E2-EPF UCP regulates stability and functions of missense mutant pVHL via ubiquitin mediated proteolysis.

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Park, Kyeong-Su; Kim, Ju Hee; Shin, Hee Won; Chung, Kyung-Sook; Im, Dong-Soo; Lim, Jung Hwa; Jung, Cho-Rok

2015-10-26

Missense mutation of VHL gene is frequently detected in type 2 VHL diseases and linked to a wide range of pVHL functions and stability. Certain mutant pVHLs retain ability to regulate HIFs but lose their function by instability. In this case, regulating of degradation of mutant pVHLs, can be postulated as therapeutic method. The stability and cellular function of missense mutant pVHLs were determine in HEK293T transient expressing cell and 786-O stable cell line. Ubiquitination assay of mutant VHL proteins was performed in vitro system. Anticancer effect of adenovirus mediated shUCP expressing was evaluated using ex vivo mouse xenograft assay. Three VHL missense mutants (V155A, L158Q, and Q164R) are directly ubiquitinated by E2-EPF UCP (UCP) in vitro. Mutant pVHLs are more unstable than wild type in cell. Missense mutant pVHLs interact with UCP directly in both in vitro and cellular systems. Lacking all of lysine residues of pVHL result in resistance to ubiquitination thereby increase its stability. Missense mutant pVHLs maintained the function of E3 ligase to ubiquitinate HIF-1α in vitro. In cells expressing mutant pVHLs, Glut-1 and VEGF were relatively upregulated compared to their levels in cells expressing wild-type. Depletion of UCP restored missense mutant pVHLs levels and inhibited cell growth. Adenovirus-mediated shUCP RNA delivery inhibited tumor growth in ex vivo mouse xenograft model. These data suggest that targeting of UCP can be one of therapeutic method in type 2 VHL disease caused by unstable but functional missense mutant pVHL.

VHL Frameshift Mutation as Target of Nonsense-Mediated mRNA Decay in Drosophila melanogaster and Human HEK293 Cell Line

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Lucia Micale

2009-01-01

Full Text Available There are many well-studied examples of human phenotypes resulting from nonsense or frameshift mutations that are modulated by Nonsense-Mediated mRNA Decay (NMD, a process that typically degrades transcripts containing premature termination codons (PTCs in order to prevent translation of unnecessary or aberrant transcripts. Different types of germline mutations in the VHL gene cause the von Hippel-Lindau disease, a dominantly inherited familial cancer syndrome with a marked phenotypic variability and age-dependent penetrance. By generating the Drosophila UAS:Upf1D45B line we showed the possible involvement of NMD mechanism in the modulation of the c.172delG frameshift mutation located in the exon 1 of Vhl gene. Further, by Quantitative Real-time PCR (QPCR we demonstrated that the corresponding c.163delG human mutation is targeted by NMD in human HEK 293 cells. The UAS:Upf1D45B line represents a useful system to identify novel substrates of NMD pathway in Drosophila melanogaster. Finally, we suggest the possible role of NMD on the regulation of VHL mutations.

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

the international diagnostic criteria. We found an overall penetrance of 87% at age 60 years. When considering only vHL patients who have not attended surveillance, 20% will still be asymptomatic at age 60 years. This should be considered in the context of genetic counselling, especially when assessing the risk...... of vHL in asymptomatic adult first-degree relatives who are often not genetically tested.European Journal of Human Genetics advance online publication, 14 December 2016; doi:10.1038/ejhg.2016.173....

VHL-mediated hypoxia regulation of cyclin D1 in renal carcinoma cells.

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Bindra, Ranjit S; Vasselli, James R; Stearman, Robert; Linehan, W Marston; Klausner, Richard D

2002-06-01

Renal cell carcinoma is associated with mutation of the von Hippel-Lindau (VHL) tumor suppressor gene. Cell lines derived from these tumors cannot exit the cell cycle when deprived of growth factors, and the ability to exit the cell cycle can be restored by the reintroduction of wild-type protein VHL (pVHL). Here, we report that cyclin D1 is overexpressed and remains inappropriately high in during contact inhibition in pVHL-deficient cell lines. In addition, hypoxia increased the expression of cyclin D1 specifically in pVHL-negative cell lines into which pVHL expression was restored. Hypoxic-induction of cyclin D1 was not observed in other pVHL-positive cell lines. This suggests a model whereby in some kidney cell types, pVHL may regulate a proliferative response to hypoxia, whereas the loss of pVHL leads to constitutively elevated cyclin D1 and abnormal proliferation under normal growth conditions.

Diagnostic Genetics at a Distance: Von Hippel-Lindau Disease and a Novel Mutation

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Clare Brookes

2013-01-01

Full Text Available Genetic testing at a distance is commonplace where members of a family with a segregating germline mutation are geographically separated. For the most part, this challenge is addressed through the intervention of health professionals in taking and/or processing blood samples for subsequent couriering of DNA to a referral laboratory. In some circumstances, however, the collecting of pivotal clinical material may involve direct patient involvement. We describe such a situation where noninvasive saliva samples were provided by members of a family manifesting Von Hippel-Lindau (VHL disease. The analysis identified a novel mutation in the VHL gene that was used to exclude other family members as being at risk of VHL disease.

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

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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

Management Strategies and Outcomes for VHL-related Craniospinal Hemangioblastomas

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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.

Somatic VHL gene alterations in MEN2-associated medullary thyroid carcinoma

International Nuclear Information System (INIS)

Koch, Christian A; Brouwers, Frederieke M; Vortmeyer, Alexander O; Tannapfel, Andrea; Libutti, Steven K; Zhuang, Zhengping; Pacak, Karel; Neumann, Hartmut PH; Paschke, Ralf

2006-01-01

Germline mutations in RET are responsible for multiple endocrine neoplasia type 2 (MEN2), an autosomal dominantly inherited cancer syndrome that is characterized by medullary thyroid carcinoma (MTC), pheochromocytoma, and parathyroid hyperplasia/adenoma. Recent studies suggest a 'second hit' mechanism resulting in amplification of mutant RET. Somatic VHL gene alterations are implicated in the pathogenesis of MEN2 pheochromocytomas. We hypothesized that somatic VHL gene alterations are also important in the pathogenesis of MEN2-associated MTC. We analyzed 6 MTCs and 1 C-cell hyperplasia (CCH) specimen from 7 patients with MEN2A and RET germline mutations in codons 609, 618, 620, or 634, using microdissection, microsatellite analysis, phosphorimage densitometry, and VHL mutation analysis. First, we searched for allelic imbalance between mutant and wild-type RET by using the polymorphic markers D10S677, D10S1239, and RET on thyroid tissue from these patients. Evidence for RET amplification by this technique could be demonstrated in 3 of 6 MTCs. We then performed LOH analysis using D3S1038 and D3S1110 which map to the VHL gene locus at 3p25/26. VHL gene deletion was present in 3 MTCs. These 3 MTCs also had an allelic imbalance between mutant and wild-type RET. Mutation analysis of the VHL gene showed a somatic frameshift mutation in 1 MTC that also demonstrated LOH at 3p25/26. In the 2 other MTCs with allelic imbalance of RET and somatic VHL gene deletion, no somatic VHL mutation could be detected. The CCH specimen did neither reveal RET imbalance nor somatic VHL gene alterations. These data suggest that a RET germline mutation is necessary for development of CCH, that allelic imbalance between mutant and wild-type RET may set off tumorigenesis, and that somatic VHL gene alterations may not play a major role in tumorigenesis of MEN2A-associated MTC

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

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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.

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

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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.

Novel interactions of the von Hippel-Lindau (pVHL) tumor suppressor with the CDKN1 family of cell cycle inhibitors

OpenAIRE

Giovanni Minervini; Raffaele Lopreiato; Raissa Bortolotto; Antonella Falconieri; Geppo Sartori; Silvio C. E. Tosatto

2017-01-01

Germline inactivation of the von Hippel-Lindau (VHL) tumor suppressor predisposes patients to develop different highly vascularized cancers. pVHL targets the hypoxia-inducible transcription factor (HIF-1?) for degradation, modulating the activation of various genes involved in hypoxia response. Hypoxia plays a relevant role in regulating cell cycle progression, inducing growth arrest in cells exposed to prolonged oxygen deprivation. However, the exact molecular details driving this transition...

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.

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

International Nuclear Information System (INIS)

Oh, Jong-Ryool; Min, Jung-Joon; Kulkarui, Harshad; Carreras, Cecilia; Schalch, Georg; Baum, Richard P.

2012-01-01

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

Acute Vhl gene inactivation induces cardiac HIF-dependent erythropoietin gene expression.

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Marta Miró-Murillo

Full Text Available Von Hippel Lindau (Vhl gene inactivation results in embryonic lethality. The consequences of its inactivation in adult mice, and of the ensuing activation of the hypoxia-inducible factors (HIFs, have been explored mainly in a tissue-specific manner. This mid-gestation lethality can be also circumvented by using a floxed Vhl allele in combination with an ubiquitous tamoxifen-inducible recombinase Cre-ER(T2. Here, we characterize a widespread reduction in Vhl gene expression in Vhl(floxed-UBC-Cre-ER(T2 adult mice after dietary tamoxifen administration, a convenient route of administration that has yet to be fully characterized for global gene inactivation. Vhl gene inactivation rapidly resulted in a marked splenomegaly and skin erythema, accompanied by renal and hepatic induction of the erythropoietin (Epo gene, indicative of the in vivo activation of the oxygen sensing HIF pathway. We show that acute Vhl gene inactivation also induced Epo gene expression in the heart, revealing cardiac tissue to be an extra-renal source of EPO. Indeed, primary cardiomyocytes and HL-1 cardiac cells both induce Epo gene expression when exposed to low O(2 tension in a HIF-dependent manner. Thus, as well as demonstrating the potential of dietary tamoxifen administration for gene inactivation studies in UBC-Cre-ER(T2 mouse lines, this data provides evidence of a cardiac oxygen-sensing VHL/HIF/EPO pathway in adult mice.

Solid renal tumor severity in von Hippel Lindau disease is related to germline deletion length and location.

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Maranchie, Jodi K; Afonso, Anoushka; Albert, Paul S; Kalyandrug, Sivaram; Phillips, John L; Zhou, Shubo; Peterson, James; Ghadimi, Bijan M; Hurley, Katheen; Riss, Joseph; Vasselli, James R; Ried, Thomas; Zbar, Berton; Choyke, Peter; Walther, McClellan M; Klausner, Richard D; Linehan, W Marston

2004-01-01

von Hippel Lindau disease (VHL) is an autosomal dominant familial cancer syndrome linked to alteration of the VHL tumor suppressor gene. Affected patients are predisposed to develop pheochromocytomas and cystic and solid tumors of the kidney, CNS, pancreas, retina, and epididymis. However, organ involvement varies considerably among families and has been shown to correlate with the underlying germline alteration. Clinically, we observed a paradoxically lower prevalence of renal cell carcinoma (RCC) in patients with complete germline deletion of VHL. To determine if a relationship existed between the type of VHL deletion and disease, we retrospectively evaluated 123 patients from 55 families with large germline VHL deletions, including 42 intragenic partial deletions and 13 complete VHL deletions, by history and radiographic imaging. Each individual and family was scored for cystic or solid involvement of CNS, pancreas, and kidney, and for pheochromocytoma. Germline deletions were mapped using a combination of fluorescent in situ hybridization (FISH) and quantitative Southern and Southern blot analysis. An age-adjusted comparison demonstrated a higher prevalence of RCC in patients with partial germline VHL deletions relative to complete deletions (48.9 vs. 22.6%, p=0.007). This striking phenotypic dichotomy was not seen for cystic renal lesions or for CNS (p=0.22), pancreas (p=0.72), or pheochromocytoma (p=0.34). Deletion mapping revealed that development of RCC had an even greater correlation with retention of HSPC300 (C3orf10), located within the 30-kb region of chromosome 3p, immediately telomeric to VHL (52.3 vs. 18.9%, p <0.001), suggesting the presence of a neighboring gene or genes critical to the development and maintenance of RCC. Careful correlation of genotypic data with objective phenotypic measures will provide further insight into the mechanisms of tumor formation. Copyright 2003 Wiley-Liss, Inc.

Compromised JMJD6 histone demethylase activity impacts on VHL gene repression in preeclampsia.

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Alahari, Sruthi; Post, Martin; Rolfo, Alessandro; Weksberg, Rosanna; Caniggia, Isabella

2018-01-24

The von Hippel Lindau (VHL) protein is a key executor of the cellular hypoxic response that is compromised in preeclampsia, a serious disorder complicating 5-7% of pregnancies. To date, the mechanisms controlling VHL gene expression in the human placenta remain elusive. We examined VHL epigenetic regulation in normal pregnancy and in preeclampsia, a pathology characterized by placental hypoxia. Placentae were obtained from early-onset (E-PE: n=56; <34 weeks of gestation) and late onset preeclampsia (L-PE: n=19; ≥ 34 weeks of gestation). Placentae from healthy normotensive age-matched preterm and term pregnancies (PTC: n=43; TC: n=23) were included as controls. We measured the activity of Jumonji domain containing protein 6 (JMJD6), a Fe2+ and oxygen-dependent histone demethylase, and examined its function in the epigenetic control of VHL. JMJD6 regulates VHL gene expression in the human placenta. VHL downregulation in preeclampsia is dependent on decreased JMJD6 demethylase activity due to hypoxia and reduced Fe2+ bioavailability. Chromatin immunoprecipitation assays revealed decreased association of JMJD6 and its histone targets with the VHL promoter. Findings in preeclampsia were corroborated in a murine model of pharmacological hypoxia using FG-4592. Placentae from FG-4592 treated mice exhibited reduced VHL levels, accompanied by placental morphological alterations and reduced pup weights. Notably, Fe2+ supplementation rescued JMJD6 histone demethylase activity in histone from E-PE and FG-4592-treated mice. Our study uncovers novel epigenetic regulation of VHL and its functional consequences for altered oxygen and iron homeostasis in preeclampsia. Copyright © 2018 Endocrine Society

Von Hippel-Lindau Disease

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Hes Frederik J

2005-11-01

Full Text Available Abstract A germline mutation in the Von-Hippel Lindau (VHL gene predisposes carriers to development of abundantly vascularised tumours in the retina, cerebellum, spine, kidney, adrenal gland and pancreas. Most VHL patients die from the consequences of cerebellar haemangioblastoma or renal cell carcinoma. The VHL gene is a tumour suppressor gene and is involved in angiogenesis by regulation of the activity of hypoxia-inducible factor 1-α (HIF1-α. Clinical diagnosis of VHL can be confirmed by molecular genetic analysis of the VHL gene, which is informative in virtually all VHL families. A patient with (suspicion for VHL is an indication for genetic counselling and periodical examination.

A case of von Hippel-Lindau disease with exudative maculopathy

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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.

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

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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

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.

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

Pancreatic involvement in Korean patients with von Hippel-Lindau disease

International Nuclear Information System (INIS)

Lee, Kwang-Hyuck; Lee, Jae-Seung; Kim, Bum-Jin; Lee, Jong-Kyun; Kim, Seong-Hyun; Kim, Seung-Hoon; Lee, Kyu-Taek

2009-01-01

The aim of this study was to describe pancreatic involvement in von Hippel-Lindau (VHL) disease and to document the changes that occur in pancreatic lesions. We retrospectively analyzed the medical records and CT scans of 18 VHL patients who were diagnosed between 1994 and 2007 at the Samsung Medical Center. The clinical history with a detailed family history, biochemical test results, and imaging studies of the pancreas, adrenal glands, and kidneys were reviewed. Genetic analysis was performed in 12 patients. The changes in pancreatic lesions, such as an increase in cystic lesions, calcifications, and dilatation of the pancreatic duct, were analyzed in patients who had CT scans at least 1 year apart. Pancreatic lesions existed in 89% (16/18) of the patients. All 16 patients had multiple cystic lesions. Two patients had co-existing neuroendocrine tumors (NET), and two patients had co-existing serous cystadenomas (SCA). At least one of three features of pancreatic lesions (cystic lesions, calcifications, and dilatation of the pancreatic duct) progressed in all nine patients who had CT scans 1 year apart. Pancreatic involvement in VHL disease was relatively common in Korean patients. The most common type of pancreatic involvement was a multiple cystic lesion. NET and SCA existed in approximately 10% of VHL patients with pancreatic involvement. Pancreatic lesions in VHL disease progressed, at least according to radiological images. (author)

VHL-dependent regulation of a β-dystroglycan glycoform and glycogene expression in renal cancer.

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Aggelis, Vassilis; Craven, Rachel A; Peng, Jianhe; Harnden, Patricia; Schaffer, Lana; Hernandez, Gilberto E; Head, Steven R; Maher, Eamonn R; Tonge, Robert; Selby, Peter J; Banks, Rosamonde E

2013-11-01

Identification of novel biomarkers and targets in renal cell carcinoma (RCC) remains a priority and one cellular compartment that is a rich potential source of such molecules is the plasma membrane. A shotgun proteomic analysis of cell surface proteins enriched by cell surface biotinylation and avidin affinity chromatography was explored using the UMRC2- renal cancer cell line, which lacks von Hippel-Lindau (VHL) tumour suppressor gene function, to determine whether proteins of interest could be detected. Of the 814 proteins identified ~22% were plasma membrane or membrane-associated, including several with known associations with cancer. This included β-dystroglycan, the transmembrane subunit of the DAG1 gene product. VHL-dependent changes in the form of β-dystroglycan were detected in UMRC2-/+VHL transfectants. Deglycosylation experiments showed that this was due to differential sialylation. Analysis of normal kidney cortex and conventional RCC tissues showed that a similar change also occurred in vivo. Investigation of the expression of genes involved in glycosylation in UMRC2-/+VHL cells using a focussed microarray highlighted a number of enzymes involved in sialylation; upregulation of bifunctional UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE) was validated in UMRC2- cells compared with their +VHL counterparts and also found in conventional RCC tissue. These results implicate VHL in the regulation of glycosylation and raise interesting questions regarding the extent and importance of such changes in RCC.

Prognostic and predictive value of VHL gene alteration in renal cell carcinoma: a meta-analysis and review.

Science.gov (United States)

Kim, Bum Jun; Kim, Jung Han; Kim, Hyeong Su; Zang, Dae Young

2017-02-21

The von Hippel-Lindau (VHL) gene is often inactivated in sporadic renal cell carcinoma (RCC) by mutation or promoter hypermethylation. The prognostic or predictive value of VHL gene alteration is not well established. We conducted this meta-analysis to evaluate the association between the VHL alteration and clinical outcomes in patients with RCC. We searched PUBMED, MEDLINE and EMBASE for articles including following terms in their titles, abstracts, or keywords: 'kidney or renal', 'carcinoma or cancer or neoplasm or malignancy', 'von Hippel-Lindau or VHL', 'alteration or mutation or methylation', and 'prognostic or predictive'. There were six studies fulfilling inclusion criteria and a total of 633 patients with clear cell RCC were included in the study: 244 patients who received anti-vascular endothelial growth factor (VEGF) therapy in the predictive value analysis and 419 in the prognostic value analysis. Out of 663 patients, 410 (61.8%) had VHL alteration. The meta-analysis showed no association between the VHL gene alteration and overall response rate (relative risk = 1.47 [95% CI, 0.81-2.67], P = 0.20) or progression free survival (hazard ratio = 1.02 [95% CI, 0.72-1.44], P = 0.91) in patients with RCC who received VEGF-targeted therapy. There was also no correlation between the VHL alteration and overall survival (HR = 0.80 [95% CI, 0.56-1.14], P = 0.21). In conclusion, this meta-analysis indicates that VHL gene alteration has no prognostic or predictive value in patients with clear cell RCC.

E2-EPF UCP targets pVHL for degradation and associates with tumor growth and metastasis.

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Jung, Cho-Rok; Hwang, Kyung-Sun; Yoo, Jinsang; Cho, Won-Kyung; Kim, Jin-Man; Kim, Woo Ho; Im, Dong-Soo

2006-07-01

The von Hippel-Lindau tumor suppressor, pVHL, forms part of an E3 ubiquitin ligase complex that targets specific substrates for degradation, including hypoxia-inducible factor-1alpha (HIF-1alpha), which is involved in tumor progression and angiogenesis. It remains unclear, however, how pVHL is destabilized. Here we show that E2-EPF ubiquitin carrier protein (UCP) associates with and targets pVHL for ubiquitin-mediated proteolysis in cells, thereby stabilizing HIF-1alpha. UCP is detected coincidently with HIF-1alpha in human primary liver, colon and breast tumors, and metastatic cholangiocarcinoma and colon cancer cells. UCP level correlates inversely with pVHL level in most tumor cell lines. In vitro and in vivo, forced expression of UCP boosts tumor-cell proliferation, invasion and metastasis through effects on the pVHL-HIF pathway. Our results suggest that UCP helps stabilize HIF-1alpha and may be a new molecular target for therapeutic intervention in human cancers.

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

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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.

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

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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.

Understanding familial and non-familial renal cell cancer

NARCIS (Netherlands)

Bodmer, Daniëlle; van den Hurk, Wilhelmina; van Groningen, Jan J. M.; Eleveld, Marc J.; Martens, Gerard J. M.; Weterman, Marian A. J.; van Kessel, Ad Geurts

2002-01-01

Molecular genetic analysis of familial and non-familial cases of conventional renal cell carcinoma (RCC) revealed a critical role(s) for multiple genes on human chromosome 3. For some of these genes, e.g. VHL, such a role has been firmly established, whereas for others, definite confirmation is

Understanding familial and non-familial renal cell cancer.

NARCIS (Netherlands)

Bodmer, D.; Hurk, W.H. van den; Groningen, J.J.M. van; Eleveld, M.J.; Martens, G.J.M.; Weterman, M.A.J.; Geurts van Kessel, A.H.M.

2002-01-01

Molecular genetic analysis of familial and non-familial cases of conventional renal cell carcinoma (RCC) revealed a critical role(s) for multiple genes on human chromosome 3. For some of these genes, e.g. VHL, such a role has been firmly established, whereas for others, definite confirmation is

Pancreatic cyst development: insights from von Hippel-Lindau disease

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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.

MR imaging of von Hippel-Lindau disease

International Nuclear Information System (INIS)

Sato, Y.; Waziri, M.H.; Smith, W.L.; Frey, E.E.; Franken, E.A.

1986-01-01

Sixteen patients with von Hippel-Lindau disease (VH-L) and 11 asymptomatic family members underwent a total of 29 central nervous system (CNS) and 23 body MR imaging evaluations during a 2-year study period. Nineteen CNS and spinal lesions and nine abdominal visceral lesions were identified on MR imaging and were confirmed at surgery or by other imaging modalities. MR imaging is superior to CT in the evaluation of intraocular vitreous abnormalities and cerebellar and spinal hemangioblastomas because of superior tissue characterization and lack of bone artifacts. MR imaging adequately demonstrated the abdominal visceral lesions. MR imaging is a sensitive and reliable imaging modality for the various lesions of VH-L

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

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...... a germline VHL mutation, the evolutionary principles of contingency and convergence in tumor development are complementary. In this small set of patients with early stage VHL-associated tumors, there is reduced mutation burden and limited evidence of intra-tumor heterogeneity....

Cyr61/CCN1 and CTGF/CCN2 mediate the proangiogenic activity of VHL-mutant renal carcinoma cells.

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Chintalapudi, Mastan R; Markiewicz, Margaret; Kose, Nurgun; Dammai, Vincent; Champion, Kristen J; Hoda, Rana S; Trojanowska, Maria; Hsu, Tien

2008-04-01

The von Hippel-Lindau (VHL) protein serves as a negative regulator of hypoxia-inducible factor (HIF)-alpha subunits. Since HIF regulates critical angiogenic factors such as vascular endothelial growth factor (VEGF) and lesions in VHL gene are present in a majority of the highly vascularized renal cell carcinoma (RCC), it is believed that deregulation of the VHL-HIF pathway is crucial for the proangiogenic activity of RCC. Although VEGF has been confirmed as a critical angiogenic factor upregulated in VHL-mutant cells, the efficacy of antiangiogenic therapy specifically targeting VEGF signaling remains modest. In this study, we developed a three-dimensional in vitro assay to evaluate the ability of RCC cells to promote cord formation by the primary human dermal microvascular endothelial cells (HDMECs). Compared with VHL wild-type cells, VHL-mutant RCC cells demonstrated a significantly increased proangiogenic activity, which correlated with increased secretion of cysteine-rich 61 (Cyr61)/cysteine-rich 61-connective tissue growth factor-nephroblastoma overexpressed (CCN) 1, connective tissue growth factor (CTGF)/CCN2 and VEGF in conditioned culture medium. Both CCN proteins are required for HDMEC cord formation as shown by RNA interference knockdown experiments. Importantly, the proangiogenic activities conferred by the CCN proteins and VEGF are additive, suggesting non-overlapping functions. Expression of the CCN proteins is at least partly dependent on the HIF-2alpha function, the dominant HIF-alpha isoform expressed in RCC. Finally, immunohistochemical staining of Cyr61/CCN1 and CTGF/CCN2 in RCC tissue samples showed that increased expression of these proteins correlates with the loss of VHL protein expression. These findings strengthened the notion that the hypervascularized phenotype of RCC is afforded by multiple proangiogenic factors that function in parallel pathways.

Pathology of the Nervous System in Von Hippel-Lindau Disease

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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. 

Cyr61/CCN1 and CTGF/CCN2 mediate the pro-angiogenic activity of VHL mutant renal carcinoma cells

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Chintalapudi, Mastan R.; Markiewicz, Margaret; Kose, Nurgun; Dammai, Vincent; Champion, Kristen J.; Hoda, Rana S.; Trojanowska, Maria; Hsu, Tien

2008-01-01

The von Hippel-Lindau (VHL) protein serves as a negative regulator of hypoxia inducible factor-alpha subunit (HIF-α). Since HIF regulates critical angiogenic factors such as vascular endothelial growth factor (VEGF) and lesions in VHL gene are present in a majority of the highly vascularized renal cell carcinoma (RCC), it is believed that deregulation of the VHL-HIF pathway is crucial for the pro-angiogenic activity of RCC. Although VEGF has been confirmed as a critical angiogenic factor up-regulated in VHL mutant cells, the efficacy of anti-angiogenic therapy specifically targeting VEGF signaling remains modest. In this study we developed a three-dimensional in vitro assay to evaluate the ability of RCC cells to promote cord formation by the primary human dermal microvascular endothelial cells (HDMECs). Compared to VHL wild-type cells, VHL mutant RCC cells demonstrated a significantly increased pro-angiogenic activity, which correlated with increased secretion of Cyr61/CCN1, CTGF/CCN2 and VEGF in conditioned culture medium. Both CCN proteins are required for HDMEC cord formation as shown by RNAi knock-down experiments. Importantly, the pro-angiogenic activities conferred by the CCN proteins and VEGF are additive, suggesting non-overlapping functions. Expression of the CCN proteins is at least partly dependent on the HIF-2α function, the dominant HIF-α isoform expressed in RCC. Finally, immunohistochemical staining of Cyr61/CCN1 and CTGF/CCN2 in renal cell carcinoma tissue samples showed that increased expression of these proteins correlates with loss of VHL protein expression. These findings strengthened the notion that the hypervascularized phenotype of RCC is afforded by multiple pro-angiogenic factors that function in parallel pathways. PMID:18212329

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

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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.

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

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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

2016-07-01

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. 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. 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. 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. © The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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

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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 CRL2 VHL 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.

Potent and selective chemical probe of hypoxic signalling downstream of HIF-α hydroxylation via VHL inhibition

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Frost, Julianty; Galdeano, Carles; Soares, Pedro; Gadd, Morgan S.; Grzes, Katarzyna M.; Ellis, Lucy; Epemolu, Ola; Shimamura, Satoko; Bantscheff, Marcus; Grandi, Paola; Read, Kevin D.; Cantrell, Doreen A.; Rocha, Sonia; Ciulli, Alessio

2016-11-01

Chemical strategies to using small molecules to stimulate hypoxia inducible factors (HIFs) activity and trigger a hypoxic response under normoxic conditions, such as iron chelators and inhibitors of prolyl hydroxylase domain (PHD) enzymes, have broad-spectrum activities and off-target effects. Here we disclose VH298, a potent VHL inhibitor that stabilizes HIF-α and elicits a hypoxic response via a different mechanism, that is the blockade of the VHL:HIF-α protein-protein interaction downstream of HIF-α hydroxylation by PHD enzymes. We show that VH298 engages with high affinity and specificity with VHL as its only major cellular target, leading to selective on-target accumulation of hydroxylated HIF-α in a concentration- and time-dependent fashion in different cell lines, with subsequent upregulation of HIF-target genes at both mRNA and protein levels. VH298 represents a high-quality chemical probe of the HIF signalling cascade and an attractive starting point to the development of potential new therapeutics targeting hypoxia signalling.

Von Hippel–Lindau disease

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Juhara Haron

2017-04-01

Full Text Available Von Hippel–Lindau (VHL disease is a rare autosomal dominantly inherited multisystem disorder characterised by the development of a variety of benign and malignant tumours. We report a case of VHL disease that was inherited by a daughter from her father, who both presented at a young age with progressive headache and were found to have a posterior fossa haemangioblastoma (HB on magnetic resonance imaging (MRI. Multiple benign pancreatic and renal cysts were also noted in both patients.

Trichloroethylene exposure and somatic mutations of the VHL gene in patients with Renal Cell Carcinoma

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Fevotte Joelle

2007-11-01

Full Text Available Abstract Background We investigated the association between exposure to trichloroethylene (TCE and mutations in the von Hippel-Lindau (VHL gene and the subsequent risk for renal cell carcinoma (RCC. Methods Cases were recruited from a case-control study previously carried out in France that suggested an association between exposures to high levels of TCE and increased risk of RCC. From 87 cases of RCC recruited for the epidemiological study, 69 were included in the present study. All samples were evaluated by a pathologist in order to identify the histological subtype and then be able to focus on clear cell RCC. The majority of the tumour samples were fixed either in formalin or Bouin's solutions. The majority of the tumours were of the clear cell RCC subtype (48 including 2 cystic RCC. Mutation screening of the 3 VHL coding exons was carried out. A descriptive analysis was performed to compare exposed and non exposed cases of clear cell RCC in terms of prevalence of mutations in both groups. Results In the 48 cases of RCC, four VHL mutations were detected: within exon 1 (c.332G>A, p.Ser111Asn, at the exon 2 splice site (c.463+1G>C and c.463+2T>C and within exon 3 (c.506T>C, p.Leu169Pro. No difference was observed regarding the frequency of mutations in exposed versus unexposed groups: among the clear cell RCC, 25 had been exposed to TCE and 23 had no history of occupational exposure to TCE. Two patients with a mutation were identified in each group. Conclusion This study does not confirm the association between the number and type of VHL gene mutations and exposure to TCE previously described.

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 to...

Lack of a functional VHL gene product sensitizes renal cell carcinoma cells to the apoptotic effects of the protein synthesis inhibitor verrucarin A.

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Woldemichael, Girma M; Turbyville, Thomas J; Vasselli, James R; Linehan, W Marston; McMahon, James B

2012-08-01

Verrucarin A (VA) is a small molecule derived from the fungal plant pathogen Myrothecium verrucaria and was identified as a selective inhibitor of clear cell renal cell carcinoma (CCRCC) cell proliferation in a high-throughput screen of a library of naturally occurring small molecules. CCRCC arises as a result of loss-of-function mutations in the von Hippel-Lindau (VHL) gene. Here we show that VA inhibits protein translation initiation culminating in apoptosis through the extrinsic signaling pathway. Reintroduction of the VHL gene in CCRCC cells afforded resistance to VA's apoptotic effects. This resistance is mediated in part by the formation of stress granules that entrap signaling molecules that initiate the apoptotic signaling cascade. The VHL gene product was found to be a component of stress granules that develop as result of VA treatment. These findings reveal an important role for the VHL gene product in cytotoxic stress response and have important implications for the rational development of VA-related compounds in chemotherapeutic targeting of CCRCC.

Chorionic gonadotropin regulates the transcript level of VHL, p53, and HIF-2alpha in human granulosa lutein cells.

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Herr, D; Keck, C; Tempfer, C; Pietrowski, Detlef

2004-12-01

The ovarian corpus luteum plays a critical role in reproduction being the primary source of circulating progesterone. After ovulation the corpus luteum is build by avascular granulosa lutein cells through rapid vascularization regulated by gonadotropic hormones. The present study was performed to investigate whether this process might be influenced by the human chorionic gonadotropin (hCG)-dependent expression of different tumor suppressor genes and hypoxia dependent transcription factors. RNA was isolated from cultured granulosa lutein cells, transcribed into cDNA, and the transcript level of following genes were determined: RB-1, VHL, NF-1, NF-2, Wt-1, p53, APC, and hypoxia inducible factor-1 (HIF-1), -2, and -3alpha. Additionally, the influence of hCG on the expression of VHL, p53, and HIf2alpha were investigated. We demonstrate that in human granulosa lutein cells the tumor suppressor genes RB-1, VHL, NF-1, NF-2, Wt-1, p53, and APC and the hypoxia dependent transcription factors HIF-1alpha, -2alpha, and -3alpha are expressed. In addition, we showed that hCG regulates the expression of p53, VHL, and HIF-2alpha. Our results indicate that hCG may determine the growth and development of the corpus luteum by mediating hypoxic and apoptotic pathways in human granulosa lutein cells. Copyright 2004 Wiley-Liss, Inc.

Lack of a Functional VHL Gene Product Sensitizes Renal Cell Carcinoma Cells to the Apoptotic Effects of the Protein Synthesis Inhibitor Verrucarin A

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Girma M. Woldemichael

2012-08-01

Full Text Available Verrucarin A (VA is a small molecule derived from the fungal plant pathogen Myrothecium verrucaria and was identified as a selective inhibitor of clear cell renal cell carcinoma (CCRCC cell proliferation in a high-throughput screen of a library of naturally occurring small molecules. CCRCC arises as a result of loss-of-function mutations in the von Hippel-Lindau (VHL gene. Here we show that VA inhibits protein translation initiation culminating in apoptosis through the extrinsic signaling pathway. Reintroduction of the VHL gene in CCRCC cells afforded resistance to VA's apoptotic effects. This resistance is mediated in part by the formation of stress granules that entrap signaling molecules that initiate the apoptotic signaling cascade. The VHL gene product was found to be a component of stress granules that develop as result of VA treatment. These findings reveal an important role for the VHL gene product in cytotoxic stress response and have important implications for the rational development of VA-related compounds in chemotherapeutic targeting of CCRCC.

Lack of a Functional VHL Gene Product Sensitizes Renal Cell Carcinoma Cells to the Apoptotic Effects of the Protein Synthesis Inhibitor Verrucarin A12

Science.gov (United States)

Woldemichael, Girma M; Turbyville, Thomas J; Vasselli, James R; Linehan, W Marston; McMahon, James B

2012-01-01

Verrucarin A (VA) is a small molecule derived from the fungal plant pathogen Myrothecium verrucaria and was identified as a selective inhibitor of clear cell renal cell carcinoma (CCRCC) cell proliferation in a high-throughput screen of a library of naturally occurring small molecules. CCRCC arises as a result of loss-of-function mutations in the von Hippel-Lindau (VHL) gene. Here we show that VA inhibits protein translation initiation culminating in apoptosis through the extrinsic signaling pathway. Reintroduction of the VHL gene in CCRCC cells afforded resistance to VA's apoptotic effects. This resistance is mediated in part by the formation of stress granules that entrap signaling molecules that initiate the apoptotic signaling cascade. The VHL gene product was found to be a component of stress granules that develop as result of VA treatment. These findings reveal an important role for the VHL gene product in cytotoxic stress response and have important implications for the rational development of VA-related compounds in chemotherapeutic targeting of CCRCC. PMID:22952429

Two-stage resection of a bilateral pheochromocytoma and pancreatic neuroendocrine tumor in a patient with von Hippel-Lindau disease: A case report

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Yutaka Endo

Full Text Available Introduction: von Hippel-Lindau disease (vHL disease is a hereditary disease in which tumors and cysts develop in many organs, in association with central nervous system hemangioblastomas, pheochromocytomas, and pancreatic tumors. We herein report a case of vHL disease (type 2A associated with bilateral pheochromocytomas, pancreatic neuroendocrine tumors (PNET, and cerebellar hemangioblastomas treated via pancreatectomy after adrenalectomy. Case presentation: A 51-year-old woman presented with a cerebellar tumor, bilateral hypernephroma, and pancreatic tumor detected during a medical checkup. 18F-fluorodeoxyglucose positron emission tomography–computed tomography revealed a bilateral adrenal gland tumor and a tumor in the head of the pancreas, while an abdominal computed tomography examination revealed a 30-mm tumor with strong enhancement in the head of the pancreas. Cranial magnetic resonance imaging showed a hemangioblastoma in the cerebellum. Therefore, a diagnosis of vHL disease (type 2A was made. Her family medical history included renal cell carcinoma in her father and bilateral adrenal pheochromocytoma and spinal hemangioblastoma in her brother. A detailed examination of endocrine function showed that the adrenal mass was capable of producing catecholamine. Treatment of the pheochromocytoma was prioritized, and therefore, laparoscopic left adrenalectomy and subtotal resection of the right adrenal gland were performed. Once the postoperative steroid levels were replenished, subtotal stomach-preserving pancreatoduodenectomy was performed for the PNET. After a good postoperative course, the patient was discharged in remission on the 11th day following surgery. Histopathological examination findings indicated NET G2 (MIB-1 index 10–15% pT3N0M0 Stage II A and microcystic serous cystadenoma throughout the resected specimen. The patient is scheduled to undergo treatment for the cerebellar hemangioblastoma. Conclusion: A two-staged resection

A Review of Von Hippel-Lindau Syndrome

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Neha Varshney

2017-08-01

Full Text Available Von Hippel-Lindau syndrome (VHL is a familial neoplastic condition seen in approximately 1 in 36,000 live births. It is caused by germline mutations of the tumor suppressor gene VHL, located on the short arm of chromosome 3. While the majority of the affected individuals have a positive family history, up to 20% of cases arise from de novo mutations. VHL syndrome is characterized by the presence of benign and malignant tumors affecting the central nervous system, kidneys, adrenals, pancreas, and reproductive organs. Common manifestations include hemangioblastomas of the brain, spinal cord, and retina; pheochromocytoma and paraganglioma; renal cell carcinoma; pancreatic cysts and neuroendocrine tumors; and endolymphatic sac tumors. Diagnosis of VHL is prompted by clinical suspicion and confirmed by molecular testing. Management of VHL patients is complex and multidisciplinary. Routine genetic testing and surveillance using various diagnostic techniques are used to help monitor disease progression and implement treatment options. Despite recent advances in clinical diagnosis and management, life expectancy for VHL patients remains low at 40–52 years. This article provides an overview of the major clinical, histological, and radiological findings, as well as treatment modalities.

Metastatic Renal Cell Carcinoma versus Pancreatic Neuroendocrine Tumor in von Hippel-Lindau Disease: Treatment with Interleukin-2

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Christopher Williams

2005-01-01

Full Text Available Differentiating between clear cell neuroendocrine tumor (NET of the pancreas and renal cell carcinoma (RCC metastatic to the pancreas can be challenging in patients with von Hippel-Lindau disease (VHL. The clear cell features of both NET and RCC in VHL patients may lead to misdiagnosis, inaccurate staging, and alternative treatment. We present a patient in which this occurred. As clear cell NETs closely resembling metastatic RCC are distinctive neoplasms of VHL and metastatic RCC to the pancreas in the VHL population is rare, careful pathologic examination should be performed prior to subjecting patients to definitive surgical or medical therapies.

