused by mutations of the VHL tumor suppressor gene on the short arm of chromosome 3, and clinical manifestations develop if both alleles are inactivated according to the two-hit hypothesis. VHL mutations are more frequent in the coding region and occur occasionally in the splicing region of the gene. Previously, we reported that the loss of heterozygosity (LOH of the VHL gene is common in squamous cell carcinoma tissues of the tongue. Case Presentation We describe a case of squamous cell carcinoma in the tongue caused by a point mutation in the splicing region of the VHL gene and discuss its association with VHL disease. Sequence analysis of DNA extracted from the tumor and peripheral blood of the patient with squamous cell carcinoma revealed a heterozygous germline mutation (c. 340 + 5 G > C in the splice donor sequence in intron 1 of the VHL gene. RT-PCR analysis of the exon1/intron1 junction in RNA from tumor tissue detected an unspliced transcript. Analysis of LOH using a marker with a heterozygous mutation of nucleotides (G or C revealed a deletion of the mutant C allele in the carcinoma tissues. Conclusions The fifth nucleotide G of the splice donor site of the VHL gene is important for the efficiency of splicing at that site. The development of tongue cancer in this patient was not associated with VHL disease because the mutation occurred in only a single allele of the VHL gene and that allele was deleted in tumor cells.

  9. The Diseases of the Medici Family and the Use of Phytotherapy

    OpenAIRE

    Donatella Lippi

    2007-01-01

    The Medici Project is a paleopathological and historico-medical research, based on the exhumation of corpses of the Medici Family buried in the Medici Chapels (Florence, San Lorenzo). The scientific research carried out on these remains permits us to reconstruct habits and causes of death of members of this famous family of Italian Renaissance. The comparison between the literary sources and the paleopathological evidence is also important to reconstruct different therapies. Physicians, who a...

  10. Characterization of a disease-causing Glu119-Lys mutation in the low-density lipoprotein receptor gene in two Danish families with heterozygous familial hypercholesterolemia

    DEFF Research Database (Denmark)

    Jensen, H K; Jensen, T G; Jensen, L G

    1994-01-01

    Mutations in the gene for the low-density lipoprotein receptor (LDL receptor) cause the autosomal dominant inherited disease familial hypercholesterolemia (FH). In 15 Danish patients with heterozygous FH we have screened exon 4 of the LDL receptor gene for point mutations and small rearrangements...... employing genomic DNA amplification and bidirectional solid-phase sequencing. Two subjects were found to be heterozygous for a guanine to adenine base substitution at nucleotide position 418 of the LDL receptor cDNA. This point mutation results in an amino acid change from glutamic acid to lysine at amino...... acid residue 119 in the third repeat of the cysteine-rich ligand binding domain of the mature LDL receptor. Disruption of LDL receptor function by the Glu119-Lys mutation was confirmed by site-directed mutagenesis and expression in COS-7 cells. By Western blotting the mutation was found to affect...

  11. Lipoprotein(a) as a risk factor for maternal cardiovascular disease mortality in kindreds with familial combined hyperlipidemia or familial hypertriglyceridemia.

    Science.gov (United States)

    Kim, H; Marcovina, S M; Edwards, K L; McKnight, B; Bradley, C M; McNeely, M J; Psaty, B M; Motulsky, A G; Austin, M A

    2001-09-01

    Most but not all epidemiologic studies have shown that lipoprotein(a) [Lp(a)] is a risk factor for cardiovascular disease (CVD). Lp(a) levels are also strongly genetically influenced. The purpose of this study was to evaluate the association between Lp(a) levels in adult offspring and parental CVD mortality in 61 kindreds with familial forms of hyperlipidemia. The study sample consisted of offspring-parent pairs in which offspring had fasting Lp(a) measurements and parents had 20-year vital status data and standardized cause-of-death classification if deceased. Linear regression analyses, using a robust variance estimator, were performed separately for 241 offspring with known maternal history (114 mothers) and 194 offspring with known paternal history (93 fathers). Maternal history of CVD mortality was significantly (p=0.004) associated with 2.4-fold higher median Lp(a) levels in offspring compared with those with no maternal history, independent of diabetes, lipid-lowering medications and hormone use. No association was observed between paternal CVD mortality and offspring Lp(a) levels (p=0.505). Adjusting for apolipoprotein(a) kringle 4 number did not alter these parent-specific associations. In conclusion, Lp(a) levels in offspring may be associated with maternal but not paternal history of CVD mortality. This parent-specific finding needs to be confirmed in other samples of high-risk families.

