Acute Hyperglycemia Associated with Anti-Cancer Medication

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Yul Hwangbo

2017-03-01

Full Text Available Hyperglycemia during chemotherapy occurs in approximately 10% to 30% of patients. Glucocorticoids and L-asparaginase are well known to cause acute hyperglycemia during chemotherapy. Long-term hyperglycemia is also frequently observed, especially in patients with hematologic malignancies treated with L-asparaginase-based regimens and total body irradiation. Glucocorticoid-induced hyperglycemia often develops because of increased insulin resistance, diminished insulin secretion, and exaggerated hepatic glucose output. Screening strategies for this condition include random glucose testing, hemoglobin A1c testing, oral glucose loading, and fasting plasma glucose screens. The management of hyperglycemia starts with insulin or sulfonylurea, depending on the type, dose, and delivery of the glucocorticoid formulation. Mammalian target of rapamycin (mTOR inhibitors are associated with a high incidence of hyperglycemia, ranging from 13% to 50%. Immunotherapy, such as anti-programmed death 1 (PD-1 antibody treatment, induces hyperglycemia with a prevalence of 0.1%. The proposed mechanism of immunotherapy-induced hyperglycemia is an autoimmune process (insulitis. Withdrawal of the PD-1 inhibitor is the primary treatment for severe hyperglycemia. The efficacy of glucocorticoid therapy is not fully established and the decision to resume PD-1 inhibitor therapy depends on the severity of the hyperglycemia. Diabetic patients should achieve optimized glycemic control before initiating treatment, and glucose levels should be monitored periodically in patients initiating mTOR inhibitor or PD-1 inhibitor therapy. With regard to hyperglycemia caused by anti-cancer therapy, frequent monitoring and proper management are important for promoting the efficacy of anti-cancer therapy and improving patients' quality of life.

Severe hypertriglyceridemia-related acute pancreatitis.

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Stefanutti, Claudia; Labbadia, Giancarlo; Morozzi, Claudia

2013-04-01

Acute pancreatitis is a potentially life-threatening complication of severe hypertriglyceridemia. In some cases, inborn errors of metabolism such as lipoprotein lipase deficiency, apoprotein C-II deficiency, and familial hypertriglyceridemia have been reported as causes of severe hypertriglyceridemia. More often, severe hypertriglyceridemia describes various clinical conditions characterized by high plasma levels of triglycerides (>1000 mg/dL), chylomicron remnants, or intermediate density lipoprotein like particles, and/or chylomicrons. International guidelines on the management of acute pancreatitis are currently available. Standard therapeutic measures are based on the use of lipid-lowering agents (fenofibrate, gemfibrozil, niacin, Ω-3 fatty acids), low molecular weight heparin, and insulin in diabetic patients. However, when standard medical therapies have failed, non-pharmacological approaches based upon the removal of triglycerides with therapeutic plasma exchange can also provide benefit to patients with severe hypertriglyceridemia and acute pancreatitis. Plasma exchange could be very helpful in reducing triglycerides levels during the acute phase of hyperlipidemic pancreatitis, and in the prevention of recurrence. The current evidence on management of acute pancreatitis and severe hypertriglyceridemia, focusing on symptoms, treatment and potential complications is reviewed herein. © 2013 The Authors. Therapeutic Apheresis and Dialysis © 2013 International Society for Apheresis.

The first description of severe anemia associated with acute kidney injury and adult minimal change disease: a case report

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Qian Yimei

2009-01-01

Full Text Available Abstract Introduction Acute kidney injury in the setting of adult minimal change disease is associated with proteinuria, hypertension and hyperlipidemia but anemia is usually absent. Renal biopsies exhibit foot process effacement as well as tubular interstitial inflammation, acute tubular necrosis or intratubular obstruction. We recently managed a patient with unique clinical and pathological features of minimal change disease, who presented with severe anemia and acute kidney injury, an association not previously reported in the literature. Case presentation A 60-year-old Indian-American woman with a history of hypertension and diabetes mellitus for 10 years presented with progressive oliguria over 2 days. Laboratory data revealed severe hyperkalemia, azotemia, heavy proteinuria and progressively worsening anemia. Urine eosinophils were not seen. Emergent hemodialysis, erythropoietin and blood transfusion were initiated. Serologic tests for hepatitis B, hepatitis C, anti-nuclear antibodies, anti-glomerular basement membrane antibodies and anti-neutrophil cytoplasmic antibodies were negative. Complement levels (C3, C4 and CH50 were normal. Renal biopsy unexpectedly displayed 100% foot process effacement. A 24-hour urine collection detected 6.38 g of protein. Proteinuria and anemia resolved during six weeks of steroid therapy. Renal function recovered completely. No signs of relapse were observed at 8-month follow-up. Conclusion Adult minimal change disease should be considered when a patient presents with proteinuria and severe acute kidney injury even when accompanied by severe anemia. This report adds to a growing body of literature suggesting that in addition to steroid therapy, prompt initiation of erythropoietin therapy may facilitate full recovery of renal function in acute kidney injury.

Pharmacologic therapy for acute pancreatitis

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Kambhampati, Swetha; Park, Walter; Habtezion, Aida

2014-01-01

While conservative management such as fluid, bowel rest, and antibiotics is the mainstay of current acute pancreatitis management, there is a lot of promise in pharmacologic therapies that target various aspects of the pathogenesis of pancreatitis. Extensive review of preclinical studies, which include assessment of therapies such as anti-secretory agents, protease inhibitors, anti-inflammatory agents, and anti-oxidants are discussed. Many of these studies have shown therapeutic benefit and improved survival in experimental models. Based on available preclinical studies, we discuss potential novel targeted pharmacologic approaches that may offer promise in the treatment of acute pancreatitis. To date a variety of clinical studies have assessed the translational potential of animal model effective experimental therapies and have shown either failure or mixed results in human studies. Despite these discouraging clinical studies, there is a great clinical need and there exist several preclinical effective therapies that await investigation in patients. Better understanding of acute pancreatitis pathophysiology and lessons learned from past clinical studies are likely to offer a great foundation upon which to expand future therapies in acute pancreatitis. PMID:25493000

Anti-infection treatment of iatrogenic acute radiation sickness

International Nuclear Information System (INIS)

Zhang Shulan; Ke Xiaoyan; Jia Tengzhen

2006-01-01

Objective: To occumulatle experience of anti-infection treatment in acute radiation sickness (ARS) induced by medical treatment in order to provide beneficial help for victims of accidental of acute radiation sickness. Methods: The changes of peripheral blood indices, body temperature and clinical symptoms of 17 cases who were clinically irradiated with 6.0-7.2 Gy X-rays were observed both before peripheral blood stem cell transplantation(PBSCT) and after anti-infection treatment. Results: WBC count began to decrease to below 1 x 10 9 /L from the 8th to 10th days after irradiation and maintained at row level for 4 days or for 13.3 days if the patients had not received rhG-CSF treatment. In 29.4% of patients the body temperature was higher than 38.5 degree C. After comprehensive enviromental protection and anti-infection treatment, all patients could successfully tide over the period of bone marrow depression without appearance of the typical critical phase of ARS. Conclusion: PBSCT and rhG-CSF treatment can reduce the time span for reconstruction of bone marrow. Comprehensive enviromental protection and combined anti-infection treatment are key points fm successful treatment. (authors)

Soluble E-Cadherin: An Early Marker of Severity in Acute Pancreatitis

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A. Sewpaul

2009-01-01

Full Text Available Background/Aims. At present, there is no simple test for predicting severity in acute pancreatitis. We investigated the use of an assay of soluble E-cadherin (sE-cadherin. Methods. Concentrations of sE-cadherin, from 19 patients with mild acute pancreatitis, 7 patients with severe acute pancreatitis, 11 patients with other acute gastrointestinal pathologies, and 12 healthy subjects were measured using a commercially available sandwich ELISA kit based on two monoclonal antibodies specific to the extracellular fragment of human E-cadherin. Measurements were made at 12 hours or less from onset of pain and also at 24 and 48 hours after onset of pain. Results. Mean (standard deviation concentration of sE-cadherin in patients with severe acute pancreatitis at <12 hours was 17780 ng/mL (7853, significantly higher than that of healthy volunteers 5180 ng/mL (1350, =.0039, patients with other gastrointestinal pathologies 7358 ng/mL (6655, =.0073, and also significantly higher than that of patients with mild pancreatitis, 7332 ng/mL (2843, =.0019. Discussion. Serum sE-cadherin could be an early (within 12 hours objective marker of severity in acute pancreatitis. This molecule warrants further investigation in the form of a large multicentre trial.

Treatment of extremely severe acute hemopoietic radiation sickness beagles with RhG-CSF and RhIL-11

International Nuclear Information System (INIS)

Zhao Jianzhi; Zhang Ri; Li Ming; Xing Shuang; Luo Qingliang; Zhang Xueguang; Miao Jingcheng; Zhu Nankang

2010-01-01

Objective: To evaluate the effects of treatment combined recombinant human G-CSF (rhG-CSF) and recombinant human interleukin-11 (rhIL-11) on severe acute hemopoietic radiation sickness (ARS) beagles. Methods: Beagles were irradiated with 4.5 Gy 60 Co γ-ray to establish ARS models, and animals were divided into the irradiated control group and the supportive care and combined cytokines treatment cohort. After irradiation the irradiated control beagles was given no treatment, the supportive care beagles received purely symptomatic treatment including blood transfusion and anti-infection while the combined cytokines treatment beagles received rhG-CSF and rhIL-11 subcutaneously for three weeks besides symptomatic treatment.Results After irradiation, all kinds of cells' population declined sharply, but rebounded to normal basically in the combined cytokines treatment rate in the cohort. The mean blood transfusion volume of cytokines in the cohort and the period of blood transfusion all were less than those in the supportive care cohort (P<0.01). The period of administrated antibiotic of cytokines in the cohort was shorter than that in the supportive care cohort (P<0.05). In the observe period of 45 d, survival rate in the irradiated controls cohort was 0%, in the supportive care cohort was 80%, and in the combined cytokines treatment cohort was 100%(P<0.01). Conclusion: Administration of rhG-CSF and rhIL-11 early after irradiation and continued daily, in combined with supportive care in severe acute hemopoietic radiation sickness beagles can improve hematopoietic function restoration, stimulate blood cells to restore to the normal level quickly, significantly decrease the reguired volume of blood transfusion, shorten the period of anti-infection and increase survival of irradiated canines. (authors)

Human immunodeficiency virus seroconversion presenting with acute inflammatory demyelinating polyneuropathy: a case report

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Sloan Derek J

2008-12-01

Full Text Available Abstract Introduction Acute Human Immunodeficiency Virus infection is associated with a range of neurological conditions. Guillain-Barré syndrome is a rare presentation; acute inflammatory demyelinating polyneuropathy is the commonest form of Guillain-Barré syndrome. Acute inflammatory demyelinating polyneuropathy has occasionally been reported in acute Immunodeficiency Virus infection but little data exists on frequency, management and outcome. Case presentation We describe an episode of Guillain-Barré syndrome presenting as acute inflammatory demyelinating polyneuropathy in a 30-year-old man testing positive for Immunodeficiency Virus, probably during acute seroconversion. Clinical suspicion was confirmed by cerebrospinal fluid analysis and nerve conduction studies. Rapid clinical deterioration prompted intravenous immunoglobulin therapy and early commencement of highly active anti-retroviral therapy. All symptoms resolved within nine weeks. Conclusion Unusual neurological presentations in previously fit patients are an appropriate indication for Immunodeficiency-Virus testing. Highly active anti-retroviral therapy with adequate penetration of the central nervous system should be considered as an early intervention, alongside conventional therapies such as intravenous immunoglobulin.

A Fatal Case of Severe Hemolytic Disease of Newborn Associated with Anti-Jkb

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Kim, Won Duck

2006-01-01

The Kidd blood group is clinically significant since the Jk antibodies can cause acute and delayed transfusion reactions as well as hemolytic disease of newborn (HDN). In general, HDN due to anti-Jkb incompatibility is rare and it usually displays mild clinical symptoms with a favorable prognosis. Yet, we apparently experienced the second case of HDN due to anti-Jkb with severe clinical symptoms and a fatal outcome. A female patient having the AB, Rh(D)-positive boodtype was admitted for jaundice on the fourth day after birth. At the time of admission, the patient was lethargic and exhibited high pitched crying. The laboratory data indicated a hemoglobin value of 11.4 mg/dL, a reticulocyte count of 14.9% and a total bilirubin of 46.1 mg/dL, a direct bilirubin of 1.1 mg/dL and a strong positive result (+++) on the direct Coomb's test. As a result of the identification of irregular antibody from the maternal serum, anti-Jkb was detected, which was also found in the eluate made from infant's blood. Despite the aggressive treatment with exchange transfusion and intensive phototherapy, the patient died of intractable seizure and acute renal failure on the fourth day of admission. Therefore, pediatricians should be aware of the clinical courses of hemolytic jaundice due to anti-Jkb, and they should be ready to treat this disease with active therapeutic interventions. PMID:16479082

Anti-inflammatory, anti-proliferative and anti-atherosclerotic effects of quercetin in human in vitro and in vivo models

NARCIS (Netherlands)

Kleemann, R.; Verschuren, L.; Morrison, M.; Zadelaar, A.S.M.; Erk, M.J. van; Wielinga, P.Y.; Kooistra, T.

2011-01-01

Objective: Polyphenols such as quercetin may exert several beneficial effects, including those resulting from anti-inflammatory activities, but their impact on cardiovascular health is debated. We investigated the effect of quercetin on cardiovascular risk markers including human C-reactive protein

Pro- and anti-angiogenic factors in human skeletal muscle in response to acute exercise and training

DEFF Research Database (Denmark)

Høier, Birgitte; Nordsborg, Nikolai; Andersen, Søren

2012-01-01

This study examined the effect of acute exercise and 4 weeks of aerobic training on skeletal muscle gene and protein expression of pro- and anti-angiogenic factors in 14 young male subjects. Training consisted of 60 min of cycling (~ 60% of VO2 max), 3 times/week. Biopsies were obtained from m. v....... lateralis before and after training. Muscle interstitial fluid was collected during cycling at week 0 and 4. Training increased (P ... to acute exercise increased similarly (>6-fold; P training. Resting protein levels of soluble VEGF receptor-1 in interstitial fluid, and of VEGF, Thrombospondin-1 (TSP-1) and Tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) in muscle, were unaffected by training, whereas e...

Pazopanib-Induced Severe Acute Pancreatitis

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Kazumichi Kawakubo

2015-08-01

Full Text Available Pazopanib is an oral angiogenesis inhibitor targeting vascular endothelial growth factor receptors, platelet-derived growth factor receptors, and c-Kit approved for the treatment of renal cell carcinoma and soft tissue sarcoma. Nonselective kinase inhibitors, such as sunitinib and sorafenib, are known to be associated with acute pancreatitis. There are few case reports of severe acute pancreatitis induced by pazopanib treatment. We present a case of severe acute pancreatitis caused by pazopanib treatment for cutaneous angiosarcoma. The patient was an 82-year-old female diagnosed with cutaneous angiosarcoma. She had been refractory to docetaxel treatment and began pazopanib therapy. Three months after pazopanib treatment, CT imaging of the abdomen showed the swelling of the pancreas and surrounding soft tissue inflammation without abdominal pain. After she continued pazopanib treatment for 2 months, she presented with nausea and appetite loss. Abdominal CT showed the worsening of the surrounding soft tissue inflammation of the pancreas. Serum amylase and lipase levels were 296 and 177 IU/l, respectively. She was diagnosed with acute pancreatitis induced by pazopanib treatment and was managed conservatively with discontinuation of pazopanib, but the symptoms did not improve. Subsequently, an abdominal CT scan demonstrated the appearance of a pancreatic pseudocyst. She underwent endoscopic ultrasound-guided pseudocyst drainage using a flared-end fully covered self-expandable metallic stent. Then, the symptoms resolved without recurrence. Due to the remarkable progress of molecular targeted therapy, the oncologist should know that acute pancreatitis was recognized as a potential adverse event of pazopanib treatment and could proceed to severe acute pancreatitis.

False-Positive Results in a Recombinant Severe Acute Respiratory Syndrome-Associated Coronavirus (SARS-CoV) Nucleocapsid Enzyme-Linked Immunosorbent Assay Due to HCoV-OC43 and HCoV-229E Rectified by Western Blotting with Recombinant SARS-CoV Spike Polypeptide

OpenAIRE

Woo, Patrick C. Y.; Lau, Susanna K. P.; Wong, Beatrice H. L.; Chan, Kwok-Hung; Hui, Wai-Ting; Kwan, Grace S. W.; Peiris, J. S. Malik; Couch, Robert B.; Yuen, Kwok-Yung

2004-01-01

Using paired serum samples obtained from patients with illness associated with increases in anti-human coronavirus OC43 (HCoV-OC43) or anti-HCoV-229E antibodies, we examined the possibility of false-positive results detected in a recombinant severe acute respiratory syndrome (SARS)-associated coronavirus (SARS-CoV) nucleocapsid protein immunoglobulin G enzyme-linked immunosorbent assay (ELISA). Three of the 21 and 1 of the 7 convalescent-phase serum samples from persons with increases in anti...

[Determinant-based classification of acute pancreatitis severity. International multidisciplinary classification of acute pancreatitis severity: the 2013 German edition

NARCIS (Netherlands)

Layer, P.; Dellinger, E.P.; Forsmark, C.E.; Levy, P.; Maravi-Poma, E.; Shimosegawa, T.; Siriwardena, A.K.; Uomo, G.; Whitcomb, D.C.; Windsor, J.A.; Petrov, M.S.; Geenen, E.J.M. van; et al.,

2013-01-01

OBJECTIVE: The aim of this study was to develop a new international classification of acute pancreatitis severity on the basis of a sound conceptual framework, comprehensive review of published evidence, and worldwide consultation. BACKGROUND: The Atlanta definitions of acute pancreatitis severity

Gut DNA viromes of Malawian twins discordant for severe acute malnutrition

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The bacterial component of the human gut microbiota undergoes a definable program of postnatal development. Evidence is accumulating that this program is disrupted in children with severe acute malnutrition (SAM) and that their persistent gut microbiota immaturity, which is not durably repaired with...

Prevalence of serum anti-neuronal autoantibodies in patients admitted to acute psychiatric care

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Schou, M; Sæther, S G; Borowski, K

2016-01-01

BACKGROUND: Autoimmune encephalitis associated with anti-neuronal antibodies may be challenging to distinguish from primary psychiatric disorders. The significance of anti-neuronal antibodies in psychiatric patients without clear evidence of autoimmune encephalitis is unknown. We investigated...... the serum prevalence of six anti-neuronal autoantibodies in a cohort of unselected patients admitted to acute psychiatric care. METHOD: Serum was drawn from 925 patients admitted to acute psychiatric in-patient care. Psychiatric diagnoses were set according to International Classification of Diseases (ICD......)-10 criteria. Antibody analysis was performed with an indirect immunofluorescence test for N-methyl d-aspartate receptor (NMDAR) antibodies and five other anti-neuronal autoantibodies of the immunoglobulin (Ig) classes IgA, IgG and IgM isotype. RESULTS: Anti-neuronal autoantibodies were found in 11...

Human models of acute lung injury

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Alastair G. Proudfoot

2011-03-01

Full Text Available Acute lung injury (ALI is a syndrome that is characterised by acute inflammation and tissue injury that affects normal gas exchange in the lungs. Hallmarks of ALI include dysfunction of the alveolar-capillary membrane resulting in increased vascular permeability, an influx of inflammatory cells into the lung and a local pro-coagulant state. Patients with ALI present with severe hypoxaemia and radiological evidence of bilateral pulmonary oedema. The syndrome has a mortality rate of approximately 35% and usually requires invasive mechanical ventilation. ALI can follow direct pulmonary insults, such as pneumonia, or occur indirectly as a result of blood-borne insults, commonly severe bacterial sepsis. Although animal models of ALI have been developed, none of them fully recapitulate the human disease. The differences between the human syndrome and the phenotype observed in animal models might, in part, explain why interventions that are successful in models have failed to translate into novel therapies. Improved animal models and the development of human in vivo and ex vivo models are therefore required. In this article, we consider the clinical features of ALI, discuss the limitations of current animal models and highlight how emerging human models of ALI might help to answer outstanding questions about this syndrome.

Severe asthma: anti-IgE or anti-IL-5?

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Evgenia Papathanassiou

2016-11-01

Full Text Available Severe asthma is a discrete clinical entity characterised by recurrent exacerbations, reduced quality of life and poor asthma control as ordinary treatment regimens remain inadequate. Difficulty in managing severe asthma derives partly from the multiple existing phenotypes and our inability to recognise them. Though the exact pathogenetic pathway of severe allergic asthma remains unclear, it is known that numerous inflammatory cells and cytokines are involved, and eosinophils represent a key inflammatory cell mediator. Anti-IgE (omalizumab and anti-IL-5 (mepolizumab antibodies are biological agents that interfere in different steps of the Th2 inflammatory cascade and are licensed in severe asthma. Both exhibit a favourable clinical outcome as they reduce exacerbation rate and improve asthma control and quality of life, while mepolizumab also induces an oral steroid sparing effect. Nevertheless, it is still questionable which agent is more suitable in the management of severe allergic asthma since no comparable studies have been conducted. Omalizumab's established effectiveness in clinical practice over a long period is complemented by a beneficial effect on airway remodelling process mediated mainly through its impact on eosinophils and other parameters strongly related to eosinophilic inflammation. However, it is possible that mepolizumab through nearly depleting eosinophils could have a similar effect on airway remodelling. Moreover, to date, markers indicative of the patient population responding to each treatment are unavailable although baseline eosinophils and exacerbation rate in the previous year demonstrate a predictive value regarding anti-IL-5 therapy effectiveness. On the other hand, a better therapeutic response for omalizumab has been observed when low forced expiratory volume in 1 sec, high-dose inhaled corticosteroids and increased IgE concentrations are present. Consequently, conclusions are not yet safe to be drawn based on

Radiolabelled anti-human fibrin antibody: a new thrombus-detecting agent

International Nuclear Information System (INIS)

Bosnjakovic, V.; Jankovic, B.D.; Horvat, J.; Cvoric, J.

1977-01-01

Rabbit anti-human fibrin globulin (A.F.G.) was labelled with iodine ( 131 I) and used as a thrombus-detecting agent. 131 I-A.F.G. labelled thrombi were displayed by means of a gamma scintillation camera. Normal subjects and patients with thrombo-phlebitis of legs, acute fibrin depositions other than thrombi, and chronic varicosities were examined. The 131 I-A.F.G. technique detected both formed thrombi and those that were forming and could discriminate between acute thrombosis and chronic varicosities. Thrombo-phlebitis and extravascular fibrin depositions were best demonstrated between 24 and 72 hours after 131 I-A.F.G. injection. Radiolabelled A.F.G. in normal veins and chronic varicosities was best displayed within 6 hours of injection. (author)

New phytochemicals as potential human anti-aging compounds: Reality, promise, and challenges.

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Corrêa, Rúbia C G; Peralta, Rosane M; Haminiuk, Charles W I; Maciel, Giselle Maria; Bracht, Adelar; Ferreira, Isabel C F R

2018-04-13

Aging is an inevitable process influenced by genetic, lifestyle, and environmental factors. Indirect evidence shows that several phytochemicals can have anti-aging capabilities, although direct evidence in this field is still limited. This report aims to provide a critical review on aspects related to the use of novel phytochemicals as anti-aging agents, to discuss the obstacles found when performing most anti-aging study protocols in humans, and to analyze future perspectives. In addition to the extensively studied resveratrol, epicatechin, quercetin, and curcumin, new phytochemicals have been reported to act as anti-aging agents, such as the amino acid L-theanine isolated from green tea, and the lignans arctigenin and matairesinol isolated from Arctium lappa seeds. Furthermore, this review discusses the application of several new extracts rich in phytochemicals with potential use in anti-aging therapies. Finally, this review also discusses the most important biomarkers to test anti-aging interventions, the necessity of conducting epidemiological studies and the need of clinical trials with adequate study protocols for humans.

Anti-NMDA Receptor Encephalitis Presenting as an Acute Psychotic Episode in a Young Woman: An Underdiagnosed yet Treatable Disorder

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Shikma Keller

2014-01-01

Full Text Available Anti-NMDA receptor (NMDAR encephalitis is a recently identified autoimmune disorder with prominent psychiatric symptoms. Patients usually present with acute behavioral change, psychosis, catatonic symptoms, memory deficits, seizures, dyskinesias, and autonomic instability. In female patients an ovarian teratoma is often identified. We describe a 32-year-old woman who presented with acute psychosis. Shortly after admission, she developed generalized seizures and deteriorated into a catatonic state. Although ancillary tests including MRI, electroencephalogram, and cerebrospinal fluid (CSF analysis were unremarkable, the presentation of acute psychosis in combination with recurrent seizures and a relentless course suggested autoimmune encephalitis. The patient underwent pelvic ultrasound which disclosed a dermoid cyst and which led to an urgent cystectomy. Plasmapheresis was then initiated, yielding partial response over the next two weeks. Following the detection of high titers of anti-NMDAR antibodies in the CSF, the patient ultimately received second line immunosuppressive treatment with rituximab. Over several months of cognitive rehabilitation a profound improvement was eventually noted, although minor anterograde memory deficits remained. In this report we call for attention to the inclusion of anti-NMDAR encephalitis in the differential diagnosis of acute psychosis. Prompt diagnosis is critical as early immunotherapy and tumor removal could dramatically affect outcomes.

Nonsteroidal anti-inflammatory drugs for treatment of acute gout

NARCIS (Netherlands)

van Durme, Caroline M. P. G.; Wechalekar, Mihir D.; Landewé, Robert B. M.

2015-01-01

Are nonsteroidal anti-inflammatory drugs (NSAIDs) associated with better outcomes than cyclooxygenase inhibitors, glucocorticoids, IL-1 inhibitors or placebo in the treatment of acute gout? NSAIDs are not significantly associated with a difference in pain reduction compared with cyclooxygenase

Production of human anti-HLA monoclonal antibodies

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Walker, M.C.; Mercier, F.; Roger, J.; Varin, M.

1986-03-01

Only 40% of the several hundred anti-HLA murine monoclonal antibodies (MAbs) that have been made detect HLA-A,B,C or DR specificities previously defined by human alloantisera, the range of recognized specificities is very narrow, and few of the MAbs have proven useful as tissue typing reagents. In hopes of obtaining HLA typing reagents, the authors are developing a protocol for the production of human anti-HLA MAbs from HLA-antigen (Ag) immunized peripheral blood B cells of volunteering renal patients, immunized to one or more HLA Ags through therapeutic blood transfusions. A simple enrichment of the donor B cells has not been sufficient for anti-HLA MAb production, the authors are currently delineating the conditions necessary for increasing the number of HLA-specific donor B cells by in vitro stimulation with cells expressing the HLA Ag to which the B cell donor is immunized. For the production of MAbs, the stimulated B cells are transformed with Epstein-Barr virus and subsequently fused with KR-4 lymphoblastoid cells. Hybridomas are selected by HAT and Ouabain. Supernatants are screened for anti-HLA activity against lymphocyte targets expressing the original immunizing HLA Ag by complement mediated /sup 51/Cr release assay. Antibody specificity is determined by the complement-dependent microcytotoxicity test used for HLA typing.

Contribution of herpesvirus specific CD8 T cells to anti-viral T cell response in humans.

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Elena Sandalova

Full Text Available Herpesviruses infect most humans. Their infections can be associated with pathological conditions and significant changes in T cell repertoire but evidences of symbiotic effects of herpesvirus latency have never been demonstrated. We tested the hypothesis that HCMV and EBV-specific CD8 T cells contribute to the heterologous anti-viral immune response. Volume of activated/proliferating virus-specific and total CD8 T cells was evaluated in 50 patients with acute viral infections: 20 with HBV, 12 with Dengue, 12 with Influenza, 3 with Adenovirus infection and 3 with fevers of unknown etiology. Virus-specific (EBV, HCMV, Influenza pentamer+ and total CD8 T cells were analyzed for activation (CD38/HLA-DR, proliferation (Ki-67/Bcl-2(low and cytokine production. We observed that all acute viral infections trigger an expansion of activated/proliferating CD8 T cells, which differs in size depending on the infection but is invariably inflated by CD8 T cells specific for persistent herpesviruses (HCMV/EBV. CD8 T cells specific for other non-related non persistent viral infection (i.e. Influenza were not activated. IL-15, which is produced during acute viral infections, is the likely contributing mechanism driving the selective activation of herpesvirus specific CD8 T cells. In addition we were able to show that herpesvirus specific CD8 T cells displayed an increased ability to produce the anti-viral cytokine interferon-gamma during the acute phase of heterologous viral infection. Taken together, these data demonstrated that activated herpesvirus specific CD8 T cells inflate the activated/proliferating CD8 T cells population present during acute viral infections in human and can contribute to the heterologous anti-viral T cell response.

Treatment of severe acute pancreatitis

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Praznik Ivan

2014-01-01

Full Text Available Acute pancreatitis is an acute inflammatory process of the pancreas with variable involvement of other regional tissues or other organ systems. The severe form of the disease occurs in 10-20% of cases, and usually requires prolonged hospitalization due to a frequent local and systemic complications. Additionally, considerable mortality despite diagnostic and therapeutic advances, makes this disease a serious health problem nowadays. The aim of this study was to conduct a review of randomized controlled trials to determine differences in the efficiency between standard methods of treatment for severe acute pancreatitis and new treatment ways in terms of decreased mortality. Search of the 'Medline' database of original scientific papers and systematic review articles was made, using a combination of the following keywords: acute pancreatitis, treatment, mortality. In total 914 papers were found, published in the last 13 years; 14 of 64 randomized controlled clinical trials met the selection criteria and were eligible for inclusion. From a total of 16 papers, the conservative treatment was related to 11, which includes some of the new treatment methods, while the effects of new methods of treatment have been the subject of research in the four studies. Combined endoscopic and surgical treatment was applied in only one study. The largest sample of 290 patients was included in the study with platelet activation factor antagonist, while the smallest sample of 22 patients was used in the study that compared total parenteral with enteral nutrition. Continuous regional arterial infusion of protease inhibitors in combination with antibiotics, intravenous supplementation of alanyl-glutamine dipeptide and the early, high-volume continuous veno-venous hemofiltration showed the best results in the treatment of patients with severe acute pancreatitis. Also, the use of low molecular weight heparin and enteral nutrition significantly reduced mortality.

THE PANC 3 SCORE PREDICTING SEVERITY OF ACUTE PANCREATITIS.

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Beduschi, Murilo Gamba; Mello, André Luiz Parizi; VON-Mühlen, Bruno; Franzon, Orli

2016-03-01

About 20% of cases of acute pancreatitis progress to a severe form, leading to high mortality rates. Several studies suggested methods to identify patients that will progress more severely. However, most studies present problems when used on daily practice. To assess the efficacy of the PANC 3 score to predict acute pancreatitis severity and its relation to clinical outcome. Acute pancreatitis patients were assessed as to sex, age, body mass index (BMI), etiology of pancreatitis, intensive care need, length of stay, length of stay in intensive care unit and mortality. The PANC 3 score was determined within the first 24 hours after diagnosis and compared to acute pancreatitis grade of the Revised Atlanta classification. Out of 64 patients diagnosed with acute pancreatitis, 58 met the inclusion criteria. The PANC 3 score was positive in five cases (8.6%), pancreatitis progressed to a severe form in 10 cases (17.2%) and five patients (8.6%) died. Patients with a positive score and severe pancreatitis required intensive care more often, and stayed for a longer period in intensive care units. The PANC 3 score showed sensitivity of 50%, specificity of 100%, accuracy of 91.4%, positive predictive value of 100% and negative predictive value of 90.6% in prediction of severe acute pancreatitis. The PANC 3 score is useful to assess acute pancreatitis because it is easy and quick to use, has high specificity, high accuracy and high predictive value in prediction of severe acute pancreatitis.

Human coronavirus and severe acute respiratory infection in Southern Brazil.

Science.gov (United States)

Trombetta, Hygor; Faggion, Heloisa Z; Leotte, Jaqueline; Nogueira, Meri B; Vidal, Luine R R; Raboni, Sonia M

2016-05-01

Human coronaviruses (HCoVs) are an important cause of respiratory tract infection and are responsible for causing the common cold in the general population. Thus, adequate surveillance of HCoV is essential. This study aimed to analyze the impact of HCoV infections and their relation to severe acute respiratory infection (SARI) in a hospitalized population in Southern Brazil. A cross-sectional study was conducted at a tertiary care hospital, and assessed inpatients under investigation for SARI by the hospital epidemiology department, and all patients who had nasopharyngeal aspirates collected from January 2012 to December 2013 to detect respiratory viruses (RVs). Viral infection was detected by multiplex reverse transcriptase polymerase chain reaction (RT-PCR), with primers specific to the subtypes HCoV-229E/NL63 and OC43/HKU1. The overall positivity rate was 58.8% (444/755), and HCoVs were detected in 7.6% (n = 34) of positive samples. Children below two years of age were most frequently affected (62%). Comorbidities were more likely to be associated with HCoVs than with other RVs. Immunosuppression was an independent risk factor for HCoV infection (OR = 3.5, 95% CI 1.6-7.6). Dyspnea was less frequently associated with HCoV infection (p infected with HCoV (9%) died from respiratory infection. HCoVs are important respiratory pathogens, especially in hospitalized children under 2 years of age and in immunosuppressed patients. They may account for a small proportion of SARI diagnoses, increased need for mechanical ventilation, intensive care unit admission, and death.

Anti-inflammatory treatment for carditis in acute rheumatic fever.

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Cilliers, Antoinette; Adler, Alma J; Saloojee, Haroon

2015-05-28

Rheumatic heart disease remains an important cause of acquired heart disease in developing countries. Although prevention of rheumatic fever and management of recurrences have been well established, optimal management of active rheumatic carditis remains unclear. This is an update of a review published in 2003, and previously updated in 2009 and 2012. To assess the effects, both harmful and beneficial, of anti-inflammatory agents such as aspirin, corticosteroids and other drugs in preventing or reducing further valvular damage in patients with acute rheumatic fever. We searched the Cochrane Central Register of Controlled Trials (2013, Issue 9 of 12), MEDLINE (Ovid, 1948 to 2013 October Week 1), EMBASE (Ovid, 1980 to 2013 Week 41) and Latin American Caribbean Health Sciences Literature (LILACS) (1982 to 17 October 2013). We last searched Index Medicus (1950 to April 2001) in 2001. We checked reference lists of identified studies and applied no language restrictions. Randomised controlled trials comparing anti-inflammatory agents (e.g. aspirin, steroids, immunoglobulins, pentoxifylline) versus placebo or controls, or comparing any of the anti-inflammatory agents versus one another, in adults and children with acute rheumatic fever diagnosed according to Jones, or modified Jones, criteria. The presence of cardiac disease one year after treatment was the major outcome criterion selected. Two review authors extracted data and assessed risk of bias using the methodology outlined in the Cochrane Handbook of Systematic Reviews of Interventions. Standard methodological procedures as expected by The Cochrane Collaboration were used. No new studies were included in this update. Eight randomised controlled trials involving 996 people were selected for inclusion in the review. Researchers compared several steroidal agents such as corticotrophin, cortisone, hydrocortisone, dexamethasone, prednisone and intravenous immunoglobulin versus aspirin, placebo or no treatment. Six

Selenium intoxication with selenite broth resulting in acute renal failure and severe gastritis

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Kamble P

2009-01-01

Full Text Available Selenium (Se is an essential trace element in human and animal nutrition. It is also widely utilized in industrial processes. Reports of acute selenium toxicity in humans are rare. We report a case of a 23-year-old female who consumed about 100 mL of liquid selenite broth and presented with severe nausea, vomiting, abdominal pain, hematemesis and acute renal failure (ARF. The serum selenium level was significantly increased. Gastro-duodenoscopy revealed severe corrosive gastritis. Renal biopsy showed features of acute tubular necrosis (ATN, affecting primarily the proximal tubules. The patient was managed with gastric lavage, blood transfusions, infusion of fresh frozen plasma (FFP and platelet concentrates and hemo-dialysis. The patient was discharged five weeks after admission and her renal functions reco-vered completely by eight weeks after admission. She continues to be on regular follow-up for any possible sequelae of mucosal corrosive damage. This case highlights a case of selenium intoxication from selenite broth resulting in ARF and corrosive gastritis. The recovery was complete.

Chinese herbal medicine for severe acute respiratory syndrome

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Liu, Jianping; Manheimer, Eric; Shi, Yi

2004-01-01

To review randomized controlled trials (RCTs) evaluating the effects of Chinese herbal medicine for treating severe acute respiratory syndrome (SARS) systematically.......To review randomized controlled trials (RCTs) evaluating the effects of Chinese herbal medicine for treating severe acute respiratory syndrome (SARS) systematically....

Factors associated with severe human Rift Valley fever in Sangailu, Garissa County, Kenya.

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A Desirée LaBeaud

2015-03-01

Full Text Available Mosquito-borne Rift Valley fever virus (RVFV causes acute, often severe, disease in livestock and humans. To determine the exposure factors and range of symptoms associated with human RVF, we performed a population-based cross-sectional survey in six villages across a 40 km transect in northeastern Kenya.A systematic survey of the total populations of six Northeastern Kenyan villages was performed. Among 1082 residents tested via anti-RVFV IgG ELISA, seroprevalence was 15% (CI95%, 13-17%. Prevalence did not vary significantly among villages. Subject age was a significant factor, with 31% (154/498 of adults seropositive vs. only 2% of children ≤15 years (12/583. Seroprevalence was higher among men (18% than women (13%. Factors associated with seropositivity included a history of animal exposure, non-focal fever symptoms, symptoms related to meningoencephalitis, and eye symptoms. Using cluster analysis in RVFV positive participants, a more severe symptom phenotype was empirically defined as having somatic symptoms of acute fever plus eye symptoms, and possibly one or more meningoencephalitic or hemorrhagic symptoms. Associated with this more severe disease phenotype were older age, village, recent illness, and loss of a family member during the last outbreak. In multivariate analysis, sheltering livestock (aOR = 3.5 CI95% 0.93-13.61, P = 0.065, disposing of livestock abortus (aOR = 4.11, CI95% 0.63-26.79, P = 0.14, and village location (P = 0.009 were independently associated with the severe disease phenotype.Our results demonstrate that a significant proportion of the population in northeastern Kenya has been infected with RVFV. Village and certain animal husbandry activities were associated with more severe disease. Older age, male gender, herder occupation, killing and butchering livestock, and poor visual acuity were useful markers for increased RVFV infection. Formal vision testing may therefore prove to be a helpful, low-technology tool

Leiden Mutation and the Course of Severe Acute Pancreatitis

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A. V. Ershov

2013-01-01

Full Text Available Objective: to evaluate the impact of Leiden mutation on the course of severe acute pancreatitis. Subjects and methods. One hundred and twelve people were examined. Group 1 comprised 50 patients diagnosed with severe acute pancreatitis without coagulation factor V (Leiden mutation. Group 2 included 42 patients with severe acute pancreatitis who were found to have Leiden mutation. Acute pancreatitis was first diagnosed in both groups. Group 3 consisted of 20 apparently healthy individuals (a control group. The severity of the underlying disease was determined in accordance with the clinical and laboratory parameters recommended by the I. I. Dzhanelidze Saint Petersburg Research Institute of Emergence Care. Results. This investigation revealed an association of Leiden mutation with trends in the development of acute pancreatitis. Group 2 exhibited a more severe disease: large focal pancreatic necrosis was twice more common and infectious complications developed more frequently; more aggressive and radical treatments were more often used. The patients with Leiden mutation had higher mortality rates (33% in the Leiden mutation group and 24% in the non-mutation group. Conclusion. The findings should be kept in mind in elaborating new diagnostic methods and principles in the treatment of the underlying disease and in the prevention of its complications in patients with severe acute pancreatitis. Key words: acute pancreatitis, Leiden mutation.

In-Patient Treatment of Severe Acute Malnutrition

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Rytter, Maren Johanne Heilskov

Severe acute malnutrition is a serious health problem among children in low-income countries. Particularly malnourished children requiring in-hospital treatment are at high risk of dying. This dissertation investigates possible reasons for this high mortality, by following a group of 120 children...... during their in-hospital treatment of severe acute malnutrition at Mwanamugimu Nutrition Unit in Kampala, Uganda. We assessed how malnutrition affected the children’s immune system, by measuring the size of their thymus gland with ultrasound. We examined characteristics of children with the serious form...... of malnutrition, Kwashiorkor, where the children develop oedema. Finally, we explored symptoms, findings or treatments given that were associated with a higher risk of death in the children. Hopefully, these findings may contribute to improving the treatment offered to children with severe acute malnutrition....

Severe acute respiratory syndrome (SARS)

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SARS; Respiratory failure - SARS ... Complications may include: Respiratory failure Liver failure Heart failure ... 366. McIntosh K, Perlman S. Coronaviruses, including severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). ...

Anti-NMDAR encephalitis, a mimicker of acute infectious encephalitis and a review of the literature

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Darren Wong

2014-01-01

Full Text Available Anti-N-methyl-d-aspartate receptor encephalitis has become an increasingly recognized etiology of acute psychosis in young patients. The diverse constellation of symptoms allows for misdiagnosis as an infectious, psychological, or toxicological entity resulting in delays in treatment with increasing morbidity. We describe a case of anti-NMDAR encephalitis that was a particular challenge to diagnose. Practitioners should maintain a high index of suspicion for anti-NMDAR and related neuroautoimmune syndromes, especially in young patients that present with acute mental status decline or dyskinesia.

Cross reactivity of commercial anti-dengue immunoassays in patients with acute Zika virus infection.

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Felix, Alvina Clara; Souza, Nathalia C Santiago; Figueiredo, Walter M; Costa, Angela A; Inenami, Marta; da Silva, Rosangela M G; Levi, José Eduardo; Pannuti, Claudio Sergio; Romano, Camila Malta

2017-08-01

Several countries have local transmission of multiple arboviruses, in particular, dengue and Zika viruses, which have recently spread through many American countries. Cross reactivity among Flaviviruses is high and present a challenge for accurate identification of the infecting agent. Thus, we evaluated the level of cross reactivity of anti-dengue IgM/G Enzyme-Linked Immunosorbent Assays (ELISA) from three manufacturers against 122 serum samples obtained at two time-points from 61 patients with non-dengue confirmed Zika virus infection. All anti-dengue ELISAs cross reacted with serum from patients with acute Zika infection at some level and a worrisome number of seroconversion for dengue IgG and IgM was observed. These findings may impact the interpretation of currently standard criteria for dengue diagnosis in endemic regions. © 2017 Wiley Periodicals, Inc.

Determinants of maximal oxygen uptake in severe acute hypoxia

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Calbet, J A L; Boushel, Robert Christopher; Rådegran, G

2003-01-01

To unravel the mechanisms by which maximal oxygen uptake (VO2 max) is reduced with severe acute hypoxia in humans, nine Danish lowlanders performed incremental cycle ergometer exercise to exhaustion, while breathing room air (normoxia) or 10.5% O2 in N2 (hypoxia, approximately 5,300 m above sea......: 1) reduction of PiO2, 2) impairment of pulmonary gas exchange, and 3) reduction of maximal cardiac output and peak leg blood flow, each explaining about one-third of the loss in VO2 max....

Reactivity of eleven anti-human leucocyte monoclonal antibodies with lymphocytes from several domestic animals

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Aasted, Bent; Blixenkrone-Møller, Merete; Larsen, Else Bang

1988-01-01

Nine commercially available monoclonal antibodies and two monoclonal antibodies from The American Type Culture Collection, raised against various human leucocyte surface antigens, were tested on lymphocytes from cow, sheep, goat, swine, horse, cat, dog, mink, and rabbit as well as man. Four...... antibodies bound to lymphocytes from some of the animals. These were the antibodies against CD8 and CD4 antigen, the antibody to C3b-receptor, and the antibody to the HLA-DR antigen. The CD8 antigen-reactive antibody reacted with lymphocytes from mink, cat, dog, and sheep, while the CD4 antigen......-reactive antibody reacted with lymphocytes from mink. The anti-C3b-R antibody reacted with lymphocytes from horse, swine, dog, and cat, and the anti-HLA-DR reacted with lymphocytes from cow, goat, sheep, horse, dog, cat, and mink....

MODERN MANAGEMENT OF ACUTE RESPIRATORY INFECTIONS IN CHILDREN. RECOURSES OF SYSTEM ANTI INFLAMMATORY TREATMENT

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O.V. Zaitseva

2008-01-01

Full Text Available A problem of etiology and pathogenesis of acute respiratory infections in children are observed in this article. Modern approach to management of its treatment in pediatric patients, including often ailing children, is described. Authors give characteristics to main directions of treatment of obstructive syndrome. An experience of anti-inflammatory therapy with fenspiride (eurespal in children of different age is summa ized in this article.Key words: often ailing children, acute respiratory infections, bronchoobstructive syndrome, anti-inflammatory treatment, fenspiride.

Anti-E Alloimmunization: A Rare Cause of Severe Fetal Hemolytic Disease Resulting in Pregnancy Loss

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An-Shine Chao

2009-01-01

Full Text Available We report a case of severe intrauterine hemolysis caused by sole anti-E alloimmunization. A 36-year-old multipara woman presented with hydrops fetalis at 27 weeks of gestation. She had a history of previous neonatal death. In this pregnancy, she was found to have very high titer of anti-E antibody. Ultrasonography detected marked skin edema, cardiomegaly, hepatosplenomegaly, pleural effusion, ascites, placentomegaly, and polyhydramnios. The Doppler peak systolic velocity in the middle cerebral artery was 0.8 m/s, indicating severe fetal anemia. Multiple intrauterine transfusions for the anemic fetus were administered. However, persistent severe fetal anemia and placentomegaly caused poor neonatal death and mirror syndrome in the mother. Uncommon red blood cell alloimmunization has to be watched for early in any population, especially in a woman with a history of unexplained perinatal loss.

Anti-virus effect of traditional Chinese medicine Yi-Fu-Qing granule on acute respiratory tract infections.

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Li, Anyuan; Xie, Yanying; Qi, Fanghua; Li, Jie; Wang, Peng; Xu, Shulan; Zhao, Lin

2009-08-01

Yi-Fu-Qing granule is a traditional Chinese medicine for the treatment of acute respiratory tract infections. The present study sought to investigate the anti-virus effects of Yi-Fu-Qing granule on acute respiratory infections with respiratory syncytial virus (RSV) and human adenoviruses type 3 (Ad3). The cytotoxicity of Yi-Fu-Qing granule was evaluated by the neutral red assay on HeLa cells. The antiviral effect of Yi-Fu-Qing granule was tested by observing the cytopathogenic effect (CPE) with a compound mixture of Isatis leaf as the positive control drug. The results indicated that the highest non-toxicity concentration of Yi-Fu-Qing granule on Hela cells was 1:100. The CPE reduction assay showed that Yi-Fu-Qing granule inhibited RSV and Ad3 replication at a concentration of 1:100. Thus, Yi-Fu-Qing granule may have a significant antivirus effect on acute respiratory tract infections with RSV and Ad3 infections and this could prove useful for further antivirus research on acute respiratory tract infections.

Improving estimates of the burden of severe acute malnutrition and predictions of caseload for programs treating severe acute malnutrition

DEFF Research Database (Denmark)

Bulti, Assaye; Briend, André; Dale, Nancy M

2017-01-01

Background: The burden of severe acute malnutrition (SAM) is estimated using unadjusted prevalence estimates. SAM is an acute condition and many children with SAM will either recover or die within a few weeks. Estimating SAM burden using unadjusted prevalence estimates results in significant...

Acute severe asthma presenting in late pregnancy.

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Holland, S M; Thomson, K D

2006-01-01

Asthma is the commonest pre-existing medical condition to complicate pregnancy. Acute severe asthma in pregnancy is rare, but poses difficult problems. In particular, the decision about when and where to deliver the fetus is complex, since maternal response to asthma treatment is unpredictable. We report the successful management of a parturient presenting with acute severe asthma at 37 weeks' gestation. The controversies involved and the importance of adopting a multi-disciplinary team approach to optimise maternal and neonatal outcomes are discussed.

Adolescent with acute psychosis due to anti-N-methyl-D-aspartate receptor encephalitis: successful recovery

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Jonuskaite, Dovile; Kalibatas, Paulius; Praninskiene, Ruta; Zalubiene, Asta; Jucaite, Aurelija; Cerkauskiene, Rimante

2017-01-01

Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is a relatively new autoimmune disorder of the central nervous system. We report the first case of anti-NMDAR autoimmune encephalitis combined with anti-voltage-gated potassium channel (anti-VGKC) antibodies in Lithuania in a 16-year-old girl. The patient was admitted to psychiatry unit because of an acute psychotic episode. She was unsuccessfully treated with antipsychotics, and electroconvulsive therapy was initiated because of he...

Anti-actin IgA antibodies in severe coeliac disease.

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Granito, A; Muratori, P; Cassani, F; Pappas, G; Muratori, L; Agostinelli, D; Veronesi, L; Bortolotti, R; Petrolini, N; Bianchi, F B; Volta, U

2004-08-01

Anti-actin IgA antibodies have been found in sera of coeliacs. Our aim was to define the prevalence and clinical significance of anti-actin IgA in coeliacs before and after gluten withdrawal. One hundred and two biopsy-proven coeliacs, 95 disease controls and 50 blood donors were studied. Anti-actin IgA were evaluated by different methods: (a) antimicrofilament positivity on HEp-2 cells and on cultured fibroblasts by immunofluorescence; (b) anti-actin positivity by enzyme-linked immuosorbent assay (ELISA); and (c) presence of the tubular/glomerular pattern of anti-smooth muscle antibodies on rat kidney sections by immunofluorescence. Antimicrofilament IgA were present in 27% of coeliacs and in none of the controls. Antimicrofilament antibodies were found in 25 of 54 (46%) coeliacs with severe villous atrophy and in three of 48 (6%) with mild damage (P < 0.0001). In the 20 patients tested, antimicrofilaments IgA disappeared after gluten withdrawal in accordance with histological recovery. Our study shows a significant correlation between antimicrofilament IgA and the severity of intestinal damage in untreated coeliacs. The disappearance of antimicrofilament IgA after gluten withdrawal predicts the normalization of intestinal mucosa and could be considered a useful tool in the follow-up of severe coeliac disease.

In Vitro and In Vivo Antitumor Effect of Anti-CD33 Chimeric Receptor-Expressing EBV-CTL against CD33+ Acute Myeloid Leukemia

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A. Dutour

2012-01-01

Full Text Available Genetic engineering of T cells with chimeric T-cell receptors (CARs is an attractive strategy to treat malignancies. It extends the range of antigens for adoptive T-cell immunotherapy, and major mechanisms of tumor escape are bypassed. With this strategy we redirected immune responses towards the CD33 antigen to target acute myeloid leukemia. To improve in vivo T-cell persistence, we modified human Epstein Barr Virus-(EBV- specific cytotoxic T cells with an anti-CD33.CAR. Genetically modified T cells displayed EBV and HLA-unrestricted CD33 bispecificity in vitro. In addition, though showing a myeloablative activity, they did not irreversibly impair the clonogenic potential of normal CD34+ hematopoietic progenitors. Moreover, after intravenous administration into CD33+ human acute myeloid leukemia-bearing NOD-SCID mice, anti-CD33-EBV-specific T cells reached the tumor sites exerting antitumor activity in vivo. In conclusion, targeting CD33 by CAR-modified EBV-specific T cells may provide additional therapeutic benefit to AML patients as compared to conventional chemotherapy or transplantation regimens alone.

LPS-induced lung inflammation in marmoset monkeys - an acute model for anti-inflammatory drug testing.

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Sophie Seehase

Full Text Available Increasing incidence and substantial morbidity and mortality of respiratory diseases requires the development of new human-specific anti-inflammatory and disease-modifying therapeutics. Therefore, new predictive animal models that closely reflect human lung pathology are needed. In the current study, a tiered acute lipopolysaccharide (LPS-induced inflammation model was established in marmoset monkeys (Callithrix jacchus to reflect crucial features of inflammatory lung diseases. Firstly, in an ex vivo approach marmoset and, for the purposes of comparison, human precision-cut lung slices (PCLS were stimulated with LPS in the presence or absence of the phosphodiesterase-4 (PDE4 inhibitor roflumilast. Pro-inflammatory cytokines including tumor necrosis factor-alpha (TNF-α and macrophage inflammatory protein-1 beta (MIP-1β were measured. The corticosteroid dexamethasone was used as treatment control. Secondly, in an in vivo approach marmosets were pre-treated with roflumilast or dexamethasone and unilaterally challenged with LPS. Ipsilateral bronchoalveolar lavage (BAL was conducted 18 hours after LPS challenge. BAL fluid was processed and analyzed for neutrophils, TNF-α, and MIP-1β. TNF-α release in marmoset PCLS correlated significantly with human PCLS. Roflumilast treatment significantly reduced TNF-α secretion ex vivo in both species, with comparable half maximal inhibitory concentration (IC(50. LPS instillation into marmoset lungs caused a profound inflammation as shown by neutrophilic influx and increased TNF-α and MIP-1β levels in BAL fluid. This inflammatory response was significantly suppressed by roflumilast and dexamethasone. The close similarity of marmoset and human lungs regarding LPS-induced inflammation and the significant anti-inflammatory effect of approved pharmaceuticals assess the suitability of marmoset monkeys to serve as a promising model for studying anti-inflammatory drugs.

Increased oxidative stress and anaerobic energy release, but blunted Thr172-AMPKα phosphorylation, in response to sprint exercise in severe acute hypoxia in humans.

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Morales-Alamo, David; Ponce-González, Jesús Gustavo; Guadalupe-Grau, Amelia; Rodríguez-García, Lorena; Santana, Alfredo; Cusso, Maria Roser; Guerrero, Mario; Guerra, Borja; Dorado, Cecilia; Calbet, José A L

2012-09-01

AMP-activated protein kinase (AMPK) is a major mediator of the exercise response and a molecular target to improve insulin sensitivity. To determine if the anaerobic component of the exercise response, which is exaggerated when sprint is performed in severe acute hypoxia, influences sprint exercise-elicited Thr(172)-AMPKα phosphorylation, 10 volunteers performed a single 30-s sprint (Wingate test) in normoxia and in severe acute hypoxia (inspired Po(2): 75 mmHg). Vastus lateralis muscle biopsies were obtained before and immediately after 30 and 120 min postsprint. Mean power output and O(2) consumption were 6% and 37%, respectively, lower in hypoxia than in normoxia. O(2) deficit and muscle lactate accumulation were greater in hypoxia than in normoxia. Carbonylated skeletal muscle and plasma proteins were increased after the sprint in hypoxia. Thr(172)-AMPKα phosphorylation was increased by 3.1-fold 30 min after the sprint in normoxia. This effect was prevented by hypoxia. The NAD(+)-to-NADH.H(+) ratio was reduced (by 24-fold) after the sprints, with a greater reduction in hypoxia than in normoxia (P exercise in human skeletal muscle is altered in severe acute hypoxia, which abrogated Thr(172)-AMPKα phosphorylation, likely due to lower LKB1 activation by SIRT1.

[Causes and management of severe acute liver damage during pregnancy].

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Sepulveda-Martinez, Alvaro; Romero, Carlos; Juarez, Guido; Hasbun, Jorge; Parra-Cordero, Mauro

2015-05-01

Abnormalities in liver function tests appear in 3% of pregnancies. Severe acute liver damage can be an exclusive condition of pregnancy (dependent or independent of pre-eclampsia) or a concomitant disease. HELLP syndrome and acute fatty liver of pregnancy are the most severe liver diseases associated with pregnancy. Both appear during the third trimester and have a similar clinical presentation. Acute fatty liver may be associated with hypoglycemia and HELLP syndrome is closely linked with pre-eclampsia. Among concomitant conditions, fulminant acute hepatitis caused by medications or virus is the most severe disease. Its clinical presentation may be hyper-acute with neurological involvement and severe coagulation disorders. It has a high mortality and patients should be transplanted. Fulminant hepatic failure caused by acetaminophen overdose can be managed with n-acetyl cysteine. Because of the high fetal mortality rate, the gestational age at diagnosis is crucial.

Anti-N-methyl-D-aspartate receptor encephalitis associated with acute Toxoplasma gondii infection: A case report.

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Cai, Xiaotang; Zhou, Hui; Xie, Yongmei; Yu, Dan; Wang, Zhiling; Ren, Haitao

2018-02-01

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis has been recognized as the most frequent autoimmune encephalitis in children. Several infectious agents have been implicated in anti-NMDA encephalitis. A previously healthy immunocompetent 9-year-old girl first presented with seizures, headaches and vomiting. Cerebrospinal fluid and brain magnetic resonance imaging were normal. After one week onset, the patient gradually developed unexplained personality and behavior changes, accompanied by fever and seizures again. Repeated CSF analysis revealed a slightly lymphocytic predominant pleocytosis and positive anti-NMDAR antibody. A variety of pathogenic examinations were negative, except for positive toxoplasma IgM and IgG. The patient was diagnoses for anti-NMDA encephalitis associated with acute acquired toxoplasma gondii infection. The patient received 10 days azithromycin for treatment of acquired toxoplasma infection. The parents refuse immunotherapy because substantial recovery from clinical symptoms. The patient was substantially recovered with residual mild agitation after therapy for acquired toxoplasma gondii infection. Two months later, the patient was completely devoid of symptoms, and the levels of serum IgM and IgG of toxoplasma gondii were decreased. Acquired toxoplasma gondii infection may trigger anti-NMDAR encephalitis in children, which has not been reported previously. Clinicians should assess the possibility of toxoplasma gondii infection when evaluating a patient with anti-NMDA encephalitis.

Study on acute toxicity of anti-vertigo granule on mice

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Wen, Zhonghua; Hao, Shaojun; Xie, Guoqi; Li, Jun; Su, Feng; Liu, Xiaobin; Wang, Xidong; Zhang, Zhengchen

2018-04-01

To observe the effect of anti - glare particles on acute toxicity of mice. Methods: 40 male and female mice weighing 18 - 21 g were randomly divided into anti - glare granule group and normal saline control group. The maximum volume of anti - glare particles (0.94 g/ml) was administered before the experiment. Results: the oral toxicity of the suspension was very small. The maximal concentration of mice was given at the maximum volume of gastric perfusion, and it was given three times in 1st. The cumulative maximum tolerance dose was 112.8g/kg per day. The dose was 226 times of clinical dosage and no death was found in mice. Conclusion: the toxicity of Kangxuan granules is very small and it can be considered safe in clinical use.

Human mesenchymal stem cells reduce the severity of acute lung injury in a sheep model of bacterial pneumonia.

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Asmussen, Sven; Ito, Hiroshi; Traber, Daniel L; Lee, Jae W; Cox, Robert A; Hawkins, Hal K; McAuley, Daniel F; McKenna, David H; Traber, Lillian D; Zhuo, Hanjing; Wilson, Jennifer; Herndon, David N; Prough, Donald S; Liu, Kathleen D; Matthay, Michael A; Enkhbaatar, Perenlei

2014-09-01

Human bone marrow-derived mesenchymal stem (stromal) cells (hMSCs) improve survival in mouse models of acute respiratory distress syndrome (ARDS) and reduce pulmonary oedema in a perfused human lung preparation injured with Escherichia coli bacteria. We hypothesised that clinical grade hMSCs would reduce the severity of acute lung injury (ALI) and would be safe in a sheep model of ARDS. Adult sheep (30-40 kg) were surgically prepared. After 5 days of recovery, ALI was induced with cotton smoke insufflation, followed by instillation of live Pseudomonas aeruginosa (2.5×10(11) CFU) into both lungs under isoflurane anaesthesia. Following the injury, sheep were ventilated, resuscitated with lactated Ringer's solution and studied for 24 h. The sheep were randomly allocated to receive one of the following treatments intravenously over 1 h in one of the following groups: (1) control, PlasmaLyte A, n=8; (2) lower dose hMSCs, 5×10(6) hMSCs/kg, n=7; and (3) higher-dose hMSCs, 10×10(6) hMSCs/kg, n=4. By 24 h, the PaO2/FiO2 ratio was significantly improved in both hMSC treatment groups compared with the control group (control group: PaO2/FiO2 of 97±15 mm Hg; lower dose: 288±55 mm Hg (p=0.003); higher dose: 327±2 mm Hg (p=0.003)). The median lung water content was lower in the higher-dose hMSC-treated group compared with the control group (higher dose: 5.0 g wet/g dry [IQR 4.9-5.8] vs control: 6.7 g wet/g dry [IQR 6.4-7.5] (p=0.01)). The hMSCs had no adverse effects. Human MSCs were well tolerated and improved oxygenation and decreased pulmonary oedema in a sheep model of severe ARDS. NCT01775774 for Phase 1. NCT02097641 for Phase 2. 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.

