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Biomedical subjects

H Knobler

Publications and source records attributed to H Knobler.

At least 19 recordsLinked to original sources
PubMed2005

TNF-{alpha}, chronic hepatitis C and diabetes: a novel triad.

Patients with chronic hepatitis C virus (HCV) infection have a significantly increased prevalence of type 2 DM compared to controls or HBV-infected patients, independent of the presence of cirrhosis. Moreover, antecedent HCV infection markedly increases the risk of developing DM in susceptible subjects. Even non-diabetic HCV patients have insulin resistance and specific defects in the insulin-signalling pathway. Activation of the tumour necrosis factor (TNF)-alpha system has a pivotal role in the inflammatory process of chronic hepatitis C, and TNF-alpha levels correlate with the degree of inflammation. TNF-alpha is known to cause insulin resistance, with similar defects in the insulin signalling pathway to those described in HCV infection. A model of mice transgenic for the HCV core protein demonstrated insulin resistance, glucose intolerance, and elevated intrahepatic TNF-alpha mRNA; all of which were ameliorated by anti-TNF-alpha antibodies. In addition, diabetic HCV patients have significantly higher levels of soluble TNF-alpha receptors, compared to non-diabetic HCV patients and controls. TNF-alpha may be the link between HCV infection and diabetes, suggesting an additional mechanism of diabetes with important implications for prognosis and therapy.

Diabetes Mellitus, Type 2↗
PubMed2005

Hypophosphataemia in old patients is associated with the refeeding syndrome and reduced survival.

OBJECTIVES: Previous studies found that hypophosphataemia (HP) a common finding in hospitalised patients associated with unfavourable outcome, but they did not focus on old patients. The aim of the current study was to determine the prevalence, associated risk factors and potential clinical consequences of HP detected during hospitalisation in a geriatric medical centre. DESIGN: Case-control study. SETTING: A total of 312-bed geriatric division. SUBJECTS: We compared 325 patients aged >or=65 years with at least one episode of HP-group defined by serum phosphate <or=0.77 mmol L(-1) with 326 patients without HP (non-HP group). MEASUREMENTS: Evaluation included baseline anamnesis, demographic and laboratory data. Patients in both groups were followed up to 2.7 years and clinical outcome recorded included length of hospitalisation, in-hospital and long-term survival. RESULTS: About 14.1% of 2307 elderly had HP. Patients in the HP-group compared with the non-HP group had significantly more weight loss, lower albumin levels, more sepsis and received threefold more glucose-containing infusions and twofold more food supplementations (P < 0.0001). HP was detected on average on the 10.9 +/- 21.5 days of hospitalisation. Patients in the HP-group compared with the non-HP group, had significantly longer hospitalisation period (P < 0.0001) and reduced long-term survival (P = 0.003) with threefold increased mortality rates. In a multivariate analysis, HP was not found to be an independent predictor of mortality. CONCLUSIONS: The HP was common among old hospitalised patients. Clinical characteristics of the HP-group, the time-course and strong association with glucose and food supplementation, are compatible with the refeeding syndrome, described previously in malnourished patients. HP was associated with significantly reduced survival.

Aged↗
PubMed2001

The role of hyperglycemia in acute stroke.

BACKGROUND: Ischemic stroke is a leading cause of death and long-term disability, and hyperglycemia is believed to aggravate cerebral ischemia. OBJECTIVES: To review animal and human studies on the relationship between hyperglycemia and brain ischemia that elucidate some of the mechanisms for the deleterious effect of hyperglycemia. To discuss present and future clinical recommendations for glucose control. METHODS: Computerized data sources and published indexes and articles from 1976 through 2000 were searched for human studies that evaluated the association between stroke and hyperglycemia, and studies focused on experimental models of hyperglycemic animals with focal and global brain ischemia. RESULTS: Most human studies have shown that in acute stroke, admission hyperglycemia in patients with or without diabetes is associated with a worse clinical outcome than in patients without hyperglycemia. This association is more consistent in the nonlacunar type of stroke. Animal studies support these findings by showing both in global and in focal postischemic models that hyperglycemia exaggerates the following damaging processes: intracellular acidosis, accumulation of extracellular glutamate, brain edema formation, blood-brain barrier disruption, and tendency for hemorrhagic transformation. Insulin treatment of hyperglycemic animals was found to have a beneficial effect in focal and global brain ischemia, which may be mediated by the glucose-reduction effect or by a direct neuroprotection. CONCLUSIONS: Most studies show the deleterious effect of early hyperglycemia, especially in patients with nonlacunar focal or global ischemia. Clinical trials of intensive insulin treatment are needed. Meanwhile simple measures to avoid excessive hyperglycemia are recommended.

Animals↗
PubMed2001

Cholesterol lowering in the older population: time for reassessment?