  12. PKD2 mutation in an Iranian autosomal dominant polycystic kidney disease family with misleading linkage analysis data.

    Science.gov (United States)

    Entezam, Mona; Khatami, Mohammad Reza; Saddadi, Fereshteh; Ayati, Mohsen; Roozbeh, Jamshid; Keramatipour, Mohammad

    2016-06-01

    Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic renal disorder caused by mutation in 2 genes PKD1 and PKD2. Thus far, no mutation is identified in approximately 10% of ADPKD families, which can suggest further locus heterogeneity. Owing to the complexity of direct mutation detection, linkage analysis can initially identify the responsible gene in appropriate affected families. Here, we evaluated an Iranian ADPKD family apparently unlinked to both PKD1 and PKD2 genes. This is one of the pioneer studies in genetic analysis of ADPKD in Iranian population. Linkage reanalysis was performed by regenotyping of flanking microsatellite markers in 8 individuals of the ADPKD family. Direct mutation analysis was performed by Sanger sequencing. Mutation analysis revealed a pathogenic mutation (c.1094+1G>A) in the PKD2 gene in the proband. Analyzing 2 healthy and 4 clinically affected members confirmed the correct segregation of the mutation within the family and also ruled out the disease in 1 suspected individual. Misinterpretation of the linkage data was due to the occurrence of 1 crossing over between the PKD2 intragenic and the nearest downstream marker (D4S2929). Homozygosity of upstream markers caused the recombination indistinguishable. Although analysis of additive informative polymorphic markers can overcome the misleading haplotype data, it is limited because of the lack of other highly polymorphic microsatellite markers closer to the gene. Direct mutation screening can identify the causative mutation in the apparently unlinked pedigree; moreover, it is the only approach to achieve the confirmed diagnosis in individuals with equivocal imaging results.

  13. Profile of diseases prevalent in a tribal locality in Jharkhand, India: A family medicine practitioner′s perspective

    Directory of Open Access Journals (Sweden)

    Sumit Kumar

    2015-01-01

    Full Text Available Background: Majority of Indian population is dependent on general practitioners (GPs for medical services at primary care level in India. They are most preferred and considered to be first contact person for medical services at primary care level. But advances in medical science has put more emphasis on specialist culture and average Bachelor of Medicine and Bachelor of Surgery (MBBS graduates who are working as general physician are gradually feeling themselves less competent because they are less exposed to latest advances in treatment of diseases. Amidst such scenario, Christian Medical College (CMC has come up with an idea: "The refer less and resolve more initiative". It has started a decentralized 2-year family medicine distance diploma course (Postgraduate Diploma in Family Medicine (PGDFM now accredited by Dr. MGR Medical University, Chennai, Tamil Nadu, that trains the GPs to become family medicine specialist. Materials and Methods: As component of PGDFM course, this study was conducted to provide better understanding of prevalent ailments and common treatment provided by the GPs in the community at present giving key insight of current practice in rural area by a registered family medicine practitioner. Results: As part of study, among 500 patients evaluated, three most common diagnosis were upper respiratory infections (URIs; 18%, acute gastroenteritis including water-borne diseases (15.8%, and anemia (10.4%. Treatment given to these patients comprised of mostly of antipyretic, analgesic, and antimicrobial agents. Most common drug prescribed was paracetamol for fever. Other common drugs prescribed were amoxicillin/clavulanic acid, chloroquine, artemisin derivative, doxycycline, co-trimoxazole, miltefosine, cephalexin, ceftriaxone sodium, cefixime, oral rehydration salts, ranitidine, omeprazole, pantoprazole, metronidazole, albendazole, ondansetron, diclofenac sodium, piroxicam, ibuprofen, diphenhydramine, codeine-sulfate, amlodipine

  14. Family history of neurodegenerative and vascular diseases in ALS: a population-based study

    NARCIS (Netherlands)

    Huisman, M. H. B.; de Jong, S. W.; Verwijs, M. C.; Schelhaas, H. J.; van der Kooi, A. J.; de Visser, M.; Veldink, J. H.; van den Berg, L. H.