Etiology, clinical profile, severity and outcome of acute pancreatitis in relation to bed side index for severity of acute pancreatitis bisap and CT severity index [CTSI] scores

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Bezwada Srinivasa Rao, Matta SreeVani, V.Sarat Chandra

2014-11-01

Full Text Available Background: Acute pancreatitis is an inflammatory process of the pancreas with involvement of regional tissues or remote organ systems and with potentially devastating consequences. Early prediction of outcome of acute pancreatitis within 24 hrs by clinically based bed Side Index of Severity of Acute Pancreatitis [BISAP] Score and radiological based CT Severity Index [CTSI] later on being useful in initiation of early treatment, assessing severity, to prevent morbidity and mortality. In those who survive, it can progress to chronic pancreatitis resulting in malabsorption and permanent diabetes. Aim: The aim was to study aetiology, clinical profile, severity, outcome of acute pancreatitis in relation to BISAP Score and CTSI. Materials and Methods: This was an observational and prospective study. The present study enrolled 55 patients who were diagnosed as acute pancreatitis and patients with chronic pancreatitis were excluded from the study. Vital data like pulse rate, blood Pressure, temperature, respiratory rate, conscious level using Glasgow coma scale, serum amylase, lipase, Chest x-ray, US abdomen and CT abdomen [both CECT & NCCT] were done. BISAP Score was obtained at the time of presentation or within 24 hours of presentation and radiological based CT Severity Index [CTSI] was calculated using the Balthazar grading system and Necrosis Scoring system to assess the severity, morbidity and mortality. The results: In this study, the most common aetiology being alcohol intake followed by gall stones. BISAP Score 3 had organ dysfunction and Score 4 had 100% mortality. The relation between CTSI score and Organ dysfunction showed increased organic dysfunction and higher mortality with higher CTSI Scores. p value < 0.0001 was calculated using Pearson Chi-square test and found to be statistically significant. Conclusions: Both BISAP and CTSI scores had positive correlation with morbidity and mortality.

Association of serum anti-rotavirus immunoglobulin A antibody seropositivity and protection against severe rotavirus gastroenteritis: analysis of clinical trials of human rotavirus vaccine.

Science.gov (United States)

Cheuvart, Brigitte; Neuzil, Kathleen M; Steele, A Duncan; Cunliffe, Nigel; Madhi, Shabir A; Karkada, Naveen; Han, Htay Htay; Vinals, Carla

2014-01-01

Clinical trials of the human rotavirus vaccine Rotarix™ (RV1) have demonstrated significant reductions in severe rotavirus gastroenteritis (RVGE) in children worldwide. However, no correlate of vaccine efficacy (VE) has yet been established. This paper presents 2 analyses which aimed to investigate whether serum anti-RV IgA measured by ELISA 1 or 2 mo post-vaccination can serve as a correlate of efficacy against RVGE: (1) In a large Phase III efficacy trial (Rota-037), the Prentice criteria for surrogate endpoints was applied to anti-RV IgA seropositivity 1 mo post-vaccination. These criteria determine whether a significant vaccine group effect can be predicted from the surrogate, namely seropositivity (anti-RV IgA concentration>20 U/mL); (2) Among other GSK-sponsored RV1 VE studies, 8 studies which assessed immunogenicity at 1 or 2 mo post-vaccination in all or a sub-cohort of enrolled subjects and had at least 10 RVGE episodes were included in a meta-analysis to measure the regression between clinical VE and VE predicted from immunogenicity (VE1). In Rota-037, anti-RV IgA seropositivity post-vaccination was associated with a lower incidence of any or severe RVGE, however, the proportion of vaccine group effect explained by seropositivity was only 43.6% and 32.7% respectively. This low proportion was due to the vaccine group effect observed in seronegative subjects. In the meta-analysis, the slope of the regression between clinical VE and VE1 was statistically significant. These two independent analyses support the hypothesis that post-vaccination anti-RV IgA seropositivity (antibody concentration ≥20 U/mL) may serve as a useful correlate of efficacy in clinical trials of RV1 vaccines.

First-in-Man Intrathecal Application of Neurite Growth-Promoting Anti-Nogo-A Antibodies in Acute Spinal Cord Injury.

Science.gov (United States)

Kucher, Klaus; Johns, Donald; Maier, Doris; Abel, Rainer; Badke, Andreas; Baron, Hagen; Thietje, Roland; Casha, Steven; Meindl, Renate; Gomez-Mancilla, Baltazar; Pfister, Christian; Rupp, Rüdiger; Weidner, Norbert; Mir, Anis; Schwab, Martin E; Curt, Armin

2018-05-01

Neutralization of central nervous system neurite growth inhibitory factors, for example, Nogo-A, is a promising approach to improving recovery following spinal cord injury (SCI). In animal SCI models, intrathecal delivery of anti-Nogo-A antibodies promoted regenerative neurite growth and functional recovery. This first-in-man study assessed the feasibility, safety, tolerability, pharmacokinetics, and preliminary efficacy of the human anti-Nogo-A antibody ATI355 following intrathecal administration in patients with acute, complete traumatic paraplegia and tetraplegia. Patients (N = 52) started treatment 4 to 60 days postinjury. Four consecutive dose-escalation cohorts received 5 to 30 mg/2.5 mL/day continuous intrathecal ATI355 infusion over 24 hours to 28 days. Following pharmacokinetic evaluation, 2 further cohorts received a bolus regimen (6 intrathecal injections of 22.5 and 45 mg/3 mL, respectively, over 4 weeks). ATI355 was well tolerated up to 1-year follow-up. All patients experienced ≥1 adverse events (AEs). The 581 reported AEs were mostly mild and to be expected following acute SCI. Fifteen patients reported 16 serious AEs, none related to ATI355; one bacterial meningitis case was considered related to intrathecal administration. ATI355 serum levels showed dose-dependency, and intersubject cerebrospinal fluid levels were highly variable after infusion and bolus injection. In 1 paraplegic patient, motor scores improved by 8 points. In tetraplegic patients, mean total motor scores increased, with 3/19 gaining >10 points, and 1/19 27 points at Week 48. Conversion from complete to incomplete SCI occurred in 7/19 patients with tetraplegia. ATI335 was well tolerated in humans; efficacy trials using intrathecal antibody administration may be considered in acute SCI.

Sevoflurane therapy for life-threatening acute severe asthma: a case report.

Science.gov (United States)

Ruszkai, Zoltán; Bokrétás, Gergely Péter; Bartha, Péter Töhötöm

2014-10-01

Acute severe asthma is a life-threatening form of bronchial constriction in which the progressively worsening airway obstruction is unresponsive to the usual appropriate bronchodilator therapy. Pathophysiological changes restrict airflow, which leads to premature closure of the airway on expiration, impaired gas exchange, and dynamic hyperinflation ("air-trapping"). Additionally, patients suffering from asthma for a prolonged period of time usually have serious comorbidities. These conditions constitute a challenge during the treatment of this disease. Therapeutic interventions are designed to reduce airway resistance and improve respiratory status. To achieve therapeutic goals, appropriate bronchodilator treatment is indispensable, and mechanical ventilation under adequate sedation may also be required. The volatile anesthetic agent, sevoflurane, meets both criteria; therefore, its use can be beneficial and should be considered. A 67-yr-old Caucasian male presented with acute life-threatening asthma provoked by an assumed upper airway infection and non-steroidal anti-inflammatory drug antipyretics, complicated by chronic atrial fibrillation and hemodynamic instability. Due to frequent premature ventricular contractions, conventional treatment was considered unsafe and discontinued, and sevoflurane inhalation was initiated via the AnaConDa (Anaesthetic Conserving Device). Symptoms of life-threatening bronchospasm resolved, and the patient's respiratory status improved within hours. Adequate sedation was also achieved without any hemodynamic adverse effects. The volatile anesthetic agent, sevoflurane, is used widely in anesthesia practice. Its utility for treatment of refractory bronchospasm has been appreciated for years; however, its administration was difficult within the environment of the intensive care unit due to the need for an anesthesia machine and a scavenging system. The introduction of the AnaConDa eliminates these obstacles and makes the use of

Untangling the Roles of Anti-Apoptosis in Regulating Programmed Cell Death using Humanized Yeast Cells

International Nuclear Information System (INIS)

Clapp, Caitlin; Portt, Liam; Khoury, Chamel; Sheibani, Sara; Eid, Rawan; Greenwood, Matthew; Vali, Hojatollah; Mandato, Craig A.; Greenwood, Michael T.

2012-01-01

-apoptosis, we screened a human heart cDNA expression library in yeast cells undergoing PCD due to the conditional expression of a mammalian pro-apoptotic Bax cDNA. Analysis of the multiple Bax suppressors identified revealed several previously known as well as a large number of clones representing potential novel anti-apoptotic sequences. The focus of this review is to report on recent achievements in the use of humanized yeast in genetic screens to identify novel stress-induced PCD suppressors, supporting the use of yeast as a unicellular model organism to elucidate anti-apoptotic and cell survival mechanisms.

Rapid Evolution from the First Episode of Acute Pancreatitis to Chronic Pancreatitis in Human Subjects

OpenAIRE

Elie Aoun; Adam Slivka; Dionysios J Papachristou; David C Whitcomb; Ferga C Gleeson; Georgios I Papachristou

2007-01-01

Context Growing evidence suggests that recurrent acute pancreatitis leads to chronic pancreatitis, but this sequence is seldom reported in human subjects. The sentinel acute pancreatitis event hypothesis suggests that an initial episode of acute pancreatitis is the first step in a complicated series of events ultimately leading to chronic pancreatitis. Objective To identify patients who evolved from recurrent acute pancreatitis to chronic pancreatitis. Setting The Severity of Acute Pancreatit...

Lysine clonixinate versus dipyrone (metamizole) for the acute treatment of severe migraine attacks: a single-blind, randomized study

OpenAIRE

Krymchantowski,Abouch Valenty; Carneiro,Henrique; Barbosa,Jackeline; Jevoux,Carla

2008-01-01

BACKGROUND AND OBJECTIVE: Nonsteroidal anti-inflammatory drugs (NSAID) are effective to treat migraine attacks. Lysine clonixinate (LC) and dipyrone (metamizol) have been proven effective to treat acute migraine. The aim of this study was to evaluate the efficacy and tolerability of the intravenous formulations of LC and dipyrone in the treatment of severe migraine attacks. METHOD: Thirty patients (28 women, 2 men), aged 18 to 48 years with migraine according the International Headache Societ...

Anti-complement activities of human breast-milk.

Science.gov (United States)

Ogundele, M O

1999-08-01

It has long been observed that the human milk possesses significant anti-inflammatory properties, while simultaneously protecting the infant against many intestinal and respiratory pathogens. There is, however, a paucity of information on the degree and extent of this anti-inflammatory activity. In the present study, the inhibitory effects of different fractions of human milk on serum complement activity were analysed. Colostrum and milk samples from healthy voluntary lactating donors at different postpartum ages were obtained and pooled normal human serum was used as source of complement in a modified CH50 assay. Inherent complement activity in human milk was also investigated by measuring the deposition of an activated C3 fragment on a serum-sensitive bacteria, and by haemolytic assays. Most whole- and defatted-milk samples consistently showed a dose-dependent inhibition of the serum complement activity. This inhibition was greater in mature milk compared to transitional milk samples. It was enhanced by inactivation of milk complement, and diminished by centrifugation of milk samples, which partly removed fat and larger protein components including casein micelles. Inherent complement activity in human milk was also demonstrated by haemolysis of sensitised sheep erythrocytes and deposition of C3 fragments on solid-phase bacteria. These activities were highest in the colostrum and gradually decreased as lactation proceeded. Several natural components abundant in the fluid phase of the human breast-milk have been shown to be inhibitors of complement activation in vitro. Their physiological significance probably reside in their ability to prevent inflammatory-induced tissue damage of the delicate immature gastrointestinal tract of the new-born as well as the mammary gland itself, which may arise from ongoing complement activation.

Construction and Characterization of a Humanized Anti-Epstein-Barr Virus gp350 Antibody with Neutralizing Activity in Cell Culture

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Jerome E. Tanner

2018-04-01

Full Text Available Acute Epstein-Barr virus (EBV infection in immunosuppressed transplant patients can give rise to a malignant B-cell proliferation known as post-transplant lymphoproliferative disease (PTLD. The EBV major virion surface glycoprotein (gp350 is a principal target of naturally occurring neutralizing antibodies and is viewed as the best target to prevent acute infection and PTLD in at-risk transplant recipients. We have constructed a humanized (hu version of the murine anti-gp350 neutralizing monoclonal antibody 72a1. The hu72a1 IgG1 antibody displayed no significant anti-mouse activity, recognized both gp350 and its splice variant gp220 as well as a gp350 peptide that was shown to constitute the principal EBV gp350 neutralizing epitope when tested in immunoassays. Hu72a1 antibody blocked in vitro EBV infection of B cells at a level which equaled that of a mouse-human chimeric 72a1 antibody construct. This work provides a further structural and immunological understanding of the 72a1 antibody interaction with EBV gp350, and constitutes a launch point for future anti-EBV therapeutic antibodies designed to block EBV infection and prevent PTLD while eliminating the deleterious antigenic murine features of the original 72a1 antibody.

Effect of peripheral morphine in a human model of acute inflammatory pain

DEFF Research Database (Denmark)

Lillesø, J; Hammer, N A; Pedersen, J L

2000-01-01

Several studies have demonstrated the presence of opioid inducible receptors on peripheral nerves and peripheral antinociceptive effects of opioids. However, the effects of peripheral opioid administration in man are controversial. Our study used a randomized, double-blind, placebo-controlled, th......Several studies have demonstrated the presence of opioid inducible receptors on peripheral nerves and peripheral antinociceptive effects of opioids. However, the effects of peripheral opioid administration in man are controversial. Our study used a randomized, double-blind, placebo......-controlled, three-way crossover design in a human model of acute inflammatory pain (heat injury). We studied 18 healthy volunteers who each received morphine locally (2 mg), morphine systemically (2 mg), or placebo on three separate study days. The subjects received morphine infiltration subcutaneously (s.c.). 1 h......, but local morphine infiltration neither reduced pain during the burn, nor primary or secondary hyperalgesia to mechanical and heat stimuli after the burn. In conclusion, peripherally applied morphine had no acute antinociceptive effects in this human model of acute inflammatory pain....

Predominant antitumor effects by fully human anti-TRAIL-receptor2 (DR5) monoclonal antibodies in human glioma cells in vitro and in vivo

Science.gov (United States)

Nagane, Motoo; Shimizu, Saki; Mori, Eiji; Kataoka, Shiro; Shiokawa, Yoshiaki

2010-01-01

Tumor necrosis factor–related apoptosis-inducing ligand (TRAIL/Apo2 L) preferentially induces apoptosis in human tumor cells through its cognate death receptors DR4 or DR5, thereby being investigated as a potential agent for cancer therapy. Here, we applied fully human anti-human TRAIL receptor monoclonal antibodies (mAbs) to specifically target one of death receptors for TRAIL in human glioma cells, which could also reduce potential TRAIL-induced toxicity in humans. Twelve human glioma cell lines treated with several fully human anti-human TRAIL receptor mAbs were sensitive to only anti-DR5 mAbs, whereas they were totally insensitive to anti-DR4 mAb. Treatment with anti-DR5 mAbs exerted rapid cytotoxicity and lead to apoptosis induction. The cellular sensitivity was closely associated with cell-surface expression of DR5. Expression of c-FLIPL, Akt, and Cyclin D1 significantly correlated with sensitivity to anti-DR5 mAbs. Primary cultures of glioma cells were also relatively resistant to anti-DR5 mAbs, exhibiting both lower DR5 and higher c-FLIPL expression. Downregulation of c-FLIPL expression resulted in the sensitization of human glioma cells to anti-DR5 mAbs, whereas overexpression of c-FLIPL conferred resistance to anti-DR5 mAb. Treatment of tumor-burden nude mice with the direct agonist anti-DR5 mAb KMTR2 significantly suppressed growth of subcutaneous glioma xenografts leading to complete regression. Similarly, treatment of nude mice bearing intracerebral glioma xenografts with KMTR2 significantly elongated lifespan without tumor recurrence. These results suggest that DR5 is the predominant TRAIL receptor mediating apoptotic signals in human glioma cells, and sensitivity to anti-DR5 mAbs was determined at least in part by the expression level of c-FLIPL and Akt. Specific targeting of death receptor pathway through DR5 using fully human mAbs might provide a novel therapeutic strategy for intractable malignant gliomas. PMID:20511188

Human parvovirus B19 in childhood acute lymphoblastic leukaemia in Basrah.

Science.gov (United States)

Ibrahem, Wijdan Nazar; Hasony, Hassan Jaber; Hassan, Jenan Ghulam

2014-01-01

To investigate the association of human parvovirus B19 infection with the onset of acute lymphoblastic leukaemia and its effect on TEL-AML-1 fusion gene and the presence of mutant P53. The case-control study was conducted at Basrah Hospital for Paediatrics and Gynaecology, Basrah, Iraq, from May 2009 to April 2010. A total of 100 blood samples were collected from 40 newly diagnosed cases and 60 healthy children to serve as control matched by age and gender. Human parvovirus B19-IgG and anti-P53 antibody were detected by enzyme-linked immunosorbent assay and TEL-AML-1 fusion gene was detected by reverse transcriptase-polymerase chain reaction on extracted ribonucleic acid from fresh blood samples using specified primers. SPSS 15 was used for statistical analysis. A higher proportion of human parvovirus B19-positive cases was found in leukaemic patients (n=19; 47.5%) compared to 12 (20%) in the control group (pparvovirus-B19 infection as 10 (71.4%) of TEL-AML-1 translocation-positive cases had human parvovirus-B19 IgG. On the other hand, there was no association between such infections and P53 gene mutation in the patients. Human parvovirus-B19 infection is common in the population, with higher prevalence among leukaemic patients with significant association between human parvovirus-B19 and TEL-AML-1 fusion gene in patients of acute lymphoblastic leukaemia.

Acute nonsteroidal anti-inflammatory drug-induced colitis

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Massimo Tonolini

2013-01-01

Full Text Available Resulting from direct toxicity on the bowel mucosa, nonsteroidal anti-inflammatory drug (NSAID-induced colitis is an underestimated although potentially serious condition. Plain abdominal radiographs and multidetector computed tomography allow to identify a right-sided acute colitis with associated pericolonic inflammation, progressively diminished changes along the descending and sigmoid colon, and rectal sparing, consistent with the hypothesized pathogenesis of NSAID colitis. Increased awareness of this condition should reduce morbidity through both prevention and early recognition. High clinical suspicion and appropriate patient questioning, together with consistent instrumental findings, negative biochemistry, and stool investigations should help physicians not to miss this important diagnosis.

[A case of favourable outcome of severe acute intoxication with an animal poison after a bite by the monocled cobra].

Science.gov (United States)

Livanov, G A; Batotsyrenkov, B V; Lodiagin, A N; Andrianov, A Iu; Kuznetsov, O A; Loladze, A T; Baranov, D V

2014-01-01

This paper reports a case of severe acute intoxication with an animal poison after a bite by the monocled cobra. Combined treatment including artificial lung ventilation, infusion-detoxication and desensitizing (hormonal) therapy, hemosorption, correction of metabolic disorders with cytoflavin, antibacterial therapy had positive effect on the patient's condition and ensured the favourable outcome ofpotentially lethal poisoning without the use ofa specific anti-snake venom serum.

Prophylactic Treatment with Adlay Bran Extract Reduces the Risk of Severe Acute Radiation Dermatitis: A Prospective, Randomized, Double-Blind Study

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Chih-Jen Huang

2015-01-01

Full Text Available Acute radiation dermatitis is a frequent adverse effect in patients with breast cancer undergoing radiotherapy, but there are only a small number of studies providing evidence-based interventions for this clinical condition. Adlay is a cereal crop that has been previously shown to have anti-inflammatory and antioxidant properties. In this study, we seek to evaluate the effectiveness of oral prophylactic treatment with adlay bran extract in reducing the risk of severe acute radiation dermatitis. A total of 110 patients with breast cancer undergoing radiotherapy were analyzed. Using a prospective, randomized, double-blind design, 73 patients received oral treatment with adlay bran extract and 37 patients received olive oil (placebo. Treatment was started at the beginning of radiation therapy and continued until the termination of radiation treatment. Our results showed that the occurrence of severe acute radiation dermatitis (RTOG grade 2 or higher was significantly lower in patients treated with oral adlay bran extract compared to placebo (45.2% versus 75.7%, adjusted odds ratio 0.24. No serious adverse effects from adlay bran treatment were noted. In conclusion, prophylactic oral treatment with adlay bran extract reduces the risk of severe acute radiation dermatitis and may have potential use in patients with breast cancer undergoing radiotherapy.

Human Parvovirus B19 in childhood acute lymphoblastic leukaemia in basrah

International Nuclear Information System (INIS)

Ibrahem, W.N.; Hasony, H.J.; Hassan, J.G.

2014-01-01

Objective: To investigate the association of human parvovirus B19 infection with the onset of acute lymphoblastic leukaemia and its effect on TEL-AML-1 fusion gene and the presence of mutant P53. Methods: The case-control study was conducted at Basrah Hospital for Paediatrics and Gynaecology, Basrah, Iraq, from May 2009 to April 2010. A total of 100 blood samples were collected from 40 newly diagnosed cases and 60 healthy children to serve as control matched by age and gender. Human parvovirus B19-IgG and anti-P53 antibody were detected by enzyme-linked immunosorbent assay and TEL-AML-1 fusion gene was detected by reverse transcriptase-polymerase chain reaction on extracted ribonucleic acid from fresh blood samples using specified primers. SPSS 15 was used for statistical analysis. Results: A higher proportion of human parvovirus B19-positive cases was found in leukaemic patients (n=19; 47.5%) compared to 12 (20%) in the control group (p<0.05). There was significant association between Tel-Amyl-1 translocation and human parvovirus-B19 infection as 10 (71.4%) of TEL-AML-1 translocation-positive cases had human parvovirus-B19 IgG. On the other hand, there was no association between such infections and P53 gene mutation in the patients. Conclusion: Human parvovirus-B19 infection is common in the population, with higher prevalence among leukaemic patients with significant association between human parvovirus-B19 and TEL-AML-1 fusion gene in patients of acute lymphoblastic leukaemia. (author)

Etiology, Severity and Recurrence of Acute Pancreatitis in Southern Taiwan

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Chun-Hao Chen

2006-01-01

Conclusion: Alcoholic pancreatitis was the major etiology of acute pancreatitis in southern Taiwan, exhibiting a strong male predominance and higher risk of severe CT grading. Abnormal serum triglyceride was independently associated with the severity of acute pancreatitis. Alcoholic pancreatitis had a higher risk of recurrence than other etiologies.

Severe acute maternal morbidity and maternal death audit - a rapid ...

African Journals Online (AJOL)

Severe acute maternal morbidity and maternal death audit - a rapid diagnostic tool for evaluating maternal care. L Cochet, R.C. Pattinson, A.P. Macdonald. Abstract. Objective. To analyse severe acute maternal morbidity (SAMM) and maternal mortality in the Pretoria region over a 2-year period (2000 - 2001). Setting.

Identification of anti-virulence compounds that disrupt quorum-sensing regulated acute and persistent pathogenicity.

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Melissa Starkey

2014-08-01

Full Text Available Etiological agents of acute, persistent, or relapsing clinical infections are often refractory to antibiotics due to multidrug resistance and/or antibiotic tolerance. Pseudomonas aeruginosa is an opportunistic Gram-negative bacterial pathogen that causes recalcitrant and severe acute chronic and persistent human infections. Here, we target the MvfR-regulated P. aeruginosa quorum sensing (QS virulence pathway to isolate robust molecules that specifically inhibit infection without affecting bacterial growth or viability to mitigate selective resistance. Using a whole-cell high-throughput screen (HTS and structure-activity relationship (SAR analysis, we identify compounds that block the synthesis of both pro-persistence and pro-acute MvfR-dependent signaling molecules. These compounds, which share a benzamide-benzimidazole backbone and are unrelated to previous MvfR-regulon inhibitors, bind the global virulence QS transcriptional regulator, MvfR (PqsR; inhibit the MvfR regulon in multi-drug resistant isolates; are active against P. aeruginosa acute and persistent murine infections; and do not perturb bacterial growth. In addition, they are the first compounds identified to reduce the formation of antibiotic-tolerant persister cells. As such, these molecules provide for the development of next-generation clinical therapeutics to more effectively treat refractory and deleterious bacterial-human infections.

Structural Analysis of Major Species Barriers between Humans and Palm Civets for Severe Acute Respiratory Syndrome Coronavirus Infections

Energy Technology Data Exchange (ETDEWEB)

Li, Fang (UMM)

2008-09-23

It is believed that a novel coronavirus, severe acute respiratory syndrome coronavirus (SARS-CoV), was passed from palm civets to humans and caused the epidemic of SARS in 2002 to 2003. The major species barriers between humans and civets for SARS-CoV infections are the specific interactions between a defined receptor-binding domain (RBD) on a viral spike protein and its host receptor, angiotensin-converting enzyme 2 (ACE2). In this study a chimeric ACE2 bearing the critical N-terminal helix from civet and the remaining peptidase domain from human was constructed, and it was shown that this construct has the same receptor activity as civet ACE2. In addition, crystal structures of the chimeric ACE2 complexed with RBDs from various human and civet SARS-CoV strains were determined. These structures, combined with a previously determined structure of human ACE2 complexed with the RBD from a human SARS-CoV strain, have revealed a structural basis for understanding the major species barriers between humans and civets for SARS-CoV infections. They show that the major species barriers are determined by interactions between four ACE2 residues (residues 31, 35, 38, and 353) and two RBD residues (residues 479 and 487), that early civet SARS-CoV isolates were prevented from infecting human cells due to imbalanced salt bridges at the hydrophobic virus/receptor interface, and that SARS-CoV has evolved to gain sustained infectivity for human cells by eliminating unfavorable free charges at the interface through stepwise mutations at positions 479 and 487. These results enhance our understanding of host adaptations and cross-species infections of SARS-CoV and other emerging animal viruses.

Virus Type and Genomic Load in Acute Bronchiolitis: Severity and Treatment Response With Inhaled Adrenaline.

Science.gov (United States)

Skjerven, Håvard O; Megremis, Spyridon; Papadopoulos, Nikolaos G; Mowinckel, Petter; Carlsen, Kai-Håkon; Lødrup Carlsen, Karin C

2016-03-15

Acute bronchiolitis frequently causes infant hospitalization. Studies on different viruses or viral genomic load and disease severity or treatment effect have had conflicting results. We aimed to investigate whether the presence or concentration of individual or multiple viruses were associated with disease severity in acute bronchiolitis and to evaluate whether detected viruses modified the response to inhaled racemic adrenaline. Nasopharyngeal aspirates were collected from 363 infants with acute bronchiolitis in a randomized, controlled trial that compared inhaled racemic adrenaline versus saline. Virus genome was identified and quantified by polymerase chain reaction analyses. Severity was assessed on the basis of the length of stay and the use of supportive care. Respiratory syncytial virus (83%) and human rhinovirus (34%) were most commonly detected. Seven other viruses were present in 8%-15% of the patients. Two or more viruses (maximum, 7) were detected in 61% of the infants. Virus type or coinfection was not associated with disease severity. A high genomic load of respiratory syncytial virus was associated with a longer length of stay and with an increased frequency of oxygen and ventilatory support use. Treatment effect of inhaled adrenaline was not modified by virus type, load or coinfection. In infants hospitalized with acute bronchiolitis, disease severity was not associated with specific viruses or the total number of viruses detected. A high RSV genomic load was associated with more-severe disease. NCT00817466 and EudraCT 2009-012667-34. © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

ACUTE LYMPHOBLASTIC LEUKEMIA WITHOUT CIRCULATING BLASTS PRESENTING AS SEVERE HYPERCALCEMIA

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Z. Oloomi

2007-05-01

Full Text Available Hypercalcemia complicating malignancy is a rare complication in pediatric age group. In this article, we present a case with acute lymphoblastic leukemia presenting as severe hypercalcemia. A 10 years old girl presented with an acute onset of fever, nausea, vomiting, loss of weight, costovertebral pain and frequency. She was admitted with a presumptive diagnosis of acute pyelonephritis. Her examination showed mild hepatosplenomegaly. In laboratory studies she had sever hypercalcemia. Despite the absence of circulating blast, bone marrow aspiration was diagnostic of acute lymphoblastic leukemia. The hypercalcemia was initially treated with intravenous hydration and furosemide but the serum calcium levels normalized only after the beginning of specific chemotherapy. Hypercalcemia represents an emergency in children, and acute leukemia must be considered in differential diagnosis even when there are no circulating blasts.

Transcatheter embolization of pseudoaneurysms complicating acute severe pancreatitis

International Nuclear Information System (INIS)

Wu Hanping; Liang Huimin; Zheng Chuansheng; Feng Gansheng

2005-01-01

Objective: To evaluate the therapeutic roles of transcatheter embolization in patients with pseudoaneurysms complicating acute severe pancreatitis. Methods: Seven patients who suffered from pseudoaneurysms complicating acute severe pancreatitis received abdominal angiography and were treated with transcatheter embolization. The angiographic findings, complications related to the procedure and post- embolization, and rebleeding were observed. Results: The pseudoaneurysms developed at the splenic artery (n=5), right gastroepiploic artery (n=1), and left gastric artery (n=1), respectively. Findings of active bleeding were observed in 3 patients. Six of them were embolized with coils, and the bleedings were stopped immediately. Rebleeding occurred 14-60 days after the embolization in 3 patients, and in one of them, another pseudo aneurysm was observed in repeated angiography and was successfully treated by repeated embolization. No causes of bleeding were found in repeated angiography in the other 2 patients, who died from severe hemorrhage. One pseudo aneurysm was embolized with gelfoam granule. The gastrointestinal bleeding was not controlled and the patient died 3 days later. Procedure related complications occurred in 2 patients. One was celiac trunk rupture during angiography, the other was intima dissecting in splenic artery. Severe post procedure complications occurred in none of the patients. Conclusion: Transcatheter embolization is safe and relatively effective in the management of pseudoaneurysms complicating acute severe pancreatitis. (authors)

Diagnostic value of liver scintigraphy in fulminant hepatitis and severe acute hepatitis

International Nuclear Information System (INIS)

Shiomi, Susumu; Ikeoka, Naoko; Minowa, Takami; Kuroki, Tetsuo; Harihara, Shigeyoshi; Yamamoto, Sukeo; Ochi, Hironobu; Monna, Takeyuki

1985-01-01

Liver scintigraphy was performed in 12 cases with fulminant hepatitis, in 8 cases with severe acute hepatitis and in 44 cases with acute hepatitis. Scintiphotoes of severe hepatitis showed reduction of liver size, marked visualization of the bone marrow and the spleen, so this pattern was useful to differentiate from acute hepatitis. Relative size of the liver calculated by A.L.I. (anterior liver index) showed significant reduction in severe hepatitis compared with that of acute hepatitis. Three of five patients with died of severe hepatitis showed high uptake in the lung and ribs, but none of fifteen patients with severe hepatitis who recovered showed the abnormal accumulation in the lung and in the ribs. (author)

Management preferences of pediatricians in moderate and severe acute asthma.

Science.gov (United States)

Arga, Mustafa; Bakirtas, Arzu; Catal, Ferhat; Derinoz, Oksan; Topal, Erdem; Demirsoy, M Sadik; Turktas, Ipek

2013-05-01

To assess and compare management preferences of physicians for moderate and severe acute asthma based on case scenarios and to determine the factors influencing their decisions. A questionnaire based on the Global Initiative on Asthma (GINA) guideline and comprising eight questions on management of acute asthma was delivered to participants of two national pediatric congresses. Management of moderate and severe acute asthma cases was evaluated by two clinical case scenarios for estimation of acute attack severity, initial treatment, treatment after 1h, and discharge recommendations. A uniform answer box comprising the possible choices was provided just below the questions, and respondents were requested to tick the answers they thought was appropriate. Four-hundred and eighteen questionnaires were analyzed. All questions regarding moderate and severe acute asthma case scenarios were answered accurately by 15.8% and 17.0% of physicians, respectively. The initial treatment of moderate and severe cases was known by 100.0% and 78.2% of physicians, respectively. Knowledge of the appropriate plan for treatment after 1h was low both for moderate (45.0%) and severe attacks (35.4%). Discharge recommendations were adequate in 32.5% and 70.8% of physicians for moderate and severe attacks, respectively. Multiple logistic regression analysis revealed that working at a hospital with a continuing medical education program was the only significant predictor of a correct response to all questions regarding severe attacks (p = .04; 95%CI, 1.02-3.21). No predictors were found for information on moderate attacks. Pediatricians have difficulty in planning treatment after 1 hour both for moderate and severe asthma attacks. Postgraduate education programs that target physicians in hospitals without continuing medical education facilities may improve guideline adherence.

Young Children's Acute Stress After a Burn Injury: Disentangling the Role of Injury Severity and Parental Acute Stress.

Science.gov (United States)

Haag, Ann-Christin; Landolt, Markus A

2017-09-01

Although injury severity and parental stress are strong predictors of posttraumatic adjustment in young children after burns, little is known about the interplay of these variables. This study aimed at clarifying mediation processes between injury severity and mother's, father's, and young child's acute stress. Structural equation modeling was used to examine the relationships between injury severity and parental and child acute stress. Parents of 138 burn-injured children (ages 1-4 years) completed standardized questionnaires on average 19 days postinjury. Sixteen children (11.7%) met Diagnostic and Statistical Manual of Mental Disorders, 5th edition, preschool criteria for posttraumatic stress disorder (excluding time criterion). The model revealed a significant mediation of maternal acute stress, with the effect of injury severity on a child's acute stress mediated by maternal acute stress. Paternal acute stress failed to serve as a mediating variable. Our findings confirm mothers' crucial role in the posttraumatic adjustment of young children. Clinically, mothers' acute stress should be monitored. © 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

Non-oncogenic Acute Viral Infections Disrupt Anti-cancer Responses and Lead to Accelerated Cancer-Specific Host Death

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Frederick J. Kohlhapp

2016-10-01

Full Text Available In light of increased cancer prevalence and cancer-specific deaths in patients with infections, we investigated whether infections alter anti-tumor immune responses. We report that acute influenza infection of the lung promotes distal melanoma growth in the dermis and leads to accelerated cancer-specific host death. Furthermore, we show that during influenza infection, anti-melanoma CD8+ T cells are shunted from the tumor to the infection site, where they express high levels of the inhibitory receptor programmed cell death protein 1 (PD-1. Immunotherapy to block PD-1 reverses this loss of anti-tumor CD8+ T cells from the tumor and decreases infection-induced tumor growth. Our findings show that acute non-oncogenic infection can promote cancer growth, raising concerns regarding acute viral illness sequelae. They also suggest an unexpected role for PD-1 blockade in cancer immunotherapy and provide insight into the immune response when faced with concomitant challenges.

Study of chronic hemolytic anaemia patients in Rio de Janeiro: prevalence of anti-human parvovirus B19 IgG antibodies and the developement aplastic crises

Directory of Open Access Journals (Sweden)

SANT'ANNA Anadayr L.M.

2002-01-01

Full Text Available The prevalence of anti-human parvovirus B19 IgG antibodies was determined in sera from 165 chronic hemolytic anemia patients, receiving medical care at Instituto Estadual de Hematologia (IEHE, Rio de Janeiro, during the year of 1994. This sample represents around 10% of the chronic hemolytic anemia patients attending at IEHE. Most of these patients (140 have sickle cell disease. Anti-B19 IgG antibodies were detected in 32.1% of patients. No statistically significant difference (p > 0.05 was seen between IgG antibody prevalence in male (27.8% and female (35.5% patients. Anti-B19 IgG antibodies were more frequent in older (37.6% than younger (28.2% than 20 years old patients, although this difference had no statistical significance (p > 0.05. Anti-B19 IgG antibody prevalence showed that 67.9% of patients enrolled in the study were susceptible to B19 acute infection. With the aim to detect acute B19 infection, patients follow up continued until February 1996. During this period four patients presented transient aplastic crisis due to human parvovirus B19 as confirmed by the detection of specific IgM antibodies. All four patients were younger than 20 years old, and 3 were younger than 10 years old. Three of them were sickle cell disease patients. Three of the four acute B19 infection occurred during 1994 springtime.

Impact of Childhood Nutritional Status on Pathogen Prevalence and Severity of Acute Diarrhea.

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Tickell, Kirkby D; Pavlinac, Patricia B; John-Stewart, Grace C; Denno, Donna M; Richardson, Barbra A; Naulikha, Jaqueline M; Kirera, Ronald K; Swierczewski, Brett E; Singa, Benson O; Walson, Judd L

2017-11-01

Children with acute and chronic malnutrition are at increased risk of morbidity and mortality following a diarrheal episode. To compare diarrheal disease severity and pathogen prevalence among children with and without acute and chronic malnutrition, we conducted a cross-sectional study of human immunodeficiency virus-uninfected Kenyan children aged 6-59 months, who presented with acute diarrhea. Children underwent clinical and anthropometric assessments and provided stool for bacterial and protozoal pathogen detection. Clinical and microbiological features were compared using log binomial regression among children with and without wasting (mid-upper arm circumference ≤ 125 mm) or stunting (height-for-age z score ≤ -2). Among 1,363 children, 7.0% were wasted and 16.9% were stunted. After adjustment for potential confounders, children with wasting were more likely than nonwasted children to present with at least one Integrated Management of Childhood Illness danger sign (adjusted prevalence ratio [aPR]: 1.3, 95% confidence interval [CI]: 1.0 to 1.5, P = 0.05), severe dehydration (aPR: 2.4, 95% CI: 1.5 to 3.8, P malnutrition which may be explained by a delay in care-seeking or diminished immune response to infection. Combating social determinants and host risk factors associated with severe disease, rather than specific pathogens, may reduce the disparities in poor diarrhea-associated outcomes experienced by malnourished children.

[PREVENTION AND CORRECTION OF PULMONARY COMPLICATIONS FOR SEVERE ACUTE PANCREATITIS].

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Fedorkiv, M B

2015-06-01

Increased of proinflammatory cytokines levels, including interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-alpha) on severe acute pancreatitis causes vasodilatation, increased permeability of the wall, accumulation of fluid in lung tissue and pleural sinuses. Transudate from acute parapancreatyc clusters of hot liquid and abdomen falls into the chest cavity through microscopic defects in the diaphragm due to the formation of pathological pleural-peritoneal connections or the relevant pressure gradient between the abdominal and pleural cavities. Remediation and removal of acute parapancreatyc clusters combined with the use of a multicomponent drug infusion therapy Cytoflavin provide a reduction in the frequency of pulmonary complications of acute pancreatitis from 48.3 to 31.0%. Use of the drug Cytoflavin reduces the severity of endogenous intoxication and mortality from acute lung injury from 12.9 to 6.1%.

Determinant-Based Classification of Acute Pancreatitis Severity: An International Multidisciplinary Consultation

NARCIS (Netherlands)

Dellinger, E.P.; Forsmark, C.E.; Layer, P.; Levy, P.; Maravi-Poma, E.; Petrov, M.S.; Shimosegawa, T.; Siriwardena, A.K.; Uomo, G.; Whitcomb, D.C.; Windsor, J.A.; Geenen, E.J.M. van; et al.,

2012-01-01

OBJECTIVE:: To develop a new international classification of acute pancreatitis severity on the basis of a sound conceptual framework, comprehensive review of published evidence, and worldwide consultation. BACKGROUND:: The Atlanta definitions of acute pancreatitis severity are ingrained in the

International Multidisciplinary Classification of Acute Pancreatitis Severity: The 2013 Spanish Edition

NARCIS (Netherlands)

Maraví-Poma, E.; Patchen Dellinger, E.; Forsmark, C. E.; Layer, P.; Lévy, P.; Shimosegawa, T.; Siriwardena, A. K.; Uomo, G.; Whitcomb, D. C.; Windsor, J. A.; Petrov, M. S.; Abu Hilal, M.; Abu-Zidan, F. M.; Acosta, J. M.; Ainsworth, A. P.; Aizcorbe Garralda, M.; Alagozlu, H.; Al'aref, S. J.; Albeniz Arbizu, E.; Alhajeri, A.; Almeida, J. L.; Ammori, B. J.; Andersson, R.; Ardengh, J. C.; Arroyo-Sanchez, A. S.; Arvanitakis, M.; Ashley, S. W.; Aygencel, G.; Ayoub, W. A.; Baillie, J.; Bala, M.; Ball, C. G.; Banks, P. A.; Baron, T. H.; Barreto, S. G.; Basaranoglu, M.; Beger, H. G.; Bernal Monterde, V.; Besselink, M. G.; Bharwani, N.; Bhasin, D. K.; Bong, J. J.; Botoi, G.; Bruennler, T.; Bruno, M. J.; Cairoli, E.; Carter, C. R.; Cernea, D.; Chari, S. T.; Chooklin, S.

2014-01-01

Objective: To develop a new classification of acute pancreatitis severity on the basis of a sound conceptual framework, comprehensive review of the published evidence, and worldwide consultation. Backgrounds: The Atlanta definitions of acute pancreatitis severity are ingrained in the lexicon of

Plasma total anti-oxidant capacity correlates inversely with the extent of acute appendicitis: a case control study

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Devay Seda

2006-03-01

Full Text Available Abstract Background The role of free oxygen radicals in inflammatory conditions is well known. Free radicals cause lipid peroxidation of cellular membranes resulting in cell death. The purpose of this study was to investigate the levels of total anti-oxidant status (TAS, as a marker of anti-oxidant defense system and malondialdehyde (MDA, as a marker of oxidative stress, in the plasma of patients with acute appendicitis. Methods Fifty-one adult patients with a median age of 31 years who underwent operations with a preoperative diagnosis of acute appendicitis were included in this prospective study. Blood samples for C-reactive protein (CRP, MDA and TAS were collected preoperatively. Groups were compared by using the Mann-Whitney U test. Results There were 27 patients with acute phlagmenous appendicitis and 19 patients with advanced appendicitis (10 gangrenous and 9 perforated appendicitis, while 5 negative explorations were documented. No significant differences in WBC counts and MDA levels between groups were encountered. Plasma CRP was significantly higher in patients with perforated appendicitis, but not in the other groups. In advanced appendicitis group, TAS level was significantly lower than the other groups. On the other hand, plasma TAS level in acute phlagmenous appendicitis group was significantly higher. Conclusion A decrease in plasma total anti-oxidant capacity might be a predictor of the progression of inflammation to the perforation in acute appendicitis.

Anti-C1q autoantibodies in patients with neuromyelitis optica spectrum disorders.

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Yoshikura, Nobuaki; Kimura, Akio; Hayashi, Yuichi; Inuzuka, Takashi

2017-09-15

We examined anti-complement C1q (C1q) autoantibody levels in serum and cerebrospinal fluid (CSF) samples of patients with neuromyelitis optica spectrum disorders (NMOSD). We analyzed the correlations between anti-C1q autoantibody levels and the clinical and other CSF characteristics of NMOSD. Serum and CSF anti-C1q autoantibody levels increased during the acute phase of NMOSD, reverting to the same levels as controls during remission. CSF anti-C1q autoantibody levels during the acute phase correlated with several markers reflecting disease severity, Expanded Disability Status Scale worsening, spinal cord lesion length in cases with myelitis, CSF protein and interleukin-6 levels, and CSF/serum albumin ratios. Copyright © 2017 Elsevier B.V. All rights reserved.

Gammaherpesvirus Co-infection with Malaria Suppresses Anti-parasitic Humoral Immunity.

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Caline G Matar

2015-05-01

Full Text Available Immunity to non-cerebral severe malaria is estimated to occur within 1-2 infections in areas of endemic transmission for Plasmodium falciparum. Yet, nearly 20% of infected children die annually as a result of severe malaria. Multiple risk factors are postulated to exacerbate malarial disease, one being co-infections with other pathogens. Children living in Sub-Saharan Africa are seropositive for Epstein Barr Virus (EBV by the age of 6 months. This timing overlaps with the waning of protective maternal antibodies and susceptibility to primary Plasmodium infection. However, the impact of acute EBV infection on the generation of anti-malarial immunity is unknown. Using well established mouse models of infection, we show here that acute, but not latent murine gammaherpesvirus 68 (MHV68 infection suppresses the anti-malarial humoral response to a secondary malaria infection. Importantly, this resulted in the transformation of a non-lethal P. yoelii XNL infection into a lethal one; an outcome that is correlated with a defect in the maintenance of germinal center B cells and T follicular helper (Tfh cells in the spleen. Furthermore, we have identified the MHV68 M2 protein as an important virus encoded protein that can: (i suppress anti-MHV68 humoral responses during acute MHV68 infection; and (ii plays a critical role in the observed suppression of anti-malarial humoral responses in the setting of co-infection. Notably, co-infection with an M2-null mutant MHV68 eliminates lethality of P. yoelii XNL. Collectively, our data demonstrates that an acute gammaherpesvirus infection can negatively impact the development of an anti-malarial immune response. This suggests that acute infection with EBV should be investigated as a risk factor for non-cerebral severe malaria in young children living in areas endemic for Plasmodium transmission.

Semiquantitative dynamic computed tomography to predict response to anti-platelet therapy in acute cerebral infarction

International Nuclear Information System (INIS)

Chokyu, K.; Shimizu, K.; Fukumoto, M.; Mori, T.; Mokudai, T.; Mori, K.

2002-01-01

We investigated whether dynamic computed tomography (CT) in patients with acute cerebral infarction could identify patients likely to respond to anti-platelet therapy. Seventy patients underwent semiquantitative dynamic CT within 6 h as well as cerebral angiography. All then received anti-platelet therapy with a thromboxane A2 synthetase inhibitor. Peak value (pv) and time-to-peak (tp) (time-density curves) for the Sylvian fissure were extracted from dynamic CT data and standardizing interpatient data, two indices, PV/TP index and TP index, were prepared following a standard semiquantitative manner. Both PV/TP index and TP index were effective in discriminating between 48 responders (modified Rankin scale (mRS): 0 to 2) and 22 non-responders (mRS: 3 to 5, or death: 6; both P 1.1) and non-compensated rCBF. Intermediate PV/TP values could not predict outcome. Dynamic CT prior to therapy can identify patients with acute cerebral infarction who are treatable with anti-platelet therapy alone. (orig.)

Microbiota is immature in moderate and severe acute malnutrition

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Ahmed, Tahmeed

2014-01-01

Full text: Globally 19 million under-five children suffer from severe acute malnutrition (SAM) while 51.5 million children have moderate acute malnutrition (MAM). These two conditions, together known as acute malnutrition, are responsible for 14.6% of all under-five deaths. Case fatality rate can be reduced with treatment of SAM, which however, is not readily available everywhere. Even with effective treatment, recovery can be slow and relapse not uncommon. Lack of nutrients is one of the causes of acute malnutrition but other factors including infections, inter- and intra-generational factors are also believed to play important roles in the etiology. The gut microbiota is another factor; however its relationship with nutritional interventions and therapeutic response is poorly understood. We studied the gut microbiota of children suffering from severe and moderate acute malnutrition in Bangladesh. Children with SAM were studied during the acute phase, nutritional rehabilitation and follow up in icddr,b Hospital, Dhaka. During the nutritional rehabilitation phase, the children were randomized to either RUTF or a combination of local diets (khichuri and halwa). Children with MAM were randomly selected from a birth cohort in a slum settlement and so were healthy controls. Gut microbiota were identified using 16S rRNA datasets generated from monthly fecal samples obtained from the healthy control children. ‘Relative microbiota maturity index’ and ‘microbiota-for-age Z-score’ were computed from a model developed from the age-discriminatory bacterial species identified in the healthy and acutely malnourished children. The index and the Z-score compare maturation of an acutely malnourished child’s fecal microbiota relative to healthy children of similar chronological age. Our results indicate that SAM is associated with relative immaturity of the gut microbiota. Moreover, treatment with either RUTF or the local diets is associated with incomplete recovery of

Protective Effect of Tetrandrine on Sodium Taurocholate-Induced Severe Acute Pancreatitis

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Xian-lin Wu

2015-01-01

Full Text Available Tet is a type of alkaloid extracted from Stephania tetrandra, and it has recently been demonstrated that Tet can protect against inflammation and free radical injury and inhibit the release of inflammatory mediators. The present study was designed to observe the protective effect of Tet on sodium taurocholate-induced severe acute pancreatitis (SAP. The rat model of SAP was induced by retrograde bile duct injection of sodium taurocholate and then treated with Verapamil and Tet. The results showed that Tet can reduce NF-κB activation in pancreas issue, inhibit the SAP cascade, and improve SAP through inducing pancreas acinar cell apoptosis and stabilizing intracellular calcium in the pancreas, thus mitigating the damage to the pancreas. Our study revealed that Tet may reduce systemic inflammatory response syndrome (SIRS and multiple organ dysfunction syndromes (MODS to protect against damage, and these roles may be mediated through the NF-κB pathway to improve the proinflammatory/anti-inflammatory imbalance.

Anti-Inflammatory Effects of Licorice and Roasted Licorice Extracts on TPA-Induced Acute Inflammation and Collagen-Induced Arthritis in Mice

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Ki Rim Kim

2010-01-01

Full Text Available The anti-inflammatory activity of licorice (LE and roated licorice (rLE extracts determined in the murine phorbol ester-induced acute inflammation model and collagen-induced arthritis (CIA model of human rheumatoid arthritis. rLE possessed greater activity than LE in inhibiting phorbol ester-induced ear edema. Oral administration of LE or rLE reduced clinical arthritis score, paw swelling, and histopathological changes in a murine CIA. LE and rLE decreased the levels of proinflammatory cytokines in serum and matrix metalloproteinase-3 expression in the joints. Cell proliferation and cytokine secretion in response to type II collagen or lipopolysaccharide stimulation were suppressed in spleen cells from LE or rLE-treated CIA mice. Furthermore, LE and rLE treatment prevented oxidative damages in liver and kidney tissues of CIA mice. Taken together, LE and rLE have benefits in protecting against both acute inflammation and chronic inflammatory conditions including rheumatoid arthritis. rLE may inhibit the acute inflammation more potently than LE.

Severe acute respiratory syndrome: lessons and uncertainties.

NARCIS (Netherlands)

Kullberg, B.J.; Voss, A.

2003-01-01

The outbreak of severe acute respiratory syndrome (SARS) has produced scientific and epidemiological discoveries with unprecedented speed, and this information has been spread instantaneously to the global health community through the internet. Within a few weeks, the coronavirus associated with

Systematic review of severe acute liver injury caused by terbinafine.

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Yan, Jun; Wang, Xiaolin; Chen, Shengli

2014-08-01

Terbinafine is an effective antimicrobial agent against dermatophytes, cryptococcus and other fungi. It is the preferred drug to treat onychomycosis. However, severe acute hepatitis from oral terbinafine administration has been recently reported. To describe a representative case, and review the literature regarding the best evidence on treatment and prognosis of severe acute hepatitis caused by oral terbinafine. The literature was searched for publications on severe hepatitis caused by terbinafine using MEDLINE, China Biology Medicine Disc, and the VIP Medical Information Resource System. Related references were searched manually. Seventeen English and three Chinese references of case reports were included after eliminating duplicate publications. No randomized control studies were found. Liver enzyme levels were found to have been increased significantly. Abdominal ultrasound demonstrated cholestasis. Severe acute liver injury is a known, but unusual complication of terbinafine exposure. The prognosis is often good with appropriate treatment. Liver function assessment before treatment and periodic monitoring 4-6 weeks after initiation of treatment is recommended.

Role of bedside index for severity of acute pancreatitis (bisap score in predicting outcome in acute pancreatitis

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Shahnawaz Bashir Bhat

2015-12-01

Full Text Available Objective: To investigate the role of Bedside index for severity of acute pancreatitis (BISAP score in predicting the outcome of acute pancreatitis. Methods: This single hospital based prospective study included fifty patients of acute pancreatitis admitted within 48 hours of onset of symptoms, who were divided into two groups according to admission BISAP score. BISAP score 3 (severe acute pancreatitis. The ability of BISAP score to predict mortality, morbidity and hospital stay in acute pancreatitis patients was analyzed. Results: A BISAP score of >3 was associated with increased risk of development of transient organ failure, persistent organ failure and pancreatic necrosis (Statistically significant. Mortality in group with BISAP and #8805;3 was 23.5% (4 patients which was statistically higher than group with BISAP score and #706;3 (0 patients (p=0.019.The mean duration of hospital stay of patients in group with BISAP score < 3 was 7.58 +/- 4.04 days and in group with BISAP score and #8805;3 was 15.35 +/- 1.66.(p=0.02. Conclusion: Bedside index for severity in acute pancreatitis (BISAP score, at admission is an excellent score in predicting the mortality, morbidity and hospital stay and hence management protocol in patients admitted with acute pancreatitis. [J Contemp Med 2015; 5(4.000: 215-220

Assessment of PANC3 score in predicting severity of acute pancreatitis

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Avreen Singh Shah

2017-01-01

Full Text Available Introduction: Acute pancreatitis is inflammatory process of the pancreas associated with local and systemic complications. At present, there are lots of scores (such as Ransons, APACHE II, bedside index for severity in acute pancreatitis that help us in predicting severity at the time of admission but these are time consuming or require complex calculation and are costly. Material and Methods: PANC3 Scoring System is one of the better systems because the three criteria used (hematocrit, body mass index, and pleural effusion are simple, easy to assess, readily available, and economic. In this prospective study, 100 cases were evaluated to see the prospects of PANC3 scoring in predicting the severity of acute pancreatitis as decided by modified Marshals score. Results: The results showed that PANC3 score had a 96.43% specificity, 75% sensitivity, 80% positive predictive value, and 95.29% negative predictive value. Conclusion: Hence, the PANC3 score is a cost-effective, promising score that helps in predicting the severity of acute pancreatitis leading to prompt treatment and early referral to higher center.

Human Physiological Responses to Acute and Chronic Cold Exposure

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Stocks, Jodie M.; Taylor, Nigel A. S.; Tipton, Michael J.; Greenleaf, John E.

2001-01-01

When inadequately protected humans are exposed to acute cold, excessive body heat is lost to the environment and unless heat production is increased and heat loss attenuated, body temperature will decrease. The primary physiological responses to counter the reduction in body temperature include marked cutaneous vasoconstriction and increased metabolism. These responses, and the hazards associated with such exposure, are mediated by a number of factors which contribute to heat production and loss. These include the severity and duration of the cold stimulus; exercise intensity; the magnitude of the metabolic response; and individual characteristics such as body composition, age, and gender. Chronic exposure to a cold environment, both natural and artificial, results in physiological alterations leading to adaptation. Three quite different, but not necessarily exclusive, patterns of human cold adaptation have been reported: metabolic, hypothermic, and insulative. Cold adaptation has also been associated with an habituation response, in which there is a desensitization, or damping, of the normal response to a cold stress. This review provides a comprehensive analysis of the human physiological and pathological responses to cold exposure. Particular attention is directed to the factors contributing to heat production and heat loss during acute cold stress, and the ability of humans to adapt to cold environments.

Case report: Severe hemolytic disease of the fetus and newborn due to anti-C+G.

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Jernman, Riina; Stefanovic, Vedran; Korhonen, Anu; Haimila, Katri; Sareneva, Inna; Sulin, Kati; Kuosmanen, Malla; Sainio, Susanna

2015-01-01

Anti-G is commonly present with anti-D and/or anti-C and can confuse serological investigations. in general, anti-G is not considered a likely cause of severe hemolytic disease of the fetus and newborn (HDFN), but it is important to differentiate it from anti-D in women who should be administered anti-D immunoglobulin prophylaxis. We report one woman with three pregnancies severely affected by anti-C+G requiring intrauterine treatment and a review of the literature. In our case, the identification of the correct antibody was delayed because the differentiation of anti-C+G and anti-D+C was not considered important during pregnancy since the father was D-. In addition, anti-C+G and anti-G titer levels were not found to be reliable as is generally considered in Rh immunization. Severe HDFN occurred at a maternal anti-C+G antibody titer of S and anti-G titer of 1 in comparison with the critical titer level of 16 or more in our laboratory. close collaboration between the immunohematology laboratory and the obstetric unit is essential. In previously affected families, early assessment for fetal anemia is required even when titers are low.

Halofuginone has anti-proliferative effects in acute promyelocytic leukemia by modulating the transforming growth factor beta signaling pathway.

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Lorena L de Figueiredo-Pontes

Full Text Available Promyelocytic leukemia-retinoic acid receptor alpha (PML-RARα expression in acute promyelocytic leukemia (APL impairs transforming growth factor beta (TGFβ signaling, leading to cell growth advantage. Halofuginone (HF, a low-molecular-weight alkaloid that modulates TGFβ signaling, was used to treat APL cell lines and non-obese diabetic/severe combined immunodeficiency (NOD/SCID mice subjected to transplantation with leukemic cells from human chorionic gonadotrophin-PML-RARα transgenic mice (TG. Cell cycle analysis using incorporated bromodeoxyuridine and 7-amino-actinomycin D showed that, in NB4 and NB4-R2 APL cell lines, HF inhibited cellular proliferation (P<0.001 and induced apoptosis (P = 0.002 after a 24-hour incubation. Addition of TGFβ revealed that NB4 cells were resistant to its growth-suppressive effects and that HF induced these effects in the presence or absence of the cytokine. Cell growth inhibition was associated with up-regulation of TGFβ target genes involved in cell cycle regulation (TGFB, TGFBRI, SMAD3, p15, and p21 and down-regulation of MYC. Additionally, TGFβ protein levels were decreased in leukemic TG animals and HF in vivo could restore TGFβ values to normal. To test the in vivo anti-leukemic activity of HF, we transplanted NOD/SCID mice with TG leukemic cells and treated them with HF for 21 days. HF induced partial hematological remission in the peripheral blood, bone marrow, and spleen. Together, these results suggest that HF has anti-proliferative and anti-leukemic effects by reversing the TGFβ blockade in APL. Since loss of the TGFβ response in leukemic cells may be an important second oncogenic hit, modulation of TGFβ signaling may be of therapeutic interest.

Acute myocardial infarction as first manifestation of primary anti phospholipid syndrome in a twenty-four years old patient

International Nuclear Information System (INIS)

Uribe, Carlos E; Cardenas, Juan M; Cabrales, Jaime; Bohorquez, Ricardo; Roa, Nubia I; Beltran, Javier; Urina, Manuel

2005-01-01

Primary anti phospholipid syndrome is usually manifested with deep venous thrombosis, pulmonary thromboembolism and arterial thrombosis, including cerebrovascular accidents. We report the case of a previously healthy young patient who suffered acute myocardial infarction as the first manifestation of a primary anti phospholipid syndrome

[Multidisciplinar international classification of the severity of acute pancreatitis: Italian version 2013].

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Uomo, G; Patchen Dellinger, E; Forsmark, C E; Layer, P; Lévy, P; Maravì-Poma, E; Shimosegawa, T; Siriwardena, A K; Whitcomb, D C; Windsor, J A; Petrov, M S

2013-12-01

The aim of this paper was to present the 2013 Italian edition of a new international classification of acute pancreatitis severity. The Atlanta definitions of acute pancreatitis severity are ingrained in the lexicon of pancreatologists but suboptimal because these definitions are based on empiric description of occurrences that are merely associated with severity. A personal invitation to contribute to the development of a new international classification of acute pancreatitis severity was sent to all surgeons, gastroenterologists, internists, intensivists, and radiologists who are currently active in clinical research on acute pancreatitis. A global web-based survey was conducted and a dedicated international symposium was organized to bring contributors from different disciplines together and discuss the concept and definitions. The new international classification is based on the actual local and systemic determinants of severity, rather than description of events that are correlated with severity. The local determinant relates to whether there is (peri)pancreatic necrosis or not, and if present, whether it is sterile or infected. The systemic determinant relates to whether there is organ failure or not, and if present, whether it is transient or persistent. The presence of one determinant can modify the effect of another such that the presence of both infected (peri)pancreatic necrosis and persistent organ failure have a greater effect on severity than either determinant alone. The derivation of a classification based on the above principles results in 4 categories of severity-mild, moderate, severe, and critical. This classification provides a set of concise up-to-date definitions of all the main entities pertinent to classifying the severity of acute pancreatitis in clinical practice and research.

Design, synthesis, and structure–activity relationships of 2-benzylidene-1-indanone derivatives as anti-inflammatory agents for treatment of acute lung injury

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Xiao S

2018-04-01

Full Text Available Siyang Xiao,1,* Wenxin Zhang,1,* Hongjin Chen,1 Bo Fang,1 Yinda Qiu,2 Xianxin Chen,1 Lingfeng Chen,1 Sheng Shu,1 Yunjie Zhao,1 Zhiguo Liu,1 Guang Liang1 1Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China; 2College of Life and Environmental Science, Wenzhou University, Wenzhou, Zhejiang, China *These authors contributed equally to this work Purpose: The purpose of this study was to design and synthesize novel 2-benzylidene-1-indanone derivatives for treatment of acute lung injury. Methods: A series of 39 novel 2-benzylidene-indanone structural derivatives were synthesized and evaluated for anti-inflammatory activity in lipopolysaccharide (LPS-stimulated murine primary macrophages. Results: Most of the obtained compounds effectively inhibited the LPS-induced expression of IL-6 and TNF-α. The most active compound, 8f, was found to significantly reduce LPS-induced pulmonary inflammation, as reflected by reductions in the concentration of total protein, inflammatory cell count, as well as the lung wet/dry ratio in bronchoalveolar lavage (BAL fluid. Furthermore, 8f effectively inhibited mRNA expression of several inflammatory cytokines after LPS challenge in vitro and in vivo. Administration of 8f also blocked LPS-induced activation of the proinflammatory NF-κB/MAPK signaling pathway. Conclusion: The simple synthetic preparation and biological properties of these derivatives make these 2-benzylidene-indanone scaffolds promising new entities for the development of anti-inflammatory therapeutics for the treatment of acute lung injury. Keywords: indanone, acute lung injury, drug design, anti-inflammation, synthesis

Severe hypertriglyceridemia in diabetic ketoacidosis accompanied by acute pancreatitis: case report.