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

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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.

Molecular analysis of the von hippel-lindau disease gene.

Science.gov (United States)

Chernoff, A; Kasparcova, V; Linehan, W M; Stolle, C A

2001-01-01

Von Hippel-Lindau (VHL) disease is an autosomal dominant disorder that predisposes the affected individual to develop characteristic tumors. These include CNS hemangioblastoma, retinal angiomas, endolymphatic sac tumors, pancreatic cysts and tumors, epididymal cystadenomas, pheochromocytomas, renal cysts, and clear-cell renal carcinoma. The VHL gene was localized to 3p25 and then isolated by Latif et al. (1). The gene contains three exons with an open reading frame of 852 nucleotides, which encode a predicted protein of 284 amino acids. The VHL protein is believed to have several functions. It is involved in transcription regulation through its inhibition of elongation by binding to the B and C subunits of elongin. Mutations of VHL allow the B and C subunits to bind with the A subunit. This complex then overcomes "pausing" of RNA polymerase during mRNA transcription (2,3). Several studies suggest that the VHL protein is also involved in regulation of hypoxia-inducible transcripts, particularly vascular endothelial growth factor (VEGF), by altering mRNA stability (4,5). Therefore, VHL gene mutations permit the overexpression of VEGF under normoxic conditions, which leads to the angiogenesis believed to be required for tumor growth. The VHL-elongin BC complex (VBC) also binds two other proteins-CUL2 and Rbx1-in a complex that has structural similarity to other E3 ubiquitin ligase complexes (6). Such complexes mediate the degradation of cell-cycle regulatory proteins.

The allele frequency of two single nucleotide polymorphisms in the von Hippel-Lindau (VHL) tumor suppressor gene in the Taiwanese population.

Science.gov (United States)

Wang, Wen-Chung; Chen, Hui-Ju; Shu, Wei-Pang; Tsai, Yi-Chang; Lai, Yen-Chein

2011-10-01

The von Hippel-Lindau (VHL) tumor suppressor gene located on chromosome 3p25-26 is implicated in VHL disease. Two informative single nucleotide polymorphisms are at positions 19 and 1149 on the nucleotide sequence from Gene Bank NM_000551. In this study we examined the allele frequencies at these two loci in the Taiwanese population and compared the results to those from European ethnic populations. The allele frequency was examined in 616 healthy individuals including 301 university students and 315 neonates. Both A/G polymorphisms were investigated using restriction fragment length polymorphism analysis created by restriction enzymes, BsaJ I and Acc I. Among these subjects, the allele frequencies at 19 SNP and 1149 SNP for variant G were 0.130 and 0.133, respectively. And these results were significant differences from those of the Caucasian populations. In addition, 90% of the tested subjects had identical genotypes at these two loci suggesting the existence of nonrandom association of alleles. We found that the G allele frequency at these two loci in the Taiwanese population is much lower than that in people from Western countries. This phenomenon may be attributed to ethnic effects. Copyright © 2011. Published by Elsevier B.V.

Cloning and characterization of a mouse gene with homology to the human von Hippel-Lindau disease tumor suppressor gene: implications for the potential organization of the human von Hippel-Lindau disease gene.

Science.gov (United States)

Gao, J; Naglich, J G; Laidlaw, J; Whaley, J M; Seizinger, B R; Kley, N

1995-02-15

The human von Hippel-Lindau disease (VHL) gene has recently been identified and, based on the nucleotide sequence of a partial cDNA clone, has been predicted to encode a novel protein with as yet unknown functions [F. Latif et al., Science (Washington DC), 260: 1317-1320, 1993]. The length of the encoded protein and the characteristics of the cellular expressed protein are as yet unclear. Here we report the cloning and characterization of a mouse gene (mVHLh1) that is widely expressed in different mouse tissues and shares high homology with the human VHL gene. It predicts a protein 181 residues long (and/or 162 amino acids, considering a potential alternative start codon), which across a core region of approximately 140 residues displays a high degree of sequence identity (98%) to the predicted human VHL protein. High stringency DNA and RNA hybridization experiments and protein expression analyses indicate that this gene is the most highly VHL-related mouse gene, suggesting that it represents the mouse VHL gene homologue rather than a related gene sharing a conserved functional domain. These findings provide new insights into the potential organization of the VHL gene and nature of its encoded protein.

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.

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.

Understanding familial and non-familial renal cell cancer.

Science.gov (United States)

Bodmer, Daniëlle; van den Hurk, Wilhelmina; van Groningen, Jan J M; Eleveld, Marc J; Martens, Gerard J M; Weterman, Marian A J; van Kessel, Ad Geurts

2002-10-01

Molecular genetic analysis of familial and non-familial cases of conventional renal cell carcinoma (RCC) revealed a critical role(s) for multiple genes on human chromosome 3. For some of these genes, e.g. VHL, such a role has been firmly established, whereas for others, definite confirmation is still pending. Additionally, a novel role for constitutional chromosome 3 translocations as risk factors for conventional RCC development is rapidly emerging. Also, several candidate loci have been mapped to other chromosomes in both familial and non-familial RCCs of distinct histologic subtypes. The MET gene on chromosome 7, for example, was found to be involved in both forms of papillary RCC. A PRCC-TFE3 fusion gene is typically encountered in t(X;1)-positive non-familial papillary RCCs and results in abrogation of the cell cycle mitotic spindle checkpoint in a dominant-negative fashion, thus leading to RCC. Together, these data turn human RCC into a model system in which different aspects of both familial and non-familial syndromes may act as novel paradigms for cancer development.

Renal cell tumors with clear cell histology and intact VHL and chromosome 3p: a histological review of tumors from the Cancer Genome Atlas database.

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Favazza, Laura; Chitale, Dhananjay A; Barod, Ravi; Rogers, Craig G; Kalyana-Sundaram, Shanker; Palanisamy, Nallasivam; Gupta, Nilesh S; Williamson, Sean R

2017-11-01

Clear cell renal cell carcinoma is by far the most common form of kidney cancer; however, a number of histologically similar tumors are now recognized and considered distinct entities. The Cancer Genome Atlas published data set was queried (http://cbioportal.org) for clear cell renal cell carcinoma tumors lacking VHL gene mutation and chromosome 3p loss, for which whole-slide images were reviewed. Of the 418 tumors in the published Cancer Genome Atlas clear cell renal cell carcinoma database, 387 had VHL mutation, copy number loss for chromosome 3p, or both (93%). Of the remaining, 27/31 had whole-slide images for review. One had 3p loss based on karyotype but not sequencing, and three demonstrated VHL promoter hypermethylation. Nine could be reclassified as distinct or emerging entities: translocation renal cell carcinoma (n=3), TCEB1 mutant renal cell carcinoma (n=3), papillary renal cell carcinoma (n=2), and clear cell papillary renal cell carcinoma (n=1). Of the remaining, 6 had other clear cell renal cell carcinoma-associated gene alterations (PBRM1, SMARCA4, BAP1, SETD2), leaving 11 specimens, including 2 high-grade or sarcomatoid renal cell carcinomas and 2 with prominent fibromuscular stroma (not TCEB1 mutant). One of the remaining tumors exhibited gain of chromosome 7 but lacked histological features of papillary renal cell carcinoma. Two tumors previously reported to harbor TFE3 gene fusions also exhibited VHL mutation, chromosome 3p loss, and morphology indistinguishable from clear cell renal cell carcinoma, the significance of which is uncertain. In summary, almost all clear cell renal cell carcinomas harbor VHL mutation, 3p copy number loss, or both. Of tumors with clear cell histology that lack these alterations, a subset can now be reclassified as other entities. Further study will determine whether additional entities exist, based on distinct genetic pathways that may have implications for treatment.

Preventive medicine for von Hippel-Lindau disease-associated pancreatic neuroendocrine tumors.

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Krauss, Tobias; Ferrara, Alfonso Massimiliano; Links, Thera P; Wellner, Ulrich; Bancos, Irina; Kvachenyuk, Andrey; Villar Gómez de Las Heras, Karina; Yukina, Marina; Petrov, Roman; Bullivant, Garrett; von Duecker, Laura; Jadhav, Swati S; Ploeckinger, Ursula; Welin, Staffan; Schalin-Jantti, Camilla; Gimm, Oliver; Pfeifer, Marija; Ngeow, Joanne; Hasse-Lazar, Kornelia; Sanso, Gabriela; Qi, Xiao-Ping; Ugurlu, Umit; Diaz, Rene Eduardo; Wohllk, Nelson; Peczkowska, Mariola; Aberle, Jens; Lourenço, Delmar Muniz; Pereira, Maria Adelaide; Fragoso, Maria Candida Barisson Villares; Hoff, Ana O; Almeida, Madson Queiroz; Violante, Alice H D; Quidute, Ana R P; Zhang, Zheiwei; Recasens, Monica; Robles Diaz, Luis; Kunavisarut, Tada; Wannachalee, Taweesak; Sirinvaravong, Sirinart; Jonasch, Eric; Grozinsky-Glasberg, Simona; Fraenkel, Merav; Beltsevich, Dmitry; Egorov, Viacheslav I; Bausch, Dirk; Schott, Matthias; Tiling, Nikolaus; Pennelli, Gianmaria; Zschiedrich, Stefan; Därr, Roland; Ruf, Juri; Denecke, Timm; Link, Karl-Heinrich; Zovato, Stefania; von Dobschuetz, Ernst; Yaremchuk, Svetlana; Amthauer, Holger; Makay, Ozer; Patocs, Attila; Walz, Martin K; Huber, Tobias B; Seufert, Jochen; Hellman, Per; Kim, Raymond H; Kuchinskaya, Ekaterina; Schiavi, Francesca; Malinoc, Angelica; Reisch, Nicole; Jarzab, Barbara; Barontini, Marta; Januszewicz, Andrzej; Shah, Nalini; Young, William; Opocher, Giuseppe; Eng, Charis; Neumann, Hartmut P H; Bausch, Birke

2018-05-10

Pancreatic neuroendocrine tumors (PanNETs) are rare in von Hippel-Lindau disease (VHL) but cause serious morbidity and mortality. Management guidelines for VHL-PanNETs continue to be based on limited evidence, and survival data to guide surgical management are lacking. We established the European-American-Asian-VHL-PanNET-Registry to assess data for risks for metastases, survival and long-term outcomes to provide best management recommendations. Of 2,330 VHL patients, 273 had a total of 484 PanNETs. Median age at diagnosis of PanNET was 35 years (range 10-75). Fifty-five (20%) patients had metastatic PanNETs. Metastatic PanNETs were significantly larger (median size 5 vs 2 cm; P1.5 cm in diameter were operated. Ten-year survival was significantly longer in operated vs non-operated patients, in particular for PanNETs <2.8cm vs ≥2.8 cm (94% vs 85% by 10 years; P=0.020; 80% vs 50% at 10 years; P=0.030). This study demonstrates that patients with PanNET approaching the cut-off diameter of 2.8 cm should be operated. Mutations in exon 3, especially of codons 161/167 are at enhanced risk for metastatic PanNETs. Survival is significantly longer in operated non-metastatic VHL-PanNETs.

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...

Zr-89-Bevacizumab PET Visualizes Disease Manifestations in Patients with von Hippel-Lindau Disease

NARCIS (Netherlands)

Oosting, Sjoukje F.; van Asselt, Sophie J.; Brouwers, Adrienne H.; Bongaerts, Alfons H. H.; Steinberg, Julia D. J.; de Jong, Johan; Lub-de Hooge, Marjolijn N.; Horst-Schrivers, van der Anouk N. A.; Walenkamp, Annemiek M. E.; Hoving, Eelco W.; Sluiter, Wim J.; Zonnenberg, Bernard A.; de Vries, Elisabeth G. E.; Links, Thera P.

2016-01-01

Patients with von Hippel-Lindau disease (VHL) are at risk to develop multiple tumors. The growth of lesions is unpredictable, and regular surveillance is critical for early treatment to control local damage. Vascular endothelial growth factor A (VEGF-A) produced locally is supposed to play an

Systemic Sunitinib Malate Treatment for Advanced Juxtapapillary Retinal Hemangioblastomas Associated with von Hippel-Lindau Disease.

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Knickelbein, Jared E; Jacobs-El, Naima; Wong, Wai T; Wiley, Henry E; Cukras, Catherine A; Meyerle, Catherine B; Chew, Emily Y

2017-01-01

To describe the clinical course of advanced juxtapapillary retinal capillary hemangioblastomas (RCH) associated with von Hippel-Lindau (VHL) disease treated with systemic sunitinib malate, an agent that inhibits both anti-vascular endothelial growth factor and anti-platelet-derived growth factor signaling. Observational case review. Three patients with advanced VHL-related juxtapapillary RCH treated with systemic sunitinib malate. Patient 1 was followed routinely every 4 months while on systemic sunitinib prescribed by her oncologist for metastatic pancreatic neuroendocrine and kidney tumors. Patients 2 and 3 were part of a prospective clinical trial evaluating the use of systemic sunitinib for ocular VHL lesions during a period of 9 months. Visual acuity, size of RCH, and degree of exudation were recorded at each visit. Optical coherence tomography (OCT) and fluorescein angiography were also obtained at some visits. Visual acuity, size of RCH, and degree of exudation. Three patients with advanced VHL-associated juxtapapillary RCH were treated with systemic sunitinib malate. While none of the patients lost vision during therapy, treatment with sunitinib malate did not improve visual acuity or reduce the size of RCH. Improvements in RCH-associated retinal edema were observed in two patients. All patients experienced multiple adverse effects, including thyroid toxicity, thrombocytopenia, nausea, fatigue, jaundice, and muscle aches. Two of the three patients had to discontinue treatment prematurely and the third required dose reduction. Systemic sunitinib malate may be useful in slowing progression of ocular disease from VHL-associated RCH. However, significant systemic adverse effects limited its use in this small series, and systemic sunitinib malate may not be safe for treatment of RCH when used at the doses described in this report. Further studies are required to determine if this medication used at lower doses with different treatment strategies, other

Fluorodeoxyglucose positron emission tomography-computed tomography scan in von Hippel-Lindau syndrome: a case report and review of literature

International Nuclear Information System (INIS)

Solav, Shrikant; Bhandari, Ritu

2012-01-01

Von Hippel-Lindau (VHL) syndrome is a hereditary autosomal dominant disorder caused by defective tumor suppression gene at 3p25-p26. The gene for VHL disease is found on chromosome 3, and is inherited in a dominant fashion. The VHL gene is a tumor suppressor gene. This means that its role in a normal cell is to stop the uncontrolled growth and proliferation. It is characterized by abnormal growth of blood vessels. It strikes the eyes, central nervous system, kidneys, endocrine glands, etc. It predisposes the patient to retinal angiomas, central nervous system hemangioblastoma, renal cell carcinoma (RCC), pheochromocytomas, islet cell tumor of the pancreas, endolymphatic sac tumors, renal, pancreatic, epididymal cysts. We present a case of familial VHL syndrome whose Fluorine 18-fluorodeoxyglucose positron emission tomography-computed tomography scan was truly positive for adrenal pheochromocytoma but was falsely negative for RCC. Review of literature related to this entity is made. (author)

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

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.

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...... asymmetrical, and had similar late gadolinium enhancement patterns. Ischemic stroke and severe white matter lesions were more frequent among family A men, but neither family A nor family B men had overt renal disease. Family A and family B heterozygotes had less severe or no clinical manifestations...

Modelling the effects of penetrance and family size on rates of sporadic and familial disease.

Science.gov (United States)

Al-Chalabi, Ammar; Lewis, Cathryn M

2011-01-01

Many complex diseases show a diversity of inheritance patterns ranging from familial disease, manifesting with autosomal dominant inheritance, through to simplex families in which only one person is affected, manifesting as apparently sporadic disease. The role of ascertainment bias in generating apparent patterns of inheritance is often overlooked. We therefore explored the role of two key parameters that influence ascertainment, penetrance and family size, in rates of observed familiality. We develop a mathematical model of familiality of disease, with parameters for penetrance, mutation frequency and family size, and test this in a complex disease: amyotrophic lateral sclerosis. Monogenic, high-penetrance variants can explain patterns of inheritance in complex diseases and account for a large proportion of those with no apparent family history. With current demographic trends, rates of familiality will drop further. For example, a variant with penetrance 0.5 will cause apparently sporadic disease in 12% of families of size 10, but 80% of families of size 1. A variant with penetrance 0.9 has only an 11% chance of appearing sporadic in families of a size similar to those of Ireland in the past, compared with 57% in one-child families like many in China. These findings have implications for genetic counselling, disease classification and the design of gene-hunting studies. The distinction between familial and apparently sporadic disease should be considered artificial. Copyright © 2011 S. Karger AG, Basel.

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...

Disease severity in familial cases of IBD.

Science.gov (United States)

Andreu, M; Márquez, L; Domènech, E; Gisbert, J P; García, V; Marín-Jiménez, I; Peñalva, M; Gomollón, F; Calvet, X; Merino, O; Garcia-Planella, E; Vázquez-Romero, N; Esteve, M; Nos, P; Gutiérrez, A; Vera, I; Cabriada, J L; Martín, M D; Cañas-Ventura, A; Panés, J

2014-03-01

Phenotypic traits of familial IBD relative to sporadic cases are controversial, probably related to limited statistical power of published evidence. To know if there are phenotype differences between familial and sporadic IBD, evaluating the prospective Spanish registry (ENEIDA) with 11,983 cases. 5783 patients (48.3%) had ulcerative colitis (UC) and 6200 (51.7%) Crohn's disease (CD). Cases with one or more 1st, 2nd or 3rd degree relatives affected by UC/CD were defined as familial case. In UC and CD, familial cases compared with sporadic cases had an earlier disease onset (UC: 33 years [IQR 25-44] vs 37 years [IQR 27-49]; p<0.0001); (CD: 27 years [IQR 21-35] vs 29 years [IQR 22-40]; p<0.0001), higher prevalence of extraintestinal immune-related manifestations (EIMs) (UC: 17.2% vs 14%; p=0.04); (CD: 30.1% vs 23.6%; p<0.0001). Familial CD had higher percentage of ileocolic location (42.7% vs 51.8%; p=0.0001), penetrating behavior (21% vs 17.6%; p=0.01) and perianal disease (32% vs 27.1%; p=0.003). Differences are not influenced by degree of consanguinity. When a sufficiently powered cohort is evaluated, familial aggregation in IBD is associated to an earlier disease onset, more EIMs and more severe phenotype in CD. This feature should be taken into account at establishing predictors of disease course. © 2013.

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.

A multinodular goiter as the initial presentation of a renal cell carcinoma harbouring a novel VHL mutation

Directory of Open Access Journals (Sweden)

Silva Eduardo

2006-10-01

Full Text Available Abstract Background Secondary involvement of the thyroid gland is rare. Often the origin of the tumor is difficult to identify from the material obtained by fine-needle aspiration cytology. Renal cell carcinoma of the clear-cell type is one of the more common carcinomas to metastasize to the thyroid gland. Somatic mutations of the von Hippel-Lindau tumor suppressor gene are associated with the sporadic form of this tumor. We aimed to illustrate the potential utility of DNA based technologies to search for specific molecular markers in order to establish the anatomic site of origin. Case Presentation A 54-yr-old Caucasian male complaining of a rapidly increasing neck tumor was diagnosed as having a clear-cell tumor by fine-needle aspiration cytology. A positive staining for cytokeratin as well as for vimentin and CD10 in the absence of staining for thyroglobulin, calcitonin and TTF1 suggested a renal origin confirmed by computed tomography. Using frozen RNA, obtained from cells left inside the needle used for fine needle aspiration cytology, it was possible to identify a somatic mutation (680 delA in the VHL gene. Conclusion In the presence of a clear-cell tumor of the thyroid gland, screening for somatic mutations in the VHL gene in material derived from thyroid aspirates might provide additional information to immunocytochemical studies and therefore plays a contributory role to establish the final diagnosis. Moreover, in a near future, this piece of information might be useful to define a targeted therapy.

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...... for impairments by taking on adult responsibilities, and in some families, a child had the role as main caregiver. The increasing need for care could cause conflicts between the role as family member and family caregiver. The burden of care within the family could fragment and isolate the family. CONCLUSIONS......: 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...

Chronic Disease Management in Family Practice: Clinical Note.

Science.gov (United States)

1998-03-01

disease management in the family practice selling. This paper discusses chronic disease management in the family practice selling....Chronic disease management is the process of evaluating and treating a medical condition or disease state which can not be readily cured so as to...minimize it’s negative impact on the individual. Examples of chronic disease management include the treatment of hypertension, diabetes, osteoporosis

Management of Gene Variants of Unknown Significance

DEFF Research Database (Denmark)

Alosi, Daniela; Bisgaard, Marie Luise; Hemmingsen, Sophie Nowak

2017-01-01

by germline mutations in the VHL gene, which predispose to the development of multiple tumors such as central nervous system hemangioblastomas and renal cell carcinoma (RCC). Objective: We propose a method for the evaluation of VUS pathogenicity through our experience with the VHL missense mutation c.241C...... (IHC); 3) Assessment of the variant’s impact on protein structure and function, using multiple databases, in silico algorithms, and reports of functional studies. Results: Only one family member had clinical signs of vHL with early-onset RCC. IHC analysis showed no VHL protein expressed in the tumor...

[Heredity in renal and prostatic neoplasia].

Science.gov (United States)

Prayer Galetti, T; D'Arrigo, L; De Zorzi, L; Patarnello, T

1997-09-01

RCC, but some are associated with high risk of pheochromocytoma and low risk of RCC. The VHL gene is evolutionary conserved and encodes for a specific protein (pVHL). VHL protein downregulates transcriptional elongation and so suppresses the expression of proto-oncogenes and growth factors. Recently reintroduction of wild-type, non mutant, VHL gene into VHL deficient RCC cell line 786-O had no demonstrable effect on their in vitro growth but inhibited their ability to form tumors in nude mice. So far, VHL mutations or hypermethylations have been found in 76% of sporadic RCC. On the contrary, up to now, no 3p allele loss or VHL mutations have been detected in pRCC. Preliminary studies in familiar pRCC are pointing on genetic changes on chromosomes 1, 7, 16 and 17. As far as prostate cancer is regarded, men with a family history of prostate cancer have an age dependent, significantly increased PCa risk. For familiar clustering, of PCa the two main factors are early age at onset of the disease and the number of multiple affected family members. Hereditary prostate cancer is a subset of familiar prostate cancer with a pattern of distribution consistent with Mendelian inheritance. Hereditary prostate cancer is clinically defined as a clustering of 3 or more relatives within any nuclear family; or the occurrence of prostate cancer in each of 3 generations in either the probands paternal or maternal lineage; or a cluster of 2 relatives affected within 55 years of age or less. Therefore, hereditary prostate cancer may be seen as a multistep carcinogenesis, and clustering may be explained by Mendelian inheritance of a rare (frequency in population 0.36%) dominant, highly penetrant, allele. The estimated cumulative risk of developing PCa, is 88% for carriers as compared with 5% for non carriers. There are conflicting reports of an associated increased incidence of breast cancer in female relatives of men with familiar prostate cancer. In conclusion, there is a clear associatio

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)

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.

Epidemiology and prevention of coronary heart disease in families.

Science.gov (United States)

Higgins, M

2000-04-01

Although family histories are used primarily to aid in diagnosis and risk assessment, their value is enhanced when the family is considered as a unit for research and disease prevention. The value of a family history of coronary heart disease (CHD) is increased when the age, sex, number of relatives, and age at onset of disease are incorporated in a quantitative family risk score. Medical and lifestyle risk factors that aggregate in families include dyslipidemia, hypertension, obesity, hyperfibrinogenemia, diabetes mellitus, smoking habits, eating patterns, alcohol consumption, physical activity, and socioeconomic status. Advances in detecting and understanding interactions between genetic susceptibility and modifiable risk factors should lead to improvements in prevention and treatment. However, working with families can be difficult. In the United States, families are usually small, are often widely dispersed, and may not be intact. Family histories may be unknown, affected relatives may be dead, and secular trends mask similarities among generations. Many exposures occur outside the home, and families change over time. Ethical, legal, and social issues arise when dealing with families. Nevertheless, opportunities are missed when research, clinical practice, and prevention focus on individual patients. Greater emphasis on families is needed to reduce the burden of CHD.

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, a...

The von Hippel-Lindau tumor suppressor gene inhibits hepatocyte growth factor/scatter factor-induced invasion and branching morphogenesis in renal carcinoma cells.

Science.gov (United States)

Koochekpour, S; Jeffers, M; Wang, P H; Gong, C; Taylor, G A; Roessler, L M; Stearman, R; Vasselli, J R; Stetler-Stevenson, W G; Kaelin, W G; Linehan, W M; Klausner, R D; Gnarra, J R; Vande Woude, G F

1999-09-01

Loss of function in the von Hippel-Lindau (VHL) tumor suppressor gene occurs in familial and most sporadic renal cell carcinomas (RCCs). VHL has been linked to the regulation of cell cycle cessation (G(0)) and to control of expression of various mRNAs such as for vascular endothelial growth factor. RCC cells express the Met receptor tyrosine kinase, and Met mediates invasion and branching morphogenesis in many cell types in response to hepatocyte growth factor/scatter factor (HGF/SF). We examined the HGF/SF responsiveness of RCC cells containing endogenous mutated (mut) forms of the VHL protein (VHL-negative RCC) with that of isogenic cells expressing exogenous wild-type (wt) VHL (VHL-positive RCC). We found that VHL-negative 786-0 and UOK-101 RCC cells were highly invasive through growth factor-reduced (GFR) Matrigel-coated filters and exhibited an extensive branching morphogenesis phenotype in response to HGF/SF in the three-dimensional (3D) GFR Matrigel cultures. In contrast, the phenotypes of A498 VHL-negative RCC cells were weaker, and isogenic RCC cells ectopically expressing wt VHL did not respond at all. We found that all VHL-negative RCC cells expressed reduced levels of tissue inhibitor of metalloproteinase 2 (TIMP-2) relative to the wt VHL-positive cells, implicating VHL in the regulation of this molecule. However, consistent with the more invasive phenotype of the 786-0 and UOK-101 VHL-negative RCC cells, the levels of TIMP-1 and TIMP-2 were reduced and levels of the matrix metalloproteinases 2 and 9 were elevated compared to the noninvasive VHL-positive RCC cells. Moreover, recombinant TIMPs completely blocked HGF/SF-mediated branching morphogenesis, while neutralizing antibodies to the TIMPs stimulated HGF/SF-mediated invasion in vitro. Thus, the loss of the VHL tumor suppressor gene is central to changes that control tissue invasiveness, and a more invasive phenotype requires additional genetic changes seen in some but not all RCC lines. These

Von Willebrand's Disease in Two Families of Doberman Pinschers

OpenAIRE

Johnstone, I. B.; Crane, S.

1981-01-01

The history, clinical symptoms and laboratory results in two families of Doberman pinschers with von Willebrand's disease are described. The affected animals illustrate the rather nonspecific bleeding problems that may be encountered in mild and moderate forms of this disease. In both families a bleeding diathesis was suspected when one member of the family underwent surgery with serious postoperative bleeding complications. These cases illustrate the importance of a thorough presurgical hist...

Importância do exame oftalmológico na doença de von Hippel-Lindau The importance of the ophthalmological examination in von Hippel-Lindau disease

Directory of Open Access Journals (Sweden)

Ricardo Evangelista Marrocos de Aragão

2009-08-01

Full Text Available Von Hippel-Lindau (VHL é uma síndrome tumoral autossômica dominante. Esses tumores incluem hemangioblastoma da retina e sistema nervoso central (CSN, carcinoma de células renais, feocromocitoma, tumores de pâncreas, cistoadenoma de rins, pâncreas e epidídimo. Os sintomas mais comuns são perda da visão, aumento da pressão intracraniana, déficits neurológicos, aumento da pressão arterial sistêmica paradoxal e dor local. Relatamos o caso de um paciente com perda de visão e história de hemangiomas cerebelares cujo diagnóstico de VHL foi feito após exame oftalmológico.Von Hippel-Lindau (VHL disease is an autossomical, dominant inherited tumour syndrom. These tumours may include haemangioblastoma in the retina and central nervous system (CNS, renal cell carcinoma, phaeochromocytoma, islet cell tumours of the pancreas, cystadenoma in the kidney, pancreas, and epididymis. The most common symptoms include: loss of vision, raised intracranial pressure, neurological deficits, paroxysmal raised blood pressure and local pain. We report herein a 29-year-old man with visual loss and cerebellar haemangioblastoma that despite neurological manifestations the diagnosis of VHL was established after the ophthalmological examanination.

Exome sequencing in a family segregating for celiac disease

NARCIS (Netherlands)

Szperl, A M; Ricaño-Ponce, I; Li, J K; Deelen, P; Kanterakis, A; Plagnol, V; van Dijk, Freerk; Westra, H J; Trynka, G; Mulder, C. J.; Swertz, M; Wijmenga, Cisca; Zheng, H C H

Celiac disease is a multifactorial disorder caused by an unknown number of genetic factors interacting with an environmental factor. Hence, most patients are singletons and large families segregating with celiac disease are rare. We report on a three-generation family with six patients in which the

The emotional experiences of family carers in Huntington disease.

Science.gov (United States)

Williams, Janet K; Skirton, Heather; Paulsen, Jane S; Tripp-Reimer, Toni; Jarmon, Lori; McGonigal Kenney, Meghan; Birrer, Emily; Hennig, Bonnie L; Honeyford, Joann

2009-04-01

This paper is a report of a study conducted to examine the emotional experience of caregiving by family carers of people with Huntington disease and to describe strategies they used to deal with that experience. Huntington disease, commonly diagnosed in young to middle adulthood, is an inherited single gene disorder involving loss of cognitive, motor and neuropsychiatric function. Many family members become caregivers as well as continuing as parents and wage earners. The emotional aspects of caregiving contribute to mental health risks for family members. Focus groups were conducted with 42 adult carers of people with Huntington disease in four United States and two Canadian Huntington disease centers between 2001 and 2005. Data were analyzed through descriptive coding and thematic analysis. All participants reported multiple aspects of emotional distress. Being a carer was described as experiencing disintegration of one's life. Carers attempted to cope by seeking comfort from selected family members, anticipating the time when the care recipient had died and/or using prescription medications. Spousal carers were distressed by the loss of their relationship with their spouse and dealt with this by no longer regarding the person as an intimate partner. Carers were concerned about the disease risk for children in their families and hoped for a cure. Emotional distress can compromise the well-being of family carers, who attempt to maintain multiple roles. Nurses should monitor carer mental health, identify sources of emotional distress and support effective strategies used by carers to mediate distress.

Exploring parent-sibling communication in families of children with sickle cell disease.

Science.gov (United States)

Graff, J Carolyn; Hankins, Jane S; Hardy, Belinda T; Hall, Heather R; Roberts, Ruth J; Neely-Barnes, Susan L

2010-01-01

Communication within families of children with sickle cell disease is important yet has not been adequately investigated. Focus group interviews were conducted with parents of children with sickle cell disease to explore parent-sibling communication about sickle cell disease. Communication was influenced by attributes and behaviors of the parent, the child with sickle cell disease, and the sibling; extended family, neighbors, friends, and church members or social networks; and available, accessible resources related to the child's health, child's school, and parent employment. Outcomes that influenced and were influenced by factors within and outside the parent-sibling dyad and nuclear family included parent satisfaction, parent roles, family intactness, and status attainment. These findings support previous research with African-American families and expand our views of the importance of educating parents, family members, and others about sickle cell disease. The findings suggest a need to explore sibling perception of this communication, parent and sibling perception of the impact of frequent hospitalizations and clinic visits on the sibling and family, and variations within families of children with sickle cell disease.

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.

Úskalí života s onemocněním Von Hippel - Lindau

OpenAIRE

ŠEREDOVÁ, Eva

2014-01-01

Morbus Von Hippel Lindau (VHL) is still an unkonwn term for many people. It refers to a genetic oncological desease affecting 1/39000 to 1/50000 persons. VHL is connected with a great deal of manifestation. It is a disease with a very unstable prognosis. Those diagnosed with VHL require medical care by a large number of specialists. However, an early detection may significantly improve the quality of patients´ life. The disease is manifestated by numerous negative side effects, which is the m...

Premature cardiovascular disease in young women with heterozygous familial hypercholesterolemia

NARCIS (Netherlands)

van der Graaf, Anouk; Hutten, Barbara A.; Kastelein, John J. P.; Vissers, Maud N.

2006-01-01

Heterozygous familial hypercholesterolemia is associated with elevated low-density lipoprotein cholesterol levels and the development of premature cardiovascular disease. Despite this general statement, data regarding the incidence of cardiovascular disease in young women with familial

Norrie's disease in an Asian family.

OpenAIRE

Harendra de Silva, D G; de Silva, D B

1988-01-01

Norrie's disease, a congenital progressive oculo-acoustico-cerebral degenerative condition, is a sex linked recessive disorder. Previously described as atrophia oculi congeneti, it is associated with bilateral pseudotumour of the retina, lens, and corneal opacities, and phthisis bulbi. Some patients develop progressive deterioration of mental function and hearing. We report a Sri Lankan family with typical features of Norrie's disease.

[Genetic counseling and testing for families with Alzheimer's disease].

Science.gov (United States)

Kowalska, Anna

2004-01-01

With the identification of the genes responsible for autosomal dominant early-onset familial Alzheimer's disease (FAD genes), there is a considerable interest in the application of this genetic information in medical practice through genetic testing and counseling. Pathogenic mutations in the PSEN1 and PSEN2 genes encoding presenilin-1 and -2, and the APP gene encoding amyloid b precursor protein, account for 18-50% of familial EOAD cases with autosomal dominant pattern of inheritance. A clinical algorithm of genetic testing and counseling proposed for families with AD has been presented here. A screening for mutations in the APP, PSEN1, and PSEN2 genes is available to individuals with AD symptoms and at-risk children or siblings of patients with early-onset disease determined by a known mutation. In an early-onset family, a known mutation in an affected patient puts the siblings and children at a 50% risk of inheriting the same mutation. The goal of genetic testing is to identify at-risk individuals in order to facilitate early and effective treatments in the symptomatic person based on an individual's genotype and strategies to delay the onset of disease in the presymptomatic mutation carriers. However, there are several arguments against the use of genetic testing both presymptomatically (unpredictable psychological consequences of information about a genetic defect for family members) and as a diagnostic tool for the differential diagnosis of dementia in general practice (a risk of errors in an interpretation of mutation penetrance and its secondary effects on family members, especially for novel mutations; the possibility of coexistence of another form of dementia at the presence of a mutation). Currently, APOE genotyping for presymptomatic individuals with a family history of late-onset disease is not recommended. The APOE4 allele may only confer greater risk for disease, but its presence is not conclusive for the development of AD.

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.

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

2011-01-01

To determine the specific components of family history and personal characteristics related to disease perceptions about breast, colon, and ovarian cancers. 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. 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. 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.

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.

MANAGEMENT OF ENDOCRINE DISEASE: Outcome of adrenal sparing surgery in heritable pheochromocytoma.

Science.gov (United States)

Castinetti, F; Taieb, D; Henry, J F; Walz, M; Guerin, C; Brue, T; Conte-Devolx, B; Neumann, H P H; Sebag, F

2016-01-01

The management of hereditary pheochromocytoma has drastically evolved in the last 20 years. Bilateral pheochromocytoma does not increase mortality in MEN2 or von Hippel-Lindau (VHL) mutation carriers who are followed regularly, but these mutations induce major morbidities if total bilateral adrenalectomy is performed. Cortical sparing adrenal surgery may be proposed to avoid definitive adrenal insufficiency. The surgical goal is to leave sufficient cortical tissue to avoid glucocorticoid replacement therapy. This approach was achieved by the progressive experience of minimally invasive surgery via the transperitoneal or retroperitoneal route. Cortical sparing adrenal surgery exhibits management of all patients with MEN2 or VHL hereditary pheochromocytoma. Hereditary pheochromocytoma is a rare disease, and a randomized trial comparing cortical sparing vs classical adrenalectomy is probably not possible. This lack of data most likely explains why cortical sparing surgery has not been adopted in most expert centers that perform at least 20 procedures per year for the treatment of this disease. This review examined recent data to provide insight into the technique, its indications, and the results and subsequent follow-up in the management of patients with hereditary pheochromocytoma with a special emphasis on MEN2. © 2016 European Society of Endocrinology.

Family Aggregation of Human T-Lymphotropic Virus 1-Associated Diseases: a Systematic Review

Directory of Open Access Journals (Sweden)

Carolina Alvarez

2016-10-01

Full Text Available Human T-lymphotropic virus 1 (HTLV-1 is a retrovirus that produces a persistent infection. Two transmission routes (from mother to child and via sexual intercourse favor familial clustering of HTLV-1. It is yet unknown why most HTLV-1 carriers remain asymptomatic while about 10% of them develop complications. HTLV-1 associated diseases were originally described as sporadic entities, but familial presentations have been reported. To explore what is known about family aggregation of HTLV-1-associated diseases we undertook a systematic review. We aimed at answering whether, when and where family aggregation of HTLV-1-associated diseases was reported, which relatives were affected and which hypotheses were proposed to explain aggregation. We searched MEDLINE, abstract books of HTLV conferences and reference lists of selected papers. Search terms used referred to HTLV-1 infection, and HTLV-1-associated diseases, and family studies. HTLV-1-associated diseases considered are adult T-cell leukemia/lymphoma (ATLL, HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP, HTLV-1-associated uveitis, and infective dermatitis. Seventy-four records reported HTLV-1-associated diseases in more than one member of the same family and were included. Most reports came from HTLV-1-endemic countries, mainly Japan (n=30 and Brazil (n=10. These reports described a total of 270 families in which more than one relative had HTLV-1-associated diseases. In most families, different family members suffered from the same disease (n=221. The diseases most frequently reported were ATLL (114 families and HAM/TSP (101 families. Most families (n=142 included two to four affected individuals. The proportion of ATLL patients with family history of ATLL ranged from 2% to 26%. The proportion of HAM/TSP patients with family history of HAM/TSP ranged from 1% to 48%. The predominant cluster types for ATLL were clusters of siblings and parent-child pairs and for HAM/TSP, an

[Clinical study on patients with renal-cell carcinoma accompanied with Von Hippel-Lindau disease treated with radiofrequency ablation].

Science.gov (United States)

Nao, Tomoya; Shimamoto, Tsutomu; Karashima, Takashi; Kamei, Maiko; Fukuhara, Hideo; Fukata, Satoshi; Satake, Hirofumi; Ashida, Shingo; Yamasaki, Ichiro; Kamata, Masayuki; Inoue, Keiji; Yamanishi, Tomoaki; Ogawa, Yasuhiro; Ito, Satoshi; Shuin, Taro

2014-09-01

We report 12 renal cell carcinomas in 6 patients with Von Hippel-Lindau (VHL) disease treated with radiofrequency ablation (RFA). The mean age of the patients was 46 (range 38-53) years (male : 4, female : 2). Computed tomography (CT)-guided transcutaneous RFA was performed under conscious sedation with local anesthetics. The mean size of the tumors was 2.4 (range 0.7-8.1) cm. Nine of the 12 tumors (75%) were locally well controlled. However, 3 tumors in 2 patients developed visceral metastases after RFA. While minimal flank pain, nausea, perinephritic hematoma and lumbago were observed, there was no major complication during or after the procedure. The therapy with CT-guided transcutaneous RFA is efficient and minimal invasive for renal cell carcinoma in patients with VHL, leading to preservation of renal function.