    2011-01-01

    To determine whether the frequency of Parkinson disease (PD), dementia, and vascular diseases in relatives of patients with amyotrophic lateral sclerosis (ALS) differs from the frequency of those diseases in relatives of controls, providing further information about the association between these

  15. Autosomal dominant polycystic liver disease in a family without polycystic kidney disease associated with a novel missense protein kinase C substrate 80K-H mutation.

    Science.gov (United States)

    Peces, Ramón; Drenth, Joost P H; Te Morsche, Rene H M; González, Pedro; Peces, Carlos

    2005-12-28

    Polycystic liver disease (PLD) is characterized by the presence of multiple bile duct-derived epithelial cysts scattered in the liver parenchyma. PLD can manifest itself in patients with severe autosomal dominant polycystic kidney disease (ADPKD). Isolated autosomal dominant polycystic liver disease (ADPLD) is genetically distinct from PLD associated with ADPKD, although it may have similar pathogenesis and clinical manifestations. Recently, mutations in two causative genes for ADPLD, independently from ADPKD, have been identified. We report here a family (a mother and her daughter) with a severe form of ADPLD not associated with ADPKD produced by a novel missense protein kinase C substrate 80K-H (PRKCSH) mutation (R281W). This mutation causes a severe phenotype, since the two affected subjects manifested signs of portal hypertension. Doppler sonography, computed tomography (CT) and magnetic resonance (MR) imaging are effective in documenting the underlying lesions in a non-invasive way.

  16. Individual and family strengths: an examination of the relation to disease management and metabolic control in youth with type 1 diabetes.

    Science.gov (United States)

    Mackey, Eleanor Race; Hilliard, Marisa E; Berger, Sarah Shafer; Streisand, Randi; Chen, Rusan; Holmes, Clarissa

    2011-12-01

    We examined the association of youths' positive qualities, family cohesion, disease management, and metabolic control in Type 1 diabetes. Two-hundred fifty-seven youth-parent dyads completed the Family Cohesion subscale of the Family Environment Scale, the Diabetes Behavior Rating Scale, 24-hour diabetes interview, and youth completed the Positive Qualities subscale of the Youth Self Report (YSR-PQ). Structural equation modeling demonstrated that YSR-PQ scores were associated with metabolic control mediated by associations with more family cohesion and better disease management. That is, youth with higher YSR-PQ scores had more cohesive families, better disease management, and, indirectly, better metabolic control. Family cohesion was indirectly associated with better metabolic control mediated by its association with better disease management, but not mediated by its association with YSR-PQ scores. Youth who reported more positive qualities, as measured by the YSR-PQ subscale, had better disease management and metabolic control through the association with more family cohesion. However, the current results did not support an alternative hypothesis that cohesive families display better diabetes management mediated by higher YSR-PQ scores.

  17. Rare Germline Copy Number Variations and Disease Susceptibility in Familial Melanoma.

    Science.gov (United States)

    Shi, Jianxin; Zhou, Weiyin; Zhu, Bin; Hyland, Paula L; Bennett, Hunter; Xiao, Yanzi; Zhang, Xijun; Burke, Laura S; Song, Lei; Hsu, Chih Hao; Yan, Chunhua; Chen, Qingrong; Meerzaman, Daoud; Dagnall, Casey L; Burdette, Laurie; Hicks, Belynda; Freedman, Neal D; Chanock, Stephen J; Yeager, Meredith; Tucker, Margaret A; Goldstein, Alisa M; Yang, Xiaohong R