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Hahn, Suk Jae; Park, Jung-hyun; Lee, Jong Ho; Lee, Jun Kyu; Kim, Kyoung-Ah

2010-09-01

We report a case of diabetic ketoacidosis (DKA) and hypertriglyceridemia (severely elevated to 15,240 mg/dL) complicated by acute pancreatitis, which was treated successfully with insulin therapy and conservative management. A 20-yr-old woman with a history of type 1 diabetes came to the emergency department 7 months after discontinuing insulin therapy. DKA, severe hypertriglyceridemia and acute pancreatitis were diagnosed, with DKA suspected of contributing to the development of the other conditions. In Korea, two cases of DKA-induced hypertriglyceridemia and 13 cases of hypertriglyceridemia-induced acute pancreatitis have been previously reported separately.

Sitaxsentan-Induced Acute Severe Hepatitis Treated with Glucocorticoid Therapy

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Marcus W Chin

2012-01-01

Full Text Available Endothelin receptor antagonists are commonly used in the treatment of pulmonary hypertension. Sitaxsentan, a selective endothelin A receptor blocker, induces a mild transaminitis in approximately 3% to 5% of patients, but rarely an acute severe hepatitis. A case involving a 61-year-old female with sitaxsentan-induced acute severe liver failure is presented. Depite withdrawal of therapy, her liver tests failed to improve. After six weeks of monitoring, the patient was administered high-dose corticosteroids, with a good clinical and biochemical response. While endothelin receptor antagonists are postulated to cause hepatitis by inhibition of a bile salt transporter pump, an immune-mediated or idiosyncratic mechanism should be considered.

VGKC complex antibodies in pediatric severe acute encephalitis: a study and literature review.

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Lin, Jainn-Jim; Lin, Kuang-Lin; Hsia, Shao-Hsuan; Wang, Huei-Shyong; Chiu, Cheng-Hsun; CHEESE Study Group

2013-08-01

Antibodies to surface proteins like voltage-gated potassium channel (VGKC) complexes are increasingly found in different neurologic diseases and encephalitis in adults and recently, in children. Detecting such antibodies can help identify forms of encephalitis that may respond to immuno-therapies. However, there are few reports on VGKC complex antibodies in pediatric severe acute encephalitis. This study retrospectively reviewed antibodies to VGKC, leucine-rich glioma-inactivated 1 (Lgi1), and contactin-associated protein-like 2 (Caspr2) in 46 children with severe acute encephalitis. Published cases of VGKC complex antibodies in pediatric encephalitis in the period of 2000-2012 were also reviewed. Elevated VGKC complex antibodies (>100pM) were detected in one of the 46 children with severe acute encephalitis. The 4-year and 6-month-old girl presented with seizure and disturbed consciousness. Viral PCR/culture and serologic evidence of influenza A infection was noted. She also had complications of epilepsy, impaired cognition, and altered behavior and psychology. Antibodies to Lgi1 and Caspr2 were not detected. Ten previously published reports revealed that VGKC complex antibodies can occur in children with limbic encephalitis and acute or sub-acute encephalitis. The incidence of VGKC complex antibodies in pediatric severe acute encephalitis is not high with only one (2.2%) of 46 children in this study. And, this is the first report on the association of VGKC complex antibodies and patients with influenza A-related severe acute encephalitis. The mechanism of VGKC complex antibodies in pediatric severe acute encephalitis warrants further study. Copyright © 2012 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Severe asthma exacerbation: role of acute Chlamydophila pneumoniae and Mycoplasma pneumoniae infection.

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Cosentini, Roberto; Tarsia, Paolo; Canetta, Ciro; Graziadei, Giovanna; Brambilla, Anna Maria; Aliberti, Stefano; Pappalettera, Maria; Tantardini, Francesca; Blasi, Francesco

2008-05-30

Chlamydophila pneumoniae and Mycoplasma pneumoniae are associated with acute exacerbation of bronchial asthma (AEBA). The aim of this study was to evaluate the correlation between these acute bacterial infections and the severity of AEBA. We prospectively analysed consecutive patients admitted to the Emergency Department with acute asthma exacerbation. In every patient peak expiratory flow (PEF) measurement was performed on admission, and spirometry during follow-up. Serology for Chlamydophila and Mycoplasma pneumoniae was performed on admission and after 4-8 weeks. Fifty-eight patients completed the study. Acute atypical infections (AAI) was observed in 22/58 cases; we found single acute C. pneumoniae in 19 cases, single acute M. pneumoniae in 2 cases, and double acute infection in one case. Functional impairment on admission was greater in patients with AAI than in patients without AAI (PEF 205 +/- 104 L/min vs 276 +/- 117 p = 0.02) and persisted until visit 2 (FEV1% 76.30 +/- 24.54 vs FEV1% 92.91 +/- 13.89, p = 0.002). Moreover, the proportion of patients who presented with severe AEBA was significantly greater in the group with AAI than in the group without AAI (15/22 vs 12/36, p = 0.01; OR 4.29, 95% CI 1.38-13.32). Our data suggest an association between acute atypical infection and a more severe AEBA.

Design, synthesis, and structure-activity relationships of 2-benzylidene-1-indanone derivatives as anti-inflammatory agents for treatment of acute lung injury.

Science.gov (United States)

Xiao, Siyang; Zhang, Wenxin; Chen, Hongjin; Fang, Bo; Qiu, Yinda; Chen, Xianxin; Chen, Lingfeng; Shu, Sheng; Zhang, Yali; Zhao, Yunjie; Liu, Zhiguo; Liang, Guang

2018-01-01

The purpose of this study was to design and synthesize novel 2-benzylidene-1-indanone derivatives for treatment of acute lung injury. A series of 39 novel 2-benzylidene-indanone structural derivatives were synthesized and evaluated for anti-inflammatory activity in lipopolysaccharide (LPS)-stimulated murine primary macrophages. Most of the obtained compounds effectively inhibited the LPS-induced expression of IL-6 and TNF-α. The most active compound, 8f , was found to significantly reduce LPS-induced pulmonary inflammation, as reflected by reductions in the concentration of total protein, inflammatory cell count, as well as the lung wet/dry ratio in bronchoalveolar lavage (BAL) fluid. Furthermore, 8f effectively inhibited mRNA expression of several inflammatory cytokines after LPS challenge in vitro and in vivo. Administration of 8f also blocked LPS-induced activation of the proinflammatory NF-κB/MAPK signaling pathway. The simple synthetic preparation and biological properties of these derivatives make these 2-benzylidene-indanone scaffolds promising new entities for the development of anti-inflammatory therapeutics for the treatment of acute lung injury.

Design, synthesis, and structure–activity relationships of 2-benzylidene-1-indanone derivatives as anti-inflammatory agents for treatment of acute lung injury

Science.gov (United States)

Chen, Hongjin; Fang, Bo; Qiu, Yinda; Chen, Xianxin; Chen, Lingfeng; Shu, Sheng; Zhang, Yali; Zhao, Yunjie; Liu, Zhiguo; Liang, Guang

2018-01-01

Purpose The purpose of this study was to design and synthesize novel 2-benzylidene-1-indanone derivatives for treatment of acute lung injury. Methods A series of 39 novel 2-benzylidene-indanone structural derivatives were synthesized and evaluated for anti-inflammatory activity in lipopolysaccharide (LPS)-stimulated murine primary macrophages. Results Most of the obtained compounds effectively inhibited the LPS-induced expression of IL-6 and TNF-α. The most active compound, 8f, was found to significantly reduce LPS-induced pulmonary inflammation, as reflected by reductions in the concentration of total protein, inflammatory cell count, as well as the lung wet/dry ratio in bronchoalveolar lavage (BAL) fluid. Furthermore, 8f effectively inhibited mRNA expression of several inflammatory cytokines after LPS challenge in vitro and in vivo. Administration of 8f also blocked LPS-induced activation of the proinflammatory NF-κB/MAPK signaling pathway. Conclusion The simple synthetic preparation and biological properties of these derivatives make these 2-benzylidene-indanone scaffolds promising new entities for the development of anti-inflammatory therapeutics for the treatment of acute lung injury. PMID:29719375

Characterization of a Novel Humanized Anti-CD20 Antibody with Potent Anti-Tumor Activity against Non-Hodgkin's Lymphoma

Directory of Open Access Journals (Sweden)

Haifeng Zhang

2013-09-01

Full Text Available Background: Rituximab, a mouse Fab and human Fc chimeric antibody, has been widely used to treat Non-Hodgkin's lymphoma (NHL. However, only 48% of patients respond to the treatment and complete response rate is below 10%. Also, immunogenicity was reported in 17-20% patients receiving the treatment, making it unsuitable for long term diseases such as autoimmune disorders. It has been a hot research field to “humanize” rituximab toward improved efficacy and reduced immunogenicity. Methods: In this study, an advanced antibody humanization technology was applied to the sequence of the anti-CD20 antibody 2B8, its sequence of which was based on the original murine monoclonal antibody of rituximab in Roche. The complementarity-determining regions (CDRs of the humanized antibodies were further optimized through computer-aided molecular dock. Results: Five novel humanized anti-CD20 antibodies 1-5(1635, 1534, 3637, 1634 and 1536 were generated and their immunogenicity was significantly decreased when compared to rituximab. The novel humanized anti-CD20 antibodies 1-5 retained the binding activity of their murine counterpart, as demonstrated by the fluorescence-activated cell-sorting analysis (FACS. When compared to rituximab, the humanized antibodies still have the similar properties on both complement-dependent cytotoxicity (CDC and antibody-dependent cell-mediated cytotoxicity (ADCC. Furthermore, its anti-tumor efficacy in xenograft model is comparable to that of rituximab. Conclusion: The humanized anti-CD20 antibodies 1-5 have lower immunogenicity than rituximab. And at the same time, they still retain the anti-tumor effect both in vitro and vivo.

Imaging in severe acute respiratory syndrome (SARS)

International Nuclear Information System (INIS)

Antonio, G.E.; Wong, K.T.; Chu, W.C.W.; Hui, D.S.C.; Cheng, F.W.T.; Yuen, E.H.Y.; Chung, S.S.C.; Fok, T.F.; Sung, J.J.Y.; Ahuja, A.T.

2003-01-01

Severe acute respiratory syndrome (SARS) is a highly infectious disease caused by a novel coronavirus, and has become pandemic within a short period of time. Imaging plays an important role in the diagnosis, management and follow-up of patients with SARS. The current status of imaging in SARS is presented in this review

Severe acute malnutrition and infection

Science.gov (United States)

Jones, Kelsey D J; Berkley, James A

2014-01-01

Severe acute malnutrition (SAM) is associated with increased severity of common infectious diseases, and death amongst children with SAM is almost always as a result of infection. The diagnosis and management of infection are often different in malnourished versus well-nourished children. The objectives of this brief are to outline the evidence underpinning important practical questions relating to the management of infectious diseases in children with SAM and to highlight research gaps. Overall, the evidence base for many aspects covered in this brief is very poor. The brief addresses antimicrobials; antipyretics; tuberculosis; HIV; malaria; pneumonia; diarrhoea; sepsis; measles; urinary tract infection; nosocomial Infections; soil transmitted helminths; skin infections and pharmacology in the context of SAM. The brief is structured into sets of clinical questions, which we hope will maximise the relevance to contemporary practice. PMID:25475887

MR imaging of acute pancreatitis: Correlation of abdominal wall edema with severity scores

Energy Technology Data Exchange (ETDEWEB)

Yang, Ru, E-mail: yangru0904@163.com [Sichuan Key laboratory of Medical Imaging, Department of Radiology, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000 (China); Jing, Zong Lin, E-mail: jzl325@163.com [Sichuan Key laboratory of Medical Imaging, Department of Radiology, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000 (China); Zhang, Xiao Ming, E-mail: zhangxm@nsmc.edu.cn [Sichuan Key laboratory of Medical Imaging, Department of Radiology, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000 (China); Tang, Wei, E-mail: tw-n-g-up@163.com [Sichuan Key laboratory of Medical Imaging, Department of Radiology, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000 (China); Xiao, Bo, E-mail: xiaoboimaging@163.com [Sichuan Key laboratory of Medical Imaging, Department of Radiology, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000 (China); Huang, Xiao Hua, E-mail: nc_hxh1966@yahoo.com.cn [Sichuan Key laboratory of Medical Imaging, Department of Radiology, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000 (China); Yang, Lin, E-mail: llinyangmd@163.com [Sichuan Key laboratory of Medical Imaging, Department of Radiology, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000 (China); Feng, Zhi Song, E-mail: fengzhisong@medmail.com.cn [Department of Gastroenterology, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000 (China)

2012-11-15

Objective: To study MRI findings of abdominal wall edema (AWE) in acute pancreatitis as well as correlations between AWE and the severity of acute pancreatitis according to the MR severity index (MRSI) and the Acute Physiology And Chronic Healthy Evaluation III (APACHE III) scoring system. Materials and methods: A total of 160 patients with AP admitted to our institution between December 2009 and March 2011 were included in this study. MRI was performed within 48 h after admission. MRI findings of acute pancreatitis were noted, including AWE on the MRI. The abdominal wall area was divided into quarters, and each area involved was recorded as 1 point to score the severity of AWE. The severity of acute pancreatitis was studied using both the MRSI and the APACHE III scoring system. Spearman correlation of AWE with the MRSI and the APACHE III scoring system was analyzed. Results: In 160 patients with acute pancreatitis, 53.8% had AWE on MRI. The average AWE score was 1.2 {+-} 1.4 points. The prevalence of AWE was 30.5%, 64.5% and 100% in mild, moderate and severe AP, respectively, according to MRSI. AWE on MRI was correlated with MRSI scores (r = 0.441, p = 0.000). According to APACHE III scores, the averages were 2.0 {+-} 1.1 and 2.6 {+-} 1.1 points in mild AP and severe AP, respectively (P = 0.016). AWE was slightly correlated with the APACHE III scores (r = 0.222, p = 0.005). Conclusion: AWE on MRI in acute pancreatitis is common, which may be a supplementary indicator in determining the severity of AP.

Anti-leukemic activity and tolerability of anti-human CD47 monoclonal antibodies

Science.gov (United States)

Pietsch, E C; Dong, J; Cardoso, R; Zhang, X; Chin, D; Hawkins, R; Dinh, T; Zhou, M; Strake, B; Feng, P-H; Rocca, M; Santos, C Dos; Shan, X; Danet-Desnoyers, G; Shi, F; Kaiser, E; Millar, H J; Fenton, S; Swanson, R; Nemeth, J A; Attar, R M

2017-01-01

CD47, a broadly expressed cell surface protein, inhibits cell phagocytosis via interaction with phagocyte-expressed SIRPα. A variety of hematological malignancies demonstrate elevated CD47 expression, suggesting that CD47 may mediate immune escape. We discovered three unique CD47-SIRPα blocking anti-CD47 monoclonal antibodies (mAbs) with low nano-molar affinity to human and cynomolgus monkey CD47, and no hemagglutination and platelet aggregation activity. To characterize the anti-cancer activity elicited by blocking CD47, the mAbs were cloned into effector function silent and competent Fc backbones. Effector function competent mAbs demonstrated potent activity in vitro and in vivo, while effector function silent mAbs demonstrated minimal activity, indicating that blocking CD47 only leads to a therapeutic effect in the presence of Fc effector function. A non-human primate study revealed that the effector function competent mAb IgG1 C47B222-(CHO) decreased red blood cells (RBC), hematocrit and hemoglobin by >40% at 1 mg/kg, whereas the effector function silent mAb IgG2σ C47B222-(CHO) had minimal impact on RBC indices at 1 and 10 mg/kg. Taken together, our findings suggest that targeting CD47 is an attractive therapeutic anti-cancer approach. However, the anti-cancer activity observed with anti-CD47 mAbs is Fc effector dependent as are the side effects observed on RBC indices. PMID:28234345

[International multidisciplinary classification of acute pancreatitis severity: the 2013 Spanish edition].

Science.gov (United States)

Maraví-Poma, E; Patchen Dellinger, E; Forsmark, C E; Layer, P; Lévy, P; Shimosegawa, T; Siriwardena, A K; Uomo, G; Whitcomb, D C; Windsor, J A; Petrov, M S

2014-05-01

To develop a new classification of acute pancreatitis severity on the basis of a sound conceptual framework, comprehensive review of the published evidence, and worldwide consultation. The Atlanta definitions of acute pancreatitis severity are ingrained in the lexicon of specialist in pancreatic diseases, but are suboptimal because these definitions are based on the empiric description of events not associated with severity. A personal invitation to contribute to the development of a new classification of acute pancreatitis severity was sent to all surgeons, gastroenterologists, internists, intensivists and radiologists currently active in the field of clinical acute pancreatitis. The invitation was not limited to members of certain associations or residents of certain countries. A global web-based survey was conducted, and a dedicated international symposium was organized to bring contributors from different disciplines together and discuss the concept and definitions. The new classification of severity is based on the actual local and systemic determinants of severity, rather than on the description of events that are non-causally associated with severity. The local determinant relates to whether there is (peri) pancreatic necrosis or not, and if present, whether it is sterile or infected. The systemic determinant relates to whether there is organ failure or not, and if present, whether it is transient or persistent. The presence of one determinant can modify the effect of another, whereby the presence of both infected (peri) pancreatic necrosis and persistent organ failure has a greater impact upon severity than either determinant alone. The derivation of a classification based on the above principles results in four categories of severity: mild, moderate, severe, and critical. This classification is the result of a consultative process among specialists in pancreatic diseases from 49 countries spanning North America, South America, Europe, Asia, Oceania and

A review of human anti-globulin antibody (HAGA, HAMA, HACA, HAHA) responses to monoclonal antibodies. Not four letter words.

Science.gov (United States)

Mirick, G R; Bradt, B M; Denardo, S J; Denardo, G L

2004-12-01

The United States Food and Drug Administration (FDA) has approved unconjugated monoclonal antibodies (MAbs) for immunotherapy (IT) of B-cell lymphoma, breast cancer and acute myeloid leukemia. More recently, approval has been given for conjugated ZevalinTM ((90)yttrium ibritumomab tiuxetan, IDEC-Y2B8, Biogen Idec, Cambridge, MA) and BexxarTM ((131)I-tositumomab, Corixa, Corp., Seattle, WA and GlaxoSmithKline, Philadelphia, PA) anti-CD20 MAbs for use in radioimmunotherapy (RIT) of non-Hodgkin's lymphoma (NHL), thus redefining the standard care of cancer patients. Because of, and despite a lack of basis for concern about allergic reactions due to human antibody responses to these foreign proteins, assays were developed to determine HAGA (human anti-globulin antibody) levels that developed in patient sera following treatment with MAbs. Strategies were also devised to ''humanize'' MAbs and to temporarily block patient immune function with drugs in order to decrease the seroconversion rates, with considerable success. On the other hand, a survival advantage has been observed in some patients who developed a HAGA following treatment. This correlates with development of an anti-idiotype antibody cascade directed toward the MAbs used to treat these patients. What follows is a selective review of HAGA and its effect on cancer treatment over the past 2 decades.

A review of human anti-globulin antibody (HAGA, HAMA, HACA, HAHA) responses to monoclonal antibodies. Not four letter words

International Nuclear Information System (INIS)

Mirick, G. R.; Bradt, B. M.; Denardo, S. J.; Denardo, G. L.

2004-01-01

The United States Food and Drugs Administration (FDA) has approved unconjugated monoclonal antibodies (MAbs) for immunotherapy (IT) of B-cell lymphoma, breast cancer and acute myeloid leukemia. More recently, approval has been given for conjugated ZevalinTM ( 9 0yttrium ibritumomab tiuxetan, IDEC-Y2B8, Biogen Idec, Cambridge, MA) and BexxarTM ( 1 31I-tositumomab, Corixa, Corp., Seattle, WA and GlaxoSmithKline, Philadelphia, PA) antiCD20 MAns for use in radioimmunotherapy (RIT) of non-Hodgikin's lymphoma (NHL), thus redefining the standard care of cancer patients. Because of, and despite a lack of basis for concern about allergic reactions due to human antibody responses to these foreign proteins, essays were developed to determine HAGE (human anti-globulin antibody) levels that developed in patient sera following treatment with MAbs. Strategies were also devised to humanize MAbs and to temporarily block patient immune function with drugs in order to decrease the seroconversion rates, with considerable success. On the other hand, a survival advantage has been observed in some patients who developed a HAGA following treatment. This correlates with development of an anti-idiotype antibody cascade directed toward the MAbs used to treat these patients. What follows is a selective review of HAGA and its effect on cancer treatment over the past 2 decades

Preclinical evaluation of WYE-687, a mTOR kinase inhibitor, as a potential anti-acute myeloid leukemia agent

International Nuclear Information System (INIS)

Cheng, Feng; Wang, Lingling; Shen, Yunfeng; Xia, Jun; Chen, Heng; Jiang, Yuanqiang; Lu, Mize

2016-01-01

Mammalian target of rapamycin (mTOR) as a potential drug target for treatment of acute myeloid leukemia (AML). Here, we investigated the potential anti-leukemic activity by WYE-687, a potent mTOR kinase inhibitor. We demonstrated that WYE-687 potently inhibited survival and proliferation of established (HL-60, U937, AML-193 and THP-1 lines) and human AML progenitor cells. Yet, same WYE-687 treatment was non-cytotoxic to the primary peripheral blood mononuclear leukocytes (PBMCs) isolated from healthy donors. WYE-687 induced caspase-dependent apoptotic death in above AML cells/progenitor cells. On the other hand, the pan-caspase inhibitor (Z-VAD-FMK), the caspase-3 specific inhibitor (Z-DEVD-FMK) or the caspase-9 specific inhibitor (z-LEHD-fmk) attenuated WYE-687-induced cytotoxicity. At the molecular level, WYE-687 concurrently inhibited activation of mTORC1 (p70S6K1 and S6 phosphorylations) and mTORC2 (AKT Ser-473 and FoxO1/3a phosphorylations), whiling downregulating mTORC1/2-regulated genes (Bcl-xL and hypoxia-inducible factor 1/2α) in both HL-60/U937 cells and human AML progenitor cells. In vivo, oral administration of WYE-687 potently inhibited U937 leukemic xenograft tumor growth in severe combined immunodeficient (SCID) mice, without causing significant toxicities. In summary, our results demonstrate that targeting mTORC1/2 by WYE-687 leads to potent antitumor activity in preclinical models of AML. - Highlights: • WYE-687 inhibits survival and proliferation of human AML cells/progenitor cells. • WYE-687 induces apoptotic death of human AML cells/progenitor cells. • WYE-687 inhibits mTORC1/2 activation in human AML cells/progenitor cells. • WYE-687 inhibits U937 xenograft growth in SCID mice.

Preclinical evaluation of WYE-687, a mTOR kinase inhibitor, as a potential anti-acute myeloid leukemia agent

Energy Technology Data Exchange (ETDEWEB)

Cheng, Feng; Wang, Lingling; Shen, Yunfeng; Xia, Jun; Chen, Heng; Jiang, Yuanqiang, E-mail: jiangyuanqiangwuxi@163.com; Lu, Mize, E-mail: lumizewuxi9@sina.com

2016-02-05

Mammalian target of rapamycin (mTOR) as a potential drug target for treatment of acute myeloid leukemia (AML). Here, we investigated the potential anti-leukemic activity by WYE-687, a potent mTOR kinase inhibitor. We demonstrated that WYE-687 potently inhibited survival and proliferation of established (HL-60, U937, AML-193 and THP-1 lines) and human AML progenitor cells. Yet, same WYE-687 treatment was non-cytotoxic to the primary peripheral blood mononuclear leukocytes (PBMCs) isolated from healthy donors. WYE-687 induced caspase-dependent apoptotic death in above AML cells/progenitor cells. On the other hand, the pan-caspase inhibitor (Z-VAD-FMK), the caspase-3 specific inhibitor (Z-DEVD-FMK) or the caspase-9 specific inhibitor (z-LEHD-fmk) attenuated WYE-687-induced cytotoxicity. At the molecular level, WYE-687 concurrently inhibited activation of mTORC1 (p70S6K1 and S6 phosphorylations) and mTORC2 (AKT Ser-473 and FoxO1/3a phosphorylations), whiling downregulating mTORC1/2-regulated genes (Bcl-xL and hypoxia-inducible factor 1/2α) in both HL-60/U937 cells and human AML progenitor cells. In vivo, oral administration of WYE-687 potently inhibited U937 leukemic xenograft tumor growth in severe combined immunodeficient (SCID) mice, without causing significant toxicities. In summary, our results demonstrate that targeting mTORC1/2 by WYE-687 leads to potent antitumor activity in preclinical models of AML. - Highlights: • WYE-687 inhibits survival and proliferation of human AML cells/progenitor cells. • WYE-687 induces apoptotic death of human AML cells/progenitor cells. • WYE-687 inhibits mTORC1/2 activation in human AML cells/progenitor cells. • WYE-687 inhibits U937 xenograft growth in SCID mice.

Effect of riluzole on acute pain and hyperalgesia in humans

DEFF Research Database (Denmark)

Hammer, N A; Lillesø, J; Pedersen, J L

1999-01-01

Riluzole modulates several transmitter systems which may be involved in nociception. Antinociceptive effects have been shown in animal studies, but there are no human data. Therefore, we have examined the acute analgesic effect of riluzole in a human model of inflammatory pain induced by a thermal...... injury on the distal leg (47 degrees C, 7 min, 12.5 cm2) in 20 healthy volunteers. Hyperalgesia to mechanical and heat stimuli were examined by von Frey hairs and thermodes. We used a randomized, double-blind, placebo-controlled design, and subjects received riluzole 100 mg or placebo for 2 days...

Severe asthma exacerbation: role of acute Chlamydophila pneumoniae and Mycoplasma pneumoniae infection

Directory of Open Access Journals (Sweden)

Pappalettera Maria

2008-05-01

Full Text Available Abstract Background Chlamydophila pneumoniae and Mycoplasma pneumoniae are associated with acute exacerbation of bronchial asthma (AEBA. The aim of this study was to evaluate the correlation between these acute bacterial infections and the severity of AEBA. Methods We prospectively analysed consecutive patients admitted to the Emergency Department with acute asthma exacerbation. In every patient peak expiratory flow (PEF measurement was performed on admission, and spirometry during follow-up. Serology for Chlamydophila and Mycoplasma pneumoniae was performed on admission and after 4–8 weeks. Results Fifty-eight patients completed the study. Acute atypical infections (AAI was observed in 22/58 cases; we found single acute C. pneumoniae in 19 cases, single acute M. pneumoniae in 2 cases, and double acute infection in one case. Functional impairment on admission was greater in patients with AAI than in patients without AAI (PEF 205 ± 104 L/min vs 276 ± 117 p = 0.02 and persisted until visit 2 (FEV1% 76.30 ± 24.54 vs FEV1% 92.91 ± 13.89, p = 0.002. Moreover, the proportion of patients who presented with severe AEBA was significantly greater in the group with AAI than in the group without AAI (15/22 vs 12/36, p = 0.01; OR 4.29, 95% CI 1.38–13.32. Conclusion Our data suggest an association between acute atypical infection and a more severe AEBA.

Comparison of an anti-rabies human monoclonal antibody combination with human polyclonal anti-rabies immune globulin

NARCIS (Netherlands)

Goudsmit, Jaap; Marissen, Wilfred E.; Weldon, William C.; Niezgoda, Michael; Hanlon, Cathleen A.; Rice, Amy B.; Kruif, John de; Dietzschold, Bernhard; Bakker, Alexander B. H.; Rupprecht, Charles E.

2006-01-01

The World Health Organization estimates human mortality from endemic canine rabies to be 55,000 deaths/year. Limited supply hampers the accessibility of appropriate lifesaving treatment, particularly in areas where rabies is endemic. Anti-rabies antibodies are key to protection against lethal

Tocilizumab-Induced Acute Liver Injury in Adult Onset Still’s Disease

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Michael Drepper

2013-01-01

Full Text Available Background. Tocilizumab, a monoclonal humanized anti-IL-6 receptor antibody, is used in treatment of refractory adult onset Still’s disease (AOSD. Mild to moderate liver enzyme elevation is a well-known side effect, but severe liver injury has only been reported in 3 cases in the literature. Case. A young female suffering from corticoid and methotrexate refractory AOSD was treated by tocilizumab. After 19 months of consecutive treatment, she developed acute severe liver injury. Liver biopsy showed extensive hepatocellular necrosis with ballooned hepatocytes, highly suggestive of drug-induced liver injury. No other relevant drug exposure beside tocilizumab was recorded. She recovered totally after treatment discontinuation and an initial 3-day course of intravenous N-acetylcysteine with normalization of liver function tests after 6 weeks. Conclusion. Acute severe hepatitis can be associated with tocilizumab as documented in this case. Careful monitoring of liver function tests is warranted during tocilizumab treatment.

Thrombopoietin as Early Biomarker of Disease Severity in Patients With Acute Pancreatitis.

Science.gov (United States)

Lupia, Enrico; Pigozzi, Luca; Pivetta, Emanuele; Bosco, Ornella; Vizio, Barbara; Loiacono, Maria; Lucchiari, Manuela; Battista, Stefania; Morello, Fulvio; Moiraghi, Corrado; Mengozzi, Giulio; Montrucchio, Giuseppe

2017-02-01

To study the concentrations of thrombopoietin (TPO), a growth factor recently involved in the pathogenesis of experimental acute pancreatitis (AP), and its potential role as an early diagnostic and prognostic biomarker in patients with AP. Thrombopoietin was measured in 44 AP patients, 18 patients with nonpancreatic acute abdominal pain, and 18 healthy volunteers. Acute pancreatitis severity was classified on the basis of the 2012 International Atlanta Symposium on Acute Pancreatitis criteria. Thrombopoietin levels did not differ between AP patients and control subjects, whereas these were higher in patients with moderately severe or severe AP compared with those with mild AP. Receiver operating characteristic curve analysis of TPO for severe AP diagnosis showed an area under the curve of 0.80. A cutoff value of 31.48 pg/mL showed the highest sensitivity, allowing to rule out severe AP when TPO was lower, whereas TPO higher than 98.23 pg/mL was associated with severe AP with high specificity (93.5%). Furthermore, TPO levels were greater in AP patients developing organ dysfunction or sepsis and in nonsurvivors compared with survivors. Our data provide the first evidence for TPO as potential early prognostic biomarker in AP patients. High TPO levels at hospital admission may predict organ dysfunction, sepsis, and fatal outcome in AP patients.

Experimental evidence of obesity as a risk factor for severe acute pancreatitis.

Science.gov (United States)

Frossard, Jean-Louis; Lescuyer, Pierre; Pastor, Catherine M

2009-11-14

The incidence of acute pancreatitis, an inflammation of the pancreas, is increasing worldwide. Pancreatic injury is mild in 80%-90% of patients who recover without complications. The remaining patients may develop a severe disease with local complications such as acinar cell necrosis, abscess and remote organ injury including lung injury. The early prediction of the severity of the disease is an important goal for physicians in management of patients with acute pancreatitis in order to optimize the therapy and to prevent organ dysfunction and local complications. For that purpose, multiple clinical scale scores have been applied to patients with acute pancreatitis. Recently, a new problem has emerged: the increased severity of the disease in obese patients. However, the mechanisms by which obesity increases the severity of acute pancreatitis are unclear. Several hypotheses have been suggested: (1) obese patients have an increased inflammation within the pancreas; (2) obese patients have an increased accumulation of fat within and around the pancreas where necrosis is often located; (3) increase in both peri- and intra-pancreatic fat and inflammatory cells explain the high incidence of pancreatic inflammation and necrosis in obese patients; (4) hepatic dysfunction associated with obesity might enhance the systemic inflammatory response by altering the detoxification of inflammatory mediators; and (5) ventilation/perfusion mismatch leading to hypoxia associated with a low pancreatic flow might reduce the pancreatic oxygenation and further enhance pancreatic injury. Recent experimental investigations also show an increased mortality and morbidity in obese rodents with acute pancreatitis and the implication of the adipokines leptin and adiponectin. Such models are important to investigate whether the inflammatory response of the disease is enhanced by obesity. It is exciting to speculate that manipulation of the adipokine milieu has the potential to influence the

Mosaic Evolution of the Severe Acute Respiratory Syndrome Coronavirus

Science.gov (United States)

Stavrinides, John; Guttman, David S.

2004-01-01

Severe acute respiratory syndrome (SARS) is a deadly form of pneumonia caused by a novel coronavirus, a viral family responsible for mild respiratory tract infections in a wide variety of animals including humans, pigs, cows, mice, cats, and birds. Analyses to date have been unable to identify the precise origin of the SARS coronavirus. We used Bayesian, neighbor-joining, and split decomposition phylogenetic techniques on the SARS virus replicase, surface spike, matrix, and nucleocapsid proteins to reveal the evolutionary origin of this recently emerging infectious agent. The analyses support a mammalian-like origin for the replicase protein, an avian-like origin for the matrix and nucleocapsid proteins, and a mammalian-avian mosaic origin for the host-determining spike protein. A bootscan recombination analysis of the spike gene revealed high nucleotide identity between the SARS virus and a feline infectious peritonitis virus throughout the gene, except for a 200- base-pair region of high identity to an avian sequence. These data support the phylogenetic analyses and suggest a possible past recombination event between mammalian-like and avian-like parent viruses. This event occurred near a region that has been implicated to be the human receptor binding site and may have been directly responsible for the switch of host of the SARS coronavirus from animals to humans. PMID:14671089

Severe Hypertriglyceridemia in Diabetic Ketoacidosis Accompanied by Acute Pancreatitis: Case Report

OpenAIRE

Hahn, Suk Jae; Park, Jung-hyun; Lee, Jong Ho; Lee, Jun Kyu; Kim, Kyoung-Ah

2010-01-01

We report a case of diabetic ketoacidosis (DKA) and hypertriglyceridemia (severely elevated to 15,240 mg/dL) complicated by acute pancreatitis, which was treated successfully with insulin therapy and conservative management. A 20-yr-old woman with a history of type 1 diabetes came to the emergency department 7 months after discontinuing insulin therapy. DKA, severe hypertriglyceridemia and acute pancreatitis were diagnosed, with DKA suspected of contributing to the development of the other co...

Clinical significance of transforming growth factor β1 in the diagnosis of the severity of acute pancreatitis

Directory of Open Access Journals (Sweden)

Михаил Викторович Клименко

2015-03-01

Full Text Available Aim. Determine the clinical-diagnostic and prognostic value of transforming growth factor ß1 (TGF-ß1 at different degrees of severity of acute pancreatitis (AP on the basis of studying the characteristics of content of anti-inflammatory cytokine in serum to create a diagnostic algorithm severity and course of AP.Methods. It is analyzed the data for the study of nature of the transforming growth factor ß1 (TGF-ß1 content in the serum of 94 patients with AP varying severity (mild case of AP-20 patients, average case - 12, severe case -62 in the first 24-48 hours and 7-10 days of hospitalization.Results. Analysis of the data can reliably assert that the value of TGF-ß1 in the first 48 hours of admission to correlate with AP severity. It is proposed the use of TGF-ß1 level in clinical and diagnostic complex of diagnostic of AP severity in the first 48 hours of hospitalization. If the patient has TGF-β1≤70.0 ng / ml it is mild AP. If the level of cytokine ≥70.1 ng / ml produce differentiation between moderate and severe AP. At the level of cytokine ≥120.1 ng / ml it is severe AP and diagnosis is completed. In the case of the definition of TGF-β1 in the range of> 80.1 - <120.0 ng / ml AP degree uncertain and requires further observation and examination.Conclusions. Diagnostic thresholds of AP severity are determined. It is allowed use of TGF-β1 in a modern complex AP diagnostics. It is proven a diagnostic and prognostic significance level of anti-inflammatory cytokine TGF-ß1

Intramuscular anti-D in chronic immune thrombocytopenia children with severe thrombocytopenia.

Science.gov (United States)

Sirachainan, Nongnuch; Anurathapan, Usanarat; Chuansumrit, Ampaiwan; Songdej, Duantida; Wongwerawattanakoon, Pakawan; Hutspardol, Sakara; Kitpoka, Pimpun

2013-12-01

Nine patients with chronic immune thrombocytopenia and platelet counts anti-D. Phase 1 was anti-D daily for 5 days, followed by phase 2, anti-D weekly for 12 weeks and withheld when platelet counts ≥ 20 × 10(9) /L, and then phase 3 was anti-D once every 2 weeks for 24 weeks. According to the International Working Group criteria, in phase 1, 66.7% of patients responded to the treatment. In phases 2 and 3, 11.1% (0-41.7%) and 7.7% (0-33.3%) of total episodes of follow up, respectively, responded to the treatment. Therefore, intramuscular anti-D given at a dose of 10 mcg/kg for 5 days is an alternative method to raise platelet counts in chronic immune thrombocytopenia children with severe thrombocytopenia where the intravenous form of anti-D is not available. © 2013 The Authors. Pediatrics International © 2013 Japan Pediatric Society.

C4d-negative antibody-mediated rejection with high anti-angiotensin II type I receptor antibodies in absence of donor-specific antibodies.

Science.gov (United States)

Fuss, Alexander; Hope, Christopher M; Deayton, Susan; Bennett, Greg Donald; Holdsworth, Rhonda; Carroll, Robert P; Coates, P Toby H

2015-07-01

Acute antibody-mediated rejection can occur in absence of circulating donor-specific antibodies. Agonistic antibodies targeting the anti-angiotensin II type 1 receptor (anti-AT1 R) are emerging as important non-human leucocyte antigen (HLA) antibodies. Elevated levels of anti-angiotensin II receptor antibodies were first observed in kidney transplant recipients with malignant hypertension and allograft rejection. They have now been studied in three separate kidney transplant populations and associate to frequency of rejection, severity of rejection and graft failure. We report 11 cases of biopsy-proven, Complement 4 fragment d (C4d)-negative, acute rejection occurring without circulating donor-specific anti-HLA antibodies. In eight cases, anti-angiotensin receptor antibodies were retrospectively examined. The remaining three subjects were identified from our centre's newly instituted routine anti-angiotensin receptor antibody screening. All subjects fulfilled Banff 2013 criteria for antibody-mediated rejection and all responded to anti-rejection therapy, which included plasma exchange and angiotensin receptor blocker therapy. These cases support the routine assessment of anti-AT1 R antibodies in kidney transplant recipients to identify subjects at risk. Further studies will need to determine optimal assessment protocol and the effectiveness of pre-emptive treatment with angiotensin receptor blockers. © 2015 Asian Pacific Society of Nephrology.

Human bocavirus infection as a cause of severe acute respiratory tract infection in children.

Science.gov (United States)

Moesker, F M; van Kampen, J J A; van der Eijk, A A; van Rossum, A M C; de Hoog, M; Schutten, M; Smits, S L; Bodewes, R; Osterhaus, A D M E; Fraaij, P L A

2015-10-01

In 2005 human bocavirus (HBoV) was discovered in respiratory tract samples of children. The role of HBoV as the single causative agent for respiratory tract infections remains unclear. Detection of HBoV in children with respiratory disease is frequently in combination with other viruses or bacteria. We set up an algorithm to study whether HBoV alone can cause severe acute respiratory tract infection (SARI) in children. The algorithm was developed to exclude cases with no other likely cause than HBoV for the need for admission to the paediatric intensive care unit (PICU) with SARI. We searched for other viruses by next-generation sequencing (NGS) in these cases and studied their HBoV viral loads. To benchmark our algorithm, the same was applied to respiratory syncytial virus (RSV)-positive patients. From our total group of 990 patients who tested positive for a respiratory virus by means of RT-PCR, HBoV and RSV were detected in 178 and 366 children admitted to our hospital. Forty-nine HBoV-positive patients and 72 RSV-positive patients were admitted to the PICU. We found seven single HBoV-infected cases with SARI admitted to PICU (7/49, 14%). They had no other detectable virus by NGS. They had much higher HBoV loads than other patients positive for HBoV. We identified 14 RSV-infected SARI patients with a single RSV infection (14/72, 19%). We conclude that our study provides strong support that HBoV can cause SARI in children in the absence of viral and bacterial co-infections. Copyright © 2015 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Human bocavirus in children with acute respiratory infections in Vietnam.

Science.gov (United States)

Tran, Dinh Nguyen; Nguyen, Tran Quynh Nhu; Nguyen, Tuan Anh; Hayakawa, Satoshi; Mizuguchi, Masashi; Ushijima, Hiroshi

2014-06-01

Acute respiratory infections are the major cause of morbidity and mortality globally. Human bocavirus (HBoV), a novel virus, is recognized to increasingly associate with previously unknown etiology respiratory infections in young children. In this study, the epidemiological, clinical, and molecular characteristics of HBoV infections were described in hospitalized Vietnamese pediatric patients. From April 2010 to May 2011, 1,082 nasopharyngeal swab samples were obtained from patients with acute respiratory infections at the Children's Hospital 2, Ho Chi Minh City, Vietnam. Samples were screened for HBoV by PCR and further molecularly characterized by sequencing. HBoV was found in 78 (7.2%) children. Co-infection with other viruses was observed in 66.7% of patients infected with HBoV. Children 12-24 months old were the most affected age group. Infections with HBoV were found year-round, though most cases occurred in the dry season (December-April). HBoV was possible to cause severe diseases as determined by higher rates of hypoxia, pneumonia, and longer hospitalization duration in patients with HBoV infection than in those without (P-value infection with HBoV did not affect the disease severity. The phylogenetic analysis of partial VP1 gene showed minor variations and all HBoV sequences belonged to species 1 (HBoV1). In conclusion, HBoV1 was circulating in Vietnam and detected frequently in young children during dry season. Acute respiratory infections caused by HBoV1 were severe enough for hospitalization, which implied that HBoV1 may have an important role in acute respiratory infections among children. © 2013 Wiley Periodicals, Inc.

Human rotavirus subgroups and severity of associated diarrhoea in Ghana.

Science.gov (United States)

Armah, George E.; Hori, Hiroki; Anyanful, Akwasi; Addo, Julius A.; Commey, Joseph O.; Kamiya, Hitoshi; Nkrumah, Francis K.

1995-11-01

In a 12 month study of children with acute diarrhoea seeking medical care in 2 hospitals in Accra, Ghana, 16.3% were found to be infected with human rotaviruses (HRV). Vomiting and diarrhoea were the main symptoms observed. HRV infection was frequently associated with severe diarrhoea. Vomiting was however less frequent in HRV associated diarrhoea than in non HRV diarrhoea. No significant association was observed between the severity of dehydration and HRV infection. Subgroup II HRV was the predominant subgroup identified with the dominant serotypes being HRV serotypes 1 and 4. Poly-acrylamide gel electrophoresis of HRV RNAs isolated from 40 positive stool samples revealed the existence of 7 distinct electrophoretic migration patterns in the study population.

Current possibilities of anti-inflammatory therapy in children with acute respiratory diseases

OpenAIRE

E. E. Lokshina; O. V. Zaytseva

2017-01-01

The paper gives an update on the pathogenesis of acute respiratory diseases, the basis for which is inflammation of the airway mucosal lining. It reflects the results of a comparative clinical trial of the efficacy and safety of the anti-inflammatory drug fenspiride used in the combination therapy for respiratory diseases in children. The findings allow one to recommend the use of fenspiride to treat this condition in children.

Current possibilities of anti-inflammatory therapy in children with acute respiratory diseases

Directory of Open Access Journals (Sweden)

E. E. Lokshina

2017-01-01

Full Text Available The paper gives an update on the pathogenesis of acute respiratory diseases, the basis for which is inflammation of the airway mucosal lining. It reflects the results of a comparative clinical trial of the efficacy and safety of the anti-inflammatory drug fenspiride used in the combination therapy for respiratory diseases in children. The findings allow one to recommend the use of fenspiride to treat this condition in children.

Severe Acute Pancreatitis in Pregnancy

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Bahiyah Abdullah

2015-01-01

Full Text Available This is a case of a pregnant lady at 8 weeks of gestation, who presented with acute abdomen. She was initially diagnosed with ruptured ectopic pregnancy and ruptured corpus luteal cyst as the differential diagnosis. However she then, was finally diagnosed as acute hemorrhagic pancreatitis with spontaneous complete miscarriage. This is followed by review of literature on this topic. Acute pancreatitis in pregnancy is not uncommon. The emphasis on high index of suspicion of acute pancreatitis in women who presented with acute abdomen in pregnancy is highlighted. Early diagnosis and good supportive care by multidisciplinary team are crucial to ensure good maternal and fetal outcomes.

Anti-glomerular basement membrane: A rare cause of renal failure in children

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Indira Agarwal

2017-01-01

Full Text Available Anti-glomerular basement membrane (GBM disease is a rare cause of acute renal failure and known to have bad prognosis regarding renal functions recovery and patient survival specially when diagnosed late and presents with severe renal failure that requires dialysis. We report a case of 11-year-old child with acute renal failure secondary to anti-GBM disease and associated with antineutrophil cytoplasmic antibody-positive vasculitis. He was treated with plasmapheresis, steroids, and cyclophosphamide with recovery of his kidney functions.

Severe renal failure in acute bacterial pyelonephritis: Do not forget corticosteroids

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Sqalli Tarik

2010-01-01

Full Text Available Acute renal failure (ARF is a rare complication of acute pyelonephritis in adult immunocompetent patients. Recovery of renal function usually occurs if antibiotics are promptly initiated. However, long-term consequences of renal scarring due to acute pyelonephritis are probably underestimated, and some patients present with prolonged renal failure despite adequate antibiotic therapy. We report two cases of severe ARF complicating bacterial pyelonephritis successfully treated with corticosteroids in association with conventional antibiotics.

[Multiple organ failure complicating a severe acute necrotising pancreatitis secondary of a severe hypertriglyceridemia: a case report].

Science.gov (United States)

Degardin, J; Pons, B; Ardisson, F; Gallego, J-P; Thiery, G

2013-09-01

We report the case of a 42-year-old man admitted for a multi-organ failure with a coma, a hemodynamic instability, a respiratory distress syndrome, an acute renal failure and a thrombocytopenia. The blood samples highlighted a milky serum and allowed to diagnose an acute pancreatitis associated with a major dyslipidemia: hypertriglyceridemia 11,800 mg/dL and hypercholesterolemia 1195 mg/dL. The CT-scans do not reveal any cerebral abnormalities but highlighted pancreatic lesions without biliary obstruction. A multi-organ failure complicating a severe acute pancreatitis secondary of a major hypertriglyceridemia was mentioned. Despite the absence of clear guidelines, a session of plasma exchange was started in emergency. Symptomatic treatment with protective ventilation, vasopressors, continuous heparin and insulin was continued. The clinical and biological course was good in parallel of the normalization of lipid abnormalities. The patient was discharged at day 17 with a lipid-lowering therapy. We discuss the various treatments available for the management of acute pancreatitis complicating a severe hypertriglyceridemia and their actual relevance in the absence of clear recommendations. Copyright © 2013. Published by Elsevier SAS.

Assessment of PANC3 Score in Predicting Severity of Acute ...

African Journals Online (AJOL)

2017-05-18

May 18, 2017 ... us in predicting severity at the time of admission but these are time consuming or .... and Acute pancreatitis classification working group)[3] to assess the severity of ... belonged to 30–45 years age group, with mean age of.

Molecular typing and epidemiology profiles of human adenovirus infection among paediatric patients with severe acute respiratory infection in China.

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Li, Yamin; Zhou, Weimin; Zhao, Yanjie; Wang, Yanqun; Xie, Zhengde; Lou, Yongliang; Tan, Wenjie

2015-01-01

Human adenoviruses (HAdVs) have been recognised as pathogens that cause a broad spectrum of diseases. The studies on HAdV infection among children with severe acute respiratory infection (SARI) are limited. To investigate the prevalence, epidemiology, and genotype of HAdV among children with SARI in China. Nasopharyngeal aspirates (NPAs) or induced sputum (IS) was collected from hospitalised children with SARIs in Beijing (representing Northern China; n = 259) and Zhejiang Province (representing Eastern China; n = 293) from 2007 to 2010. The prevalence of HAdV was screened by polymerase chain reaction (PCR), followed by sequence typing of PCR fragments that targeted the second half of the hexon gene. In addition, co-infection with other human respiratory viruses, related epidemiological profiles and clinical presentations were investigated. In total, 76 (13.8%) of 552 SARI patients were positive for HAdV, and the infection rates of HAdV in Northern and Eastern China were 20.1% (n = 52) and 8.2% (n = 24), respectively. HAdV co-infection with other respiratory viruses was frequent (infection rates: Northern China, 90.4%; Eastern China, 70.8%). The peak seasons for HAdV-B infection was winter and spring. Additionally, members of multiple species (Human mastadenovirus B, C, D and E) were circulating among paediatric patients with SARI, of which HAdV-B (34/52; 65.4%) and HAdV-C (20/24, 83.3%) were the most predominant in Northern and Eastern China, respectively. These findings provide a benchmark for future epidemiology and prevention strategies for HAdV.

Depression of Complement Regulatory Factors in Rat and Human Renal Grafts Is Associated with the Progress of Acute T-Cell Mediated Rejection.

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Kazuaki Yamanaka

Full Text Available The association of complement with the progression of acute T cell mediated rejection (ATCMR is not well understood. We investigated the production of complement components and the expression of complement regulatory proteins (Cregs in acute T-cell mediated rejection using rat and human renal allografts.We prepared rat allograft and syngeneic graft models of renal transplantation. The expression of Complement components and Cregs was assessed in the rat grafts using quantitative real-time PCR (qRT-PCR and immunofluorescent staining. We also administered anti-Crry and anti-CD59 antibodies to the rat allograft model. Further, we assessed the relationship between the expression of membrane cofactor protein (MCP by immunohistochemical staining in human renal grafts and their clinical course.qRT-PCR results showed that the expression of Cregs, CD59 and rodent-specific complement regulator complement receptor 1-related gene/protein-y (Crry, was diminished in the rat allograft model especially on day 5 after transplantation in comparison with the syngeneic model. In contrast, the expression of complement components and receptors: C3, C3a receptor, C5a receptor, Factor B, C9, C1q, was increased, but not the expression of C4 and C5, indicating a possible activation of the alternative pathway. When anti-Crry and anti-CD59 mAbs were administered to the allograft, the survival period for each group was shortened. In the human ATCMR cases, the group with higher MCP expression in the grafts showed improved serum creatinine levels after the ATCMR treatment as well as a better 5-year graft survival rate.We conclude that the expression of Cregs in allografts is connected with ATCMR. Our results suggest that controlling complement activation in renal grafts can be a new strategy for the treatment of ATCMR.

Severe HDN due to anti-Ce that required exchange tranfusion.

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Wagner, T; Resch, B; Legler, T J; Mossier, C; Helmberg, W; Köhler, M; Lanzer, G

2000-05-01

Rh system antibodies are commonly encountered in blood bank practice as well as during pregnancy. Nevertheless, no examples of anti-Ce (RH7) have been reported as a cause of HDN that requires exchange transfusion. A 38-year-old woman in her fourth pregnancy was typed as blood group O D+, C-, c+, E+, e-. Anti-C and anti-e were detected in her serum during a routine prenatal work-up. Further evaluation, including flow cytometric analysis, revealed the presence of a strong anti-Ce and a weak anti-e. Her partner was typed as group A D+, C+, c-, E-, e+. A seemingly healthy male infant was delivered at 40 weeks of gestation. The infant's RBCs were typed as group O D-, C+, c+, E+, e+ with a positive DAT (titer 128). Twenty-five hours after birth, the baby had to be transferred to the neonatal intensive care unit because of rapidly rising total serum bilirubin. Despite intensive treatment, including double phototherapy, albumin infusion, and the administration of furosemide and IVIG, the total serum bilirubin level increased during the following day and exchange transfusion with 2 units of type O D-, C-, c+, E+, e- had to be performed; this resulted in a prompt decrease in total serum bilirubin without relapse. Anti-Ce caused severe HDN requiring exchange transfusion. This highlights the need for a close follow-up throughout pregnancy if unexpected RBC antibodies are present, to permit the provision of compatible blood in case of a rare antibody.

Humanized CD7 nanobody-based immunotoxins exhibit promising anti-T-cell acute lymphoblastic leukemia potential

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Yu Y

2017-03-01

all immunotoxins still maintained the ability to bind specifically to CD7-positive T lymphocyte strains without binding to CD7-negative control cells. Laser scanning confocal microscopy revealed that these proteins can be endocytosed into the cytoplasm after binding with CD7-positive cells and that this phenomenon was not observed in CD7-negative cells. WST-8 experiments showed that all immunotoxins retained the highly effective and specific growth inhibition activity in CD7-positive cell lines and primary T-cell acute lymphoblastic leukemia (T-ALL cells. Further in vivo animal model experiments showed that humanized dhuVHH6-PE38 immunotoxin can tolerate higher doses and extend the survival of NOD-Prkdcem26Il2rgem26Nju (NCG mice transplanted with CEM cells without any obvious decrease in body weight. Further studies on NCG mice model with patient-derived T-ALL cells, dhuVHH6-PE38 treatment, significantly prolonged mice survival with ~40% survival improvement. However, it was also noticed that although dhuVHH6-PE-LR showed strong antitumor effect in vitro, its in vivo antitumor efficacy was disappointing. Conclusion: We have successfully constructed a targeted CD7 molecule-modified nanobody (CD7 molecule-improved nanobody immunotoxin dhuVHH6-PE38 and demonstrated its potential for treating CD7-positive malignant tumors, especially T-cell acute lymphoblastic leukemia. Keywords: CD7, humanized nanobody, T-cell acute lymphoblastic leukemia, patient-derived xenograft model, recombinant immunotoxins, Pseudomonas exotoxin A

Effects of abdominal fat distribution parameters on severity of acute pancreatitis.

LENUS (Irish Health Repository)

O'Leary, D P

2012-07-01

Obesity is a well-established risk factor for acute pancreatitis. Increased visceral fat has been shown to exacerbate the pro-inflammatory milieu experienced by patients. This study aimed to investigate the relationship between the severity of acute pancreatitis and abdominal fat distribution parameters measured on computed tomography (CT) scan.

A review of human anti-globulin antibody (HAGA, HAMA, HACA, HAHA) responses to monoclonal antibodies. Not four letter words

Energy Technology Data Exchange (ETDEWEB)

Mirick, G. R.; Bradt, B. M.; Denardo, S. J.; Denardo, G. L. [Calfornia Univ., Sacramento (United States). Davis Medical Center

2004-12-01

The United States Food and Drugs Administration (FDA) has approved unconjugated monoclonal antibodies (MAbs) for immunotherapy (IT) of B-cell lymphoma, breast cancer and acute myeloid leukemia. More recently, approval has been given for conjugated ZevalinTM ({sup 9}0yttrium ibritumomab tiuxetan, IDEC-Y2B8, Biogen Idec, Cambridge, MA) and BexxarTM ({sup 1}31I-tositumomab, Corixa, Corp., Seattle, WA and GlaxoSmithKline, Philadelphia, PA) antiCD20 MAns for use in radioimmunotherapy (RIT) of non-Hodgikin's lymphoma (NHL), thus redefining the standard care of cancer patients. Because of, and despite a lack of basis for concern about allergic reactions due to human antibody responses to these foreign proteins, essays were developed to determine HAGE (human anti-globulin antibody) levels that developed in patient sera following treatment with MAbs. Strategies were also devised to humanize MAbs and to temporarily block patient immune function with drugs in order to decrease the seroconversion rates, with considerable success. On the other hand, a survival advantage has been observed in some patients who developed a HAGA following treatment. This correlates with development of an anti-idiotype antibody cascade directed toward the MAbs used to treat these patients. What follows is a selective review of HAGA and its effect on cancer treatment over the past 2 decades.

Twin pregnancy complicated by severe hemolytic disease of the fetus and newborn due to anti-g and anti-C.

Science.gov (United States)

Trevett, Thomas N; Moise, Kenneth J

2005-11-01

Hemolytic disease of the fetus and newborn caused by anti-G antibodies is rare, and in most previously reported cases, leads to a mild anemia. The RhG antigen is usually found in association with both RhD and RhC. We report a case of a twin pregnancy affected by both anti-G and anti-C alloantibodies leading to severe hemolytic disease of the fetus and newborn requiring multiple intrauterine transfusions and prolonged postnatal therapy. A patient with a prolonged history of previously affected pregnancies due to anti-D and anti-C was subsequently found to be affected with anti-G instead. She required aggressive therapy during her pregnancy, initially with intravenous immune globulin and plasmapheresis until umbilical blood sampling and intrauterine transfusions were feasible. Although hemolytic disease of the fetus and newborn due to anti-G antibodies is rare and usually mild, these pregnancies should be followed up closely and in utero therapy should be offered if necessary.

Huperzine A ameliorates damage induced by acute myocardial infarction in rats through antioxidant, anti-apoptotic and anti-inflammatory mechanisms.

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Sui, Xizhong; Gao, Changqing

2014-01-01

Huperzine A (HupA), an alkaloid used in traditional Chinese medicine and isolated from Huperzia serrata, has been shown to possess diverse biological activities. The present study was undertaken to evaluate the cardioprotective potential of HupA in myocardial ischemic damage using a rat model of acute myocardial infarction. HupA significantly diminished the infarct size and inhibited the activities of myocardial enzymes, including creatine kinase (CK), the MB isoenzyme of creatine kinase (CK-MB), lactate dehydrogenase (LDH) and cardiac troponin T (cTnT). A significantly reduced activity of malondialdehyde (MDA) and elevated activities of superoxide dismutase (SOD), of the non-enzymatic scavenger enzyme, glutathione (GSH), as well as of glutathione peroxidase (GSH-PX) were found in the HupA-treated groups. Furthermore, decreased protein levels of caspase-3 and Bax, and increased levels of Bcl-2 were observed in the infarcted hearts of the rats treated with various concentrations of HupA. In addition, treatment with HupA markedly inhibited the expression of the nuclear factor-κB (NF-κB) subunit p65, tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). These findings suggest that the cardioprotective potential of HupA is associated with its antioxidant, anti-apoptotic and anti-inflammatory properties in acute myocardial infarction in rats.

Acute severe neck pain and dysphagia following cervical maneuver: diagnostic approach.

Science.gov (United States)

Trendel, D; Bonfort, G; Lapierre-Combes, M; Salf, E; Barberot, J-P

2014-04-01

Overlooking an etiologic hypothesis in acute neck pain with dysphagia may lead to misdiagnosis. A 51-year-old man who had received cervical manipulation came to the emergency unit with evolutive acute neck pain, cervical spine stiffness and odynophagia, without fever or other signs of identified pathology. Cervical X-ray and CT angiography of the supra-aortic vessels ruled out traumatic etiology (fracture or arterial dissection) and revealed an accessory bone, orienting diagnosis toward retropharyngeal abscess, which was, however, belied by endoscopy performed under general anesthesia. A second CT scan with contrast injection and tissue phase ruled out infection, revealing a retropharyngeal calcification inducing retropharyngeal edema. Evolution under analgesics was favorable within 13 days. Given a clinical triad associating acute neck pain, cervical spine stiffness and odynophagia, traumatic or infectious etiology was initially suspected. Cervical CT diagnosed calcific tendinitis of the longus colli, revealing a pathognomic retropharyngeal calcification. Secondary to hydroxyapatite deposits anterior to the odontoid process of the axis, this is a rare form of tendinopathy, usually showing favorable evolution in 10-15 days under analgesic and anti-inflammatory treatment. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Assessment and Management of Acute Severe Mitral Regurgitation in the Intensive Care Unit.

Science.gov (United States)

Leitman, Marina; Tyomkin, Vladimir; Raanani, Ehud; Sharony, Ram; Tzatskin, Ludmila; Peleg, Eli; Blatt, Alex; Vered, Zvi

2017-03-01

Acute severe mitral regurgitation (MR) is a serious medical condition. Whilst clear guidelines exist regarding the management of chronic MR, acute severe MR is usually treated on an individual basis. Currently, few data exist regarding acute MR in the era of primary coronary interventions (PCI). The present study included patients admitted to the Department of Cardiology during recent years with acute severe MR of different etiologies, and an analysis of these data in the light of previous investigations. The digital database of the present authors' hospital was searched for patients diagnosed with severe MR between 2008 and 2015. From a total of 228 patients identified, 19 with primary MR and 17 with secondary (functional) MR were admitted to the Department of Cardiology. The clinical data and outcome of these patients were analyzed. Among patients with MR due to acute myocardial infarction (MI), 13 had functional MR and six had MR due to mechanical complications, namely rupture of the papillary muscle or chordae tendineae. Among patients with MR not in the setting of MI, 13 had primary MR and four had functional MR. Patients with MR due to acute MI were more often in cardiogenic shock or had pulmonary edema and had a higher mortality. The strongest predictor of mortality was the presence of shock, followed by female gender, hypertension, age ≥68 years; previous MI and pulmonary edema were also predictors of mortality. In patients with acute MI and secondary MR, PCI to the culprit coronary artery was associated with a lesser degree of MR on follow up. Patients with severe MR are at high risk of in-hospital death. Patients with functional MR are likely to benefit from prompt PCI to the culprit artery, and for those with primary MR urgent surgery is life-saving.

The severe acute respiratory syndrome epidemic in mainland China dissected

NARCIS (Netherlands)

W.-C. Cao (Wu-Chun); S.J. de Vlas (Sake); J.H. Richardus (Jan Hendrik)

2011-01-01

textabstractThis paper provides a review of a recently published series of studies that give a detailed and comprehensive documentation of the severe acute respiratory syndrome (SARS) epidemic in mainland China, which severely struck the country in the spring of 2003. The epidemic spanned a large

Therapeutic administration of a recombinant human monoclonal antibody reduces the severity of chikungunya virus disease in rhesus macaques.