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.

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

BACKGROUND: Collaboration between family caregivers and health professionals in specialised hospitals or community-based primary healthcare systems can be challenging. During the course of severe chronic disease, several health professionals might be involved at a given time, and the patient......'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...

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 ...

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

Science.gov (United States)

Ranthe, Mattis Flyvholm; Carstensen, Lisbeth; Oyen, Nina; Tfelt-Hansen, Jacob; Christiansen, Michael; McKenna, William J; Wohlfahrt, Jan; Melbye, Mads; Boyd, Heather A

2012-08-28

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. Studies suggest that fatal cardiovascular events and less severe cardiovascular diseases may co-occur in families. Consequently, a family history of premature death may indicate a familial cardiac frailty that predisposes to early cardiovascular disease. We ascertained family history of premature death (age Denmark from 1950 to 2008 and followed this cohort for early cardiovascular disease (age history of premature cardiovascular death in first-degree relatives were 1.72 (95% confidence interval [CI]: 1.68 to 1.77), 2.21 (95% CI: 2.11 to 2.31), and 1.94 (95% CI: 1.70 to 2.20), respectively. With ≥2 cardiovascular deaths in a family, corresponding IRRs were 3.30 (95% CI: 2.77 to 3.94), 5.00 (95% CI: 3.87 to 6.45), and 6.18 (95% CI: 3.32 to 11.50). The IRR for any early cardiovascular disease given a family history of premature noncardiovascular death was significantly lower, 1.12 (95% CI: 1.10 to 1.14) (p(cardiac vs. noncardiac) history of premature cardiovascular death was consistently and significantly associated with a risk of early cardiovascular disease, suggesting an inherited cardiac vulnerability. These results should be kept in mind when assessing cardiovascular disease risk in persons with a family history of premature cardiovascular death. Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Bcl-2 family-regulated apoptosis in health and disease

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Grant Dewson

2010-04-01

Full Text Available Grant Dewson, Ruth M KluckMolecular Genetics of Cancer Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, AustraliaAbstract: Apoptotic cell death is essential for embryonic development, tissue homeostasis, and a well-functioning immune system, with aberrant apoptosis contributing to numerous disease conditions. Inadequate cell death is a major contributing factor to tumorigenesis, while excess cell death contributes to neurodegeneration and autoimmune disease. The major pathway of apoptotic cell death, the mitochondrial pathway, is controlled by the Bcl-2 family of proteins. The members of this family, more than 17 in humans, share significant sequence and structural homology, and fulfil either prosurvival or proapoptotic roles. Specific interactions between these functionally polar proteins, and their relative expression levels, govern the susceptibility of each cell to toxic insults. Here we review the current understanding on how apoptotic cell death is controlled by this important protein family. We also discuss how excessive or insufficient cell death can contribute to disease, and how targeting the Bcl-2 family offers novel therapeutic opportunities.Keywords: apoptosis, Bcl-2, cancer, cytochrome c, mitochondria

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

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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.

Norrie disease and exudative vitreoretinopathy in families with affected female carriers.

Science.gov (United States)

Shastry, B S; Hiraoka, M; Trese, D C; Trese, M T

1999-01-01

Norrie disease (ND) is a rare X-linked recessive disorder characterized by congenital blindness, which is often associated with sensorineural hearing loss and mental retardation. X-linked familial exudative vitreoretinopathy (FEVR) is a hereditary disorder characterized by an abnormality of the peripheral retina and is not associated with systemic diseases. X-linked recessive disorders generally do not affect females. Here we show that female carriers can be associated with manifestation of an X-linked disorder. A four-generation family with an affected female, and a history of congenital blindness and hearing loss, was identified through the pro-band. A second family, with a full-term female infant, was evaluated through ophthalmic examinations and found to exhibit ocular features, such as retinal folds, retinal detachment and peripheral exudates. Peripheral blood specimens were collected from several affected and unaffected family members. DNA was extracted and analyzed by single-strand conformation polymorphism (SSCP) following polymerase chain reaction (PCR) amplification of the exons of the Norrie disease gene. The amplified products were sequenced by the dideoxy chain termination method. In an X-linked four-generation family, a novel missense (A118D) mutation in the third exon of the Norrie disease gene, was identified. The mutation was transmitted through three generations and cosegregated with the disease. The affected maternal grandmother and the unaffected mother carried the same mutation in one of their alleles. In an unrelated sporadic family, a heterozygous missense mutation (C96Y) was identified in the third exon of the Norrie disease gene in an affected individual. Analysis of exon-1 and 2 of the Norrie disease gene did not reveal any additional sequence alterations in these families. The mutations were not detected in the unaffected family members and the 116 normal unrelated controls, suggesting that they are likely to be the pathogenic mutations

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.

Primary prevention in patients with a strong family history of coronary heart disease.

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Burke, Lora A

2003-01-01

The interplay of genetic and environmental factors places first-degree relatives of individuals with premature coronary heart disease at greater risk of developing the disease than the general population. Disease processes, such as dyslipidemia, hypertension, and glucose and insulin metabolism, and lifestyle habits, such as eating and exercise patterns, as well as socioeconomic status aggregate in families with coronary heart disease. The degree of risk associated with a family history varies with the degree of relationship and the age at onset of disease. All individuals with a family history of premature heart disease should have a thorough coronary risk assessment performed, which can be initiated in an office visit. Absolute risk for coronary heart disease determination will predict the intensity of preventive interventions. This article reviews the components of risk determination and primary prevention in individuals with a strong family history of coronary heart disease.

The impact of disease on family members: a critical aspect of medical care.

Science.gov (United States)

Golics, Catherine Jane; Basra, Mohammad Khurshid Azam; Finlay, Andrew Yule; Salek, Sam

2013-10-01

Most existing health-related quality of life research concerns the impact of disease on patients. However, in several medical specialties including dermatology, oncology, and physical and mental disability, studies have been carried out investigating the impact of disease on the lives of families of patients. The aim of this paper is to review the literature which relates to the impact of disease on family members of patients. The OVIDSP Medline was selected as the primary database, Searches were limited to sources published in English. 158 papers were identified for review. The definition of "family" varied across the literature, and a broad definition was accepted in this review. This review shows that a wide variety of aspects of family members' lives can be affected, including emotional, financial, family relationships, education and work, leisure time, and social activities. Many of these themes are linked to one another, with themes including financial impact and social impact being linked to emotional impact. Some positive aspects were also identified from the literature, including family relationships growing stronger. Several instruments exist to measure the impact of illness on the family, and most are disease or specialty- specific. The impact of disease on families of patients is often unrecognised and underestimated. Taking into account the quality of life of families as well as patients can offer the clinician a unique insight into issues such as family relationships and the effect of treatment decisions on the patient's close social group of partner and family.

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.

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

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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.

Family history of Alzheimer’s disease limits improvement in cognitive function after bariatric surgery

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Michael L Alosco

2014-06-01

Full Text Available Background/Objective: Bariatric surgery can reverse cognitive impairments associated with obesity. However, such benefits may be attenuated in individuals with a predisposing risk for cognitive impairment such as family history of Alzheimer’s disease. Methods: In all, 94 bariatric surgery participants completed a computerized cognitive test battery before and 12 weeks after surgery. Family history of Alzheimer’s disease was obtained through self-report. Results: In the overall sample, cognitive function improved in memory and attention/executive function 12 weeks post-surgery. Repeated measures showed similar rates of improvements in attention/executive function between patients with and without a family history of Alzheimer’s disease. In contrast, only individuals without a family history of Alzheimer’s disease exhibited post-operative improvements in memory. A family history of Alzheimer’s disease was associated with greater post-surgery rates of cognitive impairment. Conclusions: Family history of Alzheimer’s disease may limit post-surgery cognitive benefits. Future studies should examine whether weight loss can modify the course of cognitive decline in patients at-risk for Alzheimer’s disease.

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

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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

Familial associations between polycystic ovarian syndrome and common diseases.

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Moini, Ashraf; Eslami, Bita

2009-03-01

The goal of this study was focused on two subjects. First, to determine possible association between PCOS and family history of breast cancer, ovarian cancer, endometrial cancer, heart attack, thrombosis, diabetes and cardiovascular disease (CVD). Second, to evaluate maternal and paternal transmission in PCOS patients with positive family history of a disease. A cross-sectional study was conducted in 549 infertile women (273 with PCOS and 276 controls) in Arash hospital of Tehran, Iran, between 2007 and 2008 by using questionnaire. In this analysis, there were significantly increased number of women with the positive family history of diabetes among PCOS group (28.21% vs. 19.20%, p=0.01). Meanwhile, four women in PCOS group had self history of diabetes while no one in the control group reported diabetes. A statistically significant positive family history of breast cancer was found among the control group (4.35% vs. 1.30%, p=0.02). Endometrial cancer and diabetes were observed in mother or mother's side of the family but heart attack and thrombosis manifested in father or father's side of the family more. There were no statistically significant differences in a positive individual or family history of ovarian cancer, endometrial cancer, heart attack, thrombosis and CVD between the two groups. In the present study, women and their relatives with PCOS had an increased prevalence of diabetes and it is more common in mother's side of the family.

von Hippel-Lindau development in children and adolescents

DEFF Research Database (Denmark)

Launbjerg, Karoline; Bache, Iben; Galanakis, Michael

2017-01-01

on expert opinions. We aimed to describe the course of vHL development in children and adolescents, focusing on age at first manifestation, manifestation frequencies, and types. The prevalence of vHL diagnosis as well as manifestations in childhood were evaluated based on 99 patients, who had started......The autosomal dominant von Hippel-Lindau disease (vHL) is associated with a lifelong risk of tumor development, especially retinal and CNS hemangioblastomas, pheochromocytoma, and renal cell carcinoma. Knowledge of paediatric vHL development is limited, and current surveillance guidelines are based...... surveillance before 18 years: 37 Danish patients from the national vHL research database and 62 international patients reported in 15 articles. Overall, 70% (69 of 99) developed manifestations before 18 years (median age at first manifestation: 12 years (range: 6–17 years)). Thirty per cent (30 of 99) had...

Memory binding and white matter integrity in familial Alzheimer’s disease

Science.gov (United States)

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

2015-01-01

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

Phenotypic concordance in familial inflammatory bowel disease (IBD). Results of a nationwide IBD Spanish database.

Science.gov (United States)

Cabré, Eduard; Mañosa, Míriam; García-Sánchez, Valle; Gutiérrez, Ana; Ricart, Elena; Esteve, Maria; Guardiola, Jordi; Aguas, Mariam; Merino, Olga; Ponferrada, Angel; Gisbert, Javier P; Garcia-Planella, Esther; Ceña, Gloria; Cabriada, José L; Montoro, Miguel; Domènech, Eugeni

2014-07-01

Disease outcome has been found to be poorer in familial inflammatory bowel disease (IBD) than in sporadic forms, but assessment of phenotypic concordance in familial IBD provided controversial results. We assessed the concordance for disease type and phenotypic features in IBD families. Patients with familial IBD were identified from the IBD Spanish database ENEIDA. Families in whom at least two members were in the database were selected for concordance analysis (κ index). Concordance for type of IBD [Crohn's disease (CD) vs. ulcerative colitis (UC)], as well as for disease extent, localization and behaviour, perianal disease, extraintestinal manifestations, and indicators of severe disease (i.e., need for immunosuppressors, biological agents, and surgery) for those pairs concordant for IBD type, were analyzed. 798 out of 11,905 IBD patients (7%) in ENEIDA had familial history of IBD. Complete data of 107 families (231 patients and 144 consanguineous pairs) were available for concordance analyses. The youngest members of the pairs were diagnosed with IBD at a significantly younger age (p<0.001) than the oldest ones. Seventy-six percent of pairs matched up for the IBD type (κ=0.58; 95%CI: 0.42-0.73, moderate concordance). There was no relevant concordance for any of the phenotypic items assessed in both diseases. Familial IBD is associated with diagnostic anticipation in younger individuals. Familial history does not allow predicting any phenotypic feature other than IBD type. Copyright © 2013 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

Genetic basis of cancer of the kidney: disease-specific approaches to therapy.

Science.gov (United States)

Linehan, W Marston; Vasselli, James; Srinivasan, Ramaprasad; Walther, McClellan M; Merino, Maria; Choyke, Peter; Vocke, Cathy; Schmidt, Laura; Isaacs, Jennifer S; Glenn, Gladys; Toro, Jorge; Zbar, Berton; Bottaro, Donald; Neckers, Len

2004-09-15

Studies during the past two decades have shown that kidney cancer is not a single disease; it is made up of a number of different types of cancer that occur in this organ. Clear cell renal carcinoma is characterized by mutation of the VHL gene. The VHL gene product forms a heterotrimeric complex with elongin C, elongin B, and Cul-2 to target hypoxia-inducible factors 1 and 2alpha for ubiquitin-mediated degradation. VHL-/- clear cell renal carcinoma overexpresses epidermal growth factor receptor and transforming growth factor alpha. Both hypoxia-inducible factor 1alpha and the epidermal growth factor receptor are potential therapeutic targets in clear cell renal carcinoma. Studies of the hereditary form of renal cell carcinoma (RCC) associated with hereditary papillary renal carcinoma (HPRC) determined that the c-Met proto-oncogene on chromosome 7 is the gene for HPRC and for a number of sporadic papillary RCCs. The HPRC c-Met mutations are activating mutations in the tyrosine kinase domain of the gene. The gene for a new form of hereditary RCC (Birt Hogg Dubé syndrome) associated with cutaneous tumors, lung cysts, and colon polyps or cancer has recently been identified. Studies are currently under way to determine what type of gene BHD is and how damage to this gene leads to kidney cancer. Individuals affected with hereditary leiomyomatosis renal cell carcinoma are at risk for the development of cutaneous leiomyomas, uterine leiomyomas (fibroids), and type 2 papillary RCC. The HLRC gene has been found to be the Krebs cycle enzyme, fumarate hydratase. Studies are under way to understand the downstream pathway of this cancer gene.

Emerging models for mobilizing family support for chronic disease management: a structured review.

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Rosland, Ann-Marie; Piette, John D

2010-03-01

We identify recent models for programmes 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. 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. Programmes with three separate foci were identified: (1) Programmes that guide family members in setting goals for supporting patient self-care behaviours have led to improved implementation of family support roles, but have mixed success improving patient outcomes. (2) Programmes 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 behaviours. (3) Programmes 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. The next generation of programmes to improve family support for chronic disease management incorporate a variety of strategies. Future research can define optimal clinical situations for family support programmes, the most effective combinations of support strategies, and how best to integrate family support programmes into comprehensive models of chronic disease care.

Familial benign chronic neutropenia associated with periodontal disease. A case report.

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Deasy, M J; Vogel, R I; Macedo-Sobrinho, B; Gertzman, G; Simon, B

1980-04-01

A rare case report of periodontal disease associated with familial benign chronic neutropenia is presented. The medical, dental and family histories as well as clinical and histologic observations are described and discussed.

Deriving consumer-facing disease concepts for family health histories using multi-source sampling.

Science.gov (United States)

Hulse, Nathan C; Wood, Grant M; Haug, Peter J; Williams, Marc S

2010-10-01

The family health history has long been recognized as an effective way of understanding individuals' susceptibility to familial disease; yet electronic tools to support the capture and use of these data have been characterized as inadequate. As part of an ongoing effort to build patient-facing tools for entering detailed family health histories, we have compiled a set of concepts specific to familial disease using multi-source sampling. These concepts were abstracted by analyzing family health history data patterns in our enterprise data warehouse, collection patterns of consumer personal health records, analyses from the local state health department, a healthcare data dictionary, and concepts derived from genetic-oriented consumer education materials. Collectively, these sources yielded a set of more than 500 unique disease concepts, represented by more than 2500 synonyms for supporting patients in entering coded family health histories. We expect that these concepts will be useful in providing meaningful data and education resources for patients and providers alike.

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.

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....

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

Impact of chronic obstructive pulmonary disease on family functioning.

Science.gov (United States)

Kanervisto, Merja; Paavilainen, Eija; Astedt-Kurki, Päivi

2003-01-01

The purpose of this study was to ascertain family dynamics of Finnish patients with severe chronic obstructive pulmonary disease (COPD) on the basis of Barnhill's framework for healthy family functioning. This study used description and comparison and an interview-administered questionnaire and survey. Participants were patients with COPD and their family members (n = 65) living in the Tampere University Hospital catchment area. The sample consisted of families of home oxygen therapy patients (n = 36) and families of inpatients (n = 29). Families consisted of patients and their family members. Data were collected from patients by interview-administered questionnaires and from family members by survey. The instrument used was the Family Dynamics Measure 2, operationalized and tested by the American Family Research Group. Families of home oxygen therapy patients experienced significantly more mutuality (P =.03) and made decisions about their illness and life significantly more independently (P =.05) than families of inpatients. Families of home oxygen therapy patients handled change significantly more flexibly (P =.03) than families of inpatients. For the most part, families of both patient groups functioned well, but overall family functioning was clearly better in families of home oxygen therapy patients. The sample included some dysfunctional and even severely dysfunctional families. The results of this study cannot be generalized beyond the study sample because of the small sample size, but they provide suggestions for developing the care of patients with COPD and their families.

Dyadic confirmatory factor analysis of the inflammatory bowel disease family responsibility questionnaire.

Science.gov (United States)

Greenley, Rachel Neff; Reed-Knight, Bonney; Blount, Ronald L; Wilson, Helen W

2013-09-01

Evaluate the factor structure of youth and maternal involvement ratings on the Inflammatory Bowel Disease Family Responsibility Questionnaire, a measure of family allocation of condition management responsibilities in pediatric inflammatory bowel disease. Participants included 251 youth aged 11-18 years with inflammatory bowel disease and their mothers. Item-level descriptive analyses, subscale internal consistency estimates, and confirmatory factor analyses of youth and maternal involvement were conducted using a dyadic data-analytic approach. Results supported the validity of 4 conceptually derived subscales including general health maintenance, social aspects, condition management tasks, and nutrition domains. Additionally, results indicated adequate support for the factor structure of a 21-item youth involvement measure and strong support for a 16-item maternal involvement measure. Additional empirical support for the validity of the Inflammatory Bowel Disease Family Responsibility Questionnaire was provided. Future research to replicate current findings and to examine the measure's clinical utility is warranted.

A novel Norrie disease pseudoglioma gene mutation, c.-1_2delAAT, responsible for Norrie disease in a Chinese family

OpenAIRE

Zhang, Xin-Yu; Jiang, Wei-Ying; Chen, Lu-Ming; Chen, Su-Qin

2013-01-01

AIM:To investigate the genetic findings and phenotypic characteristics of a Chinese family with Norrie disease (ND).METHODS:Molecular genetic analysis and clinical examinations were performed on a Chinese family with ND. Mutations in the Norrie disease pseudoglioma (NDP) gene were detected by direct sequencing. Haplotypes were constructed and compared with the phenotypes in the family. Evolutionary comparisons and mutant open reading frame (ORF) prediction were also undertaken.RESULTS:Two fam...

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.

Genetic defect causing familial Alzheimer's disease maps on chromosome 21

Energy Technology Data Exchange (ETDEWEB)

St. George-Hyslop, P.H.; Tanzi, R.E.; Polinsky, R.J.; Haines, J.L.; Nee, L.; Watkins, P.C.; Myers, R.H.; Feldman, R.G.; Pollen, D.; Drachman, D.; Growdon, J.

1987-02-20

Alzheimer's disease is a leading cause of morbidity and mortality among the elderly. Several families have been described in which Alzheimer's disease is caused by an autosomal dominant gene defect. The chromosomal location of this defective gene has been discovered by using genetic linkage to DNA markers on chromosome 21. The localization on chromosome 21 provides an explanation for the occurrence of Alzheimer's disease-like pathology in Down syndrome. Isolation and characterization of the gene at this locus may yield new insights into the nature of the defect causing familial Alzheimer's disease and possibly, into the etiology of all forms of Alzheimer's disease.

Periodontal disease in three siblings with familial neutropenia.

Science.gov (United States)

Kirstilä, V; Sewón, L; Laine, J

1993-06-01

The periodontal status and treatment of three teenagers in a Finnish family with familial neutropenia is described. The mother was also diagnosed with neutropenia. At initial examination, the 15-year-old male and the 10-year-old female had severe periodontitis, whereas the 13-year-old male had oral ulcerations but no significant periodontal disease. The two siblings with periodontitis were treated and followed approximately 5 years. It was concluded that periodontal therapy including scaling, surgery, and use of antimicrobial agents can be successful in patients with familial neutropenia, and that such patients are not necessarily candidates for full mouth extraction. The role of granulocyte colony-stimulating factor in which was used in the treatment of these patients remains to be established.

[Analysis of gene mutation in a Chinese family with Norrie disease].

Science.gov (United States)

Zhang, Tian-xiao; Zhao, Xiu-li; Hua, Rui; Zhang, Jin-song; Zhang, Xue

2012-09-01

To detect the pathogenic mutation in a Chinese family with Norrie disease. Clinical diagnosis was based on familial history, clinical sign and B ultrasonic examination. Peripheral blood samples were obtained from all available members in a Chinese family with Norrie disease. Genomic DNA was extracted from lymphocytes by the standard SDS-proteinase K-phenol/chloroform method. Two coding exons and all intron-exon boundaries of the NDP gene were PCR amplified using three pairs of primers and subjected to automatic DNA sequence. The causative mutation was confirmed by restriction enzyme analysis and genotyping analysis in all members. Sequence analysis of NDP gene revealed a missense mutation c.220C > T (p.Arg74Cys) in the proband and his mother. Further mutation identification by restriction enzyme analysis and genotyping analysis showed that the proband was homozygote of this mutation. His mother and other four unaffected members (III3, IV4, III5 and II2) were carriers of this mutation. The mutant amino acid located in the C-terminal cystine knot-like domain, which was critical motif for the structure and function of NDP. A NDP missense mutation was identified in a Chinese family with Norrie disease.

A model for intra-familial distribution of an infectious disease (Chagas' disease

Directory of Open Access Journals (Sweden)

M. F. Feitosa

1993-06-01

Full Text Available A probabilistic model for intra-familial distribution of infectous disease is proposed and applied to the prevalence of positive serology for Trypanosoma cruzi infection in Northeastern Brazilian sample. This double with one tail excess model fits satisfactorily to the data and its interpretation says that around 51% of these 982 families are free of infection risk; among those that are at risk, 3% have a high risk (0.66, probably due to high domestic infestation of the vector bug; while 97% show a small risk (0.11, probably due to accidental, non-domestic transmission.

Balancing needs as a family caregiver in Huntington's disease

DEFF Research Database (Denmark)

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

2015-01-01

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...... and the need for care for affected familymember(s). As the disease progressed, the balance was skewed, and thefamily caregivers’ participation in social activities gradually decreased,resulting in experiences of isolation and frustration. In later stages of thedisease, the need for care gradually overshadowed...... the caregivers’ ownactivities, and they put their own life on hold. Health professionals andsocial workers should acknowledge that family caregivers balance theirneeds and considerations in coping with HD. They should, therefore,tailor healthcare services and social support to family caregivers’ needsduring...

Brief report: development of the inflammatory bowel disease family responsibility questionnaire.

Science.gov (United States)

Greenley, Rachel Neff; Doughty, Alyssa; Stephens, Mike; Kugathasan, Subra

2010-03-01

To present psychometric data on youth and parent versions of the Inflammatory Bowel Disease-Family Responsibility Questionnaire (IBD-FRQ), a measure of family involvement in IBD management. Fifty-eight adolescents with inflammatory bowel disease (IBD), along with 55 mothers and 26 fathers completed the IBD-FRQ, a demographics questionnaire, and a measure of family involvement in decision making in non-IBD domains. Medical information was obtained via chart review. Support for the internal consistency of the IBD-FRQ was obtained. Evidence of validity was documented via moderate to high intercorrelations among reporters. Youth involvement increased with youth age, while maternal and paternal involvement decreased with youth age. Across all reporters, maternal involvement was higher than paternal involvement. Preliminary analyses offer support for the measure's reliability and validity. The measure shows promise as a means of assessing family involvement in IBD condition management; however, further validation studies are needed.

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

This paper discusses the misclassification that occurs when relying solely on routine register data in family studies of disease clustering. A register study of familial aggregation of schizophrenia is used as an example. The familial aggregation is studied using a regression model for the disease...... before this time are misclassified as disease-free. Two methods are presented to adjust for this misclassification: regression calibration and an EM-type algorithm. These methods are used in the schizophrenia example where the large effect of having a schizophrenic mother hardly shows any signs of bias...

Cardiovascular disease in patients with genotyped familial hypercholesterolemia in Norway during 1994-2009, a registry study.

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Mundal, Liv; Veierød, Marit B; Halvorsen, Thomas; Holven, Kirsten B; Ose, Leiv; Iversen, Per Ole; Tell, Grethe S; Leren, Trond P; Retterstøl, Kjetil

2016-12-01

Background Familial hypercholesterolaemia increases the risk for cardiovascular disease. The primary aim of the present study was to describe sex differences in incidence and prevalence of cardiovascular disease leading to hospitalisation in a complete cohort of genotyped familial hypercholesterolaemia patients. Design and methods In this registry study data on 5538 patients with verified genotyped familial hypercholesterolaemia were linked to data on all Norwegian cardiovascular disease hospitalisations, and hospitalisations due to pre-eclampsia/eclampsia, congenital heart defects and diabetes. Results During 1994-2009 a total of 1411 of familial hypercholesterolaemia patients were hospitalised, and ischaemic heart disease was reported in 90% of them. Mean (SD) age at first hospitalisation and first re-hospitalisation was 45.1 (16.5) and 47.6 (16.3) years, respectively, with no sex differences ( P = 0.66 and P = 0.93, respectively). More men (26.9%) than women (24.1%) with familial hypercholesterolaemia were hospitalised ( P = 0.02). The median (25th-75th percentile) number of hospital admissions was four (two to seven) per familial hypercholesterolaemia patient, with no sex differences ( P = 0.87). Despite having familial hypercholesterolaemia at the time of hospitalisation, the diagnosis of familial hypercholesterolaemia was registered in only 45.7% of the patients at discharge. Conclusion Most cardiovascular disease hospitalisations were due to ischaemic heart disease. Familial hypercholesterolaemia patients were first time hospitalised at age 45.1 years, with no significant sex differences in age, which are important novel findings. The awareness and registration of the familial hypercholesterolaemia diagnosis during the hospital stays were disturbingly low.

Bap1 and Pbrm1: Determinants of Tumor Grade and mTOR Activation in VHL-Deficient Mouse Models of Renal Cell Carcinoma.

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Leung, Janet Y; Kim, William Y

2017-08-01

Large genome sequencing efforts have identified frequent mutations in the histone-modifying and chromatin-remodeling genes BAP1 and PBRM1 in clear cell renal cell carcinoma (ccRCC). In this issue of Cancer Discovery , Gu and colleagues model these genetic events in mice and report that dual inactivation of Vhl with either Bap1 or Pbrm1 results in faithful genetically engineered murine models of ccRCC. Moreover, their work establishes that Bap1 and Pbrm1 are determinants of tumor grade and mTORC1 activation and provocatively suggests that the cell of origin of ccRCC may lie in PAX8-expressing Bowman capsule cells. Cancer Discov; 7(8); 802-4. ©2017 AACR See related article by Gu et al., p. 900 . ©2017 American Association for Cancer Research.

Familial transmission of chronic obstructive pulmonary disease in adoptees: a Swedish nationwide family study.

Science.gov (United States)

Zöller, Bengt; Li, Xinjun; Sundquist, Jan; Sundquist, Kristina

2015-04-13

Familial clustering of chronic obstructive pulmonary disease (COPD) is well established, but the familial risk of COPD has not been determined among adoptees. The aim was to determine whether the familial transmission of COPD is related to disease in biological and/or adoptive parents. Historic cohort study. 80,214 (50% females). The Swedish Multi-Generation Register was used to follow all Swedish-born adoptees born in 1932-2004 (n=80,214) between 1 January 1964 and 31 December 2010 for COPD (n=1978). The risk of COPD was estimated in adoptees with at least one biological parent with COPD but no adoptive parent with COPD (n=162) compared with adoptees without a biological or adoptive parent with COPD. The risk of COPD was also determined in adoptees with at least one adoptive parent but no biological parent with COPD (n=110), and in adoptees with both affected biological and adoptive parents (n=162). COPD in adoptees. Adoptees with COPD in at least one biological parent but no adoptive parent were more likely to have COPD than adoptees without a biological or adoptive parent with COPD (standardised incidence ratio, SIR=1.98 (95% CI 1.69 to 2.31)). The familial SIR for adoptees with both a biological parent and an adoptive parent with COPD was 1.68 (95% CI 1.39 to 2.00). Adoptees with at least one adoptive parent with COPD but no biological parent with COPD were not at an increased risk of COPD (SIR=1.12 (95% CI 0.92 to 1.35)). The findings of the study show that the familial transmission of COPD is associated with COPD in biological but not adoptive parents, suggesting that genetic or early life factors are important in the familial transmission of COPD. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Gaucher disease in a family from Maranhão

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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.

The SPINK gene family and celiac disease susceptibility

NARCIS (Netherlands)

Wapenaar, M.C.; Monsuur, A.J.; Poell, J.; Slot, R. van 't; Meijer, J.W.R.; Meijer, G.A.; Mulder, C.J.; Mearin, M.L.; Wijmenga, C.

2007-01-01

The gene family of serine protease inhibitors of the Kazal type (SPINK) are functional and positional candidate genes for celiac disease (CD). Our aim was to assess the gut mucosal gene expression and genetic association of SPINK1, -2, -4, and -5 in the Dutch CD population. Gene expression was

The SPINK gene family and celiac disease susceptibility

NARCIS (Netherlands)

Wapenaar, Martin C.; Monsuur, Alienke J.; Poell, Jos; Slot, Ruben Van 't; Meijer, Jos W. R.; Meijer, Gerrit A.; Mulder, Chris J.; Mearin, Maria Luisa; Wijmenga, Cisca

The gene family of serine protease inhibitors of the Kazal type (SPINK) are functional and positional candidate genes for celiac disease (CD). Our aim was to assess the gut mucosal gene expression and genetic association of SPINK1, -2, -4, and -5 in the Dutch CD population. Gene expression was

The Interleukin-20 Cytokine Family in Liver Disease

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Esther Caparrós

2018-05-01

Full Text Available The three main causes of inflammation and chronic injury in the liver are viral hepatitis, alcohol consumption, and non-alcoholic steatohepatitis, all of which can lead to liver fibrosis, cirrhosis, and hepatocellular carcinoma, which in turn may prompt the need for liver transplant. The interleukin (IL-20 is a subfamily part of the IL-10 family of cytokines that helps the liver respond to damage and disease, they participate in the control of tissue homeostasis, and in the immunological responses developed in this organ. The best-studied member of the family in inflammatory balance of the liver is the IL-22 cytokine, which on the one hand may have a protective role in fibrosis progression but on the other may induce liver tissue susceptibility in hepatocellular carcinoma development. Other members of the family might also carry out this dual function, as some of them share IL receptor subunits and signal through common intracellular pathways. Investigators are starting to consider the potential for targeting IL-20 subfamily members in liver disease. The recently explored role of miRNA in the transcriptional regulation of IL-22 and IL-24 opens the door to promising new approaches for controlling the local immune response and limiting organ injury. The IL-20RA cytokine receptor has also been classified as being under miRNA control in non-alcoholic steatohepatitis. Moreover, researchers have proposed combining anti-inflammatory drugs with IL-22 as a hepatoprotective IL for alcoholic liver disease (ALD treatment, and clinical trials of ILs for managing severe alcoholic-derived liver degeneration are ongoing. In this review, we focus on exploring the role of the IL-20 subfamily of cytokines in viral hepatitis, ALD, non-alcoholic steatohepatitis, and hepatocellular carcinoma, as well as delineating the main strategies explored so far in terms of therapeutic possibilities of the IL-20 subfamily of cytokines in liver disease.

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

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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.

NDP gene mutations in 14 French families with Norrie disease.

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Royer, Ghislaine; Hanein, Sylvain; Raclin, Valérie; Gigarel, Nadine; Rozet, Jean-Michel; Munnich, Arnold; Steffann, Julie; Dufier, Jean-Louis; Kaplan, Josseline; Bonnefont, Jean-Paul

2003-12-01

Norrie disease is a rare X-inked recessive condition characterized by congenital blindness and occasionally deafness and mental retardation in males. This disease has been ascribed to mutations in the NDP gene on chromosome Xp11.1. Previous investigations of the NDP gene have identified largely sixty disease-causing sequence variants. Here, we report on ten different NDP gene allelic variants in fourteen of a series of 21 families fulfilling inclusion criteria. Two alterations were intragenic deletions and eight were nucleotide substitutions or splicing variants, six of them being hitherto unreported, namely c.112C>T (p.Arg38Cys), c.129C>G (p.His43Gln), c.133G>A (p.Val45Met), c.268C>T (p.Arg90Cys), c.382T>C (p.Cys128Arg), c.23479-1G>C (unknown). No NDP gene sequence variant was found in seven of the 21 families. This observation raises the issue of misdiagnosis, phenocopies, or existence of other X-linked or autosomal genes, the mutations of which would mimic the Norrie disease phenotype. Copyright 2003 Wiley-Liss, Inc.

[Analysis of the NDP gene in a Chinese family with X-linked recessive Norrie disease].

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Mei, Libin; Huang, Yanru; Pan, Qian; Liang, Desheng; Wu, Lingqian

2015-05-01

The purpose of the current research was to investigate the NDP (Norrie disease protein) gene in one Chinese family with Norrie disease (ND) and to characterize the related clinical features. Clinical data of the proband and his family members were collected. Complete ophthalmic examinations were carried out on the proband. Genomic DNA was extracted from peripheral blood leukocytes of 35 family members. Molecular analysis of the NDP gene was performed by polymerase chain reaction and direct sequencing of all exons and flanking regions. A hemizygous NDP missense mutation c.362G > A (p.Arg121Gln) in exon 3 was identified in the affected members, but not in any of the unaffected family individuals. The missense mutation c.362G > A in NDP is responsible for the Norrie disease in this family. This discovery will help provide the family members with accurate and reliable genetic counseling and prenatal diagnosis.

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

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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.

Egr-1 and serum response factor are involved in growth factors- and serum-mediated induction of E2-EPF UCP expression that regulates the VHL-HIF pathway.

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Lim, Jung Hwa; Jung, Cho-Rok; Lee, Chan-Hee; Im, Dong-Soo

2008-11-01

E2-EPF ubiquitin carrier protein (UCP) has been shown to be highly expressed in common human cancers and target von Hippel-Lindau (VHL) for proteosomal degradation in cells, thereby stabilizing hypoxia-inducible factor (HIF)-1alpha. Here, we investigated cellular factors that regulate the expression of UCP gene. Promoter deletion assay identified binding sites for early growth response-1 (Egr-1) and serum response factor (SRF) in the UCP promoter. Hepatocyte or epidermal growth factor (EGF), or phorbol 12-myristate 13-acetate induced UCP expression following early induction of Egr-1 expression in HeLa cells. Serum increased mRNA and protein levels of SRF and UCP in the cell. By electrophoretic mobility shift and chromatin immunoprecipitation assays, sequence-specific DNA-binding of Egr-1 and SRF to the UCP promoter was detected in nuclear extracts from HeLa cells treated with EGF and serum, respectively. Overexpression of Egr-1 or SRF increased UCP expression. RNA interference-mediated depletion of endogenous Egr-1 or SRF impaired EGF- or serum-mediated induction of UCP expression, which was required for cancer cell proliferation. Systemic delivery of EGF into mice also increased UCP expression following early induction of Egr-1 expression in mouse liver. The induced UCP expression by the growth factors or serum increased HIF-1alpha protein level under non-hypoxic conditions, suggesting that the Egr-1/SRF-UCP-VHL pathway is in part responsible for the increased HIF-1alpha protein level in vitro and in vivo. Thus, growth factors and serum induce expression of Egr-1 and SRF, respectively, which in turn induces UCP expression that positively regulates cancer cell growth.

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

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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.

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

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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.

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...

76 FR 3909 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Family...

Science.gov (United States)

2011-01-21

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Family History and Diamond..., discussion, and evaluation of ``Family History and Diamond Blackfan Anemia, DD11-010, initial review...

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.

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

Novel mutations in Norrie disease gene in Japanese patients with Norrie disease and familial exudative vitreoretinopathy.

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Kondo, Hiroyuki; Qin, Minghui; Kusaka, Shunji; Tahira, Tomoko; Hasebe, Haruyuki; Hayashi, Hideyuki; Uchio, Eiichi; Hayashi, Kenshi

2007-03-01

To search for mutations in the Norrie disease gene (NDP) in Japanese patients with familial exudative vitreoretinopathy (FEVR) and Norrie disease (ND) and to delineate the mutation-associated clinical features. Direct sequencing after polymerase chain reaction of all exons of the NDP gene was performed on blood collected from 62 probands (31 familial and 31 simplex) with FEVR, from 3 probands with ND, and from some of their family members. The clinical symptoms and signs in the patients with mutations were assessed. X-inactivation in the female carriers was examined in three FEVR families by using leukocyte DNA. Four novel mutations-I18K, K54N, R115L, and IVS2-1G-->A-and one reported mutation, R97P, in the NDP gene were identified in six families. The severity of vitreoretinopathy varied among these patients. Three probands with either K54N or R115L had typical features of FEVR, whereas the proband with R97P had those of ND. Families with IVS2-1G-->A exhibited either ND or FEVR characteristics. A proband with I18K presented with significant phenotypic heterogeneity between the two eyes. In addition, affected female carriers in a family harboring the K54N mutation presented with different degrees of vascular abnormalities in the periphery of the retina. X-inactivation profiles indicated that the skewing was not significantly different between affected and unaffected women. These observations indicate that mutations of the NDP gene can cause ND and 6% of FEVR cases in the Japanese population. The X-inactivation assay with leukocytes may not be predictive of the presence of a mutation in affected female carriers.

A psychometric evaluation of the PedsQL™ Family Impact Module in parents of children with sickle cell disease

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Hoffmann Raymond G

2009-04-01

Full Text Available Abstract Background Caring for a child with a chronic condition, such as sickle cell disease, can have a significant impact on parents and families. In order to provide comprehensive care and support to these families, psychometrically sound instruments are needed as an initial step in measuring the impact of chronic diseases on parents and families. We sought to evaluate the psychometric properties of the PedsQL™ Family Impact Module in populations of children with and without sickle cell disease. In addition, we sought to determine the correlation between parent's well being and their proxy report of their child's health-related quality of life (HRQL. Methods We conducted a cross-sectional study of parents of children with and without sickle cell disease who presented to an urban hospital-based sickle cell disease clinic and an urban primary care clinic. We assessed the HRQL and family functioning of both groups of parents utilizing the PedsQL™ Family Impact Module. The reliability, validity and factor structure of the instrument were determined and scores from the instrument were correlated with scores from parent-proxy report of their child's HRQL using the PedsQL™ 4.0 Generic Core Scales. Results Parents of 170 children completed the module (97 parents of children with sickle cell disease and 73 parents of children without sickle cell disease. The Family Impact Module had high ceiling effects but was reliable (Cronbach's alpha > 0.80 in all scales. The empirical factor structure was generally consistent with the theoretical factor structure and supported construct validity. The Family Impact Module discriminated between parents of children with severe sickle cell disease from parents of children with mild disease or no disease in the areas of communication and worry. There were no significant differences across any of the subscales between parents of children with mild sickle cell disease and those with no disease. Parents with higher

Clinical relevance of apolipoprotein E genotyping based on a family history of Alzheimer's disease.