    2016-12-01

    Mounting evidence suggests that copy number variations (CNVs) can contribute to cancer susceptibility. The main goal of this study was to evaluate the role of germline CNVs in melanoma predisposition in high-risk melanoma families. We used genome-wide tiling comparative genomic hybridization and single nucleotide polymorphism arrays to characterize CNVs in 335 individuals (240 melanoma cases) from American melanoma-prone families (22 with germline CDKN2A or CDK4 mutations). We found that the global burden of overall CNVs (or deletions or duplications separately) was not significantly associated with case-control or CDKN2A/CDK4 mutation status after accounting for the familial dependence. However, we identified several rare CNVs that either involved known melanoma genes (e.g., PARP1, CDKN2A) or cosegregated with melanoma (duplication on 10q23.23, 3p12.2 and deletions on 8q424.3, 2q22.1) in families without mutations in known melanoma high-risk genes. Some of these CNVs were correlated with expression changes in disrupted genes based on RNASeq data from a subset of melanoma cases included in the CNV study. These results suggest that rare cosegregating CNVs may influence melanoma susceptibility in some melanoma-prone families and genes found in our study warrant further evaluation in future genetic analyses of melanoma. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  18. Missed opportunities in primary care: the importance of identifying depression through screening, family history, and chronic disease management.

    Science.gov (United States)

    Maradiegue, Ann H; Khan, Fakiha

    2013-02-01

    This study explored the adequacy of depression screening in a community health center. The medical charts of individuals (N = 90) enrolled at a community health center were randomly selected, reviewed, and compared to current standard-of-care guidelines for four elements: family history, screening for depression, control of chronic illnesses, and missed opportunities for preventive care. Family history documentation collected by the providers was limited and 44.4% had no family history. There was no routine depression screening process, although 48.9% of the clients had red flags (warning signals) for depression. Laboratory values used for screening control of chronic disease in the medical records were: fasting glucose levels ⩽100 mg/dL (46%), total cholesterol levels ⩽200 mg/dL (38%), and blood pressure ⩽120/80 mmHg (23%). The results highlight the need to focus on depression screening as part of preventive care and the management of chronic disease in the primary care setting. Copyright 2013, SLACK Incorporated.

  19. The diseases of the medici family and the use of phytotherapy.

    Science.gov (United States)

    Lippi, Donatella

    2007-09-01

    The Medici Project is a paleopathological and historico-medical research, based on the exhumation of corpses of the Medici Family buried in the Medici Chapels (Florence, San Lorenzo). The scientific research carried out on these remains permits us to reconstruct habits and causes of death of members of this famous family of Italian Renaissance. The comparison between the literary sources and the paleopathological evidence is also important to reconstruct different therapies. Physicians, who assisted the most important persons of the Medici Family, have left a rich literature about their patients: the treatments were based on the use of plants and natural substances. Analyzing these sources is of unique importance and throws light on the therapeutical choices of the time.

  20. The Diseases of the Medici Family and the Use of Phytotherapy

    Directory of Open Access Journals (Sweden)

    Donatella Lippi

    2007-01-01

    Full Text Available The Medici Project is a paleopathological and historico-medical research, based on the exhumation of corpses of the Medici Family buried in the Medici Chapels (Florence, San Lorenzo. The scientific research carried out on these remains permits us to reconstruct habits and causes of death of members of this famous family of Italian Renaissance. The comparison between the literary sources and the paleopathological evidence is also important to reconstruct different therapies. Physicians, who assisted the most important persons of the Medici Family, have left a rich literature about their patients: the treatments were based on the use of plants and natural substances. Analyzing these sources is of unique importance and throws light on the therapeutical choices of the time.