Hypercholesterolaemia is an established major risk factor for coronary heart disease (CHD) in the general population. In the vast majority of studies that focused on this particular age group and carefully eliminated other confounding factors such as co-morbid conditions, hypercholesterolaemia was a risk factor for CHD in the older population. Because the prevalence of CHD increases with advancing age, studies that consider not only the relative risk attributed to cholesterol but also the absolute numbers of people affected, show hypercholesterolaemia to be an even stronger risk factor in the elderly. Large primary and secondary prevention studies of HMG-CoA reductase inhibitors (statins) in the elderly have shown a reduction in major coronary events similar to that observed in the younger age group. The role of hypercholesterolaemia as a risk factor for stroke is less clear, and a major limitation is the heterogeneous nature of the disease. Nevertheless, most studies that evaluated non-haemorrhagic strokes separately showed a positive association with cholesterol levels, and statin therapy is effective in preventing stroke. These data provide a rationale for treating older hypercholesterolaemic people with statins, not only to prevent CHD, but also to prevent stroke.

Adult↗
PubMed2000

[Jet lag causing or exacerbating psychiatric disorders].

Desynchronization of circadian rhythmicity resulting from rapid travel through at least 4 time zones leads to symptoms of jet lag syndrome. The most commonly experienced symptoms in normal individuals are sleep disorders, difficulties with concentrating, irritability, mild depression, fatigue, and gastrointestinal disturbances. There is strong evidence relating affective disorders to circadian rhythm abnormalities, such as occur in jet lag. Less convincing suggestions relate jet lag to psychosis. We presume, relying on the literature and our accumulated experience, that in predisposed individuals jet lag may play a role in triggering exacerbation of, or de novo affective disorders, as well as, though less convincing, schizophreniform psychosis or even schizophrenia. An illustrative case vignette exemplifies the possible relationship between jet lag following eastbound flight and psychotic manifestations.

Antipsychotic Agents↗
PubMed2000

Increased risk of type 2 diabetes in noncirrhotic patients with chronic hepatitis C virus infection.

OBJECTIVES: To investigate whether patients with chronic hepatitis C virus (HCV) infection without evidence of cirrhosis have an increased risk of diabetes mellitus (DM) and to evaluate possible risk factors for diabetes in this group. PATIENTS AND METHODS: We conducted a case-control study of 45 consecutive eligible patients with HCV infection and no clinical, scintigraphic, or histological evidence of cirrhosis, and a control group of 90 subjects without liver disease matched by age, sex, and body mass index and similar in their origin distribution. Eighty-eight patients with chronic hepatitis B virus (HBV) infection with no evidence of cirrhosis were also evaluated. The diagnosis of diabetes was based on the 1997 American Diabetes Association criteria. RESULTS: Fifteen patients (33%) with HCV infection were found to have type 2 diabetes compared with 5.6% in the control group without liver disease (P < .001) and 12% in the group with HBV infection (P = .004). Comparison of the patients with and without diabetes revealed that positive family history of diabetes, HCV 1b genotype, and a more severe liver histology were significantly associated with DM. CONCLUSIONS: Patients with chronic HCV infection have an increased prevalence of type 2 diabetes, and this prevalence is independent of cirrhosis. The pathogenesis is intriguing, appears to be unique to HCV, and requires further study.

Adult↗
PubMed1999

Fatty liver--an additional and treatable feature of the insulin resistance syndrome.

To test the hypothesis that fatty liver coexists with other metabolic abnormalities of the insulin resistance syndrome, and responds to their amelioration, we prospectively studied 48 consecutive patients with chronically elevated liver enzymes and clinical, ultrasound and histological findings consistent with fatty infiltration of the liver. Most of the patients were overweight or obese (64%) with increased waist circumference which closely relates to visceral fat. Only 10% of the patients had normal glucose tolerance: 44% had diabetes mellitus, 29% impaired glucose tolerance, and 17% were hyperinsulinaemic. The most common dyslipidaemia found was hypertriglyceridaemia and/or low HDL-C (86%). Dietary intervention and follow-up (median 24 months), supplemented by oral hypoglycaemic or lipid-lowering drugs as needed, resulted not only in weight loss (mean 3.7 kg), decreased fasting blood glucose (p < 0.005) and improvement in serum lipid profile (p < 0.02 for both triglycerides or HDL-C) but also in an improvement of serum liver enzymes in 96%, which became normal in more than half of the patients. Thus, fatty liver was strongly associated with many features of the insulin resistance syndrome, and follow-up revealed a high potential for reversibility and a benign course.

Alanine Transaminase↗
PubMed1999

Nitrofurantoin-induced immune-mediated lung and liver disease.