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Luckhoff, Hilmar K; Brand, Theresa; van Velden, Dawid P; Kidd, Martin; Fisher, Leslie R; van Rensburg, Susan J; Kotze, Maritha J

2015-01-01

Having a family history of Alzheimer' s disease (AD) may potentiate cumulative risk associated with phenotypic expression of the ε-4 allele of the apolipoprotein E (APOE) gene. In this study, we compared the genotype distribution and allele frequencies of APOE ε-2 (rs7412) and ε -4 (rs429358) in 537 South African individuals participating in a chronic disease screening program, in order to establish whether AD family history modulates the expression of their dyslipidemic effects. Significant differences in the genotype distribution for APOE ε-2 (p=0.034) as well as APOE ε-4 (p=0.038) were found between study participants with (n=67) and without (n=470) a family history of AD. LDL cholesterol levels were inversely associated with physical activity in the study group with a positive family history of AD (pfamilial hypercholesterolemia, clinical inquiry regarding family history was identified as an important determinant of eligibility for APOE genotyping performed in the context of chronic disease risk management. To our knowledge, this is the first study to demonstrate the modulating influence of AD family history on expression of a dyslipidemic phenotype associated with the APOE ε-4 allele. Our findings provide the scientific rationale supporting a novel clinical application for APOE genotyping as a means of identifying a genetic subgroup of dyslipidemic patients set to derive the greatest benefit from early lifestyle-based interventions aimed at decreasing cumulative risk for cardiovascular disease and prevention of AD later in life.

Specific deficit of colour-colour short-term memory binding in sporadic and familial Alzheimer's disease.

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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.

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

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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

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...... for conducting life in an HD family. A framework that implies that being informed and making use of genetic services expresses greater moral responsibility than conducting life without drawing on these resources. The moral imperative of engagement in medical genetics is challenged here by two pieces...... nor the imagined solutions of medical genetics are as unproblematic and straightforward as might be thought. To assist our understanding of the moral aspects of living with severe familial disease, the ethnographic analysis is aligned with bioethical reflections that place the concrete concerns...

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

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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.

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.

[Systemic family therapy in the context of Alzheimer's disease: a theoretical and practical approach].

Science.gov (United States)

Cantegreil-Kallen, Inge; Rigaud, Anne-Sophie

2009-12-01

Alzheimer's disease has a negative impact on family relationships and may trigger conflicts between the main caregiver and other family members. The systemic approach evidences the impact of dementia on structural and functional characteristics of the family system. Systemic family therapy is especially indicated in crisis situations such as emergency hospitalization or institutionalization of the patient, and when the family members do not agree on when and how to introduce care and support services at the patient's home. In this case, the aim of the intervention is to restore the communication between all the family members in order to find an agreement for the best management of the patients. Since September 2006, systemic family therapy has been offered in the memory clinic of the Broca Hospital to families having a member suffering from Alzheimer's disease. The involvement of the families was accomplished by the direct participation of the patient, main caregiver (spouse), grown-up children and grandchildren. The aim was to obtain an agreement for the access of support and care services at home from all the family members. The intervention was based on a step-by-step procedure and comprehended five sessions. The primary results of a pilot study are presented.

Adult family members and their resemblance of coronary heart disease risk factors: The Cardiovascular Disease Study in Finnmark

International Nuclear Information System (INIS)

Brenn, Tormod

1997-01-01

Coronary heart disease tends to run in families, and the familial resemblance of major risk factors for the disease was examined among various types of adult family members. Family units were assembled from a total of 4,738 men and women who took part in a cross sectional health survey in four Norwegian municipalities where all inhabitants between 20 and 52 years of age were invited. After adjusting for age and other confounders, correlation coefficients were derived as a measure of the degree of resemblance. Viewed across all types of investigated familial relationships, similarity was found to be stronger for total cholesterol than for high-density lipoprotein cholesterol and triglycerides, and also stronger for systolic than for diastolic blood pressure. Between husbands and wives (3,060 subjects), correlations were small (between 0.02 and 0.06), except for 0.11 for total cholesterol. Lipid and blood pressure correlations ranged from 0.13 to 0.27 for parents and their offspring (471 subjects, p < 0.05) and from 0.11 to 0.22 among siblings (2,166 subjects, p < 0.01). Sibling correlations were consistent across age groups. Furthermore, reports from each individual on daily smoking (yes or no) revealed that husbands and wives had similar habits in 63.5% of all marriages as compared with the expected 49.4% had no smoking similarity at all been present. Smoking concordance was also demonstrated among siblings (p < 0.01). The persistent pattern of lipid and blood pressure aggregation among genetically related individuals from 20 to 52 years of age and the much weaker such similarity between husbands and wives, point towards genes or commonly shared environment at early ages as a major reason why coronary heart disease runs in families

Familial aggregation of Parkinson’s disease and coaggregation with neuropsychiatric diseases: a population-based cohort study

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Liu FC

2018-05-01

Full Text Available Fu-Chao Liu,1,2,* Huan-Tang Lin,1,2,* Chang-Fu Kuo,2–4 Mei-Yun Hsieh,4 Lai-Chu See,3,5,6 Huang-Ping Yu1,2,7 1Department of Anesthesiology, Chang Gung Memorial Hospital, Taoyuan, Taiwan; 2College of Medicine, Chang Gung University, Taoyuan, Taiwan; 3Division of Rheumatology, Allergy and Immunology, Chang Gung Memorial Hospital, Taoyuan, Taiwan; 4Office for Big Data Research, Chang Gung Memorial Hospital, Taoyuan, Taiwan; 5Department of Public Health, College of Medicine, Chang Gung University, Taoyuan, Taiwan; 6Biostatistics Core Laboratory, Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan; 7Department of Anesthesiology, Xiamen Changgung Hospital, Xiamen, China *These authors contributed equally to this work Background: Individuals with a family history of Parkinson’s disease (PD appear to have a higher risk of developing PD and other neuropsychiatric diseases. However, estimates of the relative risks (RRs of PD and the roles of genetic and environmental factors in PD susceptibility are unclear. The aim of this study was to examine familial aggregation and genetic contributions to PD and the RRs of other neuropsychiatric diseases in relatives of PD patients. Methods: In this population-based family cohort study, the records of all individuals actively registered in the Taiwan National Health Insurance Research Database in 2015 were queried (N=24,349,599. In total, 149,187 individuals with a PD-affected parent, 3,698 with an affected offspring, 3,495 with an affected sibling, and 15 with an affected twin were identified. Diagnoses of PD were ascertained between January 1, 1999, and December 31, 2015. The prevalence and RRs of PD and other neuropsychiatric diseases in individuals with first-degree relatives with PD, as well as the contributions of heritability and environmental factors to PD susceptibility were investigated. Results: The prevalence of PD was 0.46% in the general population and 0.52% in individuals with

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

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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.

Clinical reinvestigation and linkage analysis in the family with Episkopi blindness (Norrie disease).

OpenAIRE

Wolff, G; Mayerová, A; Wienker, T F; Atalianis, P; Ioannou, P; Warburg, M

1992-01-01

We present the results of a clinical and genetic reinvestigation of the Cypriot family affected by an X chromosomally inherited eye disease originally published by Taylor et al, who coined the term Episkopi blindness. The pedigree was extended to 160 members, including 16 affected males out of 48 males at risk for the disease, most of whom were seen by one of us (PA). Affected males are blind with no associated symptoms and apparently are not mentally retarded. Thirty-nine family members agre...

A novel Norrie disease pseudoglioma gene mutation, c.-1_2delAAT, responsible for Norrie disease in a Chinese family.

Science.gov (United States)

Zhang, Xin-Yu; Jiang, Wei-Ying; Chen, Lu-Ming; Chen, Su-Qin

2013-01-01

To investigate the genetic findings and phenotypic characteristics of a Chinese family with Norrie disease (ND). Molecular genetic analysis and clinical examinations were performed on a Chinese family with ND. Mutations in the Norrie disease pseudoglioma (NDP) gene were detected by direct sequencing. Haplotypes were constructed and compared with the phenotypes in the family. Evolutionary comparisons and mutant open reading frame (ORF) prediction were also undertaken. Two family members with ocular manifestations were diagnosed with ND. No signs of sensorineural hearing loss were observed in either patient, while one of them showed signs of mild mental retardation. A novel heterozygous mutation in the NDP gene, c.-1_2delAAT, was detected in both patients. The mutation and the mutation bearing haplotype co-segregated with the ND phenotype in males and was transmitted from their mothers and/or grandmothers (II:2). The male without ND did not harbor the mutation. The mutation occurred at the highly conserved nucleotides. ORF finder predicted that the mutation would lead to the production of a truncated protein that lacks the first 11 N-terminal amino acids. A novel mutation, c.-1_2delAAT in the NDP gene, was identified in a Chinese family with ND. This mutation caused ND without obvious sensorineural hearing loss. Mental disorder was found in one but not the other patients. The clinical heterogeneity in the family indicated that other genetic variants and epigenetic factors may also play a role in the disease presentation.

Comorbidity in patients with chronic obstructive pulmonary disease in family practice: a cross sectional study.

Science.gov (United States)

García-Olmos, Luis; Alberquilla, Angel; Ayala, Victoria; García-Sagredo, Pilar; Morales, Leticia; Carmona, Montserrat; de Tena-Dávila, María José; Pascual, Mario; Muñoz, Adolfo; Salvador, Carlos H; Monteagudo, Jose L

2013-01-16

Chronic obstructive pulmonary disease (COPD) is frequent and often coexists with other diseases. The aim of this study was to quantify the prevalence of COPD and related chronic comorbidity among patients aged over 40 years visiting family practices in an area of Madrid. An observational, descriptive, cross-sectional study was conducted in a health area of the Madrid Autonomous Region (Comunidad Autónoma de Madrid). The practice population totalled 198,670 persons attended by 129 Family Physicians (FPs), and the study population was made up of persons over the age of 40 years drawn from this practice population. Patients were deemed to have COPD if this diagnosis appeared on their clinical histories. Prevalence of COPD; prevalence of a further 25 chronic diseases in patients with COPD; and standardised prevalence ratios, were calculated. Prevalence of COPD in family medicine was 3.2% (95% CI 3.0-3.3) overall, 5.3% among men and 1.4% among women; 90% of patients presented with comorbidity, with a mean of 4 ± 2.04 chronic diseases per patient, with the most prevalent related diseases being arterial hypertension (52%), disorders of lipid metabolism (34%), obesity (25%), diabetes (20%) and arrhythmia (15%). After controlling for age and sex, the observed prevalence of the following ten chronic diseases was higher than expected: heart failure; chronic liver disease; asthma; generalised artherosclerosis; osteoporosis; ischaemic heart disease; thyroid disease; anxiety/depression; arrhythmia; and obesity. Patients with COPD, who are frequent in family practice, have a complex profile and pose a clinical and organisational challenge to FPs.

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

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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

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.

Science.gov (United States)

Wilson, Carlene J; de la Haye, Kayla; Coveney, John; Hughes, Donna L; Hutchinson, Amanda; Miller, Caroline; Prichard, Ivanka; Ward, Paul; Koehly, Laura M

2016-09-13

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. 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 risk using social network approaches and to compare

Co-existence of classic familial lecithin-cholesterol acyl transferase deficiency and fish eye disease in the same family

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H S Mahapatra

2015-01-01

Full Text Available We report a family with a rare genetic disorder arising out of mutation in the gene that encodes for the enzyme lecithin-cholesterol acyltransferase (LCAT. The proband presented with nephrotic syndrome, hemolytic anemia, cloudy cornea, and dyslipidemia. Kidney biopsy showed certain characteristic features to suggest LCAT deficiency, and the enzyme activity in the serum was undetectable. Mother and younger sister showed corneal opacity and dyslipidemia but no renal or hematological involvement. These two members had a milder manifestation of the disease called fish eye disease. This case is presented to emphasize the importance of taking family history and doing a good clinical examination in patients with nephrotic syndrome and carefully analyze the lipid fractions in these subset of patients.

Clinical Study on Patients with Renal-Cell Carcinoma Accompanied with Von Hippel Lindau Disease Treated with Radiofrequency Ablation

OpenAIRE

波越, 朋也; 島本, 力; 辛島, 尚; 亀井, 麻依子; 福原, 秀雄; 深田, 聡; 佐竹, 宏文; 蘆田, 真吾; 山崎, 一郎; 鎌田, 雅行; 井上, 啓史; 山西, 伴明; 小川, 恭弘; 伊藤, 悟志; 執印, 太郎

2014-01-01

We report 12 renal cell carcinomas in 6 patients with Von Hippel-Lindau (VHL) disease treated with radiofrequency ablation (RFA). The mean age of the patients was 46 (range 38-53) years (male : 4, female : 2). Computed tomography (CT)-guided transcutaneous RFA was performed under conscious sedation with local anesthetics. The mean size of the tumors was 2.4 (range 0.7-8.1) cm. Nine of the 12 tumors (75%) were locally well controlled. However, 3 tumors in 2 patients developed visceral metastas...

Relation between family history, obesity and risk for diabetes and heart disease in Pakistani children

International Nuclear Information System (INIS)

Basit, A.; Hakeem, R.; Hydrie, M.Z.; Ahmadani, M.Y.; Masood, Q.

2004-01-01

Objective: To assess the differences in relative risk of developing diabetes and CHD, obesity, fasting blood glucose, insulin and lipids of children having family history of diabetes or heart disease in first or second degree relatives as compared to control group. Design: Children were given a questionnaire to collect demographic data and to assess their dietary habits and family history. Anthropometric measurements and blood samples for fasting blood glucose, insulin and lipids of 8-10 years old children from 4 schools was taken. Subjects: Children having positive family history of diabetes (n=44) or heart disease (n=16) in first or second degree relatives were compared with a control group (n=39). Results: Children having positive family history for diabetes had slightly higher mean values for BMI, waist circumference, arm fat % as compared to the controls but the differences were not statistically significant. Overweight children (>85th Percentile of BMI for age) did not differ significantly in terms of various risk indicators however those who were in the uppermost tertile of arm fat % had significantly higher total Cholesterol, Triglycerides, LDL-C, LDL:HDL and Insulin levels (P<0.05 in each case). Conclusion: Diabetes and CVD risks from positive family history for the disease are probably mediated through increased body fat percentage. Thus even when information about family history of disease is lacking, arm-fat-percentage could be used as an important screening tool for determining the risk status of children. (author)

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

Molecular analysis of the NDP gene in two families with Norrie disease.

Science.gov (United States)

Rivera-Vega, M Refugio; Chiñas-Lopez, Silvet; Vaca, Ana Luisa Jimenez; Arenas-Sordo, M Luz; Kofman-Alfaro, Susana; Messina-Baas, Olga; Cuevas-Covarrubias, Sergio Alberto

2005-04-01

To describe the molecular defects in the Norrie disease protein (NDP) gene in two families with Norrie disease (ND). We analysed two families with ND at molecular level through polymerase chain reaction, DNA sequence analysis and GeneScan. Two molecular defects found in the NDP gene were: a missense mutation (265C > G) within codon 97 that resulted in the interchange of arginine by proline, and a partial deletion in the untranslated 3' region of exon 3 of the NDP gene. Clinical findings were more severe in the family that presented the partial deletion. We also diagnosed the carrier status of one daughter through GeneScan; this method proved to be a useful tool for establishing female carriers of ND. Here we report two novel mutations in the NDP gene in Mexican patients and propose that GeneScan is a viable mean of establishing ND carrier status.

A novel Norrie disease pseudoglioma gene mutation, c.-1_2delAAT, responsible for Norrie disease in a Chinese family

Directory of Open Access Journals (Sweden)

Xin-Yu Zhang

2013-12-01

Full Text Available AIM:To investigate the genetic findings and phenotypic characteristics of a Chinese family with Norrie disease (ND.METHODS:Molecular genetic analysis and clinical examinations were performed on a Chinese family with ND. Mutations in the Norrie disease pseudoglioma (NDP gene were detected by direct sequencing. Haplotypes were constructed and compared with the phenotypes in the family. Evolutionary comparisons and mutant open reading frame (ORF prediction were also undertaken.RESULTS:Two family members with ocular manifestations were diagnosed with ND. No signs of sensorineural hearing loss were observed in either patient, while one of them showed signs of mild mental retardation. A novel heterozygous mutation in the NDP gene, c.-1_2delAAT, was detected in both patients. The mutation and the mutation bearing haplotype co-segregated with the ND phenotype in males and was transmitted from their mothers and/or grandmothers (II:2. The male without ND did not harbor the mutation. The mutation occurred at the highly conserved nucleotides. ORF finder predicted that the mutation would lead to the production of a truncated protein that lacks the first 11 N-terminal amino acids.CONCLUSION:A novel mutation, c.-1_2delAAT in the NDP gene, was identified in a Chinese family with ND. This mutation caused ND without obvious sensorineural hearing loss. Mental disorder was found in one but not the other patients. The clinical heterogeneity in the family indicated that other genetic variants and epigenetic factors may also play a role in the disease presentation.

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.

Evaluation of the norrie disease gene in a family with incontinentia pigmenti.

Science.gov (United States)

Shastry, B S; Trese, M T

2000-01-01

Incontinentia pigmenti (IP) is an ectodermal multisystem disorder which can affect dental, ocular, cardiac and neurologic structures. The ocular changes of IP can have a very similar appearance to the retinal detachment of X-linked familial exudative vitreoretinopathy, which has been shown to be caused by the mutations in the Norrie disease gene. Therefore, it is of interest to determine whether similar mutations in the gene can account for the retinal pathology in patients with IP. To test our hypothesis, we have analyzed the entire Norrie disease gene for a family with IP, by single strand conformational polymorphism followed by DNA sequencing. The sequencing data revealed no disease-specific sequence alterations. These data suggest that ocular findings of IP are perhaps associated with different genes and there is no direct relationship between the genotype and phenotype. Copyright 2000 S. Karger AG, Basel

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.

Familial aggregation of arthritis-related diseases in seropositive and seronegative rheumatoid arthritis: a register-based case-control study in Sweden.

Science.gov (United States)

Frisell, Thomas; Hellgren, Karin; Alfredsson, Lars; Raychaudhuri, Soumya; Klareskog, Lars; Askling, Johan

2016-01-01

Our objective was to estimate the risk of developing rheumatoid arthritis (RA) associated with a family history of non-RA arthritis-related diseases. This familial co-aggregation is of clinical interest since it is often encountered when assessing family history of RA specifically, but also informative on the genetic overlap between these diseases. Since anticitrullinated peptide antibodies/rheumatoid factor (RF)-positive and RF-negative RA have both specific and shared genetic factors, the familial co-aggregation was assessed separately for seropositive and seronegative disease. Nested case-control study in prospectively recorded Swedish total population data. The Multi-Generation Register identified first-degree relatives. RA and arthritis-related diseases were ascertained through the nationwide patient register. RA serology was based on International Classification of Diseases tenth revision coded diagnoses, mainly reflecting RF. Familial risks were calculated using conditional logistic regression. Results were replicated using the Swedish rheumatology register. Familial co-aggregation was found between RA and every studied arthritis-related disease, but the magnitude varied widely, from juvenile idiopathic arthritis (JIA) (seropositive RA OR=3.98 (3.01 to 5.26); seronegative RA OR=5.70 (3.47 to 9.36)) to osteoarthritis (seropositive RA OR=1.03 (1.00 to 1.06); seronegative RA OR=1.05 (1.00 to 1.09)). The familial co-aggregation pattern of non-RA arthritis-related diseases was overall similar for seropositive and seronegative RA. Among those with family history of RA, relatives' other arthritis-related diseases conferred little or no additional risk. Although family history of several arthritis-related diseases may be useful to predict RA (eg, lupus and JIA), others (eg, osteoarthritis and arthralgia) are less useful. Seropositive and seronegative RA had rather similar familial co-aggregation patterns with arthritis-related diseases, suggesting that the two RA

Fabry Disease in Families With Hypertrophic Cardiomyopathy: Clinical Manifestations in the Classic and Later-Onset Phenotypes.

Science.gov (United States)

Adalsteinsdottir, Berglind; Palsson, Runolfur; Desnick, Robert J; Gardarsdottir, Marianna; Teekakirikul, Polakit; Maron, Martin; Appelbaum, Evan; Neisius, Ulf; Maron, Barry J; Burke, Michael A; Chen, Brenden; Pagant, Silvere; Madsen, Christoffer V; Danielsen, Ragnar; Arngrimsson, Reynir; Feldt-Rasmussen, Ulla; Seidman, Jonathan G; Seidman, Christine E; Gunnarsson, Gunnar Th

2017-08-01

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). Familial screening of at-risk relatives identified mutations in 16 family A members (8 men and 8 heterozygotes) and 25 family B members (10 men and 15 heterozygotes). Clinical assessments, α-galactosidase A (α-GalA) activities, glycosphingolipid substrate levels, and in vitro mutation expression were used to categorize p.D322E as a classic FD mutation and p.I232T as a later-onset FD mutation. In vitro expression revealed that p.D322E and p.I232T had α-GalA activities of 1.4% and 14.9% of the mean wild-type activity, respectively. Family A men had markedly decreased α-GalA activity and childhood-onset classic manifestations, except for angiokeratoma and cornea verticillata. Family B men had residual α-GalA activity and developed FD manifestations in adulthood. Despite these differences, all family A and family B men >30 years of age had left ventricular hypertrophy, which was mainly asymmetrical, and had similar late gadolinium enhancement patterns. Ischemic stroke and severe white matter lesions were more frequent among family A men, but neither family A nor family B men had overt renal disease. Family A and family B heterozygotes had less severe or no clinical manifestations. Men with classic or later-onset FD caused by GLA missense mutations developed prominent and similar cardiovascular disease at similar ages, despite markedly different α-GalA activities. © 2017 American Heart Association, Inc.

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…

[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.

Molecular characterization of a virus from the family Luteoviridae associated with cotton blue disease.

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Corrêa, R L; Silva, T F; Simões-Araújo, J L; Barroso, P A V; Vidal, M S; Vaslin, M F S

2005-07-01

Cotton blue disease is an aphid-transmitted cotton disease described in Brazil in 1962 as Vein Mosaic "var. Ribeirão Bonito". At present it causes economically important losses in cotton crops if control measures are not implemented. The observed symptoms and mode of transmission have prompted researchers to speculate that cotton blue disease could be attributed to a member of the family Luteoviridae, but there was no molecular evidence supporting this hypothesis. We have amplified part of the genome of a virus associated with this disease using degenerate primers for members of the family Luteoviridae. Sequence analysis of the entire capsid and a partial RdRp revealed a virus probably belonging to the genus Polerovirus. Based on our results we propose that cotton blue disease is associated with a virus with the putative name Cotton leafroll dwarf virus (CLRDV).

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...... to airflow obstruction in COPD. These phenotypes show independent aggregation within families of individuals with COPD, suggesting that different genetic factors influence these disease processes....... 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...

Malignant peripheral nerve sheath tumours in inherited disease

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Evans D

2012-10-01

Full Text Available Abstract Background Malignant peripheral nerve sheath tumours (MPNST are rare tumours known to occur at high frequency in neurofibromatosis 1 (NF1, but may also occur in other cancer prone syndromes. Methods The North West Regional Genetic Register covers a population of 4.1 million and was interrogated for incidence of MPNST in 12 cancer prone syndromes. Age, incidence and survival curves were generated for NF1. Results Fifty two of 1254 NF1 patients developed MPNST, with MPNST also occurring in 2/181 cases of schwannomatosis and 2/895 NF2 patients. Three cases were also noted in TP53 mutation carriers. However, there were no cases amongst 5727BRCA1/2 carriers and first degree relatives, 2029 members from Lynch syndrome families, nor amongst 447 Familial Adenomatous Polyposis, 202 Gorlin syndrome, nor 87 vHL cases. Conclusion MPNST is associated with schwannomatosis and TP53 mutations and is confirmed at high frequency in NF1. It appears to be only increased in NF2 amongst those that have been irradiated. The lifetime risk of MPNST in NF1 is between 9–13%.

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

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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.

Primary prevention of cardiovascular diseases: a cost study in family practices.

NARCIS (Netherlands)

Bekker-Grob, E.W. de; Dulmen, S. van; Berg, M. van den; Verheij, R.A.; Slobbe, L.C.J.

2011-01-01

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

Evaluation of Gene-Based Family-Based Methods to Detect Novel Genes Associated With Familial Late Onset Alzheimer Disease

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Maria V. Fernández

2018-04-01

Full Text Available Gene-based tests to study the combined effect of rare variants on a particular phenotype have been widely developed for case-control studies, but their evolution and adaptation for family-based studies, especially studies of complex incomplete families, has been slower. In this study, we have performed a practical examination of all the latest gene-based methods available for family-based study designs using both simulated and real datasets. We examined the performance of several collapsing, variance-component, and transmission disequilibrium tests across eight different software packages and 22 models utilizing a cohort of 285 families (N = 1,235 with late-onset Alzheimer disease (LOAD. After a thorough examination of each of these tests, we propose a methodological approach to identify, with high confidence, genes associated with the tested phenotype and we provide recommendations to select the best software and model for family-based gene-based analyses. Additionally, in our dataset, we identified PTK2B, a GWAS candidate gene for sporadic AD, along with six novel genes (CHRD, CLCN2, HDLBP, CPAMD8, NLRP9, and MAS1L as candidate genes for familial LOAD.

Individual and family strengths: an examination of the relation to disease management and metabolic control in youth with type 1 diabetes.

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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.

The validity of the family history method for identifying Alzheimer disease.

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Li, G; Aryan, M; Silverman, J M; Haroutunian, V; Perl, D P; Birstein, S; Lantz, M; Marin, D B; Mohs, R C; Davis, K L

1997-05-01

To examine the validity of the family history method for identifying Alzheimer disease (AD) by comparing family history and neuropathological diagnoses. Seventy-seven former residents of the Jewish Home and Hospital for the Aged, New York, NY, with neuropathological evaluations on record were blindly assessed for the presence of dementia and, if present, the type of dementia through family informants by telephone interviews. The Alzheimer's Disease Risk Questionnaire was used to collect demographic information and screen for possible dementia. If dementia was suspected, the Dementia Questionnaire was administered to assess the course and type of dementia, i.e., primary progressive dementia (PPD, likely AD), multiple infarct dementia, mixed dementia (i.e., PPD and multiple infarct dementia), and other dementias based on the modified Diagnostic and Statistical Manual of Mental Disorders, Third Edition, criteria. Sixty (77.9%) of 77 elderly subjects were classified as having dementia and 17 (22.1%) were without dementia by family history evaluation. Of the 60 elderly subjects with dementia, 57 (95%) were found at autopsy to have had neuropathological changes related to dementia. The sensitivity of the family history diagnosis for dementia with related neuropathological change was 0.84 (57 of 68) and the specificity was 0.67 (6 of 9). Using family history information to differentiate the type of dementia, the sensitivity for definite or probable AD (with or without another condition) was 0.69 (36 of 51) and the specificity was 0.73 (19 of 26). The majority (9 of 15) of patients testing false negative for PPD had a history of stroke associated with onset of memory changes, excluding a diagnosis of PPD. Identifying dementia, in general, and AD, in particular, has an acceptable sensitivity and specificity. As is true for direct clinical diagnosis, the major issue associated with misclassifying AD in a family history assessment is the masking effects of a coexisting non

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...

Is Autism a Member of a Family of Diseases Resulting from Genetic/Cultural Mismatches? Implications for Treatment and Prevention

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Staci D. Bilbo

2012-01-01

Full Text Available 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.

Management of patients with coronary heart disease in family medicine: correlates of quality of care.

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Tušek-Bunc, Ksenija; Petek, Davorina

2018-04-10

Family medicine plays an important role in quality of care (QoC) of coronary heart disease (CHD) patients. This study's aim was to determine the quality of secondary cardiovascular disease prevention in the everyday practice of family physicians. This study was observational cross-sectional. About 36 randomly selected family medicine practices stratified by size and location in Slovenia. CHD patients randomly selected from a patient register available in family medicine practices. The instrument for assessment of quality included a form for collecting data from medical records, a general practice assessment questionnaire and a patient questionnaire. QoC was defined by two composite variables, namely risk factor registration and CHD patient process of care, as the two care outcomes. In multivariate analysis, we performed multilevel regression analysis to identify the associations between QoC, the patient and the practice characteristics. The final sample included 423 CHD patients from 36 family medicine practices. Risk factor registration was associated with the practice organisation score (P = 0.004), practice size (P = 0.042), presence of comorbid atherosclerotic diseases (P = 0.043) and a lower age of CHD patients (P = 0.001). CHD patient process of care was associated with the practice organisation score (0.045) and a lower age of CHD patients (P = 0.035). The most important factors affecting the quality of CHD patient care were linked to the organisational characteristics of the family medicine practices.

Premature Coronary Artery Disease due to Homozygous Familial Hypercholesterolemia in a 12-Year-Old Girl

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Filiz Ekici

2018-03-01

Full Text Available Background: Homozygous familial hypercholesterolemia is a rare inherited metabolic disease caused by low-density lipoprotein receptor abnormality. Patients with homozygous familial hypercholesterolemia have an increased risk of cardiovascular complication that usually occurs in the first decade of life. Here, we report a 12-year-old girl with an unpredicted presentation for coronary artery disease and found to have homozygous familial hypercholesterolemia. Case Report: A 12-year-old girl was admitted to our unit with syncope. Chest X-ray showed bilateral diffuse pneumonic consolidation and mild cardiomegaly. We detected stable ST depression by electrocardiography. Echocardiography showed normal systolic functions. Troponin-1 levels were high (66 mcg/dL, upper limit: 0.04 mcg/dL. Influenza A virus DNA was detected by the respiratory viral panel. After her successful treatment for acute pneumonia and myocarditis due to Influenza A virus, her syncope attacks persisted. Marked ST elevation was observed during exercise electrocardiography. Coronary angiography showed severe occlusions in the coronary arteries. High serum levels of total cholesterol (756 mg/dL and low-density lipoprotein-C (556 mg/dL were noticed. She had no tendon xanthomas. Medical histories revealed that her family members were diagnosed with heterozygous familial hypercholesterolemia. A coronary bypass surgery was performed. Statin and ezetimibe treatments were started. We also planned lipid apheresis. Conclusion: Children with homozygous familial hypercholesterolemia may present with symptoms of premature coronary heart disease requiring a routine lipid test and careful anamnesis.

Familial polycystic ovarian disease.

Science.gov (United States)

Givens, J R

1988-12-01

Emphasis is placed on the heterogeneity of the phenotypic presentation of PCOD. It is the common expression of an unknown number of disorders and thus is a sign and not a specific diagnosis. Two essential features are arrested follicular maturation and atresia of follicles. Normal folliculogenesis is described, emphasizing that a large number of areas could be subject to derangement causing PCOD. Any interference of the finely balanced sequence of events can lead to PCOD. The genetic defect causing familial PCOD is unknown and the initiating event remains undefined. Three families are described that illustrate four features of familial PCOD. A number of associated disorders such as diabetes, hyperinsulinemia, obesity, and hypertension are described. The potential importance of agents that modulate the LH and FSH activity that may cause PCOD is emphasized. The theoretic means by which similar male and female gonadal abnormalities may be coupled in families through growth factors EGF and alpha TGF are presented.

Family History

Science.gov (United States)

Your family history includes health information about you and your close relatives. Families have many factors in common, including their genes, ... as heart disease, stroke, and cancer. Having a family member with a disease raises your risk, but ...

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).

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

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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.

A novel c.240_241insGG mutation in NDP gene in a family with Norrie disease.

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Andarva, Monavvar; Jamshidi, Javad; Ghaedi, Hamid; Daftarian, Narsis; Emamalizadeh, Babak; Alehabib, Elham; Taghavi, Shaghyegh; Pouriran, Ramin; Darvish, Hossein

2018-03-01

Norrie disease (ND) is a rare, X-linked recessive disorder with the main characteristic of early childhood blindness. The aim of the present study was to identify the genetic cause of the disease and the phenotypic characteristics of the patients in an Iranian family with four affected males with ND. Norrie disease pseudoglioma (NDP) gene was sequenced and clinical examination was performed on patients. A GG dinucleotide insertion in exon 3 (c.240_241insGG) of NDP was detected in all patients. The mutation caused a frameshift and an early stop codon (p.Phe81Glyfs*23). A novel mutation was found in the NDP gene in the affected males of the family. As the mutation was absent in the normal male members of the family, it should be the genetic cause of the disease. © 2017 Optometry Australia.

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

Genotype-phenotype variations in five Spanish families with Norrie disease or X-linked FEVR.

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Riveiro-Alvarez, Rosa; Trujillo-Tiebas, Maria José; Gimenez-Pardo, Ascension; Garcia-Hoyos, Maria; Cantalapiedra, Diego; Lorda-Sanchez, Isabel; Rodriguez de Alba, Marta; Ramos, Carmen; Ayuso, Carmen

2005-09-02

Norrie disease (OMIM 310600) is a rare X-linked disorder characterized by congenital blindness in males. Approximately 40 to 50% of the cases develop deafness and mental retardation. X-linked familial exudative vitreoretinopathy (XL-FEVR) is a hereditary ocular disorder characterized by a failure of peripheral retinal vascularization. Both X-linked disorders are due to mutations in the NDP gene, which encodes a 133 amino acid protein called Norrin, but autosomal recessive (AR) and autosomal dominant (AD) forms of FEVR have also been described. In this study, we report the molecular findings and the related phenotype in five Spanish families affected with Norrie disease or XL-FEVR due to mutations of the NDP gene. The study was conducted in 45 subjects from five Spanish families. These families were clinically diagnosed with Norrie disease or similar conditions. The three exons of the NDP gene were analyzed by automatic DNA sequencing. Haplotype analyses were also performed. Two new nonsense mutations, apart from other mutations previously described in the NDP gene, were found in those patients affected with ND or X-linked FEVR. An important genotype-phenotype variation was found in relation to the different mutations of the NDP gene. In fact, the same mutation may be responsible for different phenotypes. We speculate that there might be other molecular factors that interact in the retina with Norrin, which contribute to the resultant phenotypes.

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

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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

Patient-centered care in chronic disease management: a thematic analysis of the literature in family medicine.

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Hudon, Catherine; Fortin, Martin; Haggerty, Jeannie; Loignon, Christine; Lambert, Mireille; Poitras, Marie-Eve

2012-08-01

The objective was to provide a synthesis of the results of the research and discourse lines on main dimensions of patient-centered care in the context of chronic disease management in family medicine, building on Stewart et al.'s model. We developed search strategies for the Medline, Embase, and Cochrane databases, from 1980 to April 2009. All articles addressing patient-centered care in the context of chronic disease management in family medicine were included. A thematic analysis was performed using mixed codification, based on Stewart's model of patient-centered care. Thirty-two articles were included. Six major themes emerged: (1) starting from the patient's situation; (2) legitimizing the illness experience; (3) acknowledging the patient's expertise; (4) offering realistic hope; (5) developing an ongoing partnership; (6) providing advocacy for the patient in the health care system. The context of chronic disease management brings forward new dimensions of patient-centered care such as legitimizing the illness experience, acknowledging patient expertise, offering hope and providing advocacy. Chronic disease management calls for the adaptation of the family physician's role to patients' fluctuating needs. Literature also suggests the involvement of the family physician in care transitions as a component of patient-centered care. Crown Copyright © 2012. Published by Elsevier Ireland Ltd. All rights reserved.

A comparative study of LRRK2, PINK1 and genetically undefined familial Parkinson's disease.

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Nishioka, Kenya; Kefi, Mounir; Jasinska-Myga, Barbara; Wider, Christian; Vilariño-Güell, Carles; Ross, Owen A; Heckman, Michael G; Middleton, Lefkos T; Ishihara-Paul, Lianna; Gibson, Rachel A; Amouri, Rim; Ben Yahmed, Samia; Ben Sassi, Samia; Zouari, Mourad; El Euch, Ghada; Farrer, Matthew J; Hentati, Faycal

2010-04-01

Genetic classification of Parkinson's disease (PD) subtypes may become the preferred diagnostic tool for neurologists. Herein we compare clinical features from a large cohort of patients with familial PD of unknown aetiology or attributable to distinct genetic forms. Comprehensive neurological examinations were performed in 231 familial PD patients from Tunisia. Analysis was previously performed to screen for mutations in leucine rich repeat kinase 2 (LRRK2), PTEN induced kinase 1 (PINK1) and parkin (PRKN). Clinical features were compared between patients with genetically undefined PD (n=107) and those with LRRK2 (n=73) and PINK1 (n=42) mutations using regression analyses adjusted for gender, age of onset and disease duration. PRKN cases (n=9) were too few for meaningful statistical analysis. In comparison with genetically undefined patients, LRRK2 mutation carriers had more severe motor symptoms (median Unified Parkinson's Disease Rating Scale scores approximately 1.6 times higher, pundefined patients. As expected, PINK1 patients had younger ages and ages at disease onset, and a longer disease duration compared with LRRK2 mutation carriers and genetically undefined patients. Clinical differences between LRRK2, PINK1 and genetically undefined familial PD appear more pronounced than previously appreciated, and may prove useful in clinical practice. As future therapies are targeted to specific protein abnormalities, identifying the genetic causes and associated clinical and pathological features will determine diagnosis, preventative medicine and drug intervention strategies.

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

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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

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 ...

Are quality of family life and disease severity related in childhood atopic dermatitis?

Science.gov (United States)

Ben-Gashir, M A; Seed, P T; Hay, R J

2002-09-01

Atopic dermatitis (AD) can be traumatizing to family life. Little is known about the relationship between quality of life in AD and disease severity. To document family quality of life and relate this to severity of AD in children, for a 6-month period from a given point in time. These data are part of a longitudinal study conducted in two parts of the UK to investigate risk factors for AD severity and its impact on quality of life. and methods Thetargetedpopulation comprised children with AD aged 5-10 years in a primary-care setting. The general practitioners identified potential subjects and the UK diagnostic criteria for AD were used to verify the diagnosis. Both the children and their parents were interviewed. Eczema severity was assessed using a modified form of the SCORAD (SCORe Atopic Dermatitis) Index (SCORAD-D) from which parents' score of itching and sleep loss were excluded. The quality of family life was quantified by the Dermatitis Family Impact (DFI) questionnaire. These two parameters were evaluated on two occasions 6 months apart. Multiple regression analysis was used to investigate the relationship between the quality of family life and the severity of the AD in the children, at a specific point in time and over the following 6-month period. Of the 116 children attending the first visit, mean age 8 years, 106 attended the second visit (91%) and were included in the analysis. Quality of family life was shown to be significantly affected in 48 (45%) cases at the first visit and 38 (36%) cases at the second visit. The initial means of the DFI and SCORAD-D were 2.4 and 8.2, respectively. Six months later the mean final DFI and SCORAD-D were 1.9 and 7.7, respectively. Using multiple regression on the first and second visits, each unit increase in SCORAD-D was associated with 0.21 [95% confidence interval (CI) 0.06-0.37 P = 0.008] and 0.37 (95% CI 0.15-0.59, P = 0.001) units increase in quality of family life, respectively. This relationship remained

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.