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Rebecca Broeckel

2017-06-01

Full Text Available Chikungunya virus (CHIKV is a mosquito-borne virus that causes a febrile syndrome in humans associated with acute and chronic debilitating joint and muscle pain. Currently no licensed vaccines or therapeutics are available to prevent or treat CHIKV infections. We recently isolated a panel of potently neutralizing human monoclonal antibodies (mAbs, one (4N12 of which exhibited prophylactic and post-exposure therapeutic activity against CHIKV in immunocompromised mice. Here, we describe the development of an engineered CHIKV mAb, designated SVIR001, that has similar antigen binding and neutralization profiles to its parent, 4N12. Because therapeutic administration of SVIR001 in immunocompetent mice significantly reduced viral load in joint tissues, we evaluated its efficacy in a rhesus macaque model of CHIKV infection. Rhesus macaques that were treated after infection with SVIR001 showed rapid elimination of viremia and less severe joint infiltration and disease compared to animals treated with SVIR002, an isotype control mAb. SVIR001 reduced viral burden at the site of infection and at distant sites and also diminished the numbers of activated innate immune cells and levels of pro-inflammatory cytokines and chemokines. SVIR001 therapy; however, did not substantively reduce the induction of CHIKV-specific B or T cell responses. Collectively, these results show promising therapeutic activity of a human anti-CHIKV mAb in rhesus macaques and provide proof-of-principle for its possible use in humans to treat active CHIKV infections.

Features associated with underlying HIV infection in severe acute ...

African Journals Online (AJOL)

NRUs) in Malawi with severe acute malnutrition (SAM) are infected with HIV. There are many similarities in the clinical presentation of SAM and HIV. It is important to identify HIV infected children, in order to improve case management.

Anti-inflammatory treatment and risk of depression in 91,842 patients with acute coronary syndrome and 91,860 individuals without acute coronary syndrome in Denmark

DEFF Research Database (Denmark)

Wium-Andersen, Ida Kim; Wium-Andersen, Marie Kim; Jørgensen, Martin Balslev

2017-01-01

Background We examined if treatment with acetylsalicylic acid (ASA), non-steroid anti-inflammatory drugs (NSAID), or statins after acute coronary syndrome (ACS) are associated with decreased risk of depression. Method This register-based cohort study included all individuals with a first...

High affinity anti-TIM-3 and anti-KIR monoclonal antibodies cloned from healthy human individuals.

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Stefan Ryser

Full Text Available We report here the cloning of native high affinity anti-TIM-3 and anti-KIR IgG monoclonal antibodies (mAbs from peripheral blood mononuclear cells (PBMC of healthy human donors. The cells that express these mAbs are rare, present at a frequency of less than one per 105 memory B-cells. Using our proprietary multiplexed screening and cloning technology CellSpot™ we assessed the presence of memory B-cells reactive to foreign and endogenous disease-associated antigens within the same individual. When comparing the frequencies of antigen-specific memory B-cells analyzed in over 20 screening campaigns, we found a strong correlation of the presence of anti-TIM-3 memory B-cells with memory B-cells expressing mAbs against three disease-associated antigens: (i bacterial DNABII proteins that are a marker for Gram negative and Gram positive bacterial infections, (ii hemagglutinin (HA of influenza virus and (iii the extracellular domain of anaplastic lymphoma kinase (ALK. One of the native anti-KIR mAbs has similar characteristics as lirilumab, an anti-KIR mAb derived from immunization of humanized transgenic mice that is in ongoing clinical trials. It is interesting to speculate that these native anti-TIM-3 and anti-KIR antibodies may function as natural regulatory antibodies, analogous to the pharmacological use in cancer treatment of engineered antibodies against the same targets. Further characterization studies are needed to define the mechanisms through which these native antibodies may function in healthy and disease conditions.

Oxidative stress and inflammation: liver responses and adaptations to acute and regular exercise.

Science.gov (United States)

Pillon Barcelos, Rômulo; Freire Royes, Luiz Fernando; Gonzalez-Gallego, Javier; Bresciani, Guilherme

2017-02-01

The liver is remarkably important during exercise outcomes due to its contribution to detoxification, synthesis, and release of biomolecules, and energy supply to the exercising muscles. Recently, liver has been also shown to play an important role in redox status and inflammatory modulation during exercise. However, while several studies have described the adaptations of skeletal muscles to acute and chronic exercise, hepatic changes are still scarcely investigated. Indeed, acute intense exercise challenges the liver with increased reactive oxygen species (ROS) and inflammation onset, whereas regular training induces hepatic antioxidant and anti-inflammatory improvements. Acute and regular exercise protocols in combination with antioxidant and anti-inflammatory supplementation have been also tested to verify hepatic adaptations to exercise. Although positive results have been reported in some acute models, several studies have shown an increased exercise-related stress upon liver. A similar trend has been observed during training: while synergistic effects of training and antioxidant/anti-inflammatory supplementations have been occasionally found, others reported a blunting of relevant adaptations to exercise, following the patterns described in skeletal muscles. This review discusses current data regarding liver responses and adaptation to acute and regular exercise protocols alone or combined with antioxidant and anti-inflammatory supplementation. The understanding of the mechanisms behind these modulations is of interest for both exercise-related health and performance outcomes.

Pancreatic Enzyme Replacement Therapy in Children with Severe Acute Malnutrition : A Randomized Controlled Trial

NARCIS (Netherlands)

Bartels, Rosalie H.; Bourdon, Celine; Potani, Isabel; Mhango, Brian; van den Brink, Deborah A.; Mponda, John S.; Kobold, Anneke C. Muller; Bandsma, Robert H.; van Hensbroek, Michael Boele; Voskuijl, Wieger P.

Objective: To assess the benefits of pancreatic enzyme replacement therapy (PERT) in children with complicated severe acute malnutrition. Study design: We conducted a randomized, controlled trial in 90 children aged 6-60 months with complicated severe acute malnutrition at the Queen Elizabeth

Pancreatic Enzyme Replacement Therapy in Children with Severe Acute Malnutrition: A Randomized Controlled Trial

NARCIS (Netherlands)

Bartels, Rosalie H.; Bourdon, Céline; Potani, Isabel; Mhango, Brian; van den Brink, Deborah A.; Mponda, John S.; Muller Kobold, Anneke C.; Bandsma, Robert H.; Boele van Hensbroek, Michael; Voskuijl, Wieger P.

2017-01-01

Objective To assess the benefits of pancreatic enzyme replacement therapy (PERT) in children with complicated severe acute malnutrition. Study design We conducted a randomized, controlled trial in 90 children aged 6-60 months with complicated severe acute malnutrition at the Queen Elizabeth Central

Clinical report of an extremely severe bone marrow form of acute radiation sickness

International Nuclear Information System (INIS)

Qiao Jianhui; Yu Changlin; Luo Weidong; Guo Mei; Wang Danhong; Sun Qiyun; Zhang Shi; Zhang Xigang; Li Guang; Niu Wenkai; Chen Jiankui; Li Xiaobing; Ge Feijiao; Ai Huisheng

2007-01-01

Objective: To sum up the experiences from the diagnosis and treatment of patient B subjected to an accidental 60 Co exposure on October 21st, 2004, in Jining, Shandong Province, China. Methods: Radiation dose of B was assessed by analysis of chromosome aberration and microneucleus assay, simulation test of the accident site, autopsy and electron spin resonance (ESR). The ultimate clinical diagnosis was based on analysis of irradiation dose, clinical manifestations and laboratory results. In therapeutical aspects, total environmental protection, HLA-identical allogeneic peripheral blood stem cell transplantation (PBSCT), anti- infection and protection managements of organs were given. Results: Patient B was diagnosed as extremely severe bone marrow form of acute radiation sickness (ARS). HLA-identical allogeneic PBSCT was performed on the patient from his brother on the 7th day after the accident. The hematopoietic recovery began on the 9th day after transplantation. The patient acquired permanent full donor' engraftment without graft versus host disease (GVHD), But the radiation injury was continuing and the patient complicated with polyinfection in lung, and cardiac insufficiency. On the 45th day after the accident, patient B was performed with tracheotomy and maintained ventilation with respirator. On the 75th day after the accident, patient B died of multiple organ failure. Conclusions: Early triage diagnosis and total environmental protection should be performed as soon as possible for extremely severe bone marrow form of ARS. It is very important to perform a successful HLA-identical allogeneic PBSCT, in order to extend the life time of the patient. Multiple organ injuries and infections of bacteria and fungi usually occurred on this kind of patients, so intense measures of anti-infection and protection of multiple organs should be taken. The important and difficult point in the treatment of this kind ARS might be for help the immune-reconstruction and tissue

Analysis of images of acute human and animal leukaemia

International Nuclear Information System (INIS)

Feinermann, Emmanuel

1981-01-01

This research thesis first proposes a review of the development of stereology: historical backgrounds, basic principles. It discusses the choices regarding instrumentation: Coulter counter (principle and theory), quantitative analysis of particles, image analyser (optical microscope, epidiascope, scanners, detection, electronic pencil, computers, programming and data processing system), and stereo-logical parameters. The author then reports the stereo-logical study of acute human leukaemia: definition, classification, determination of spherical particle size distribution, lympho-blast size distributions. He reports the comparative study of rat L 5222 leukaemia and Brown Norway rat acute myelocytic leukaemia, and discusses their relationship with acute human leukaemia

The Study on Acute and Subacute Toxicity and Anti-Cancer Effects of cultivated wild ginseng Herbal acupuncture

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Ki-Rok, Kwon

2003-06-01

Full Text Available Objectives : The purpose of this study was to investigate acute and subacute toxicity and sarcoma-180 anti-cancer effects of herbal acupuncture with cultivated wild ginseng (distilled in mice and rats. Methods : Balb/c mice were injected intravenous with cultivated wild ginseng herbal acupuncture for LD50 and acute toxicity test. Sprague-Dawley rats were injected intravenous with cultivated wild ginseng herbal acupuncture for subacute toxicity test. The cultivated wild ginseng herbal-acupuncture was injected at the tail vein of mice. Results : 1. In acute LD50 toxicity test, there was no mortality thus unable to attain the value. 2. Examining the toxic response in the acute toxicity test, there was no sign of toxication. 3. In acute toxic test, running biochemical serum test couldn't yield any differences between the control and experiment groups. 4. In subacute toxicity test, there was no sign of toxication in the experimental groups and didn't show any changes in weight compared to the normal group. 5. In subacute toxicity test, biochemical serum test showed significant increase of Total albumin, Albumin, and Glucose in the experimental group I compared with the control group. Significant decrease of GOT, ALP, GPT, and Triglyceride were shown. In experiment group II, only Glucose showed significant increase compared with the control group. 6. Measuring survival rate for anti-cancer effects of Sarcoma-180 cancer cell line, all the experimental groups showed significant increase in survival rate. 7. Measuring NK cell activity rate, no significant difference was shown throughout the groups. 8. Measuring Interleukin-2 productivity rate, all the experimental groups didn't show significant difference. 9. For manifestation of cytokine mRNA, significant decrease of interleukin-10 was witnessed in the experimental group compared to the control group. Conclusion : According to the results, we can conclude cultivated wild ginseng herbal acupuncture

Home-based therapy for severe acute malnutrition with ready-to-use food

Science.gov (United States)

Severe acute malnutrition is a devastating condition afflicting children under 5 years in many developing countries, but concentrated in sub-Saharan Africa. This paper examines the development of home-based lipid-nutrient therapeutic foods for the treatment of acute malnutrition in sub-Saharan Afric...

Acute Severe Aortic Regurgitation: Imaging with Pathological Correlation.

Science.gov (United States)

Janardhanan, Rajesh; Pasha, Ahmed Khurshid

2016-03-01

Acute aortic regurgitation (AR) is an important finding associated with a wide variety of disease processes. Its timely diagnosis is of utmost importance. Delay in diagnosis could prove fatal. We describe a case of acute severe AR that was timely diagnosed using real time three-dimensional (3D) transesophageal echocardiogram (3D TEE). Not only did it diagnose but also the images obtained by 3D TEE clearly matched with the pathologic specimen. Using this sophisticated imaging modality that is mostly available at the tertiary centers helped in the timely diagnosis, which lead to the optimal management saving his life. Echocardiography and especially 3D TEE can diagnose AR very accurately. Surgical intervention is the definitive treatment but medical therapy is utilized to stabilize the patient initially.

[Characterization of severe acute occupational poisoning accidents in China between 1989 and 2003].

Science.gov (United States)

Zhang, Min; Li, Tao; Wang, Huan-Qiang; Wang, Hong-Fei; Chen, Shu-Yang; Du, Xie-Yi; Zhang, Shuang; Qin, Jian

2006-12-01

To analyze severe acute occupational poisoning accidents reported in China between 1989 and 2003, and to study the characteristics of severe acute occupational poisoning accidents and provide scientific evidences for prevention and control strategies. The data from the national occupational poisoning case reporting system were analyzed with descriptive methods. (1) There were 506 acute severe occupational poisoning accidents for 15 years with 4 657 workers poisoned. The total poisoning rate was 54.8%, and the total mortality was 16.5%. The average poisoning age was (31.9 +/- 9.8) years old and the average death age was (33.7 +/- 10.3) years old. The poisoning accidents occurred more in men than in women. (2) There were more than 112 chemicals which caused these poisoning accidents. Most of the accidents caused by hydrogen sulfide, carbon monoxide, benzene and homologs, metal and metalloid and carbon dioxide, and the types of chemicals varied in different types of industries. (3) The accidents mainly occurred in chemical industry, manufacture, water disposal industry, mining and construction industry, and the risk was higher in some jobs than others, such as cleanout, machine maintenance and repair, production, mine and digging. The accidents occurred more frequently from April to August each year. (1) The control over the severe acute occupational poisoning is urgent. (2) The trend of the characteristics of severe acute occupational poisoning accidents is centralized in the high risk industries, poisons and jobs. (3) The characteristics of the accidents varied in different types of industries. (4) It is the key point to strengthen the supervision on poisoning.

Viruses as Sole Causative Agents of Severe Acute Respiratory Tract Infections in Children.

Science.gov (United States)

Moesker, Fleur M; van Kampen, Jeroen J A; van Rossum, Annemarie M C; de Hoog, Matthijs; Koopmans, Marion P G; Osterhaus, Albert D M E; Fraaij, Pieter L A

2016-01-01

Respiratory syncytial virus (RSV) and influenza A viruses are known to cause severe acute respiratory tract infections (SARIs) in children. For other viruses like human rhinoviruses (HRVs) this is less well established. Viral or bacterial co-infections are often considered essential for severe manifestations of these virus infections. The study aims at identifying viruses that may cause SARI in children in the absence of viral and bacterial co-infections, at identifying disease characteristics associated with these single virus infections, and at identifying a possible correlation between viral loads and disease severities. Between April 2007 and March 2012, we identified children (acute respiratory tract infection (ARTI) (controls). Data were extracted from the clinical and laboratory databases of our tertiary care paediatric hospital. Patient specimens were tested for fifteen respiratory viruses with real-time reverse transcriptase PCR assays and we selected patients with a single virus infection only. Typical bacterial co-infections were considered unlikely to have contributed to the PICU or MC admission based on C-reactive protein-levels or bacteriological test results if performed. We identified 44 patients admitted to PICU with SARI and 40 patients admitted to MC with ARTI. Twelve viruses were associated with SARI, ten of which were also associated with ARTI in the absence of typical bacterial and viral co-infections, with RSV and HRV being the most frequent causes. Viral loads were not different between PICU-SARI patients and MC-ARTI patients. Both SARI and ARTI may be caused by single viral pathogens in previously healthy children as well as in children with a medical history. No relationship between viral load and disease severity was identified.

Anti-Inflammatory Effect of Emblica officinalis in Rodent Models of Acute and Chronic Inflammation: Involvement of Possible Mechanisms

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Mahaveer Golechha

2014-01-01

Full Text Available Emblica officinalis, commonly known as amla in Ayurveda, is unarguably the most important medicinal plant for prevention and treatment of various ailments. The present study investigated the anti-inflammatory activity of hydroalcoholic extract of Emblica officinalis (HAEEO. Acute inflammation in rats was induced by the subplantar injection of carrageenan, histamine, serotonin, and prostaglandin E2 and chronic inflammation was induced by the cotton pellet granuloma. Intraperitoneal (i.p. administration of HAEEO at all the tested doses (300, 500, and 700 mg/kg significantly (P<0.001 inhibited rat paw edema against all phlogistic agents and also reduced granuloma formation. However, at the dose of 700 mg/kg, HAEEO exhibited maximum anti-inflammatory activity in all experimental models, and the effects were comparable to that of the standard anti-inflammatory drugs. Additionally, in paw tissue the antioxidant activity of HAEEO was also measured and it was found that HAEEO significantly (P<0.001 increased glutathione, superoxide dismutase, and catalase activity and subsequently reduced lipid peroxidation evidenced by reduced malondialdehyde. Taken all together, the results indicated that HAEEO possessed potent anti-inflammatory activity and it may hold therapeutic promise in the management of acute and chronic inflammatory conditions.

Water permeability is a measure of severity in acute appendicitis.

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Pini, Nicola; Pfeifle, Viktoria A; Kym, Urs; Keck, Simone; Galati, Virginie; Holland-Cunz, Stefan; Gros, Stephanie J

2017-12-01

Acute appendicitis is the most common indication for pediatric abdominal emergency surgery. Determination of the severity of appendicitis on clinical grounds is challenging. Complicated appendicitis presenting with perforation, abscess or diffuse peritonitis is not uncommon. The question remains why and when acute appendicitis progresses to perforation. The aim of this study was to assess the impact of water permeability on the severity of appendicitis. We show that AQP1 expression and water permeability in appendicitis correlate with the stage of inflammation and systemic infection parameters, leading eventually to perforation of the appendix. AQP1 is also expressed within the ganglia of the enteric nervous system and ganglia count increases with inflammation. Severity of appendicitis can be correlated with water permeability measured by AQP1 protein expression and increase of ganglia count in a progressive manner. This introduces the question if regulation of water permeability can present novel curative or ameliorating therapeutic options.

Social, dietary and clinical correlates of oedema in children with severe acute malnutrition

DEFF Research Database (Denmark)

Rytter, Maren Johanne Heilskov; Namusoke, Hanifa; Babirekere-Iriso, Esther

2015-01-01

BACKGROUND: Severe acute malnutrition is a serious public health problem, and a challenge to clinicians. Why some children with malnutrition develop oedema (kwashiorkor) is not well understood. The objective of this study was to investigate socio-demographic, dietary and clinical correlates...... of oedema, in children hospitalised with severe acute malnutrition. METHODS: We recruited children with severe acute malnutrition admitted to Mulago Hospital, Uganda. Data was collected using questionnaires, clinical examination and measurement of blood haemoglobin, plasma c-reactive protein and α1-acid...... glycoprotein. Correlates of oedema were identified using multiple logistic regression analysis. RESULTS: Of 120 children included, 77 (64%) presented with oedematous malnutrition. Oedematous children were slightly older (17.7 vs. 15.0 months, p = 0.006). After adjustment for age and sex, oedematous children...

Anti-Cytotoxic and Anti-Inflammatory Effects of the Macrolide Antibiotic Roxithromycin in Sulfur Mustard-Exposed Human Airway Epithelial Cells

National Research Council Canada - National Science Library

Gao1, Radharaman Ray2, Yan Xiao3, Peter E. Barker3 and Prab, Xiugong

2006-01-01

.... In this study, the anti-cytotoxic and anti-inflammatory effects of a representative macrolide antibiotic, roxithromycin, were tested in vitro using SM-exposed normal human small airway epithelial (SAE...

ANTI-IGE THERAPY FOR SEVERE ASTHMA IN CHILDREN: TWO-YEAR TRIAL

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T.Yu. Kulichenko

2010-01-01

Full Text Available The article summarizes a two-year experience of treating children and adolescents with severe uncontrolled atopic asthma using Omalizumab. This treatment facilitated to achieve full asthma control in 70% of patients and partial control in 30% of patients. Anti-Ig Etherapy contributes to reduce the frequency of asthma relapses 77%, and the number of those seeking emergency medical treatment, particularly no need for in-patient asthma care. Thanks to treatment, lung function parameters improve, particularly in children with low bronchial patency parameters even after administration of broncholytics. Thanks to treatment with omalizumab, the dosage of inhalant glucocorticosteroids is reduced 1.5 to 2.5 times in 75% patients. Treatment tolerance in all children is satisfactory, no serious adverse events associated with the medication or any system side effects are registered in patients. Anti-IgE therapy is a good alternative to use of high and ultra-high doses of inhalant glucocorticosteroids in children with severe atopic asthma. Key words: omalizumab, anti-IgE-antibodies, treatment-resistant asthma, atopic asthma, treatment, children, adolescents, asthma control. (Pediatric Pharmacology. – 2010; 7(3:57-65

Anti-inflammatory and antioxidant effects of infliximab on acute lung injury in a rat model of intestinal ischemia/reperfusion.

Science.gov (United States)

Guzel, Ahmet; Kanter, Mehmet; Guzel, Aygul; Pergel, Ahmet; Erboga, Mustafa

2012-06-01

The purpose of this study was to investigate the role of infliximab on acute lung injury induced by intestinal ischemia/reperfusion (I/R). A total of 30 male Wistar albino rats were divided into three groups: sham, I/R and I/R+ infliximab; each group contain 10 animals. Sham group animals underwent laparotomy without I/R injury. After I/R groups animals underwent laparotomy, 1 h of superior mesenteric artery ligation were followed by 1 h of reperfusion. In the infliximab group, 3 days before I/R, infliximab (3 mg/kg) was administered by intravenously. All animals were sacrificed at the end of reperfusion and lung tissues samples were obtained for biochemical and histopathological investigation in all groups. To date, no more biochemical and histopathological changes on intestinal I/R injury in rats by infliximab treatment have been reported. Infliximab treatment significantly decreased the elevated tissue malondialdehyde levels and increased of reduced superoxide dismutase, and glutathione peroxidase enzyme activities in lung tissues samples. Intestinal I/R caused severe histopathological injury including edema, hemorrhage, increased thickness of the alveolar wall and a great number of inflammatory cells that infiltrated the interstitium and alveoli. Infliximab treatment significantly attenuated the severity of intestinal I/R injury. Furthermore, there is a significant reduction in the activity of inducible nitric oxide synthase and arise in the expression of surfactant protein D in lung tissue of acute lung injury induced by intestinal I/R with infliximab therapy. It was concluded that infliximab treatment might be beneficial in acute lung injury, therefore, shows potential for clinical use. Because of its anti-inflammatory and antioxidant effects, infliximab pretreatment may have protective effects in acute lung injury induced by intestinal I/R.

Human anti-CCR4 minibody gene transfer for the treatment of cutaneous T-cell lymphoma.

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Thomas Han

Full Text Available Although several therapeutic options have become available for patients with Cutaneous T-cell Lymphoma (CTCL, no therapy has been curative. Recent studies have demonstrated that CTCL cells overexpress the CC chemokine receptor 4 (CCR4.In this study, a xenograft model of CTCL was established and a recombinant adeno-associated viral serotype 8 (AAV8 vector expressing a humanized single-chain variable fragment (scFv-Fc fusion (scFvFc or "minibody" of anti-CCR4 monoclonal antibody (mAb h1567 was evaluated for curative treatment. Human CCR4+ tumor-bearing mice treated once with intravenous infusion of AAV8 virions encoding the h1567 (AAV8-h1567 minibody showed anti-tumor activity in vivo and increased survival. The AAV8-h1567 minibody notably increased the number of tumor-infiltrating Ly-6G+ FcγRIIIa(CD16A+ murine neutrophils in the tumor xenografts over that of AAV8-control minibody treated mice. Furthermore, in CCR4+ tumor-bearing mice co-treated with AAV8-h1567 minibody and infused with human peripheral blood mononuclear cells (PBMCs, marked tumor infiltration of human CD16A+ CD56+ NK cells was observed. The h1567 minibody also induced in vitro ADCC activity through both mouse neutrophils and human NK cells.Overall, our data demonstrate that the in vivo anti-tumor activity of h1567 minibody is mediated, at least in part, through CD16A+ immune effector cell ADCC mechanisms. These data further demonstrate the utility of the AAV-minibody gene transfer system in the rapid evaluation of candidate anti-tumor mAbs and the potency of h1567 as a potential novel therapy for CTCL.

Clinical significance of serum anti-human papillomavirus 16 and 18 antibodies in cervical neoplasia.

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Chay, Doo Byung; Cho, Hanbyoul; Kim, Bo Wook; Kang, Eun Suk; Song, Eunseop; Kim, Jae-Hoon

2013-02-01

To estimate the clinical significance of serum anti-human papillomavirus (HPV) antibodies and high-risk cervical HPV DNA in cervical neoplasia. The study population comprised patients who were histopathologically diagnosed with cervical intraepithelial neoplasia (CIN) 1 (n=64), CIN 2 and 3 (n=241), cervical cancer (n=170), and normal control participants (n=975). Cervical HPV DNA tests were performed through nucleic acid hybridization assay tests, and serum anti-HPV 16 and 18 antibodies were measured by competitive immunoassay. The associations of HPV DNA and anti-HPV antibodies were evaluated with demographic characteristics and compared according to the levels of disease severity. Anti-HPV antibodies were also investigated with clinicopathologic parameters, including survival data. Among various demographic characteristics, factors involving sexual behavior had a higher tendency of HPV DNA positivity and HPV seropositivity. Human papillomavirus DNA mean titer and positivity were both increased in patients with cervical neoplasia compared with those with normal control participants, but there was no statistical difference among types of cervical neoplasia. Serum anti-HPV 16 antibodies were also able to differentiate cervical neoplasia from a normal control participant and furthermore distinguished CIN 1 from CIN 2 and 3 (odd ratio 2.87 [1.43-5.78], P=.002). In cervical cancer, HPV 16 seropositivity was associated with prolonged disease-free survival according to the univariable analysis (hazard ratio=0.12 [0.01-0.94], P=.044). Serum anti-HPV 16 antibodies can distinguish cervical neoplasia from a normal control and has the advantage of identifying high-grade CIN. Moreover, in cervical cancer, HPV 16 seropositivity may be associated with a more favorable prognosis. II.

Acute sensorineural hearing loss and severe otalgia due to scrub typhus

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Kim Dong-Min

2009-10-01

Full Text Available Abstract Background Scrub typhus is an acute febrile illness caused by Orientia tsutsugamushi. Case presentations We encountered a patient with sensorineural hearing loss complicating scrub typhus, and three patients with scrub typhus who complained of otalgia, which was sudden onset, severe, paroxysmal, intermittent yet persistent pain lasting for several seconds, appeared within 1 week after the onset of fever and rash. The acute sensorineural hearing loss and otalgia were resolved after antibiotic administration. Conclusion When patients in endemic areas present with fever and rash and have sensorineural hearing loss or otalgia without otoscopic abnormalities, clinicians should suspect scrub typhus and consider empirical antibiotic therapy.

Benralizumab: a unique IL-5 inhibitor for severe asthma

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Tan LD

2016-04-01

Full Text Available Laren D Tan,1 Jennifer M Bratt,2 Dorottya Godor,3 Samuel Louie,2 Nicholas J Kenyon2 1Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, School of Medicine, Loma Linda University, Loma Linda, CA, USA; 2Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, School of Medicine, University of California Davis, Sacramento, CA, USA; 3School of Medicine, Semmelweis University, Budapest, Hungary Abstract: The presence of eosinophilic inflammation is a characteristic feature of chronic and acute inflammation in asthma. An estimated 5%–10% of the 300 million people worldwide who suffer from asthma have a severe form. Patients with eosinophilic airway inflammation represent approximately 40%–60% of this severe asthmatic population. This form of asthma is often uncontrolled, marked by refractoriness to standard therapy, and shows persistent airway eosinophilia despite glucocorticoid therapy. This paper reviews personalized novel therapies, more specifically benralizumab, a humanized anti-IL-5Rα antibody, while also being the first to provide an algorithm for potential candidates who may benefit from anti-IL-5Rα therapy. Keywords: asthma, eosinophils, asthma treatments, benralizumab, IL-5, IL-5Rα, MEDI-563

Three-Dimensional Human Bronchial-Tracheal Epithelial Tissue-Like Assemblies (TLAs) as Hosts for Severe Acute Respiratory Syndrome (SARS)-CoV Infection

Science.gov (United States)

Suderman, M. T.; McCarthy, M.; Mossell, E.; Watts, D. M.; Peters, C. J.; Shope, R.; Goodwin, T. J.

2006-01-01

A three-dimensional (3-D) tissue-like assembly (TLA) of human bronchial-tracheal mesenchymal (HBTC) cells with an overlay of human bronchial epithelial (BEAS-2B) cells was constructed using a NASA Bioreactor to survey the infectivity of SARS-CoV. This TLA was inoculated with a low passage number Urbani strain of SARS-CoV. At selected intervals over a 10-day period, media and cell aliquots of the 3-D TLA were harvested for viral titer assay and for light and electron microscopy examination. All viral titer assays were negative in both BEAS-2B two-dimensional monolayer and TLA. Light microscopy immunohistochemistry demonstrated antigen-antibody reactivity with anti-SARS-CoV polyclonal antibody to spike and nuclear proteins on cell membranes and cytoplasm. Coronavirus Group 2 cross-reactivity was demonstrated by positive reaction to anti-FIPV 1 and anti-FIPV 1 and 2 antibodies. TLA examination by transmission electron microscopy indicated increasing cytoplasmic vacuolation with numerous electron-dense bodies measuring 45 to 270 nm from days 4 through 10. There was no evidence of membrane blebbing, membrane duplication, or fragmentation of organelles in the TLAs. However, progressive disruption of endoplasmic reticulum was observed throughout the cells. Antibody response to SARS-CoV specific spike and nucleocapsid glycoproteins, cross-reactivity with FIPV antibodies, and the cytoplasmic pathology suggests this HBTE TLA model is permissive to SARS-CoV infection.

Severe and acute complications of biologics in psoriasis.

Science.gov (United States)

Oussedik, Elias; Patel, Nupur U; Cash, Devin R; Gupta, Angela S; Feldman, Steven R

2017-12-01

Biologic therapies have revolutionized the approach to immune-mediated diseases such as psoriasis. Due to their favorable safety profiles and excellent efficacy, biologic agents are considered the gold standard for moderate-to-severe psoriasis. The aim of this paper is to saliently review the severe and acute complications of the Food and Drug Administration (FDA) approved biologic agents for psoriasis. Reviewed agents include tumor necrosis factor alpha inhibitors (etanercept, infliximab, and adalimumab), interleukin 12/23 inhibitors (ustekinumab), and interleukin 17 (IL-17) inhibitors (secukinumab and ixekizumab). While malignancies, serious infections, and major adverse cardiovascular events have been reported, their association with biologic therapy are not hypothesized as causal. However, IL-17 inhibitors appear to cause exacerbations and new cases of inflammatory bowel disease. While more long-term studies are warranted in understanding the biologic's long-term side effect profile, short-term studies have confirmed that the biologics are some of the safest treatment options for psoriasis. Nevertheless, certain populations yield higher risk to acute complications with the biologics than others - physicians must use their judgement and vigilance when monitoring and treating patients undergoing therapy with biological agents.

Bovine lactoferricin is anti-inflammatory and anti-catabolic in human articular cartilage and synovium.

Science.gov (United States)

Yan, Dongyao; Chen, Di; Shen, Jie; Xiao, Guozhi; van Wijnen, Andre J; Im, Hee-Jeong

2013-02-01

Bovine lactoferricin (LfcinB) is a multi-functional peptide derived from proteolytic cleavage of bovine lactoferrin. LfcinB was found to antagonize the biological effects mediated by angiogenic growth factors such as vascular endothelial growth factor (VEGF) and fibroblast growth factor 2 (FGF-2) in endothelial cells. However, the effect of LfcinB on human articular cartilage remained unknown. Here, our findings demonstrate that LfcinB restored the proteoglycan loss promoted by catabolic factors (interleukin-1β) IL-1β and FGF-2 in vitro and ex vivo. Mechanistically, LfcinB attenuated the effects of IL-1β and FGF-2 on the expression of cartilage-degrading enzymes (MMP-1, MMP-3, and MMP-13), destructive cytokines (IL-1β and IL-6), and inflammatory mediators (iNOS and TLR2). LfcinB induced protective cytokine expression (IL-4 and IL-10), and downregulated aggrecanase basal expression. LfcinB specifically activated ERK MAPK and Akt signaling pathways, which may account for its anti-inflammatory activity. We also revealed that LfcinB exerted similar protective effects on human synovial fibroblasts challenged by IL-1β, with minimal cytotoxicity. Collectively, our results suggest that LfcinB possesses potent anti-catabolic and anti-inflammatory bioactivities in human articular tissues, and may be utilized for the prevention and/or treatment of OA in the future. Copyright © 2012 Wiley Periodicals, Inc.

Absence of anti-HMG-CoA reductase autoantibodies in severe self-limited statin-related myopathy.

Science.gov (United States)

Floyd, James S; Brody, Jennifer A; Tiniakou, Eleni; Psaty, Bruce M; Mammen, Andrew

2016-06-01

Patients with self-limited statin-related myopathy improve spontaneously when statins are stopped. In contrast, patients with statin-associated autoimmune myopathy have autoantibodies recognizing 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGCR) and usually require immunosuppressive therapy to control their disease. On initial presentation, it can sometimes be difficult to distinguish between these 2 diseases, as both present with muscle pain, weakness, and elevated serum creatine kinase (CK) levels. The goal of this study was to determine whether patients with severe self-limited statin-related myopathy also make anti-HMGCR autoantibodies. We screened 101 subjects with severe self-limited cerivastatin-related myopathy for anti-HMGCR autoantibodies. No patient with severe self-limited cerivastatin-related myopathy had anti-HMGCR autoantibodies. Anti-HMGCR autoantibody testing can be used to help differentiate whether a patient has self-limited myopathy due to cerivastatin or autoimmune statin-associated myopathy; these findings may apply to other statins as well. Muscle Nerve 54: 142-144, 2016. © 2016 Wiley Periodicals, Inc.

INFLAMMATORY MARKERS IN ACUTE ISCHAEMIC STROKE IN RELATION TO CLINICAL SEVERITY AND EARLY OUTCOME

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S. Gopi

2018-01-01

Full Text Available BACKGROUND Biochemical markers of inflammation could be useful to predict severity of stroke in acute phase. Stroke is the third cause of mortality and the first cause of disability. Recent literature have demonstrated that inflammation contributes to all phases of atherosclerosis. The results of researchers suggest that atherosclerosis is an inflammatory disease. The aim of the study is to assess the1. Level of peripheral inflammatory markers in acute ischaemic stroke and their relation to severity of acute stroke. 2. Value of inflammatory markers in predicting the short-term outcome and disability at the end of six months. MATERIALS AND METHODS This is a prospective case control study for 6 months done from September 2014 to August 2016 in 100 patients of acute ischaemic stroke within first 5 days of symptom onset in comparison >18 years of age with 50 age and sex matched controls. Blood samples for all cases and controls were sent for erythrocyte sedimentation rate, Neutrophil-to-Lymphocyte Ratio (NLR, hs-C-reactive protein, mean platelet volume, serum ferritin, serum albumin and S. gamma-glutamyl transferase at admission. RESULTS The mean values of ESR, NLR, hs-CRP in all the cases are higher when compared to the controls and are statistically significant, whereas the mean values of MPV, S. ferritin, S. albumin and GGT in cases are lower when compared to controls, but are within normal range and difference is statistically significant except ferritin. ESR, hs-CRP has significant correlation with severity of acute ischaemic stroke. The mean values of these markers increased with increase in severity. Serum albumin has significant correlation with severity of acute ischaemic stroke with mean values of these markers decreasing with increase in severity of stroke. There is no significant correlation of the inflammatory markers in present study with the short-term outcome. CONCLUSION Inflammation plays an important role in the pathogenesis of non

Humanized CD7 nanobody-based immunotoxins exhibit promising anti-T-cell acute lymphoblastic leukemia potential.

Science.gov (United States)

Yu, Yuan; Li, Jialu; Zhu, Xuejun; Tang, Xiaowen; Bao, Yangyi; Sun, Xiang; Huang, Yuhui; Tian, Fang; Liu, Xiaomei; Yang, Lin

2017-01-01

Nanobodies, named as VHHs (variable domain of heavy chain of HCAb [heavy-chain antibodies]), are derived from heavy-chain-only antibodies that circulate in sera of camelids. Their exceptional physicochemical properties, possibility of humanization, and unique antigen recognition properties make them excellent candidates for targeted delivery of biologically active components, including immunotoxins. In our previous efforts, we have successfully generated the monovalent and bivalent CD7 nanobody-based immunotoxins, which can effectively trigger the apoptosis of CD7-positive malignant cells. To pursue the possibility of translating those immunotoxins into clinics, we humanized the nanobody sequences (designated as dhuVHH6) as well as further truncated the Pseudomonas exotoxin A (PE)-derived PE38 toxin to produce a more protease-resistant form, which is named as PE-LR, by deleting majority of PE domain II. Three new types of immunotoxins, dhuVHH6-PE38, dVHH6-PE-LR, and dhuVHH6-PE-LR, were successfully constructed. These recombinant immunotoxins were expressed in Escherichia coli and showed that nanobody immunotoxins have the benefits of easy soluble expression in a prokaryotic expression system. Flow cytometry results revealed that all immunotoxins still maintained the ability to bind specifically to CD7-positive T lymphocyte strains without binding to CD7-negative control cells. Laser scanning confocal microscopy revealed that these proteins can be endocytosed into the cytoplasm after binding with CD7-positive cells and that this phenomenon was not observed in CD7-negative cells. WST-8 experiments showed that all immunotoxins retained the highly effective and specific growth inhibition activity in CD7-positive cell lines and primary T-cell acute lymphoblastic leukemia (T-ALL) cells. Further in vivo animal model experiments showed that humanized dhuVHH6-PE38 immunotoxin can tolerate higher doses and extend the survival of NOD-Prkdc em26 Il2rg em26 Nju (NCG) mice

Ulinastatin Reduces T Cell Apoptosis in Rats with Severe Acute ...

African Journals Online (AJOL)

in rats with severe acute pancreatitis (SAP) and to elucidate its underlying molecular mechanism. Methods: Thirty .... on T lymphocytes apoptosis in SAP rat model and elucidated ..... oxygen radicals, the exhaustion of adenine nucleotide and ...

[Identifying the severe acute pancreatitis].

Science.gov (United States)

Acevedo Tizón, Anais; Targarona Modena, Javier; Málaga Rodríguez, Germán; Barreda Cevasco, Luis

2011-01-01

To compare patients with acute necrotizing pancreatitis without any additional complications during their hospital stay (Group A) versus patients with Acute Necrotizing Pancreatitis with additional complications during their hospital stay (Group B). Data obtained from a pre-existing base from hospitalized patients with diagnosis of acute necrotizing pancreatitis in the specialized unit of "Unidad de Pancreatitis Aguda Grave del Hospital Nacional Edgardo Rebagliati Martins" between 2000 and 2010. Data included patients with diagnosis of acute necrotizing pancreatitis, of ages 18 and over. Data from 215 patients with acute necrotizing pancreatitis was included. Patients from Group A represented 32% (68) and from Group B 68% (147). Group A had a average of 39 hospitalized days and Group B had an average of 56 days (p=0.01). From Group A 22% had more than 50% of necrosis while 43% of Group B had this extension of necrosis (p pancreatitis, based on the presence of necrosis, behave likewise. It is an extended necrosis, described as more than 50% of pancreatic necrosis, and not the presence itself which will determine additional complications during the course of disease and a greater mortality.

Severe glandular tularemia in a patient treated with anti-tumour necrosis factor for psoriatic arthritis

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Ruxandra Calin

2017-07-01

Full Text Available A case of severe glandular tularemia in a patient receiving anti-tumour necrosis factor (TNF therapy is reported here. The patient required prolonged treatment with doxycycline–ciprofloxacin due to early relapse after ciprofloxacin was stopped. Tularemia may have a more severe course in patients receiving anti-TNF. This may thus be an indication for more aggressive treatment.

Soluble CD163 is increased in patients with acute pancreatitis independent of disease severity.

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Karrasch, Thomas; Brünnler, Tanja; Hamer, Okka W; Schmid, Karin; Voelk, Markus; Herfarth, Hans; Buechler, Christa

2015-10-01

Macrophages are crucially involved in the pathophysiology of acute pancreatitis. Soluble CD163 (sCD163) is specifically released from macrophages and systemic levels are increased in inflammatory diseases. Here, sCD163 was measured in serum of 50 patients with acute pancreatitis to find out possible associations with disease activity. Admission levels of systemic sCD163 were nearly three-fold higher in patients with acute pancreatitis compared to controls. In patients sCD163 did not correlate with C-reactive protein and leukocyte count as established markers of inflammation. Levels were not associated with disease severity assessed by the Schroeder score, Balthazar score, Acute Physiology, Age, and Chronic Health Evaluation (Apache) II score and peripancreatic necrosis score. Soluble CD163 was not related to complications of acute pancreatitis. These data show that serum sCD163 is increased in acute pancreatitis indicating activation of macrophages but is not associated with disease severity and outcome. Copyright © 2015 Elsevier Inc. All rights reserved.

Non-infectious chemotherapy-associated acute toxicities during childhood acute lymphoblastic leukemia therapy

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Schmiegelow, Kjeld; Müller, Klaus; Mogensen, Signe Sloth; Mogensen, Pernille Rudebeck; Wolthers, Benjamin Ole; Stoltze, Ulrik Kristoffer; Tuckuviene, Ruta; Frandsen, Thomas

2017-01-01

During chemotherapy for childhood acute lymphoblastic leukemia, all organs can be affected by severe acute side effects, the most common being opportunistic infections, mucositis, central or peripheral neuropathy (or both), bone toxicities (including osteonecrosis), thromboembolism, sinusoidal obstruction syndrome, endocrinopathies (especially steroid-induced adrenal insufficiency and hyperglycemia), high-dose methotrexate-induced nephrotoxicity, asparaginase-associated hypersensitivity, pancreatitis, and hyperlipidemia. Few of the non-infectious acute toxicities are associated with clinically useful risk factors, and across study groups there has been wide diversity in toxicity definitions, capture strategies, and reporting, thus hampering meaningful comparisons of toxicity incidences for different leukemia protocols. Since treatment of acute lymphoblastic leukemia now yields 5-year overall survival rates above 90%, there is a need for strategies for assessing the burden of toxicities in the overall evaluation of anti-leukemic therapy programs. PMID:28413626

Anti-Inflammatory and Antinociceptive Effects of Salbutamol on Acute and Chronic Models of Inflammation in Rats: Involvement of an Antioxidant Mechanism

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Hulya Uzkeser

2012-01-01

Full Text Available The possible role of β-2 adrenergic receptors in modulation of inflammatory and nociceptive conditions suggests that the β-2 adrenergic receptor agonist, salbutamol, may have beneficial anti-inflammatory and analgesic effects. Therefore, in this study, we induced inflammatory and nociceptive responses with carrageenan-induced paw edema or cotton-pellet-induced granuloma models, both of which result in oxidative stress. We hypothesized that salbutamol would prevent inflammatory and nociceptive responses by stimulating β-2 adrenergic receptors and the prevention of generation of ROS during the acute inflammation process in rats. Both doses of salbutamol used in the study (1 and 2 mg/kg effectively blocked the acute inflammation and inflammatory nociception induced by carrageenan. In the cotton-pellet-induced granuloma test, both doses of salbutamol also significantly decreased the weight of granuloma tissue on the cotton pellets when compared to the control. Anti-inflammatory and analgesic effects of salbutamol were found to be comparable with those of indomethacin. Salbutamol decreased myeloperoxidase (MPO activity and lipid peroxidation (LPO level and increased the activity of superoxide dismutase (SOD and level of glutathione (GSH during the acute phase of inflammation. In conclusion, salbutamol can decrease acute and chronic inflammation, possibly through the stimulation of β-2 adrenergic receptors. This anti-inflammatory effect may be of significance in asthma treatment, where inflammation also takes part in the etiopathology. This study reveals that salbutamol has significant antioxidative effects, which at least partially explain its anti-inflammatory capabilities. These findings presented here may also shed light on the roles of β-2 adrenergic receptors in inflammatory and hyperalgesic conditions.

Spontaneous acute spinal subdural hematoma: spontaneous recovery from severe paraparesis--case report and review.

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Payer, Michael; Agosti, Reto

2010-11-01

Spontaneous idiopathic acute spinal subdural hematomas are highly exceptional. Neurological symptoms are usually severe, and rapid diagnosis with MRI is mandatory. Surgical evacuation has frequently been used therapeutically; however, spontaneous recovery in mild cases has also been reported. We present a case of spontaneous recovery from severe paraparesis after spontaneous acute SSDH, and review the English-speaking literature.

Clinical profile, degree of severity and underlying factors of acute pancreatitis among a group of Bangladeshi patients

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Indrajit Kumar Datta

2018-01-01

Full Text Available Background and objectives: Acute pancreatitis is a common condition for hospital admission. In Bangladesh, no study has yet investigated the clinical profile, degree of severity and underlying factors of acute pancreatitis. The aim of the present study was to determine the clinical profile, degree of severity and underlying factors of acute pancreatitis in a cohort of Bangladeshi patients. Methods: This prospective study was conducted from April 2016 to March 2017 on patients admitted with acute pancreatitis at Bangladesh Institute of Research and Rehabilitation in Diabetes, Endocrine and Metabolic Disorders (BIRDEM General Hospital, Dhaka, Bangladesh. History and clinical features of each patient was systematically recorded. Diagnosis of acute pancreatitis was made by clinical findings, serum amylase and lipase levels (> 3 times the upper limit of normal values, evidences of acute pancreatitis by ultrasonography and computed tomography (CT. Severity of acute pancreatitis was classified according to the revised version of Atlanta classification. Results: A total of 40 patients with acute pancreatitis were enrolled in the study. Male and female were equally distributed. The mean age was 44.3±2.7 years. Among 40 cases, 26 (65.0% and 14 (35% had moderate and severe acute pancreatitis respectively. No specific clinical feature including ascites or pleural effusion was found significantly related to severity of the disease. Gall stone and metabolic (hypertriglyceridaemia/hypercalcemia causes were present in 62.5% cases, but none had significant association with the severity of the disease. Conclusion: The present study has demonstrated that no specific observed clinical feature or underlying factor was related to the degree of severity of acute pancreatitis in a cohort of Bangladeshi patients. IMC J Med Sci 2018; 12(1: 06-10

Severe acute pancreatitis : Improving outcome

NARCIS (Netherlands)

van Brunschot, S.

2018-01-01

This thesis contains results of 8 years of clinical research performed to improve the treatment of patients with acute pancreatitis. The first part of this thesis focusses on diagnostics and the prevention of complications. The applicability of the revised Atlanta classification for acute

Predictors of oedema among children hospitalized with severe acute malnutrition in Jimma University Hospital, Ethiopia

DEFF Research Database (Denmark)

Girma, Tsinuel; Kæstel, Pernille; Mølgaard, Christian

2013-01-01

Severe acute malnutrition has two main clinical manifestations, i.e., oedematous and non-oedematous. However, factors of oedema are not well established.......Severe acute malnutrition has two main clinical manifestations, i.e., oedematous and non-oedematous. However, factors of oedema are not well established....

Fish oil, but not soy bean or olive oil enriched infusion decreases histopathological severity of acute pancreatitis in rats without affecting eicosanoid synthesis.

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Kilian, Maik; Heukamp, Ina; Gregor, Ja Ilja; Schimke, Ingolf; Kristiansen, Glen; Wenger, Frank Axel

2011-12-01

Different dietary fatty acids affect eicosanoid metabolism in different ways, thus influencing the pro- and anti-inflammatory balance of prostaglandins and leukotrienes. Therefore, we analyzed the impact of [n-3], [n-6], and [n-9] fatty acids on eicosanoid metabolism and histopathology in acute pancreatitis in rats. Seventy-five male Sprague-Dawley rats were randomized into five groups (n = 15). Group 1 underwent only laparotomy, while in groups, 2-5 pancreatitis was induced. Groups 1 and 2 were then given saline infusion, groups 3-5 received fat emulsion (group 3: rich in [n-6], group 4: rich in [n-9], group 5: rich in [n-3] fatty acids) for another 18 h. Infusion rich in [n-3] fatty acids significantly decreased histopathological severity of pancreatitis, compared to all other groups. There was no difference concerning the concentrations of prostaglandins and leukotrienes between all groups. Parenteral infusion rich in [n-3] fatty acids reduced histopathological severity of acute pancreatitis in rats without changing eicosanoid metabolism at the endpoint.

Factors secreted from dental pulp stem cells show multifaceted benefits for treating acute lung injury in mice.

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Wakayama, Hirotaka; Hashimoto, Naozumi; Matsushita, Yoshihiro; Matsubara, Kohki; Yamamoto, Noriyuki; Hasegawa, Yoshinori; Ueda, Minoru; Yamamoto, Akihito

2015-08-01

Acute respiratory distress syndrome (ARDS) is a severe inflammatory disorder characterized by acute respiratory failure, resulting from severe, destructive lung inflammation and irreversible lung fibrosis. We evaluated the use of stem cells derived from human exfoliated deciduous teeth (SHEDs) or SHED-derived serum-free conditioned medium (SHED-CM) as treatments for bleomycin (BLM)-induced mice acute lung injury (ALI), exhibiting several pathogenic features associated with the human disease ARDS. Mice with BLM-induced ALI with or without SHED or SHED-CM treatment were examined for weight loss and survival. The lung tissue was characterized by histological and real-time quantitative polymerase chain reaction analysis. The effects of SHED-CM on macrophage differentiation in vitro were also assessed. A single intravenous administration of either SHEDs or SHED-CM attenuated the lung injury and weight loss in BLM-treated mice and improved their survival rate. Similar recovery levels were seen in the SHEDs and SHED-CM treatment groups, suggesting that SHED improves ALI by paracrine mechanisms. SHED-CM contained multiple therapeutic factors involved in lung-regenerative mechanisms. Importantly, SHED-CM attenuated the BLM-induced pro-inflammatory response and generated an anti-inflammatory/tissue-regenerating environment, accompanied by the induction of anti-inflammatory M2-like lung macrophages. Furthermore, SHED-CM promoted the in vitro differentiation of bone marrow-derived macrophages into M2-like cells, which expressed high levels of Arginase1, CD206 and Ym-1. Our results suggest that SHED-secreted factors provide multifaceted therapeutic effects, including a strong M2-inducing activity, for treating BLM-induced ALI. This work may open new avenues for research on stem cell-based ARDS therapies. Copyright © 2015 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Antibody-dependent cellular cytotoxicity (ADCC) activity of a novel anti-PD-L1 antibody avelumab (MSB0010718C) on human tumor cells

OpenAIRE

Boyerinas, Benjamin; Jochems, Caroline; Fantini, Massimo; Heery, Christopher R.; Gulley, James L.; Tsang, Kwong Yok; Schlom, Jeffrey

2015-01-01

Several anti-PD1/PD-L1 monoclonal antibodies (MAb) are currently providing evidence of clinical benefit in subsets of cancer patients. The mode of action of these MAbs is to inhibit PD1 on immune cells interacting with PD-L1 on tumor cells. These MAbs are either designed or engineered to eliminate antibody-dependent cell-mediated cytotoxicity (ADCC), which, however, has been implicated as an important mechanism in several highly effective MAb-mediated cancer therapies. A fully human anti-PD-L...

Severe Hyperthyroidism Presenting with Acute ST Segment Elevation Myocardial Infarction

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Dayan Zhou

2015-01-01

Full Text Available Introduction. Acute myocardial infarction is life-threatening. A cardiac troponin rise accompanied by typical symptoms, ST elevation or depression is diagnostic of acute myocardial infarction. Here, we report an unusual case of a female who was admitted with chest pain. However, she did not present with a typical profile of an acute myocardial infarction patient. Case Presentation. A 66-year-old Han nationality female presented with chest pain. The electrocardiogram (ECG revealed arched ST segment elevations and troponin was elevated. However, the coronary angiography showed a normal coronary arterial system. Thyroid function tests showed that this patient had severe hyperthyroidism. Conclusion. Our case highlights the possibility that hyperthyroidism may cause a large area of myocardium injury and ECG ST segment elevation. We suggest routine thyroid function testing in patients with chest pain.

Anti-proliferative activity of 2,6-dichloro-9- or 7-(ethoxycarbonylmethyl)-9H- or 7H-purines against several human solid tumour cell lines.

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Morales, Fátima; Ramírez, Alberto; Conejo-García, Ana; Morata, Cynthia; Marchal, Juan A; Campos, Joaquín M

2014-04-09

As leads we took several benzo-fused seven- and six-membered scaffolds linked to the pyrimidine or purine moieties with notable anti-proliferative activity against human breast, colon and melanoma cancerous cell lines. We then decided to maintain the double-ringed nitrogenous bases and change the other components to the ethyl acetate moiety. This way six purine and two 5-fluorouracil derivatives were obtained and evaluated against the MCF-7, HCT-116, A-375 and G-361 cancer cell lines. Two QSARs are obtained between the anti-proliferative IC₅₀ values for compounds 26-33 and the clog P against the melanoma cell lines A-375 and G-361. Our results show that two of the analogues [ethyl 2-(2,6-dichloro-9H- or 7H-purine-9- or 7-yl)acetates (30 and 33, respectively)] are potent cytotoxic agents against all the tumour cell lines assayed, showing single-digit micromolar IC₅₀ values. This exemplifies the potential of our previously reported purine compounds to qualify as lead structures for medicinal chemistry campaigns, affording simplified analogues easy to synthesize and with a noteworthy bioactivity. The selective activity of 30 and 33 against the melanoma cell line A-375, via apoptosis, supposes a great advantage for a future therapeutic use. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

VEGF Promotes Malaria-Associated Acute Lung Injury in Mice

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Carapau, Daniel; Pena, Ana C.; Ataíde, Ricardo; Monteiro, Carla A. A.; Félix, Nuno; Costa-Silva, Artur; Marinho, Claudio R. F.; Dias, Sérgio; Mota, Maria M.

2010-01-01

The spectrum of the clinical presentation and severity of malaria infections is broad, ranging from uncomplicated febrile illness to severe forms of disease such as cerebral malaria (CM), acute lung injury (ALI), acute respiratory distress syndrome (ARDS), pregnancy-associated malaria (PAM) or severe anemia (SA). Rodent models that mimic human CM, PAM and SA syndromes have been established. Here, we show that DBA/2 mice infected with P. berghei ANKA constitute a new model for malaria-associated ALI. Up to 60% of the mice showed dyspnea, airway obstruction and hypoxemia and died between days 7 and 12 post-infection. The most common pathological findings were pleural effusion, pulmonary hemorrhage and edema, consistent with increased lung vessel permeability, while the blood-brain barrier was intact. Malaria-associated ALI correlated with high levels of circulating VEGF, produced de novo in the spleen, and its blockage led to protection of mice from this syndrome. In addition, either splenectomization or administration of the anti-inflammatory molecule carbon monoxide led to a significant reduction in the levels of sera VEGF and to protection from ALI. The similarities between the physiopathological lesions described here and the ones occurring in humans, as well as the demonstration that VEGF is a critical host factor in the onset of malaria-associated ALI in mice, not only offers important mechanistic insights into the processes underlying the pathology related with malaria but may also pave the way for interventional studies. PMID:20502682

Anti-Cyclic Citrullinated Peptide Antibodies and Severity of Interstitial Lung Disease in Women with Rheumatoid Arthritis

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Alberto Daniel Rocha-Muñoz

2015-01-01

Full Text Available Objective. To evaluate whether serum titers of second-generation anticyclic citrullinated peptide antibodies (anti-CCP2 are associated with the severity and extent of interstitial lung disease in rheumatoid arthritis (RA-ILD. Methods. In across-sectional study, 39 RA-ILD patients confirmed by high-resolution computed tomography (HRCT were compared with 42 RA without lung involvement (RA only. Characteristics related to RA-ILD were assessed in all of the patients and serum anti-CCP2 titers quantified. Results. Higher anti-CCP2 titers were found in RA-ILD compared with RA only (medians 77.9 versus 30.2 U/mL, P<0.001. In the logistic regression analysis after adjustment for age, disease duration (DD, smoke exposure, disease activity, functioning, erythrocyte sedimentation rate, and methotrexate (MTX treatment duration, the characteristics associated with RA-ILD were higher anti-CCP2 titers (P=0.003 and + RF (P=0.002. In multivariate linear regression, the variables associated with severity of ground-glass score were anti-CCP2 titers (P=0.02 and with fibrosis score DD (P=0.01, anti-CCP2 titers (P<0.001, and MTX treatment duration (P<0.001. Conclusions. Anti-CCP2 antibodies are markers of severity and extent of RA-ILD in HRCT. Further longitudinal studies are required to identify if higher anti-CCP2 titers are associated with worst prognosis in RA-ILD.

Role of Acute Lesion Topography in Initial Ischemic Stroke Severity and Long-Term Functional Outcomes.

Science.gov (United States)

Wu, Ona; Cloonan, Lisa; Mocking, Steven J T; Bouts, Mark J R J; Copen, William A; Cougo-Pinto, Pedro T; Fitzpatrick, Kaitlin; Kanakis, Allison; Schaefer, Pamela W; Rosand, Jonathan; Furie, Karen L; Rost, Natalia S

2015-09-01

Acute infarct volume, often proposed as a biomarker for evaluating novel interventions for acute ischemic stroke, correlates only moderately with traditional clinical end points, such as the modified Rankin Scale. We hypothesized that the topography of acute stroke lesions on diffusion-weighted magnetic resonance imaging may provide further information with regard to presenting stroke severity and long-term functional outcomes. Data from a prospective stroke repository were limited to acute ischemic stroke subjects with magnetic resonance imaging completed within 48 hours from last known well, admission NIH Stroke Scale (NIHSS), and 3-to-6 months modified Rankin Scale scores. Using voxel-based lesion symptom mapping techniques, including age, sex, and diffusion-weighted magnetic resonance imaging lesion volume as covariates, statistical maps were calculated to determine the significance of lesion location for clinical outcome and admission stroke severity. Four hundred ninety subjects were analyzed. Acute stroke lesions in the left hemisphere were associated with more severe NIHSS at admission and poor modified Rankin Scale at 3 to 6 months. Specifically, injury to white matter (corona radiata, internal and external capsules, superior longitudinal fasciculus, and uncinate fasciculus), postcentral gyrus, putamen, and operculum were implicated in poor modified Rankin Scale. More severe NIHSS involved these regions, as well as the amygdala, caudate, pallidum, inferior frontal gyrus, insula, and precentral gyrus. Acute lesion topography provides important insights into anatomic correlates of admission stroke severity and poststroke outcomes. Future models that account for infarct location in addition to diffusion-weighted magnetic resonance imaging volume may improve stroke outcome prediction and identify patients likely to benefit from aggressive acute intervention and personalized rehabilitation strategies. © 2015 American Heart Association, Inc.

[Clinical analysis of acute encephalocele during operation in 21 patients with severe craniocerebral injury].

Science.gov (United States)

Zhuang, Qiang; Qu, Chun-cheng; Liang, Wen-zhi; Qin, Hao; Yu, Rui

2011-03-08

To analyze the clinical features of acute intra-operative encephalocele and the proper prophylactic-therapeutic measures for severe craniocerebral injury. The clinical data were collected and analyzed for 21 patients with severe head injuries who suffered acute intra-operative encephalocele from June 2008 to May 2010. There were 12 males and 9 females with an age range of 18 - 69 years old. Among these patients, 6 died with a mortality rate of 28.5%. It was lower than that reported in literatures. One patient died post-operatively of severe brain swelling and intracranial infection secondary to leakage of cerebrospinal fluid. Four patients died of severe craniocerebral injury, brain swelling and brain stem failure. And 1 patient died after his guardian abandoned the treatment. The follow-up period for the remaining 15 surviving patients was 3 - 6 months. According to the Glasgow outcome score (GOS), there were a favorable prognosis (n = 9), moderate disabilities (n = 5) and severe disability (n = 1). The probability of acute intra-operative encephalocele may be predicted in advance with a combination of clinical features and computed tomographic scans. The therapeutic success rate of acute encephalocele will be boosted by taking protective and therapeutic measures pre- and intra-operatively.

Association of interleukin-8 and neutrophils with nasal symptom severity during acute respiratory infection.

Science.gov (United States)

Henriquez, Kelsey M; Hayney, Mary S; Xie, Yaoguo; Zhang, Zhengjun; Barrett, Bruce

2015-02-01

Using a large data set (n = 811), the relationship between acute respiratory infection illness severity and inflammatory biomarkers was investigated to determine whether certain symptoms are correlated more closely than others with the inflammatory biomarkers, interleukin-8 (IL-8) and nasal neutrophils. Participants with community acquired acute respiratory infection underwent nasal lavage for IL-8 and neutrophil testing, in addition to multiplex polymerase chain reaction (PCR) methods for the detection and identification of respiratory viruses. Information about symptoms was obtained throughout the duration of the illness episode using the well-validated Wisconsin Upper Respiratory Symptom Survey (WURSS-21). Global symptom severity was calculated by the area under the curve (AUC) plotting duration versus WURSS total. Of the specimens tested, 56% were positively identified for one or more of nine different respiratory viruses. During acute respiratory infection illness, both IL-8 and neutrophils positively correlate with AUC (r(s) = 0.082, P = 0.022; r(s)  = 0.080, P = 0.030). IL-8 and neutrophils correlate with nasal symptom severity: runny nose (r = 0.13, P = acute respiratory infection. Further research is necessary to determine if the concentration of these or other biomarkers can predict the overall duration and severity of acute respiratory infection illness. © 2014 Wiley Periodicals, Inc.