  1. Association between the Family Nutrition and Physical Activity screening tool and cardiovascular disease risk factors in 10-year old children

    Science.gov (United States)

    Yee, Kimbo Edward

    Purpose. To examine the association of the Family Nutrition and Physical Activity (FNPA) screening tool, a behaviorally based screening tool designed to assess the obesogenic family environment and behaviors, with cardiovascular disease (CVD) risk factors in 10-year old children. Methods. One hundred nineteen children were assessed for body mass index (BMI), percent body fat (%BF), waist circumference (WC), total cholesterol, HDL-cholesterol, and resting blood pressure. A continuous CVD risk score was created using total cholesterol to HDL-cholesterol ratio (TC:HDL), mean arterial pressure (MAP), and WC. The FNPA survey was completed by parents. The associations between the FNPA score and individual CVD risk factors and the continuous CVD risk score were examined using correlation analyses. Results. Approximately 35% of the sample were overweight (19%) or obese (16%). The mean FNPA score was 24.6 +/- 2.5 (range 18 to 29). Significant correlations were found between the FNPA score and WC (r = -.35, prisk score (r = -.22, p = .02). No significant association was found between the FNPA score and TC:HDL (r=0.10, p=0.88) or MAP (r=-0.12, p=0.20). Conclusion. Children from a high-risk, obesogenic family environment as indicated with a lower FNPA score have a higher CVD risk factor profile than children from a low-risk family environment.

  2. Endolymphatic sac tumour in von Hippel-Lindau disease: management strategies.

    Science.gov (United States)

    Zanoletti, E; Girasoli, L; Borsetto, D; Opocher, G; Mazzoni, A; Martini, A

    2017-10-01

    Endolymphatic sac tumour (ELST) is infrequent, as emerges from small series reported in the literature. It is a slow-growing malignancy with local aggressiveness and a low risk of distant metastases. It is often misdiagnosed because of the late onset of symptoms and difficulty in obtaining a biopsy. Its frequency is higher in von Hippel-Lindau (VHL) disease (a genetic systemic syndrome involving multiple tumours), with a prevalence of around 25%. The diagnosis is based on radiology, with specific patterns on contrast-enhanced MRI and typical petrous bone erosion on bone CT scan. Our experience of ELST in the years between 2012-2015 concerns 7 cases, one of which was bilateral, in patients with VHL disease. Four of the 7 patients underwent 5 surgical procedures at our institution. Each case is described in detail, including clinical symptoms, and the intervals between symptom onset, diagnosis and therapy. Postoperative morbidity was low after early surgery on small tumours, whereas extensive surgery for large tumours was associated with loss of cranial nerve function (especially VII, IX, X). The critical sites coinciding with loss of neurological function were the fallopian canal, jugular foramen, petrous apex and intradural extension into the posterior cranial fossa. Early surgery on small ELST is advocated for patients with VHL disease, in whom screening enables a prompt diagnosis and consequently good prognosis. © Copyright by Società Italiana di Otorinolaringologia e Chirurgia Cervico-Facciale, Rome, Italy.

  3. Two Siblings with Familial Chylomicronemia Syndrome: Disease Course and Effectiveness of Early Treatment

    Directory of Open Access Journals (Sweden)

    Hanan AL Azkawi

    2010-01-01

    Full Text Available There are no adequate data that evaluate the safety and effectiveness of lowering triglyceride levels in very young children. The authors report a family with two male siblings, 7 and 4 years old, affected by familial hyperchylomicronemia. The oldest was diagnosed at birth during evaluation of jaundice, and the youngest showed asymptomatic hypertriglyceridemia by 6 months of age. Due to high triglyceride levels, Gemfibrozil (a fibric acid derivative was started at diagnosis. Close clinical followup and laboratory monitoring of these children showed no side effects from the drug, and the risk of acute pancreatitis was significantly reduced.

  4. Familial Alzheimer’s disease modelling using induced pluripotent stem cell technology

    OpenAIRE

    Mohamet, Lisa; Miazga, Natalie J; Ward, Christopher M.

    2014-01-01

    Alzheimer’s disease (AD) is a progressive neurodegenerative disease in which patients exhibit gradual loss of memory that impairs their ability to learn or carry out daily tasks. Diagnosis of AD is difficult, particularly in early stages of the disease, and largely consists of cognitive assessments, with only one in four patients being correctly diagnosed. Development of novel therapeutics for the treatment of AD has proved to be a lengthy, costly and relatively unproductive process with attr...