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

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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.

Can Children Enhance Their Family's Health Knowledge? An Infectious Disease Prevention Program.

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Sedighi, Iraj; Nouri, Shahla; Sadrosadat, Taravat; Nemati, Reza; Shahbazi, Mojgan

2012-12-01

The purpose of this study is to propose an innovative method of knowledge transfer that aims to improve health literacy about pediatric infectious diseases prevention in families. Children have an appreciable role in this scheme. This study is a before and after trial that has been conducted in Hamedan in 2009. After changing seven infectious disease topics into childish poems, we selected five kindergartens randomly and taught these poetries to the children. Teaching process held after a pretest containing 24 questions that examined 103 of parents about mentioned topics. The same post-test was given after 4 months of teaching process. The mean of correct answers to the pretest was 59.22% comparable with 81.00% for post-test (P<0.00). Gender and knowledge degree could not change the results significantly. Assuming one's correct answers to the questions as his/her Knowledge Mark, the mean of this variable increased to 5.32 by this method. This cost-effective and joyful method had successful results in promoting health knowledge. Children are able to play an active role in family's health situation. Learning within family atmosphere without any obligations makes our scheme a solution for paving the knowledge transferring way.

Heterogeneous Genetic Background of the Association of Pheochromocytoma/Paraganglioma and Pituitary Adenoma: Results From a Large Patient Cohort

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Dénes, Judit; Swords, Francesca; Rattenberry, Eleanor; Stals, Karen; Owens, Martina; Cranston, Treena; Xekouki, Paraskevi; Moran, Linda; Kumar, Ajith; Wassif, Christopher; Fersht, Naomi; Baldeweg, Stephanie E.; Morris, Damian; Lightman, Stafford; Agha, Amar; Rees, Aled; Grieve, Joan; Powell, Michael; Boguszewski, Cesar Luiz; Dutta, Pinaki; Thakker, Rajesh V.; Srirangalingam, Umasuthan; Thompson, Chris J.; Druce, Maralyn; Higham, Claire; Davis, Julian; Eeles, Rosalind; Stevenson, Mark; O'Sullivan, Brendan; Taniere, Phillipe; Skordilis, Kassiani; Gabrovska, Plamena; Barlier, Anne; Webb, Susan M.; Aulinas, Anna; Drake, William M.; Bevan, John S.; Preda, Cristina; Dalantaeva, Nadezhda; Ribeiro-Oliveira, Antônio; Garcia, Isabel Tena; Yordanova, Galina; Iotova, Violeta; Evanson, Jane; Grossman, Ashley B.; Trouillas, Jacqueline; Ellard, Sian; Stratakis, Constantine A.; Maher, Eamonn R.; Roncaroli, Federico

2015-01-01

Context: Pituitary adenomas and pheochromocytomas/paragangliomas (pheo/PGL) can occur in the same patient or in the same family. Coexistence of the two diseases could be due to either a common pathogenic mechanism or a coincidence. Objective: The objective of the investigation was to study the possible coexistence of pituitary adenoma and pheo/PGL. Design: Thirty-nine cases of sporadic or familial pheo/PGL and pituitary adenomas were investigated. Known pheo/PGL genes (SDHA-D, SDHAF2, RET, VHL, TMEM127, MAX, FH) and pituitary adenoma genes (MEN1, AIP, CDKN1B) were sequenced using next generation or Sanger sequencing. Loss of heterozygosity study and pathological studies were performed on the available tumor samples. Setting: The study was conducted at university hospitals. Patients: Thirty-nine patients with sporadic of familial pituitary adenoma and pheo/PGL participated in the study. Outcome: Outcomes included genetic screening and clinical characteristics. Results: Eleven germline mutations (five SDHB, one SDHC, one SDHD, two VHL, and two MEN1) and four variants of unknown significance (two SDHA, one SDHB, and one SDHAF2) were identified in the studied genes in our patient cohort. Tumor tissue analysis identified LOH at the SDHB locus in three pituitary adenomas and loss of heterozygosity at the MEN1 locus in two pheochromocytomas. All the pituitary adenomas of patients affected by SDHX alterations have a unique histological feature not previously described in this context. Conclusions: Mutations in the genes known to cause pheo/PGL can rarely be associated with pituitary adenomas, whereas mutation in a gene predisposing to pituitary adenomas (MEN1) can be associated with pheo/PGL. Our findings suggest that genetic testing should be considered in all patients or families with the constellation of pheo/PGL and a pituitary adenoma. PMID:25494863

Heterogeneous genetic background of the association of pheochromocytoma/paraganglioma and pituitary adenoma: results from a large patient cohort.

Science.gov (United States)

Dénes, Judit; Swords, Francesca; Rattenberry, Eleanor; Stals, Karen; Owens, Martina; Cranston, Treena; Xekouki, Paraskevi; Moran, Linda; Kumar, Ajith; Wassif, Christopher; Fersht, Naomi; Baldeweg, Stephanie E; Morris, Damian; Lightman, Stafford; Agha, Amar; Rees, Aled; Grieve, Joan; Powell, Michael; Boguszewski, Cesar Luiz; Dutta, Pinaki; Thakker, Rajesh V; Srirangalingam, Umasuthan; Thompson, Chris J; Druce, Maralyn; Higham, Claire; Davis, Julian; Eeles, Rosalind; Stevenson, Mark; O'Sullivan, Brendan; Taniere, Phillipe; Skordilis, Kassiani; Gabrovska, Plamena; Barlier, Anne; Webb, Susan M; Aulinas, Anna; Drake, William M; Bevan, John S; Preda, Cristina; Dalantaeva, Nadezhda; Ribeiro-Oliveira, Antônio; Garcia, Isabel Tena; Yordanova, Galina; Iotova, Violeta; Evanson, Jane; Grossman, Ashley B; Trouillas, Jacqueline; Ellard, Sian; Stratakis, Constantine A; Maher, Eamonn R; Roncaroli, Federico; Korbonits, Márta

2015-03-01

Pituitary adenomas and pheochromocytomas/paragangliomas (pheo/PGL) can occur in the same patient or in the same family. Coexistence of the two diseases could be due to either a common pathogenic mechanism or a coincidence. The objective of the investigation was to study the possible coexistence of pituitary adenoma and pheo/PGL. Thirty-nine cases of sporadic or familial pheo/PGL and pituitary adenomas were investigated. Known pheo/PGL genes (SDHA-D, SDHAF2, RET, VHL, TMEM127, MAX, FH) and pituitary adenoma genes (MEN1, AIP, CDKN1B) were sequenced using next generation or Sanger sequencing. Loss of heterozygosity study and pathological studies were performed on the available tumor samples. The study was conducted at university hospitals. Thirty-nine patients with sporadic of familial pituitary adenoma and pheo/PGL participated in the study. Outcomes included genetic screening and clinical characteristics. Eleven germline mutations (five SDHB, one SDHC, one SDHD, two VHL, and two MEN1) and four variants of unknown significance (two SDHA, one SDHB, and one SDHAF2) were identified in the studied genes in our patient cohort. Tumor tissue analysis identified LOH at the SDHB locus in three pituitary adenomas and loss of heterozygosity at the MEN1 locus in two pheochromocytomas. All the pituitary adenomas of patients affected by SDHX alterations have a unique histological feature not previously described in this context. Mutations in the genes known to cause pheo/PGL can rarely be associated with pituitary adenomas, whereas mutation in a gene predisposing to pituitary adenomas (MEN1) can be associated with pheo/PGL. Our findings suggest that genetic testing should be considered in all patients or families with the constellation of pheo/PGL and a pituitary adenoma.

The in vitro and in vivo effects of re-expressing methylated von Hippel-Lindau tumor suppressor gene in clear cell renal carcinoma with 5-aza-2'-deoxycytidine.

Science.gov (United States)

Alleman, Wade G; Tabios, Ray L; Chandramouli, Gadisetti V R; Aprelikova, Olga N; Torres-Cabala, Carlos; Mendoza, Arnulfo; Rogers, Craig; Rodgers, Craig; Sopko, Nikolai A; Linehan, W Marston; Vasselli, James R

2004-10-15

Clear cell renal carcinoma (ccRCC) is strongly associated with loss of the von Hippel-Lindau (VHL) tumor suppressor gene. The VHL gene is functionally lost through hypermethylation in up to 19% of sporadic ccRCC cases. We theorized that re-expressing VHL silenced by methylation in ccRCC cells, using a hypo-methylating agent, may be an approach to treatment in patients with this type of cancer. We test the ability of two hypo-methylating agents to re-express VHL in cell culture and in mice bearing human ccRCC and evaluate the effects of re-expressed VHL in these models. Real-time reverse transcription-PCR was used to evaluate the ability of zebularine and 5-aza-2'-deoxycytidine (5-aza-dCyd) to re-express VHL in four ccRCC cell lines with documented VHL gene silencing through hypermethylation. We evaluated if the VHL re-expressed after hypo-methylating agent treatment could recreate similar phenotypic changes in ccRCC cells observed when the VHL gene is re-expressed via transfection in cell culture and in a xenograft mouse model. Finally we evaluate global gene expression changes occurring in our cells, using microarray analysis. 5-Aza-dCyd was able to re-express VHL in our cell lines both in culture and in xenografted murine tumors. Well described phenotypic changes of VHL expression including decreased invasiveness into Matrigel, and decreased vascular endothelial growth factor and glucose transporter-1 expression were observed in the treated lines. VHL methylated ccRCC xenografted tumors were significantly reduced in size in mice treated with 5-aza-dCyd. Mice bearing nonmethylated but VHL-mutated tumors showed no tumor shrinkage with 5-aza-dCyd treatment. Hypo-methylating agents may be useful in the treatment of patients having ccRCC tumors consisting of cells with methylated VHL.

Seizures in E200K familial and sporadic Creutzfeldt-Jakob disease.

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Appel, S; Chapman, J; Cohen, O S; Rosenmann, H; Nitsan, Z; Blatt, I

2015-03-01

Although seizures (other than myoclonus) are frequently reported in Creutzfeldt-Jakob disease (CJD), their frequency, clinical manifestations, and effect on the disease course is unknown. To characterize the frequency of seizures in E200K familial and sporadic CJD, to describe its semiology, EEG and MRI findings. In this retrospective study, we reviewed all patients with CJD who were seen in the Sheba Medical Center between the years 2003-2012 and underwent clinical evaluation, genetic testing, EEG and MRI studies. The diagnosis of seizures was carried out based on documentation of episodes consistent with seizures or episode of unresponsiveness correlated with ictal activity in EEG. Sixty-four probable patients with CJD were included in the study, 57 (89%) with E200K familial (fCJD) and 7 (11%) with sporadic (sCJD). Seizures occurred in 8 patients: 3 of 7 (43%) in patients with sCJD compared to 5/57 (9%) in patients with E200K fCJD (P = 0.04, chi-square test). Two of E200K fCJD patients with seizures had other non-prion etiologies for seizures (brain metastasis, known history of temporal lobe epilepsy which started 44 years before the diagnosis of CJD). Seizures occurred late in the course of the disease with an average of 12 days between the onset of seizures and death. Seizures in E200K fCJD were infrequent and occurred late in the disease course. This difference suggests that E200K fCJD represents a separate subtype of the disease with distinct clinical characteristics. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

Directory of Open Access Journals (Sweden)

Louise Aas Nielsen

2015-10-01

Full Text Available 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.

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

Disease-related social situation in family of children with chronic kidney disease--parents` assessment. A multicentre study.

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Kiliś-Pstrusińska, Katarzyna; Medyńska, Anna; Adamczyk, Piotr; Bałasz-Chmielewska, Irena; Grenda, Ryszard; Kluska-Jóźwiak, Agnieszka; Leszczyńska, Beata; Olszak-Szot, Ilona; Miklaszewska, Monika; Szczepańska, Maria; Tkaczyk, Marcin; Wasilewska, Anna; Zachwieja, Katarzyna; Zajączkowska, Maria; Ziółkowska, Helena; Zagożdżon, Ilona; Zwolińska, Danuta

2014-01-01

Chronic kidney disease (CKD) in children burdens life of patients and their families. Little is known about parents` assessment of families' social situation. However, the knowledge of the details of a patient's and his family's life standards might influence modification and optimization of applied therapy. Therefore, the main goal of the present study was to explore the selected elements of life situation of patients suffering with CKD as well as their parents, depending on the CKD stage and appropriate treatment. Cross-sectional national study was conducted. A total of 203 children with CKD and 388 their parent-proxies (196 women and 192 men) were enrolled into this study. Patient data and questionnaires filled by both parents, concerning social-demographic parameters and assessment of changes in families after CKD diagnosis in the child, were analysed. CKD children are being brought up in proper families whose financial situation is not good. Children need help in process of education. Perception of current situation differed between both parents in the change of the income source, taking care of CKD child, change in social relations and evaluating relations with medical staff. Parents do not obtain proper support from social workers. Families of CKD children require support in area of financial and educational help for school children. The discrepancies in evaluation of family situation between mothers and fathers of ill children might be the source of conflicts possibly resulting in worsening the outcome for CKD children.

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.

Exploring caregiver burden experienced by family caregivers of patients with End-Stage Renal Disease in Nigeria

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Yemisi Okikiade Oyegbile

Full Text Available Background: Family caregivers in many African countries bear the burden of caregiving alone, with the paucity of research, especially for caregivers of End-Stage Renal Disease patients, having concealed their needs. Aim: To explore the caregiver burden of family caregivers of End-Stage Renal Disease (ESRD patients in South-West Nigeria. Design: Following a complementary mixed method data collection strategy, the quantitative data was collected using the Zarit Burden Interview questionnaire to measure the burden of caregiving. Qualitative data was thereafter obtained through in-depth, individual interviews and was analysed using content analysis. Settings: The three research settings consisted of two state hospitals and one private hospital that provide renal care in South-West Nigeria. Result: The mean burden of caregiving for the sample was 50.18 thus indicating that family caregivers experienced moderate to severe burden, which is high compared to the other studies. The participants’ experiences of caregiving revealed the following categories: total dependence, acceptance of caregiving role, competing responsibilities, financial sacrifice and “not making mistakes”. Conclusion: Understanding the extent of caregiver burden, what constitutes burden to family caregivers in low/middle-income countries, and the difficulties associated with caregiving for care-recipients with ESRD, allows appropriate strategies and interventions to be developed. Keywords: End Stage Renal Disease, Family caregivers, Caregiver burden, Complementary mixed methods, Nigeria

Polygenic risk score is associated with increased disease risk in 52 Finnish breast cancer families

OpenAIRE

Muranen, Taru A.; Mavaddat, Nasim; Khan, Sofia; Fagerholm, Rainer; Pelttari, Liisa; Lee, Andrew; Aittom?ki, Kristiina; Blomqvist, Carl; Easton, Douglas F.; Nevanlinna, Heli

2016-01-01

The risk of developing breast cancer is increased in women with family history of breast cancer and particularly in families with multiple cases of breast or ovarian cancer. Nevertheless, many women with a positive family history never develop the disease. Polygenic risk scores (PRSs) based on the risk effects of multiple common genetic variants have been proposed for individual risk assessment on a population level. We investigate the applicability of the PRS for risk prediction within breas...

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

Science.gov (United States)

2011-03-14

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Family History and Diamond Blackfan Anemia, DD11- 010, Initial Review Correction: This notice was published in the Federal Register on...

Molecular and phenotypic analysis of a family with autosomal recessive cone-rod dystrophy and Stargardt disease.

NARCIS (Netherlands)

Ijzer, Suzanne; Born, L.I. van den; Zonneveld, M.N.; Lopez, I.; Ayyagari, R.; Teye-Botchway, L.; Mota-Vieira, L.; Cremers, F.P.M.; Koenekoop, R.K.

2007-01-01

PURPOSE: To identify the causative gene mutations in three siblings with severe progressive autosomal recessive cone-rod dystrophy (arCRD) and their fifth paternal cousin with Stargardt disease (STGD1) and to specify the phenotypes. METHODS: We evaluated eight sibs of one family, three family

Resilience as a concept for understanding family caregiving of adults with Chronic Obstructive Pulmonary Disease (COPD): an integrative review.

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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.

Families Affected by Huntington's Disease Report Difficulties in Communication, Emotional Involvement, and Problem Solving.

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Jona, Celine M H; Labuschagne, Izelle; Mercieca, Emily-Clare; Fisher, Fiona; Gluyas, Cathy; Stout, Julie C; Andrews, Sophie C

2017-01-01

Family functioning in Huntington's disease (HD) is known from previous studies to be adversely affected. However, which aspects of family functioning are disrupted is unknown, limiting the empirical basis around which to create supportive interventions. The aim of the current study was to assess family functioning in HD families. We assessed family functioning in 61 participants (38 HD gene-expanded participants and 23 family members) using the McMaster Family Assessment Device (FAD; Epstein, Baldwin and Bishop, 1983), which provides scores for seven domains of functioning: Problem Solving; Communication; Affective Involvement; Affective Responsiveness; Behavior Control; Roles; and General Family Functioning. The most commonly reported disrupted domain for HD participants was Affective Involvement, which was reported by 39.5% of HD participants, followed closely by General Family Functioning (36.8%). For family members, the most commonly reported dysfunctional domains were Affective Involvement and Communication (both 52.2%). Furthermore, symptomatic HD participants reported more disruption to Problem Solving than pre-symptomatic HD participants. In terms of agreement between pre-symptomatic and symptomatic HD participants and their family members, all domains showed moderate to very good agreement. However, on average, family members rated Communication as more disrupted than their HD affected family member. These findings highlight the need to target areas of emotional engagement, communication skills and problem solving in family interventions in HD.

Inflammatory bowel disease: Greek patients' perspective on quality of life, information on the disease, work productivity and family support.

Science.gov (United States)

Viazis, Nikos; Mantzaris, Gerasimos; Karmiris, Konstantinos; Polymeros, Dimitrios; Kouklakis, George; Maris, Theofanis; Karagiannis, John; Karamanolis, Dimitrios G

2013-01-01

The aim of this study was to identify inflammatory bowel disease (IBD) patients' perspectives regarding everyday life issues. From October 2010 till April 2011, 1,181 IBD patients completed an anonymous questionnaire through the internet (827 cases) or at the outpatient clinic of the participating centers (354 cases), aiming to identify: a) the impact of disease on social life, emotional status and work productivity; b) the source of disease information; and c) the level of support from family members and friends. Fifty-five percent of the patients reported that IBD interferes with their social life, while 65% felt stressed, 60% depressed and 19% tired because of it. Disease information (physician/ internet) was reported only by 31%, while 26% admitted not discussing their therapy with their gastroenterologist. Forty percent felt that the health service they receive is not satisfactory, with 76% desiring more gastroenterologists, 67% more outpatient clinics, 49% more dieticians and 42% more psychologists specialized in IBD. IBD interfered with working capacity in 40% of the participants, while 57% needed time off of work (ranging from 1-20 days per year). One of three patients (32%) has not informed his work environment about the disease; however, 88% had the support of their family and friends for coping with it. Greek IBD patients claim that health-related social life, emotional status and work productivity are severely affected by their disease, whereas they complain about lack of information regarding the therapy. These unmet demands call for immediate action by healthcare providers and society.

Premature Valvular Heart Disease in Homozygous Familial Hypercholesterolemia.

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Fahed, Akl C; Shibbani, Kamel; Andary, Rabih R; Arabi, Mariam T; Habib, Robert H; Nguyen, Denis D; Haddad, Fady F; Moubarak, Elie; Nemer, Georges; Azar, Sami T; Bitar, Fadi F

2017-01-01

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.

[Chronic obstructive pulmonary disease: sense of coherence and family support versus anxiety and depression].

Science.gov (United States)

Tselebis, A; Bratis, D; Pachi, A; Moussas, G; Karkanias, A; Harikiopoulou, M; Theodorakopoulou, E; Kosmas, E; Ilias, I; Siafakas, N; Vgontzas, A; Tzanakis, N

2013-01-01

Chronic Obstructive Pulmonary Disease (COPD) is mainly related to smoking habit and is characterized by airflow limitation that is not fully reversible. The airflow limitation is usually both progressive and associated with an abnormal inflammatory response of the lungs to noxious particles or gases. Worldwide and in Greece, COPD constitutes a major epidemiological issue. Incidence of depression and anxiety is high in the COPD population. Most studies on depression and anxiety in COPD deal with factors that are positively correlated with both of these comorbidities. The aim of our study was to assess whether two variables, sense of coherence (SOC) and perception of family support (FS), are negatively correlated with depressive and anxiety symptoms in outpatients with COPD. According to Aaron Antonovsky, sense of coherence refers to the ability of individuals to make sense of and manage events. Studies in other diseases suggest that sense of family support has a significant impact on the course and outcome of the disease, yet a limited number of reports across literature addresses the role of family support in COPD patients. In our present study one hundred twenty two (98 men and 24 women) outpatients with pure COPD were included. Age and years of education were recorded. Severity of COPD was assessed with spirometry before and after bronchodilation. All patients replied to self- administered questionnaires on depression (Beck Depression Inventory, BDI), anxiety (Spielberger State-Trait Anxiety Scale, STAI), family support (Family Support Scale, FSS-13) and sense of coherence (Sense of Coherence Scale, SOC). According to our results the mean BDI depression score was 11.65 (SD 7.35), mean trait anxiety score was 40.69 (SD 11.19), mean SOC score was 54.62 (SD 7.40) and mean FS score was 64.58 (SD 11.63). Women patients had higher anxiety scores and lower sense of family support compared to men. Significant negative correlations were evidenced between depression and

In silico analysis of a disease-causing mutation in PCDH15 gene in a consanguineous Pakistani family with Usher phenotype

OpenAIRE

Shamim Saleha; Muhammad Ajmal; Muhammad Jamil

2016-01-01

AIM: To map Usher phenotype in a consanguineous Pakistani family and identify disease-associated mutation in a causative gene to establish phenotype-genotype correlation. METHODS: A consanguineous Pakistani family in which Usher phenotype was segregating as an autosomal recessive trait was ascertained. On the basis of results of clinical investigations of affected members of this family disease was diagnosed as Usher syndrome (USH). To identify the locus responsible for the Usher phenotype...

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.

Disease Heritability Inferred from Familial Relationships Reported in Medical Records.

Science.gov (United States)

Polubriaginof, Fernanda C G; Vanguri, Rami; Quinnies, Kayla; Belbin, Gillian M; Yahi, Alexandre; Salmasian, Hojjat; Lorberbaum, Tal; Nwankwo, Victor; Li, Li; Shervey, Mark M; Glowe, Patricia; Ionita-Laza, Iuliana; Simmerling, Mary; Hripcsak, George; Bakken, Suzanne; Goldstein, David; Kiryluk, Krzysztof; Kenny, Eimear E; Dudley, Joel; Vawdrey, David K; Tatonetti, Nicholas P

2018-05-15

Heritability is essential for understanding the biological causes of disease but requires laborious patient recruitment and phenotype ascertainment. Electronic health records (EHRs) passively capture a wide range of clinically relevant data and provide a resource for studying the heritability of traits that are not typically accessible. EHRs contain next-of-kin information collected via patient emergency contact forms, but until now, these data have gone unused in research. We mined emergency contact data at three academic medical centers and identified 7.4 million familial relationships while maintaining patient privacy. Identified relationships were consistent with genetically derived relatedness. We used EHR data to compute heritability estimates for 500 disease phenotypes. Overall, estimates were consistent with the literature and between sites. Inconsistencies were indicative of limitations and opportunities unique to EHR research. These analyses provide a validation of the use of EHRs for genetics and disease research. Copyright © 2018 Elsevier Inc. All rights reserved.

Autosomal dominant polycystic kidney disease in a family with mosaicism and hypomorphic allele.

Science.gov (United States)

Reiterová, Jana; Štekrová, Jitka; Merta, Miroslav; Kotlas, Jaroslav; Elišáková, Veronika; Lněnička, Petr; Korabečná, Marie; Kohoutová, Milada; Tesař, Vladimír

2013-03-15

Autosomal dominant polycystic kidney disease (ADPKD) is the most common form of inherited kidney disease that results in renal failure. ADPKD is a systemic disorder with cysts and connective tissue abnormalities involving many organs. ADPKD caused by mutations in PKD1 gene is significantly more severe than the cases caused by PKD2 gene mutations. The large intra-familial variability of ADPKD highlights a role for genetic background. Here we report a case of ADPKD family initially appearing unlinked to the PKD1 or PKD2 loci and the influence of mosaicism and hypomorphic allele on the variability of the clinical course of the disease. A grandmother with the PKD1 gene mutation in mosaicism (p.Val1105ArgfsX4) and with mild clinical course of ADPKD (end stage renal failure at the age of 77) seemed to have ADPKD because of PKD2 gene mutation. On the other hand, her grandson had a severe clinical course (end stage renal disease at the age of 45) in spite of the early treatment of mild hypertension. There was found by mutational analysis of PKD genes that the severe clinical course was caused by PKD1 gene frameshifting mutation inherited from his father and mildly affected grandmother in combination with inherited hypomorphic PKD1 allele with described missense mutation (p.Thr2250Met) from his clinically healthy mother. The sister with two cysts and with PKD1 hypomorphic allele became the kidney donor to her severely affected brother. We present the first case of ADPKD with the influence of mosaicism and hypomorphic allele of the PKD1 gene on clinical course of ADPKD in one family. Moreover, this report illustrates the role of molecular genetic testing in assessing young related kidney donors for patients with ADPKD.

The Role of Family in a Dietary Risk Reduction Intervention for Cardiovascular Disease

Directory of Open Access Journals (Sweden)

Tracy L. Schumacher

2016-09-01

Full Text Available Diet is an essential strategy for the prevention of primary and secondary cardiovascular disease (CVD events. The objectives were to examine: how families at increased risk of CVD perceived personal risk, their motivations to make dietary changes, their understanding of diet, and the influence of other family members. Individuals (>18 years who completed an Australian family-based CVD risk reduction program were invited to a semi-structured telephone interview. Responses were recorded, transcribed verbatim and analysed using a systematic deductive approach with coding derived from key concepts developed as part of the interview structure. Seventeen participants from eight families were interviewed (aged 18–70 years, 47% male, five with CVD diagnosis. Key themes indicated both intrinsic and extrinsic motivations to improve heart health, variations in risk perception, recognition of the role diet plays in heart health, and the extent of family influences on eating patterns. Discrepancies between perceived and actual CVD risk perception impacted on perceived “need” to modify current dietary patterns towards heart health recommendations. Therefore, strategies not reliant on risk perception are needed to engage those with low risk perception. This could involve identifying and accessing the family “ringleader” to influence involvement and capitalising on personal accountability to other family members.

The Role of Family in a Dietary Risk Reduction Intervention for Cardiovascular Disease.

Science.gov (United States)

Schumacher, Tracy L; Burrows, Tracy L; Thompson, Deborah I; Callister, Robin; Spratt, Neil J; Collins, Clare E

2016-09-30

Diet is an essential strategy for the prevention of primary and secondary cardiovascular disease (CVD) events. The objectives were to examine: how families at increased risk of CVD perceived personal risk, their motivations to make dietary changes, their understanding of diet, and the influence of other family members. Individuals (>18 years) who completed an Australian family-based CVD risk reduction program were invited to a semi-structured telephone interview. Responses were recorded, transcribed verbatim and analysed using a systematic deductive approach with coding derived from key concepts developed as part of the interview structure. Seventeen participants from eight families were interviewed (aged 18-70 years, 47% male, five with CVD diagnosis). Key themes indicated both intrinsic and extrinsic motivations to improve heart health, variations in risk perception, recognition of the role diet plays in heart health, and the extent of family influences on eating patterns. Discrepancies between perceived and actual CVD risk perception impacted on perceived "need" to modify current dietary patterns towards heart health recommendations. Therefore, strategies not reliant on risk perception are needed to engage those with low risk perception. This could involve identifying and accessing the family "ringleader" to influence involvement and capitalising on personal accountability to other family members.

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.

The Wnt signaling pathway in familial exudative vitreoretinopathy and Norrie disease.

Science.gov (United States)

Warden, Scott M; Andreoli, Christopher M; Mukai, Shizuo

2007-01-01

The Wnt signaling pathway is highly conserved among species and has an important role in many cell biological processes throughout the body. This signaling cascade is involved in regulating ocular growth and development, and recent findings indicate that this is particularly true in the retina. Mutations involving different aspects of the Wnt signaling pathway are being linked to several diseases of retinal development. The aim of this article is to first review the Wnt signaling pathway. We will then describe two conditions, familial exudative vitreoretinopathy (FEVR) and Norrie disease (ND), which have been shown to be caused in part by defects in the Wnt signaling cascade.

Isoform-specific interactions of the von Hippel-Lindau tumor suppressor protein

OpenAIRE

Minervini, Giovanni; Mazzotta, Gabriella M.; Masiero, Alessandro; Sartori, Elena; Corr?, Samantha; Potenza, Emilio; Costa, Rodolfo; Tosatto, Silvio C. E.

2015-01-01

Deregulation of the von Hippel-Lindau tumor suppressor protein (pVHL) is considered one of the main causes for malignant renal clear-cell carcinoma (ccRCC) insurgence. In human, pVHL exists in two isoforms, pVHL19 and pVHL30 respectively, displaying comparable tumor suppressor abilities. Mutations of the p53 tumor suppressor gene have been also correlated with ccRCC insurgence and ineffectiveness of treatment. A recent proteomic analysis linked full length pVHL30 with p53 pathway regulation t...

Science.gov (United States)

Zanoletti, E.; Borsetto, D.; Opocher, G.; Mazzoni, A.; Martini, A.

2017-01-01

SUMMARY 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. PMID:29165437

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.

Clinical reinvestigation and linkage analysis in the family with Episkopi blindness (Norrie disease).

Science.gov (United States)

Wolff, G; Mayerová, A; Wienker, T F; Atalianis, P; Ioannou, P; Warburg, M

1992-11-01

We present the results of a clinical and genetic reinvestigation of the Cypriot family affected by an X chromosomally inherited eye disease originally published by Taylor et al, who coined the term Episkopi blindness. The pedigree was extended to 160 members, including 16 affected males out of 48 males at risk for the disease, most of whom were seen by one of us (PA). Affected males are blind with no associated symptoms and apparently are not mentally retarded. Thirty-nine family members agreed to blood sampling for genetic investigations. RFLP analysis was performed using probes from the region known to be deleted in some Norrie patients and polymorphic markers (DXS77, DXS7, MAOA, DXS255) from the proximal short arm of the X chromosome. There was no deletion for any of the probes in the affected males. Linkage analysis yielded positive lod scores for all informative markers (Z (DXS255, theta = 0) = 6.54, Z (MAOA, theta = 0) = 2.23, Z (DXS7, theta = 0) = 2.13). Thus, the conclusion that Episkopi blindness and Norrie disease (NDP, MIM *310600) are the same entity based on clinical evidence is now reinforced by gene mapping.

Premature Valvular Heart Disease in Homozygous Familial Hypercholesterolemia

Directory of Open Access Journals (Sweden)

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.

Development of a family nursing model for prevention of cancer and other noncommunicable diseases through an appreciative inquiry.

Science.gov (United States)

Jongudomkarn, Darunee; Macduff, Colin

2014-01-01

Cancer and non-communicable diseases are a major issue not only for the developed but also developing countries. Public health and primary care nursing offer great potential for primary and secondary prevention of these diseases through community and family-based approaches. Within Thailand there are related established educational curricula but less is known about how graduate practitioners enact ideas in practice and how these can influence policy at local levels. The aim of this inquiry was to develop family nursing practice in primary care settings in the Isaan region or Northeastern Thailand and to distill what worked well into a nursing model to guide practice. An appreciative inquiry approach involving analysis of written reports, focus group discussions and individual interviews was used to synthesize what worked well for fourteen family nurses involved in primary care delivery and to build the related model. Three main strategies were seen to offer a basis for optimal care delivery, namely: enacting a participatory action approach mobilizing families' social capital; using family nursing process; and implementing action strategies within communities. These were distilled into a new conceptual model. The model has some features in common with related community partnership models and the World Health Organization Europe Family Health Nurse model, but highlights practical strategies for family nursing enactment. The model offers a basis not only for planning and implementing family care to help prevent cancer and other diseases but also for education of nurses and health care providers working in communities. This articulation of what works in this culture also offers possible transference to different contexts internationally, with related potential to inform health and social care policies, and international development of care models.

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 =

A family with unusual Waardenburg syndrome type I (WSI), cleft lip (palate), and Hirschsprung disease is not linked to PAX 3.

Science.gov (United States)

Pierpont, J W; St Jacques, D; Seaver, L H; Erickson, R P

1995-03-01

An unusual family with Waardenburg syndrome type 1 (WSI), cleft lip (palate), and Hirschsprung disease is not linked to the PAX 3 gene since there is an obligate crossover which has occurred between PAX 3 DNA markers and the disorder in this family. This family may also have anticipation of the WSI traits as the proband's grandmother is nonpenetrant, his mother has dystopia canthorum, and severe cleft lip (palate), while the proband has dystopia canthorum, severe cleft lip (palate), and Hirschsprung disease. Thus, a locus other than PAX 3 is implicated in this Waardenburg-like syndrome with Hirschsprung disease and cleft lip (palate).

Families Affected by Huntington’s Disease Report Difficulties in Communication, Emotional Involvement, and Problem Solving

Science.gov (United States)

Jona, Celine M.H.; Labuschagne, Izelle; Mercieca, Emily-Clare; Fisher, Fiona; Gluyas, Cathy; Stout, Julie C.; Andrews, Sophie C.

2017-01-01

Background: Family functioning in Huntington’s disease (HD) is known from previous studies to be adversely affected. However, which aspects of family functioning are disrupted is unknown, limiting the empirical basis around which to create supportive interventions. Objective: The aim of the current study was to assess family functioning in HD families. Methods: We assessed family functioning in 61 participants (38 HD gene-expanded participants and 23 family members) using the McMaster Family Assessment Device (FAD; Epstein, Baldwin and Bishop, 1983), which provides scores for seven domains of functioning: Problem Solving; Communication; Affective Involvement; Affective Responsiveness; Behavior Control; Roles; and General Family Functioning. Results: The most commonly reported disrupted domain for HD participants was Affective Involvement, which was reported by 39.5% of HD participants, followed closely by General Family Functioning (36.8%). For family members, the most commonly reported dysfunctional domains were Affective Involvement and Communication (both 52.2%). Furthermore, symptomatic HD participants reported more disruption to Problem Solving than pre-symptomatic HD participants. In terms of agreement between pre-symptomatic and symptomatic HD participants and their family members, all domains showed moderate to very good agreement. However, on average, family members rated Communication as more disrupted than their HD affected family member. Conclusion: These findings highlight the need to target areas of emotional engagement, communication skills and problem solving in family interventions in HD. PMID:28968240

Naxos disease in an Arab family is not caused by the Pk2157del2 mutation; evidance for exclusion of the plakoglobin gene

International Nuclear Information System (INIS)

Stuhmann, M.; El-Harith, A.; Bukhari, Iqbal A.

2004-01-01

Nax os disease is a rare hereditary disorder characterized by palmoplantar keratoderma, woolly hair and cardiomyopathy. This study aims to determine whether Naxos disease in a Saudi Arab family is caused by the Pk2157del2 mutation that was identified in Greek families from Naxos Island where the disease had originally been described. This study was undertaken at King Fahad Hospital of the University, Al-Khobar, and the Medical University of Hannover, in the spring of 2003. Naxos disease has been encountered in a 2-year-old girl and her 30-year-old aunt of a Saudi Arab family. Deoxyribonucleic acid samples of this family were analyzed by polymerase chain-reaction (PCR) amplification of the respective region of the plakoglobin gene, and direct nucleotide sequencing of the PCR-products. Segregation analysis was performed employing the newly detected IVS11+22G/A polymorphism. Molecular genetic analysis of the DNA sample of the child diagnosed with Naxos disease showed absence of the Pk2157del2 mutation. In addition, the segregation analysis revealed heterozygosity for IVS11+22G/A in the affected girl. Absence of the Pk2157del2 frameshift in the affected child proved that Naxos disease in this Saudi Arab family is not caused by the same mutation that was identified in the Greek families. Furthermore, heterozygosity for the IVS11+22G/A polymorphism provided evidence for exclusion of the plakoglobin gene in this consanguineous family. (author)

Methyl-CpG-Binding Protein (MBD) Family: Epigenomic Read-Outs Functions and Roles in Tumorigenesis and Psychiatric Diseases.

Science.gov (United States)

Gigek, Carolina Oliveira; Chen, Elizabeth Suchi; Smith, Marilia Arruda Cardoso

2016-01-01

Epigenetics is the study of the heritable changes on gene expression that are responsible for the regulation of development and that have an impact on several diseases. However, it is of equal importance to understand how epigenetic machinery works. DNA methylation is the most studied epigenetic mark and is generally associated with the regulation of gene expression through the repression of promoter activity and by affecting genome stability. Therefore, the ability of the cell to interpret correct methylation marks and/or the correct interpretation of methylation plays a role in many diseases. The major family of proteins that bind methylated DNA is the methyl-CpG binding domain proteins, or the MBDs. Here, we discuss the structure that makes these proteins a family, the main functions and interactions of all protein family members and their role in human disease such as psychiatric disorders and cancer. © 2015 Wiley Periodicals, Inc.

Outcome of ABCA4 disease-associated alleles in autosomal recessive retinal dystrophies: retrospective analysis in 420 Spanish families.

Science.gov (United States)

Riveiro-Alvarez, Rosa; Lopez-Martinez, Miguel-Angel; Zernant, Jana; Aguirre-Lamban, Jana; Cantalapiedra, Diego; Avila-Fernandez, Almudena; Gimenez, Ascension; Lopez-Molina, Maria-Isabel; Garcia-Sandoval, Blanca; Blanco-Kelly, Fiona; Corton, Marta; Tatu, Sorina; Fernandez-San Jose, Patricia; Trujillo-Tiebas, Maria-Jose; Ramos, Carmen; Allikmets, Rando; Ayuso, Carmen

2013-11-01

To provide a comprehensive overview of all detected mutations in the ABCA4 gene in Spanish families with autosomal recessive retinal disorders, including Stargardt's disease (arSTGD), cone-rod dystrophy (arCRD), and retinitis pigmentosa (arRP), and to assess genotype-phenotype correlation and disease progression in 10 years by considering the type of variants and age at onset. Case series. A total of 420 unrelated Spanish families: 259 arSTGD, 86 arCRD, and 75 arRP. Spanish families were analyzed through a combination of ABCR400 genotyping microarray, denaturing high-performance liquid chromatography, and high-resolution melting scanning. Direct sequencing was used as a confirmation technique for the identified variants. Screening by multiple ligation probe analysis was used to detect possible large deletions or insertions in the ABCA4 gene. Selected families were analyzed further by next generation sequencing. DNA sequence variants, mutation detection rates, haplotypes, age at onset, central or peripheral vision loss, and night blindness. Overall, we detected 70.5% and 36.6% of all expected ABCA4 mutations in arSTGD and arCRD patient cohorts, respectively. In the fraction of the cohort where the ABCA4 gene was sequenced completely, the detection rates reached 73.6% for arSTGD and 66.7% for arCRD. However, the frequency of possibly pathogenic ABCA4 alleles in arRP families was only slightly higher than that in the general population. Moreover, in some families, mutations in other known arRP genes segregated with the disease phenotype. An increasing understanding of causal ABCA4 alleles in arSTGD and arCRD facilitates disease diagnosis and prognosis and also is paramount in selecting patients for emerging clinical trials of therapeutic interventions. Because ABCA4-associated diseases are evolving retinal dystrophies, assessment of age at onset, accurate clinical diagnosis, and genetic testing are crucial. We suggest that ABCA4 mutations may be associated with a

Socioeconomic status and impact of treatment on families of children with congenital heart disease

International Nuclear Information System (INIS)

Mughal, A.R.; Sidiq, M.; Hyder, S.N.; Qureshi, A.U.