Chemical composition, acute toxicity, antioxidant and anti-inflammatory activities of Moroccan Tetraclinis articulata L.

OpenAIRE

El Jemli, Meryem; Kamal, Rabie; Marmouzi, Ilias; Doukkali, Zouhra; Bouidida, El Houcine; Touati, Driss; Nejjari, Rachid; El Guessabi, Lahcen; Cherrah, Yahia; Alaoui, Katim

2016-01-01

Hydro-distilled essential oil (EO) from the leaves of the western Mediterranean and Moroccan endemic plant Tetraclinis articulata was analyzed by GC/MS and examined for its acute toxicity on mice, in order to establish the safe doses. Furthermore, the anti-Inflammatory activity was evaluated based on carrageenan and trauma induced rats paw edema and the antioxidant potential has been investigated using different methods including DPPH radical-scavenging assay, Trolox equivalent antioxidant ca...

Challenges of estimating the annual caseload of severe acute malnutrition

DEFF Research Database (Denmark)

Deconinck, Hedwig; Pesonen, Anaïs; Hallarou, Mahaman

2016-01-01

Introduction: Reliable prospective estimates of annual severe acute malnutrition (SAM) caseloads for treatment are needed for policy decisions and planning of quality services in the context of competing public health priorities and limited resources. This paper compares the reliability of SAM...

Analysis of factors influencing survival in patients with severe acute pancreatitis.

Science.gov (United States)

Kim, Yeon Ji; Kim, Dae Bum; Chung, Woo Chul; Lee, Ji Min; Youn, Gun Jung; Jung, Yun Duk; Choi, Sooa; Oh, Jung Hwan

2017-08-01

Acute pancreatitis (AP) ranges from a mild and self-limiting disease to a fulminant illness with significant morbidity and mortality. Severe acute pancreatitis (SAP) is defined as persistent organ failure lasting for 48 h. We aimed to determine the factors that predict survival and mortality in patients with SAP. We reviewed a consecutive series of patients who were admitted with acute pancreatitis between January 2003 and January 2013. A total of 1213 cases involving 660 patients were evaluated, and 68 cases with SAP were selected for the study. Patients were graded based on the Computer Tomography Severity Index (CTSI), the bedside index for severity (BISAP), and Ranson's criteria. The frequency of SAP was 5.6% (68/1213 cases). Among these patients, 17 died due to pancreatitis-induced causes. We compared several factors between the survivor (n = 51) and non-survivor (n = 17) groups. On multivariate analysis, there were significant differences in the incidence of diabetes mellitus (p = .04), Ranson score (p = .03), bacteremia (p = .05) and body mass index (BMI) (p = .02) between the survivor and non-survivor groups. Bacteremia, high Ranson score, DM, and lower BMI were closely associated with mortality in patients with SAP. When patients with SAP show evidence of bacteremia or diabetes, aggressive treatment is necessary. For the prediction of disease mortality, the Ranson score might be a useful tool in SAP.

Anti-Inflammatory Thioredoxin Family Proteins for Medicare, Healthcare and Aging Care

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Junji Yodoi

2017-09-01

Full Text Available Human thioredoxin (TRX is a 12-kDa protein with redox-active dithiol in the active site -Cys-Gly-Pro-Cys-, which is induced by biological stress due to oxidative damage, metabolic dysfunction, chemicals, infection/inflammation, irradiation, or hypoxia/ischemia-reperfusion. Our research has demonstrated that exogenous TRX is effective in a wide variety of inflammatory diseases, including viral pneumonia, acute lung injury, gastric injury, and dermatitis, as well as in the prevention and amelioration of food allergies. Preclinical and clinical studies using recombinant TRX (rhTRX are now underway. We have also identified substances that induce the expression of TRX in the body, in vegetables and other plant ingredients. Skincare products are being developed that take advantage of the anti-inflammatory and anti-allergic action of TRX. Furthermore, we are currently engaged in the highly efficient production of pure rhTRX in several plants, such as lettuce, grain and rice.

Severe glandular tularemia in a patient treated with anti-tumour necrosis factor for psoriatic arthritis.

Science.gov (United States)

Calin, Ruxandra; Caumes, Eric; Reibel, Florence; Ali Mohamed, Anzime; Brossier, Florence; Foltz, Violaine; Boussouar, Samia; Fautrel, Bruno; Maurin, Max; Katlama, Christine; Pourcher, Valérie

2017-07-01

A case of severe glandular tularemia in a patient receiving anti-tumour necrosis factor (TNF) therapy is reported here. The patient required prolonged treatment with doxycycline-ciprofloxacin due to early relapse after ciprofloxacin was stopped. Tularemia may have a more severe course in patients receiving anti-TNF. This may thus be an indication for more aggressive treatment. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Risk Factors for Acute Kidney Injury in Severe Rhabdomyolysis

Science.gov (United States)

Rodríguez, Eva; Soler, María J.; Rap, Oana; Barrios, Clara; Orfila, María A.; Pascual, Julio

2013-01-01

Background Acute kidney injury (AKI) is a life-threatening complication of severe rhabdomyolysis. This study was conducted to assess risk factors for AKI and to develop a risk score for early prediction. Methods Retrospective observational cohort study with a 9-year follow-up, carried out in an acute-care teaching-affiliated hospital. A total of 126 patients with severe rhabdomyolysis defined as serum creatine kinase (CK) > 5,000 IU/L fulfilled the inclusion criteria. Univariate and logistic regression analyses were performed to determine risk factors for AKI. Based on the values obtained for each variable, a risk score and prognostic probabilities were estimated to establish the risk for developing AKI. Results The incidence of AKI was 58%. Death during hospitalization was significantly higher among patients with AKI, compared to patients without AKI (19.2% vs 3.6%, p = 0.008). The following variables were independently associated with AKI: peak CK (odds ratio [OR] 4.9, 95%CI 1.4-16.8), hypoalbuminemia (rhabdomyolysis may be useful in clinical practice, particularly to implement early preventive measures. PMID:24367578

Psychosocial stimulation interventions for children with severe acute malnutrition: a systematic review

NARCIS (Netherlands)

Daniel, Allison I.; Bandsma, Robert H.; Lytvyn, Lyubov; Voskuijl, Wieger P.; Potani, Isabel; van den Heuvel, Meta

2017-01-01

Background The WHO Guidelines for the inpatient treatment of severely malnourished children include a recommendation to provide sensory stimulation or play therapy for children with severe acute malnutrition (SAM). This systematic review was performed to synthesize evidence around this

Early plasmapheresis in patients with severe hypertriglyceridemia induced acute pancreatitis

OpenAIRE

Nasa, Prashant; Alexander, George; Kulkarni, Amitabh; Juneja, Deven; Sehra, Sudhish; Agarwal, Rajesh; Koul, Kandy

2015-01-01

Hypertriglyceridemia can cause severe diseases such as acute pancreatitis (AP) and coronary artery disease. The routine management of hypertriglyceridemia is dietary restriction of fat and lipid-lowering medications to manage the secondary or precipitating causes of hypertriglyceridemia. However, in cases of AP with severe hypertriglyceridemia (SHTG) (triglycerides [TG] >1000 mg/dl) rapid reduction of TG levels to well below 1000 mg/dl can improve outcome and prevent further episodes of pancr...

Overdose pattern and outcome in paracetamol-induced acute severe hepatotoxicity

Science.gov (United States)

Craig, Darren G N; Bates, Caroline M; Davidson, Janice S; Martin, Kirsty G; Hayes, Peter C; Simpson, Kenneth J

2011-01-01

AIMS Paracetamol (acetaminophen) hepatotoxicity is the commonest cause of acute liver failure (ALF) in the UK. Conflicting data regarding the outcomes of paracetamol-induced ALF resulting from different overdose patterns are reported. METHODS Using prospectively defined criteria, we have analysed the impact of overdose pattern upon outcome in a cohort of 938 acute severe liver injury patients admitted to the Scottish Liver Transplantation Unit. RESULTS Between 1992 and 2008, 663 patients were admitted with paracetamol-induced acute severe liver injury. Of these patients, 500 (75.4%) had taken an intentional paracetamol overdose, whilst 110 (16.6%) had taken an unintentional overdose. No clear overdose pattern could be determined in 53 (8.0%). Unintentional overdose patients were significantly older, more likely to abuse alcohol, and more commonly overdosed on compound narcotic/paracetamol analgesics compared with intentional overdose patients. Unintentional overdoses had significantly lower admission paracetamol and alanine aminotransferase concentrations compared with intentional overdoses. However, unintentional overdoses had greater organ dysfunction at admission, and subsequently higher mortality (unintentional 42/110 (38.2%), intentional 128/500 (25.6%), P paracetamol overdose is associated with increased mortality compared with intentional paracetamol overdose, despite lower admission paracetamol concentrations. Alternative prognostic criteria may be required for unintentional paracetamol overdoses. PMID:21219409

A percutaneous drainage protocol for severe and moderately severe acute pancreatitis.

Science.gov (United States)

Sugimoto, Motokazu; Sonntag, David P; Flint, Greggory S; Boyce, Cody J; Kirkham, John C; Harris, Tyler J; Carr, Sean M; Nelson, Brent D; Barton, Joshua G; Traverso, L William

2015-11-01

According to the revised Atlanta classification, severe and moderately severe acute pancreatitis (AP) includes patients with pancreatic and peripancreatic collections with or without organ failure. These collections suggest the presence of pancreatic juice leakage. The aim of this study was to evaluate the efficacy of a percutaneous catheter drainage (PCD) protocol designed to control leakage and decrease disease severity. Among 663 patients with clinical AP, 122 were classified as moderately severe or severe AP (all had collections). The computed tomography severity index (CTSI) score was calculated. The indication for PCD was based on progressive clinical signs and symptoms. Drain patency, position, and need for additional drainage sites were assessed using CT scans and drain studies initially every 3 days using a proactive protocol. Drain fluid was examined for amylase concentration and microbiological culture. Clinicopathological variables for patients with and without PCD were compared. Since there was no mortality, we used prolonged drainage time to measure the success of PCD. Within the group treated with PCD, variables that resulted in prolonged drainage time were analyzed. PCD was used in 47/122 (39 %) patients of which 33/47 (70 %) had necrosis. PCD cases had a median CTSI of 8 and were classified as moderately severe AP (57 %) and severe AP (43 %). Inhospital mortality was zero. Surgical necrosectomy was not required for patients with necrosis. Independent risk factors for prolonged drainage time were persistent organ failure >48 h (P = 0.001), CTSI 8-10 (P = 0.038), prolonged duration of amylase-rich fluid in drains (P drainage fluid resulting in a mortality rate of zero.

Physical activity level among children recovering from severe acute malnutrition

DEFF Research Database (Denmark)

Babirekere-Iriso, Esther; Rytter, Maren Johanne Heilskov; Namusoke, Hanifa

2018-01-01

OBJECTIVE: To assess the level and predictors of physical activity at discharge among children recovering from severe acute malnutrition (SAM). METHODS: We conducted a prospective study among 69 children 6 - 59 months of age admitted with SAM for nutritional rehabilitation at Mulago National...

Neonatal bronchial hyperresponsiveness precedes acute severe viral bronchiolitis in infants

DEFF Research Database (Denmark)

Chawes, Bo L K; Poorisrisak, Porntiva; Johnston, Sebastian L

2012-01-01

Respiratory syncytial virus and other respiratory tract viruses lead to common colds in most infants, whereas a minority develop acute severe bronchiolitis often requiring hospitalization. We hypothesized that such an excessive response to respiratory tract viral infection is caused by host factors...

Anti-inflammatory activity and sub-acute toxicity of artemetin.

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Sertié, J A; Basile, A C; Panizza, S; Matida, A K; Zelnik, R

1990-02-01

The 5-hydroxy-3,6,7,3',4'-pentamethoxyflavone (artemetin) from Cordia verbenacea DC (Boraginaceae) showed marked anti-inflammatory activity using various experimental models in rats. Artemetin significantly inhibited carrageenin-induced paw edema following oral doses from 30.4 to 153.9 mg.kg-1. The doses of 102.6 and 153.9 mg.kg-1 showed an inhibitory effect similar to that of 50.0 mg.kg-1 of calcium phenylbutazone. The ED50 value of artemetin in rats was estimated to be 67.07 mg.kg-1. Repeated administration of artemetin at doses of 67.07 mg.kg-1 for a 6-day period reduced granuloma formation with a response comparable to that of 20.0 mg.kg-1 of calcium phenylbutazone. This same dose of artemetin also reduced the vascular permeability to intracutaneous histamine. Sub-acute toxicological experiments indicated a very low toxicity.

Human anti-CAIX antibodies mediate immune cell inhibition of renal cell carcinoma in vitro and in a humanized mouse model in vivo.

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Chang, De-Kuan; Moniz, Raymond J; Xu, Zhongyao; Sun, Jiusong; Signoretti, Sabina; Zhu, Quan; Marasco, Wayne A

2015-06-11

Carbonic anhydrase (CA) IX is a surface-expressed protein that is upregulated by the hypoxia inducible factor (HIF) and represents a prototypic tumor-associated antigen that is overexpressed on renal cell carcinoma (RCC). Therapeutic approaches targeting CAIX have focused on the development of CAIX inhibitors and specific immunotherapies including monoclonal antibodies (mAbs). However, current in vivo mouse models used to characterize the anti-tumor properties of fully human anti-CAIX mAbs have significant limitations since the role of human effector cells in tumor cell killing in vivo is not directly evaluated. The role of human anti-CAIX mAbs on CAIX(+) RCC tumor cell killing by immunocytes or complement was tested in vitro by antibody-dependent cell-mediated cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC) and antibody-dependent cellular phagocytosis (ADCP) as well as on CAIX(+) RCC cellular motility, wound healing, migration and proliferation. The in vivo therapeutic activity mediated by anti-CAIX mAbs was determined by using a novel orthotopic RCC xenograft humanized animal model and analyzed by histology and FACS staining. Our studies demonstrate the capacity of human anti-CAIX mAbs that inhibit CA enzymatic activity to result in immune-mediated killing of RCC, including nature killer (NK) cell-mediated ADCC, CDC, and macrophage-mediated ADCP. The killing activity correlated positively with the level of CAIX expression on RCC tumor cell lines. In addition, Fc engineering of anti-CAIX mAbs was shown to enhance the ADCC activity against RCC. We also demonstrate that these anti-CAIX mAbs inhibit migration of RCC cells in vitro. Finally, through the implementation of a novel orthotopic RCC model utilizing allogeneic human peripheral blood mononuclear cells in NOD/SCID/IL2Rγ(-/-) mice, we show that anti-CAIX mAbs are capable of mediating human immune response in vivo including tumor infiltration of NK cells and activation of T cells, resulting in

Presença de anticorpo anti-Lutheran B em paciente com leucemia linfóide aguda Anti-Lutheran B in a patient with acute lymphoblastic leukemia

Directory of Open Access Journals (Sweden)

Maria do Rosário F. Roberti

2007-06-01

Full Text Available Leucemias agudas necessitam de suporte hemoterápico para serem tratadas adequadamente. A presença do anticorpo anti-Lutheran B e a alta freqüência do antígeno em nossa população dificulta o tratamento de doenças hematológicas que necessitam de suporte transfusional, tais como a leucemia linfóide aguda (LLA. Alternativas de tratamento hemoterápico são abordadas neste artigo. Descreve-se o caso de uma paciente com LLA e anticorpo anti-Lutheran B. A dificuldade em encontrar sangue compatível levou os autores a adotarem estratégia conservadora no tratamento hemoterápico. O uso de eritropoetina e a adoção de protocolo quimioterápico individualizado viabilizaram os resultados obtidos.Acute leukemia needs hemotherapeutic support to be successfully treated. The Lutheran B antibody, specifically the high frequency of this antigen in our population, has made it difficult to treat hematological malignancies that need transfusional support, including acute lymphoblastic leukemia. Finding compatible blood is complex and so the authors adopted a conservative treatment strategy. The prescription of epoetin and an individualized chemotherapy protocol may improve results. We describe a case report of a patient with anti-Lutheran B antibody and how difficulties to find compatible blood were solved.

Safety and efficacy of opicinumab in acute optic neuritis (RENEW)

DEFF Research Database (Denmark)

Cadavid, Diego; Balcer, Laura J; Galetta, Steven L

2017-01-01

BACKGROUND: The human monoclonal antibody opicinumab (BIIB033, anti-LINGO-1) has shown remyelinating activity in preclinical studies. We therefore assessed the safety and tolerability, and efficacy of opicinumab given soon after a first acute optic neuritis episode. METHODS: This randomised, doub...

Anti-Erwinia asparaginase antibodies during treatment of childhood acute lymphoblastic leukemia and their relationship to outcome

DEFF Research Database (Denmark)

Albertsen, BK; Schmiegelow, Kjeld; Schrøder, Henrik

2002-01-01

PURPOSE: A case-control study was performed to determine whether patients who had been treated with Erwinia asparaginase as part of their treatment for childhood acute lymphoblastic leukemia (ALL) and who showed relapsed of their disease more often developed anti-asparaginase antibodies than...... (median follow-up 70 months). Anti- Erwinia asparaginase antibodies were measured (ELISA method) during maintenance therapy after asparaginase treatment (30,000 IU/m(2) daily for 10 days in all patients plus twice weekly for 2 weeks in intermediate-risk and high-risk ALL patients). RESULTS: The overall...... incidence of anti- Erwinia asparaginase antibodies was 8% (3 of 39 patients). There was no statistically significant difference in the incidence of antibody formation between patients who had suffered relapse (1 of 13) and those who had not (2 of 26). In two of the three patients who developed antibodies...

Human Metapneumovirus Infection in Jordanian Children: Epidemiology and Risk Factors for Severe Disease

Science.gov (United States)

Schuster, Jennifer E.; Khuri-Bulos, Najwa; Faouri, Samir; Shehabi, Asem; Johnson, Monika; Wang, Li; Fonnesbeck, Christopher; Williams, John V.; Halasa, Natasha

2016-01-01

Background Human metapneumovirus (HMPV) is a leading cause of acute respiratory tract infection (ARTI) in young children. Our objectives were to define HMPV epidemiology and circulating strains and determine markers of severe disease in Jordanian children. Methods We conducted a prospective study March 16, 2010-March 31, 2013 using quantitative RT-PCR to determine the frequency of HMPV infection among children <2 years old admitted with fever and/or acute respiratory illness to a major government hospital in Amman, Jordan. Results HMPV was present in 273/3168 (8.6%) of children presenting with ARTI. HMPV A2, B1, and B2, but not A1, were detected during the 3-year period. HMPV-infected children were older and more likely to be diagnosed with bronchopneumonia than HMPV-negative children. HMPV-infected children with lower respiratory tract infection (LRTI) had higher rates of cough and shortness of breath than children with LRTI infected with other or no identifiable viruses. Symptoms and severity were not different between children with HMPV only compared with HMPV co-infection. Children with HMPV subgroup A infection were more likely to require supplemental oxygen. In a multivariate analysis, HMPV subgroup A and age <6 months were independently associated with supplemental oxygen requirement. Conclusions HMPV is a leading cause of acute respiratory tract disease in Jordanian children <2 years old. HMPV A and young age were associated with severe disease. Ninety percent of HMPV-infected hospitalized children were full-term and otherwise healthy, in contrast to high-income nations; thus, factors contributing to disease severity likely vary depending on geographic and resource differences. PMID:26372450

Case Report: Human Bocavirus Associated Pneumonia as Cause of Acute Injury, Cologne, Germany.

Science.gov (United States)

Krakau, Michael; Gerbershagen, Kathrin; Frost, Ulrich; Hinzke, Markus; Brockmann, Michael; Schildgen, Verena; Gomann, Axel; Limmroth, Volker; Dormann, Arno; Schildgen, Oliver

2015-10-01

Although the human bocavirus (HBoV) is known since a decade, limited information about its pathogenesis is available due to the lack of an animal model. Thus, clinical cases and studies are the major source of novel information about the course of infection and the related pathophysiology.In this context, a clinical case of an adult patient suffering from severe HBoV-pneumonia is described that was associated with loss of consciousness followed by acute rib fracture and subsequent neurological disorder.Following initial global respiratory dysfunction the clinical respiratory symptoms recovered but the neurological symptoms maintained after weaning and intensive care in the stroke unit. During the initial phase, an acute active HBoV infection was confirmed by positive polymerase chain reactions from bronchoalveolar lavage fluid and serum.The case further demonstrates that HBoV can cause severe pneumonia, induce secondary disease also in adults, and may be associated with neurological symptoms as previously assumed.

The Study on Acute Subacute Toxicity and Anti-cancer Effect of K-herbal-acupuncture

Directory of Open Access Journals (Sweden)

Kwang-Ho, Kim

2003-02-01

Full Text Available Objectives : The purpose of this study was to investigate Acute· Subacute Toxicity and Anti-cancer Effect of K-Herbal-acupuncture in mice and rats. Methods : Balb/c mice were injected intraperitoneally with K- herbal-acupuncture for LD50 and acute toxicity test. Sprague-Dawley rats were injected intraperitoneally with K-herbal-acupuncture for subacute toxicity test. K-Herbal-acupuncture was injected on abdomen of mice with S-180 cancer cell line. Result : 1. LD50 of K-Herbal-acupuncture was limited 4×10-3ml/kg～2×10-3ml/kg by the test. 2. In acute toxicity test, all of mice were down to the moving reflex, but the weight of mice was increased in treatment group, compared with the normal group. (p<0.05 3. In acute toxicity test of serum biochemical values of mice, glucose was increased in treatment II group, total cholesterol was increased both treatments.(p<0.05 4. In subacute toxicity test, the clinical signs of toxication was down to the moving reflex, but it is not severe like acute toxicity test, and observed weight loss at the treatments. 5. In subacute toxicity test, liver weight was decreased compared with the normal group. (p<0.05 6. In subacute toxicity test of complete blood count test (CBC of rat, HCT was decreased in treatments, compared with the normal group.(p<0.05 7. In subacute toxicity test of serum biochemical values of rat, uric acid and triglyceride were decreased, and glucose was increased in treatment groups compared with the control group. (p<0.05 8. Median survival time was increased about 45% in treatment groups compared with the control group.(p<0.05 9. Natural killer cell activity was increased in B16F10 lung cancer model, but it was not in sarcoma-180 abdomen cancer. 10. In interleukin-2 productivity test, treatment groups didn't show significant change in lung cancer and abdomen cancer, compared with the normal group.(p<0.005 11. In making an examination of metastatic cancer with the naked eye, melanoma

Clinical Factors and Viral Load Influencing Severity of Acute Hepatitis A.

Science.gov (United States)

Lee, Hyun Woong; Chang, Dong-Yeop; Moon, Hong Ju; Chang, Hye Young; Shin, Eui-Cheol; Lee, June Sung; Kim, Kyung-Ah; Kim, Hyung Joon

2015-01-01

Clinical manifestations of hepatitis A virus (HAV) infection vary from mild to fulminant hepatic failure (FHF) in adults. We investigated the relationship between laboratory findings, including viral load, and clinical outcomes in patients with acute hepatitis A (AHA) and evaluated predictive factors for severe acute hepatitis (s-AH). We analyzed the clinical manifestations of AHA in 770 patients. Patients with a prothrombin time (PT) of less than 40% of normal were classified as s-AH and included 4 patients with FHF, 11 patients with acute renal failure, and 3 patients with prolonged jaundice (n = 128). Other patients were defined as mild acute hepatitis (m-AH) (n = 642). Serum samples were obtained from 48 patients with acute hepatitis A. Among them, 20 with s-AH, and 28 with m-AH, were tested for HAV RNA titer. In a multivariate analysis, age (HR = 1.042, P = 0.041), peak creatinine (HR = 4.014, P = 0.001), bilirubin (HR = 1.153, P = 0.003), alanine aminotransferase (ALT) (HR = 1.001, P hepatitis A.

Clinical Factors and Viral Load Influencing Severity of Acute Hepatitis A

Science.gov (United States)

Lee, Hyun Woong; Chang, Dong-Yeop; Moon, Hong Ju; Chang, Hye Young; Shin, Eui-Cheol; Lee, June Sung; Kim, Kyung-Ah; Kim, Hyung Joon

2015-01-01

Background and Aims Clinical manifestations of hepatitis A virus (HAV) infection vary from mild to fulminant hepatic failure (FHF) in adults. We investigated the relationship between laboratory findings, including viral load, and clinical outcomes in patients with acute hepatitis A (AHA) and evaluated predictive factors for severe acute hepatitis (s-AH). Methods We analyzed the clinical manifestations of AHA in 770 patients. Patients with a prothrombin time (PT) of less than 40% of normal were classified as s-AH and included 4 patients with FHF, 11 patients with acute renal failure, and 3 patients with prolonged jaundice (n = 128). Other patients were defined as mild acute hepatitis (m-AH) (n = 642). Serum samples were obtained from 48 patients with acute hepatitis A. Among them, 20 with s-AH, and 28 with m-AH, were tested for HAV RNA titer. Results In a multivariate analysis, age (HR = 1.042, P = 0.041), peak creatinine (HR = 4.014, P = 0.001), bilirubin (HR = 1.153, P = 0.003), alanine aminotransferase (ALT) (HR = 1.001, Phepatitis A. PMID:26090677

Acute Radiation Syndrome Severity Score System in Mouse Total-Body Irradiation Model.

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Ossetrova, Natalia I; Ney, Patrick H; Condliffe, Donald P; Krasnopolsky, Katya; Hieber, Kevin P

2016-08-01

Radiation accidents or terrorist attacks can result in serious consequences for the civilian population and for military personnel responding to such emergencies. The early medical management situation requires quantitative indications for early initiation of cytokine therapy in individuals exposed to life-threatening radiation doses and effective triage tools for first responders in mass-casualty radiological incidents. Previously established animal (Mus musculus, Macaca mulatta) total-body irradiation (γ-exposure) models have evaluated a panel of radiation-responsive proteins that, together with peripheral blood cell counts, create a multiparametic dose-predictive algorithm with a threshold for detection of ~1 Gy from 1 to 7 d after exposure as well as demonstrate the acute radiation syndrome severity score systems created similar to the Medical Treatment Protocols for Radiation Accident Victims developed by Fliedner and colleagues. The authors present a further demonstration of the acute radiation sickness severity score system in a mouse (CD2F1, males) TBI model (1-14 Gy, Co γ-rays at 0.6 Gy min) based on multiple biodosimetric endpoints. This includes the acute radiation sickness severity Observational Grading System, survival rate, weight changes, temperature, peripheral blood cell counts and radiation-responsive protein expression profile: Flt-3 ligand, interleukin 6, granulocyte-colony stimulating factor, thrombopoietin, erythropoietin, and serum amyloid A. Results show that use of the multiple-parameter severity score system facilitates identification of animals requiring enhanced monitoring after irradiation and that proteomics are a complementary approach to conventional biodosimetry for early assessment of radiation exposure, enhancing accuracy and discrimination index for acute radiation sickness response categories and early prediction of outcome.

Pancreatic Enzyme Replacement Therapy in Children with Severe Acute Malnutrition: A Randomized Controlled Trial.

Science.gov (United States)

Bartels, Rosalie H; Bourdon, Céline; Potani, Isabel; Mhango, Brian; van den Brink, Deborah A; Mponda, John S; Muller Kobold, Anneke C; Bandsma, Robert H; Boele van Hensbroek, Michael; Voskuijl, Wieger P

2017-11-01

To assess the benefits of pancreatic enzyme replacement therapy (PERT) in children with complicated severe acute malnutrition. We conducted a randomized, controlled trial in 90 children aged 6-60 months with complicated severe acute malnutrition at the Queen Elizabeth Central Hospital in Malawi. All children received standard care; the intervention group also received PERT for 28 days. Children treated with PERT for 28 days did not gain more weight than controls (13.7 ± 9.0% in controls vs 15.3 ± 11.3% in PERT; P = .56). Exocrine pancreatic insufficiency was present in 83.1% of patients on admission and fecal elastase-1 levels increased during hospitalization mostly seen in children with nonedematous severe acute malnutrition (P Children who died had low fecal fatty acid split ratios at admission. Exocrine pancreatic insufficiency was not improved by PERT, but children receiving PERT were more likely to be discharged with every passing day (P = .02) compared with controls. PERT does not improve weight gain in severely malnourished children but does increase the rate of hospital discharge. Mortality was lower in patients on PERT, a finding that needs to be investigated in a larger cohort with stratification for edematous and nonedematous malnutrition. Mortality in severe acute malnutrition is associated with markers of poor digestive function. ISRCTN.com: 57423639. Copyright © 2017 Elsevier Inc. All rights reserved.

Transjugular intrahepatic portosystemic shunt for severe jaundice in patients with acute Budd-Chiari syndrome.

Science.gov (United States)

He, Fu-Liang; Wang, Lei; Zhao, Hong-Wei; Fan, Zhen-Hua; Zhao, Meng-Fei; Dai, Shan; Yue, Zhen-Dong; Liu, Fu-Quan

2015-02-28

To evaluate the feasibility of transjugular intrahepatic portosystemic shunt (TIPS) for severe jaundice secondary to acute Budd-Chiari syndrome (BCS). From February 2009 to March 2013, 37 patients with severe jaundice secondary to acute BCS were treated. Sixteen patients without hepatic venule, hepatic veins (HV) obstruction underwent percutaneous angioplasty of the inferior vena cava (IVC) and/or HVs. Twenty-one patients with HV occlusion underwent TIPS. Serum bilirubin, liver function, demographic data and operative data of the two groups of patients were analyzed. Twenty-one patients underwent TIPS and the technical success rate was 100%, with no technical complications. Sixteen patients underwent recanalization of the IVC and/or HVs and the technical success rate was 100%. The mean procedure time for TIPS was 84.0±12.11 min and angioplasty was 44.11±5.12 min (Pjaundice in either group. Severe jaundice is not a contraindication for TIPS in patients with acute BCS and TIPS is appropriate for severe jaundice due to BCS.

Improving estimates of numbers of children with severe acute malnutrition using cohort and survey data

DEFF Research Database (Denmark)

Isanaka, Sheila; Boundy, Ellen O neal; Grais, Rebecca F

2016-01-01

Severe acute malnutrition (SAM) is reported to affect 19 million children worldwide. However, this estimate is based on prevalence data from cross-sectional surveys and can be expected to miss some children affected by an acute condition such as SAM. The burden of acute conditions is more...

Clearance of 131I-labeled murine monoclonal antibody from patients' blood by intravenous human anti-murine immunoglobulin antibody

International Nuclear Information System (INIS)

Stewart, J.S.; Sivolapenko, G.B.; Hird, V.; Davies, K.A.; Walport, M.; Ritter, M.A.; Epenetos, A.A.

1990-01-01

Five patients treated with intraperitoneal 131I-labeled mouse monoclonal antibody for ovarian cancer also received i.v. exogenous polyclonal human anti-murine immunoglobulin antibody. The pharmacokinetics of 131I-labeled monoclonal antibody in these patients were compared with those of 28 other patients receiving i.p.-radiolabeled monoclonal antibody for the first time without exogenous human anti-murine immunoglobulin, and who had no preexisting endogenous human anti-murine immunoglobulin antibody. Patients receiving i.v. human anti-murine immunoglobulin antibody demonstrated a rapid clearance of 131I-labeled monoclonal antibody from their circulation. The (mean) maximum 131I blood content was 11.4% of the injected activity in patients receiving human anti-murine immunoglobulin antibody compared to 23.3% in patients not given human anti-murine immunoglobulin antibody. Intravenous human anti-murine immunoglobulin antibody decreased the radiation dose to bone marrow (from 131I-labeled monoclonal antibody in the vascular compartment) 4-fold. Following the injection of human anti-murine immunoglobulin antibody, 131I-monoclonal/human anti-murine immunoglobulin antibody immune complexes were rapidly transported to the liver. Antibody dehalogenation in the liver was rapid, with 87% of the injected 131I excreted in 5 days. Despite the efficient hepatic uptake of immune complexes, dehalogenation of monoclonal antibody was so rapid that the radiation dose to liver parenchyma from circulating 131I was decreased 4-fold rather than increased. All patients developed endogenous human anti-murine immunoglobulin antibody 2 to 3 weeks after treatment

[Preparation and preliminary application of rabbit anti-human PON2 antibodies(paraoxonase-2)].

Science.gov (United States)

Chen, Miao; Yang, Jin-Ju; Li, Shu-Zhen; Liu, Xiao-Lan; Liu, Ying; Zhang, Lin-Jie; Gao, Jian-En; Sun, Qi-Hong

2008-07-01

To preparation and characterize the rabbit polyclonal antibodies against human PON2 (paraoxonase-2). A fragment of human PON2 gene which was of low homology with rabbits but of higher hydrophilicity and immunogenicity was selected for recombinant expression in prokaryotic expression system. The rabbits were immunized with the purified GST fusion protein 3 times. The specificity and sensitivity of the anti-human PON2 polyclonal antibodies were detected by Western blot and indirect immunofluorescence. The GST-PON2 fusion protein was highly expressed in Ecoli with a molecular weight of 46 kDa. Western blot analysis proved the rabbit polyclonal antibodies could specifically recognize 39 kDa native PON2 protein expressed in several cells and tissues, such as HeLa cells, U937 cells, and human liver tissue. Indirect immunofluorescence analysis confirmed that PON2 protein was located in the cytoplasm of SY5Y cells. The rabbit polyclonal antibodies against human PON2 can specifically recognize natural protein expressed in human cells and tissues, Which can be used for further study and clinical detection of human PON2.

Celiac Disease in Children with Severe Acute Malnutrition (SAM): A Hospital Based Study.

Science.gov (United States)

Beniwal, Neetu; Ameta, Gaurav; Chahar, Chandra Kumar

2017-05-01

To evaluate the prevalence and clinical features of Celiac disease among children with severe acute malnutrition (SAM). This prospective observational study was conducted in PBM Children Hospital, Bikaner from July 2012 through December 2013. All consecutively admitted children with SAM were recruited. All subjects were screened for Celiac disease by serological test for IgA-anti tissue Transglutaminase (IgA tTG) antibodies. All seropositive children underwent upper gastrointestinal endoscopy for small bowel biopsy for the confirmation. Clinical features of patients with and without celiac disease were compared. The sero-prevalence (IgA tTg positivity) of Celiac disease was found to be 15.38% while prevalence of biopsy confirmed Celiac disease was 14.42% among SAM children. Abdominal distension, diarrhea, anorexia, constipation, pain in abdomen, vitamin deficiencies, edema, clubbing and mouth ulcers were more common in patients of Celiac disease compared to patients without Celiac disease but the difference was statistically significant only for abdominal distension and pain abdomen. There is a high prevalence of Celiac disease in SAM. Screening for Celiac disease (especially in presence of pain abdomen and abdominal distension) should be an essential part of work-up in all children with SAM.

Contribution of inhibitory receptor glycoprotein iib / iiia in coronary angioplasty and acute coronary syndrome, about 152 patients

International Nuclear Information System (INIS)

Sellami, Walid

2007-01-01

The aim of our study was to evaluate the immediate results and long-term intake of anti-GP IIb / IIIa inhibitors for patients with acute coronary syndrome treated with coronary angioplasty. The use of anti-GP IIb / IIIa is a valid therapeutic option in patients with acute coronary syndrome with signs of severity and for patients undergoing complex angioplasty. Adverse effects of anti-GP IIb / IIIa can be seen to encourage vigilance and careful monitoring during the administration of these molecules and perfect knowledge of their pharmacological properties for appropriate use.

Severe Neurotoxicity Following Ingestion of Tetraethyl Lead

OpenAIRE

Wills, Brandon K.; Christensen, Jason; Mazzoncini, Joe; Miller, Michael

2010-01-01

Organic lead compounds are potent neurotoxins which can result in death even from small exposures. Traditionally, these compounds are found in fuel stabilizers, anti-knock agents, and leaded gasoline. Cases of acute organic lead intoxication have not been reported for several decades. We report a case of a 13-year-old Iraqi male who unintentionally ingested a fuel stabilizer containing 80–90% tetraethyl lead, managed at our combat support hospital. The patient developed severe neurologic symp...

Acute hypothyroidism in a severely ill surgical patient

DEFF Research Database (Denmark)

Mogensen, T; Hjortsø, N C

1988-01-01

A case of acute postoperative hypothyroidism in a 62-year old woman is presented. One month before emergency admission because of a perforated gastric ulcer the patient had normal thyroid function, despite removal of a thyroid adenoma 20 years earlier. Following surgery the patient developed circ...... circulatory instability, renal insufficiency, hypothermia and immeasurable concentrations of thyroxine (T4) and triiodothyronine (T3). Treatment with triiodothyronine was commenced but the patient died following an episode of severe hypotension....

Relationship of Renal Function Tests and Electrolyte Levels with Severity of Dehydration in Acute Diarrhea.

Science.gov (United States)

Gauchan, E; Malla, K K

2015-01-01

Acute diarrheal illness constitutes a major cause of morbidity and mortality in children in developing countries. Most of the complications of diarrhea occur due to excessive fluid and electrolyte loss; adverse complications are seen more with increasing severity of dehydration. This study was conducted to identify the relation of renal function and electrolyte abnormalities in children with varying severity of dehydration. This study was carried out in Manipal Teaching Hospital, Pokhara, Nepal over duration of one year. The aims were to find out the association of renal function and electrolyte disturbances with type of diarrhea, severity of dehydration and their relation to outcome. All children more than one month and less than 15 years with acute diarrhea were included in the study. Data were entered and analyzed by SPSS version 19. Statistical analysis applied was Chi-square test. A p-value of Dehydration was associated more with Acute Watery Diarrhea than with Invasive Diarrhea. Renal function and electrolyte abnormalities were seen more in Acute Watery Diarrhea with increasing levels of blood urea, serum creatinine and abnormal levels of serum sodium seen with increased severity of dehydration. Abnormalities in renal function and electrolytes correlated significantly with severity of dehydration. The outcome of patients correlated with severity of dehydration with mortality occurring in 18.1% of patients with Severe dehydration, 0.8% of Some dehydration with no mortality in the No dehydration group.

Monoclonal anti-human factor VII antibodies. Detection in plasma of a second protein antigenically and genetically related to factor VII.

OpenAIRE

Broze, G J; Hickman, S; Miletich, J P

1985-01-01

Several murine monoclonal anti-human Factor VII antibodies were produced using hybridoma technology. Two noncompetitive monoclonal antibodies were used to examine by Western blotting the Factor VII cross-reactive material (CRM) in normal human plasma and three commercially available congenitally Factor VII-deficient plasmas, and to construct a facile "sandwich" immunoassay for plasma Factor VII. A second, previously undescribed, form of Factor VII CRM was detected in human plasma, which on We...

What’s new in the management of severe acute pancreatitis?

OpenAIRE

Mallédant, Yannick; Malbrain, Manu L. N. G.; Reuter, Daniel A.

2015-01-01

International audience; Acute pancreatitis (AP) is a leading cause of hospitalization for gastrointestinal disorders [1]. Because of a substantially high mortality of up to 20–30 % in severe cases, early identification of patients who might require transfer to an intensive care unit (ICU) is essential...

Anti-liver-kidney microsome antibody type 1 recognizes human cytochrome P450 db1.

Science.gov (United States)

Gueguen, M; Yamamoto, A M; Bernard, O; Alvarez, F

1989-03-15

Anti-liver-kidney microsome antibody type 1 (LKM1), present in the sera of a group of children with autoimmune hepatitis, was recently shown to recognize a 50 kDa protein identified as rat liver cytochromes P450 db1 and db2. High homology between these two members of the rat P450 IID subfamily and human P450 db1 suggested that anti-LKM1 antibody is directed against this human protein. To test this hypothesis, a human liver cDNA expression library in phage lambda GT-11 was screened using rat P450 db1 cDNA as a probe. Two human cDNA clones were found to be identical to human P450 db1 by restriction mapping. Immunoblot analysis using as antigen, the purified fusion protein from one of the human cDNA clones showed that only anti-LKM1 with anti-50 kDa reactivity recognized the fusion protein. This fusion protein was further used to develop an ELISA test that was shown to be specific for sera of children with this disease. These results: 1) identify the human liver antigen recognized by anti-LKM1 auto-antibodies as cytochrome P450 db1, 2) allow to speculate that mutation on the human P450 db1 gene could alter its expression in the hepatocyte and make it auto-antigenic, 3) provide a simple and specific diagnostic test for this disease.

Chemical composition, acute toxicity, antioxidant and anti-inflammatory activities of Moroccan Tetraclinis articulata L.

Science.gov (United States)

El Jemli, Meryem; Kamal, Rabie; Marmouzi, Ilias; Doukkali, Zouhra; Bouidida, El Houcine; Touati, Driss; Nejjari, Rachid; El Guessabi, Lahcen; Cherrah, Yahia; Alaoui, Katim

2017-07-01

Hydro-distilled essential oil (EO) from the leaves of the western Mediterranean and Moroccan endemic plant Tetraclinis articulata was analyzed by GC/MS and examined for its acute toxicity on mice, in order to establish the safe doses. Furthermore, the anti-Inflammatory activity was evaluated based on carrageenan and trauma induced rats paw edema and the antioxidant potential has been investigated using different methods including DPPH radical-scavenging assay, Trolox equivalent antioxidant capacity (TEAC) and Ferric-reducing antioxidant power assay (FRAP). The major identified compounds in GC/MS analysis were bornyl acetate (26.81%), camphor (22.40%) and α-pinene (7.16%), with 25 other minor constituents. No mortalities in acute toxicity were observed, indicating that the LD 50 of T. articulata essential oil is highest than 5 g/kg. In the anti-inflammatory test based on chemical and mechanical induced trauma, the EO demonstrated an effective reduce swelling by 64.71 ± 9.38% and 69.09 ± 6.02% respectively obtained 6 h after administration at the dose of 200 mg/kg when compared to the control groups. Moreover in the antioxidant testing battery, T. articulata essential oil showed a promising scavenging effect measured by DPPH, TEAC and ferric-reducing power assays with IC 50 values of 12.05 ± 0.24 mg/mL, 8.90 ± 0.17 mg/mL and 0.15 ± 0.01 mg/mL respectively. These results suggest that, the EO from the leaves of T. articulata constitutes a valuable source of anti-inflammatory and antioxidant metabolites. These findings argue for the possible integration of this oil in pharmaceutical, cosmetic and food industries.

Chemical composition, acute toxicity, antioxidant and anti-inflammatory activities of Moroccan Tetraclinis articulata L.

Directory of Open Access Journals (Sweden)

Meryem El Jemli

2017-07-01

Full Text Available Hydro-distilled essential oil (EO from the leaves of the western Mediterranean and Moroccan endemic plant Tetraclinis articulata was analyzed by GC/MS and examined for its acute toxicity on mice, in order to establish the safe doses. Furthermore, the anti-Inflammatory activity was evaluated based on carrageenan and trauma induced rats paw edema and the antioxidant potential has been investigated using different methods including DPPH radical-scavenging assay, Trolox equivalent antioxidant capacity (TEAC and Ferric-reducing antioxidant power assay (FRAP. The major identified compounds in GC/MS analysis were bornyl acetate (26.81%, camphor (22.40% and α-pinene (7.16%, with 25 other minor constituents. No mortalities in acute toxicity were observed, indicating that the LD50 of T. articulata essential oil is highest than 5 g/kg. In the anti-inflammatory test based on chemical and mechanical induced trauma, the EO demonstrated an effective reduce swelling by 64.71 ± 9.38% and 69.09 ± 6.02% respectively obtained 6 h after administration at the dose of 200 mg/kg when compared to the control groups. Moreover in the antioxidant testing battery, T. articulata essential oil showed a promising scavenging effect measured by DPPH, TEAC and ferric-reducing power assays with IC50 values of 12.05 ± 0.24 mg/mL, 8.90 ± 0.17 mg/mL and 0.15 ± 0.01 mg/mL respectively. These results suggest that, the EO from the leaves of T. articulata constitutes a valuable source of anti-inflammatory and antioxidant metabolites. These findings argue for the possible integration of this oil in pharmaceutical, cosmetic and food industries.

The urgent need for a harmonized severity scoring system for acute allergic reactions

DEFF Research Database (Denmark)

Muraro, Antonella; Fernandez-Rivas, Montserrat; Beyer, Kirsten

2018-01-01

The accurate assessment and communication of the severity of acute allergic reactions is important to patients, clinicians, researchers, the food industry, public health and regulatory authorities. Severity has different meanings to different stakeholders with patients and clinicians rating...... of different stakeholder groups. We propose a novel approach to develop and then validate a harmonized scoring system for acute allergic reactions, based on a data-driven method that is informed by clinical and patient experience and other stakeholders' perspectives. We envisage two formats: (i) a numerical...... the significance of particular symptoms very differently. Many severity scoring systems have been generated, most focusing on the severity of reactions following exposure to a limited group of allergens. They are heterogeneous in format, none has used an accepted developmental approach and none has been validated...

A case of severe acute kidney injury by near-drowning.

Science.gov (United States)

Seong, Eun Young; Rhee, Harin; Lee, Naria; Lee, Sung Jun; Song, Sang Heon; Lee, Dong Won; Lee, Soo Bong; Sol, Mee Young; Kwak, Ihm Soo

2012-02-01

Acute kidney injury (AKI) secondary to near-drowning is rarely described and poorly understood. Only few cases of severe isolated AKI resulting from near-drowning exist in the literature. We report a case of near-drowning who developed to isolated AKI due to acute tubular necrosis (ATN) requiring dialysis. A 21-yr-old man who recovered from near-drowning in freshwater 3 days earlier was admitted to our hospital with anuria and elevated level of serum creatinine. He needed five sessions of hemodialysis and then renal function recovered spontaneously. Renal biopsy confirmed ATN. We review the existing literature on near-drowning-induced AKI and discuss the possible pathogenesis.

111-Indium-labelled platelets for diagnosis of acute kidney transplant rejection and monitoring of prostacyclin anti-rejection treatment

International Nuclear Information System (INIS)

Leithner, C.; Pohanka, E.; Schwarz, M.; Sinzinger, H.; Syre, G.

1984-01-01

33 patients were examined daily under a gamma camera after weekly injections of 111-In-labelled autologous platelets over a period of at least 4 weeks after transplantation. A group of 33 patients with long-term stable and well-functioning grafts served as controls. By means of a computerized recording technique, platelet trapping in the graft was measured and expressed as platelet-uptake index (PUI). The method worked well for the early diagnosis of acute rejection signified by an increase in PUI, accompanied by a shortening of platelet half life (t/2). 6 patients suffering from acute rejection received infusions of prostacyclin in addition to conventional high-dose methylprednisolone therapy. In 4 cases the PUI decreased again and an improvement in graft function was observed. Prostacyclin infusion treatment was applied also in 12 patients with histologically-proven chronic transplant rejection. Decreased platelet consumption by the graft and a temporary improvement in transplant function were achieved. We suggest that prostacyclin could enrich the possibilities of anti-rejection treatment by providing a tool for the suppression of platelet trapping in the graft. The platelet scan served as a useful method for the early detection of acute rejection, as well as the monitoring of prostacyclin anti-rejection treatment. (Autor)

Children with severe acute malnutrition : New diagnostic and treatment strategies

NARCIS (Netherlands)

Bartels, R.H.

2018-01-01

Forty-five percent of worldwide deaths in children under-5 years of age is directly or indirectly attributable to poor nutrition. Tackling the global problem of malnutrition and of severe acute malnutrition (SAM) in particular, to increase health, quality of life, and to reduce under-5 mortality, is

Anti-GBM disease and ANCA during dengue infection.

Science.gov (United States)

Lizarraga, Karlo J; Florindez, Jorge A; Daftarian, Pirouz; Andrews, David M; Ortega, Luis M; Mendoza, Jair Munoz; Contreras, Gabriel N; Nayer, Ali

2015-02-01

Anti-glomerular basement membrane (GBM) disease is a severe inflammatory renal disorder due to pathogenic autoantibodies directed mainly against the α3 chain of type IV collagen. In ~1/4 of patients with anti-GBM disease, antineutrophil cytoplasmic antibodies (ANCA) predominantly with myeloperoxidase (MPO) specificity can be detected. Although the inciting stimuli leading to the development of an immune response against the type IV collagen and neutrophils are unknown, evidence indicates that both genetic and environmental factors play a role. Of note, molecular mimicry between self-antigens and nonself-antigens such as antigenic determinants of microorganisms has been implicated in the pathogenesis of anti-GBM disease and ANCA-associated vasculitis. A mosquito-borne viral illness highly prevalent in the tropics and subtropics, dengue can be complicated by acute renal failure, proteinuria, hematuria and glomerulonephritis. We present a 66-year-old woman who was diagnosed with dengue infection and rapidly progressive glomerulonephritis during an outbreak of dengue in Honduras in the summer of 2013. Renal biopsy revealed severe crescentic glomerulonephritis. Immunofluorescence examination demonstrated strong linear IgG deposition along glomerular capillary walls. Serologic tests demonstrated antibodies against GBM, MPO and platelet glycoproteins. The patient was diagnosed with anti-GBM disease associated with p-ANCA with MPO specificity. Despite heavy immunosuppression and plasmapheresis, IgG titers against dengue virus continued to rise confirming the diagnosis of acute dengue infection. We present the first reported case of anti-GBM disease associated with p-ANCA with MPO specificity during dengue infection. This report calls for a heightened awareness of autoimmunity leading to crescentic glomerulonephritis in patients with dengue infection.

Acute pancreatitis and acute renal failure following multiple hornet stings

Directory of Open Access Journals (Sweden)

N. Sharma

2006-04-01

Full Text Available Hymenoptera is a class of insects that sting in order to subdue their prey. Humans coming into accidental contact with these insects results in stings that may cause from mild local reaction like weal formation around the sting site to severe systemic reactions such as intravascular hemolysis, acute renal failure, pulmonary edema, cerebral edema, and rarely pancreatitis. We report here the clinical course of a patient who developed concurrent acute pancreatitis and pigment-induced acute renal failure after multiple hornet stings.

Pathogen- and host-directed anti-inflammatory activities of macrolide antibiotics.

Science.gov (United States)

Steel, Helen C; Theron, Annette J; Cockeran, Riana; Anderson, Ronald; Feldman, Charles

2012-01-01

Macrolide antibiotics possess several, beneficial, secondary properties which complement their primary antimicrobial activity. In addition to high levels of tissue penetration, which may counteract seemingly macrolide-resistant bacterial pathogens, these agents also possess anti-inflammatory properties, unrelated to their primary antimicrobial activity. Macrolides target cells of both the innate and adaptive immune systems, as well as structural cells, and are beneficial in controlling harmful inflammatory responses during acute and chronic bacterial infection. These secondary anti-inflammatory activities of macrolides appear to be particularly effective in attenuating neutrophil-mediated inflammation. This, in turn, may contribute to the usefulness of these agents in the treatment of acute and chronic inflammatory disorders of both microbial and nonmicrobial origin, predominantly of the airways. This paper is focused on the various mechanisms of macrolide-mediated anti-inflammatory activity which target both microbial pathogens and the cells of the innate and adaptive immune systems, with emphasis on their clinical relevance.

Risk factors for death in children during inpatient treatment of severe acute malnutrition

DEFF Research Database (Denmark)

Rytter, Maren Johanne Heilskov; Babirekere-Iriso, Esther; Namusoke, Hanifa

2017-01-01

BACKGROUND: Children who receive in-hospital treatment of severe acute malnutrition often have high mortality rates, and the reasons are not well understood. OBJECTIVE: We assessed risk factors for death in children who were treated for malnutrition in a hospital. DESIGN: In a prospective...... observational study of 120 children who were receiving in-hospital treatment of severe acute malnutrition in Uganda with therapeutic formulas F-75 and F-100, we collected data on symptoms, clinical findings, plasma markers of refeeding syndrome (electrolytes and phosphate), and acute phase reactants......% CI: 1.9, 13.3), which was an association that remained after adjustment for potential confounders (HR: 69.5; 95% CI: 7.0, 694.6). CONCLUSIONS: Refeeding syndrome may occur in children who are treated for malnutrition, even with moderately low plasma phosphate, and, in particular, in children...

Acute toxicity and anti-fatigue activity of polysaccharide-rich extract from corn silk.

Science.gov (United States)

Zhao, He-Peng; Zhang, Yang; Liu, Zhuo; Chen, Jiang-Yue; Zhang, Song-Yan; Yang, Xiu-Dong; Zhou, Hong-Li

2017-06-01

The aim of this study was to evaluate the safety and potential of PCS as the anti-fatigue functional food. PCS was prepared by water extracting-alcohol precipitating method, and its chemical compositions of monosaccharide were analyzed. Then, acute toxicity and anti-fatigue activity of PCS were evaluated. PCS is composed of Rha, Arab, Xyl, Man, Glu, and Gal, its molar ratio is 0.17: 0.30: 0.26: 0.35: 1.00: 0.57. No mortality and general symptoms of toxicity were observed in the PCS treated mice (7.5, 15, and 20g/kg body weight), the body weight and food consumption were not significantly changed compared with the normal control group. The relative weights of main organ, and biochemical indicators also did not markedly change. PCS can significantly prolong the duration of the swimming time to exhaustion in mice, decrease BUN, LA levels, increase LDH activities, and the contents of HG in the PCS treated mice. The dose of 400mg/kg body weight is the optimal dose for anti-fatigue activity both in male and female mice. In conclusion, PCS is a promising traditional natural-based therapeutic remedy for relieving fatigue with high safety. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Severe acute dehydration in a desert rodent elicits a transcriptional response that effectively prevents kidney injury.

Science.gov (United States)

MacManes, Matthew David

2017-08-01

Animals living in desert environments are forced to survive despite severe heat, intense solar radiation, and both acute and chronic dehydration. These animals have evolved phenotypes that effectively address these environmental stressors. To begin to understand the ways in which the desert-adapted rodent Peromyscus eremicus survives, reproductively mature adults were subjected to 72 h of water deprivation, during which they lost, on average, 23% of their body weight. The animals reacted via a series of changes in the kidney, which included modulating expression of genes responsible for reducing the rate of transcription and maintaining water and salt balance. Extracellular matrix turnover appeared to be decreased, and apoptosis was limited. In contrast to the canonical human response, serum creatinine and other biomarkers of kidney injury were not elevated, suggesting that changes in gene expression related to acute dehydration may effectively prohibit widespread kidney damage in the cactus mouse. Copyright © 2017 the American Physiological Society.

Human T cell recognition of the blood stage antigen Plasmodium hypoxanthine guanine xanthine phosphoribosyl transferase (HGXPRT in acute malaria

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Woodberry Tonia

2009-06-01

Full Text Available Abstract Background The Plasmodium purine salvage enzyme, hypoxanthine guanine xanthine phosphoribosyl transferase (HGXPRT can protect mice against Plasmodium yoelii pRBC challenge in a T cell-dependent manner and has, therefore, been proposed as a novel vaccine candidate. It is not known whether natural exposure to Plasmodium falciparum stimulates HGXPRT T cell reactivity in humans. Methods PBMC and plasma collected from malaria-exposed Indonesians during infection and 7–28 days after anti-malarial therapy, were assessed for HGXPRT recognition using CFSE proliferation, IFNγ ELISPOT assay and ELISA. Results HGXPRT-specific T cell proliferation was found in 44% of patients during acute infection; in 80% of responders both CD4+ and CD8+ T cell subsets proliferated. Antigen-specific T cell proliferation was largely lost within 28 days of parasite clearance. HGXPRT-specific IFN-γ production was more frequent 28 days after treatment than during acute infection. HGXPRT-specific plasma IgG was undetectable even in individuals exposed to malaria for at least two years. Conclusion The prevalence of acute proliferative and convalescent IFNγ responses to HGXPRT demonstrates cellular immunogenicity in humans. Further studies to determine minimal HGXPRT epitopes, the specificity of responses for Plasmodia and associations with protection are required. Frequent and robust T cell proliferation, high sequence conservation among Plasmodium species and absent IgG responses distinguish HGXPRT from other malaria antigens.

Saudi anti-human cancer plants database (SACPD): A collection of plants with anti-human cancer activities.

Science.gov (United States)

Al-Zahrani, Ateeq Ahmed

2018-01-30

Several anticancer drugs have been developed from natural products such as plants. Successful experiments in inhibiting the growth of human cancer cell lines using Saudi plants were published over the last three decades. Up to date, there is no Saudi anticancer plants database as a comprehensive source for the interesting data generated from these experiments. Therefore, there was a need for creating a database to collect, organize, search and retrieve such data. As a result, the current paper describes the generation of the Saudi anti-human cancer plants database (SACPD). The database contains most of the reported information about the naturally growing Saudi anticancer plants. SACPD comprises the scientific and local names of 91 plant species that grow naturally in Saudi Arabia. These species belong to 38 different taxonomic families. In Addition, 18 species that represent16 family of medicinal plants and are intensively sold in the local markets in Saudi Arabia were added to the database. The website provides interesting details, including plant part containing the anticancer bioactive compounds, plants locations and cancer/cell type against which they exhibit their anticancer activity. Our survey revealed that breast, liver and leukemia were the most studied cancer cell lines in Saudi Arabia with percentages of 27%, 19% and 15%, respectively. The current SACPD represents a nucleus around which more development efforts can expand to accommodate all future submissions about new Saudi plant species with anticancer activities. SACPD will provide an excellent starting point for researchers and pharmaceutical companies who are interested in developing new anticancer drugs. SACPD is available online at https://teeqrani1.wixsite.com/sapd.

Platelet-rich plasma (PRP) treatment of sports-related severe acute hamstring injuries.

Science.gov (United States)

Guillodo, Yannick; Madouas, Gwénaelle; Simon, Thomas; Le Dauphin, Hermine; Saraux, Alain

2015-01-01

hamstring injury is the most common musculoskeletal disorder and one of the main causes of missed sporting events. Shortening the time to return to play (TTRTP) is a priority for athletes and sports medicine practitioners. platelet-rich plasma (PRP) injection at the site of severe acute hamstring injury increases the healing rate and shortens the TTRTP. Cohort study. all patients with ultrasonography and MRI evidence of severe acute hamstring injury between January 2012 and March 2014 were offered PRP treatment. Those who accepted received a single intramuscular PRP injection within 8 days post-injury; the other patients served as controls. The same standardized rehabilitation program was used in both groups. A physical examination and ultrasonography were performed 10 and 30 days post-injury, then a phone interview 120 days post-injury, to determine the TTRTP at the pre-injury level. of 34 patients, 15 received PRP and 19 did not. Mean TTRTP at the pre-injury level was 50.9±10.7 days in the PRP group and 52.8±15.7 days in the control group. The difference was not statistically significant. a single intramuscular PRP injection did not shorten the TTRTP in sports people with severe acute hamstring injuries.

Acute oral toxicity and anti-inflammatory activity of hydroalcoholic extract from Lampaya medicinalis Phil in rats.

Science.gov (United States)

Morales, Glauco; Paredes, Adrián; Olivares, Alberto; Bravo, Jaime

2014-03-26

Algesia and inflammation are related with several pathological conditions. It is known that many drugs available for the treatment of these problems cause unwanted side effects. This study was aimed at evaluating acute toxicity and anti-inflammatory activity of Lampaya medicinalis Phil. (Verbenaceae) widely used in the folk medicine of Northern Chile against rheumatism, arthritis and body joints pain. Oral administration of hydroalcoholic extract (HAE) at the highest dose of 3000 mg/ Kg body weight resulted in no mortalities or evidence of significant behavioral changes. Histological examination revealed normal architecture and no significant adverse effects were observed on the liver, kidney, heart, lung or ovaries and testicles. The results suggest that the oral administration of hydroalcoholic extract (HAE) from Lampaya medicinalis did not produce any toxic effect in rats. Hydroalcoholic extract (HAE) significantly inhibited the carrageenan-induced rat paw edema in dose - response relationship, at test doses of 37.5, 75, 150 and 300 mg/Kg body weight. Maximum inhibition (61.98 ± 2.69%) was noted at 300 mg/Kg after 2 h of drug treatment carrageenan induced paw edema, whereas indomethacin produced 47.90 ± 1.16% of inhibition. The inhibitory values of edema at 3 h postcarrageenan were 31.04 ± 0.75%, 40.51 ± 2.36%, 48.97 ± 1.14% and 56.87 ± 0.41% for 37.5, 75, 150, and 300 mg/kg of extract respectively. Indomethacin (10 mg/Kg) gave a percentage inhibition of 49.44 ± 1.44. HAE (300 and 150 mg/kg) induced an anti-inflammatory effect greater than (or comparable) with the effect of indomethacin from 2nd to 4th hours of the experiment. Our results reveal for first time that compounds contained in the hydroalcoholic extract of Lampaya medicinalis Phil exert anti-inflammatory effect and the oral administration is safe and non toxic up to dose level 3000 mg/kg body weight. The anti-inflammatory activity may be associated with the presence of flavonoids. These

Mechanisms of Host Receptor Adaptation by Severe Acute Respiratory Syndrome Coronavirus

Energy Technology Data Exchange (ETDEWEB)

Wu, Kailang; Peng, Guiqing; Wilken, Matthew; Geraghty, Robert J.; Li, Fang (UMMC)

2012-12-10

The severe acute respiratory syndrome coronavirus (SARS-CoV) from palm civets has twice evolved the capacity to infect humans by gaining binding affinity for human receptor angiotensin-converting enzyme 2 (ACE2). Numerous mutations have been identified in the receptor-binding domain (RBD) of different SARS-CoV strains isolated from humans or civets. Why these mutations were naturally selected or how SARS-CoV evolved to adapt to different host receptors has been poorly understood, presenting evolutionary and epidemic conundrums. In this study, we investigated the impact of these mutations on receptor recognition, an important determinant of SARS-CoV infection and pathogenesis. Using a combination of biochemical, functional, and crystallographic approaches, we elucidated the molecular and structural mechanisms of each of these naturally selected RBD mutations. These mutations either strengthen favorable interactions or reduce unfavorable interactions with two virus-binding hot spots on ACE2, and by doing so, they enhance viral interactions with either human (hACE2) or civet (cACE2) ACE2. Therefore, these mutations were viral adaptations to either hACE2 or cACE2. To corroborate the above analysis, we designed and characterized two optimized RBDs. The human-optimized RBD contains all of the hACE2-adapted residues (Phe-442, Phe-472, Asn-479, Asp-480, and Thr-487) and possesses exceptionally high affinity for hACE2 but relative low affinity for cACE2. The civet-optimized RBD contains all of the cACE2-adapted residues (Tyr-442, Pro-472, Arg-479, Gly-480, and Thr-487) and possesses exceptionally high affinity for cACE2 and also substantial affinity for hACE2. These results not only illustrate the detailed mechanisms of host receptor adaptation by SARS-CoV but also provide a molecular and structural basis for tracking future SARS-CoV evolution in animals.