  5. Dientamoeba fragilis: a family cluster of disease associated with marked peripheral eosinophilia.

    Science.gov (United States)

    Gray, Timothy James; Kwan, Yiu L; Phan, Thuy; Robertson, Graham; Cheong, Elaine Y L; Gottlieb, Thomas

    2013-09-01

    Dientamoeba fragilis has emerged as an important and underrecognized cause of gastrointestinal illness. We report a familial cluster of D. fragilis associated with marked peripheral eosinophilia and gastrointestinal symptoms. Dientamoeba fragilis infection should be considered in the setting of unexplained eosinophilia. If confirmed, screening of household members should be considered.

  6. [Information for family members with an increased risk for a genetic disease

    NARCIS (Netherlands)

    Gordijn, B.

    2006-01-01

    After a genetic diagnosis a physician might deem it important to inform family members of his counselee who might have an increased risk of having a certain genetic predisposition. Against this background this contribution analyzes the following ethical questions: 1. To what extent is the physician

  7. Pityriasis Rotunda: A Case Report of Familial Disease in an American-Born Black Patient

    Directory of Open Access Journals (Sweden)

    Emily G. Lefkowitz

    2016-03-01

    Full Text Available Pityriasis rotunda is an uncommon dermatosis with an unusual geographic and racial distribution. The skin disorder is characterized by sharply defined, perfectly circular, scaly patches with no inflammatory changes. Notably, it may be associated with underlying malignancy or chronic infection. We report an uncommon familial case in an American-born female.

  8. Autoimmune disease in individuals and close family members and susceptibility to non-Hodgkin's lymphoma

    DEFF Research Database (Denmark)

    Mellemkjaer, Lene; Pfeiffer, Ruth M; Engels, Eric A

    2008-01-01

    Rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and Sjögren's syndrome have been consistently associated with an increased risk of non-Hodgkin's lymphoma (NHL). This study was initiated to evaluate the risks of NHL associated with a personal or family history of a wide range...

  9. Identification of a novel mutation in the CLCN5 gene in a Chinese family with Dent-1 disease.

    Science.gov (United States)

    Zhang, Hao; Wang, Chun; Yue, Hua; Hu, Wei-Wei; Gu, Jie-Mei; He, Jin-Wei; Fu, Wen-Zhen; Liu, Yu-Juan; Zhang, Zeng; Zhang, Zhen-Lin

    2014-02-01

    Dent disease comprises a group of X-linked recessive inherited renal tubular disorders, the symptoms of which include low-molecular-weight proteinuria (LMWP), hypercalciuria, nephrocalcinosis, and progressive renal failure. We sought to characterize the clinical manifestations and to identify the mutations associated with this disease in Chinese patients. In total, 155 DNA samples were collected from one affected individual, four of his family members, and 150 healthy donors. All 12 exons and the exon-intron boundaries of the CLCN5 gene were amplified and directly sequenced in this Chinese family. The proband demonstrated osteomalacia, which had resulted in more than 10 fractures, LMWP, and renal failure. A single base 'G' deletion at nucleotide 246 (c. 246delG) was identified in exon 5 of the CLCN5 gene in this patient, resulting in a frame shift mutation (fsX) that changed the Threonine (Thr) residue in position 83 to Proline (Pro). The proband's mother was found to be a carrier of this mutation. The present study suggests that a novel frameshift mutation (c. 246delG) in exon 5 of the CLCN5 gene is responsible for Dent disease in this case. Our findings also expand the known spectrum of CLCN5 mutations. © 2014 Asian Pacific Society of Nephrology.