2011-01-01

Objective: To assess the socioeconomic status, treatment being offered and the impact of congenital heart disease treatment on families. Study Design: Observational study. Place and Duration of Study: The Children's Hospital / Institute of Child Health, Lahore, from first March to 31 August 2010. Methodology: All patients undergoing a cardiac surgical or angiographic intervention were enrolled. Socioeconomic status was assessed by Kuppuswamy socioeconomic status scale with income group modification. The impact was measured by the source of financing, effect on family financing source and schooling and health of siblings. Results: Of 211 patients undergoing treatment in the study period, surgery was the definitive treatment in 164 (77.7%) and angiographic intervention in 47 (22.3%) patients. Male to female ratio was 1.5:1. The mean age of the patient was 39.1 +- 3.2 months (range 01 day to 15 years). Majority of families belonged to middle (66.4%, n=140) and lower (27%, n=57) socioeconomic class. The mean cost of medicines and disposable was PKR 78378.2 +- 8845.9 (US$ 933.1 +- 105.3) in open heart surgery, PKR 12581 +- 7010.8 (US$ 149.8 +- 83.5) in closed heart surgery and PKR 69091 + 60906 in angiographic interventions. In 63.1% patients, families contributed towards these costs either completely (12.3%) or partly (50.8%) with significant contribution from the hospital. Adverse effect on families ranged from leave without pay to losing jobs or business (46%), and selling their assets (11.3%). It also affected schooling and health of siblings (22.7% and 26.1% respectively). Conclusion: Majority of children with congenital heart disease belonged to middle and lower socioeconomic status in this study. Main definitive treatment was surgery. The cost of health care facilities posed a marked socioeconomic burden on those families. (author)

Socioeconomic status and impact of treatment on families of children with congenital heart disease.

Science.gov (United States)

Mughal, Abdul Razzaq; Sadiq, Masood; Hyder, Syed Najam; Qureshi, Ahmad Usaid; A Shah, S Salman; Khan, Mohammad Asim; Nasir, Jamal Abdul

2011-07-01

To assess the socioeconomic status, treatment being offered and the impact of congenital heart disease treatment on families. Observational study. The Children's Hospital / Institute of Child Health, Lahore, from 1st March to 31st August 2010. All patients undergoing a cardiac surgical or angiographic intervention were enrolled. Socioeconomic status was assessed by Kuppuswamy socioeconomic status scale with income group modification. The impact was measured by the source of financing, effect on family financing source and schooling and health of siblings. Of 211 patients undergoing treatment in the study period, surgery was the definitive treatment in 164 (77.7%) and angiographic intervention in 47 (22.3%) patients. Male to female ratio was 1.5:1. The mean age of the patient was 39.1 + 3.2 months (range 01 day to 15 years). Majority of families belonged to middle (66.4%, n=140) and lower (27%, n=57) socioeconomic class. The mean cost of medicines and disposables was PKR 78378.2 ± 8845.9 (US$ 933.1 ± 105.3) in open heart surgery, PKR 12581 ± 7010.8 (US$ 149.8 ± 83.5) in closed heart surgery and PKR 69091 + 60906 in angiographic interventions. In 63.1% patients, families contributed towards these costs either completely (12.3%) or partly (50.8%) with significant contribution from the hospital. Adverse effect on families ranged from leave without pay to losing jobs or business (46%), and selling their assets (11.3%). It also affected schooling and health of siblings (22.7% and 26.1% respectively). Majority of children with congenital heart disease belonged to middle and lower socioeconomic status in this study. Main definitive treatment was surgery. The cost of health care facilities posed a marked socioeconomic burden on those families.

Attitudes toward Management of Sickle Cell Disease and Its Complications: A National Survey of Academic Family Physicians

Directory of Open Access Journals (Sweden)

Arch G. Mainous

2015-01-01

Full Text Available Objective. Sickle cell disease (SCD is a disease that requires a significant degree of medical intervention, and family physicians are one potential provider of care for patients who do not have access to specialists. The extent to which family physicians are comfortable with the treatment of and concerned about potential complications of SCD among their patients is unclear. Our purpose was to examine family physician’s attitudes toward SCD management. Methods. Data was collected as part of the Council of Academic Family Medicine Educational Research Alliance (CERA survey in the United States and Canada that targeted family physicians who were members of CERA-affiliated organizations. We examined attitudes regarding management of SCD. Results. Overall, 20.4% of respondents felt comfortable with treatment of SCD. There were significant differences in comfort level for treatment of SCD patients depending on whether or not physicians had patients who had SCD, as well as physicians who had more than 10% African American patients. Physicians also felt that clinical decision support (CDS tools would be useful for treatment (69.4% and avoiding complications (72.6% in managing SCD patients. Conclusions. Family physicians are generally uncomfortable with managing SCD patients and recognize the utility of CDS tools in managing patients.

Familial risk of inflammatory bowel disease

DEFF Research Database (Denmark)

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

2014-01-01

of familial CD cases was 12,15 percent of total CD cases and familial UC accounted for and 8,84 percent of total UC cases from 2007-2011. Patterns of IBD risk in family members to IBD-affected individuals appear from Table 1. The risk of CD was 9-fold increased in 1. degree relatives to at least two...... 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...... individuals with IBD, 7.8 -fold increased in 1. degree relatives to one family member with CD, and even 2.8-fold increased if the 1. degree relative had UC. The same pattern was observed for risk of UC. Second-degree relatives to patients with CD or UC were also at significantly increased risk not only...

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...

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:

Moral landscapes and everyday life in families with Huntington's disease: aligning ethnographic description and bioethics.

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Huniche, Lotte

2011-06-01

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 1998-2002 involving multi-sited ethnography to argue that medical genetics provides a particular framework for conducting life in an HD family. A framework that implies that being informed and making use of genetic services expresses greater moral responsibility than conducting life without drawing on these resources. The moral imperative of engagement in medical genetics is challenged here by two pieces of ethnographic analysis. The first concerns a person who, as described by a family member, does not engage with medical genetics but who brings to the fore other culturally legitimate concerns, priorities and areas of responsibility. The second figures a genetic counselling session where neither the knowledge nor the imagined solutions of medical genetics are as unproblematic and straightforward as might be thought. To assist our understanding of the moral aspects of living with severe familial disease, the ethnographic analysis is aligned with bioethical reflections that place the concrete concerns of those personally involved centre stage in the development of theoretical stances that aim to assist reflections in practice. Copyright © 2010 Elsevier Ltd. All rights reserved.

Availability and quality of coronary heart disease family history in primary care medical records: implications for cardiovascular risk assessment.

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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.

TDP-43 pathology in familial frontotemporal dementia and motor neuron disease without Progranulin mutations.

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Seelaar, H.; Schelhaas, H.J.; Azmani, A.; Kusters, B.; Rosso, S.; Majoor-Krakauer, D.F.; Rijik, M.C. de; Rizzu, P.; Brummelhuis, M. Ten; Doorn, P.A. van; Kamphorst, W.; Willemsen, R.; Swieten, J. van

2007-01-01

Frontotemporal dementia is accompanied by motor neuron disease (FTD + MND) in approximately 10% of cases. There is accumulating evidence for a clinicopathological overlap between FTD and MND based on observations of familial aggregation and neuropathological findings of ubiquitin-positive neuronal

TDP-43 pathology in familial frontotemporal dementia and motor neuron disease without Progranulin mutations

NARCIS (Netherlands)

H. Seelaar (Harro); H. Jurgen Schelhaas; A. Azmani (Asma); B. Küsters (Benno); S.M. Rosso (Sonia); D.F. Majoor-Krakauer (Danielle); M.C. de Rijik (Maarten); P. Rizzu (Patrizia); M. ten Brummelhuis (Ming); P.A. van Doorn (Pieter); W. Kamphorst (Wouter); R. Willemsen (Rob); J.C. van Swieten (John)

2007-01-01

textabstractFrontotemporal dementia is accompanied by motor neuron disease (FTD + MND) in ∼10% of cases. There is accumulating evidence for a clinicopathological overlap between FTD and MND based on observations of familial aggregation and neuropathological findings of ubiquitin-positive neuronal

Behavioral and Pharmacological Adherence in Pediatric Sickle Cell Disease: Parent-Child Agreement and Family Factors Associated With Adherence.

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Klitzman, Page H; Carmody, Julia K; Belkin, Mary H; Janicke, David M

2018-01-01

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. © The Author 2017. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

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

Experiences of caring for a family member with Parkinson's disease: a meta-synthesis.

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Theed, Rachael; Eccles, Fiona; Simpson, Jane

2017-10-01

The aim of this qualitative meta-synthesis was to search and then synthesise family caregivers' experiences of providing care to individuals with Parkinson's disease (PD). A systematic search resulted in the identification of 11 qualitative studies. Noblit and Hare's seven-stage approach was used to provide a higher-order interpretation of how family caregivers' experienced the effects of taking on a caregiving role. The process of reciprocal translation resulted in four overarching themes: (1) the need to carry on as usual - 'the caregiver must continue with his life'; (2) the importance of support in facilitating coping - 'I'm still going back to the support group'; (3) the difficult balancing act between caregiving and caregiver needs - 'I cannot get sick because I'm a caregiver'; (4) conflicts in seeking information and knowledge - 'maybe better not to know'. The themes reflected different aspects of family caregivers' lives that were affected as a result of caring for a relative diagnosed with PD and these raise challenges for more simplistic theories of family caring and appropriate support structures. The findings also highlight several recommendations for clinical practice.

R47H Variant of TREM2 Associated With Alzheimer Disease in a Large Late-Onset Family

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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

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

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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.

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: traditio......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...

Impact of chronic obstructive pulmonary disease (COPD) on patient's life and his family.

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Kupryś-Lipińska, Izabela; Kuna, Piotr

2014-01-01

activity (82.78%) and family life (79.3%). COPD had significant (moderate or severe) effect on sport (60.85%) and life activity (38.44%), as well as on work (34.9%), but the greatest impact, leading up to the resignation of the activity: on sport practice (21.75%), sexual intercourse (12.6%) and hobbies (11.49%). The disease severity (GOLD 2013 C/D) was the independent factor which reduced all forms of activity. In patients' opinion smoking had negative impact on their health (52,65%) and the family budget (41.83%). The negative impact of smoking on family relations was declared by 16.38% of respondents. Among the factors which favor effective quit from addiction were: age ≥ 65 years and more seere degree of obturation (III/IV GOLD 2010). The results of the study confirmed the significant impact of the disease and addiction to smoking not only on patients' life but also on their families.

In silico analysis of a disease-causing mutation in PCDH15 gene in a consanguineous Pakistani family with Usher phenotype

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Shamim Saleha

2016-05-01

Full Text Available AIM: To map Usher phenotype in a consanguineous Pakistani family and identify disease-associated mutation in a causative gene to establish phenotype-genotype correlation. METHODS: A consanguineous Pakistani family in which Usher phenotype was segregating as an autosomal recessive trait was ascertained. On the basis of results of clinical investigations of affected members of this family disease was diagnosed as Usher syndrome (USH. To identify the locus responsible for the Usher phenotype in this family, genomic DNA from blood sample of each individual was genotyped using microsatellite Short Tandem Repeat (STR markers for the known Usher syndrome loci. Then direct sequencing was performed to find out disease associated mutations in the candidate gene. RESULTS: By genetic linkage analysis, the USH phenotype of this family was mapped to PCDH15 locus on chromosome 10q21.1. Three different point mutations in exon 11 of PCDH15 were identified and one of them, c.1304A>C was found to be segregating with the disease phenotype in Pakistani family with Usher phenotype. This, c.1304A>C transversion mutation predicts an amino-acid substitution of aspartic acid with an alanine at residue number 435 (p.D435A of its protein product. Moreover, in silico analysis revealed conservation of aspartic acid at position 435 and predicated this change as pathogenic. CONCLUSION: The identification of c.1304A>C pathogenic mutation in PCDH15 gene and its association with Usher syndrome in a consanguineous Pakistani family is the first example of a missense mutation of PCDH15 causing USH1 phenotype. In previous reports, it was hypothesized that severe mutations such as truncated protein of PCDH15 led to the Usher I phenotype and that missense variants are mainly responsible for non-syndromic hearing impairment.

In silico analysis of a disease-causing mutation in PCDH15 gene in a consanguineous Pakistani family with Usher phenotype.

Science.gov (United States)

Saleha, Shamim; Ajmal, Muhammad; Jamil, Muhammad; Nasir, Muhammad; Hameed, Abdul

2016-01-01

To map Usher phenotype in a consanguineous Pakistani family and identify disease-associated mutation in a causative gene to establish phenotype-genotype correlation. A consanguineous Pakistani family in which Usher phenotype was segregating as an autosomal recessive trait was ascertained. On the basis of results of clinical investigations of affected members of this family disease was diagnosed as Usher syndrome (USH). To identify the locus responsible for the Usher phenotype in this family, genomic DNA from blood sample of each individual was genotyped using microsatellite Short Tandem Repeat (STR) markers for the known Usher syndrome loci. Then direct sequencing was performed to find out disease associated mutations in the candidate gene. By genetic linkage analysis, the USH phenotype of this family was mapped to PCDH15 locus on chromosome 10q21.1. Three different point mutations in exon 11 of PCDH15 were identified and one of them, c.1304A>C was found to be segregating with the disease phenotype in Pakistani family with Usher phenotype. This, c.1304A>C transversion mutation predicts an amino-acid substitution of aspartic acid with an alanine at residue number 435 (p.D435A) of its protein product. Moreover, in silico analysis revealed conservation of aspartic acid at position 435 and predicated this change as pathogenic. The identification of c.1304A>C pathogenic mutation in PCDH15 gene and its association with Usher syndrome in a consanguineous Pakistani family is the first example of a missense mutation of PCDH15 causing USH1 phenotype. In previous reports, it was hypothesized that severe mutations such as truncated protein of PCDH15 led to the Usher I phenotype and that missense variants are mainly responsible for non-syndromic hearing impairment.

Dupuytren’s and Ledderhose Diseases in a Family with LMNA-Related Cardiomyopathy and a Novel Variant in the ASTE1 Gene

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Michael V. Zaragoza

2017-11-01

Full Text Available Dupuytren’s disease (palmar fibromatosis involves nodules in fascia of the hand that leads to flexion contractures. Ledderhose disease (plantar fibromatosis is similar with nodules of the foot. While clinical aspects are well-described, genetic mechanisms are unknown. We report a family with cardiac disease due to a heterozygous LMNA mutation (c.736C>T, p.Gln246Stop with palmar/plantar fibromatosis and investigate the hypothesis that a second rare DNA variant increases the risk for fibrotic disease in LMNA mutation carriers. The proband and six family members were evaluated for the cardiac and hand/feet phenotypes and tested for the LMNA mutation. Fibroblast RNA studies revealed monoallelic expression of the normal LMNA allele and reduced lamin A/C mRNAs consistent with LMNA haploinsufficiency. A novel, heterozygous missense variant (c.230T>C, p.Val77Ala in the Asteroid Homolog 1 (ASTE1 gene was identified as a potential risk factor in fibrotic disease using exome sequencing and family studies of five family members: four LMNA mutation carriers with fibromatosis and one individual without the LMNA mutation and no fibromatosis. With a possible role in epidermal growth factor receptor signaling, ASTE1 may contribute to the increased risk for palmar/plantar fibromatosis in patients with Lamin A/C haploinsufficiency.

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

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... 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 ...

Transgenic Fatal Familial Insomnia Mice Indicate Prion Infectivity-Independent Mechanisms of Pathogenesis and Phenotypic Expression of Disease

OpenAIRE

Bouybayoune, I.; Mantovani, S.; Del Gallo, F.; Bertani, I.; Restelli, E.; Comerio, L.; Tapella, L.; Baracchi, F.; Fernández-Borges, N.; Mangieri, M.; Bisighini, C.; Beznoussenko, G..V.; Paladini, A.; Balducci, C.; Micotti, E.

2015-01-01

Author Summary Genetic prion diseases are degenerative brain disorders caused by mutations in the gene encoding the prion protein (PrP). Different PrP mutations cause different diseases, including Creutzfeldt-Jakob disease (CJD) and fatal familial insomnia (FFI). The reason for this variability is not known, but assembly of the mutant PrPs into distinct aggregates that spread in the brain by promoting PrP aggregation may contribute to the disease phenotype. We previously generated transgenic ...

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

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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...

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...

SORL1 rare variants: a major risk factor for familial early-onset Alzheimer's disease.

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Nicolas, G; Charbonnier, C; Wallon, D; Quenez, O; Bellenguez, C; Grenier-Boley, B; Rousseau, S; Richard, A-C; Rovelet-Lecrux, A; Le Guennec, K; Bacq, D; Garnier, J-G; Olaso, R; Boland, A; Meyer, V; Deleuze, J-F; Amouyel, P; Munter, H M; Bourque, G; Lathrop, M; Frebourg, T; Redon, R; Letenneur, L; Dartigues, J-F; Génin, E; Lambert, J-C; Hannequin, D; Campion, D

2016-06-01

The SORL1 protein plays a protective role against the secretion of the amyloid β peptide, a key event in the pathogeny of Alzheimer's disease. We assessed the impact of SORL1 rare variants in early-onset Alzheimer's disease (EOAD) in a case-control setting. We conducted a whole exome analysis among 484 French EOAD patients and 498 ethnically matched controls. After collapsing rare variants (minor allele frequency ≤1%), we detected an enrichment of disruptive and predicted damaging missense SORL1 variants in cases (odds radio (OR)=5.03, 95% confidence interval (CI)=(2.02-14.99), P=7.49.10(-5)). This enrichment was even stronger when restricting the analysis to the 205 cases with a positive family history (OR=8.86, 95% CI=(3.35-27.31), P=3.82.10(-7)). We conclude that predicted damaging rare SORL1 variants are a strong risk factor for EOAD and that the association signal is mainly driven by cases with positive family history.

Prevalence of a positive family history of type 2 diabetes in women with polycystic ovarian disease.

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Fox, R

1999-12-01

The known association between insulin resistance and polycystic ovarian disease (PCOD) has been studied by determination of the prevalence of a positive family history of diabetes in a consecutive series of oligomenorrheic women with polycystic ovaries and eumenorrheic women with normal ovaries who served as controls. A significantly greater proportion of the families of the patients with PCOD had at least one member affected by type 2 diabetes (39.1% of the PCOD group and 7.6% of the controls; p PCOD had an increased prevalence of type 2 diabetes within their families. Paternal and maternal family members affected were in similar proportions, there being no evidence of preferential transmission through the female line in this study. The increased prevalence of type 2 diabetes in the families of women with polycystic ovaries is further evidence for the association between PCOD and insulin resistance, and provides a possible explanation for the familial nature of the ovarian disorder.

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

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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.

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

Science.gov (United States)

Schumacher, Tracy L; Burrows, Tracy L; Thompson, Deborah I; Spratt, Neil J; Callister, Robin; Collins, Clare E

2015-08-21

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.

Transmissible familial Creutzfeldt-Jakob disease associated with five, seven, and eight extra octapeptide coding repeats in the PRNP gene

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Goldfarb, L.G.; Brown, P.; McCombie, W.R.; Gibbs, C.J. Jr.; Gajdusek, D.C. (National Inst. of Health, Bethesda, MD (United States)); Goldgaber, D. (State Univ. of New York, Stony Brook (United States)); Swergold, G.D. (National Inst. of Health, Bethesda, MD (United States)); Wills, P.R. (Univ. of Auckland (New Zealand)); Cervenakova, L. (Inst. of Preventive and Clinical Medicine, Bratislava (Czechoslovakia)); Baron, H. (Searle Pharmaceuticals, Paris (France))

1991-12-01

The PRNP gene, encoding the amyloid precursor protein that is centrally involved in Creutzfeldt-Jakob disease (CJD), has an unstable region of five variant tandem octapeptide coding repeats between codons 51 and 91. The authors screened a total of 535 individuals for the presence of extra repeats in this region, including patients with sporadic and familial forms of spongiform encephalopathy, members of their families, other neurological and non-neurological patients, and normal controls. They identified three CJD families (in each of which the proband's disease was neuropathologically confirmed and experimentally transmitted to primates) that were heterozygous for alleles with 10, 12, or 13 repeats, some of which had wobble nucleotide substitutions. They also found one individual with 9 repeats and no nucleotide substitutions who had no evidence of neurological disease. These observations, together with data on published British patients with 11 and 14 repeats, strongly suggest that the occurrence of 10 or more octapeptide repeats in the encoded amyloid precursor protein predisposes to CJD.

Inflammatory bowel disease in children and adolescents: mental health and family functioning.

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Engstrom, I

1999-04-01

Inflammatory bowel disease in children and adolescents often leads to an extremely complex somatic and psychiatric situation. The psychological effect of inflammatory bowel disease warrants further investigation, especially concerning salutogenetic factors that may lead to good mental health despite bad somatic conditions. These studies used a multimethod design comprising both semiquantitative measures, such as rating scales and questionnaires, and qualitative in-depth interviews with both the child and his or her parents. Clinical comparison groups of matched children with diabetes and chronic tension headaches and matched children without chronic physical disease were examined. Inflammatory bowel disease often leads to psychiatric sequelae. Emotional disorders, especially depression and anxiety symptoms, were found to be common. Self-esteem was lowered. A subgroup of children with good mental health despite bad somatic conditions was found. They exhibited certain characteristics, including good knowledge of the disease, an internal locus of control, a good family climate, and an open social network. This study shows that the well-being of a chronically ill child depends not only on the course of the physical disease but also on the psychological and social complications that often seem to accompany a disease of this kind. The importance of taking good care of the psychosocial aspects of inflammatory bowel disease within the comprehensive treatment program is discussed.

Financial burdens and mental health needs in families of children with congenital heart disease.

Science.gov (United States)

McClung, Nancy; Glidewell, Jill; Farr, Sherry L

2018-04-06

To examine the financial burdens and mental health needs of families of children with special healthcare needs (CSHCN) with congenital heart disease (CHD). Data from the 2009-2010 National Survey of Children with Special Health Care Needs (NS-CSHCN) were used to examine parent-reported financial burdens (out-of-pocket expenses, financial problems, employment impact, caregiving hours) and family members' need for mental health services in families of CSHCN with CHD. Multivariable logistic regression was used to compare financial burdens and family members' need for mental health services among CSHCN with and without CHD. Among CSHCN with CHD, multivariable logistic regression, stratified by age (0-5 and 6-17 years), was used to assess characteristics associated with the outcomes. Overall, families of 89.1% of CSHCN with CHD experienced at least one financial burden and 14.9% needed mental health services due to the child's condition. Compared with CSHCN without CHD, those with CHD had families with a higher prevalence of all financial burdens (adjusted prevalence ratio [aPR] range: 1.4-1.8) and similar family member need for mental health services (aPR = 1.3, 95% CI [1.0, 1.6]). Across both age groups, insurance type, activity limitations, and comorbidities were significantly associated with financial burdens and/or family members' need for mental health services. CSHCN with CHD, compared with those without CHD, lived in families with more financial burdens. Interventions that reduce financial burdens and improve mental health of family members are needed, especially among CSHCN with CHD who are uninsured and have comorbidities or activity limitations. © 2018 Wiley Periodicals, Inc.

[The theme of disaster in health care: profile of technical and scientific production in the specialized database on disasters of the Virtual Health Library - VHL].

Science.gov (United States)

Rocha, Vania; Ximenes, Elisa Francioli; Carvalho, Mauren Lopes de; Alpino, Tais de Moura Ariza; Freitas, Carlos Machado de

2014-09-01

In the specialized database of the Virtual Health Library (VHL), the DISASTER database highlights the importance of the theme for the health sector. The scope of this article is to identify the profiles of technical and scientific publications in the specialized database. Based on systematic searches and the analysis of results it is possible to determine: the type of publication; the main topics addressed; the most common type of disasters mentioned in published materials, countries and regions as subjects, historic periods with the most publications and the current trend of publications. When examining the specialized data in detail, it soon becomes clear that the number of major topics is very high, making a specific search process in this database a challenging exercise. On the other hand, it is encouraging that the disaster topic is discussed and assessed in a broad and diversified manner, associated with different aspects of the natural and social sciences. The disaster issue requires the production of interdisciplinary knowledge development to reduce the impacts of disasters and for risk management. In this way, since the health sector is a interdisciplinary area, it can contribute to knowledge production.

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.

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.

The health-disease process and the family health strategy: the user's perspective.

Science.gov (United States)

Santos, Débora de Souza; Tenório, Elainey de Albuquerque; Brêda, Mércia Zeviane; Mishima, Silvana Martins

2014-01-01

to analyze the meanings Primary Health Care users attribute to their health-disease process and the services used. this qualitative research uses the focus group technique to interview two groups of users the service monitors. The first is a group of elderly people and the second of pregnant women. To analyze the meanings, the discourse analysis technique and the reference framework of health promotion are used. the group of elderly, being mostly female arterial hypertension and diabetes mellitus patients, visualizes the health-disease process as the evolution of human existence controlled by divine power, signifying the health service as a blessing in the control of the disease. The Group of young pregnant women signified health as the ability for self-care and disease as the disability for that purposes, considering the Primary Health Care service as responsible for the recovery of individual and family health. the users demonstrated dissatisfaction with bureaucratic and vertical relations present at the health services. In each group, it was observed that the meanings for health and disease and meanings of the health service the users elaborated can be related.

FAMILIAL AMYLOID POLYNEUROPATHY——CLINICAL REPORT OF A FAMILY

Institute of Scientific and Technical Information of China (English)

李延峰; 郭玉璞; 池田修一; 方定华

1996-01-01

This paper reports a familial amyloid polyneumpathy (FAP) family in China. This family being investigated had 69 members of five generations. From the third generation, there have been 16 patients. The age of onset was about 3 to 5 decades. The initial symptoms were autonomic nerve symptcans, such as impotence, dyspepaia and diarrhoea, associated with the sensory loss of lower extremities. As the disease progressed. the upper extremities and motor ability were also involved. The duration of disease course wasabout 8-10 years, most patients died of infection and cacbexia. Sural biopsy in 3 patients had showed positive Congo red staining. From the clinical view, this FAP family is similar to FAP I found in Japan. Thetrue classification, however, should be confirmed by further genetic analysis.

Variability of age at onset in siblings with familial Alzheimer disease.

Science.gov (United States)

Gómez-Tortosa, Estrella; Barquero, M Sagrario; Barón, Manuel; Sainz, M Jose; Manzano, Sagrario; Payno, Maria; Ros, Raquel; Almaraz, Carmen; Gómez-Garré, Pilar; Jiménez-Escrig, Adriano

2007-12-01

Variability of age at onset (AO) of Alzheimer disease (AD) among members of the same family is important as a biological clue and because of its clinical effects. To evaluate which clinical variables influence the discrepancy in AO among affected relatives with familial AD. Clinical genetic project of Spanish kindred with AD conducted by 4 academic hospitals in Madrid, Spain. Age at onset of AD in 162 families and discrepancy in AO in intragenerational and intergenerational affected pairs were analyzed in relation to age, sex, maternal or paternal transmission, pattern of inheritance, and apolipoprotein E genotype. Maternal transmission of AD was significantly more frequent than paternal transmission (P patient was 65 years old. Discrepancy in AO among siblings was within 5 years in 44% of the families, 6 to 10 years in 29%, and more than 10 years in 27% (range, 0-22). This discrepancy was independent of the sex of the sibling pairs and was significantly lower with maternal transmission of AD (P = .02). Segregation analysis showed no differences in the inheritance pattern between families with low (5 years) AO discrepancy. Age at onset in carriers of the apolipoprotein E epsilon4 allele was slightly younger. However, among siblings, an extra apolipoprotein E epsilon4 allele was not consistently associated with earlier onset of AD. Eighty percent of patients, independent of sex or mode of transmission, were already affected at their parents' reported AO. There is a wide discrepancy in AO in affected siblings that is not clearly explained by a single clinical variable or apolipoprotein E genotype. The interaction of many factors probably determines AO in each affected individual. However, maternal transmission of AD seems to result in a similar AO in offspring, and the risk of developing dementia after the parent's reported AO decreases significantly.

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 ......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......, the biomarkers have proved insufficient predictors of dementias with a different pathology, e.g. frontotemporal dementia (FTD); furthermore, the biomarkers are not useful for early AD diagnosis. Familial dementias with a known disease-causing mutation can be extremely valuable to study; yet the biomarker...

Structure and function of the contactin-associated protein family in myelinated axons and their relationship with nerve diseases

Institute of Scientific and Technical Information of China (English)

Yan Zou; De-en Xu; Wei-feng Zhang; Hai-ying Liu; Xia Li; Xing Zhang; Xiao-fang Ma; Yang Sun; Shi-yi Jiang; Quan-hong Ma

2017-01-01

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.

The emergence of the IL-36 cytokine family as novel targets for inflammatory diseases.

Science.gov (United States)

Walsh, Patrick T; Fallon, Padraic G

2018-04-01

The recently discovered interleukin (IL)-36 family of cytokines form part of the broader IL-1 family and are emerging as important mediators of inflammatory disease. The IL-36 subfamily consists of three ligands-IL-36α, IL-36β, and IL-36γ-and the natural antagonist IL-36Ra. The cytokines exert their effects through a specific IL-36 receptor consisting of IL-36R and IL-1RAcP chains. IL-36 cytokines can direct both innate and adaptive immune responses by acting on parenchymal, stromal, and specific immune cell subsets. In humans, inactivating mutations in the gene encoding the IL-36R antagonist, which lead to unregulated IL-36R signaling, lead to an autoinflammatory condition termed deficiency of the IL-36R antagonist, which primarily manifests as a severe form of pustular psoriasis. While such discoveries have prompted deeper mechanistic studies highlighting the important role of IL-36 cytokines in psoriatic skin inflammation, it is now evident that IL-36 cytokines can also play important roles in inflammatory disorders in other organs, such as the gastrointestinal tract and the lungs. Given these emerging roles, strategies to specifically target the expression and activity of the IL-36 family have the potential to uncover novel therapeutic approaches aimed at treating inflammatory diseases in humans. © 2016 New York Academy of Sciences.

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: traditio...

Inversion (X)(p11.4q22) associated with Norrie disease in a four generation family.

Science.gov (United States)

Pettenati, M J; Rao, P N; Weaver, R G; Thomas, I T; McMahan, M R

1993-03-01

We report on a 4-generation family in which Norrie disease occurs together with a pericentric inversion of the X chromosome in all affected males and carrier females. The breakpoint in the short arm of the X chromosome appears to be at the purported location of the Norrie disease gene. This is the second report of an association between Norrie disease and a chromosome aberration involving Xp11, and the first report of a specific gene disruption, thus physical gene location, due to a pericentric chromosome inversion.

A novel nonsense mutation in the NDP gene in a Chinese family with Norrie disease

OpenAIRE

Liu, Deyuan; Hu, Zhengmao; Peng, Yu; Yu, Changhong; Liu, Yalan; Mo, Xiaoyun; Li, Xiaoping; Lu, Lina; Xu, Xiaojuan; Su, Wei; Pan, Qian; Xia, Kun

2010-01-01

Purpose Norrie disease (ND), a rare X-linked recessive disorder, is characterized by congenital blindness and, occasionally, mental retardation and hearing loss. ND is caused by the Norrie Disease Protein gene (NDP), which codes for norrin, a cysteine-rich protein involved in ocular vascular development. Here, we report a novel mutation of NDP that was identified in a Chinese family in which three members displayed typical ND symptoms and other complex phenotypes, such as cerebellar atrophy, ...

New mutation of the MPZ gene in a family with the Dejerine-Sottas disease phenotype.

Science.gov (United States)

Floroskufi, Paraskewi; Panas, Marios; Karadima, Georgia; Vassilopoulos, Demetris

2007-05-01

Charcot-Marie-Tooth disease type 1B is associated with mutations in the myelin protein zero gene. In the present study a new myelin protein zero gene mutation (c.89T>C,Ile30Thr) was detected in a family with the Dejerine-Sottas disease phenotype. The results support the hypothesis that severe, early-onset neuropathy may be related to either an alteration of a conserved amino acid or a disruption of the tertiary structure of myelin protein zero.

Cranial CT frindings of familial Alzheimer's disease

International Nuclear Information System (INIS)

Note, Toshiko; Tawara, Satoru; Tsuruta, Kazuhito; Araki, Shukuro

1982-01-01

Three cases of familial Alzheimer's disease were reported. The patients had an average of 41 years, and developed memory disturbance and pyramidal tract syndromes. Two had disturbance of gait and showed cerebellar symptoms. All three patients had hypotension, but had no hypotensive episodes, and no change in character or loss of character. Their IQ was extremely low, and encephalograms had delta theta waves dominant in right frontal region in one case, and general delta theta waves in the other two cases. Brain scintigraphy showed reflux to ventricle in case 2, but not in case 1. Cerebrospinal fluid was normal in all three cases, and chromosomes of cases 1 and 2 were normal 46 XY. CT scan showed that the cerebral cortex of all three patients was markedly shrunken, the sulci were enlarged and the ventricle was enlarged without being extremely rounded; the degree of cerebral atrophy according to Huckman et al. was mild in case 1 and moderate in cases 2 and 3. Slight cerebellar atrophy was detected in case 3. (Kaihara, S.)

Screening for NDP mutations in 44 unrelated patients with familial exudative vitreoretinopathy or Norrie disease.

Science.gov (United States)

Yang, Huiqin; Li, Shiqiang; Xiao, Xueshan; Guo, Xiangming; Zhang, Qingjiong

2012-08-01

To screen mutations in the norrin (NDP) gene in 44 unrelated Chinese patients with familial exudative vitreoretinopathy (FEVR, 38 cases) or Norrie disease (6 cases) and to describe the associated phenotypes. Of the 44 patients, mutation in FZD4, LRP5, and TSPAN12 was excluded in 38 patients with FEVR in previous study. Sanger sequencing was used to analyze the 2 coding exons and their adjacent regions of NDP in the 44 patients. Clinical data were presented for patients with mutation. NDP variants in 5 of the 6 patients with Norrie disease were identified, including a novel missense mutation (c.164G>A, p.Cys55Phe) in one patient, two known missense mutations (c.122G>A, p.Arg41Lys; c.220C>T, p.Arg74Cys) in two patients, and a gross deletion encompassing the two coding exons in two patients. Of the 5 patients, 3 had a family history and 2 were singleton cases. No mutation in NDP was detected in the 38 patients with FEVR. NDP mutations are common cause of Norrie disease but might be rare cause for FEVR in Chinese.

Age-specific incidence rates for dementia and Alzheimer disease in NIA-LOAD/NCRAD and EFIGA families: 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).

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

2014-03-01

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. 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. 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. 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. 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, 0.10 and 0.08, and 0.10 and 0.07, respectively, in the same age groups. Contrasting these

Disease evolution and outcomes in familial AML with germline CEBPA mutations

DEFF Research Database (Denmark)

Tawana, Kiran; Wang, Jun; Renneville, Aline

2015-01-01

collected from 10 CEBPA-mutated families, representing 24 members with acute myeloid leukemia (AML). Whole-exome (WES) and deep sequencing were performed to genetically profile tumors and define patterns of clonal evolution. Germline CEBPA mutations clustered within the N-terminal and were highly penetrant......, with AML presenting at a median age of 24.5 years (range, 1.75-46 years). In all diagnostic tumors tested (n = 18), double CEBPA mutations (CEBPAdm) were detected, with acquired (somatic) mutations preferentially targeting the C-terminal. Somatic CEBPA mutations were unstable throughout the disease course...

Association of Peripheral Arterial and Cardiovascular Diseases in Familial Hypercholesterolemia

International Nuclear Information System (INIS)

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

2014-01-01

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

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.

Familial cases of Norrie disease detected by copy number analysis.

Science.gov (United States)

Arai, Eisuke; Fujimaki, Takuro; Yanagawa, Ai; Fujiki, Keiko; Yokoyama, Toshiyuki; Okumura, Akihisa; Shimizu, Toshiaki; Murakami, Akira

2014-09-01

Norrie disease (ND, MIM#310600) is an X-linked disorder characterized by severe vitreoretinal dysplasia at birth. We report the results of causative NDP gene analysis in three male siblings with Norrie disease and describe the associated phenotypes. Three brothers with suspected Norrie disease and their mother presented for clinical examination. After obtaining informed consent, DNA was extracted from the peripheral blood of the proband, one of his brothers and his unaffected mother. Exons 1-3 of the NDP gene were amplified by polymerase chain reaction (PCR), and direct sequencing was performed. Multiplex ligation-dependent probe amplification (MLPA) was also performed to search for copy number variants in the NDP gene. The clinical findings of the three brothers included no light perception, corneal opacity, shallow anterior chamber, leukocoria, total retinal detachment and mental retardation. Exon 2 of the NDP gene was not amplified in the proband and one brother, even when the PCR primers for exon 2 were changed, whereas the other two exons showed no mutations by direct sequencing. MLPA analysis showed deletion of exon 2 of the NDP gene in the proband and one brother, while there was only one copy of exon 2 in the mother. Norrie disease was diagnosed in three patients from a Japanese family by clinical examination and was confirmed by genetic analysis. To localize the defect, confirmation of copy number variation by the MLPA method was useful in the present study.

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.

Norrie disease: first mutation report and prenatal diagnosis in an Indian family.

Science.gov (United States)

Ghosh, Manju; Sharma, Shipra; Shastri, Shivaram; Arora, Sadhna; Shukla, Rashmi; Gupta, Neerja; Deka, Deepika; Kabra, Madhulika

2012-11-01

Norrie Disease (ND) is a rare X-linked recessive disorder characterised by congenital blindness due to severe retinal dysgenesis. Hearing loss and intellectual disability is present in 30-50 % cases. ND is caused by mutations in the NDP gene, located at Xp11.3. The authors describe mutation analysis of a proband with ND and subsequently prenatal diagnosis. Sequence analysis of the NDP gene revealed a hemizygous missense mutation arginine to serine in codon 41 (p.Arg41Ser) in the affected child. Mother was carrier for the mutation. In a subsequent di-chorionic di-amniotic pregnancy, the authors performed prenatal diagnosis by mutation analysis on chorionic villi sample at 11 wk of gestation. The fetuses were unaffected. This is a first mutation report and prenatal diagnosis of a familial case of Norrie disease from India. The importance of genetic testing of Norrie disease for confirmation, carrier testing, prenatal diagnosis and genetic counseling is emphasized.

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

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.