Acute asthma severity identification of expert system flow in emergency department

Science.gov (United States)

Sharif, Nurul Atikah Mohd; Ahmad, Norazura; Ahmad, Nazihah; Desa, Wan Laailatul Hanim Mat

2017-11-01

Integration of computerized system in healthcare management help in smoothening the documentation of patient records, highly accesses of knowledge and clinical practices guideline, and advice on decision making. Exploit the advancement of artificial intelligent such as fuzzy logic and rule-based reasoning may improve the management of emergency department in terms of uncertainty condition and medical practices adherence towards clinical guideline. This paper presenting details of the emergency department flow for acute asthma severity identification with the embedding of acute asthma severity identification expert system (AASIES). Currently, AASIES is still in preliminary stage of system validation. However, the implementation of AASIES in asthma bay management is hope can reduce the usage of paper for manual documentation and be a pioneer for the development of a more complex decision support system to smoothen the ED management and more systematic.

Severity of Acute Infectious Mononucleosis Correlates with Cross-Reactive Influenza CD8 T-Cell Receptor Repertoires.

Science.gov (United States)

Aslan, Nuray; Watkin, Levi B; Gil, Anna; Mishra, Rabinarayan; Clark, Fransenio G; Welsh, Raymond M; Ghersi, Dario; Luzuriaga, Katherine; Selin, Liisa K

2017-12-05

Fifty years after the discovery of Epstein-Barr virus (EBV), it remains unclear how primary infection with this virus leads to massive CD8 T-cell expansion and acute infectious mononucleosis (AIM) in young adults. AIM can vary greatly in severity, from a mild transient influenza-like illness to a prolonged severe syndrome. We questioned whether expansion of a unique HLA-A2.01-restricted, cross-reactive CD8 T-cell response between influenza virus A-M1 58 (IAV-M1) and EBV BMLF1 280 (EBV-BM) could modulate the immune response to EBV and play a role in determining the severity of AIM in 32 college students. Only ex vivo total IAV-M1 and IAV-M1+EBV-BM cross-reactive tetramer + frequencies directly correlated with AIM severity and were predictive of severe disease. Expansion of specific cross-reactive memory IAV-M1 T-cell receptor (TCR) Vβ repertoires correlated with levels of disease severity. There were unique profiles of qualitatively different functional responses in the cross-reactive and EBV-specific CD8 T-cell responses in each of the three groups studied, severe-AIM patients, mild-AIM patients, and seropositive persistently EBV-infected healthy donors, that may result from differences in TCR repertoire use. IAV-M1 tetramer + cells were functionally cross-reactive in short-term cultures, were associated with the highest disease severity in AIM, and displayed enhanced production of gamma interferon, a cytokine that greatly amplifies immune responses, thus frequently contributing to induction of immunopathology. Altogether, these data link heterologous immunity via CD8 T-cell cross-reactivity to CD8 T-cell repertoire selection, function, and resultant disease severity in a common and important human infection. In particular, it highlights for the first time a direct link between the TCR repertoire with pathogenesis and the diversity of outcomes upon pathogen encounter. IMPORTANCE The pathogenic impact of immune responses that by chance cross-react to unrelated

Quantitation of anti-tetanus and anti-diphtheria antibodies by enzymoimmunoassay: methodology and applications.

Science.gov (United States)

Virella, G; Hyman, B

1991-01-01

We have developed enzymoimmunoassays (EIA) for the quantitation of antibodies (Ab) to tetanus and diphtheria toxoids (TT, DT) using Immulon I plates coated with the appropriate toxoid. A preparation of human tetanus immunoglobulin with a known concentration of anti-TT Ab was used as calibrator of the anti-TT antibody assay. The assay of anti-DT Ab is calibrated with a pool of human sera whose anti-DT Ab concentration was determined by quantitative immunoelectrophoresis, using a horse anti-DT with known Ab concentration as calibrator. A peroxidase-conjugated anti-human IgG was used in both assays. ABTS was used as substrate, and the reaction was stopped after 1 min incubation with citric acid and the OD measured at 414 nm on a Vmax reader. The assays have been applied to a variety of clinical situations. In patients suspected of having tetanus, the quantitation of antibodies has been helpful in establishing a diagnosis. In patients with a history of hypersensitivity to tetanus toxoid, verification of the levels of anti-TT antibody may prevent unnecessary and potentially harmful immunizations. The assays have also been used for the diagnostic evaluation of the humoral immune response to TT and DT, both in pediatric patients and in immunosuppressed patients. Several non-responders have been detected, and we have recently used the assay to monitor the effects of fish oil administration on the humoral immune response.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-protein C antibodies are associated with resistance to endogenous protein C activation and a severe thrombotic phenotype in antiphospholipid syndrome.

Science.gov (United States)

Arachchillage, D R J; Efthymiou, M; Mackie, I J; Lawrie, A S; Machin, S J; Cohen, H

2014-11-01

Antiphospholipid antibodies may interfere with the anticoagulant activity of activated protein C (APC) to induce acquired APC resistance (APCr). To investigate the frequency and characteristics of APCr by using recombinant human APC (rhAPC) and endogenous protein C activation in antiphospholipid syndrome (APS). APCr was assessed in APS and non-APS venous thromboembolism (VTE) patients on warfarin and normal controls with rhAPC or Protac by thrombin generation. IgG anti-protein C and anti-protein S antibodies and avidity were assessed by ELISA. APS patients showed greater resistance to both rhAPC and Protac than non-APS patients and normal controls (median normalized endogenous thrombin potential inhibition): APS patients with rhAPC, 81.3% (95% confidence interval [CI] 75.2-88.3%; non-APS patients with rhAPC, 97.7% (95% CI 93.6-101.8%; APS patients with Protac, 66.0% (95% CI 59.5-72.6%); and non-APS patients with Protac, 80.7 (95% CI 74.2-87.2%). APS patients also had a higher frequency and higher levels of anti-protein C antibodies, with 60% (15/25) high-avidity antibodies. High-avidity anti-protein C antibodies were associated with greater APCr and with a severe thrombotic phenotype (defined as the development of recurrent VTE while patients were receiving therapeutic anticoagulation or both venous and arterial thrombosis). Twelve of 15 (80%) patients with high-avidity anti-protein C antibodies were classified as APS category I. Thrombotic APS patients showed greater APCr to both rhAPC and activation of endogenous protein C by Protac. High-avidity anti-protein C antibodies, associated with greater APCr, may provide a marker for a severe thrombotic phenotype in APS. However, in patients with category I APS, it remains to be established whether anti-protein C or anti-β2 -glycoprotein I antibodies are responsible for APCr. © 2014 International Society on Thrombosis and Haemostasis.

Tyrosol and its metabolites as antioxidative and anti-inflammatory molecules in human endothelial cells.

Science.gov (United States)

Muriana, Francisco J G; Montserrat-de la Paz, Sergio; Lucas, Ricardo; Bermudez, Beatriz; Jaramillo, Sara; Morales, Juan C; Abia, Rocio; Lopez, Sergio

2017-08-01

Tyrosol (Tyr) is a phenolic compound found in virgin olive oil. After ingestion, Tyr undergoes extensive first pass intestinal/hepatic metabolism. However, knowledge about the biological effects of Tyr metabolites is scarce. We chemically synthesized Tyr glucuronate (Tyr-GLU) and sulphate (Tyr-SUL) metabolites and explored their properties against oxidative stress and inflammation in TNF-α-treated human umbilical vein endothelial cells (hECs). Tyr and Tyr-SUL prevented the rise of reactive oxygen species, the depletion of glutathione, and the down-regulation of glutathione peroxidase 1, glutamate-cysteine ligase catalytic subunit, and heme oxygenase-1 genes. Tyr-SUL and to a lower extent Tyr and Tyr-GLU prevented the phosphorylation of NF-κB signaling proteins. Tyr-GLU and Tyr-SUL also prevented the over-expression of adhesion molecules at gene, protein, and secretory levels, and the adhesion (Tyr-SUL > Tyr-GLU) of human monocytes to hECs. In vivo, Tyr, and most notably Tyr-SUL in a dose-dependent manner, ameliorated plantar and ear edemas in mice models of acute and chronic inflammation. This study demonstrates the antioxidant and/or anti-inflammatory properties of Tyr metabolites, with Tyr-SUL being the most effective.

induced acute cytotoxicity in human cervical epithelial carcinoma cells

African Journals Online (AJOL)

Molecular basis of arsenite (As +3 )-induced acute cytotoxicity in human cervical epithelial carcinoma cells. ... Libyan Journal of Medicine ... Methods: After performing cytotoxic assays on a human epithelial carcinoma cell line, expression analysis was done by quantitative polymerase chain reaction, western blotting, and ...

Acute respiratory failure requiring mechanical ventilation in severe chronic obstructive pulmonary disease (COPD).

Science.gov (United States)

Gadre, Shruti K; Duggal, Abhijit; Mireles-Cabodevila, Eduardo; Krishnan, Sudhir; Wang, Xiao-Feng; Zell, Katrina; Guzman, Jorge

2018-04-01

There are limited data on the epidemiology of acute respiratory failure necessitating mechanical ventilation in patients with severe chronic obstructive pulmonary disease (COPD). The prognosis of acute respiratory failure requiring invasive mechanical ventilation is believed to be grim in this population. The purpose of this study was to illustrate the epidemiologic characteristics and outcomes of patients with underlying severe COPD requiring mechanical ventilation.A retrospective study of patients admitted to a quaternary referral medical intensive care unit (ICU) between January 2008 and December 2012 with a diagnosis of severe COPD and requiring invasive mechanical ventilation for acute respiratory failure.We evaluated 670 patients with an established diagnosis of severe COPD requiring mechanical ventilation for acute respiratory failure of whom 47% were male with a mean age of 63.7 ± 12.4 years and Acute physiology and chronic health evaluation (APACHE) III score of 76.3 ± 27.2. Only seventy-nine (12%) were admitted with a COPD exacerbation, 27(4%) had acute respiratory distress syndrome (ARDS), 78 (12%) had pneumonia, 78 (12%) had sepsis, and 312 (47%) had other causes of respiratory failure, including pulmonary embolism, pneumothorax, etc. Eighteen percent of the patients received a trial of noninvasive positive pressure ventilation. The median duration of mechanical ventilation was 3 days (interquartile range IQR 2-7); the median duration for ICU length of stay (LOS) was 5 (IQR 2-9) days and the median duration of hospital LOS was 12 (IQR 7-22) days. The overall ICU mortality was 25%. Patients with COPD exacerbation had a shorter median duration of mechanical ventilation (2 vs 4 days; P = .04), ICU (3 vs 5 days; P = .01), and hospital stay (10 vs 13 days; P = .01). The ICU mortality (9% vs 27%; P respiratory failure. A 1-unit increase in the APACHE III score was associated with a 1% decrease and having an active cancer was associated

Severe Rhabdomyolysis Associated with Staphylococcus aureus Acute Endocarditis Requiring Surgery.

Science.gov (United States)

Ravry, Céline; Fedou, Anne-Laure; Dubos, Maria; Denes, Éric; Etchecopar, Caroline; Barraud, Olivier; Vignon, Philippe; François, Bruno

2015-12-01

Rhabdomyolysis has multiple etiologies with unclear mechanisms; however, rhabdomyolysis caused by Staphylococcus aureus infection is rare. A case report of severe rhabdomyolysis in a patient who presented with endocarditis caused by methicillin-susceptible S. aureus and review of relevant literature. The patient had a history of cardiac surgery for tetralogy of Fallot. He was admitted to the hospital because of fever and digestive symptoms. Respiratory and hemodynamic status deteriorated rapidly, leading to admission to the intensive care unit (ICU) for mechanical ventilation and vasopressor support. Laboratory tests disclosed severe rhabdomyolysis with a serum concentration of creatine kinase that peaked at 49,068 IU/L; all blood cultures grew methicillin-susceptible S. aureus. Antibiotic therapy was amoxicillin-clavulanic acid, ciprofloxacin, and gentamicin initially and was changed subsequently to oxacillin, clindamycin, and gentamicin. Transesophageal echocardiography showed vegetation on the pulmonary valve, thus confirming the diagnosis of acute endocarditis. Viral testing and computed tomography (CT) scan ruled out any obvious alternative etiology for rhabdomyolysis. Bacterial analysis did not reveal any specificity of the staphylococcal strain. The patient improved with antibiotics and was discharged from the ICU on day 26. He underwent redux surgery for valve replacement on day 53. Staphylococcal endocarditis should be suspected in cases of severe unexplained rhabdomyolysis with acute infectious symptoms.

Hematopoietic growth factors and human acute leukemia.

Science.gov (United States)

Löwenberg, B; Touw, I

1988-10-22

The study of myelopoietic maturation arrest in acute myeloblastic leukemia (AML) has been eased by availability of the human recombinant hemopoietic growth factors, macrophage colony stimulating factor (M-CSF), granulocyte-(G-CSF), granulocyte-macrophage-(GM-CSF) and multilineage stimulating factor (IL-3). Nonphysiological expansion of the leukemic population is not due to escape from control by these factors. Proliferation in vitro of AML cells is dependent on the presence of one or several factors in most cases. The pattern of factor-dependency does not correlate with morphological criteria in individual cases, and may thus offer a new tool for classification of AML. Overproduction of undifferentiated cells is not due to abnormal expression of receptors for the stimulating factors acting at an immature level. Rather, autocrine secretion of early acting lymphokines maintains proliferation of the leukemic clone. When looking at causes of leukemic dysregulation, yet undefined inhibitors of differentiation probably are of equal importance as dysequilibrated stimulation by lymphokines.

Development of new versions of anti-human CD34 monoclonal antibodies with potentially reduced immunogenicity

International Nuclear Information System (INIS)

Qian Weizhu; Wang Ling; Li Bohua; Wang Hao; Hou Sheng; Hong Xueyu; Zhang Dapeng; Guo Yajun

2008-01-01

Despite the widespread clinical use of CD34 antibodies for the purification of human hematopoietic stem/progenitor cells, all the current anti-human CD34 monoclonal antibodies (mAbs) are murine, which have the potential to elicit human antimouse antibody (HAMA) immune response. In the present study, we developed three new mouse anti-human CD34 mAbs which, respectively, belonged to class I, class II and class III CD34 epitope antibodies. In an attempt to reduce the immunogenicity of these three murine mAbs, their chimeric antibodies, which consisted of mouse antibody variable regions fused genetically to human antibody constant regions, were constructed and characterized. The anti-CD34 chimeric antibodies were shown to possess affinity and specificity similar to that of their respective parental murine antibodies. Due to the potentially better safety profiles, these chimeric antibodies might become alternatives to mouse anti-CD34 antibodies routinely used for clinical application

Clinical and laboratory assessment of dehydration severity in children with acute gastroenteritis.

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Parkin, Patricia C; Macarthur, Colin; Khambalia, Amina; Goldman, Ran D; Friedman, Jeremy N

2010-03-01

To evaluate clinical and laboratory assessment of dehydration severity in children, 1 to 36 months, with acute gastroenteritis. Clinical and laboratory measures and weight change following rehydration were collected for enrolled children. Pediatric emergency department. Likelihood ratio (LR+) and 95% confidence interval (CI): for a clinical score of 0, the LR+ was 2.2 (95% CI = 0.9-5.3); for a clinical score of 1 to 4, the LR+ was 1.3 (95% CI = 0.90-1.74); for a clinical score of 5 to 8, the LR+ was 5.2 (95% CI = 2.2-12.8); for a venous pH Dehydration Scale and laboratory measures into clinical decision-making algorithms to assess dehydration severity in children with acute gastroenteritis.

Indices of anti-dengue immunoglobulin G subclasses in adult Mexican patients with febrile and hemorrhagic dengue in the acute phase.

Science.gov (United States)

Posadas-Mondragón, Araceli; Aguilar-Faisal, José Leopoldo; Chávez-Negrete, Adolfo; Guillén-Salomón, Edith; Alcántara-Farfán, Verónica; Luna-Rojas, Lucero; Ávila-Trejo, Amanda Marineth; Del Carmen Pacheco-Yépez, Judith

2017-10-01

Heterologous secondary infections are at increased risk of developing dengue hemorrhagic fever (DHF) because of antibody-dependent enhancement (ADE). IgG subclasses can fix and activate complement and bind to Fcɣ receptors. These factors may also play an important role in the development of ADE and thus in the pathogenesis of DHF. The aim of this study was to analyze the indices of anti-dengue IgG subclasses in adult patients with febrile and hemorrhagic dengue in the acute phase. In 2013, 129 patients with dengue fever (DF) and 57 with DHF in Veracruz, Mexico were recruited for this study and anti-dengue IgM and IgG determined by capture ELISA. Anti-dengue IgG subclasses were detected by indirect ELISA. Anti-dengue IgG2 and IgG3 subclasses were detected in patients with dengue. IgG1 increased significantly in the sera of patients with both primary and secondary infections and DHF, but was higher in patients with secondary infections. The IgG4 subclass index was significantly higher in the sera of patients with DHF than in that of those with DF, who were in the early and late acute phase of both primary and secondary infection. In conclusion, indices of subclasses IgG1 and IgG4 were higher in patients with DHF. © 2017 The Societies and John Wiley & Sons Australia, Ltd.

Dynamic innate immune responses of human bronchial epithelial cells to severe acute respiratory syndrome-associated coronavirus infection.

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Tomoki Yoshikawa

2010-01-01

Full Text Available Human lung epithelial cells are likely among the first targets to encounter invading severe acute respiratory syndrome-associated coronavirus (SARS-CoV. Not only can these cells support the growth of SARS-CoV infection, but they are also capable of secreting inflammatory cytokines to initiate and, eventually, aggravate host innate inflammatory responses, causing detrimental immune-mediated pathology within the lungs. Thus, a comprehensive evaluation of the complex epithelial signaling to SARS-CoV is crucial for paving the way to better understand SARS pathogenesis. Based on microarray-based functional genomics, we report here the global gene response of 2B4 cells, a cloned bronchial epithelial cell line derived from Calu-3 cells. Specifically, we found a temporal and spatial activation of nuclear factor (NFkappaB, activator protein (AP-1, and interferon regulatory factor (IRF-3/7 in infected 2B4 cells at 12-, 24-, and 48-hrs post infection (p.i., resulting in the activation of many antiviral genes, including interferon (IFN-beta, -lambdas, inflammatory mediators, and many IFN-stimulated genes (ISGs. We also showed, for the first time, that IFN-beta and IFN-lambdas were capable of exerting previously unrecognized, non-redundant, and complementary abilities to limit SARS-CoV replication, even though their expression could not be detected in infected 2B4 bronchial epithelial cells until 48 hrs p.i. Collectively, our results highlight the mechanics of the sequential events of antiviral signaling pathway/s triggered by SARS-CoV in bronchial epithelial cells and identify novel cellular targets for future studies, aiming at advancing strategies against SARS.

The absence of exanthema is related with death and illness severity in acute enterovirus infection

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Hong-Tao Zhou

2014-11-01

Conclusions: A considerable proportion of children with an acute enterovirus infection in Guangdong Province, China during 2009–2012 presented no exanthema, and the absence of exanthema was found to be related to death and illness severity for these acute enterovirus infections. Clinicians in China should consider enterovirus as the possible pathogen when treating children with an acute pathogen infection without exanthema.

Effect of probiotics on diarrhea in children with severe acute malnutrition

DEFF Research Database (Denmark)

Grenov, Benedikte; Namusoke, Hanifa; Lanyero, Betty

2017-01-01

OBJECTIVES: To assess the effect of probiotics on diarrhea during in- and outpatient treatment of children with severe acute malnutrition (SAM). METHODS: A randomized, double-blind, placebo-controlled study was conducted involving 400 children admitted with SAM. Patients received one daily dose...

Effect of the human leukocyte antigen HLA-DRB1 and anti-cyclic citrullinated peptide on the outcome of rheumatoid arthritis patients.

Science.gov (United States)

Farouk, H M; Mansour, H E; Rahman, S A; Mostafa, A A; Shamy, H A; Zarouk, W A

2009-09-01

Our objective was to determine whether the presence of the human leukocyte antigen HLA-DRB1 locus is associated with production of anti-cyclic citrullinated peptide antibodies (anti-CCP Abs) and to what extent they are associated with increased susceptibility to and severity of rheumatoid arthritis (RA) in Egyptian patients. Twenty-nine RA patients gave informed consent to participate in a case-control study that was approved by the Ain Shams University Medical Ethics Committee. RA disease activity and severity were determined using the simplified disease activity index and Larsen scores, respectively. We used a wide scale national study on the pattern of HLA typing in normal Egyptians as a control study. Anti-CCP Abs and HLA-DRB1 typing were determined for all subjects. The alleles most strongly associated with RA were HLA-DRB1 [*01 , *04 and *06] (41.4%). RA patients with serum anti-CCP Ab titers above 60 U/mL had a significantly higher frequency of HLA-DRB1*01 (58.3%) and HLA-DRB1*04 alleles (83.3%). Significant positive correlations were found between serum and synovial anti-CCP Ab titer, RA disease activity, and severity (r = 0.87, 0.66 and 0.63, respectively; P < 0.05). HLA-DRB1 SE+ alleles [*01 and *04] were highly expressed among Egyptian RA patients. The presence of these alleles was associated with higher anti-CCP Ab titer, active and severe RA disease. Early determination of HLA-DRB1 SE+ alleles and serum anti-CCP Ab could facilitate the prediction of the clinical course and prognosis of RA when first evaluated leading to better disease control.

Effect of the human leukocyte antigen HLA-DRB1 and anti-cyclic citrullinated peptide on the outcome of rheumatoid arthritis patients

Directory of Open Access Journals (Sweden)

H.M. Farouk

2009-09-01

Full Text Available Our objective was to determine whether the presence of the human leukocyte antigen HLA-DRB1 locus is associated with production of anti-cyclic citrullinated peptide antibodies (anti-CCP Abs and to what extent they are associated with increased susceptibility to and severity of rheumatoid arthritis (RA in Egyptian patients. Twenty-nine RA patients gave informed consent to participate in a case-control study that was approved by the Ain Shams University Medical Ethics Committee. RA disease activity and severity were determined using the simplified disease activity index and Larsen scores, respectively. We used a wide scale national study on the pattern of HLA typing in normal Egyptians as a control study. Anti-CCP Abs and HLA-DRB1 typing were determined for all subjects. The alleles most strongly associated with RA were HLA-DRB1 [*01 , *04 and *06] (41.4%. RA patients with serum anti-CCP Ab titers above 60 U/mL had a significantly higher frequency of HLA-DRB1*01 (58.3% and HLA-DRB1*04 alleles (83.3%. Significant positive correlations were found between serum and synovial anti-CCP Ab titer, RA disease activity, and severity (r = 0.87, 0.66 and 0.63, respectively; P < 0.05. HLA-DRB1 SE+ alleles [*01 and *04] were highly expressed among Egyptian RA patients. The presence of these alleles was associated with higher anti-CCP Ab titer, active and severe RA disease. Early determination of HLA-DRB1 SE+ alleles and serum anti-CCP Ab could facilitate the prediction of the clinical course and prognosis of RA when first evaluated leading to better disease control.

Proinflammatory and anti-inflammatory cytokines present in the acute phase of experimental colitis treated with Saccharomyces boulardii.

Science.gov (United States)

Grijó, Nathália Nahas; Borra, Ricardo Carneiro; Sdepanian, Vera Lucia

2010-09-01

To study the proinflammatory and anti-inflammatory cytokines present in the acute phase of trinitrobenzene sulfonic acid (TNBS)-induced experimental colitis treated with Saccharomyces boulardii. Thirty male Wistar rats were divided into three groups: (1) treated group--received Saccharomyces boulardii for 14 days; (2) non-treated group--received sodium chloride solution for 14 days; (3) control group. Colitis was induced on the seventh day of the study in the treated and the non-treated groups using TNBS (10 mg) dissolved in 50% ethanol. Quantification of cytokines, including interleukin (IL)-1beta (IL-1beta), IL-6, transforming growth factor-beta (TGF-beta), IL-10 and tumor necrosis factor-alpha (TNF-alpha), in the serum and colonic tissue collected on day 14 were carried out using an enzyme-linked immunosorbent assay (ELISA). The mean concentrations of TGF-beta in both the serum and the colonic tissue of the treated group were statistically higher than that of the control group. The mean concentration of TGF-beta in the colonic tissue of the non-treated group was also statistically higher than the control group. The group treated with Saccharomyces boulardii showed increased amounts of TGF-beta, an anti-inflammatory cytokine, during the acute phase of colitis. There were no differences in the amount of TNF-alpha, IL-1beta, IL-6, and IL-10 between the treated and the non-treated or the control groups during the acute phase of experimental colitis induced by TNBS.

Dengue virus infection induces broadly cross-reactive human IgM antibodies that recognize intact virions in humanized BLT-NSG mice.

Science.gov (United States)

Jaiswal, Smita; Smith, Kenneth; Ramirez, Alejandro; Woda, Marcia; Pazoles, Pamela; Shultz, Leonard D; Greiner, Dale L; Brehm, Michael A; Mathew, Anuja

2015-01-01

The development of small animal models that elicit human immune responses to dengue virus (DENV) is important since prior immunity is a major risk factor for developing severe dengue disease. This study evaluated anti-DENV human antibody (hAb) responses generated from immortalized B cells after DENV-2 infection in NOD-scid IL2rγ(null) mice that were co-transplanted with human fetal thymus and liver tissues (BLT-NSG mice). DENV-specific human antibodies predominantly of the IgM isotype were isolated during acute infection and in convalescence. We found that while a few hAbs recognized the envelope protein produced as a soluble recombinant, a number of hAbs only recognized epitopes on intact virions. The majority of the hAbs isolated during acute infection and in immune mice were serotype-cross-reactive and poorly neutralizing. Viral titers in immune BLT-NSG mice were significantly decreased after challenge with a clinical strain of dengue. DENV-specific hAbs generated in BLT-NSG mice share some of the characteristics of Abs isolated in humans with natural infection. Humanized BLT-NSG mice provide an attractive preclinical platform to assess the immunogenicity of candidate dengue vaccines. © 2014 by the Society for Experimental Biology and Medicine.

Plumbagin exerts an immunosuppressive effect on human T-cell acute lymphoblastic leukemia MOLT-4 cells

Energy Technology Data Exchange (ETDEWEB)

Bae, Kyoung Jun; Lee, Yura [Department of Biomedical Laboratory Science, Daejeon 34824 (Korea, Republic of); Kim, Soon Ae [Department of Pharmacology, School of Medicine, Daejeon 34824 (Korea, Republic of); Kim, Jiyeon, E-mail: yeon@eulji.ac.kr [Department of Biomedical Laboratory Science, Daejeon 34824 (Korea, Republic of)

2016-04-22

Of the hematological disorders typified by poor prognoses and survival rates, T-cell acute lymphoblastic leukemia (T-ALL) is one of the most commonly diagnosed. Despite the development of new therapeutic agents, the treatment options for this cancer remain limited. In this manuscript, we investigated the anti-proliferative effects of plumbagin, mediated by the activation of mitogen-activated protein kinase (MAPK) pathways, and inhibition of NF-κB signaling; the human T-ALL MOLT-4 cell line was used as our experimental system. Plumbagin is a natural, plant derived compound, which exerts an anti-proliferative activity against many types of human cancer. Our experiments confirm that plumbagin induces a caspase-dependent apoptosis of MOLT-4 cells, with no significant cytotoxicity seen for normal peripheral blood mononuclear cells (PBMCs). Plumbagin also inhibited LPS-induced phosphorylation of p65, and the transcription of NF-κB target genes. Our results now show that plumbagin is a potent inhibitor of the NF-κB signaling pathway, and suppressor of T-ALL cell proliferation. - Highlights: • Plumbagin induces caspase-dependent apoptosis in T-ALL MOLT-4 cells. • Plumbagin activates phosphorylation of stress-activated protein kinase (SAPK) JNK and p38. • Plumbagin inhibits LPS-mediated NF-κB signaling cascade. • Plumbagin inhibits LPS-mediated transcriptional activity of pro-inflammatory cytokines.

Severe infusion reactions to infliximab: aetiology, immunogenicity and risk factors in patients with inflammatory bowel disease

DEFF Research Database (Denmark)

Steenholdt, Casper; Svenson, M; Bendtzen, K

2011-01-01

BACKGROUND: Infliximab (IFX) elicits acute severe infusion reactions in about 5% of patients with inflammatory bowel disease (IBD). AIM: To investigate the role of anti-IFX antibodies (Ab) and other risk factors. METHODS: The study included all IBD patients treated with IFX at a Danish university...... hospital until 2010 either continuously (IFX every 4-12 weeks) or episodically (reinitiation after >12 weeks). Anti-IFX Ab were measured using radioimmunoassay. RESULTS: Twenty-five (8%) of 315 patients experienced acute severe infusion reactions. Univariate analysis showed that patients who reacted were...... younger at the time of diagnosis (19 vs. 26 years, P=0.013) and at first IFX infusion (28 vs. 35 years, P=0.012). Furthermore, they more often received episodic therapy (72% vs. 31%, P

Anti-irritant and anti-inflammatory effects of glycerol and xylitol in sodium lauryl sulphate-induced acute irritation.

Science.gov (United States)

Szél, E; Polyánka, H; Szabó, K; Hartmann, P; Degovics, D; Balázs, B; Németh, I B; Korponyai, C; Csányi, E; Kaszaki, J; Dikstein, S; Nagy, K; Kemény, L; Erős, G

2015-12-01

Glycerol is known to possess anti-irritant and hydrating properties and previous studies suggested that xylitol may also have similar effects. Our aim was to study whether different concentrations of these polyols restore skin barrier function and soothe inflammation in sodium lauryl sulphate (SLS)-induced acute irritation. The experiments were performed on male SKH-1 hairless mice. The skin of the dorsal region was exposed to SLS (5%) for 3 h alone or together with 5% or 10% of glycerol respectively. Further two groups received xylitol solutions (8.26% and 16.52% respectively) using the same osmolarities, which were equivalent to those of the glycerol treatments. The control group was treated with purified water. Transepidermal water loss (TEWL) and skin hydration were determined. Microcirculatory parameters of inflammation were observed by means of intravital videomicroscopy (IVM). Furthermore, accumulation of neutrophil granulocytes and lymphocytes, the expression of inflammatory cytokines and SLS penetration were assessed, as well. Treatment with the 10% of glycerol and both concentrations of xylitol inhibited the SLS-induced elevation of TEWL and moderated the irritant-induced increase in dermal blood flow and in the number of leucocyte-endothelial interactions. All concentrations of the applied polyols improved hydration and prevented the accumulation of lymphocytes near the treatment site. At the mRNA level, neither glycerol nor xylitol influenced the expression of interleukin-1 alpha. However, expression of interleukin-1 beta was significantly decreased by the 10% glycerol treatment, while expression of tumour necrosis factor-alpha decreased upon the same treatment, as well as in response to xylitol. Higher polyol treatments decreased the SLS penetration to the deeper layers of the stratum corneum. Both of the analysed polyols exert considerable anti-irritant and anti-inflammatory properties, but the effective concentration of xylitol is lower than that of

Functional survival after acute care for severe head injury at a designated trauma center in Hong Kong.

Science.gov (United States)

Taw, Benedict B T; Lam, Alan C S; Ho, Faith L Y; Hung, K N; Lui, W M; Leung, Gilberto K K

2012-07-01

Severe head injury is known to be a major cause of early mortalities and morbidities. Patients' long-term outcome after acute care, however, has not been widely studied. We aim to review the outcome of severely head-injured patients after discharge from acute care at a designated trauma center in Hong Kong. This is a retrospective study of prospectively collected data of patients admitted with severe head injuries between 2004 and 2008. Patients' functional status post-discharge was assessed using the Extended Glasgow Outcome Score (GOSE). Of a total of 1565 trauma patients, 116 had severe head injuries and 41 of them survived acute hospital care. Upon the last follow-up, 23 (56.1%) of the acute-care survivors had improvements in their GOSE, six (11.8%) experienced deteriorations, and 12 (23.5%) did not exhibit any change. The greatest improvement was observed in patients with GOSE of 5 and 6 upon discharge, but two of the 16 patients with GOSE 2 or 3 also had a good recovery. On logistic regression analysis, old age and prolonged acute hospital stay were found to be independent predictors of poor functional outcome after a mean follow-up duration of 42 months. Multidisciplinary neurorehabilitation service is an important component of comprehensive trauma care. Despite significant early mortalities, a proportion of severely head-injured patients who survive acute care may achieve good long-term functional recovery. Copyright © 2012, Asian Surgical Association. Published by Elsevier Taiwan LLC. All rights reserved.

[Detection of fps tumor antigen with mono-specific anti-fps serum in tumors induced by acute transforming ALV].

Science.gov (United States)

Wang, Yixin; Chen, Hao; Zhao, Peng; Li, Jianliang; Cui, Zhizhong

2013-03-04

To prepare anti-fps mono-specific serum, and detect the fps antigen in tumors induced by acute transforming avian leukosis/sarcoma virus containing v-fps oncogene. Two part of v-fps gene was amplified by RT-PCR using the Fu-J viral RNA as the template. Mono-specific serum was prepared by immuning Kunming white mouse with both two recombinant infusion proteins expressed by the prokaryotic expression system. Indirect immunofluorescent assay was used to detect fps antigen in tumor tissue suspension cells and CEF infected by sarcoma supernatant. Immunohistochemical method was used to detect fps antigen in tumor tissue. The mouse mono-specific serum was specific as it had no cross reaction with classical ALV-J strains. The result reveals that the tumor tissue suspension cells, the CEF infected by sarcoma supernatant, and the slice immunohistochemistry of the sarcoma showed positive results. The anti-fps mono-specific serum was prepared, and the detection method was established, which laid the foundation for the study of viral biological characteristics and mechanism of tumourgenesis of acute transforming avian leukosis/sarcoma virus containing v-fps oncogene.

Successful Use of Extracorporeal Life Support after Double Traumatic Tracheobronchial Injury in a Patient with Severe Acute Asthma

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Xavier Valette

2011-01-01

Full Text Available We report the case of an asthmatic patient with blunt trachea and left main bronchus injuries who developed acute severe asthma after surgical repair. Despite medical treatment and ventilatory support, asthma persisted with high airway pressures and severe respiratory acidosis. We proposed venovenous extracorporeal life support for CO2 removal which allowed arterial blood gas normalization and airway pressures decrease. Extracorporeal life support was removed on day five after medical treatment of acute severe asthma. So we report the successful use of extracorporeal life support for operated double blunt tracheobronchial injury with acute severe asthma.

Total serum calcium and corrected calcium as severity predictors in acute pancreatitis

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A.A. Gutiérrez-Jiménez

2014-01-01

Conclusions: TC and ACC, measured within the first 24 hours, are useful severity predictors in acute pancreatitis, with sensitivity and predictive values comparable or superior to those of the conventional prognostic scales.

Clinical features and risk factors of acute hepatitis E with severe jaundice.

Science.gov (United States)

Xu, Bin; Yu, Hai-Bin; Hui, Wei; He, Jia-Li; Wei, Lin-Lin; Wang, Zheng; Guo, Xin-Hui

2012-12-28

To compares the clinical features of patients infected with hepatitis E virus (HEV) with or without severe jaundice. In addition, the risk factors for HEV infection with severe jaundice were investigated. We enrolled 235 patients with HEV into a cross-sectional study using multi-stage sampling to select the study group. Patients with possible acute hepatitis E showing elevated liver enzyme levels were screened for HEV infection using serologic and molecular tools.HEV infection was documented by HEV antibodies and by the detection of HEV-RNA in serum. We used χ(2) analysis, Fisher's exact test, and Student's t test where appropriate in this study. Significant predictors in the univariate analysis were then included in a forward, stepwise multiple logistic regression model. No significant differences in symptoms, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, or hepatitis B virus surface antigen between the two groups were observed. HEV infected patients with severe jaundice had significantly lower peak serum levels of γ-glutamyl-transpeptidase (GGT) (median: 170.31 U/L vs 237.96 U/L, P = 0.007), significantly lower ALB levels (33.84 g/L vs 36.89 g/L, P = 0.000), significantly lower acetylcholine esterase (CHE) levels (4500.93 U/L vs 5815.28 U/L, P = 0.000) and significantly higher total bile acid (TBA) levels (275.56 μmol/L vs 147.03 μmol/L, P = 0.000) than those without severe jaundice. The median of the lowest point time tended to be lower in patients with severe jaundice (81.64% vs 96.12%, P = 0.000). HEV infected patients with severe jaundice had a significantly higher viral load (median: 134 vs 112, P = 0.025) than those without severe jaundice. HEV infected patients with severe jaundice showed a trend toward longer median hospital stay (38.17 d vs 18.36 d, P = 0.073). Multivariate logistic regression indicated that there were significant differences in age, sex, viral load, GGT, albumin, TBA, CHE, prothrombin index, alcohol

ANTI – CORRUPTION INITIATIVES, GOOD GOVERNANCE AND HUMAN RIGHTS: THE REPUBLIC OF MACEDONIA

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Elena ANDREEVSKA

2018-05-01

Full Text Available In fighting corruption, good governance efforts rely on principles such as accountability, transparency and participation to shape anti-corruption measures. Initiatives may include establishing institutions such as anti-corruption commissions, creating mechanisms of information sharing, and monitoring governments’ use of public funds and implementation of policies. Good governance and human rights are mutually reinforcing. Human rights principles provide a set of values to guide the work of governments and other political and social actors. They also provide a set of performance standards against which these actors can be held accountable. Moreover, human rights principles inform the content of good governance efforts: they may inform the development of legislative frameworks, policies, programmers, budgetary allocations and other measures. Corruption is recognized as a serious crime in the EU, which is reflected in its many anti-corruption instruments covering existing member states. Countries wishing to join still face considerable systemic corruption issues in their public institutions. In Macedonia as one of these countries the most significant human rights problems stemmed from pervasive corruption and from the government’s failure to respect fully the rule of law. This article introduces anti-corruption work, good governance, and attempts to identify the various levels of relationship between that work and human rights with particular reference to Macedonia as an EU candidate country

Acute fulminant drug induced necrotizing pancreatitis in a patient with ankylosing spondylitis

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Pablo Miramontes

2015-03-01

Full Text Available Drug-induced acute necrotizing pancreatitis is a rare adverse event, although it has been reported in association with different drugs, including non-steroidal anti-inflammatory drugs, disease-modifying antirheumatic drugs, and analgesic agents commonly used in rheumatology. In different reviews of the pancreotoxicity of drugs, infliximab and etanercept are mentioned among all medications implicated in drug-induced pancreatitis, but clinical cases of acute pancreatitis complicating treatment with these anti-TNF-α agents have been exceptionally reported. We describe a patient with ankylosing spondylitis treated with etanercept, who developed an acute fulminant necrotizing pancreatitis that resulted in death. Doctors should pay close attention to patients taking biologic drugs in which a complaint of abdominal pain lasting for several days with no apparent cause may require a prompt referral for medical consultation.

External validation of the NOBLADS score, a risk scoring system for severe acute lower gastrointestinal bleeding.

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Tomonori Aoki

Full Text Available We aimed to evaluate the generalizability of NOBLADS, a severe lower gastrointestinal bleeding (LGIB prediction model which we had previously derived when working at a different institution, using an external validation cohort. NOBLADS comprises the following factors: non-steroidal anti-inflammatory drug use, no diarrhea, no abdominal tenderness, blood pressure ≤ 100 mmHg, antiplatelet drug use, albumin < 3.0 g/dL, disease score ≥ 2, and syncope.We retrospectively analyzed 511 patients emergently hospitalized for acute LGIB at the University of Tokyo Hospital, from January 2009 to August 2016. The areas under the receiver operating characteristic curves (ROCs-AUCs for severe bleeding (continuous and/or recurrent bleeding were compared between the original derivation cohort and the external validation cohort.Severe LGIB occurred in 44% of patients. Several clinical factors were significantly different between the external and derivation cohorts (p < 0.05, including background, laboratory data, NOBLADS scores, and diagnosis. The NOBLADS score predicted the severity of LGIB with an AUC value of 0.74 in the external validation cohort and one of 0.77 in the derivation cohort. In the external validation cohort, the score predicted the risk for blood transfusion need (AUC, 0.71, but was not adequate for predicting intervention need (AUC, 0.54. The in-hospital mortality rate was higher in patients with a score ≥ 5 than in those with a score < 5 (AUC, 0.83.Although the external validation cohort clinically differed from the derivation cohort in many ways, we confirmed the moderately high generalizability of NOBLADS, a clinical risk score for severe LGIB. Appropriate triage using this score may support early decision-making in various hospitals.

Intra-abdominal pressure and procalcitonin are valid prognostic markers of acute pancreatitis severity (intra-abdominal pressure and procalcitonin

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Stojanović Maja

2017-01-01

Full Text Available Introduction. Early assessment of the severity and etiology of acute pancreatitis is very important for further treatment procedures. The aim of the study was to investigate the association between intra-abdominal pressure (IAP and procalcitonin as an indicator of severity of acute pancreatitis. Method. The IAP is measured every 12 hours through the urinary catheter placed in the bladder, in 65 patients with acute pancreatitis. Procalcitonin is measured within 24 hours of receipt of the patient, after 48 hours and after 78 hours. These values of procalcitonin and IAP were compared to each other and in relation to the Acute Physiology, Age and Chronic Health Evaluation II (APACHE II scoring system. Patients with APACHE II score > 8 are defined with moderate and severe acute pancreatitis. Results. The values of IAP (18,1 ± 4,5 mmHg vs 8,9 ± 2,67 mmHg; p = 0,01 , procalcitonin (15,43 + 2,25 ng/ml vs 3,14 + 1,12 ng/ml; p =0,031 and APACHE II scoring system (17,3 ± 6,24 vs 6,5 ± 1,0; p = 0,013 were significantly higher in patients with moderate and severe acute pancreatitis. The increase in the value of IAP was accompanied by an increase in the value of procalcitonin (r = 0,581, p = 0,01. The sensitivity in the prediction of severe acute pancreatitis after 24 hours of receiving the patient is 91,7% for the IAP, 87,8% for procalcitonin and 84,9% for APACHE II scoring system. Conclusion. The increase in the value of the IAP is accompanied by an increase in the values of procalcitonin, also patients with higher values of APACHE II scoring sys­tem have higher values of IAP and procalcitonin. The values of IAP and procalcitonin can be used as markers of acute pancreatitis severity.

Characterization of the fetal blood transcriptome and proteome in maternal anti-fetal rejection: evidence of a distinct and novel type of human fetal systemic inflammatory response.

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Lee, Joonho; Romero, Roberto; Chaiworapongsa, Tinnakorn; Dong, Zhong; Tarca, Adi L; Xu, Yi; Chiang, Po Jen; Kusanovic, Juan Pedro; Hassan, Sonia S; Yeo, Lami; Yoon, Bo Hyun; Than, Nandor Gabor; Kim, Chong Jai

2013-10-01

The human fetus is able to mount a systemic inflammatory response when exposed to microorganisms. This stereotypic response has been termed the 'fetal inflammatory response syndrome' (FIRS), defined as an elevation of fetal plasma interleukin-6 (IL-6). FIRS is frequently observed in patients whose preterm deliveries are associated with intra-amniotic infection, acute inflammatory lesions of the placenta, and a high rate of neonatal morbidity. Recently, a novel form of fetal systemic inflammation, characterized by an elevation of fetal plasma CXCL10, has been identified in patients with placental lesions consistent with 'maternal anti-fetal rejection'. These lesions include chronic chorioamnionitis, plasma cell deciduitis, and villitis of unknown etiology. In addition, positivity for human leukocyte antigen (HLA) panel-reactive antibodies (PRA) in maternal sera can also be used to increase the index of suspicion for maternal anti-fetal rejection. The purpose of this study was to determine (i) the frequency of pathologic lesions consistent with maternal anti-fetal rejection in term and spontaneous preterm births; (ii) the fetal serum concentration of CXCL10 in patients with and without evidence of maternal anti-fetal rejection; and (iii) the fetal blood transcriptome and proteome in cases with a fetal inflammatory response associated with maternal anti-fetal rejection. Maternal and fetal sera were obtained from normal term (n = 150) and spontaneous preterm births (n = 150). A fetal inflammatory response associated with maternal anti-fetal rejection was diagnosed when the patients met two or more of the following criteria: (i) presence of chronic placental inflammation; (ii) ≥80% of maternal HLA class I PRA positivity; and (iii) fetal serum CXCL10 concentration >75th percentile. Maternal HLA PRA was analyzed by flow cytometry. The concentrations of fetal CXCL10 and IL-6 were determined by ELISA. Transcriptome analysis was undertaken after the extraction of total RNA

Bovine lactoferricin, an antimicrobial peptide, is anti-inflammatory and anti-catabolic in human articular cartilage and synovium

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Yan, Dongyao; Chen, Di; Shen, Jie; Xiao, Guozhi; van Wijnen, Andre J; Im, Hee-Jeong

2012-01-01

Bovine lactoferricin (LfcinB) is a multi-functional peptide derived from proteolytic cleavage of bovine lactoferrin. LfcinB was found to antagonize the biological effects mediated by angiogenic growth factors such as vascular endothelial growth factor (VEGF) and fibroblast growth factor 2 (FGF-2) in endothelial cells. However, the effect of LfcinB on human articular cartilage remained unknown. Here, our findings demonstrate that LfcinB restored the proteoglycan loss promoted by catabolic factors (interleukin-1 β) IL-1β and FGF-2 in vitro and ex vivo. Mechanistically, LfcinB attenuated the effects of IL-1β and FGF-2 on the expression of cartilage-degrading enzymes (MMP-1, MMP-3, and MMP-13), destructive cytokines (IL-1β and IL-6), and inflammatory mediators (iNOS and TLR2). LfcinB induced protective cytokine expression (IL-4 and IL-10), and downregulated aggrecanase basal expression. LfcinB specifically activated ERK MAPK and Akt signaling pathways, which may account for its anti-inflammatory activity. We also revealed that LfcinB exerted similar protective effects on human synovial fibroblasts challenged by IL-1β, with minimal cytotoxicity. Collectively, our results suggest that LfcinB possesses potent anti-catabolic and anti-inflammatory bioactivities in human articular tissues, and may be utilized for the prevention and/or treatment of OA in the future. PMID:22740381

Gut Bacteria Missing in Severe Acute Malnutrition, Can We Identify Potential Probiotics by Culturomics?

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Maryam Tidjani Alou

2017-05-01

Full Text Available Severe acute malnutrition is the world-leading cause of children under-five's death. Recent metagenomics studies have established a link between gut microbiota and severe acute malnutrition, describing an immaturity with a striking depletion in oxygen-sensitive prokaryotes. Amoxicillin and therapeutic diet cure most of the children with severe acute malnutrition but an irreversible disruption of the gut microbiota is suspected in the refractory and most severe cases. In these cases, therapeutic diet may be unable to reverse the microbiota alteration leading to persistent impaired development or death. In addition, as enteric sepsis is a major cause of death in this context, identification of missing gut microbes to be tested as probiotics (live bacteria that confer a benefit to the host to restore rapidly the healthy gut microbiota and prevent the gut pathogenic invasion is of foremost importance. In this study, stool samples of malnourished patients with kwashiorkor and healthy children were collected from Niger and Senegal and analyzed by culturomics and metagenomics. We found a globally decreased diversity, a decrease in the hitherto unknown diversity (new species isolation, a depletion in oxygen-sensitive prokaryotes including Methanobrevibacter smithii and an enrichment in potentially pathogenic Proteobacteria, Fusobacteria and Streptococcus gallolyticus. A complex of 12 species identified only in healthy children using culturomics and metagenomics were identified as probiotics candidates, providing a possible, defined, reproducible, safe, and convenient alternative to fecal transplantation to restore a healthy gut microbiota in malnourished children. Microbiotherapy based on selected strains has the potential to improve the current treatment of severe acute malnutrition and prevent relapse and death by reestablishing a healthy gut microbiota.

Non-infectious chemotherapy-associated acute toxicities during childhood acute lymphoblastic leukemia therapy [version 1; referees: 3 approved

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Kjeld Schmiegelow

2017-04-01

Full Text Available During chemotherapy for childhood acute lymphoblastic leukemia, all organs can be affected by severe acute side effects, the most common being opportunistic infections, mucositis, central or peripheral neuropathy (or both, bone toxicities (including osteonecrosis, thromboembolism, sinusoidal obstruction syndrome, endocrinopathies (especially steroid-induced adrenal insufficiency and hyperglycemia, high-dose methotrexate-induced nephrotoxicity, asparaginase-associated hypersensitivity, pancreatitis, and hyperlipidemia. Few of the non-infectious acute toxicities are associated with clinically useful risk factors, and across study groups there has been wide diversity in toxicity definitions, capture strategies, and reporting, thus hampering meaningful comparisons of toxicity incidences for different leukemia protocols. Since treatment of acute lymphoblastic leukemia now yields 5-year overall survival rates above 90%, there is a need for strategies for assessing the burden of toxicities in the overall evaluation of anti-leukemic therapy programs.

The severity of acute bronchiolitis in infants was associated with quality of life nine months later.

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Rolfsjord, Leif Bjarte; Skjerven, Håvard Ove; Carlsen, Kai-Håkon; Mowinckel, Petter; Bains, Karen Eline Stensby; Bakkeheim, Egil; Lødrup Carlsen, Karin C

2016-07-01

Acute bronchiolitis in infancy increases the risk of later asthma and reduced health-related quality of life (QoL). We aimed to see whether the severity of acute bronchiolitis in the first year of life was associated with QoL nine months later. The parents of 209 of 404 of children hospitalised for acute bronchiolitis in eight paediatric departments in south-east Norway at a mean four months of age (range 0-12 months) completed the Infant/Toddler Quality of Life Questionnaire sent by mail nine months after the acute illness. Disease severity was measured by length of stay and the need for supportive treatment. Interactions with gender, inclusion age, prematurity, maternal ethnicity and maternal education were examined. Reduced QoL in four domains was associated with increased length of stay and need for ventilatory support. Physical abilities and general health were associated with both severity markers, whereas bodily pain and discomfort and change in health were associated with length of stay. Ventilatory support was more negatively associated with QoL than atopic eczema and also associated with reduced parental emotions and parental time. The severity of acute bronchiolitis in infants was associated with reduced QoL nine months later. ©2016 The Authors. Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.

Acute psychosis in a pregnant patient with Graves' hyperthyroidism and anti-NMDA receptor encephalitis.

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Lu, Jesslyn; Samson, Susan; Kass, Joseph; Ram, Nalini

2015-04-22

A previously healthy 36-year-old woman presented with visual hallucinations and acute psychosis manifested predominantly as hypersexuality. Laboratory testing demonstrated elevated free thyroxine levels, suppressed thyroid-stimulating hormone levels and presence of thyroid-stimulating immunoglobulin and thyroid peroxidase (TPO) antibodies consistent with Graves' disease. Despite achieving biochemical euthyroidism, she remained profoundly hypersexual. She did not respond to additional treatment with antipsychotics and corticosteroids, prompting further evaluation. Cerebrospinal fluid analysis detected pleocytosis, elevated IgG, and presence of antibodies against anti-N-methyl-D-aspartate receptor (NMDAR), glutamic acid decarboxylase 65 and TPO. These results suggested a diagnosis of anti-NMDAR encephalitis. Prior to initiation of immunomodulator therapy, she was discovered to be pregnant with date of conception around the time of her original presentation. She received plasmapheresis with resolution of psychosis and decrease in free thyroxine levels. Graves' disease remitted during the remainder of the pregnancy but relapsed 5 months post partum. She has not had further neuropsychiatric symptoms. 2015 BMJ Publishing Group Ltd.

Antioxidation, anti-inflammation and anti-apoptosis by paeonol in LPS/d-GalN-induced acute liver failure in mice.

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Gong, Xiaobao; Yang, You; Huang, Ligua; Zhang, Qingyan; Wan, Rong-Zhen; Zhang, Peng; Zhang, Baoshun

2017-05-01

To evaluate the hepatoprotective effects and potential mechanisms of paeonol (Pae) against acute liver failure (ALF) induced by lipopolysaccharide (LPS)/d-galactosamine (d-GalN) in mice, we examined anti-oxidative, anti-inflammatory and anti-apoptotic activities of Pae. We found that Pae pretreatment markedly reduced the activities of alanine transaminase and aspartate transaminase as well as the histopathological changes induced by LPS/d-GalN. Catalase, glutathione and superoxide dismutase activities increased and reactive oxygen species activity decreased after Pae treatment compared with LPS/d-GalN treatment. Pretreatment with Pae also significantly inhibited the expression levels of iNOS, nitric oxide (NO), COX-2 and prostaglandin E 2 (PGE 2 ). In addition, Pae administration prevented the phosphorylated expression of IκB kinase, inhibitor kappa B in the nuclear factor-kappa B (NF-κB) signaling pathway, and suppressed the phosphorylated expression of extracellular signal-regulated kinase (ERK), c-jun-N-terminal kinase and p38 in the MAPK signaling pathway. Pretreatment with Pae also inhibited hepatocyte apoptosis by reducing the expression of caspases 3, 8, 9, and Bax, and increasing Bcl-2. In total, protective effects of Pae against LPS/d-GalN-induced ALF in mice are attributed to its antioxidative effect, inflammatory suppression in NF-κB and MARK signaling pathways, and inhibition of hepatocyte apoptosis inhibition. Therefore, Pae can be a potential therapeutic agent in attenuating LPS/d-GalN-induced ALF in the future. Copyright © 2017. Published by Elsevier B.V.

Management of severe subarachnoid hemorrhage (SAH) with diffusion-weighted imaging in acute stage

International Nuclear Information System (INIS)

Shamoto, Hiroshi; Shimizu, Hiroaki; Matsumoto, Yasushi; Fujiwara, Satoru; Tominaga, Teiji

2007-01-01

Determining the treatment strategy of severe subarachnoid hemorrhage (SAH) (Hunt and Kosnik Grade 4 and 5) requires objective evaluation to represent severity. In the present study, we investigated the role of diffusion-weighted imaging (DWI) in the acute stage as an objective tool. DWI was performed within 48 hours after the onset and preoperatively in 36 patients who fulfilled following the inclusion criteria: admission Hunt and Kosnik Grade 4 or 5, and Fischer Group 3. Twelve of 14 patients without abnormal findings in DWI underwent surgery in the acute stage. Although 2 of 14 patients with high age were supposed to undergo surgery in the chronic stage, 1 patient died in aneurysmal re-rupture. Glasgow outcome scales (GOS) were good recovery (GR) in 5, moderate disability (MD) in 6, standard deviation (SD) in 1 and D in 2 patients. Thirteen of 22 patients with DWI abnormality had small lesions less than 10 mm in diameter. Twelve of 13 patients underwent surgery in the acute stage, and 1 died of aneurysmal re-rupture while waiting for surgery in the chronic stage. GOS were GR in 3, MD in 4, SD in 3 and D in 3 patients. Although 5 patients with diffuse DWI lesions underwent surgery in the acute stage, 2 were SD and 3 were D. Four patients were supposed to undergo delayed surgery. However, 2 of them died of recurrent hemorrhage while waiting. GOS were SD in 2 and D in 2 patients. The present study indicates that DWI may provide objective evaluation of brain damage in severe SAH. However, since there were varieties of DWI findings and clinical courses, careful decisions must be taken in management of severe SAH patients. (author)

Sustained CD8+ T-cell responses induced after acute parvovirus B19 infection in humans

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Norbeck, Oscar; Isa, Adiba; Pöhlmann, Christoph

2005-01-01

Murine models have suggested that CD8+ T-cell responses peak early in acute viral infections and are not sustained, but no evidence for humans has been available. To address this, we longitudinally analyzed the CD8+ T-cell response to human parvovirus B19 in acutely infected individuals. We...... observed striking CD8+ T-cell responses, which were sustained or even increased over many months after the resolution of acute disease, indicating that CD8+ T cells may play a prominent role in the control of parvovirus B19 and other acute viral infections of humans, including potentially those generated...

Identification of Reversible Disruption of the Human Blood-Brain Barrier Following Acute Ischemia.

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Simpkins, Alexis N; Dias, Christian; Leigh, Richard

2016-09-01

Animal models of acute cerebral ischemia have demonstrated that diffuse blood-brain barrier (BBB) disruption can be reversible after early reperfusion. However, irreversible, focal BBB disruption in humans is associated with hemorrhagic transformation in patients receiving intravenous thrombolytic therapy. The goal of this study was to use a magnetic resonance imaging biomarker of BBB permeability to differentiate these 2 forms of BBB disruption. Acute stroke patients imaged with magnetic resonance imaging before, 2 hours after, and 24 hours after treatment with intravenous tissue-type plasminogen activator were included. The average BBB permeability of the acute ischemic region before and 2 hours after treatment was calculated using a T2* perfusion-weighted source images. Change in average permeability was compared with percent reperfusion using linear regression. Focal regions of maximal BBB permeability from the pretreatment magnetic resonance imaging were compared with the occurrence of parenchymal hematoma (PH) formation on the 24-hour magnetic resonance imaging scan using logistic regression. Signals indicating reversible BBB permeability were detected in 18/36 patients. Change in average BBB permeability correlated inversely with percent reperfusion (P=0.006), indicating that early reperfusion is associated with decreased BBB permeability, whereas sustained ischemia is associated with increased BBB disruption. Focal regions of maximal BBB permeability were significantly associated with subsequent formation of PH (P=0.013). This study demonstrates that diffuse, mild BBB disruption in the acutely ischemic human brain is reversible with reperfusion. This study also confirms prior findings that focal severe BBB disruption confers an increased risk of hemorrhagic transformation in patients treated with intravenous tissue-type plasminogen activator. © 2016 American Heart Association, Inc.

Cynomolgus macaque as an animal model for severe acute respiratory syndrome.

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James V Lawler

2006-05-01

Full Text Available The emergence of severe acute respiratory syndrome (SARS in 2002 and 2003 affected global health and caused major economic disruption. Adequate animal models are required to study the underlying pathogenesis of SARS-associated coronavirus (SARS-CoV infection and to develop effective vaccines and therapeutics. We report the first findings of measurable clinical disease in nonhuman primates (NHPs infected with SARS-CoV.In order to characterize clinically relevant parameters of SARS-CoV infection in NHPs, we infected cynomolgus macaques with SARS-CoV in three groups: Group I was infected in the nares and bronchus, group II in the nares and conjunctiva, and group III intravenously. Nonhuman primates in groups I and II developed mild to moderate symptomatic illness. All NHPs demonstrated evidence of viral replication and developed neutralizing antibodies. Chest radiographs from several animals in groups I and II revealed unifocal or multifocal pneumonia that peaked between days 8 and 10 postinfection. Clinical laboratory tests were not significantly changed. Overall, inoculation by a mucosal route produced more prominent disease than did intravenous inoculation. Half of the group I animals were infected with a recombinant infectious clone SARS-CoV derived from the SARS-CoV Urbani strain. This infectious clone produced disease indistinguishable from wild-type Urbani strain.SARS-CoV infection of cynomolgus macaques did not reproduce the severe illness seen in the majority of adult human cases of SARS; however, our results suggest similarities to the milder syndrome of SARS-CoV infection characteristically seen in young children.