  10. A novel presenilin 1 mutation (Ala275Val) as cause of early-onset familial Alzheimer disease.

    Science.gov (United States)

    Luedecke, Daniel; Becktepe, Jos S; Lehmbeck, Jan T; Finckh, Ulrich; Yamamoto, Raina; Jahn, Holger; Boelmans, Kai

    2014-04-30

    Mutations in the presenilin 1 (PS1) gene (PSEN1) are associated with familial Alzheimer disease (FAD). Here, we report on a 50-year-old patient presenting with progressive deterioration of his short-term memory and a family history of early-onset dementia. Diagnostic workup included a neuropsychological examination, structural magnetic resonance (MR) imaging, cerebrospinal fluid (CSF) biomarkers including total tau, phosphorylated tau, and Aβ42 levels, as well as sequencing relevant fragments of the genes PSEN1, PSEN2, and APP. Additionally, we were able to obtain archival paraffin-embedded cerebellar tissue from the patient's father for cosegregation analysis. Clinical, neuropsychological and MR imaging data were indicative of early-onset Alzheimer disease. Furthermore, CSF biomarkers showed a typical pattern for Alzheimer disease. DNA sequencing revealed a heterozygous nucleotide transition (c.824C>T) in exon 8 of PSEN1, leading to an amino acid change from alanine to valine at codon 275 (Ala275Val). The same mutation was found in an archival brain specimen of the patient's demented father, but not in a blood sample of the non-demented mother. This mutation alters a conserved residue in the large hydrophilic loop of PS1, suggesting pathogenic relevance. Cosegregegation analysis and the structural as well as the presumed functional role of the mutated and highly conserved residue suggest FAD causing characteristics of the novel PSEN1 mutation Ala275Val. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  11. Development and Implementation of Nonpharmacologic Protocols for the Management of Patients with Alzheimer's Disease and Their Families in a Multiracial Primary Care Setting

    Science.gov (United States)

    Austrom, Mary Guerriero; Damush, Teresa M.; Hartwell, Cora West; Perkins, Tony; Unverzagt, Frederick; Boustani, Malaz; Hendrie, Hugh C.; Callahan, Christopher M.

    2004-01-01

    Purpose. Most patients and families with dementia are cared for in primary care clinics. These clinics are seldom designed to provide the necessary comprehensive care. The purpose of this article is to describe nonpharmacologic protocols for the management of patients with Alzheimer's disease and their families that are administered as part of a…

  12. Familial breast cancer: collaborative reanalysis of individual data from 52 epidemiological studies including 58,209 women with breast cancer and 101,986 women without the disease

    NARCIS (Netherlands)

    Collaborative Group on Hormona, l Factors; van den Brandt, P.A.; Goldbohm, R.A.

    2001-01-01

    Familial breast cancer: collaborative reanalysis of individual data from 52 epidemiological studies including 58,209 women with breast cancer and 101,986 women without the disease. Collaborative Group on Hormonal Factors in Breast Cancer. BACKGROUND: Women with a family history of breast cancer are

  13. Genome-enabled selection doubles the accuracy of predicted breeding values for bacterial cold water disease resistance compared to traditional family-based selection in rainbow trout aquaculture

    Science.gov (United States)

    We have shown previously that bacterial cold water disease (BCWD) resistance in rainbow trout can be improved using traditional family-based selection, but progress has been limited to exploiting only between-family genetic variation. Genomic selection (GS) is a new alternative enabling exploitation...

  14. Whole genome sequencing of an African American family highlights toll like receptor 6 variants in Kawasaki disease susceptibility.

    Directory of Open Access Journals (Sweden)