Differential Effect of the Dopamine D3 Agonist (±-7-Hydroxy-2-(N,N-di-n-propylamino Tetralin (7-OH-DPAT on Motor Activity between Adult Wistar and Sprague-Dawley Rats after a Neonatal Ventral Hippocampus Lesion

Directory of Open Access Journals (Sweden)

Sonia Guzmán-Velázquez

2011-01-01

Full Text Available The neonatal ventral hippocampal lesion (nVHL has been widely used as an animal model for schizophrenia. Rats with an nVHL show several delayed behavioral alterations that mimic some symptoms of schizophrenia. Sprague-Dawley (SD rats with an nVHL have a decrease in D3 receptors in limbic areas, but the expression of D3 receptors in Wistar (W rats with an nVHL is unknown. The 7-Hydroxy-2-(N,N-di-n-propylamino tetralin (7-OH-DPAT has been reported as a D3-preferring agonist. Thus, we investigated the effect of (±-7-OH-DPAT (0.25 mg/kg on the motor activity in male adult W and SD rats after an nVHL. The 7-OH-DPAT caused a decrease in locomotion of W rats with an nVHL, but it did not change the locomotion of SD rats with this lesion. Our results suggest that the differential effect of 7-OH-DPAT between W and SD rats with an nVHL could be caused by a different expression of the D3 receptors. These results may have implications for modeling interactions of genetic and environmental factors involved in schizophrenia.

Clinical radiological correlation in E200K familial Creutzfeldt-Jakob disease.

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Cohen, Oren S; Chapman, Joab; Korczyn, Amos D; Siaw, Oliver L; Warman-Alaluf, Naama; Nitsan, Zeev; Appel, Shmuel; Kahana, Esther; Rosenmann, Hanna; Hoffmann, Chen

2016-12-01

The use of diffusion MRI improved the accuracy of diagnosis in Creutzfeldt-Jakob disease (CJD) and expanded our knowledge of the changes occurring in the brain during the disease. The aim of this study was to test whether in patients with E200K familial CJD (fCJD) the clinical severity correlates with the disease burden as reflected by the extent of cortical involvement in DWI MRI. Consecutive fCJD patients were examined by a neurologist who performed several tests including the CJD neurological scale (CJD-NS), MiniMental status examination (MMSE), Frontal Assessment Battery (FAB), NIH Stroke Scale (NIHSS), and the expanded disability status scale (EDSS). A simultaneously acquired MRI was analyzed by measuring the extent of cortical involvement in the DWI axial sequence. Correlations were tested for using Pearson test. Fifty-two fCJD patients (35 males, mean age 59.4 ± 5.7 years) were recruited to the study. Significant negative correlation was found between the extent of cortical involvement and the cognitive performance of the patients as reflected by their MMSE and FAB scores. In addition, a significant positive correlation was found between the MRI and the clinical disease severity scales CJD-NS and EDSS. The correlation between clinical scales of severity and cognitive dysfunction and the disease burden confirms the reliability of the CJD-NS scale. Further studies are warranted to examine whether MRI may serve not only for diagnosis but also as a biomarker for follow-up of disease progression and the efficacy of potential treatments.

Expressional and Biochemical Characterization of Rice Disease Resistance Gene Xa3/Xa26 Family

Institute of Scientific and Technical Information of China (English)

Songjie Xu; Yinglong Cao; Xianghua Li; Shiping Wang

2007-01-01

The rice (Oryza sativa L.) Xa3/Xa26 gene, conferring race-specific resistance to bacterial blight disease and encoding a leucine-rich repeat (LRR) receptor kinase-like protein, belongs to a multigene family consisting of tandem clustered homologous genes, colocalizing with several uncharacterized genes for resistance to bacterial blight or fungal blast. To provide more information on the expressional and biochemical characteristics of the Xa3/Xa26 family, we analyzed the family members. Four Xa3/Xa26 family members in the indica rice variety Teqing, which carries a bacterial blight resistance gene with a chromosomal location tightly linked to Xa3/Xa26, and five Xa3/Xa26 family members in the japonica rice variety Nipponbare, which carries at least one uncharacterized blast resistance gene, were constitutively expressed in leaf tissue. The result suggests that some of the family members may be candidates of these uncharacterized resistance genes. At least five putative N-glycosylation sites in the LRR domain of XA3/XA26 protein are not glycosylated. The XA3/XA26 and its family members MRKa and MRKc all possess the consensus sequences of paired cysteines, which putatively function in dimerization of the receptor proteins for signal transduction, immediately before the first LRR and immediately after the last LRR. However, no homo-dimer between the XA3/XA26 molecules or hetero-dimer between XA3/XA26 and MRKa or MRKc were formed, indicating that XA3/XA26 protein might function either as a monomer or a hetero-dimer formed with other protein outside of the XA3/XA26 family. These results provide valuable information for further extensive investigation into this multiple protein family.

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

A mutation in the Norrie disease gene (NDP) associated with X-linked familial exudative vitreoretinopathy.

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Chen, Z Y; Battinelli, E M; Fielder, A; Bundey, S; Sims, K; Breakefield, X O; Craig, I W

1993-10-01

Familial exudative vitreoretinopathy (FEVR) is a hereditary disorder characterized by an abnormality of the peripheral retina. Both autosomal dominant (adFEVR) and X-linked (XLFEVR) forms have been described, but the biochemical defect(s) underlying the symptoms are unknown. Molecular analysis of the Norrie gene locus (NDP) in a four generation FEVR family (shown previously to exhibit linkage to the X-chromosome markers DXS228 and MAOA (Xp11.4-p11.3)) reveals a missense mutation in the highly conserved region of the NDP gene, which caused a neutral amino acid substitution (Leu124Phe), was detected in all of the affected males, but not in the unaffected family members, nor in normal controls. The observations suggest that phenotypes of both XLFEVR and Norrie disease can result from mutations in the same gene.

The contribution of classical risk factors to cardiovascular disease in familial hypercholesterolaemia: data in 2400 patients

NARCIS (Netherlands)

Jansen, A. C. M.; van Aalst-Cohen, E. S.; Tanck, M. W.; Trip, M. D.; Lansberg, P. J.; Liem, A. H.; van Lennep, H. W. O. Roeters; Sijbrands, E. J. G.; Kastelein, J. J. P.

2004-01-01

Objective. To determine the contribution of classical risk factors to the development of cardiovascular disease (CVD) in patients with heterozygous familial hypercholesterolaemia (FH). Design. A retrospective, multi-centre, cohort study. Extensive data were collected by scrutinizing medical records

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

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...... 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...

Identification of novel missense mutations in the Norrie disease gene associated with one X-linked and four sporadic cases of familial exudative vitreoretinopathy.

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Shastry, B S; Hejtmancik, J F; Trese, M T

1997-01-01

X-linked Familial Exudative Vitreoretinopathy (XLFEVR) is a hereditary eye disorder that affects both the retina and the vitreous body. It is characterized by an abnormal vascularization of the peripheral retina. It has been previously shown by linkage and candidate gene analysis that XLFEVR and Norrie disease are allelic. In this report we describe four novel mutations (R41K, H42R, K58N, and Y120C) in the Norrie disease gene associated with one X-linked and four sporadic cases of FEVR. One mutation (H42R) was found to be segregating with the disease in three generations (X-linked family), and the others are sporadic. These sequence alterations changed the encoded amino acids in the Norrie disease protein and were not found in 17 unaffected family members or in 36 randomly selected normal individuals. This study provides additional evidence that mutations in the same gene can result in FEVR and Norrie disease. It also demonstrates that it may be beneficial for clinical diagnosis to screen for mutations in the Norrie disease gene in sporadic FEVR cases.

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...... aneurysm (AAA) strongly increases the risk of developing AAA, but it is still uncertain whether familial AAA’s develops differently than non-familial AAA’s. Objectives: To investigate whether familial AAA’s develop more aggressively than non-familial AAA’s by looking at growth rate, risk of surgery...... and rupture, as well as the size of the aneurysm at the time of diagnosis and the patient´s age at the time of operation, rupture and diagnosis. Design: Observational retrospective longitudinal study Materials: 318 patients (273 men and 45 women) with AAA diagnosed between 1996-2008 in Jutland, Denmark...

Serum neurofilament light in familial Alzheimer disease: A marker of early neurodegeneration.

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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.

Supporting change in chronic disease risk behaviours for people with a mental illness: a qualitative study of the experiences of family carers.

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Bailey, Jacqueline M; Hansen, Vibeke; Wye, Paula M; Wiggers, John H; Bartlem, Kate M; Bowman, Jennifer A

2018-03-27

People with a mental illness experience greater chronic disease morbidity and mortality, and associated reduced life expectancy, compared to those without such an illness. A higher prevalence of chronic disease risk behaviours (inadequate nutrition, inadequate physical activity, tobacco smoking, and harmful alcohol consumption) is experienced by this population. Family carers have the potential to support change in such behaviours among those they care for with a mental illness. This study aimed to explore family carers': 1) experiences in addressing the chronic disease risk behaviours of their family members; 2) existing barriers to addressing such behaviours; and 3) perceptions of potential strategies to assist them to provide risk behaviour change support. A qualitative study of four focus groups (n = 31), using a semi-structured interview schedule, was conducted with carers of people with a mental illness in New South Wales, Australia from January 2015 to February 2016. An inductive thematic analysis was employed to explore the experience of carers in addressing the chronic disease risk behaviours. Two main themes were identified in family carers' report of their experiences: firstly, that health behaviours were salient concerns for carers and that they were engaged in providing support, and secondly that they perceived a bidirectional relationship between health behaviours and mental well-being. Key barriers to addressing behaviours were: a need to attend to carers' own well-being; defensiveness on behalf of the family member; and not residing with their family member; with other behaviour-specific barriers also identified. Discussion around strategies which would assist carers in providing support for health risk behaviours identified a need for improved communication and collaboration between carers and health services accessed by their family members. Additional support from general and mental health services accessed by family members is desired to

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.

Family health and family physician’s influence on prevention of psychoactive substances abuse

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Lapčević Mirjana

2010-01-01

Full Text Available The family, as the basic social unit, has a decisive role in the health and disease of its members. It is the primary unit where health needs are formed and solved. By its own resources the family independently resolves about 75% of the total health requirements. In the paper the authors study family characteristics which influence family health and diseases, indicators of family health and the scale of life values. Also, the study evaluates social factors, communication and the influence of the usage of psychoactive substances on family health and the quality of family life. To form the personality of a child three factors are most significant: love, the feeling of safety and the presence of harmonious relationship between the parents. Life harmony in a family also depends on the quality of structural components of the personality and the interaction of motivation of its members. Early childhood determines the future personality of the adult person. At that period, habits and partially attitudes are formed. In harmonious family relationships the parents are the role model to children. Verbal and non-verbal communication enrich the relationship among people and enable efforts in supporting understanding, compassion and care for others by mutual agreement. On the scale of life values of Serbian citizens health holds the first position. Immediately following the health issue is good relationship in the family. As healthcare is not only the task of healthcare services, but also of each individual, family and the society as a whole, it is on healthcare personnel to educate the citizens how to preserve and improve their own health and the health of their family by a continual healthcare and education. Above all, this concerns avoidance of bad habits, such as smoking, immoderate alcohol consumption, narcotic abuse, physical inactivity, hypercaloric nutrition, etc. Also, it is significant to make an early recognition of disease symptoms and to turn for

Family, Community, and Health System Considerations for Reducing the Burden of Pediatric Sickle Cell Disease in Uganda Through Newborn Screening

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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.

Psychological impact of von Hippel-Lindau genetic screening in patients with a previous history of hemangioblastoma of the central nervous system.

Science.gov (United States)

Rochette, Claire; Baumstarck, Karine; Canoni-Zattara, Hélène; Abdullah, Ahmad Esmaeel; Figarella-Branger, Dominique; Pertuit, Morgane; Barlier, Anne; Castinetti, Frédéric; Pacak, Karel; Metellus, Philippe; Taïeb, David

2018-05-15

Von Hippel-Lindau (VHL) syndrome is a hereditary cancer syndrome characterized by a high risk of developing benign and malignant tumors, including central nervous system hemangioblastomas (CNS HBs). For an early diagnosis of VHL, before the occurrence of cancers (especially renal cell carcinoma), it is of huge importance to initiate VHL genetic testing in at-risk patients. The aim of the study was to assess the psychological impact of VHL genetic testing in patients previously diagnosed with a CNS HB. From 1999 until 2015, 55 patients underwent surgery for CNS HBs. Eleven patients were already screened for VHL mutations and 3 patients deceased before the start of the study. From the remaining 42 patients, 24 were accepted to be enrolled in the study. Assessment of psychological impact of VHL genetic testing was performed by measuring anxiety levels, mood disorders, quality of life, and psychological consequences of genetic screening. Twenty-one of the enrolled 24 patients underwent VHL genetic testing and 12 patients came back for the communication of positive genetic results. The baseline psychological status did not differ between these 2 groups. Patients who attended the visit of communication of genetic results had similar anxiety levels compared to those who had not. Furthermore, they also experienced an improvement in the level of anxiety and two QoL dimension scores compared to their baseline status. In summary, there is no evidence of a negative psychosocial impact of VHL genetic testing in patients with a previous history of CNS HB. We, therefore, recommend the recall of patients who have not been previously screened.

The economic cost of Alzheimer's disease: Family or public-health burden?

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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.

[Familial astrocytoma associated with von Recklinghausen's disease: report of two cases].

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Ito, Y; Oki, S; Mikami, T; Ogasawara, H; Kawamoto, Y; Sato, H; Yamaguchi, S; Hayashi, Y; Shindo, H

1997-03-01

Two cases of astrocytoma associated with von Recklinghausen's disease (neurofibromatosis type; NF-1) were reported. The first case wes a 60-year-old man who had been diagnosed as von Recklinghausen's disease on the basis of skin findings. Magnetic resonance imaging (MRI) showed a tumor in the left temporal lobe. Partial removal was performed with neuronavigator, and because of the existence of Rosenthal fiber the histological diagnosis was pilocytic astrocytoma. Radiation therapy was performed. The second case was a 6-year-old boy suffering from headache and left hemiparesis including his face. MRI showed a tumor with a cyst in the right thalamus and obstructive hydrocephalus. Initially CT-guided stereotactic biopsy was performed, and the histological diagnosis, on the basis of increased cellularity, pleomorphism and nuclear atypia without necrosis or vascular proliferation, was anaplastic astrocytoma. Radiation and chemo-immuno therapy were carried out after V-P shunt. It is well known that von Recklinghausen's disease (NF-1) is often associated with optic glioma (5-36%). In the literature, the glioma seldom occurs in other parts of the brain, supratentorial glioma especially is rare. Only two familial cases of supratentorial glioma associated with von Recklinghausen's disease have been reported. The prognosis of supratentorial glioma associated with NF-1 was poor in these reports. In this paper, the diagnostic and therapeutic problems are discussed.

Expression of REG family genes in human inflammatory bowel diseases and its regulation

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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.

Familial Screening for Left-Sided Congenital Heart Disease: What Is the Evidence? What Is the Cost?

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Daniel J. Perry

2017-12-01

Full Text Available Since the American Heart Association’s recommendation for familial screening of adults with congenital heart disease for bicuspid aortic valve, similar recommendations for other left-sided heart defects, such as hypoplastic left heart syndrome (HLHS, have been proposed. However, defining at-risk populations for these heart defects based on genetics is less straightforward due to the wide variability of inheritance patterns and non-genetic influences such as environmental and lifestyle factors. We discuss whether there is sufficient evidence to standardize echocardiographic screening for first-degree relatives of children diagnosed with HLHS. Due to variations in the inclusion of cardiac anomalies linked to HLHS and the identification of asymptomatic individuals with cardiac malformations, published studies are open to interpretation. We conclude that familial aggregation of obstructive left-sided congenital heart lesions in families with history of HLHS is not supported and recommend that additional screening should adopt a more conservative definition of what truly constitutes this heart defect. More thorough consideration is needed before embracing familial screening recommendations of families of patients with HLHS, since this could inflict serious costs on healthcare infrastructure and further burden affected families both emotionally and financially.

A novel nonsense mutation in the NDP gene in a Chinese family with Norrie disease.

Science.gov (United States)

Liu, Deyuan; Hu, Zhengmao; Peng, Yu; Yu, Changhong; Liu, Yalan; Mo, Xiaoyun; Li, Xiaoping; Lu, Lina; Xu, Xiaojuan; Su, Wei; Pan, Qian; Xia, Kun

2010-12-08

Norrie disease (ND), a rare X-linked recessive disorder, is characterized by congenital blindness and, occasionally, mental retardation and hearing loss. ND is caused by the Norrie Disease Protein gene (NDP), which codes for norrin, a cysteine-rich protein involved in ocular vascular development. Here, we report a novel mutation of NDP that was identified in a Chinese family in which three members displayed typical ND symptoms and other complex phenotypes, such as cerebellar atrophy, motor disorders, and mental disorders. We conducted an extensive clinical examination of the proband and performed a computed tomography (CT) scan of his brain. Additionally, we performed ophthalmic examinations, haplotype analyses, and NDP DNA sequencing for 26 individuals from the proband's extended family. The proband's computed tomography scan, in which the fifth ventricle could be observed, indicated cerebellar atrophy. Genome scans and haplotype analyses traced the disease to chromosome Xp21.1-p11.22. Mutation screening of the NDP gene identified a novel nonsense mutation, c.343C>T, in this region. Although recent research has shown that multiple different mutations can be responsible for the ND phenotype, additional research is needed to understand the mechanism responsible for the diverse phenotypes caused by mutations in the NDP gene.

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 8.6×10 8 (range 0.7-75×10 8 ), 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.

Novel mutation in TSPAN12 leads to autosomal recessive inheritance of congenital vitreoretinal disease with intra-familial phenotypic variability.

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Gal, Moran; Levanon, Erez Y; Hujeirat, Yasir; Khayat, Morad; Pe'er, Jacob; Shalev, Stavit

2014-12-01

Developmental malformations of the vitreoretinal vasculature are a heterogeneous group of conditions with various modes of inheritance, and include familial exudative vitreoretinopathy (FEVR), persistent fetal vasculature (PFV), and Norrie disease. We investigated a large consanguineous kindred with multiple affected individuals exhibiting variable phenotypes of abnormal vitreoretinal vasculature, consistent with the three above-mentioned conditions and compatible with autosomal recessive inheritance. Exome sequencing identified a novel c.542G > T (p.C181F) apparently mutation in the TSPAN12 gene that segregated with the ocular disease in the family. The TSPAN12 gene was previously reported to cause dominant and recessive FEVR, but has not yet been associated with other vitreoretinal manifestations. The intra-familial clinical variability caused by a single mutation in the TSPAN12 gene underscores the complicated phenotype-genotype correlation of mutations in this gene, and suggests that there are additional genetic and environmental factors involved in the complex process of ocular vascularization during embryonic development. Our study supports considering PFV, FEVR, and Norrie disease a spectrum of disorders, with clinical and genetic overlap, caused by mutations in distinct genes acting in the Norrin/β-catenin signaling pathway. © 2014 Wiley Periodicals, Inc.

Factors affecting frequency of communication about family health history with family members and doctors in a medically underserved population.

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Kaphingst, Kimberly A; Goodman, Melody; Pandya, Chintan; Garg, Priyanka; Stafford, Jewel; Lachance, Christina

2012-08-01

Family history contributes to risk for many common chronic diseases. Little research has investigated patient factors affecting communication of this information. 1061 adult community health center patients were surveyed. We examined factors related to frequency of discussions about family health history (FHH) with family members and doctors. Patients who talked frequently with family members about FHH were more likely to report a family history of cancer (p =.012) and heart disease (p history of heart disease (p = .011), meet physical activity recommendations (p = .022), seek health information frequently in newspapers (p history of some diseases, those not meeting physical activity recommendations, and those who do not frequently seek health information may not have ongoing FHH discussions. Interventions are needed to encourage providers to update patients' family histories systematically and assist patients in initiating FHH conversations in order to use this information for disease prevention and control. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Renal Cell Carcinoma Programmed Death-ligand 1, a New Direct Target of Hypoxia-inducible Factor-2 Alpha, is Regulated by von Hippel-Lindau Gene Mutation Status.

Science.gov (United States)

Messai, Yosra; Gad, Sophie; Noman, Muhammad Zaeem; Le Teuff, Gwenael; Couve, Sophie; Janji, Bassam; Kammerer, Solenne Florence; Rioux-Leclerc, Nathalie; Hasmim, Meriem; Ferlicot, Sophie; Baud, Véronique; Mejean, Arnaud; Mole, David Robert; Richard, Stéphane; Eggermont, Alexander M M; Albiges, Laurence; Mami-Chouaib, Fathia; Escudier, Bernard; Chouaib, Salem

2016-10-01

Clear cell renal cell carcinomas (ccRCC) frequently display a loss of function of the von Hippel-Lindau (VHL) gene. To elucidate the putative relationship between VHL mutation status and immune checkpoint ligand programmed death-ligand 1 (PD-L1) expression. A series of 32 renal tumors composed of 11 VHL tumor-associated and 21 sporadic RCCs were used to evaluate PD-L1 expression levels after sequencing of the three exons and exon-intron junctions of the VHL gene. The 786-O, A498, and RCC4 cell lines were used to investigate the mechanisms of PD-L1 regulation. Fisher's exact test was used for VHL mutation and Kruskal-Wallis test for PD-L1 expression. If no covariate accounted for the association of VHL and PD-L1, then a Kruskal-Wallis test was used; otherwise Cochran-Mantel-Haenzsel test was used. We also used the Fligner-Policello test to compare two medians when the distributions had different dispersions. We demonstrated that tumors from ccRCC patients with VHL biallelic inactivation (ie, loss of function) display a significant increase in PD-L1 expression compared with ccRCC tumors carrying one VHL wild-type allele. Using the inducible VHL 786-O-derived cell lines with varying hypoxia-inducible factor-2 alpha (HIF-2α) stabilization levels, we showed that PD-L1 expression levels positively correlate with VHL mutation and HIF-2α expression. Targeting HIF-2α decreased PD-L1, while HIF-2α overexpression increased PD-L1 mRNA and protein levels in ccRCC cells. Interestingly, chromatin immunoprecipitation and luciferase assays revealed a direct binding of HIF-2α to a transcriptionally active hypoxia-response element in the human PD-L1 proximal promoter in 786-O cells. Our work provides the first evidence that VHL mutations positively correlate with PD-L1 expression in ccRCC and may influence the response to ccRCC anti-PD-L1/PD-1 immunotherapy. We investigated the relationship between von Hippel-Lindau mutations and programmed death-ligand 1 expression. We

Specialist physician knowledge of chronic kidney disease: A comparison of internists and family physicians in West Africa

Directory of Open Access Journals (Sweden)

Emmanuel I. Agaba

2012-05-01

Full Text Available Background: Postgraduate training is aimed at equipping the trainee with the necessary skills to practise as an expert. Non-nephrology specialist physicians render the bulk of pre-end-stage renal disease care for patients with chronic kidney disease (CKD. We sought to ascertain the knowledge of CKD amongst non-nephrology specialist physicians who serve as trainers and examiners for a training, accrediting and certifying body in postgraduate medicine in West Africa. We also compared the knowledge of family physicians and non-nephrology internists. Methods: Self-administered questionnaires were distributed to non-nephrology specialist physicians who serve as examiners for the West African College of Physicians. Results: Only 19 (27.5% of the respondents were aware of the Kidney Disease Outcomes Quality Initiatives guidelines for CKD management. Twenty five (36.2% of the respondents had adequate knowledge of CKD. There was no significant difference in the proportion of family physicians and non-nephrology internists who had adequate knowledge of CKD (27.3% vs. 40.4% respectively; p = 0.28. Hypertension and diabetes mellitus were identified by all of the physicians as risk factors for CKD. Non-nephrology internists more frequently identified systemic lupus erythematosus as a risk factor for CKD, urinalysis with microscopy as a laboratory test for CKD evaluation, and bone disease as a complication of CKD than family physicians. Conclusion: There is a lack of adequate CKD knowledge amongst non-nephrology specialist physicians, since many of them are unaware of the CKD management guidelines. Educational efforts are needed to improve the knowledge of CKD amongst non-nephrology specialist physicians. Guidelines on CKD need to be widely disseminated amongst these physicians.

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 family expressiveness, support, and conflict are indicated for this population. Copyright © 2011 Wiley-Liss, Inc.

Functional significance of erythropoietin in renal cell carcinoma

International Nuclear Information System (INIS)

Morais, Christudas; Johnson, David W; Vesey, David A; Gobe, Glenda C

2013-01-01

One of the molecules regulated by the transcription factor, hypoxia inducible factor (HIF), is the hypoxia-responsive hematopoietic factor, erythropoietin (EPO). This may have relevance to the development of renal cell carcinoma (RCC), where mutations of the von Hippel-Lindau (VHL) gene are major risk factors for the development of familial and sporadic RCC. VHL mutations up-regulate and stabilize HIF, which in turn activates many downstream molecules, including EPO, that are known to promote angiogenesis, drug resistance, proliferation and progression of solid tumours. HIFs typically respond to hypoxic cellular environment. While the hypoxic microenvironment plays a critical role in the development and progression of tumours in general, it is of special significance in the case of RCC because of the link between VHL, HIF and EPO. EPO and its receptor, EPOR, are expressed in many cancers, including RCC. This limits the use of recombinant human EPO (rhEPO) to treat anaemia in cancer patients, because the rhEPO may be stimulatory to the cancer. EPO may also stimulate epithelial-mesenchymal transition (EMT) in RCC, and pathological EMT has a key role in cancer progression. In this mini review, we summarize the current knowledge of the role of EPO in RCC. The available data, either for or against the use of EPO in RCC patients, are equivocal and insufficient to draw a definitive conclusion

The Impact of Spiritual Care Education on the Self-Efficacy of the Family Caregivers of Elderly People with Alzheimer’s Disease

Directory of Open Access Journals (Sweden)

Azam Salamizadeh

2017-07-01

Full Text Available Background: Caring for people who suffer from Alzheimer’s disease is stressful. Family caregivers of these people usually experience physical and mental burnout and lose their efficacy in doing care-related activities. The present study aimed to examine the impacts of spiritual care education on self-efficacy of the family caregivers of people with Alzheimer’s disease. Methods: This study was conducted from October to December 2015 by using a two-group pretest-posttest quasi-experimental design. In total, 60 family caregivers of people with Alzheimer’s disease were recruited and randomly allocated to the intervention and control groups. A spiritual care educational intervention was implemented for the caregivers in the intervention group. The data were collected before and three weeks after the study intervention by using the ten-item General Self Efficacy scale. The study data were analyzed in SPSS using Chi-square and independent t-test. Results: Before the study intervention, the means of pretest self-efficacy scores in the intervention and control groups were 29.80±4.80 and 28.39±6.41, respectively. There was no significant difference between the groups regarding the mean score of self-efficacy (P=0.36. After the study, these two scores changed to 32.73±4.75 and 27.85±5.98, respectively. However, after the intervention, the mean score of self-efficacy in the intervention group was significantly higher than the control group (P=0.002. Conclusion: Spiritual care can enhance the self-efficacy of the family caregivers of people who suffer from Alzheimer’s disease. Therefore, care providers are recommended to use such spirituality-based interventions for empowering family caregivers.

"There is still so much ahead of us"-family functioning in families of palliative cancer patients.

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Kühne, Franziska; Krattenmacher, Thomas; Bergelt, Corinna; Beierlein, Volker; Herzog, Wolfgang; V Klitzing, Kai; Weschenfelder-Stachwitz, Heike; Romer, Georg; Möller, Birgit

2013-06-01

Adopting a systems approach, parental cancer has its impact on patients, spouses, and dependent children. The purpose of the current study was to examine family functioning dependent on parental disease stage and on family member perspective in families of cancer patients with adolescent children. The cross-sectional study was conducted within a German multisite research project of families before their first child-centered counseling encounter. The sample comprised individuals nested within N = 169 families. Analyses performed included analysis of covariance (ANCOVA) and intraclass correlation. Open answers were analyzed following quantitative content analysis procedures. Between 15% and 36% of family members reported dysfunctional general functioning scores. Parents indicated more dysfunctional scores on the Family Assessment Device scale Roles, and adolescents more dysfunctional Communication scores. Regarding assessment of family functioning, there was higher agreement in families with parents in a palliative situation. For adolescents with parents in palliation, incidents because of the disease tend to become more dominant, and spending time with the family tends to become even more important. As our study pointed out, parental cancer, and especially parental palliative disease, is associated with both perceived critical and positive aspects in family functioning. Supporting families in these concerns as well as encouraging perceptions of positive aspects are important components of psycho-oncological interventions for families with dependent children. PsycINFO Database Record (c) 2013 APA, all rights reserved.

Patients' and their family members' experiences of participation in care following an acute exacerbation in chronic obstructive pulmonary disease: A phenomenological-hermeneutic study.

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Andersen, Ingrid Charlotte; Thomsen, Thora Grothe; Bruun, Poul; Bødtger, Uffe; Hounsgaard, Lise

2017-12-01

To explore the experiences of patients with chronic obstructive pulmonary disease and their family members relating both to participation in care during hospitalisation for an acute exacerbation in chronic obstructive pulmonary disease, and to the subsequent day-to-day care at home. 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, knowledge of the significance of patient and family participation for recovery and subsequent everyday life is still limited. This study adopted a longitudinal design informed by ethnographic fieldwork principles. Participant observations and interviews with 15 patients and 12 family 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. Participation in care was perceived as valuable, but could be associated with tensions and increased uncertainty. While patients mostly demonstrated a reactive approach to care, family members strived to be more proactive. In hospital, preparing for discharge included an effort to find a balance between powerlessness and influence during interactions with healthcare professionals. At home, managing further recovery and self-management were characterised by navigating between mutual pressure and consideration within the family. Family members play an important role in ensuring that patients are seen, heard and understood, but want to be acknowledged more by healthcare professionals. Appropriate interactions with healthcare professionals are crucial in order to support discharge and daily self-management. Knowledge of the challenges that patients with chronic obstructive pulmonary disease and their family

Complex educational and care (geron)technology for elderly individuals/families experiencing Alzheimer's disease.

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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

Overall and domain-specific life satisfaction when living with familial Alzheimer's disease risk: A quantitative approach.

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Bergman, Mette; Graff, Caroline; Eriksdotter, Maria; Schuster, Marja; Fugl-Meyer, Kerstin S

2017-12-01

In this study, we explored life satisfaction and sense of coherence in relation to biopsychosocial variables in individuals at risk for the development of familial Alzheimer's disease. Forty nine individuals (response rate: 96%) were interviewed. Life satisfaction was found to be high for the majority of participants. Those who were older than the expected age of onset of disease, those satisfaction with life as a whole, psychological health, vocation, and economy. Women seem to be more vulnerable than men, and attention should be given to those who have not passed the age of expected symptom onset. Early and recurrent counseling and psychosocial support were found to be essential. Issues related to vocation and economy are areas of concern, and are closely associated with sense of coherence, life satisfaction, and psychological health. This study emphasizes the importance of professional teams working together with the patient and their families. © 2017 John Wiley & Sons Australia, Ltd.

The tumor necrosis factor-alpha-induced protein 8 family in immune homeostasis and inflammatory cancer diseases.

Science.gov (United States)

Luan, Y Y; Yao, Y M; Sheng, Z Y

2013-01-01

Within the immune system homeostasis is maintained by a myriad of mechanisms that include the regulation of immune cell activation and programmed cell death. The breakdown of immune homeostasis may lead to fatal inflammatory diseases. We set out to identify genes of tumor necrosis factor-alpha-induced protein 8 (TNFAIP8) family that has a functional role in the process of immune homeostasis. Tumor necrosis factor-alpha-induced protein 8 (TNFAIP8), which functions as an oncogenic molecule, is also associated with enhanced cell survival and inhibition of apoptosis. Tumor necrosis factor-alpha-induced protein 8-like 2 (TIPE2) governs immune homeostasis in both the innate and adaptive immune system and prevents hyper-responsiveness by negatively regulating signaling via T cell receptors and Toll-like receptors (TLRs). There also exist two highly homologous but uncharacterized proteins, TIPE1 and TIPE3. This review is an attempt to provide a summary of TNFAIP8 family associated with immune homeostasis and inflammatory cancer diseases.

The Danish HD Registrya nationwide family registry of HD families in Denmark

DEFF Research Database (Denmark)

Gilling, M.; Budtz-Jorgensen, E.; Boonen, S. E.

2017-01-01

-8:100 000. 1451 individuals in the DHR had the size of the HTT CAG repeat determined of which 975 had 36 CAG repeats or more (mean ± SD: 43,5 ± 4,8). Two unrelated individuals were compound heterozygous for alleles ≥36 CAGs, and 60 individuals from 34 independent families carried an intermediate allele.......The Danish Huntington's Disease Registry (DHR) is a nationwide family registry comprising 14 245 individuals from 445 Huntington's disease (HD) families of which the largest family includes 845 individuals in 8 generations. 1136 DNA and/or blood samples and 18 fibroblast cultures are stored...... in a local biobank. The birthplace of the oldest HD carrier in each of the 261 families of Danish origin was unevenly distributed across Denmark with a high number of families in the middle part of the peninsula Jutland and in Copenhagen, the capital. The prevalence of HD in Denmark was calculated to be 5...

Pharmacological rescue of mitochondrial deficits in iPSC-derived neural cells from patients with familial Parkinson's disease

DEFF Research Database (Denmark)

Cooper, Oliver; Seo, Hyemyung; Andrabi, Shaida

2012-01-01

, or the LRRK2 kinase inhibitor GW5074. Analysis of mitochondrial responses in iPSC-derived neural cells from PD patients carrying different mutations provides insight into convergence of cellular disease mechanisms between different familial forms of PD and highlights the importance of oxidative stress...... of reactive oxygen species, mitochondrial respiration, proton leakage, and intraneuronal movement of mitochondria. Cellular vulnerability associated with mitochondrial dysfunction in iPSC-derived neural cells from familial PD patients and at-risk individuals could be rescued with coenzyme Q(10), rapamycin...

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

, knowledge of the significance of patient and family participation for recovery and subsequent everyday life is still limited. DESIGN: This study adopted a longitudinal design informed by ethnographic fieldwork principles. METHODS: Participant observations and interviews with 15 patients and 12 family......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...

Risk factors for colorectal cancer in subjects with family history of the disease.

Science.gov (United States)

Fernandez, E; La Vecchia, C; D'Avanzo, B; Negri, E; Franceschi, S

1997-01-01

The relationship between lifestyle factors, past medical conditions, daily meal frequency, diet and the risk of 'familial' colorectal cancer has been analysed using data from a case-control study conducted in northern Italy. A total of 1584 colorectal cancer patients and 2879 control subjects were admitted to a network of hospitals in the Greater Milan area and the Pordenone province. The subjects included for analysis were the 112 cases and the 108 control subjects who reported a family history of colorectal cancer in first-degree relatives. Colorectal cancer cases and control subjects with family history were similarly distributed according to sex, age, marital status, years of schooling and social class. Familial colorectal cancer was associated with meal frequency, medical history of diabetes (relative risk, RR = 4.6) and cholelithiasis (RR = 5.2). Significant positive trends of increasing risk with more frequent consumption were observed for pasta (RR = 2.5, for the highest vs the lowest intake tertile), pastries (RR = 2.4), red meat (RR = 2.9), canned meat (RR = 1.9), cheese (RR = 3.5) and butter (RR = 1.9). Significant inverse associations and trends in risk were observed for consumption of poultry (RR = 0.4), tomatoes (RR = 0.2), peppers (RR = 0.3) and lettuce (RR = 0.3). Significant inverse trends in risk with increasing consumption for beta-carotene and ascorbic acid were observed (RR = 0.5 and 0.4 respectively, highest vs lowest intake tertile). These results suggest that risk factors for subjects with a family history of colorectal cancer in first-degree relatives are not appreciably different from recognized risk factors of the disease in the general population.

Familial risks of glomerulonephritis - a nationwide family study in Sweden.

Science.gov (United States)

Akrawi, Delshad Saleh; Li, Xinjun; Sundquist, Jan; Fjellstedt, Erik; Sundquist, Kristina; Zöller, Bengt

2016-08-01

Familial risks of glomerulonephritis (acute, chronic and unspecified glomerulonephritis) have not been studied. This study aims to determine the familial risks of glomerulonephritis. Individuals born from1932 onwards diagnosed with glomerulonephritis (acute [n = 7011], chronic [n = 10,242] and unspecified glomerulonephritis [n = 5762]) were included. The familial risk (Standardized incidence ratio = SIR) was calculated for individuals whose parents/full-siblings were diagnosed with glomerulonephritis compared to those whose parents/full-siblings were not. The procedure was repeated for spouses. Familial concordant risk (same disease in proband and exposed relative) and discordant risk (different disease in proband and exposed relative) of glomerulonephritis were determined. Familial concordant risks (parents/full-sibling history) were: SIR = 3.57 (95% confidence interval, 2.77-4.53) for acute glomerulonephritis, SIR = 3.84 (3.37-4.36) for chronic glomerulonephritis and SIR = 3.75 (2.85-4.83) for unspecified glomerulonephritis. High familial risks were observed if two or more relatives were affected; the SIR was 209.83 (150.51-284.87) in individuals with at least one affected parent as well as one full-sibling. The spouse risk was only moderately increased (SIR = 1.53, 1.33-1.75). Family history of glomerulonephritis is a strong predictor for glomerulonephritis, and is a potentially useful tool in clinical risk assessment. Our data emphasize the contribution of familial factors to the glomerulonephritis burden in the community. Key Messages The familial risks (full-sibling/parent history) of glomerulonephritis (acute, chronic and unspecified glomerulonephritis) have not been determined previously. The familial risks of glomerulonephritis were increased among individuals with family history of acute, chronic or unspecified glomerulonephritis. The familial risks of glomerulonephritis were slightly increased among spouses indicating a

[Optimism, family cohesion and treatment as predictors of quality of life in blood cancer diseases].

Science.gov (United States)

Lavielle-Sotomayor, Pilar; Rozen-Fuller, Etta; Bustamante-Rojano, Juan; Martínez-Murillo, Carlos

2017-01-01

Quality of life must be a part of the goals of care given to blood cancer patients and it must be used to assess the effectiveness of their treatment. The objective was to evaluate the quality of life of patients with leukemia and its relationship with psychological, familial and disease-related aspects. An analytic cross-sectional study was carried out in patients with acute leukemia at different stages of treatment. We used SF-36, Optimism and Family Cohesion scales. Quality of life was affected physically and mentally in the treatment phases aimed to mitigate the active, and the advanced stage of this disease (50.6 ± 25.6, 62 ± 14.3; 46 ± 23.2, 53.8 ± 23.4, respectively), regardless of gender, age, level of optimism and family cohesion. Patients could carry out basic functions of self-care (bathing, feeding, etcetera), but not activities of daily living (shopping, household chores, etcetera), which require a greater effort. Although the patients perceived having been affected in the emotional health area-by the presence of anxiety and depression-they did not consider that these alterations limited their ability to carry out work and everyday activities. Quality of life was most affected at mental dimension and physical dimension, mainly in patients at induction and palliative treatment. The results showed that the objectives of care aimed to reduce symptoms and maintain patient comfort are not achieved.

Smoking, caffeine, and nonsteroidal anti-inflammatory drugs in families with Parkinson disease.