Characterization of a novel coronavirus associated with severe acute respiratory syndrome

NARCIS (Netherlands)

P.A. Rota (Paul); M.S. Oberste (Steven); S.S. Monroe (Stephan); W.A. Nix (Allan); R. Campagnoli (Ray); J.P. Icenogle (Joseph); S. Penaranda; B. Bankamp (Bettina); K. Maher (Kaija); M.H. Chen (Min-hsin); S. Tong (Suxiong); A. Tamin (Azaibi); L. Lowe (Luis); M. Frace (Michael); J.L. DeRisi (Joseph); Q. Chen (Qi); D. Wang (David); D.D. Erdman (Dean); T.C. Peret (Teresa); C. Burns (Cara); T.G. Ksiazek (Thomas); P.E. Rollin (Pierre); A. Sanchez (Berenguer); S. Liffick (Stephanie); B. Holloway (Brian); J. Limor (Josef); K. McCaustland (Karen); M. Olsen-Rasmussen (Mellissa); S. Gunther; A.D.M.E. Osterhaus (Albert); C. Drosten (Christian); M.A. Pallansch (Mark); L.J. Anderson (Larry); W.J. Belline; R.A.M. Fouchier (Ron)

2003-01-01

textabstractIn March 2003, a novel coronavirus (SARS-CoV) was discovered in association with cases of severe acute respiratory syndrome (SARS). The sequence of the complete genome of SARS-CoV was determined, and the initial characterization of the viral genome is presented in this report. The

Chronic Hepatitis B with Spontaneous Severe Acute Exacerbation

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Wei-Lun Tsai

2015-11-01

Full Text Available Chronic hepatitis B virus (HBV infection is a major global health problem with an estimated 400 million HBV carriers worldwide. In the natural history of chronic hepatitis B (CHB, spontaneous acute exacerbation (AE is not uncommon, with a cumulative incidence of 10%–30% every year. While exacerbations can be mild, some patients may develop hepatic decompensation and even die. The underlying pathogenesis is possibly related to the activation of cytotoxic T lymphocyte-mediated immune response against HBV. An upsurge of serum HBV DNA usually precedes the rise of alanine aminotransferase (ALT and bilirubin. Whether antiviral treatment can benefit CHB with severe AE remains controversial, but early nucleos(tide analogues treatment seemed to be associated with an improved outcome. There has been no randomized study that compared the effects of different nucleos(tide analogues (NA in the setting of CHB with severe AE. However, potent NAs with good resistance profiles are recommended. In this review, we summarized current knowledge regarding the natural history, pathogenetic mechanisms, and therapeutic options of CHB with severe AE.

Severe hemolytic disease of the newborn due to anti-Di b treated with phototherapy and intravenous immunoglobulin.

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Oh, Eun-Jee; Jekarl, Dong Wook; Jang, Hyun-Sik; Park, Hae-Il; Park, Yeon-Joon; Choi, Hyun Ah; Chun, Chung-Sik; Kim, Yonggoo; Kim, Hyung Hoi

2008-01-01

The Di(b) antigen usually occurs with high incidence, except in certain Asian and South American Indian populations. In general, hemolysis caused by anti-Di(b) is not severe and its clinical course is benign. We report a Korean neonate with severe hemolytic disease of the newborn caused by anti-Di(b). The phenotype and genotype of the Diego blood group system of the patient and his mother were Di(a+b+) and Di(a+b-), respectively. The mother's serum and eluate from the neonate's erythrocytes contained anti-Di(b). This case was successfully managed with phototherapy and high dose iv immunoglobulin. Since most commercial antibody detection panels do not contain Di(b-) red cells, it is important to consider anti-Di(b) in cases of hemolytic disease of the newborn caused by an antibody against a high frequency antigen.

A human cytochrome P-450 is recognized by anti-liver/kidney microsome antibodies in autoimmune chronic hepatitis.

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Kiffel, L; Loeper, J; Homberg, J C; Leroux, J P

1989-02-28

1- Anti-liver/kidney microsome autoantibodies type 1 (anti-LKM1), observed in some children with chronic active hepatitis, were used to isolate their antigen in human liver microsomes. A protein, called P-LKM1 was thus purified. This protein was recognized by a rabbit antiserum directed against the related human cytochromes P-450 bufI and P-450 bufII. 2- A human liver microsomal protein immunoprecipitated with anti-LKM1 sera was also recognized by anti cytochromes P-450 bufI/II antibodies. 3- Anti-LKM1 antibodies potently inhibited microsomal bufuralol 1'-hydroxylation. These results displayed the possible identity between cytochrome P-450 bufI/II and LKM1 antigen.

Radioimmunoassay of human cardiac tropomyosin in acute myocardial infarction

International Nuclear Information System (INIS)

Cummins, P.; McGurk, B.; Littler, W.A.

1981-01-01

Tropomyosin was prepared from fresh human myocardium and antisera raised in rabbits. A sensitive radioimmunoassay was developed for the detection of human cardiac 125 I-labelled tropomyosin in human sera down to levels of 1 ng/ml. Values for human cardiac tropomyosin in normal patients ranged from less than 1 to 3 ng/ml. In 18 patients with acute myocardial infarction all had elevated tropomyosin levels ranging from 41 to above 200 ng/ml with a mean peak level of 101 ng/ml. In this study there were no false positive or false negative results. In the initial stages of infarction the time course of appearance and peak levels of cardiac tropomyosin, total creatine kinase and creatine kinase MB isoenzyme were similar. Although total creatine kinase and creatine kinase MB isoenzyme levels were normal after 72 h in patients with single, uncomplicated infarction, cardiac tropomyosin levels were still significantly elevated above normal after this time, being 30-60% of peak values. Radioimmunoassay of human cardiac tropomyosin may prove useful in the diagnosis and in the management of patients with acute myocardial infarction, particularly in the long-term postinfarction period. (author)

SEVERE (GRADE III-IV ACUTE GRAFT VERSUS HOST DISEASE AFTER ALLOGENEIC HAEMATOPOIETIC STEM CELL TRANSPLANTATION

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Irena Preložnik-Zupan

2002-09-01

Full Text Available Background. Beside greater susceptibility to infections, acute graft host disease is a consequence of the activation of donor T-cells against host antigens. Most common target organs are skin, liver and intestinal mucosis.Methods. In the 6-year period between January 1995 and December 2000, 49 patients were treated with allogeneic haematopoietic stem cell transplantation (allo-HSCT in Transplant unit, Department of Hematology, Clinical Centre Ljubljana. The standard GVHD prophylaxis regimen consisted of cyclosporine and short-course methotrexate. Severe, grade III-IV aGVHD with skin and/or gastrointestinal and/or liver involvement appeared in 16 (32% of the 49 patients.Results. Among the 16 patients with severe aGVHD, 14 had liver involvement, ten gastrointestinal and eight skin involvement. One patient had skin involvement only, the rest of them had combined involvement of two or three organ systems. Routine first-line treatment for aGVHD, given to all 16 pts with severe forms of the disease, was methylprednisolone (MP 2mg/ kg. Six patients with predominant skin involvement responded to MP. Other ten patients with mainly liver and gastrointestinal involvement needed second or even third line aGVHD treatment. These were anti-thymocyte globulin (ATG and/or monoclonal antibodies (OKT3 and/or mycophenolate mofetil (MMF and/or FK506 (tacrolimus. Seven patients died of advanced aGVHD and treatment related infection.Conclusions. Based on our experiences, we conclude that in critically ill patients with severe aGVHD, neutropenia and high risk for opportunistic infection, each day of ineffective MP therapy may have fatal consequences. Simultaneous institution of a combination of corticosteroids and a second-line drug might prove more appropriate for patients with a severe form of aGVHD.

Cardiovascular outcomes and systemic anti-inflammatory drugs in patients with severe psoriasis

DEFF Research Database (Denmark)

Ahlehoff, O; Skov, L; Gislason, G

2014-01-01

BACKGROUND: Psoriasis is a common disease and is associated with cardiovascular diseases. Systemic anti-inflammatory drugs may reduce risk of cardiovascular events. We therefore examined the rate of cardiovascular events, i.e. cardiovascular death, myocardial infarction and stroke, in patients...... with severe psoriasis treated with systemic anti-inflammatory drugs. METHODS: Individual-level linkage of administrative registries was used to perform a longitudinal nationwide cohort study. Time-dependent multivariable adjusted Cox regression was used to estimate hazard ratios (HRs) with 95% confidence...... intervals (CIs) of cardiovascular events associated with use of biological drugs, methotrexate, cyclosporine, retinoids and other antipsoriatic therapies, including topical treatments, phototherapy and climate therapy. RESULTS: A total of 6902 patients (9662 treatment exposures) with a maximum follow...

Electrocardiographic scores of severity and acuteness of myocardial ischemia predict myocardial salvage in patients with anterior ST-segment elevation myocardial infarction

DEFF Research Database (Denmark)

Fakhri, Yama; Sejersten, Maria; Schoos, Mikkel Malby

2018-01-01

inferior infarct locations. METHODS: In STEMI patients, the severity and acuteness scores were obtained from the admission ECG. Based on the ECG patients were assigned with severe or non-severe ischemia and acute or non-acute ischemia. Cardiac magnetic resonance (CMR) was performed 2-6days after primary...

[Advances in the research of zinc deficiency and zinc supplementation treatment in patients with severe burns].

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Wang, X X; Zhang, M J; Li, X B

2018-01-20

Zinc is one of the essential trace elements in human body, which plays an important role in regulating acute inflammatory response, glucose metabolism, anti-oxidation, immune and gastrointestinal function of patients with severe burns. Patients with severe burns may suffer from zinc deficiency because of insufficient amount of zinc intake from the diet and a large amount of zinc lose through wounds and urine. Zinc deficiency may affect their wound healing process and prognosis. This article reviews the characteristics of zinc metabolism in patients with severe burns through dynamic monitoring the plasma and urinary concentration of zinc. An adequate dosage of zinc supplemented to patients with severe burns by an appropriate method can increase the level of zinc in plasma and skin tissue and improve wound healing, as well as reduce the infection rates and mortality. At the same time, it is important to observe the symptoms and signs of nausea, dizziness, leukopenia and arrhythmia in patients with severe burns after supplementing excessive zinc.

The anti-oxidant effects of melatonin derivatives on human gingival fibroblasts.

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Phiphatwatcharaded, Chawapon; Puthongking, Ploenthip; Chaiyarit, Ponlatham; Johns, Nutjaree Pratheepawanit; Sakolchai, Sumon; Mahakunakorn, Pramote

2017-07-01

Aim of this in vitro study was to evaluate the anti-oxidant activity of indole ring modified melatonin derivatives as compared with melatonin in primary human gingival fibroblast (HGF) cells. Anti-oxidant activity of melatonin (MLT), acetyl-melatonin (AMLT) and benzoyl-melatonin (BMLT) was evaluated by5 standard methods as follows: 2, 2-diphenyl-1-picrylhydrazyl (DPPH); ferric ion reducing antioxidant power (FRAP); superoxide anion scavenging; nitric oxide (NO) scavenging; and thiobarbituric acid reactive substances (TBARs).Evaluation of cellular antioxidant activity (CAA) and protectivity against H 2 O 2 induced cellular damage was performed via MTT assay in HGF cells. According to the standard anti-oxidant assays, the antioxidant power of AMLT and BMLT were slightly less than MLT in FRAP and superoxide scavenging assays. In the NO scavenging and TBARs assays, BMLT and AMLT were more potent than MLT, whereas DPPH assays demonstrated that MLT was more potent than others. BMLT and AMLT had more potent anti-oxidant and protective activities against H 2 O 2 in HGF cells as compared with MLT. MLT derivatives demonstrated different anti-oxidant activities as compared with MLT, depending upon assays. These findings imply that N-indole substitution of MLT may help to improve hydrogen atom transfer to free radicals but electron transfer property is slightly decreased. Anti-oxidant and protective effects of melatonin derivatives (AMLT and BMLT) on human gingival fibroblasts imply the potential use of these molecules as alternative therapeutics for chronic inflammatory oral diseases. Copyright © 2017 Elsevier Ltd. All rights reserved.

Viral etiology, seasonality and severity of hospitalized patients with severe acute respiratory infections in the Eastern Mediterranean Region, 2007-2014.

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Horton, Katherine C; Dueger, Erica L; Kandeel, Amr; Abdallat, Mohamed; El-Kholy, Amani; Al-Awaidy, Salah; Kohlani, Abdul Hakim; Amer, Hanaa; El-Khal, Abel Latif; Said, Mayar; House, Brent; Pimentel, Guillermo; Talaat, Maha

2017-01-01

Little is known about the role of viral respiratory pathogens in the etiology, seasonality or severity of severe acute respiratory infections (SARI) in the Eastern Mediterranean Region. Sentinel surveillance for SARI was conducted from December 2007 through February 2014 at 20 hospitals in Egypt, Jordan, Oman, Qatar and Yemen. Nasopharyngeal and oropharyngeal swabs were collected from hospitalized patients meeting SARI case definitions and were analyzed for infection with influenza, respiratory syncytial virus (RSV), adenovirus (AdV), human metapneumovirus (hMPV) and human parainfluenza virus types 1-3 (hPIV1-3). We analyzed surveillance data to calculate positivity rates for viral respiratory pathogens, describe the seasonality of those pathogens and determine which pathogens were responsible for more severe outcomes requiring ventilation and/or intensive care and/or resulting in death. At least one viral respiratory pathogen was detected in 8,753/28,508 (30.7%) samples tested for at least one pathogen and 3,497/9,315 (37.5%) of samples tested for all pathogens-influenza in 3,345/28,438 (11.8%), RSV in 3,942/24,503 (16.1%), AdV in 923/9,402 (9.8%), hMPV in 617/9,384 (6.6%), hPIV1 in 159/9,402 (1.7%), hPIV2 in 85/9,402 (0.9%) and hPIV3 in 365/9,402 (3.9%). Multiple pathogens were identified in 501/9,316 (5.4%) participants tested for all pathogens. Monthly variation, indicating seasonal differences in levels of infection, was observed for all pathogens. Participants with hMPV infections and participants less than five years of age were significantly less likely than participants not infected with hMPV and those older than five years of age, respectively, to experience a severe outcome, while participants with a pre-existing chronic disease were at increased risk of a severe outcome, compared to those with no reported pre-existing chronic disease. Viral respiratory pathogens are common among SARI patients in the Eastern Mediterranean Region. Ongoing surveillance is

Accounts of severe acute obstetric complications in rural Bangladesh.

Science.gov (United States)

Sikder, Shegufta S; Labrique, Alain B; Ullah, Barkat; Ali, Hasmot; Rashid, Mahbubur; Mehra, Sucheta; Jahan, Nusrat; Shamim, Abu A; West, Keith P; Christian, Parul

2011-10-21

As maternal deaths have decreased worldwide, increasing attention has been placed on the study of severe obstetric complications, such as hemorrhage, eclampsia, and obstructed labor, to identify where improvements can be made in maternal health. Though access to medical care is considered to be life-saving during obstetric emergencies, data on the factors associated with health care decision-making during obstetric emergencies are lacking. We aim to describe the health care decision-making process during severe acute obstetric complications among women and their families in rural Bangladesh. Using the pregnancy surveillance infrastructure from a large community trial in northwest rural Bangladesh, we nested a qualitative study to document barriers to timely receipt of medical care for severe obstetric complications. We conducted 40 semi-structured, in-depth interviews with women reporting severe acute obstetric complications and purposively selected for conditions representing the top five most common obstetric complications. The interviews were transcribed and coded to highlight common themes and to develop an overall conceptual model. Women attributed their life-threatening experiences to societal and socioeconomic factors that led to delays in seeking timely medical care by decision makers, usually husbands or other male relatives. Despite the dominance of male relatives and husbands in the decision-making process, women who underwent induced abortions made their own decisions about their health care and relied on female relatives for advice. The study shows that non-certified providers such as village doctors and untrained birth attendants were the first-line providers for women in all categories of severe complications. Coordination of transportation and finances was often arranged through mobile phones, and referrals were likely to be provided by village doctors. Strategies to increase timely and appropriate care seeking for severe obstetric complications may

Accounts of severe acute obstetric complications in Rural Bangladesh

Directory of Open Access Journals (Sweden)

Sikder Shegufta S

2011-10-01

Full Text Available Abstract Background As maternal deaths have decreased worldwide, increasing attention has been placed on the study of severe obstetric complications, such as hemorrhage, eclampsia, and obstructed labor, to identify where improvements can be made in maternal health. Though access to medical care is considered to be life-saving during obstetric emergencies, data on the factors associated with health care decision-making during obstetric emergencies are lacking. We aim to describe the health care decision-making process during severe acute obstetric complications among women and their families in rural Bangladesh. Methods Using the pregnancy surveillance infrastructure from a large community trial in northwest rural Bangladesh, we nested a qualitative study to document barriers to timely receipt of medical care for severe obstetric complications. We conducted 40 semi-structured, in-depth interviews with women reporting severe acute obstetric complications and purposively selected for conditions representing the top five most common obstetric complications. The interviews were transcribed and coded to highlight common themes and to develop an overall conceptual model. Results Women attributed their life-threatening experiences to societal and socioeconomic factors that led to delays in seeking timely medical care by decision makers, usually husbands or other male relatives. Despite the dominance of male relatives and husbands in the decision-making process, women who underwent induced abortions made their own decisions about their health care and relied on female relatives for advice. The study shows that non-certified providers such as village doctors and untrained birth attendants were the first-line providers for women in all categories of severe complications. Coordination of transportation and finances was often arranged through mobile phones, and referrals were likely to be provided by village doctors. Conclusions Strategies to increase timely

Acute severe childhood asthma

African Journals Online (AJOL)

Attending school regularly. • Sleeping well at night ... and children must know exactly what to do when an acute attack occurs, and when to ... peak flow reading that is 30% below the expected level, are ... oxygen saturations < 94%, should receive high-flow oxygen ... usual of the metered dose inhaler are required to achieve.

Regional and systemic distribution of anti-tumor x anti-CD3 heteroaggregate antibodies and cultured human peripheral blood lymphocytes in a human colon cancer xenograft

International Nuclear Information System (INIS)

Nelson, H.; Ramsey, P.S.; Kerr, L.A.; McKean, D.J.; Donohue, J.H.

1990-01-01

Anti-tumor antibody (317G5) covalently coupled to an anti-CD3 antibody (OKT3) produces a heteroaggregate (HA) antibody that can target PBL to lyse tumor cells expressing the appropriate tumor Ag. The i.v. and i.p. distribution of radiolabeled HA antibody 317G5 x OKT3 and of radiolabeled cultured human PBL were studied in athymic nude mice bearing solid intraperitoneal tumor established from the human colon tumor line, LS174T. Mice were injected with 125I-labeled HA antibody, 125I-labeled anti-tumor mAb, or 111In-labeled PBL, and at designated timepoints tissues were harvested and measured for radioactivity. 125I-317G5 x OKT3 localized specifically to tumor sites. Tumor radioactivity levels (percent injected dose/gram) were lower with 125I-317G5 x OKT3 HA antibody than with 125I-317G5 anti-tumor mAb, but were similar to levels reported for other anti-tumor mAb. The major difference in radioactivity levels observed between i.v. and i.p. administration of 125I-317G5 x OKT3 was an increase in hepatic radioactivity after i.v. HA antibody administration. HA antibodies produced from F(ab')2 fragments, which exhibit decreased m. w. and decreased Fc receptor-mediated binding, demonstrated improved tumor:tissue ratios as compared to intact antibody HA. 125I-317G5 F(ab')2 x OKT3 F(ab')2 antibody levels were equivalent to intact HA antibody levels in tumor, but were lower than intact HA antibody levels in the blood, bowel, and liver. Tumor:bowel ratios (20:1 at 48 h) were highest when 317G5 F(ab')2 x OKT3 F(ab')2 was injected i.p. Autoradiography confirmed that anti-tumor x anti-CD3 HA antibodies localized specifically to intraperitoneal tumor; that i.p. administered HA antibodies penetrated tumor directly; and that i.v. administered HA antibodies distributed along tumor vasculature

SIRS score on admission and initial concentration of IL-6 as severe acute pancreatitis outcome predictors.

Science.gov (United States)

Gregoric, Pavle; Pavle, Gregoric; Sijacki, Ana; Ana, Sijacki; Stankovic, Sanja; Sanja, Stankovic; Radenkovic, Dejan; Dejan, Radenkovic; Ivancevic, Nenad; Nenad, Ivancevic; Karamarkovic, Aleksandar; Aleksandar, Karamarkovic; Popovic, Nada; Nada, Popovic; Karadzic, Borivoje; Borivoje, Karadzic; Stijak, Lazar; Stefanovic, Branislav; Branislav, Stefanovic; Milosevic, Zoran; Zoran, Milosević; Bajec, Djordje; Djordje, Bajec

2010-01-01

Early recognition of severe form of acute pancreatitis is important because these patients need more agressive diagnostic and therapeutical approach an can develope systemic complications such as: sepsis, coagulopathy, Acute Lung Injury (ALI), Acute Respiratory Distress Syndrome (ARDS), Multiple Organ Dysfunction Syndrome (MODS), Multiple Organ Failure (MOF). To determine role of the combination of Systemic Inflammatory Response Syndrome (SIRS) score and serum Interleukin-6 (IL-6) level on admission as predictor of illness severity and outcome of Severe Acute Pancreatitis (SAP). We evaluated 234 patients with first onset of SAP appears in last twenty four hours. A total of 77 (33%) patients died. SIRS score and serum IL-6 concentration were measured in first hour after admission. In 105 patients with SIRS score 3 and higher, initial measured IL-6 levels were significantly higher than in the group of remaining 129 patients (72 +/- 67 pg/mL, vs 18 +/- 15 pg/mL). All nonsurvivals were in the first group, with SIRS score 3 and 4 and initial IL-6 concentration 113 +/- 27 pg/mL. The values of C-reactive Protein (CRP) measured after 48h, Acute Physiology and Chronic Health Evaluation (APACHE II) score on admission and Ranson score showed the similar correlation, but serum amylase level did not correlate significantly with Ranson score, IL-6 concentration and APACHE II score. The combination of SIRS score on admission and IL-6 serum concentration can be early, predictor of illness severity and outcome in SAP.

Severe dysautonomia as a main feature of anti-GAD encephalitis: Report of a paediatric case and literature review.

Science.gov (United States)

Ben Achour, Nedia; Ben Younes, Thouraya; Rebai, Ibtihel; Ben Ahmed, Melika; Kraoua, Ichraf; Ben Youssef-Turki, Ilhem

2018-05-01

Anti-glutamic acid decarboxylase (anti-GAD65) antibodies are a rare cause of autoimmune encephalitis. This entity is mainly recognized in adults and very few cases were reported in children. We report on a paediatric case of anti-GAD encephalitis with severe presentation and uncontrollable dysautonomia. A 9-year-old girl was referred to our department for refractory seizures and behavioral disturbances. Brain magnetic resonance imaging (MRI) was normal. Repeat screening for antineuronal antibodies showed negative results for anti-NMDA receptor antibodies but positive results for anti-GAD65 with a low positivity of anti-Ma2 antibodies. Although a transient improvement was noticed after immunomodulatory treatment, the patient developed severe intractable autonomic imbalance including dysrythmia, alternating bradycardia/tachycardia, hypotension/hypertension, hypothermia/hyperthermia and hyperhidrosis. She deceased six months after onset. Our report intends to raise awareness of autoimmune encephalitis with anti-GAD65 antibodies which may involve extralimbic brain regions and manifest with fatal dysautonomia. We highlight the need for prompt diagnosis and aggressive management for this underdiagnosed entity in children. Copyright © 2018 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

The anti-human trafficking collaboration model and serving victims: Providers' perspectives on the impact and experience.

Science.gov (United States)

Kim, Hea-Won; Park, Taekyung; Quiring, Stephanie; Barrett, Diana

2018-01-01

A coalition model is often used to serve victims of human trafficking but little is known about whether the model is adequately meeting the needs of the victims. The purpose of this study was to examine anti-human trafficking collaboration model in terms of its impact and the collaborative experience, including challenges and lessons learned from the service providers' perspective. Mixed methods study was conducted to evaluate the impact of a citywide anti-trafficking coalition model from the providers' perspectives. Web-based survey was administered with service providers (n = 32) and focus groups were conducted with Core Group members (n = 10). Providers reported the coalition model has made important impacts in the community by increasing coordination among the key agencies, law enforcement, and service providers and improving quality of service provision. Providers identified the improved and expanded partnerships among coalition members as the key contributing factor to the success of the coalition model. Several key strategies were suggested to improve the coalition model: improved referral tracking, key partner and protocol development, and information sharing.

Increased Plasma Levels of Heme Oxygenase-1 in Human Brucellosis.

Science.gov (United States)

Chen, Zhe; Zhang, Yu-Xue; Fu, Dong-Wei; Gao, Qing-Feng; Ge, Feng-Xia; Liu, Wei-Hua

2016-08-01

Brucellosis is associated with inflammation and the oxidative stress response. Heme oxygenase-1 (HO-1) is a cytoprotective stress-responsive enzyme that has anti-inflammatory and anti-oxidant effects. Nevertheless, the role of HO-1 in human brucellosis has not yet been studied. The aim of this study was to examine the plasma levels of HO-1 in patients with brucellosis and to evaluate the ability of plasma HO-1 levels as an auxiliary diagnosis, a severity predictor, and a monitor for brucellosis treatments. A total of 75 patients with brucellosis were divided into the acute, subacute, chronic active, and chronic stable groups. An additional 20 volunteers were included as the healthy control group. The plasma HO-1 levels and other laboratory parameters were measured in all groups. Furthermore, the plasma levels of HO-1 in the acute group were compared before and after treatment. The plasma HO-1 levels were considerably increased in the acute (4.97 ± 3.55), subacute (4.98 ± 3.23), and chronic active groups (4.43 ± 3.00) with brucellosis compared to the healthy control group (1.03 ± 0.63) (p brucellosis (r = 0.707, p brucellosis status and may be used as a supplementary plasma marker for diagnosing brucellosis and monitoring its treatment.

Acute oral toxicity and anti-inflammatory activity of hydroalcoholic extract from Lampaya medicinalis Phil in rats

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Glauco Morales

2014-01-01

Full Text Available BACKGROUND: Algesia and inflammation are related with several pathological conditions. It is known that many drugs available for the treatment of these problems cause unwanted side effects. This study was aimed at evaluating acute toxicity and anti-inflammatory activity of Lampaya medicinalis Phil. (Verbenaceae widely used in the folk medicine of Northern Chile against rheumatism, arthritis and body joints pain. RESULTS: Oral administration of hydroalcoholic extract (HAE at the highest dose of 3000 mg/ Kg body weight resulted in no mortalities or evidence of significant behavioral changes. Histological examination revealed normal architecture and no significant adverse effects were observed on the liver, kidney, heart, lung or ovaries and testicles. The results suggest that the oral administration of hydroalcoholic extract (HAE from Lampaya medicinalis did not produce any toxic effect in rats. Hydroalcoholic extract (HAE significantly inhibited the carrageenan-induced rat paw edema in dose - response relationship, at test doses of 37.5, 75, 150 and 300 mg/Kg body weight. Maximum inhibition (61.98 ± 2.69% was noted at 300 mg/Kg after 2 h of drug treatment carrageenan induced paw edema, whereas indomethacin produced 47.90 ± 1.16% of inhibition. The inhibitory values of edema at 3 h postcarrageenan were 31.04±0.75%, 40.51 ± 2.36%, 48.97 ± 1.14% and 56.87 ± 0.41% for 37.5, 75, 150, and 300 mg/kg of extract respectively. Indomethacin (10 mg/Kg gave a percentage inhibition of 49.44 ± 1.44. HAE (300 and 150 mg/kg induced an anti-inflammatory effect greater than (or comparable with the effect of indomethacin from 2nd to 4th hours of the experiment. CONCLUSIONS: Our results reveal for first time that compounds contained in the hydroalcoholic extract ofLampaya medicinalis Phil exert anti-inflammatory effect and the oral administration is safe and non toxic up to dose level 3000 mg/kg body weight. The anti

Therapeutic activity of multiple common γ-chain cytokine inhibition in acute and chronic GVHD.

Science.gov (United States)

Hechinger, Anne-Kathrin; Smith, Benjamin A H; Flynn, Ryan; Hanke, Kathrin; McDonald-Hyman, Cameron; Taylor, Patricia A; Pfeifer, Dietmar; Hackanson, Björn; Leonhardt, Franziska; Prinz, Gabriele; Dierbach, Heide; Schmitt-Graeff, Annette; Kovarik, Jiri; Blazar, Bruce R; Zeiser, Robert

2015-01-15

The common γ chain (CD132) is a subunit of the interleukin (IL) receptors for IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21. Because levels of several of these cytokines were shown to be increased in the serum of patients developing acute and chronic graft-versus-host disease (GVHD), we reasoned that inhibition of CD132 could have a profound effect on GVHD. We observed that anti-CD132 monoclonal antibody (mAb) reduced acute GVHD potently with respect to survival, production of tumor necrosis factor, interferon-γ, and IL-6, and GVHD histopathology. Anti-CD132 mAb afforded protection from GVHD partly via inhibition of granzyme B production in CD8 T cells, whereas exposure of CD8 T cells to IL-2, IL-7, IL-15, and IL-21 increased granzyme B production. Also, T cells exposed to anti-CD132 mAb displayed a more naive phenotype in microarray-based analyses and showed reduced Janus kinase 3 (JAK3) phosphorylation upon activation. Consistent with a role of JAK3 in GVHD, Jak3(-/-) T cells caused less severe GVHD. Additionally, anti-CD132 mAb treatment of established chronic GVHD reversed liver and lung fibrosis, and pulmonary dysfunction characteristic of bronchiolitis obliterans. We conclude that acute GVHD and chronic GVHD, caused by T cells activated by common γ-chain cytokines, each represent therapeutic targets for anti-CD132 mAb immunomodulation. © 2015 by The American Society of Hematology.

[Acute laryngitis and epiglottitis in children].

Science.gov (United States)

Mimouni, Olivia; Nicollas, Richard; Roman, Stéphane; Triglia, Jean-Michel

2007-10-31

The anatomical characteristic of the pediatric larynx allows physicians to better understand the incidence of symptomatic and severe presentations of acute laryngitis, which are frequent pediatric emergencies. Subglottis laryngitis and epiglottitis must be distinguished from each other. These two diseases are absolutely different: the first one is essentially viral and usually moderate, even though acute respiratory distress can occur. The other (epiglottitis) is bacterial, essentially caused by Haemophilus influenza B (Hi-B), and can be life threatening. The anti Hi-B vaccine leads to a decrease of frequency but does not make them disappear. Moreover, even if a child has a history of the Hi-B vaccine, diagnosis of epiglottitis can not to be ruled out. Lastly, in case of acute laryngeal dyspnea in a child, one must think about a foreign body.

The management of acute and chronic pancreatitis.

Science.gov (United States)

Banks, Peter A; Conwell, Darwin L; Toskes, Phillip P

2010-02-01

Pancreatitis, which is most generally described as any inflammation of the pancreas, is a serious condition that manifests in either acute or chronic forms. Chronic pancreatitis results from irreversible scarring of the pancreas, resulting from prolonged inflammation. Six major etiologies for chronic pancreatitis have been identified: toxic/ metabolic, idiopathic, genetic, autoimmune, recurrent and severe acute pancreatitis, and obstruction. The most common symptom associated with chronic pancreatitis is pain localized to the upper-to-middle abdomen, along with food malabsorption, and eventual development of diabetes. Treatment strategies for acute pancreatitis include fasting and short-term intravenous feeding, fluid therapy, and pain management with narcotics for severe pain or nonsteroidal anti-inflammatories for milder cases. Patients with chronic disease and symptoms require further care to address digestive issues and the possible development of diabetes. Dietary restrictions are recommended, along with enzyme replacement and vitamin supplementation. More definitive outcomes may be achieved with surgical or endoscopic methods, depending on the role of the pancreatic ducts in the manifestation of disease.

Halofuginone ameliorates inflammation in severe acute hepatitis B virus (HBV-infected SD rats through AMPK activation

Directory of Open Access Journals (Sweden)

Zhan WL

2017-10-01

Full Text Available Weili Zhan, Yanhong Kang, Ning Chen, Chongshan Mao, Yi Kang, Jia Shang Department of Infectious Diseases, Henan Provincial People’s Hospital, Zhengzhou, Henan, China Abstract: The hepatitis B virus (HBV has caused acute and chronic liver diseases in ~350 million infected people worldwide. Halofuginone (HF is a plant alkaloid which has been demonstrated to play a crucial role in immune regulation. Our present study explored the function of HF in the immune response of HBV-infected Sprague Dawley (SD rats. Plasmid containing pCDNA3.1-HBV1.3 was injected in SD rats for the construction of an acute HBV-infected animal model. Our data showed that HF reduced the high concentrations of serum hepatitis B e-antigen, hepatitis B surface antigen, and HBV DNA induced by HBV infection. HF also reduced the number of T helper (Th17 cells and the expression of interleukin (IL-17 compared with the pCDNA3.1-HBV1.3 group. Moreover, pro-inflammatory cytokine levels (IL-17, IL-23, interferon-γ, and IL-2 were downregulated and anti-inflammatory cytokine levels (IL-4 and IL-13 were upregulated by HF. Through further research we found that the expression of AMP-activated protein kinase (AMPK and IKBA which suppressed NF-κB activation was increased while the expression of p-NF-κB P65 was decreased in pCDNA3.1-HBV1.3+HF group compared with pCDNA3.1-HBV1.3 group, indicating that HF may work through the activation of AMPK. Finally, our conjecture was further verified by using the AMPK inhibitor compound C, which counteracted the anti-inflammation effect of HF, resulting in the decreased expression of AMPK, IKBA and increased expression of p-NF-κB P65 and reduced number of Th17 cells. In our present study, HF was considered as an anti-inflammatory factor in acute HBV-infected SD rats and worked through AMPK-mediated NF-κB p65 inactivation. This study implicated HF as a potential therapeutic strategy for hepatitis B. Keywords: halofuginone, hepatitis B virus

Molecular mechanisms of severe acute respiratory syndrome (SARS

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Zabel Peter

2005-01-01

Full Text Available Abstract Severe acute respiratory syndrome (SARS is a new infectious disease caused by a novel coronavirus that leads to deleterious pulmonary pathological features. Due to its high morbidity and mortality and widespread occurrence, SARS has evolved as an important respiratory disease which may be encountered everywhere in the world. The virus was identified as the causative agent of SARS due to the efforts of a WHO-led laboratory network. The potential mutability of the SARS-CoV genome may lead to new SARS outbreaks and several regions of the viral genomes open reading frames have been identified which may contribute to the severe virulence of the virus. With regard to the pathogenesis of SARS, several mechanisms involving both direct effects on target cells and indirect effects via the immune system may exist. Vaccination would offer the most attractive approach to prevent new epidemics of SARS, but the development of vaccines is difficult due to missing data on the role of immune system-virus interactions and the potential mutability of the virus. Even in a situation of no new infections, SARS remains a major health hazard, as new epidemics may arise. Therefore, further experimental and clinical research is required to control the disease.

Experimental Study on Anti-body effects of Anti-BV on the Bee Venom Herbal Acupuncture

Directory of Open Access Journals (Sweden)

Ki Rok Kwon

2005-02-01

Full Text Available Objectives : To observe physiological anti-body effects of anti-BV, acute toxic response, measurement of LD50, and the effects of anti-body were evaluated. Methods : LD50 of Anti-Bee Venom were measured, and to analyze acute toxic responses, weight, and the anti-body effects various concentrations of Anti-BV were diluted and the survival rate was measured. Cell blood count (CBC, liver, spleen, and kidney pathologies were observed from the histological aspects. Results : Experiment was conducted to observe Anti-BV as the anti-body to the bee venom and the following results were obtained: 1. Anti-BV was injected intraperitoneally and no toxic responses were witnessed. All of the experiment subjects stayed alive during the experiment, making LD50 analysis impossible. 2. Anti-BV was injected intraperitoneally in mice and no significant weight changes were measured between the control group and the experiment groups. 3. Measuring the concentration dependent survival rate, the highest survival rate was at the concentration of 1.25×102mg/kg(1/2.000 for Anti-BV. 4. No particular results were shown in the CBC test. 5. Observation of changes in the organ tissues, Anti-BV was found to suppress blood stasis in the liver and inhibit necrosis of the cells. Conclusion : Above results suggest that Anti-BV doesn't cause any toxic responses in the body and works as an anti-body to the bee venom. Further studies must be followed to secure the findings.

Cross-Linking GPVI-Fc by Anti-Fc Antibodies Potentiates Its Inhibition of Atherosclerotic Plaque- and Collagen-Induced Platelet Activation

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Janina Jamasbi, RPh

2016-04-01

Full Text Available To enhance the antithrombotic properties of recombinant glycoprotein VI fragment crystallizable (GPVI-Fc, the authors incubated GPVI-Fc with anti-human Fc antibodies to cross-link the Fc tails of GPVI-Fc. Cross-linking potentiated the inhibition of human plaque- and collagen-induced platelet aggregation by GPVI-Fc under static and flow conditions without increasing bleeding time in vitro. Cross-linking with anti-human-Fc Fab2 was even superior to anti-human-Fc immunoglobulin G (IgG. Advanced optical imaging revealed a continuous sheath-like coverage of collagen fibers by cross-linked GPVI-Fc complexes. Cross-linking of GPVI into oligomeric complexes provides a new, highly effective, and probably safe antithrombotic treatment as it suppresses platelet GPVI-plaque interaction selectively at the site of acute atherothrombosis.

Sex-dependent anti-stress effect of an α5 subunit containing GABAA receptor positive allosteric modulator

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Sean C. Piantadosi

2016-11-01

Full Text Available Rationale: Current first-line treatments for stress-related disorders such as Major Depressive Disorder (MDD act on monoaminergic systems and take weeks to achieve a therapeutic effect with poor response and low remission rates. Recent research has implicated the GABAergic system in the pathophysiology of depression, including deficits in interneurons targeting the dendritic compartment of cortical pyramidal cells. Objectives: The present study evaluates whether SH-053-2'F-R-CH3 (denoted α5-PAM, a positive allosteric modulator selective for α5-subunit containing GABAA receptors found predominantly on cortical pyramidal cell dendrites has anti-stress effects. Methods: Female and male C57BL6/J mice were exposed to unpredictable chronic mild stress (UCMS and treated with α5-PAM acutely (30 minutes prior to assessing behavior or chronically before being assessed behaviorally. Results: Acute and chronic α5-PAM treatments produce a pattern of decreased stress-induced behaviors (denoted as behavioral emotionality across various tests in female, but not in male mice. Behavioral Z-scores calculated across a panel of tests designed to best model the range and heterogeneity of human symptomatology confirmed that acute and chronic α5-PAM treatments consistently produce significant decreases in behavioral emotionality in several independent cohorts of females. The behavioral responses to α5-PAM could not be completely accounted for by differences in drug brain disposition between female and male mice. In mice exposed to UCMS, expression of the Gabra5 gene was increased in the frontal cortex after acute treatment and in hippocampus after chronic treatment with α5-PAM in females only, and these expression changes correlated with behavioral emotionality. Conclusions: We showed that acute and chronic positive modulation of α5 subunit-containing GABAA receptors elicit anti-stress effects in a sex-dependent manner, suggesting novel therapeutic modalities.

C-reactive protein as a marker of infection in children with severe acute malnutrition in Khartoum state, Sudan

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Abdelmoneim E.M. Kheir

2017-08-01

Full Text Available Severe acute malnutrition and acute systemic infection are often synergistic in children and lead to considerable mortality. The main aim of this research was to determine whether children with severe acute malnutrition can mount an acute phase reactant response measured by C-reactive protein. This was a descriptive, cross-sectional, hospital-based study that was carried out in the five main children hospitals in Khartoum state, from November 1st, 2012 to March 1st, 2013. 132 children with severe acute malnutrition were included in the study. Data collection included history, examination and C-reactive protein measurement. The data were analyzed using Statistical Package for Social Sciences (SPSS for descriptive and inferential statistics. The main results revealed that 93(70.5% children between 12-23 months of age and most of them had marasmus. Diarrhoea was the commonest presenting symptoms in 86.4%, followed by fever and vomiting. Most of the children (82.6% had positive C-reactive protein with variable levels. In conclusion malnourished children are able to synthesize C-reactive protein in response to an infectious process and the magnitude of this response is increased in those with severe infections.

Does virus-bacteria coinfection increase the clinical severity of acute respiratory infection?

Science.gov (United States)

Damasio, Guilherme A C; Pereira, Luciane A; Moreira, Suzana D R; Duarte dos Santos, Claudia N; Dalla-Costa, Libera M; Raboni, Sonia M

2015-09-01

This retrospective cohort study investigated the presence of bacteria in respiratory secretions of patients hospitalized with acute respiratory infections and analyzed the impact of viral and bacterial coinfection on severity and the mortality rate. A total of 169 patients with acute respiratory infections were included, viruses and bacteria in respiratory samples were detected using molecular methods. Among all samples, 73.3% and 59.7% were positive for viruses and bacteria, respectively; 45% contained both virus and bacteria. Bacterial coinfection was more frequent in patients infected by community respiratory viruses than influenza A H1N1pdm (83.3% vs. 40.6%). The most frequently bacteria detected were Streptococcus pneumoniae and Haemophilus influenzae. Both species were co-detected in 54 patients and identified alone in 22 and 21 patients, respectively. Overall, there were no significant differences in the period of hospitalization, severity, or mortality rate between patients infected with respiratory viruses alone and those coinfected by viruses and bacteria. The detection of mixed respiratory pathogens is frequent in hospitalized patients with acute respiratory infections, but its impact on the clinical outcome does not appear substantial. However, it should be noted that most of the patients received broad-spectrum antibiotic therapy, which may have contributed to this favorable outcome. © 2015 Wiley Periodicals, Inc.

Severe acute respiratory syndrome--a new coronavirus from the Chinese dragon's lair

DEFF Research Database (Denmark)

Knudsen, T B; Kledal, T N; Andersen, O

2003-01-01

The recent identification of a novel clinical entity, the severe acute respiratory syndrome (SARS), the rapid subsequent spread and case fatality rates of 14-15% have prompted a massive international collaborative investigation facilitated by a network of laboratories established by the World Hea...

The autopsy-correlation of computed tomography in acute severe head injuries

International Nuclear Information System (INIS)

Tomita, Shin; Kim, Hong; Mikabe, Toshio; Karasawa, Hideharu; Watanabe, Saburo

1981-01-01

We discuss the importance of Contrast-Enhanced CT (C.E.CT) in establishing the variety of the intracranial pathological process in acute severe head injuries. During a two-and-a-half-year period (June, 1977 - December, 1979) thirty-three patients with acute severe head injuries were autopsied, all of whom had been scanned on admission. Among them, 14 patients had undergone both plain CT and C.E.CT on admission. Brain slices were examined macroscopically in three categories; brain contusion, subarachnoid hemorrhage, and intracerebral hemorrhage. Each category was then compared retrospectively with the plain CT and C.E.CT findings. C.E.CT was found to correspond much better to the autopsy finding than plain CT in the following three points: (1) C.E.CT clearly enhances the contusion areas and reveals occult contusion areas. (2) C.E.CT enhances the areas corresponding to the subarachnoid space due to the breakdown of brain-surface blood vessels. (3) C.E.CT reveals the enlargement and formation of the intracerebral hematoma by the extravasation of the intravenous contrast material from injured arterial vessels. (author)

[Characterization of severe acute occupational poisoning accidents related to irritating gases in China between 1989 and 2003].

Science.gov (United States)

Du, Xie-Yi; Zhang, Min; Wang, Huan-Qiang; Li, Tao; Wang, Hong-Fei; Chen, Shu-Yang; Zhang, Shuang; Qin, Jian; Ji, Li-Ying

2006-12-01

To analyze severe acute occupational poisoning accidents related to irritating gases reported in China between 1989 and 2003, and to study the characteristics of severe acute occupational poisoning accidents and provide scientific evidences for prevention and control strategies. The data from the national occupational poisoning case reporting system were analyzed with descriptive methods. (1) There were 92 severe acute occupational poisoning accidents related to asphyxiating gases during 15 years, which showed that there were 14.5 accidents occurred each year. Forty types of chemicals were reported to cause poisoning accidents directly. On average, there were 14.5 persons poisoned and 0.8 persons died of poisoning in each event. The number of death of poisoning reached 7 in most of the severe accidents. Chlorine was the main irritating gas resulting in poisoning accidents according to the number of accidents, cases and death. (1) The severe acute occupational poisoning related to irritating gases are more dangerous than others because of it is involved in more cases in each accident. (2) The accidents have concentricity in the certain types of chemicals, industries and jobs, and should be focused on control. (3) It is important to develop the program about early warning and forecast and the first aid.

Antibody-dependent cellular cytotoxicity (ADCC) activity of a novel anti-PD-L1 antibody avelumab (MSB0010718C) on human tumor cells

Science.gov (United States)

Fantini, Massimo; Heery, Christopher R.; Gulley, James L.; Tsang, Kwong Yok; Schlom, Jeffrey

2015-01-01

Several anti-PD1/PD-L1 monoclonal antibodies (MAb) are currently providing evidence of clinical benefit in subsets of cancer patients. The mode of action of these MAbs is to inhibit PD1 on immune cells interacting with PD-L1 on tumor cells. These MAbs are either designed or engineered to eliminate antibody-dependent cell-mediated cytotoxicity (ADCC), which, however, has been implicated as an important mechanism in several highly effective MAb-mediated cancer therapies. A fully human anti-PD-L1 MAb would potentially be able to block PD-L1/PD1 interactions and also mediate the ADCC lysis of tumor cells. MSB0010718C (designated avelumab) is a fully human IgG1 anti-PD-L1 MAb. The studies reported here demonstrate (a) the ability of avelumab to lyse a range of human tumor cells in the presence of PBMC or NK effectors; (b) IFNγ can enhance tumor cell PD-L1 expression and in some cases enhance ADCC tumor cell lysis; (c) purified NK cells are potent effectors for avelumab; (d) similar levels of avelumab-mediated ADCC lysis of tumor cells are seen using purified NK as effectors from either healthy donors or cancer patients; (e) very low levels of avelumab-mediated lysis are seen using whole PBMCs as targets; this finding complements results seen in analyses of PBMC subsets of patients receiving avelumab; and (f) the addition of IL12 to NK cells greatly enhances avelumab-mediated ADCC. These studies thus provide an additional mode of action for an anti-PD-L1 MAb and support the rationale for further studies to enhance avelumab-mediated ADCC activity. PMID:26014098

Autoimmune Polyendocrine Syndrome 3 Onset with Severe Ketoacidosis in a 74-Year-Old Woman

Directory of Open Access Journals (Sweden)

Stefano Benedini

2015-01-01

Full Text Available Type 1 diabetes mellitus (T1D, autoimmune thyroid disease, and autoimmune gastritis often occur together forming the so-called autoimmune polyendocrine syndrome type 3 (APS3. We here report a clinical case of a 74-year-old woman who presented for the first time with severe hyperglycemia and ketoacidosis diagnosed as T1D. Further clinical investigations revealed concomitant severe hypothyroidism with autoimmune thyroid disease and severe cobalamin deficiency due to chronic atrophic gastritis. The diagnosis of type 1 diabetes mellitus was confirmed by the detection of autoantibodies against glutamic acid decarboxylase 65, islet cell antibodies, and anti-insulin autoantibodies. Anti-thyroperoxidase, anti-thyroglobulin, and anti-gastric parietal cell antibodies were also clearly positive. The case emphasized that new onset diabetic ketoacidosis, hypothyroidism, and cobalamin deficiency may simultaneously occur, and one disease can mask the features of the other, thereby making diagnosis difficult. It is noteworthy that an APS3 acute episode occurred in an asymptomatic elder woman for any autoimmune diseases.

Anti-leukemic effect of a synthetic compound, (±) trans-dihydronarciclasine (HYU-01) via cell-cycle arrest and apoptosis in acute myeloid leukemia.

Science.gov (United States)

Kim, Seo Ju; Park, Hyun Ki; Kim, Ju Young; Yoon, Jin Sun; Kim, Eun Shil; Cho, Cheon-Gyu; Kim, Byoung Kook; Park, Byeong Bae; Lee, Young Yiul

2012-10-01

(±) trans-Dihydronarciclasine, isolated from Chinese medicinal plant Zephyranthes candida, has been shown to possess quite potent anti-tumoral effect against selected human cancer cell lines. However, little is known about the anti-tumoral effect of (±) trans-dihydronarciclasine in acute myeloid leukemia (AML). This study was performed to investigate the effect of a novel synthetic (±) trans-dihydronarciclasine (code name; HYU-01) in AML. The HYU-01 inhibited the proliferation of various AML cell lines including HL-60 as well as primary leukemic blasts in a dose-dependent manner. To investigate the mechanism of the anti-proliferative effect of HYU-01, cell-cycle analysis was attempted in HL-60 cells, resulting in G1 arrest. The expression levels of CDK2, CDK4, CDK6, cyclin E, and cyclin A were decreased in a time-dependent manner. In addition, HYU-01 up-regulated the expression of the p27, and markedly enhanced the binding of p27 with CDK2, 4, and 6, ultimately resulting in the decrease of their kinase activities. Furthermore, HYU-01 induced the apoptosis through the induction of proapoptotic molecules and reduction of antiapoptotic molecules in association with the activation of caspase-3, -8, and -9. These results suggest that HYU-01 may inhibit the proliferation of HL-60 cells, via apoptosis, as well as G1 block in association with the induction of p27. © 2012 The Authors APMIS © 2012 APMIS.

Acute Hemolysis Caused by Incidental Trichlorfon Exposure

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Ming-Ling Wu

2009-04-01

Full Text Available Trichlorfon (o-o-dimethyl-2,2,2-trichloro-hydroxyethylphosphate, an organophosphate, has a moderately potent anti-cholinesterase activity. Organophosphate poisoning is well known for its characteristic symptoms and signs, but acute hemolysis caused by trichlorfon is rarely reported. We present a patient who developed acute hemolysis and renal function impairment after percutaneous trichlorfon exposure. A 54-year-old man applied trichlorfon powder to his dog to kill its parasites. Half an hour later, the dog was suspected to die of cholinergic crisis and the patient felt abdominal cramping pain. Later, he developed severe nausea, vomiting, chills, high fever, and cold sweat. Laboratory work-up disclosed a picture of acute hemolysis, jaundice, renal function impairment and leukocytosis. However, there were no clinical features of acute cholinergic syndrome except gastrointestinal symptoms, and blood cholinesterase activities were also normal. He eventually had a full recovery. Trichlorfon should be added to the toxins known to cause acute hemolysis.

Acute cholecystitis: comparing clinical outcomes with TG13 severity and intended laparoscopic versus open cholecystectomy in difficult operative cases.

Science.gov (United States)

Gerard, Justin; Luu, Minh B; Poirier, Jennifer; Deziel, Daniel J

2018-03-09

The revised Tokyo Guidelines include criteria for determining the severity of acute cholecystitis with treatment algorithms based on severity. The aim of this study was to investigate the relationship of the revised Tokyo Guidelines severity grade to clinical outcomes of cholecystectomy for acute cholecystitis. We identified 66 patients with acute cholecystitis from a prior study of difficult cholecystectomy cases. We examined the relationship between severity grade and multiple variables related to perioperative and postoperative outcomes. A more severe revised Tokyo Guidelines grade was associated with a higher number of complications (p = 0.03) and a higher severity of complications (p = 0.01). Severity grade did not predict operative time, estimated blood loss, intensive care unit admission or length of stay. Compared to planned open cholecystectomy, intended laparoscopic cholecystectomy was associated with significantly fewer total and Clavien-Dindo grade 3 complications, fewer intensive care unit admissions, and shorter length of stay (p values range from 0.03 to < 0.0001). In technically difficult operations for acute cholecystitis, the revised Tokyo guidelines severity grade correlates with the number and severity of complications. However, intended performance of laparoscopic cholecystectomy rather than open cholecystectomy in difficult operations predicts broader beneficial outcomes than severity grade.

Magnetic resonance imaging versus Acute Physiology And Chronic Healthy Evaluation II score in predicting the severity of acute pancreatitis

International Nuclear Information System (INIS)

Tang Wei; Zhang Xiaoming; Xiao Bo; Zeng Nanlin; Pan Huashan; Feng Zhisong; Xu Xiaoxue

2011-01-01

Objective: To study the correlation between established magnetic resonance (MR) imaging criteria of disease severity in acute pancreatitis and the Acute Physiology And Chronic Healthy Evaluation II (APACHE II) score, and to assess the utility of each prognostic indicators in acute pancreatitis. Materials and methods: In this study there were 94 patients with acute pancreatitis (AP), all had abdominal MR imaging. MR findings were categorized into edematous and necrotizing AP and graded according to the MR severity index (MRSI). The APACHE II score was calculated within 24 h of admission, and local complications, death, duration of hospitalization and ICU were recorded. Statistical analysis was performed to determine their correlation. Results: In patients with pancreatitis, no significant correlation can be found between the APACHE II score and the MRSI score (P = 0.196). The MRSI score correlated well with morbidity (P = 0.006) but not with mortality (P = 0.137). The APACHE II score correlated well with mortality (P = 0.002) but not with the morbidity (P = 0.112). The MRSI score was superior to the APACHE II score as a predictor of the length of hospitalization (r = 0.52 vs. r = 0.35). A high MRSI and APACHE II score correlated with the need for being in the intensive care unit (ICU) (P = 0.000 and P = 0.000, respectively). Conclusion: In patients with pancreatitis, MRSI is superior to APACHE II in assessing local complications from pancreatitis but has a limited role in determining systemic complications in which the APACHE II score excels.

Antibody-Dependent Cellular Cytotoxicity Activity of a Novel Anti-PD-L1 Antibody Avelumab (MSB0010718C) on Human Tumor Cells.

Science.gov (United States)

Boyerinas, Benjamin; Jochems, Caroline; Fantini, Massimo; Heery, Christopher R; Gulley, James L; Tsang, Kwong Yok; Schlom, Jeffrey

2015-10-01

Several anti-PD-1/PD-L1 monoclonal antibodies (mAb) are currently providing evidence of clinical benefit in subsets of cancer patients. The mode of action of these mAbs is to inhibit PD-1 on immune cells interacting with PD-L1 on tumor cells. These mAbs are either designed or engineered to eliminate antibody-dependent cell-mediated cytotoxicity (ADCC), which, however, has been implicated as an important mechanism in several highly effective mAb-mediated cancer therapies. A fully human anti-PD-L1 mAb would potentially be able to block PD-1/PD-L1 interactions and also mediate the ADCC lysis of tumor cells. MSB0010718C (designated avelumab) is a fully human IgG1 anti-PD-L1 mAb. The studies reported here demonstrate (i) the ability of avelumab to lyse a range of human tumor cells in the presence of PBMC or NK effectors; (ii) IFNγ can enhance tumor cell PD-L1 expression and, in some cases, enhance ADCC tumor cell lysis; (iii) purified NK cells are potent effectors for avelumab; (iv) similar levels of avelumab-mediated ADCC lysis of tumor cells are seen using purified NK as effectors from either healthy donors or cancer patients; (v) very low levels of avelumab-mediated lysis are seen using whole PBMCs as targets; this finding complements results seen in analyses of PBMC subsets of patients receiving avelumab; and (vi) the addition of IL12 to NK cells greatly enhances avelumab-mediated ADCC. These studies thus provide an additional mode of action for an anti-PD-L1 mAb and support the rationale for further studies to enhance avelumab-mediated ADCC activity. ©2015 American Association for Cancer Research.

Essential fatty acid composition and correlates in children with severe acute malnutrition

DEFF Research Database (Denmark)

Babirekere-Iriso, Esther; Lauritzen, Lotte; Mortensen, Charlotte Gylling

2016-01-01

Background: Severe acute malnutrition (SAM) is a common condition in children living in low-income countries and may be associated with reduced polyunsaturated fatty acids (PUFA) blood levels. The purpose of this study was to describe whole blood fatty acid composition and correlates of PUFA...

Enhanced multidetector-row computed tomography (MDCT) in the diagnosis of acute appendicitis and its severity

International Nuclear Information System (INIS)

Miki, Tesshou; Ogata, Seiji; Uto, Mitsunobu; Nakazono, Toshihiro; Urata, Miyuki; Ishibe, Ryouhei; Shinyama, Shin; Nakajo, Masayuki

2005-01-01

The purpose of this study was to examine the accuracy of enhanced multidetector-row computed tomography (MDCT) in diagnosing acute appendicitis and its severity. Contrast-enhanced MD-CT 3.5 mm thick images of 23 control patients (A), and 64 patients with surgically proven acute appendicitis including 8 catarrhal (B), 28 phiegmonous (C), and 28 gangrenous (D) appendicitis patients were respectively analyzed. The number of observed major computed tomography (CT) findings for each patient group were as follows: enlarged (≥6 mm in maximum diameter) appendix (A: 5, B: 8, C: 28, D: 28), enhancement of the appendiceal wall; hyper (A: 3, B: 8, C: 27, D: 20), iso (A: 15, B: 0, C: 1, D: 2), hypo (A-C: 0, D: 4), and patched (A-C: 0, D: 2) enhancement, appendicolith (A, B: 0, C: 7, D: 13), dirty fat sign (A: 3, B: 1, C: 21, D: 28), localized ascites (A: 2, B: 0, C: 2, D: 11), and abscess formation (A-C: 0, D: 5). From the combinations of these findings, we could differentiate acute appendicitis from the control normal appendix with an accuracy of 99% and could diagnose the severity of acute appendicitis with accuracies of 92% for catarrhal appendicitis, 84% for phlegmonous appendicitis, and 92% for gangrenous appendicitis. We could also visually reconstruct the entire forms and positions of the appendices from the successive CT findings because of the high-resolution thin-slice MDCT images. MDCT is highly accurate in the diagnosis of acute appendicitis and its severity. (author)

Transmission of severe acute respiratory syndrome in dynamical small-world networks

Science.gov (United States)

Masuda, Naoki; Konno, Norio; Aihara, Kazuyuki

2004-03-01

The outbreak of severe acute respiratory syndrome (SARS) is still threatening the world because of a possible resurgence. In the current situation that effective medical treatments such as antiviral drugs are not discovered yet, dynamical features of the epidemics should be clarified for establishing strategies for tracing, quarantine, isolation, and regulating social behavior of the public at appropriate costs. Here we propose a network model for SARS epidemics and discuss why superspreaders emerged and why SARS spread especially in hospitals, which were key factors of the recent outbreak. We suggest that superspreaders are biologically contagious patients, and they may amplify the spreads by going to potentially contagious places such as hospitals. To avoid mass transmission in hospitals, it may be a good measure to treat suspected cases without hospitalizing them. Finally, we indicate that SARS probably propagates in small-world networks associated with human contacts and that the biological nature of individuals and social group properties are factors more important than the heterogeneous rates of social contacts among individuals. This is in marked contrast with epidemics of sexually transmitted diseases or computer viruses to which scale-free network models often apply.

The economic impact of the insured patients with severe chronic and acute illnesses: a qualitative approach

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Budi Aji

2014-10-01

Full Text Available Background: Little research has focused on the economic hardship among the insured with severe illnesses and high treatment costs, in particular, the consequence of poorer insurance coverage for high-cost illnesses. Therefore, we presented the case for identifying the experiences of insured patients with severe chronic and acute illnesses. This study identified a qualitative understanding of the economic impact of severe chronic and acute illnesses and household strategies to deal with high treatment costs. Design: Interviews were conducted with 19 insured households of three different health insurance programs with a family member that had been hospitalized for severe chronic or acute illnesses in either Banyumas or Margono Sukarjo hospitals in Banyumas, Central Java, Indonesia. A thematic analysis was applied to guide the interpretation of the data. Results: Insured households with a family member that had been hospitalized for severe chronic and acute illnesses were greatly affected by the high treatment costs. Four major issues emerged from this qualitative study: insured patients are still burdened with high out-of-pocket payments, households adopt various strategies to cope with the high cost of treatments, households experience financial hardships, and positive and negative perceptions of the insured regarding their health insurance coverage for acute and chronic illnesses. Conclusions: Askes and Jamsostek patients faced financial burdens from high cost sharing for hospital amenities, non-covered drugs, and treatments and other indirect costs. Meanwhile, Jamkesmas beneficiaries faced no financial burden for related medical services but were rather burdened with indirect costs for the carers. Households relied on internal resources to cover hospital bills as the first strategy, which included the mobilization of savings, sale of assets, and borrowing of money. External support was tapped secondarily and included financial support from

Radioimmunoassay of human cardiac tropomyosin in acute myocardial infarction

Energy Technology Data Exchange (ETDEWEB)

Cummins, P; McGurk, B; Littler, W A [Queen Elizabeth Hospital, Birmingham (UK)

1981-03-01

Tropomyosin was prepared from fresh human myocardium and antisera raised in rabbits. A sensitive radioimmunoassay was developed for the detection of human cardiac /sup 125/I-labelled tropomyosin in human sera down to levels of 1 ng/ml. Values for human cardiac tropomyosin in normal patients ranged from less than 1 to 3 ng/ml. In 18 patients with acute myocardial infarction all had elevated tropomyosin levels ranging from 41 to above 200 ng/ml with a mean peak level of 101 ng/ml. In this study there were no false positive or false negative results. In the initial stages of infarction the time course of appearance and peak levels of cardiac tropomyosin, total creatine kinase and creatine kinase MB isoenzyme were similar. Although total creatine kinase and creatine kinase MB isoenzyme levels were normal after 72 h in patients with single, uncomplicated infarction, cardiac tropomyosin levels were still significantly elevated above normal after this time, being 30-60% of peak valuctional hourly rate of absorption and the plasma /sup 32/P radioactivity at 60 min corrected for extracellular fluid volume provided the best app elements, the characteristics of which are determined by employing the Lagrange multiplier concept. Unknowns of the resulting simultaneous equation consist of usual nodal displacements of the whole stru element codes. Therefore, FAST should be useful in several areas for which all other codes are too unwieldy and expensivnt makers was established, in which the investigations and studies have started.