    Jihoon Kim

    Full Text Available Kawasaki disease (KD is the most common acquired pediatric heart disease. We analyzed Whole Genome Sequences (WGS from a 6-member African American family in which KD affected two of four children. We sought rare, potentially causative genotypes by sequentially applying the following WGS filters: sequence quality scores, inheritance model (recessive homozygous and compound heterozygous, predicted deleteriousness, allele frequency, genes in KD-associated pathways or with significant associations in published KD genome-wide association studies (GWAS, and with differential expression in KD blood transcriptomes. Biologically plausible genotypes were identified in twelve variants in six genes in the two affected children. The affected siblings were compound heterozygous for the rare variants p.Leu194Pro and p.Arg247Lys in Toll-like receptor 6 (TLR6, which affect TLR6 signaling. The affected children were also homozygous for three common, linked (r2 = 1 intronic single nucleotide variants (SNVs in TLR6 (rs56245262, rs56083757 and rs7669329, that have previously shown association with KD in cohorts of European descent. Using transcriptome data from pre-treatment whole blood of KD subjects (n = 146, expression quantitative trait loci (eQTL analyses were performed. Subjects homozygous for the intronic risk allele (A allele of TLR6 rs56245262 had differential expression of Interleukin-6 (IL-6 as a function of genotype (p = 0.0007 and a higher erythrocyte sedimentation rate at diagnosis. TLR6 plays an important role in pathogen-associated molecular pattern recognition, and sequence variations may affect binding affinities that in turn influence KD susceptibility. This integrative genomic approach illustrates how the analysis of WGS in multiplex families with a complex genetic disease allows examination of both the common disease-common variant and common disease-rare variant hypotheses.

  15. Familial isolated primary pigmented nodular adrenocortical disease associated with a novel low penetrance PRKAR1A gene splice site mutation

    DEFF Research Database (Denmark)

    Storr, Helen L; Metherell, Louise A; Dias, Renuka

    2010-01-01

    Primary pigmented nodular adrenocortical disease (PPNAD) is associated with inactivating germline protein kinase A regulatory subunit type 1-alpha (PRKAR1A) mutations and loss of heterozygosity at the 17q22-24 locus in approximately 50% patients. PRKAR1A mutations are observed in both isolated PP...... PPNAD (iPPNAD) and Carney complex (CNC). Most mutations result in a functionally null-allele and exhibit high penetrance. We genotyped members of an extended family for a novel PRKAR1A mutation and undertook detailed phenotyping for CNC in the affected individuals....

  16. Bactericidal/Permeability-increasing protein fold-containing family member A1 in airway host protection and respiratory disease.

    Science.gov (United States)

    Britto, Clemente J; Cohn, Lauren

    2015-05-01

    Bactericidal/permeability-increasing protein fold-containing family member A1 (BPIFA1), formerly known as SPLUNC1, is one of the most abundant proteins in respiratory secretions and has been identified with increasing frequency in studies of pulmonary disease. Its expression is largely restricted to the respiratory tract, being highly concentrated in the upper airways and proximal trachea. BPIFA1 is highly responsive to airborne pathogens, allergens, and irritants. BPIFA1 actively participates in host protection through antimicrobial, surfactant, airway surface liquid regulation, and immunomodulatory properties. Its expression is modulated in multiple lung diseases, including cystic fibrosis, chronic obstructive pulmonary disease, respiratory malignancies, and idiopathic pulmonary fibrosis. However, the role of BPIFA1 in pulmonary pathogenesis remains to be elucidated. This review highlights the versatile properties of BPIFA1 in antimicrobial protection and its roles as a sensor of environmental exposure and regulator of immune cell function. A greater understanding of the contribution of BPIFA1 to disease pathogenesis and activity may clarify if BPIFA1 is a biomarker and potential drug target in pulmonary disease.

  17. Herpesviruses dUTPases: A New Family of Pathogen-Associated Molecular Pattern (PAMP Proteins with Implications for Human Disease

    Directory of Open Access Journals (Sweden)

    Marshall V. Williams

    2016-12-01

    Full Text Available The human herpesviruses are ubiquitous viruses and have a prevalence of over 90% in the adult population. Following a primary infection they establish latency and can be reactivated over a person’s lifetime. While it is well accepted that human herpesviruses are implicated in numerous diseases ranging from dermatological and autoimmune disease to cancer, the role of lytic proteins in the pathophysiology of herpesvirus-associated diseases remains largely understudies. Only recently have we begun to appreciate the importance of lytic proteins produced during reactivation of the virus, in particular the deoxyuridine triphosphate nucleotidohydrolases (dUTPase, as key modulators of the host innate and adaptive immune responses. In this review, we provide evidence from animal and human studies of the Epstein–Barr virus as a prototype, supporting the notion that herpesviruses dUTPases are a