Science.gov (United States)

Hancock, Dana B; Martin, Eden R; Stajich, Jeffrey M; Jewett, Rita; Stacy, Mark A; Scott, Burton L; Vance, Jeffery M; Scott, William K

2007-04-01

To assess associations between Parkinson disease (PD) and putatively protective factors-smoking, caffeine (coffee, tea, and soft drinks), and nonsteroidal anti-inflammatory drugs (aspirin, ibuprofen, and naproxen). Family-based case-control study. Academic medical center clinic. A total of 356 case subjects and 317 family controls who self-reported environmental exposures. Associations between PD and environmental measures (history, status, dosage, duration, and intensity) of smoking, coffee, caffeine, nonsteroidal anti-inflammatory drugs, and non-aspirin nonsteroidal anti-inflammatory drugs were examined using generalized estimating equations with an independent correlation matrix while controlling for age and sex. Individuals with PD were significantly less likely to report ever smoking (odds ratio = 0.56; 95% confidence interval, 0.41-0.78). Additional measures of smoking revealed significant inverse associations with PD (Pcoffee drinking was inversely associated with PD (test for trend P = .05). Increasing dosage (trend P = .009) and intensity (trend P = .01) of total caffeine consumption were also inversely associated, with high dosage presenting a significant inverse association for PD (odds ratio = 0.58; 95% confidence interval, 0.34-0.99). There were no significant associations between nonsteroidal anti-inflammatory drugs and PD. Inverse associations of smoking and caffeine were corroborated using families with PD, thus emphasizing smoking and caffeine as important covariates to consider in genetic studies of PD.

Current and Potential Support for Chronic Disease Management in the United States: The Perspective of Family and Friends of Chronically Ill Adults

Science.gov (United States)

Rosland, Ann-Marie; Heisler, Michele; Janevic, Mary; Connell, Cathleen; Langa, Kenneth M.; Kerr, Eve A.; Piette, John D.

2013-01-01

Objectives Family members and friends can be an important source of self-management support for older adults with chronic diseases. We characterized the U.S. population of potential and current “disease management supporters” for people with chronic illness who are ADL-independent, the help that supporters could provide, and barriers to increasing support. Methods Nationally-representative survey of U.S. adults (N=1,722). Results 44% of respondents (representing 100 million US adults) help a family member or friend with chronic disease management; another 9% (representing 21 million US adults) are willing to start. Most are willing to assist with key tasks such as medication use and communicating with providers, although they feel constrained by privacy concerns and a lack of patient health information. Discussion The majority of U.S. adults already help or would be willing to help one of their family members or friends with chronic illness care. Supporters' specific concerns could be addressed through innovative programs. PMID:23795624

[Role of the family in the prevention of diseases of the oral cavity in children].

Science.gov (United States)

Chudinova, T A; Khusnutdinova, Z A

2000-01-01

Sociohygienic studies of hygienic knowledge with regard to prevention of dental diseases in children were carried out in 456 mothers and their 15-year-old schoolchildren in Ufa. The respondents were interviewed using specially designed questionnaires. The results allowed the authors characterize the performance of medical functions by parents from families differing by well-being and their role in hygienic upbringing of children.

Mutations in the NDP gene: contribution to Norrie disease, familial exudative vitreoretinopathy and retinopathy of prematurity.

Science.gov (United States)

Dickinson, Joanne L; Sale, Michèle M; Passmore, Abraham; FitzGerald, Liesel M; Wheatley, Catherine M; Burdon, Kathryn P; Craig, Jamie E; Tengtrisorn, Supaporn; Carden, Susan M; Maclean, Hector; Mackey, David A

2006-01-01

To examine the contribution of mutations within the Norrie disease (NDP) gene to the clinically similar retinal diseases Norrie disease, X-linked familial exudative vitreoretinopathy (FEVR), Coat's disease and retinopathy of prematurity (ROP). A dataset comprising 13 Norrie-FEVR, one Coat's disease, 31 ROP patients and 90 ex-premature babies of Norrie disease patients. Furthermore, a previously described 14-bp deletion located in the 5' unstranslated region of the NDP gene was detected in three cases of regressed ROP. A second heterozygotic 14-bp deletion was detected in an unaffected ex-premature girl. Only two of the 13 Norrie-FEVR index cases had the full features of Norrie disease with deafness and mental retardation. Two novel mutations within the coding region of the NDP gene were found, one associated with a severe disease phenotypes of Norrie disease and the other with FEVR. A deletion within the non-coding region was associated with only mild-regressed ROP, despite the presence of low birthweight, prematurity and exposure to oxygen. In full-term children with retinal detachment only 15% appear to have the full features of Norrie disease and this is important for counselling parents on the possible long-term outcome.

Familial history, age and smoking are important risk factors for disc degeneration disease in Arabic pedigrees

International Nuclear Information System (INIS)

Livshits, Gregory; Cohen, Zvi; Higla, Orabi; Yakovenko, Konstantin

2001-01-01

The present study used computed tomography imaging to evaluate the extent and pattern of the intergenerational transmission of spinal disc degeneration disease (DDD) in complex pedigrees. Contribution of a number of the potential covariates was also studied using univariate and multivariate logistic regression analysis, as well as two types of complex segregation analysis models. Among 161 individuals studied, DDD was diagnosed in 60 individuals. The number of protruded discs varied from 1 to 4, mostly in lumbar or lumbosacral regions. The average age at onset of the disease was similar for both women (36.0 years) and men (34.8 years). The proportion of the individuals affected by the DDD status of their parents ranged from 10% in families of two healthy parents to 55.5% of two affected parents (p < 0.01). The results of the logistic regression analyses and complex segregation analysis were qualitatively the same: DDD status of parents, age and smoking were the main risk factors for disc herniation in the Arabic families we examined. All analyses showed a predominating role of the family history as a risk factor for DDD in offsprings. It showed, for example, four times higher risk at age 50 for individuals with two affected parents vs. those who have two non-affected parents. However, the results of models-fitting genetic analysis, did not confirm a monogenic Mendelian pattern of inheritance

Next-generation sequencing reveals a novel NDP gene mutation in a Chinese family with Norrie disease.

Science.gov (United States)

Huang, Xiaoyan; Tian, Mao; Li, Jiankang; Cui, Ling; Li, Min; Zhang, Jianguo

2017-11-01

Norrie disease (ND) is a rare X-linked genetic disorder, the main symptoms of which are congenital blindness and white pupils. It has been reported that ND is caused by mutations in the NDP gene. Although many mutations in NDP have been reported, the genetic cause for many patients remains unknown. In this study, the aim is to investigate the genetic defect in a five-generation family with typical symptoms of ND. To identify the causative gene, next-generation sequencing based target capture sequencing was performed. Segregation analysis of the candidate variant was performed in additional family members using Sanger sequencing. We identified a novel missense variant (c.314C>A) located within the NDP gene. The mutation cosegregated within all affected individuals in the family and was not found in unaffected members. By happenstance, in this family, we also detected a known pathogenic variant of retinitis pigmentosa in a healthy individual. c.314C>A mutation of NDP gene is a novel mutation and broadens the genetic spectrum of ND.

Next-generation sequencing reveals a novel NDP gene mutation in a Chinese family with Norrie disease

Directory of Open Access Journals (Sweden)

Xiaoyan Huang

2017-01-01

Full Text Available Purpose: Norrie disease (ND is a rare X-linked genetic disorder, the main symptoms of which are congenital blindness and white pupils. It has been reported that ND is caused by mutations in the NDP gene. Although many mutations in NDP have been reported, the genetic cause for many patients remains unknown. In this study, the aim is to investigate the genetic defect in a five-generation family with typical symptoms of ND. Methods: To identify the causative gene, next-generation sequencing based target capture sequencing was performed. Segregation analysis of the candidate variant was performed in additional family members using Sanger sequencing. Results: We identified a novel missense variant (c.314C>A located within the NDP gene. The mutation cosegregated within all affected individuals in the family and was not found in unaffected members. By happenstance, in this family, we also detected a known pathogenic variant of retinitis pigmentosa in a healthy individual. Conclusion: c.314C>A mutation of NDP gene is a novel mutation and broadens the genetic spectrum of ND.

Nuclear molecular imaging of paragangliomas; Imagerie moleculaire nucleaire des paragangliomes

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Taieb, D.; Tessonnier, L.; Mundler, O. [Service central de biophysique et de medecine nucleaire, CHU de la Timone, 13 - Marseille (France)

2010-08-15

Paragangliomas (PGL) are relatively rare neural crest tumors originating in the adrenal medulla (usually called pheochromocytoma), chemoreceptors (i.e., carotid and aortic bodies) or autonomic ganglia. These tumors are highly vascular, usually benign and slow-growing. PGL may occur as sporadic or familial entities, the latter mostly in association with germline mutations of the succinate dehydrogenase (SDH) B, SDHC, SDHD, SDH5, von Hippel-Lindau (VHL), ret proto-oncogene (RET), neurofibromatosis 1 (NF1) (von Recklinghausen's disease), prolyl hydroxylase domain protein 2 (PHD2) genes and TMEM127. Molecular nuclear imaging has a central role in characterization of PGL and include: somatostatin receptor imaging ({sup 111}In, {sup 68}Ga), MIBG scintigraphy ({sup 131}I, {sup 123}I), {sup 18}F-dihydroxy-phenylalanine ({sup 18}F-DOPA) positron emission tomography (PET), and {sup 18}F-deoxyglucose ({sup 18}F-FDG) PET. The choice of the tracer is not yet fully established but the work-up of familial forms often require the combination of multiple approaches. (authors)

Glutamate-system defects behind psychiatric manifestations in a familial hemiplegic migraine type 2 disease-mutation mouse model

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Bøttger, Pernille; Pedersen, Simon Glerup; Gesslein, Bodil

2016-01-01

Migraine is a complex brain disorder, and understanding the complexity of this prevalent disease could improve quality of life for millions of people. Familial Hemiplegic Migraine type 2 (FHM2) is a subtype of migraine with aura and co-morbidities like epilepsy/seizures, cognitive impairments...

No direct association among respiratory function, disease control and family functioning in a sample of Mexican children with intermittent asthma.

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Rodriguez-Orozco, Alain Raimundo; Núñez-Tapia, Rosa María; Ramírez-Silva, Armando; Gómez-Alonso, Carlos

2013-05-15

Asthma has been linked to family disfunctioning and poor control of the disease.This study was conducted to analyze the interactions between the level of intermittent asthma control, family functioning and respiratory function and between quality of life of asthmatic patients and their caregivers.7 to 15 years old children with intermittent asthma were included. Asthma Control Test Questionnaire, Pediatric Asthma Quality of Life Questionnaire (PAQLQ) test, and flowmetry were applied to children and Pediatric Asthma Caregiver´s Quatily of Life Questionnaire (PAQCLQ) and the Family Functioning Perception Test (FF-SIL) were applied to their parents.The most affected areas of family functioning in dysfunctional families were adaptability and permeability. A medium to high strength of association was founded between the emotional function of parents and the emotional function of children, R2=0.552. The most remarkable associations were among parents' limitation of activities and parents' emotional function (r=0.837), parents' limitation of activities and child's emotional function (r=0.722), parents' emotional role and limitation of activities (r=0.837), parents' emotional role and emotional functioning of children with asthma (r=0.743) and the limitation of activities of children with asthma and the emotional function of children with asthma (r=0.870).No direct associations were founded among respiratory function, disease control and family functioning in Mexican children with intermittent asthma and emotional function of parents and children were associated in both groups.

The roles of family members, health care workers, and others in decision-making processes about genetic testing among individuals at risk for Huntington disease.

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Klitzman, Robert; Thorne, Deborah; Williamson, Jennifer; Marder, Karen

2007-06-01

To understand how individuals at risk for Huntington disease view the roles of others, e.g., family members and health care workers, in decision making about genetic testing. Twenty-one individuals (eight mutation-positive, four mutation-negative, and nine not tested) were interviewed for approximately 2 hours each. Interviewees illuminated several key aspects of the roles of family members and health care workers (in genetics and other fields) in decision making about testing that have been underexplored. Family members often felt strongly about whether an individual should get tested. Health care workers provided information and assistance with decision making and mental health referrals that were often helpful. Yet health care workers varied in knowledge and sensitivity regarding testing issues, and the quality of counseling and testing experiences can range widely. At times, health care workers without specialized knowledge of Huntington disease offered opinions of whether to test. Input from families and health care workers could also conflict with each other and with an individual's own preferences. Larger institutional and geographic contexts shaped decisions as well. Decision-making theories applied to Huntington disease testing have frequently drawn on psychological models, yet the current data highlight the importance of social contexts and relationships in testing decisions. This report, the first to our knowledge to explore individuals' perceptions of social factors (particularly family and health care worker involvement) in Huntington disease testing decisions, has critical implications for practice, education, research, and policy.

Qualitative changes in human γ-secretase underlie familial Alzheimer’s disease

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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

Dopamine-dependent neurodegeneration in Drosophila models of familial and sporadic Parkinson's disease.

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Bayersdorfer, Florian; Voigt, Aaron; Schneuwly, Stephan; Botella, José A

2010-10-01

Parkinson's disease has been found to be caused by both, genetic and environmental factors. Despite the diversity of causes involved, a convergent pathogenic mechanism might underlie the special vulnerability of dopaminergic neurons in different forms of Parkinsonism. In recent years, a number of reports have proposed dopamine as a common player responsible in the loss of dopaminergic neurons independent of its etiology. Using RNAi lines we were able to generate flies with drastically reduced dopamine levels in the dopaminergic neurons. Combining these flies with a chemically induced Parkinson model (rotenone) and a familial form of Parkinson (mutant alpha-synuclein) we were able to show a strong reduction of neurotoxicity and a protection of the dopaminergic neurons when cellular dopamine levels were reduced. These results show that dopamine homeostasis plays a central role for the susceptibility of dopaminergic neurons to environmental and genetic factors in in vivo models of Parkinson disease. (c) 2010 Elsevier Inc. All rights reserved.

Hereditary familial vestibular degenerative diseases.

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Sun, J.; Alphen, A.M. van; Wagenaar, M.; Huygen, P.L.M.; Hoogenraad, C.C.; Hasson, T.; Koekkoek, S.K.; Bohne, B.A.; Zeeuw, C.I. de

2001-01-01

Identification of genes involved in hereditary vestibular disease is growing at a remarkable pace. Mutant mouse technology can be an important tool for understanding the biological mechanism of human vestibular diseases.

A new scale to measure family members' perception of community health care services for persons with Huntington disease.

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Sousa, Valmi D; Williams, Janet K; Barnette, Jack J; Reed, David A

2010-06-01

RATIONALE, AIMS, AND OBJECTIVES: Huntington disease (HD) is a progressive genetic brain disease leading to disruptive cognitive, behavioural and physical impairments. Persons with the condition and their caregivers need appropriate and accessible health care services to help them manage the disease adequately. The purpose of this study was to evaluate the psychometric properties of a new scale that measures family members' perception of community health care services (CHCS) for persons with HD. A methodological design was used to examine the initial reliability and dimensionality of the CHCS scale among 245 family members of persons with a diagnosis of HD. Data analysis consisted of computing Cronbach's alpha coefficients, calculating the 95% confidence interval for alpha and performing item-analysis and exploratory factor analysis. Reliability of the scale based on Cronbach's alpha was 0.83. Factor analysis using principal component analysis and varimax rotation suggested that three interpretable factors underlie the scale. Factor 1, HD knowledge, had alpha = 0.82, eigenvalue of 4.67 and explained 33.42% of the variance; factor 2, HD community resources, had alpha = 0.62, eigenvalue of 1.68 and explained 12.02% of the variance; factor 3, individualized HD management, had alpha = 0.77, eigenvalue of 1.45 and explained 10.39% of the variance. Findings from this study provide evidence of both construct validity and internal consistency reliability of the CHCS scale. Further psychometric testing of the scale in other samples of family caregivers of persons with HD is warranted.

"Boring" family routines reduce non-communicable diseases: a commentary and call for action.

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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.

Effect of communication style and physician-family relationships on satisfaction with pediatric chronic disease care.

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Swedlund, Matthew P; Schumacher, Jayna B; Young, Henry N; Cox, Elizabeth D

2012-01-01

Over 8% of children have a chronic disease and many are unable to adhere to treatment. Satisfaction with chronic disease care can impact adherence. We examine how visit satisfaction is associated with physician communication style and ongoing physician-family relationships. We collected surveys and visit videos for 75 children ages 9-16 years visiting for asthma, diabetes, or sickle cell disease management. Raters assessed physician communication style (friendliness, interest, responsiveness, and dominance) from visit videos. Quality of the ongoing relationship was measured with four survey items (parent-physician relationship, child-physician relationship, comfort asking questions, and trust in the physician), while a single item assessed satisfaction. Correlations and chi square were used to assess association of satisfaction with communication style or quality of the ongoing relationship. Satisfaction was positively associated with physician to parent (p relationships (p communication style and the quality of the ongoing relationship contribute to pediatric chronic disease visit satisfaction.

Familial Mediterranean Fever

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Adem Kucuk

2014-01-01

Full Text Available Familial Mediterranean Fever is an autosomal recessive inherited disease with a course of autoinflammation, which is characterized by the episodes of fever and serositis. It affects the populations from Mediterranean basin. Genetic mutation of the disease is on MEFV gene located on short arm of Chromosome 16. The disease is diagnosed based on clinical evaluation. Amyloidosis is the most important complication. The only agent that decreases the development of amyloidosis and the frequency and severity of the episodes is colchicine, which has been used for about 40 years. In this review, we aimed to discuss especially the most recent advances about Familial Mediterranean Fever which is commonly seen in our population.

Profile of diseases prevalent in a tribal locality in Jharkhand, India: A family medicine practitioner′s perspective

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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

Diversity Prevalence of Familial Mediterranean fever Disease in the World and Iran: Systematic Review and Meta-Analysis

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Soraya Hadi

2016-06-01

Full Text Available ​ Background and objectives : Familial Mediterranean fever (FMF is an autosomal recessive disease. Generally, the Mediterranean basin is the region where the first cases of FMF have been identified. Yearly, some people undergo unnecessary surgery, due to misdiagnosis of doctors. In this study, our aim was to determine the prevalence rate and status of familial Mediterranean fever in the world and Iran which was done using meta-analysis method. Material and Methods : In this study, Google Scholar, Pubmed, Medline, Ovid, IranMedex, Irandoc, SID, Magiran databases and published written sources were searched without limit of time. Then, all the studies were collected without limitation, to determine the relevant studies were assessed. After verifying the quality of the studies, required data were extracted and analyzed using the method of meta-analysis (random effects model in the CMA software. In the end, world map of the prevalence of familial Mediterranean fever disease was traced by the GIS software. Results : The primary search identified 400 studies which only 23 studies had the required quality for inclusion in the meta-analysis. Two of the studies were related to Iran.The results of the meta-analysis showed that the overall prevalence rate of familial Mediterranean fever in the world and in Iran along with their 95% confidence intervals (in parentheses are 0.116% (0.088 - 0.144 and 0.018% (0.001 - 0.037, respectively. Since the studies were limited, the overall prevalence rate obtained from Iran does not have the capability of generalization to other regions of Iran. Conclusion : FMF in the world is prevalent in the Mediterranean and the Middle East region, among ethnic Turks, Armenians, Jews and Arabs, respectively. But FMF epidemiology is rapidly changing, due to population migrations from Mediterranean countries and the Middle East to the rest of the world and the increasing diagnostic sensitivity. The FMF has to be considered as a

Pesticide exposure and risk of Parkinson's disease: A family-based case-control study

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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.

Food insecurity and social support in families of children with sickle-cell disease.

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Santos, Isabel Nascimento Dos; Damião, Jorginete de Jesus; Fonseca, Maria de Jesus Mendes da; Cople-Rodrigues, Cláudia Dos Santos; Aguiar, Odaleia Barbosa de

2018-03-15

To examine the associations between food insecurity (IA) and social support in families of children with sickle-cell disease (DF). This cross-sectional study in families of 190 children from five to nine years old in follow-up at a hematology referral hospital in Rio de Janeiro State. IA was measured using the Brazilian food insecurity scale and social support was measured using the Brazilian version of the MOS social support survey instrument. The relation between IA and social support was analyzed by way of a multinomial logistic model. There was IA in 62.2% of the families, in moderate and severe form in, respectively, 11.1% and 7.9% of cases. In families of children with DF, levels of mild and severe food insecurity (IALe and IAGr) were found to relate inversely to levels of social support in the following dimensions: informational support (IALe OR=0.98; 95% CI 0.96-0.99 and IAGr OR=0.95; 95% CI 0.92-0.98); social interaction (IALe OR=0.98; 95% CI 0.96-0.99 and IAGr OR=0.96; 95% CI 0.93-0.99) and tangible social support (IALe OR=0.97; 95% CI 0.96-0.99 and IAGr OR=0.97; 95% CI 0.94-0.99). Considering the positive effects of social support on IA, public policies should be encouraged to assure food and nutritional security and social assistance for care for people with DF. Also, social support groups for people with DF should be strengthened. Copyright © 2018. Published by Elsevier Editora Ltda.

Familial diffuse Lewy body disease, eye movement abnormalities, and distribution of pathology.

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Brett, Francesca M; Henson, Craig; Staunton, Hugh

2002-03-01

Familial diffuse Lewy body disease (DLBD) is rare and not yet associated with a defect in the synuclein gene. In the differential diagnosis of the parkinsonian syndromes, defects in vertical gaze tend to be identified with progressive supranuclear palsy. False-positive diagnosis of progressive supranuclear palsy can occur, and defects in vertical gaze have been reported in DLBD, although so far a pure vertical gaze palsy associated with pathological abnormalities in the substrate for vertical gaze has not been described. To report the clinical and pathological findings in 2 siblings with DLBD, and to relate the distribution of the pathological abnormalities in the brainstem to centers for vertical gaze. For several years, 2 Irish siblings experienced a progressive parkinsonism-dementia complex associated in one with a defect in vertical gaze and in both with visual hallucinations. In both patients, results of pathological examination revealed (1) Lewy bodies positive for ubiquitin and alpha-synuclein together with cell loss and gliosis in the substantia nigra, locus ceruleus, and neocortex; and (2) similar findings in the rostral interstitial nucleus of the medial longitudinal fasciculus, the posterior commissure, and the interstitial nucleus of Cajal (substrates for vertical gaze). Familial DLBD (not shown to be genetically as distinct from environmentally transmitted) has been shown to exist in an Irish family. Caution should be enjoined in the interpretation of defects in vertical gaze in the differential diagnosis of the parkinsonian syndromes.

Familial steroid-sensitive idiopathic nephrotic syndrome: seven cases from three families in China

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Yonghui Xia

2013-05-01

Full Text Available OBJECTIVES: Familial steroid-sensitive idiopathic nephrotic syndrome is rare, and only approximately 3% of patients have affected siblings. METHODS: Herein, we report seven cases of patients with steroid-sensitive idiopathic nephrotic syndrome from three Chinese families. Mutational screening of the Nphs2 gene was performed in all the patients. RESULTS: All seven of the familial steroid-sensitive idiopathic nephrotic syndrome cases in our sample exhibited minimal change disease, and one case also presented with mesangial proliferative glomerulonephritis, according to the renal pathology. No significant was associations were found between Nphs2 gene mutations and the onset of proteinuria and nephrotic syndrome in these familial cases. CONCLUSIONS: The presence of minimal change disease is important, but it is not an unusual finding in patients with familial steroid-sensitive idiopathic nephrotic syndrome, which appears to be clinically benign and genetically distinct from other types of nephrosis.

Molecular basis of familial hypercholesterolemia

NARCIS (Netherlands)

Bruikman, Caroline S.; Hovingh, Gerard K.; Kastelein, John J. P.

2017-01-01

Purpose of review To provide an overview about the molecular basis of familial hypercholesterolemia. Recent findings Familial hypercholesterolemia is a common hereditary cause of premature coronary heart disease. It has been estimated that 1 in every 250 individuals has heterozygous familial

Efficient generation of dopamine neuron-like cells from skin-derived precursors with a synthetic peptide derived from von Hippel-Lindau protein.

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Kubo, Atsuhiko; Yoshida, Tetsuhiko; Kobayashi, Nahoko; Yokoyama, Takaakira; Mimura, Toshiro; Nishiguchi, Takao; Higashida, Tetsuhiro; Yamamoto, Isao; Kanno, Hiroshi

2009-12-01

Skin-derived precursors (SKPs) from mammalian dermis represent neural crest-related stem cells capable of differentiating into both neural and mesodermal progency. SKPs are of clinical interest because they serve as accessible autologous donor cells for neuronal repair for neuronal intractable diseases. However, little is known about the efficient generation of neurons from SKPs, and phenotypes of neurons generated from SKPs have been restricted. In addition, the neuronal repair using their generated neurons as donor cells has not been achieved. The von Hippel-Lindau protein (pVHL) is one of the proteins that play an important role during neuronal differentiation, and recently neuronal differentiation of neural progenitor cells by intracellular delivery of a synthetic VHL peptide derived from elongin BC-binding site has been demonstrated. In the present study, a synthetic VHL peptide derived from elongin BC-binding site was conjugated to the protein transduction domain (PTD) of HIV-TAT protein (TATVHL peptide) to facilitate entry into cells, and we demonstrate the efficient generation of cells with dopaminergic phenotype from SKPs with the intracellular delivery of TATVHL peptide, and characterized the generated cells. The TATVHL peptide-treated SKPs expressed neuronal marker proteins, particularly dopamine neuron markers, and also up-regulated mRNA levels of proneural basic helix-loop-helix factors. After the TATVHL peptide treatment, transplanted SKPs into Parkinson's disease (PD) model rats sufficiently differentiated into dopamine neuron-like cells in PD model rats, and partially but significantly corrected behavior of PD model rats. The generated dopamine neuron-like cells are expected to serve as donor cells for neuronal repair for PD.

Genetics, environment, and asthma associated with celiac disease in the extended family of an affected child.

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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.

Is dignity therapy feasible to enhance the end of life experience for people with motor neurone disease and their family carers?

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Bentley Brenda

2012-09-01

Full Text Available Abstract Background Development of interventions that address psychosocial and existential distress in people with motor neurone disease (MND or that alleviate caregiver burden in MND family carers have often been suggested in the research literature. Dignity therapy, which was developed to reduce psychosocial and existential distress at the end of life, has been shown to benefit people dying of cancer and their families. These results may not be transferable to people with MND. The objectives of this study are to assess the feasibility, acceptability and potential effectiveness of dignity therapy to enhance the end of life experience for people with motor neurone disease and their family carers. Methods/design This is a cross-sectional study utilizing a single treatment group and a pre/post test design. The study population will comprise fifty people diagnosed with MND and their nominated family carers. Primarily quantitative outcomes will be gathered through measures assessed at baseline and at approximately one week after the intervention. Outcomes for participants include hopefulness, spirituality and dignity. Outcomes for family carers include perceived caregiver burden, hopefulness and anxiety/depression. Feedback and satisfaction with the intervention will be gathered through a questionnaire. Discussion This detailed research will explore if dignity therapy has the potential to enhance the end of life experience for people with MND and their family carers, and fill a gap for professionals who are called on to address the spiritual, existential and psychosocial needs of their MND patients and families. Trial registration ACTRN Trial Number: ACTRN12611000410954

A novel mutation in ABCA1 gene causing Tangier Disease in an Italian family with uncommon neurological presentation

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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.

Xeroderma Pigmentosum - A Family

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Garg Anush

2000-01-01

Full Text Available A family of xeroderma pigmentosum is reported. Four children of different ages were afflicted with varying clinical presentation. Sequential development and progression of the disease from freckling to malignancy within the family are discussed.

Alternative allogeneic donor sources for transplantation for childhood diseases: unrelated cord blood and haploidentical family donors.

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Cairo, Mitchell S; Rocha, Vanderson; Gluckman, Eliane; Hale, Gregory; Wagner, John

2008-01-01

Allogeneic stem cell transplantation has been demonstrated to be curative in a wide variety of pediatric malignant and nonmalignant diseases, and can be traced back over 50 years ago to the original report of Thomas et al. HLA matched sibling donors have been the gold standard for pediatric recipients requiring allogeneic donors for both nonmalignant and malignant conditions. However, only 25% of potential pediatric recipients possesses an HLA-matched sibling donor, and the frequency is even less in those with genetic nonmalignant conditions because of genetically affected other siblings within the family. Therefore, 75% to 90% of potential pediatric recipients require alternative allogeneic donor cells for treatment of their underlying conditions. Potential alternative allogeneic donor sources include unrelated cord blood donors, unrelated adult donors, and haploidentical family donors. In this article we review the experience of both unrelated cord blood donor and haploidentical family donor transplants in selected pediatric malignant and nonmalignant conditions.

RBC acetyl cholinesterase: A poor man′s early diagnostic biomarker for familial alzheimer′s and Parkinson′s disease dementia

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Himmatrao Saluba Bawaskar

2015-01-01

Full Text Available Objective: Analysis of red blood cell acetyl cholinesterase (AChE in a familial Alzheimer′s diseases (AD Parkinson′s disease dementia (PDD and their first generation. Setting: General hospital, Mahad district, Raigad. Patients and Methods: Clinically diagnosed patients of AD and PDD and their asymptomatic relatives. Their blood was collected in EDTA tube and transferred to laboratory at Mumbai. Result: Median red blood cell (RBC cholinesterase levels amongst PDD, their first generation asymptomatic relatives, familial AD, asymptomatic relatives of AD, healthy controls, farmers exposed to pesticides (positive control and other neurological condition without dementia (hypertension with TIA 1, sub-dural hematoma 2, hypothyroid 1, non-familial unilateral parkinsonism without dementia 3, writers cramps 2, hyponitremia 1 and cerebral palsy with non-fluent aphasia 1. Median values of RBC AChE were 19086.78 U/L, 15666.05 U/L, 9013.11 U/L, 7806.19 U/L, 14334.57 U/L, 9785.05 U/L and 13162.60 U/L, respectively. As compared to controls, RBC AChE levels were statistically significant among PDD (P = 0.004 and significantly lowered among familial AD patients (P = 0.010, relatives of patients (P = 0.010. Interpretations: Below the normal RBC AChE level is a potential biomarker in asymptomatic relatives of familial AD patients. RBC AChE is raised than normal level in patients suffering from PDD, where AChE inhibitors are helpful. However, RBC AChE level below the normal where AChE inhibitor may not be effective.

Novel and recurrent NDP gene mutations in familial cases of Norrie disease and X-linked exudative vitreoretinopathy.

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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.

"Maybe They Don't Even Know That I Exist": Challenges Faced by Family Members and Friends of Patients with Advanced Kidney Disease.

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O'Hare, Ann M; Szarka, Jackie; McFarland, Lynne V; Vig, Elizabeth K; Sudore, Rebecca L; Crowley, Susan; Reinke, Lynn F; Trivedi, Ranak; Taylor, Janelle S

2017-06-07

Family members and friends of patients with advanced chronic illness are increasingly called on to assist with ever more complex medical care and treatment decisions arising late in the course of illness. Our goal was to learn about the experiences of family members and friends of patients with advanced kidney disease. As part of a study intended to identify opportunities to enhance advance care planning, we conducted semistructured interviews at the Veterans Affairs Puget Sound Health Care System with 17 family members and friends of patients with advanced kidney disease. Interviews were conducted between April of 2014 and May of 2016 and were audiotaped, transcribed, and analyzed inductively using grounded theory to identify emergent themes. The following three themes emerged from interviews with patients' family members and friends: ( 1 ) their roles in care and planning were fluid over the course of the patient's illness, shaped by the patients' changing needs and their readiness to involve those close to them; ( 2 ) their involvement in patients' care was strongly shaped by health care system needs. Family and friends described filling gaps left by the health care system and how their involvement in care and decision-making was at times constrained and at other times expected by providers, depending on system needs; and ( 3 ) they described multiple sources of tension and conflict in their interactions with patients and the health care system, including instances of being pitted against the patient. Interviews with family members and friends of patients with advanced kidney disease provide a window on the complex dynamics shaping their engagement in patients' care, and highlight the potential value of offering opportunities for engagement throughout the course of illness. Copyright © 2017 by the American Society of Nephrology.

Activating chronic kidney disease patients and family members through the Internet to promote integration of care

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Michael Trisolini

2004-10-01

Full Text Available Purpose: To describe the potential role of the Internet as a vehicle for improving integration of care through activating chronic kidney disease patients and their family members. Also, to describe how that potential is being developed through a website sponsored by the Medicare program in the United States. Background: The Internet is expanding at a rapid rate, and health-related websites are one of its most popular features. Efforts to promote integration of care have focused mainly on providers up to now, and more emphasis is needed on the potential roles of patients. Chronically ill patients have particular needs for improved education about their conditions and enhanced involvement in care planning and treatment decisions. Medicare developed the Dialysis Facility Compare website to serve those goals for people with chronic kidney disease. Methods: We conducted qualitative research with 140 chronic kidney disease patients and family members, and 130 renal care professionals to evaluate and improve the Dialysis Facility Compare website. A series of 19 focus groups, 13 triads (small focus groups, and 56 individual interviews were conducted in four regions of the United States and by telephone. Results: We found that the Dialysis Facility Compare website has the potential to improve integration of care for people with chronic kidney disease in at least three ways. First: by expanding the roles of patients as members of the multi-disciplinary team of caregivers treating their disease. Second: through better integration of the informal care provided in the home and community with the formal care provided by health professionals. Third: by improving coordination of between care provided in the pre-dialysis and dialysis phases of the disease. Discussion: We developed recommendations for revising and enhancing the Dialysis Facility Compare website in a number of ways to better promote patient activation and integration of care. The unique features

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

Familial Exudative Vitreoretinopathy.

Science.gov (United States)

Sızmaz, Selçuk; Yonekawa, Yoshihiro; T Trese, Michael

2015-08-01

Familial exudative vitreoretinopathy (FEVR) is a hereditary disease associated with visual loss, particularly in the pediatric group. Mutations in the NDP, FZD4, LRP5, and TSPAN12 genes have been shown to contribute to FEVR. FEVR has been reported to have X-linked recessive, autosomal dominant, and autosomal recessive inheritances. However, both the genotypic and phenotypic features are variable. Novel mutations contributing to the disease have been reported. The earliest and the most prominent finding of the disease is avascularity in the peripheral retina. As the disease progresses, retinal neovascularization, subretinal exudation, partial and total retinal detachment may occur, which may be associated with certain mutations. With early diagnosis and prompt management visual loss can be prevented with laser photocoagulation and anti-VEGF injections. In case of retinal detachment, pars plana vitrectomy alone or combined with scleral buckling should be considered. Identifying asymptomatic family members with various degrees of insidious findings is of certain importance. Wide-field imaging with fluorescein angiography is crucial in the management of this disease. The differential diagnosis includes other pediatric vitreoretinopathies such as Norrie disease, retinopathy of prematurity, and Coats' disease.

Familial Exudative Vitreoretinopathy

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Selçuk Sızmaz

2015-08-01

Full Text Available Familial exudative vitreoretinopathy (FEVR is a hereditary disease associated with visual loss, particularly in the pediatric group. Mutations in the NDP, FZD4, LRP5, and TSPAN12 genes have been shown to contribute to FEVR. FEVR has been reported to have X-linked recessive, autosomal dominant, and autosomal recessive inheritances. However, both the genotypic and phenotypic features are variable. Novel mutations contributing to the disease have been reported. The earliest and the most prominent finding of the disease is avascularity in the peripheral retina. As the disease progresses, retinal neovascularization, subretinal exudation, partial and total retinal detachment may occur, which may be associated with certain mutations. With early diagnosis and prompt management visual loss can be prevented with laser photocoagulation and anti-VEGF injections. In case of retinal detachment, pars plana vitrectomy alone or combined with scleral buckling should be considered. Identifying asymptomatic family members with various degrees of insidious findings is of certain importance. Wide-field imaging with fluorescein angiography is crucial in the management of this disease. The differential diagnosis includes other pediatric vitreoretinopathies such as Norrie disease, retinopathy of prematurity, and Coats’ disease. (Turk J Ophthalmol 2015; 45: 164-168

Mutant ApoA-1 Amyloidosis in a Family of Five Siblings With Motor Neuron Disease and Dementia

DEFF Research Database (Denmark)

Vrethema, Magnus; Mucchiano, Gerd Ingrid

2011-01-01

We present a family of fi ve siblings in which three brothers died of motor neuron disease (MND) and in two of them concomitant with dementia. A fourth brother died of myocardial infarction and was found to have extensive aortic intimal apolipoprotein A-1 (ApoA-1) derived amyloid deposits and apo...

GM2-gangliosidosis variant 0 (Sandhoff-like disease) in a family of Japanese domestic cats.

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Yamato, O; Matsunaga, S; Takata, K; Uetsuka, K; Satoh, H; Shoda, T; Baba, Y; Yasoshima, A; Kato, K; Takahashi, K; Yamasaki, M; Nakayama, H; Doi, K; Maede, Y; Ogawa, H

2004-12-04

A five-month-old, female Japanese domestic shorthair cat with proportionate dwarfism developed neurological disorders, including ataxia, decreased postural responses and generalised body and head tremors, at between two and five months of age. Leucocytosis due to lymphocytosis with abnormal cytoplasmic vacuolations was observed. The concentration of G(M2)-ganglioside in its cerebrospinal fluid was markedly higher than in normal cats, and the activities of beta-hexosaminidases A and B in its leucocytes were markedly reduced. On the basis of these biochemical data, the cat was diagnosed antemortem with G(M2)-gangliosidosis variant 0 (Sandhoff-like disease). The neurological signs became more severe and the cat died at 10 months of age. Histopathologically, neurons throughout the central nervous system were distended, and an ultrastructural study revealed membranous cytoplasmic bodies in these distended neurons. The compound which accumulated in the brain was identified as G(M2)-ganglioside, confirming G(M2)-gangliosidosis. A family study revealed that there were probable heterozygous carriers in which the activities of leucocyte beta-hexosaminidases A and B were less than half the normal value. The Sandhoff-like disease observed in this family of Japanese domestic cats is the first occurrence reported in Japan.

Information, communication, and online tool needs of Hispanic family caregivers of individuals with Alzheimer's disease and related dementias.

Science.gov (United States)

Iribarren, Sarah; Stonbraker, Samantha; Suero-Tejeda, Niurka; Granja, Maribel; Luchsinger, José A; Mittelman, Mary; Bakken, Suzanne; Lucero, Robert J

2018-03-05

To identify the information and communication needs of Hispanic family caregivers for individuals with Alzheimer's Disease and Related Dementias (ADRD) and the manner in which online tools may meet those needs. We conducted 11 participatory design sessions with 10 English- and 14 Spanish-speaking urban-dwelling Hispanic family caregivers and gathered data using a survey, collage assemblage, and audio and video recordings. Four investigators analyzed transcripts of audio recordings with a coding framework informed by several conceptual models. Participants had an average age of 59.7 years, were mostly female (79.2%), and had cared for a family member with ADRD for an average of 6.5 years. All participants accessed the Internet at least once a week with 75% ≥ daily. Most used the Internet to look up health information. All participants reported caregiver attributes including awareness of the disease symptoms or behaviors. The majority reported information needs/tasks (91.7%), communication needs/tasks (87.5%), and need for online tools (79.2%). Hispanic caregivers of individuals with ADRD reported key information and communication needs/tasks. Only Spanish-speaking participants reported Internet and technology use deficits suggesting the requirement for further technology support. Data show a need for online tools to meet the needs of caregivers.

Families of Children with Chronic Illness and the Relational Family Model

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Tanja Pate

2016-09-01

Full Text Available Families of children with chronic illness experience persistent stress. Facing the diagnosis and learning how to cope with it is a stressful experience not only for the child but also for the parents and for the whole family. The illness, with its unpredictability and treatment, disturbs their daily routine and threatens the whole family system. Parental involvement in the child’s disease management and their emotional support are crucial for effective coping and adaptation to the child’s chronic illness. The aim of this article is to present the importance of the parental role in these families through theoretical findings of the relational family model.