Management of severe acute malnutrition

African Journals Online (AJOL)

age are attributed to undernutrition, especially in developing countries. ... General principles for inpatient management of acute malnutrition can be divided into two phases, i.e. the .... malnourished child: Perspective from developing countries.

Serum tenascin-C predicts severity and outcome of acute intracerebral hemorrhage.

Science.gov (United States)

Wang, Lin-Guo; Huangfu, Xue-Qin; Tao, Bo; Zhong, Guan-Jin; Le, Zhou-Di

2018-06-01

Tenascin-C is a matricellular protein related to brain injury. We studied serum tenascin-C in acute intracerebral hemorrhage (ICH) and examined the associations with severity and outcome following the acute event. Tenascin-C samples were obtained from 162 patients with acute hemorrhagic stroke and 162 healthy controls. Poor 90-day functional outcome was defined as modified Rankin Scale score > 2. Early neurological deterioration (END) and hematoma growth (HG) were recorded at 24 h. Patients had higher tenascin-C levels than controls. Tenascin-C levels were positively correlated with hematoma volume or National Institutes of Health Stroke Scale score at baseline. Elevated tenascin-C levels were independently associated with END, HG, 90-day mortality and poor functional outcome. Moreover, tenascin-C levels significantly predicted END, HG and 90-day outcomes under receiver operating characteristic curves. An increase in serum tenascin-C level is associated with an adverse outcome in ICH patients, supporting the potential role of serum tenascin-C as a prognostic biomarker for hemorrhagic stroke. Copyright © 2018 Elsevier B.V. All rights reserved.

Severe Plasmodium ovale malaria complicated by acute respiratory distress syndrome in a young Caucasian man.

Science.gov (United States)

D'Abramo, Alessandra; Gebremeskel Tekle, Saba; Iannetta, Marco; Scorzolini, Laura; Oliva, Alessandra; Paglia, Maria Grazia; Corpolongo, Angela; Nicastri, Emanuele

2018-04-02

Although Plasmodium ovale is considered the cause of only mild malaria, a case of severe malaria due to P. ovale with acute respiratory distress syndrome is reported. A 37-year old Caucasian man returning home from Angola was admitted for ovale malaria to the National Institute for Infectious Diseases Lazzaro Spallanzani in Rome, Italy. Two days after initiation of oral chloroquine treatment, an acute respiratory distress syndrome was diagnosed through chest X-ray and chest CT scan with intravenous contrast. Intravenous artesunate and oral doxycycline were started and he made a full recovery. Ovale malaria is usually considered a tropical infectious disease associated with low morbidity and mortality. However, severe disease and death have occasionally been reported. In this case clinical failure of oral chloroquine treatment with clinical progression towards acute respiratory distress syndrome is described.

The effect of acute exercise on collagen turnover in human tendons

DEFF Research Database (Denmark)

Mørch, Lina Steinrud; Pingel, Jessica; Boesen, Mikael

2013-01-01

Mechanical loading of human tendon stimulates collagen synthesis, but the relationship between acute loading responses and training status of the tendon is not clear. We tested the effect of prolonged load deprivation on the acute loading-induced collagen turnover in human tendons, by applying...... the contra-lateral leg was used habitually. Following the procedure both Achilles tendons and calf muscles were loaded with the same absolute load during a 1-h treadmill run. Tissue collagen turnover was measured by microdialysis performed post-immobilization but pre-exercise around both Achilles tendons...... and compared to values obtained by 72-h post-exercise. Power Doppler was used to monitor alterations in intratendinous blood flow velocity of the Achilles tendon and MRI used to quantitate changes in tendon cross-section area. Acute loading resulted in an increased collagen synthesis 72 h after the run in both...

Management of severe acute malnutrition in low-income and middle-income countries

Science.gov (United States)

Kwashiorkor and marasmus, collectively termed severe acute malnutrition (SAM), account for at least 10% of all deaths among children under 5 years of age worldwide, virtually all of them in low-income and middle-income countries. A number of risk factors, including seasonal food insecurity, environm...

Acute generalized exanthematous pustulosis induced by piroxicam: a case report.

Science.gov (United States)

Cherif, Y; Jallouli, Moez; Mseddi, M; Turki, H; Bahloul, Z

2014-01-01

Acute generalized exanthematous pustulosis (AGEP) is a severe adverse cutaneous reaction characterized by an acute episode of sterile pustules over erythematous-edematous skin. The main triggering drugs are antibiotics, mainly beta-lactam and macrolides. Non-steroid anti-inflammatory drugs may rarely be responsible. We describe a case of a woman with AGEP, who presented with generalized pustulosis lesions after the use of piroxicam for renal colic. The diagnosis was confirmed by the clinical and histological correlations and the dermatosis resolved after withdrawal of the drug.

Human anti-rhesus D IgG1 antibody produced in transgenic plants

DEFF Research Database (Denmark)

Bouquin, Thomas; Thomsen, Mads; Nielsen, Leif Kofoed

2002-01-01

antigen, which is responsible for alloimmunization of RhD- mothers carrying an RhD+ fetus. Anti-RhD extracted from plants specifically reacted with RhD+ cells in antiglobulin technique, and elicited a respiratory burst in human peripheral blood mononuclear cells. Plant-derived antibody had equivalent......Transgenic plants represent an alternative to cell culture systems for producing cheap and safe antibodies for diagnostic and therapeutic use. To evaluate the functional properties of a 'plantibody', we generated transgenic Arabidopsis plants expressing full-length human IgG1 against the Rhesus D...... properties to CHO cell-produced anti-RhD antibody, indicating its potential usefulness in diagnostic and therapeutic programs....

Plasmodium coatneyi in Rhesus Macaques Replicates the Multisystemic Dysfunction of Severe Malaria in Humans

Science.gov (United States)

Cabrera-Mora, Monica; Garcia, AnaPatricia; Orkin, Jack; Strobert, Elizabeth; Barnwell, John W.; Galinski, Mary R.

2013-01-01

Severe malaria, a leading cause of mortality among children and nonimmune adults, is a multisystemic disorder characterized by complex clinical syndromes that are mechanistically poorly understood. The interplay of various parasite and host factors is critical in the pathophysiology of severe malaria. However, knowledge regarding the pathophysiological mechanisms and pathways leading to the multisystemic disorders of severe malaria in humans is limited. Here, we systematically investigate infections with Plasmodium coatneyi, a simian malaria parasite that closely mimics the biological characteristics of P. falciparum, and develop baseline data and protocols for studying erythrocyte turnover and severe malaria in greater depth. We show that rhesus macaques (Macaca mulatta) experimentally infected with P. coatneyi develop anemia, coagulopathy, and renal and metabolic dysfunction. The clinical course of acute infections required suppressive antimalaria chemotherapy, fluid support, and whole-blood transfusion, mimicking the standard of care for the management of severe malaria cases in humans. Subsequent infections in the same animals progressed with a mild illness in comparison, suggesting that immunity played a role in reducing the severity of the disease. Our results demonstrate that P. coatneyi infection in rhesus macaques can serve as a highly relevant model to investigate the physiological pathways and molecular mechanisms of malaria pathogenesis in naïve and immune individuals. Together with high-throughput postgenomic technologies, such investigations hold promise for the identification of new clinical interventions and adjunctive therapies. PMID:23509137

Phylogenetic evidence for intratypic recombinant events in a novel human adenovirus C that causes severe acute respiratory infection in children.

Science.gov (United States)

Wang, Yanqun; Li, Yamin; Lu, Roujian; Zhao, Yanjie; Xie, Zhengde; Shen, Jun; Tan, Wenjie

2016-03-10

Human adenoviruses (HAdVs) are prevalent in hospitalized children with severe acute respiratory infection (SARI). Here, we report a unique recombinant HAdV strain (CBJ113) isolated from a HAdV-positive child with SARI. The whole-genome sequence was determined using Sanger sequencing and high-throughput sequencing. A phylogenetic analysis of the complete genome indicated that the CBJ113 strain shares a common origin with HAdV-C2, HAdV-C6, HAdV-C1, HAdV-C5, and HAdV-C57 and formed a novel subclade on the same branch as other HAdV-C subtypes. BootScan and single nucleotide polymorphism analyses showed that the CBJ113 genome has an intra-subtype recombinant structure and comprises gene regions mainly originating from two circulating viral strains: HAdV-1 and HAdV-2. The parental penton base, pVI, and DBP genes of the recombinant strain clustered with the HAdV-1 prototype strain, and the E1B, hexon, fiber, and 100 K genes of the recombinant clustered within the HAdV-2 subtype, meanwhile the E4orf1 and DNA polymerase genes of the recombinant shared the greatest similarity with those of HAdV-5 and HAdV-6, respectively. All of these findings provide insight into our understanding of the dynamics of the complexity of the HAdV-C epidemic. More extensive studies should address the pathogenicity and clinical characteristics of the novel recombinant.

Severe acute respiratory syndrome in a doctor working at the Prince of Wales Hospital.

Science.gov (United States)

Wong, R S M

2003-06-01

Severe acute respiratory syndrome is a new disease that is highly contagious and is spreading in the local community and worldwide. This report is of a hospital medical officer with severe acute respiratory syndrome. He presented with sudden onset of fever, chills, myalgia, headache, and dizziness in early March 2003. He developed progressive respiratory symptoms and bilateral pulmonary infiltrates during the second week of his illness. Blood tests showed lymphopenia, mild thrombocytopenia, and prolonged activated partial thromboplastin time with normal d-dimer level. His chest condition gradually responded to ribavirin and corticosteroids, and serial chest X-ray showed resolving pulmonary infiltrates. The importance of early diagnosis lies in the potential for early treatment, leading to better response.

A case of severe acute pancreatitis with near total pancreatic necrosis diagnosed by dynamic CT scanning

International Nuclear Information System (INIS)

Takeda, Kazunori; Kakugawa, Yoichiro; Amikura, Katsumi; Miyagawa, Kikuo; Matsuno, Seiki; Sato, Toshio

1987-01-01

A 42 year-old woman with severe acute pancreatitis had drainage of the pancreatic bed, cholecystostomy and jejunostomy on admission, but symptoms were not improved. Fourteen days after admission, clinical sepsis and septisemia were recognized. Dynamic CT scanning of the pancreas showed near total pancreatic necrosis. Symptoms were improved after necrosectomy of the pancreas and debridement of the peripancreatic necrotic tissue were performed. Our experience suggests the usefulness of dynamic CT scanning for detection of pancreatic necrosis in severe acute pancreatitis. (author)

Acute Promyelocytic Leukemia Presenting with Severe Marrow Fibrosis.

Science.gov (United States)

Shah, Harsh; Bradford, Carol; Sayar, Hamid

2015-01-01

We report a case of acute promyelocytic leukemia (APL) presenting with severely fibrotic marrow. There are four other reports of similar cases in the literature. Our patient was treated with All-Transretinoic Acid- (ATRA-) containing induction chemotherapy, followed by consolidation and maintenance therapy. He achieved a complete morphologic remission with adequate count recovery in a timely fashion, and later a molecular remission was documented. The patient remains in molecular remission and demonstrates normal blood counts now more than 4 years after induction. Since the morphological appearance may not be typical and the bone marrow may not yield an aspirate for cytogenetic analysis, awareness of such entity is important to make a correct diagnosis of this potentially curable disease.

Prospects for Foamy Viral Vector Anti-HIV Gene Therapy

Directory of Open Access Journals (Sweden)

Arun K. Nalla

2016-03-01

Full Text Available Stem cell gene therapy approaches for Human Immunodeficiency Virus (HIV infection have been explored in clinical trials and several anti-HIV genes delivered by retroviral vectors were shown to block HIV replication. However, gammaretroviral and lentiviral based retroviral vectors have limitations for delivery of anti-HIV genes into hematopoietic stem cells (HSC. Foamy virus vectors have several advantages including efficient delivery of transgenes into HSC in large animal models, and a potentially safer integration profile. This review focuses on novel anti-HIV transgenes and the potential of foamy virus vectors for HSC gene therapy of HIV.

Serological analysis of human IgG and IgE anti-insulin antibodies by solid-phase radioimmunoassays

International Nuclear Information System (INIS)

Hamilton, R.G.; Rendell, M.; Adkinson, N.F. Jr.

1980-01-01

A single solid-phase assay system which is useful for quantitative measurement of both IgG and IgE anti-insulin antibodies in human serum has been developed. Insulin-specific immunoglobulins are absorbed from human serum by excess quantities of insulin-agarose. After washes to remove unbound immunoglobulins, radioiodinated Staph A or rabbit anti-human IgE is added to detect bound IgG or IgE anbitodies, respectively

[Human Metapneumovirus (hMPV) associated to severe bronchial asthmatic crisis].

Science.gov (United States)

López, M A; Kusznierz, G F; Imaz, M S; Cociglio, R; Tedeschi, F A; Zalazar, F E

2006-01-01

Human Metapneumovirus (hMPV) is a recently reported agent of acute infection in the respiratory tract. It has been found in children as well as in young adults and elders. The clinical manifestations produced by hMPV are indistinguishable from those by common respiratory virus, and can evolve from asymptomatic infection into severe pneumonia. On the other hand, some authors have described cases of bronchial asthma exacerbation associated with hMPV infection. In this work we report a case of a child who presented a severe bronchial asthmatic crisis with a suspected viral associated infection. Immunofluorescence tests yielded negative results for sincitial respiratory virus, adenovirus, a-b influenza virus and parainfluenza 1, 2, 3, virus. In an attempt to detect the presence of hMPV, a RT-PCR was carried out to amplify sequences from both N and F genes. Using this approach, a positive result for hMPV was obtained. To our knowledge, this is the first description of a case of asthma exacerbation associated to hMPV in our region. In addition, these results are similar to previous reports where it was hypothesized that, like RSV, hMPV can trigger a respiratory chronic disease as asthma.

Anti-NMDA (a-NMDAR) receptor encephalitis related to acute consumption of metamphetamine: Relevance of differential diagnosis.

Science.gov (United States)

Iriondo, O; Zaldibar-Gerrikagoitia, J; Rodríguez, T; García, J M; Aguilera, L

2017-03-01

A 19-year-old male came to the Emergency Room of our hospital due to an episode of dystonic movements and disorientation 4 days after consuming methamphetamine, which evolved to a catatonic frank syndrome and eventually to status epilepticus. Definitive diagnosis was anti-NMDA receptor encephalitis, an acute inflammation of the limbic area of autoimmune origin in which early diagnosis and treatment are key elements for the final outcome. In this case, initial normal tests and previous methamphetamine poisoning delayed diagnosis, because inhaled-methamphetamine poisoning causes similar clinical symptoms to anti-NMDA receptor encephalitis. Methamphetamine poisoning may have caused an immune response in the patient, bringing on the progress of the pathology. Copyright © 2016 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

Acute topiramate differentially affects human aggressive responding at low vs. moderate doses in subjects with histories of substance abuse and antisocial behavior.

Science.gov (United States)

Lane, Scott D; Gowin, Joshua L; Green, Charles E; Steinberg, Joel L; Moeller, F Gerard; Cherek, Don R

2009-04-01

Anticonvulsant drugs have demonstrated efficacy in the management of irritability and aggression in a variety of psychiatric populations. We examined the acute effects of topiramate on aggression using a laboratory model of human aggression (PSAP) in individuals at high risk for aggressive and violent behavior.Twelve subjects, on parole/probation and with an Axis-II personality disorder and/or a substance use disorder, received 100, 200, 300, and 400 mg in an ascending sequence, with intervening placebo doses.Subjects participated 2-3 days per week over 4-6 weeks. Due to cognitive side effects at 300 mg, two subjects only completed through the 200 mg dose. Topiramate produced an inverted U-shaped dose response curve, with increases in aggression peaking at 200 mg and a modest decrease at 400 mg. Statistical analysis revealed a polynomial trend for dose (p=0.001). The observed inverted U-shaped function in aggressive responding is consistent with non-human aggression studies of GABA-A modulators. Acute topiramate doses >400 mg may have anti-aggressive effects, but dose levels in the 200-300 mg range may produce increases in aggression and side effects.

Neurological aspects of acute radiation injuries

International Nuclear Information System (INIS)

Torubarov, F.S.; Bushmanov, A.Yu.

1999-01-01

Results of the most important clinical studies of human nervous system reactions to acute radiation, carried out at Neurology Clinic of the State Research Center of Russia - Institute of Biophysics are presented. Clinical picture of changes in the nervous system in acute radiation disease caused by homologous and heterologous external irradiation is described. Main neurological syndrome of extremely severe acute radiation disease: acute radiation encephalopathy, radiation toxic encephalopathy, and hemorrhagic syndrome of the central nervous system is distinguished. Relationship between neurological disorders and the geometry of exposure are considered [ru

Cognitive activity limitations one year post-trauma in patients admitted to sub-acute rehabilitation after severe traumatic brain injury

DEFF Research Database (Denmark)

Sommer, Jens Bak; Norup, Anne; Poulsen, Ingrid

2013-01-01

Objective: To examine cognitive activity limitations and predictors of outcome 1 year post-trauma in patients admitted to sub-acute rehabilitation after severe traumatic brain injury. Subjects: The study included 119 patients with severe traumatic brain injury admitted to centralized sub-acute re......Objective: To examine cognitive activity limitations and predictors of outcome 1 year post-trauma in patients admitted to sub-acute rehabilitation after severe traumatic brain injury. Subjects: The study included 119 patients with severe traumatic brain injury admitted to centralized sub......-acute rehabilitation in the Eastern part of Denmark during a 5-year period from 2005 to 2009. Methods: Level of consciousness was assessed consecutively during rehabilitation and at 1 year post-trauma. Severity of traumatic brain injury was classified according to duration of post-traumatic amnesia. The cognitive...... subscale of Functional Independence MeasureTM (Cog-FIM) was used to assess cognitive activity limitations. Multivariate logistic regression analyses were performed to identify predictors of an independent level of functioning. Results: The majority of patients progressed to a post-confusional level...

Detection of human-infective trypanosomes in acutely-infected Jack ...

African Journals Online (AJOL)

A diagnosis of acute canine African trypanosomosis was made by microscopic examination of blood smear. Loop-mediated isothermal amplification (LAMP) analysis, using primers specifically targeting the human serum resistanceassociated (SRA) gene, revealed a monolytic infection with Trypanosoma brucei rhodesiense ...

Infections and exposure to anti-infective agents and the risk of severe mental disorders

DEFF Research Database (Denmark)

Köhler, Ole; Petersen, Liselotte; Mors, O

2017-01-01

OBJECTIVE: Severe infections are associated with increased risks of mental disorders; however, this is the first large-scale study investigating whether infections treated with anti-infective agents in the primary care setting increase the risks of schizophrenia and affective disorders. METHOD: We...

Human Albumin Fragments Nanoparticles as PTX Carrier for Improved Anti-cancer Efficacy

Directory of Open Access Journals (Sweden)

Liang Ge

2018-06-01

Full Text Available For enhanced anti-cancer performance, human serum albumin fragments (HSAFs nanoparticles (NPs were developed as paclitaxel (PTX carrier in this paper. Human albumins were broken into fragments via degradation and crosslinked by genipin to form HSAF NPs for better biocompatibility, improved PTX drug loading and sustained drug release. Compared with crosslinked human serum albumin NPs, the HSAF-NPs showed relative smaller particle size, higher drug loading, and improved sustained release. Cellular and animal results both indicated that the PTX encapsulated HSAF-NPs have shown good anti-cancer performance. And the anticancer results confirmed that NPs with fast cellular internalization showed better tumor inhibition. These findings will not only provide a safe and robust drug delivery NP platform for cancer therapy, but also offer fundamental information for the optimal design of albumin based NPs.

Cytotoxic capacity of IL-15-stimulated cytokine-induced killer cells against human acute myeloid leukemia and rhabdomyosarcoma in humanized preclinical mouse models

Directory of Open Access Journals (Sweden)

Eva eRettinger

2012-04-01

Full Text Available Allogeneic stem cell transplantation (allo-SCT has become an important treatment modality for patients with high risk acute myeloid leukemia (AML and is also under investigation for soft tissue sarcomas. The therapeutic success is still limited by minimal residual disease (MRD status ultimately leading to patients’ relapse. Adoptive donor lymphocyte infusions (DLI based on MRD status using IL-15-expanded cytokine-induced killer (CIK cells may prevent relapse without causing graft-versus-host-disease (GvHD. To generate preclinical data we developed mouse models to study anti-leukemic- and anti-tumor-potential of CIK cells in vivo. Immunodeficient mice (NOD/SCID/IL2Rγc-, NSG were injected intravenously with human leukemic cell lines THP-1, SH-2 and with human rhabdomyosarcoma (RMS cell lines RH41 and RH30 at minimal doses required for leukemia or tumor engraftment. Mice transplanted with THP-1 or RH41 cells were randomly assigned for analysis of CIK cell treatment. Organs of mice were analyzed by flow cytometry as well as quantitative polymerase chain reaction (qPCR for engraftment of malignant cells and CIK cells. Potential of CIK cells to induce GvHD was determined by histological analysis. Tissues of the highest degree of THP-1 cell expansion included bone marrow (BM followed by liver, lung, spleen, peripheral blood (PB, and brain. RH30 and RH41 engraftment mainly took place in liver and lung, but was also detectable in spleen and PB. In spite of delayed CIK cell expansion compared with malignant cells, CIK cells injected at an effector to target cell (E:T ratio of 1:1 were sufficient for significant reduction of RH41 cells, whereas against fast-expanding THP-1 cells an E:T ratio of 250:1 was needed to achieve comparable results. Our preclinical in vivo mouse models showed a reliably 100% engraftment of malignant cells which is essential for analysis of anti-cancer therapy. Furthermore our data demonstrated that IL-15-activated CIK cells

Cytotoxic Capacity of IL-15-Stimulated Cytokine-Induced Killer Cells Against Human Acute Myeloid Leukemia and Rhabdomyosarcoma in Humanized Preclinical Mouse Models

Energy Technology Data Exchange (ETDEWEB)

Rettinger, Eva; Meyer, Vida; Kreyenberg, Hermann [Department of Pediatric Hematology, Oncology and Hemostaseology, University Children’s Hospital of Frankfurt/Main, Goethe-University Frankfurt/Main, Frankfurt/Main (Germany); Volk, Andreas [Chemotherapeutisches Forschungsinstitut, Georg-Speyer-Haus, Frankfurt/Main (Germany); Kuçi, Selim; Willasch, Andre [Department of Pediatric Hematology, Oncology and Hemostaseology, University Children’s Hospital of Frankfurt/Main, Goethe-University Frankfurt/Main, Frankfurt/Main (Germany); Koscielniak, Ewa [Department of Pediatric Oncology and Hematology, Olgahospital Stuttgart, Stuttgart (Germany); Fulda, Simone [Institute for Experimental Cancer Research in Pediatrics, Goethe-University Frankfurt/Main, Frankfurt/Main (Germany); Wels, Winfried S. [Chemotherapeutisches Forschungsinstitut, Georg-Speyer-Haus, Frankfurt/Main (Germany); Boenig, Halvard [Institute for Transfusion Medicine and Immunohematology, Goethe-University Frankfurt/Main, Division for Cell Processing, German Red Cross Blood Donor Service Baden-Württemberg-Hessen, Frankfurt/Main (Germany); Klingebiel, Thomas; Bader, Peter, E-mail: eva.rettinger@kgu.de, E-mail: peter.bader@kgu.de [Department of Pediatric Hematology, Oncology and Hemostaseology, University Children’s Hospital of Frankfurt/Main, Goethe-University Frankfurt/Main, Frankfurt/Main (Germany)

2012-04-09

Allogeneic stem cell transplantation (allo-SCT) has become an important treatment modality for patients with high-risk acute myeloid leukemia (AML) and is also under investigation for soft tissue sarcomas. The therapeutic success is still limited by minimal residual disease (MRD) status ultimately leading to patients’ relapse. Adoptive donor lymphocyte infusions based on MRD status using IL-15-expanded cytokine-induced killer (CIK) cells may prevent relapse without causing graft-versus-host-disease (GvHD). To generate preclinical data we developed mouse models to study anti-leukemic- and anti-tumor-potential of CIK cells in vivo. Immunodeficient mice (NOD/SCID/IL-2Rγc{sup −}, NSG) were injected intravenously with human leukemic cell lines THP-1, SH-2 and with human rhabdomyosarcoma (RMS) cell lines RH41 and RH30 at minimal doses required for leukemia or tumor engraftment. Mice transplanted with THP-1 or RH41 cells were randomly assigned for analysis of CIK cell treatment. Organs of mice were analyzed by flow cytometry as well as quantitative polymerase chain reaction for engraftment of malignant cells and CIK cells. Potential of CIK cells to induce GvHD was determined by histological analysis. Tissues of the highest degree of THP-1 cell expansion included bone marrow followed by liver, lung, spleen, peripheral blood (PB), and brain. RH30 and RH41 engraftment mainly took place in liver and lung, but was also detectable in spleen and PB. In spite of delayed CIK cell expansion compared with malignant cells, CIK cells injected at equal amounts were sufficient for significant reduction of RH41 cells, whereas against fast-expanding THP-1 cells 250 times more CIK than THP-1 cells were needed to achieve comparable results. Our preclinical in vivo mouse models showed a reliable 100% engraftment of malignant cells which is essential for analysis of anti-cancer therapy. Furthermore our data demonstrated that IL-15-activated CIK cells have potent cytotoxic capacity

Acute quadriplegia caused by necrotizing myopathy in a renal transplant recipient with severe pneumonia: acute onset and complete recovery.

Science.gov (United States)

Tu, Guo-Wei; Song, Jie-Qiong; Ting, Simon Kang Seng; Ju, Min-Jie; He, Hong-Yu; Dong, Ji-Hong; Luo, Zhe

2015-02-03

Critical illness polyneuropathy and myopathy are multifaceted complications that follow severe illnesses involving the sensorimotor axons and proximal skeletal muscles. These syndromes have rarely been reported among renal transplant recipients. In this paper, we report a case of acute quadriplegia caused by necrotizing myopathy in a renal transplant recipient with severe pneumonia. The muscle strength in the patient's extremities improved gradually after four weeks of comprehensive treatment, and his daily life activities were normal a year after being discharged.

Anti-phospholipid antibodies in patients with Plasmodium falciparum malaria

DEFF Research Database (Denmark)

Jakobsen, P H; Morris-Jones, S D; Hviid, L

1993-01-01

Plasma levels of antibodies against phosphatidylinositol (PI), phosphatidylcholine (PC) and cardiolipin (CL) were measured by enzyme-linked immunosorbent assay (ELISA) in patients from malaria endemic area of Sudan and The Gambia. Some Sudanese adults produced IgM antibodies against all three types...... of phospholipids (PL) during an acute Plasmodium falciparum infection. The anti-PL antibody titre returned to preinfection levels in most of the donors 30 days after the disease episode. IgG titres against PI, PC and CL were low. In Gambian children with malaria, IgM antibody titres against PI and PC were...... significantly higher in those with severe malaria than in those with mild malaria. These results show that a proportion of malaria patients produce anti-PL antibodies during infection and that titres of these antibodies are associated with the severity of disease....

Anti-Aspergillus human host defence relies on type 1 T helper (Th1), rather than type 17 T helper (Th17), cellular immunity

NARCIS (Netherlands)

L.Y.A. Chai (Louis); F. van de Veerdonk (Frank); R.J. Marijnissen (Renoud); S.C. Cheng (Shih-Chin); A.L. Khoo; M. Hectors (Magda); K. Lagrou (Katrien); A.G. Vonk (Alieke); J. Maertens (Johan); L.A.B. Joosten (Leo); B.J. Kullberg (Bart Jan); M.G. Netea (Mihai)

2010-01-01

textabstractSummary Both interferon-γ-producing type 1 T helper (Th1)- and interleukin-17 (IL-17)-producing Th17 cells have been proposed to be involved in anti-fungal host defence. Although invasive aspergillosis is one of the most severe human fungal infections, little is known regarding the

Immunotherapy of Alzheimer's disease (AD): from murine models to anti-amyloid beta (Abeta) human monoclonal antibodies.

Science.gov (United States)

Geylis, Valeria; Steinitz, Michael

2006-01-01

The deposition of amyloid beta (Abeta) protein is a key pathological feature in Alzheimer's disease (AD). In murine models of AD, both active and passive immunization against Abeta induce a marked reduction in amyloid brain burden and an improvement in cognitive functions. Preliminary results of a prematurely terminated clinical trial where AD patients were actively vaccinated with aggregated Abeta bear resemblance to those documented in murine models. Passive immunization of AD patients with anti-Abeta antibodies, in particular human antibodies, is a strategy that provides a more cautious management and control of any undesired side effects. Sera of all healthy adults contain anti-Abeta IgG autoimmune antibodies. Hence antigen-committed human B-cells are easily immortalized by Epstein-Barr virus (EBV) into anti-Abeta secreting cell lines. Two anti-Abeta human monoclonal antibodies which we recently prepared bind to the N-terminus of Abeta peptide and were shown to stain amyloid plaques in non-fixed brain sections from an AD patient. It is anticipated that specifically selected anti-Abeta human monoclonal antibodies could reduce and inhibit deposits of amyloid in brain while avoiding the cognitive decline that characterizes AD. In the future, this type of antibody may prove to be a promising immune therapy for the disease.

Both anti-TNF and CTLA4 Ig treatments attenuate the disease severity of staphylococcal dermatitis in mice.

Directory of Open Access Journals (Sweden)

Manli Na

Full Text Available RA patients being treated with biologics are known to have an increased risk of infections. We recently demonstrated that both CTLA4 Ig and anti-TNF treatment aggravate systemic Staphylococcus aureus (S. aureus infection in mice, but with distinct clinical manifestations. However, the effects of CTLA4 Ig and anti-TNF treatments on a local S. aureus infection (e.g., skin infection might differ from their effects on a systemic infection.The aim of this study was to examine the differential effects of anti-TNF versus CTLA4 Ig treatment on S. aureus skin infections in mice.Abatacept (CTLA4 Ig, etanercept (anti-TNF treatment or PBS was given to NMRI mice subcutaneously inoculated with S. aureus strain SH1000. The clinical signs of dermatitis, along with histopathological changes due to skin infection, were compared between the groups.Both CTLA4 Ig and anti-TNF treatment resulted in less severe skin infections and smaller post-infectious hyperpigmentation compared with controls. Consistent with the clinical signs of dermatitis, smaller lesion size, more epithelial hyperplasia and more granulation were found in skin biopsies from mice receiving anti-TNF compared with PBS controls. However, both CTLA4 Ig and anti-TNF therapy tended to prolong the healing time, although this finding was not statistically significant. Serum MCP-1 levels were elevated in the anti-TNF group relative to the CTLA4 Ig and PBS groups, whereas IL-6 levels were higher in PBS controls than in the other two groups. Both anti-TNF and CTLA4 Ig treatments tended to down-regulate the necrosis/apoptosis ratio in the locally infected skin tissue. Importantly, no tangible difference was found in the bacterial burden among groups.Both CTLA4 Ig and anti-TNF therapies attenuate disease severity but may prolong the healing time required for S. aureus skin infections. Neither treatment has an impact on bacterial clearance in skin tissues.

Influence of Pneumococcal Conjugate Vaccine on Acute Otitis Media with Severe Middle Ear Inflammation: A Retrospective Multicenter Study.

Science.gov (United States)

Sugino, Hirotoshi; Tsumura, Shigeru; Kunimoto, Masaru; Noda, Masuhiro; Chikuie, Daisuke; Noda, Chieko; Yamashita, Mariko; Watanabe, Hiroshi; Ishii, Hidemasa; Tashiro, Toru; Iwata, Kazuhiro; Kono, Takashi; Tsumura, Kaoru; Sumiya, Takahiro; Takeno, Sachio; Hirakawa, Katsuhiro

2015-01-01

The Japanese guidelines for acute otitis media in children recommend classifying acute otitis media by age, manifestations and local findings, and also recommend myringotomy for moderate-grade cases with severe local findings, severe-grade cases, and treatment-resistant cases. The heptavalent pneumococcal conjugate vaccine was released in Japan in February 2010. In Hiroshima City, public funding allowing free inoculation with this vaccine was initiated from January 2011, and the number of vaccinated individuals has since increased dramatically. This study investigated changes in the number of myringotomies performed to treat acute otitis media during the 5-year period from January 2008 to December 2012 at two hospitals and five clinics in the Asa Area of Hiroshima City, Japan. A total of 3,165 myringotomies for acute otitis media were performed. The rate of procedures per child-year performed in otitis media in 1-year-old infants decreased significantly in the 2 years after the introduction of public funding for heptavalent pneumococcal conjugate vaccine compared to all years before introduction (potitis media in reducing the financial burden of myringotomy. In addition, this vaccine may help prevent acute otitis media with severe middle ear inflammation in 1-year-old infants.

Marine Algae as a Potential Source for Anti-Obesity Agents

Directory of Open Access Journals (Sweden)

Chu Wan-Loy

2016-12-01

Full Text Available Obesity is a major epidemic that poses a worldwide threat to human health, as it is also associated with metabolic syndrome, type 2 diabetes and cardiovascular disease. Therapeutic intervention through weight loss drugs, accompanied by diet and exercise, is one of the options for the treatment and management of obesity. However, the only approved anti-obesity drug currently available in the market is orlistat, a synthetic inhibitor of pancreatic lipase. Other anti-obesity drugs are still being evaluated at different stages of clinical trials, while some have been withdrawn due to their severe adverse effects. Thus, there is a need to look for new anti-obesity agents, especially from biological sources. Marine algae, especially seaweeds are a promising source of anti-obesity agents. Four major bioactive compounds from seaweeds which have the potential as anti-obesity agents are fucoxanthin, alginates, fucoidans and phlorotannins. The anti-obesity effects of such compounds are due to several mechanisms, which include the inhibition of lipid absorption and metabolism (e.g., fucoxanthin and fucoidans, effect on satiety feeling (e.g., alginates, and inhibition of adipocyte differentiation (e.g., fucoxanthin. Further studies, especially testing bioactive compounds in long-term human trials are required before any new anti-obesity drugs based on algal products can be developed.

A synthetic cryptochrome inhibitor induces anti-proliferative effects and increases chemosensitivity in human breast cancer cells

Energy Technology Data Exchange (ETDEWEB)

Chun, Sung Kook [Department of Brain & Cognitive Sciences, Daegu-Gyeongbuk Institute of Science & Technology, Daegu, 711-873 (Korea, Republic of); Department of Biological Sciences, Seoul National University, Seoul, 151-747 (Korea, Republic of); Department of Brain & Cognitive Sciences, Seoul National University, Seoul, 151-747 (Korea, Republic of); Chung, Sooyoung [Department of Biological Sciences, Seoul National University, Seoul, 151-747 (Korea, Republic of); Department of Biomedical Sciences, College of Medicine, Korea University, Seoul, 136-705 (Korea, Republic of); Kim, Hee-Dae [Department of Biological Sciences, Seoul National University, Seoul, 151-747 (Korea, Republic of); Lee, Ju Hyung [Department of Systems Biology, Yonsei University College of Life Science and Biotechnology, Seoul 120-749 (Korea, Republic of); Jang, Jaebong [College of Pharmacy, Seoul National University, Seoul, 151-742 (Korea, Republic of); Kim, Jeongah; Kim, Doyeon [Department of Brain & Cognitive Sciences, Daegu-Gyeongbuk Institute of Science & Technology, Daegu, 711-873 (Korea, Republic of); Department of Biological Sciences, Seoul National University, Seoul, 151-747 (Korea, Republic of); Department of Brain & Cognitive Sciences, Seoul National University, Seoul, 151-747 (Korea, Republic of); Son, Gi Hoon [Department of Biomedical Sciences, College of Medicine, Korea University, Seoul, 136-705 (Korea, Republic of); Oh, Young J. [Department of Systems Biology, Yonsei University College of Life Science and Biotechnology, Seoul 120-749 (Korea, Republic of); Suh, Young-Ger [College of Pharmacy, Seoul National University, Seoul, 151-742 (Korea, Republic of); Lee, Cheol Soon [Gachon Clinical Trials Center, Gachon University, Incheon, 417-842 (Korea, Republic of); and others

2015-11-13

Disruption of circadian rhythm is a major cause of breast cancer in humans. Cryptochrome (CRY), a circadian transcription factor, is a risk factor for initiation of breast cancer, and it is differentially expressed between normal and breast cancer tissues. Here, we evaluated the anti-proliferative and pro-apoptotic activity of KS15, a recently discovered small-molecule inhibitor of CRY, in human breast cancer cells. First, we investigated whether KS15 treatment could promote E-box-mediated transcription by inhibiting the activity of CRY in MCF-7 human breast cancer cells. Protein and mRNA levels of regulators of cell cycle and apoptosis, as well as core clock genes, were differentially modulated in response to KS15. Next, we investigated whether KS15 could inhibit proliferation and increase sensitivity to anti-tumor drugs in MCF-7 cells. We found that KS15 decreased the speed of cell growth and increased the chemosensitivity of MCF-7 cells to doxorubicin and tamoxifen, but had no effect on MCF-10A cells. These findings suggested that pharmacological inhibition of CRY by KS15 exerts an anti-proliferative effect and increases sensitivity to anti-tumor drugs in a specific type of breast cancer. - Highlights: • Cryptochrome inhibitor (KS15) has anti-tumor activity to human breast cancer cells. • KS15 induces differential changes in cell cycle regulators and pro-apoptotic genes. • KS15 inhibits MCF-7 cell growth and enhances susceptibility to anti-tumor drugs.

A synthetic cryptochrome inhibitor induces anti-proliferative effects and increases chemosensitivity in human breast cancer cells

International Nuclear Information System (INIS)

Chun, Sung Kook; Chung, Sooyoung; Kim, Hee-Dae; Lee, Ju Hyung; Jang, Jaebong; Kim, Jeongah; Kim, Doyeon; Son, Gi Hoon; Oh, Young J.; Suh, Young-Ger; Lee, Cheol Soon

2015-01-01

Disruption of circadian rhythm is a major cause of breast cancer in humans. Cryptochrome (CRY), a circadian transcription factor, is a risk factor for initiation of breast cancer, and it is differentially expressed between normal and breast cancer tissues. Here, we evaluated the anti-proliferative and pro-apoptotic activity of KS15, a recently discovered small-molecule inhibitor of CRY, in human breast cancer cells. First, we investigated whether KS15 treatment could promote E-box-mediated transcription by inhibiting the activity of CRY in MCF-7 human breast cancer cells. Protein and mRNA levels of regulators of cell cycle and apoptosis, as well as core clock genes, were differentially modulated in response to KS15. Next, we investigated whether KS15 could inhibit proliferation and increase sensitivity to anti-tumor drugs in MCF-7 cells. We found that KS15 decreased the speed of cell growth and increased the chemosensitivity of MCF-7 cells to doxorubicin and tamoxifen, but had no effect on MCF-10A cells. These findings suggested that pharmacological inhibition of CRY by KS15 exerts an anti-proliferative effect and increases sensitivity to anti-tumor drugs in a specific type of breast cancer. - Highlights: • Cryptochrome inhibitor (KS15) has anti-tumor activity to human breast cancer cells. • KS15 induces differential changes in cell cycle regulators and pro-apoptotic genes. • KS15 inhibits MCF-7 cell growth and enhances susceptibility to anti-tumor drugs.

[Study of anti-idiotype antibodies to human monoclonal antibody].

Science.gov (United States)

Harada, R; Takahashi, N; Owaki, I; Kannagi, R; Endo, N; Morita, N; Inoue, M

1992-02-01

A human monoclonal antibody, ll-50 (IgM, lambda), was generated, which reacted specifically with a major of glycolipid present in LS174T colon cancer cells. The glycolipid antigen which reacted with the ll-50 antibody was expected to four sugar residues from its TLC mobility, and it was ascertained that the glycolipid antigen which reacted with ll-50 antibody might be Lc4 antigen [Gal beta 1----3 GLcNAc beta 1----3 Gal beta 1----4 Glc beta 1----1 Cer] judging from TLC immunostaining and ELISA when the reactivity of ll-50 antibody was tested using various pure glycolipids in 3-5 sugar residues as an antigen. Sera in patients with malignant disorders and healthy individuals were analyzed by Sandwich assay of immobilized and biotinylated ll-50 antibody. The serum of the Lc4 antigen recognized by ll-50 antibody was significantly higher in patients with malignant disorders than that in healthy individuals (p less than 0.05). Three mouse monoclonal anti-idiotype antibodies, G3, B3 and C5 (all IgG1), were generated by the immunization of BALB/c mice with ll-50 antibody. These anti-idiotype antibodies specifically bound to to human monoclonal antibody, ll-50 and had a significant inhibitory activity towards the binding of ll-50 antibody to the Lc4 antigen. This indicated that these anti-idiotype antibodies, G3, B3, and C5, were paratope-related anti-idiotype antibodies. G3, B3, and C5 were expected to define the nearest idiotope because they could mutually inhibit ll-50 antibody. Sera in patients with malignant disorders and healthy individuals were analyzed by Sandwich assay of immobilized and biotinylated anti-idiotype antibodies, G3, B3, and C5. As to the ll-50 like antibodies defined by C5 (Id-C5+), the mean serum level in patients with malignant disorders was significantly higher than that in healthy individuals (p less than 0.05). As to the ll-50 like antibodies defined by B3 (Id-B3+), the mean serum level in patients with malignant disorders was significantly higher

Prevalence of Anti Human Herpes Virus-6 IgG and its Receptor in Acute Leukemia (Membrane Cofactor Protein: MCP, CD46)

International Nuclear Information System (INIS)

Assem, M.M; El-Sharkawy, N.M.; Tarek, H.; Kamel, A.M.; Gad, W.H.; El-Rouby, M.N.; Ghaleb, F.M.

2005-01-01

CD46 is a membrane cofactor protein, which acts as a cofactor for factor I proteolytic cleavage of C3, so it protects the cells expressing it on their surface from autologous complement attack. It has been recently described as a receptor for HHV-6. Also, it has been shown to be highly expressed on malignant cells as compared to normal cells, thus playing a major role by which these cells, either cells of haematological malignancy or cells of other body cancers, can protect themselves against complement attack so they can survive and metastasize. Patients and methods: This study has been done to detect the sero prevalence of HHV-6 among 47 Egyptian adult cases of acute leukemia using the anti-HHV-6 IgG ELISA serological technique. CD46 receptor expression and immuno phenotyping technique were performed using FCM. Twenty nine of the cases were ANLL, while 18 were ALL cases. Sixteen age- and sex-matched control cases were also studied for both anti-HHV-6 IgG and CD46 receptor expression. HHV-6 IgG antibodies were encountered in 29 (100%), 14 (77.8%) and 12 (75%) of the ANLL, ALL and the control group, cases, respectively. CD46 expression was encountered in 21 (72.4%) of the ANLL cases and in 10 (55.6%) of the ALL cases. Concordance between HHV6 sero positivity and CD46 expression was encountered in 31 cases (29 positive and 2 negative). Dis concordance was encountered in 16 cases with 14 showing HHV-6 IgG sero positivity with no CD46 expression and 2 showing the reverse. The lack of significant correlation between CD46 expression and sero positivity would exclude CD46 expression as a cause of contracting HHV-6 infection in leukemic patients

Plasmodium falciparum-induced severe malaria with acute kidney injury and jaundice: a case report

Science.gov (United States)

Baswin, A.; Siregar, M. L.; Jamil, K. F.

2018-03-01

P. falciparum-induced severe malaria with life-threatening complications like acute kidney injury (AKI), jaundice, cerebral malaria, severe anemia, acidosis, and acute respiratory distress syndrome (ARDS). A 31-year-old soldier man who works in Aceh Singkil, Indonesia which is an endemic malaria area presented with a paroxysm of fever, shaking chills and sweats over four days, headache, arthralgia, abdominal pain, pale, jaundice, and oliguria. Urinalysis showed hemoglobinuria. Blood examination showed hemolytic anemia, thrombocytopenia, and hyperbilirubinemia. Falciparum malaria was then confirmed by peripheral blood smear, antimalarial medications were initiated, and hemodialysis was performed for eight times. The patient’s condition and laboratory results were quickly normalized. We report a case of P. falciparum-induced severe malaria with AKI and jaundice. The present case suggests that P. falciparum may induce severe malaria with life-threatening complications, early diagnosis and treatment is important to improve the quality of life of patients. Physicians must be alert for correct diagnosis and proper management of imported tropical malaria when patients have travel history in endemic areas.

Anti-addiction Drug Ibogaine Prolongs the Action Potential in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes.

Science.gov (United States)

Rubi, Lena; Eckert, Daniel; Boehm, Stefan; Hilber, Karlheinz; Koenig, Xaver

2017-04-01

Ibogaine is a plant alkaloid used as anti-addiction drug in dozens of alternative medicine clinics worldwide. Recently, alarming reports of life-threatening cardiac arrhythmias and cases of sudden death associated with the ingestion of ibogaine have accumulated. Using whole-cell patch clamp recordings, we assessed the effects of ibogaine and its main metabolite noribogaine on action potentials in human ventricular-like cardiomyocytes derived from induced pluripotent stem cells. Therapeutic concentrations of ibogaine and its long-lived active metabolite noribogaine significantly retarded action potential repolarization in human cardiomyocytes. These findings represent the first experimental proof that ibogaine application entails a cardiac arrhythmia risk for humans. In addition, they explain the clinically observed delayed incidence of cardiac adverse events several days after ibogaine intake. We conclude that therapeutic concentrations of ibogaine retard action potential repolarization in the human heart. This may give rise to a prolongation of the QT interval in the electrocardiogram and cardiac arrhythmias.

Function-blocking antibodies to human vascular adhesion protein-1: a potential anti-inflammatory therapy.

Science.gov (United States)

Kirton, Christopher M; Laukkanen, Marja-Leena; Nieminen, Antti; Merinen, Marika; Stolen, Craig M; Armour, Kathryn; Smith, David J; Salmi, Marko; Jalkanen, Sirpa; Clark, Michael R

2005-11-01

Human vascular adhesion protein-1 (VAP-1) is a homodimeric 170-kDa sialoglycoprotein that is expressed on the surface of endothelial cells and functions as a semicarbazide-sensitive amine oxidase and as an adhesion molecule. Blockade of VAP-1 has been shown to reduce leukocyte adhesion and transmigration in in vivo and in vitro models, suggesting that VAP-1 is a potential target for anti-inflammatory therapy. In this study we have constructed mouse-human chimeric antibodies by genetic engineering in order to circumvent the potential problems involved in using murine antibodies in man. Our chimeric anti-VAP-1 antibodies, which were designed to lack Fc-dependent effector functions, bound specifically to cell surface-expressed recombinant human VAP-1 and recognized VAP-1 in different cell types in tonsil. Furthermore, the chimeric antibodies prevented leukocyte adhesion and transmigration in vitro and in vivo. Hence, these chimeric antibodies have the potential to be used as a new anti-inflammatory therapy.

Severe neurotoxicity following ingestion of tetraethyl lead.

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Wills, Brandon K; Christensen, Jason; Mazzoncini, Joe; Miller, Michael

2010-03-01

Organic lead compounds are potent neurotoxins which can result in death even from small exposures. Traditionally, these compounds are found in fuel stabilizers, anti-knock agents, and leaded gasoline. Cases of acute organic lead intoxication have not been reported for several decades. We report a case of a 13-year-old Iraqi male who unintentionally ingested a fuel stabilizer containing 80-90% tetraethyl lead, managed at our combat support hospital. The patient developed severe neurologic symptoms including agitation, hallucinations, weakness, and tremor. These symptoms were refractory to escalating doses of benzodiazepines and ultimately required endotracheal intubation and a propofol infusion. Adjunctive therapies included chelation, baclofen, and nutrition provided through a gastrostomy tube. The patient slowly recovered and was discharged in a wheelchair 20 days after ingestion, still requiring tube feeding. Follow-up at 62 days post-ingestion revealed near-resolution of symptoms with residual slurred speech and slight limp. This case highlights the profound neurotoxic manifestations of acute organic lead compounds.

Evaluation of severity and indication for surgery in acute pancreatitis on the basis of CT in the early stage

International Nuclear Information System (INIS)

Cho, Keishouku; Nakasaku, Osamu; Kim, Jung-hyo; Hatakeyama, Gen

1985-01-01

Acute pancreatitis clinically manifests various degrees of severity. In the present study, we performed a retrospective study on 32 cases of acute pancreatitis and examined the evaluation of severity and indication for surgery in acute pancreatitis on the basis of computed tomography (CT) at the early stage (about 48 hours after onset). CT in the early stage of acute pancreatitis permits objective determination of the extent of lesion enlargement. The cases could be classified into three grades, severe, moderate, and mild, as determined by CT. It was concluded, therefore, that in the early stage CT was very useful as an indicator for emergency surgery and a helpful guide to early judgement. Emergency surgery was performed on seven of nine cases in which pancreatitis was judged to be severe on the basis of abdominal CT and clinical findings. Of the seven, four had infection in the early stage (within 48 hours after onset). Three of the four had MOF complications and died. Two of three patients without infection were relieved. The pancreatitic lesion of the cases with infection was severe as assessed via CT and the CT score was especially high. Infection in the early stage of acute pancreatitis was thus thought to be a seriouns aggravating factor. A. severe (CT score ≥ 6: surgical therapy). B. moderate (CT score = 4,5: medical therapy possible). C. mild (CT score ≤ 3: medical therapy). (author)

Anti-tau antibody administration increases plasma tau in transgenic mice and patients with tauopathy

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Yanamandra, Kiran; Patel, Tirth K.; Jiang, Hong; Schindler, Suzanne; Ulrich, Jason D.; Boxer, Adam L.; Miller, Bruce L.; Kerwin, Diana R.; Gallardo, Gilbert; Stewart, Floy; Finn, Mary Beth; Cairns, Nigel J.; Verghese, Philip B.; Fogelman, Ilana; West, Tim; Braunstein, Joel; Robinson, Grace; Keyser, Jennifer; Roh, Joseph; Knapik, Stephanie S.; Hu, Yan; Holtzman, David M.

2017-01-01

Tauopathies are a group of disorders in which the cytosolic protein tau aggregates and accumulates in cells within the brain, resulting in neurodegeneration. A promising treatment being explored for tauopathies is passive immunization with anti-tau antibodies. We previously found that administration of an anti-tau antibody to human tau transgenic mice increased the concentration of plasma tau. We further explored the effects of administering an anti-tau antibody on plasma tau. After peripheral administration of an anti-tau antibody to human patients with tauopathy and to mice expressing human tau in the central nervous system, there was a dose-dependent increase in plasma tau. In mouse plasma, we found that tau had a short half-life of 8 min that increased to more than 3 hours after administration of anti-tau antibody. As tau transgenic mice accumulated insoluble tau in the brain, brain soluble and interstitial fluid tau decreased. Administration of anti-tau antibody to tau transgenic mice that had decreased brain soluble tau and interstitial fluid tau resulted in an increase in plasma tau, but this increase was less than that observed in tau transgenic mice without these brain changes. Tau transgenic mice subjected to acute neuronal injury using 3-nitropropionic acid showed increased interstitial fluid tau and plasma tau. These data suggest that peripheral administration of an anti-tau antibody results in increased plasma tau, which correlates with the concentration of extracellular and soluble tau in the brain. PMID:28424326

Right ventricular function during acute exacerbation of severe equine asthma.

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Decloedt, A; Borowicz, H; Slowikowska, M; Chiers, K; van Loon, G; Niedzwiedz, A

2017-09-01

Pulmonary hypertension has been described in horses with severe equine asthma, but its effect on the right ventricle has not been fully elucidated. To evaluate right ventricular structure and function after a 1-week period of pulmonary hypertension secondary to acute exacerbation of severe equine asthma. Prospective study. A clinical episode of severe equine asthma was induced experimentally in six susceptible horses. Examinations in remission and on day 7 of the clinical episode included a physical examination with clinical scoring, echocardiography, arterial blood gas measurements, venous blood sampling for cardiac biomarkers, intracardiac pressure measurements, right ventricular and right atrial myocardial biopsies, airway endoscopy and bronchoalveolar lavage. After 1 month of recovery, physical examination, echocardiography and cardiac biomarker analysis were repeated. Echocardiographic and pressure measurements were compared with those in 10 healthy control horses. All horses developed clinical signs of acute pulmonary obstruction. Right heart pressures increased significantly. Altered right ventricular function could be detected by tissue Doppler and speckle tracking echocardiography. Cardiac troponin concentrations did not increase significantly, but were highly elevated in one horse which exercised in the paddock prior to sampling. Focal neutrophil infiltration was present in two myocardial samples. Even in remission, asthmatic horses showed a thicker right ventricular wall, an increased left ventricular end-systolic eccentricity index at chordal level and decreased right ventricular longitudinal strain compared with controls. The induced clinical episode was rather mild and the number of horses was limited because of the invasive nature of the study. Pulmonary obstruction in asthmatic horses induces pulmonary hypertension with right ventricular structural and functional changes. © 2017 EVJ Ltd.

Genetic diversity of human metapneumovirus in hospitalized children with acute respiratory infections in Croatia.

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Jagušić, Maja; Slović, Anamarija; Ljubin-Sternak, Sunčanica; Mlinarić-Galinović, Gordana; Forčić, Dubravko

2017-11-01

Human metapneumovirus (HMPV) is recognized as a global and frequent cause of acute respiratory tract infections among people of all ages. The objectives of this study were molecular epidemiology and evolutionary analysis of HMPV strains which produced moderate and severe acute respiratory tract infections in children in Croatia during four consecutive seasons (2011-2014). A total of 117 HMPV-positive samples collected from hospitalized pediatric patients presenting with acute respiratory tract infections and tested by direct immunofluorescence assay were first analyzed by amplifying a part of the F gene. Sixteen samples were further analyzed based on complete F, G, and SH gene sequences. HMPV genome was identified in 92 of 117 samples (78%) and the circulation of multiple lineages of HMPV was confirmed. In 2011, 2012, and 2014, subgroups A2 and B2 co-circulated, while B1 gained prevalence in 2013 and 2014. The study established the presence of a novel subcluster A2c in Croatia. This subcluster has only recently been detected in East and Southeast Asia. This study provides new insights into epidemiology and genetic diversity of HMPV in this part of Europe. © 2017 Wiley Periodicals, Inc.

What is new HLA-B27 acute anterior uveitis?

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Wakefield, Denis; Chang, John H; Amjadi, Shahriar; Maconochie, Zoe; Abu El-Asrar, Ahmed; McCluskey, Peter

2011-04-01

Acute anterior uveitis (AAU) is the most common form of uveitis, accounting for approximately 90% of all cases. Half of all cases of AAU are HLA-B27 positive. The disease is typically acute in onset, unilateral, nongranulomatous inflammation involving the iris and ciliary body, with a tendency to recurrent attacks. Approximately 50% of all patients with HLA-B27 AAU develop an associated seronegative arthritis (SNA), while approximately 25% of the patients initially diagnosed with HLA-B27 SNA develop AAU. Environmental factors play a critical role in the pathogenesis of AAU; in particular, bacterial triggers have been strongly implicated in the development of this disease. Topical corticosteroids and cycloplegic agents remain the cornerstones of treatment for AAU. Salazopirine and methotrexate are effective in decreasing recurrent attacks. Biological agents such as anti-TNF and anti-CD20 therapy may be effective in refractory severe AU but are rarely required.

Dolichos biflorus exhibits anti-inflammatory and antioxidant properties in an acute inflammatory model

Directory of Open Access Journals (Sweden)

Limi Elizabeth Mathew

2014-12-01

Full Text Available Dolichos biflorus (Muthira is a branched, suberect, and downing herb, native to most parts of India, and found at altitudes of up to 1000 m, whose seeds can be cooked and eaten. Nutrition plays a key role in building immunity and preventing noncommunicable diseases to a certain extent. The purpose of this study was to evaluate the anti-inflammatory and antioxidant effects of 70% methanolic extract of seeds of D. biflorus (DME in carrageenan-induced inflammation. DME exhibited maximum percentage of oedema inhibition at a dose of 50 mg/kg at the 3rd hour of carrageenan induction. The effect was higher than that of the standard drug Voveran. The activities of cyclooxygenase, lipoxygenase, nitric oxide synthase, myeloperoxidase, and malondialdehyde showed significant (p < 0.05 reduction whereas the activities of antioxidant enzymes, vitamins C, and reduced glutathione level were increased significantly (p < 0.05 on treatment with DME. Also levels of the acute phase protein, ceruloplasmin, were brought to their normal range in DME-treated rats. Phytochemical analysis showed that the extract contains alkaloids, flavonoids, carbohydrates, proteins, and tannins, which may contribute to its anti-inflammatory and antioxidant activity. Thus the results demonstrate the potential beneficiary effect of DME on carrageenan-induced inflammation in rats.

Acute Promyelocytic Leukemia Presenting with Severe Marrow Fibrosis

Directory of Open Access Journals (Sweden)

Harsh Shah

2015-01-01

Full Text Available We report a case of acute promyelocytic leukemia (APL presenting with severely fibrotic marrow. There are four other reports of similar cases in the literature. Our patient was treated with All-Transretinoic Acid- (ATRA- containing induction chemotherapy, followed by consolidation and maintenance therapy. He achieved a complete morphologic remission with adequate count recovery in a timely fashion, and later a molecular remission was documented. The patient remains in molecular remission and demonstrates normal blood counts now more than 4 years after induction. Since the morphological appearance may not be typical and the bone marrow may not yield an aspirate for cytogenetic analysis, awareness of such entity is important to make a correct diagnosis of this potentially curable disease.

Two distinct subtypes of hepatitis B virus-related acute liver failure are separable by quantitative serum immunoglobulin M anti-hepatitis B core antibody and hepatitis B virus DNA levels

DEFF Research Database (Denmark)

Dao, Doan Y; Hynan, Linda S; Yuan, He-Jun

2012-01-01

Hepatitis B virus (HBV)-related acute liver failure (HBV-ALF) may occur after acute HBV infection (AHBV-ALF) or during an exacerbation of chronic HBV infection (CHBV-ALF). Clinical differentiation of the two is often difficult if a previous history of HBV is not available. Quantitative measurements...... of immunoglobulin M (IgM) anti-hepatitis B core antibody (anti-HBc) titers and of HBV viral loads (VLs) might allow the separation of AHBV-ALF from CHBV-ALF. Of 1,602 patients with ALF, 60 met clinical criteria for AHBV-ALF and 27 for CHBV-ALF. Sera were available on 47 and 23 patients, respectively. A quantitative...... immunoassay was used to determine IgM anti-HBc levels, and real-time polymerase chain reaction (rtPCR) was used to determine HBV VLs. AHBV-ALFs had much higher IgM anti-HBc titers than CHBV-ALFs (signal-to-noise [S/N] ratio median: 88.5; range, 0-1,120 versus 1.3, 0-750; P

[Severe hypertriglyceridemia induced acute pancreatitis: a case report and review of the literature].

Science.gov (United States)

Herrera Del Águila, Dwight Denis; Garavito Rentería, Jorge; Linarez Medina, Karen; Lizarzaburu Rodríguez, Víctor

2015-01-01

Hypertriglyceridemia-induced acute pancreatitis occurs in about 1-4% of the cases. It is the third leading cause of pancreatitis after biliary and alcoholic etiology. Hypertriglyceridemia can be caused by primary causes, lipid metabolism disorders and secondary causes. A 32 year old man, born in Huancayo, with a history of diabetes mellitus type 2, severe mixed dyslipidemia with primary hypertriglyceridemia, was admitted to emergency with 10 days of abdominal pain with moderate intensity in epigastrium and left hypochondrium spreading to dorsal region after intake of high-fat meal. 24 hours before admission, pain exacerbates increasing intensity and causing nausea and bilious vomits. Therefore, all laboratory examinations are carried out resulting in hypertriglyceridemia-induced acute pancreatitis. For that reason, an adequate clinical history physical examination associated with laboratory and image examinations are important to consider hypertriglyceridemia as part of the etiology of acute pancreatitis.

[Total serum calcium and corrected calcium as severity predictors in acute pancreatitis].

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Gutiérrez-Jiménez, A A; Castro-Jiménez, E; Lagunes-Córdoba, R

2014-01-01

To evaluate total serum calcium (TC) and albumin-corrected calcium (ACC) as prognostic severity factors in acute pancreatitis (AP). Ninety-six patients were included in the study. They were diagnosed with AP and admitted to the Hospital Regional de Veracruz within the time frame of January 2010 to December 2012. AP severity was determined through the updated Atlanta Classification (2013). TC and ACC values were measured in the first 24hours of admittance and the percentages of sensitivity (S), specificity (Sp), positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (LR+), and negative likelihood ratio (LR-) were calculated through ROC curves and contingency tables. In accordance with the updated Atlanta Classification, 70 patients presented with mild AP, 17 with moderately severe AP, and 9 with severe AP. Of the patient total, 61.5% were women, and 69.8% presented with biliary etiology. The maximum TC cut-off point was 7.5mg/dL, with values of S, 67%; Sp, 82%; PPV, 27%, and NPV, 96%. The maximum ACC cut-off point was 7.5mg/dL, with values of S, 67%; Sp, 90%; PPV, 40%; NPV, 96%. Both had values similar to those of the Ranson and APACHE II prognostic scales. TC and ACC, measured within the first 24hours, are useful severity predictors in acute pancreatitis, with sensitivity and predictive values comparable or superior to those of the conventional prognostic scales. Copyright © 2013 Asociación Mexicana de Gastroenterología. Published by Masson Doyma México S.A. All rights reserved.

Severe acute respiratory syndrome vaccine efficacy in ferrets: whole killed virus and adenovirus-vectored vaccines.