A 60-year-old woman with multiple sclerosis and recurrent urinary tract infections (UTI) was evaluated for the recent onset of a dry cough, dyspnea on exertion, and jaundice. Investigation demonstrated interstitial lung disease with bilateral infiltrates and unilateral effusion, as well as a severe chronic active hepatitis with marked fibrosis. Other notable features were positive antinuclear antibodies and anti-smooth-muscle antibodies and the absence of any possible cause except for nitrofurantoin treatment (Macrodantin, 100 mg/day), which the patient had been taking for the previous 3 years as a prophylactic measure against UTI. The patient died of pneumococcal septicemia less than 30 days after presentation. Pulmonary or hepatic injury caused by nitrofurantoin treatment is rare; their combined occurrence is hardly ever described. Combined drug-induced pulmonary and hepatic toxicity is reviewed and should be considered early in the differential diagnosis to allow reversibility and avoid serious outcomes.

Anti-Infective Agents, Urinary↗
PubMed1998

Shear-induced platelet adhesion and aggregation on subendothelium are increased in diabetic patients.

Increased platelet aggregation has been suggested to play a role in the accelerated atherosclerosis of diabetics. However the physiological relevance of the aggregation tests has been questioned. The purpose of this study was to determine platelet activation in diabetic patients, using a novel device--the cone and plate(let) analyzer--to measure shear-induced platelet adhesion and aggregation on extracellular matrix (ECM). Whole blood platelet adhesion and aggregation in patients with noninsulin-dependent diabetes mellitus (n=82) and in nondiabetic controls (n=71) were compared. Clinical and laboratory characteristics of the diabetic patients were analyzed for possible correlation with parameters of platelet activity. Patients with diabetes had a significantly increased platelet activation compared to nondiabetic subjects, demonstrated by an increased adhesion to the ECM (surface coverage, 23% [95% confidence interval, 22-25%] vs. 19% [95% confidence interval, 18-20%], respectively) and an increased average size of the ECM-bound aggregates (54 microm2 [95% confidence interval, 51-57 microm2] vs. 47 microm2 [95% confidence interval, 43-51 microm2], respectively). Platelet adhesion in the diabetic group was found to correlate with triglyceride levels (r=0.36) and hematocrit values (r=0.31) and inversely with high-density lipoprotein cholesterol levels (r=0.30). There were no correlation, however, between parameters of platelet reactivity and duration of diabetes, vascular complications and low-density lipoprotein levels. Our data demonstrate an increased platelet adhesion and aggregation in diabetic patients and suggest a modulatory role of diabetic dyslipidemia.

Adult↗
PubMed1998

Higher incidence of diabetes in liver transplant recipients with hepatitis C.

We assessed the clinical and biochemical parameters associated with the development of posttransplantation diabetes (PTDM) in 52 liver transplant recipients followed up for 1 year. Diabetes was present before transplantation in 9.6% (5 of 52) of patients, and PTDM occurred in 23% (11 of 47) of the remaining liver transplant recipients. Of the 13 patients who had hepatitis C as the cause of their liver failure (HC-LD), 8 (62%) developed PTDM; of the 34 patients with other causes of liver failure, 3 (9%) developed PTDM (p < 0.001). Posttransplantation diabetes was also associated with the development of early posttransplantation hyperglycemia, a higher number of liver rejection episodes, and lower serum albumin levels at 6 months. The association of PTDM with HC-LD remained significant in a logistic regression model after adjustment for potential confounding variables. We conclude that PTDM is common in liver transplant recipients. Associated clinical parameters predictive of PTDM include a diagnosis of HC-LD before transplantation, the development of early hyperglycemia after transplantation, multiple episodes of posttransplantation liver rejection and low serum albumin levels at 6 months. The fact that HC-LD remained an independent risk factor for the development of PTDM may suggest a direct or immune-mediated pancreatic effect of the virus.

Adolescent↗
PubMed1997

Impaired glucose-induced insulin response in transgenic mice overexpressing the L-phosphofructokinase gene.

The selective impairment of glucose-induced insulin secretion in NIDDM can be attributed to defects in the glucose-signaling system. An alteration in the activity of phosphofructokinase (PFK), a key enzyme in the glycolytic pathway, may play a role in the abnormal glucose-induced insulin secretion. In this study, we evaluated insulin secretion in transgenic (Tg) mice overexpressing the liver-type subunit of phosphofructokinase (PFKL). Three independently derived Tg-PFKL lines showed random and postprandial hyperglycemia with diminished acute insulin response following intravenous glucose tolerance load. Isolated islets of Tg-PFKL mice exhibited a shift to the right of the glucose insulin dose curve. However, the maximal insulin secretory capacity, as well as the potentiation effect by arginine, were retained. PFK activity in Tg-PFKL islets was increased by 30-70%, because of the overexpression of PFKL. Conceivably, a selective overexpression of the PFKL isoform in Tg-PFKL mice altered the enzymatic properties of the tetrameric PFK and thereby affected glucose metabolism. A similar phenomenon was previously observed in transfected PC12-PFKL cells. The data show that overexpression of PFKL in transgenic mice was associated with diminished glucose-induced insulin response and suggest a mechanism to explain the role of beta-cell PFK activity in glucose-induced insulin secretion.

Age Factors↗
PubMed1997

[Impaired physicians: the Israel Intervention Program].

Diagnosis and treatment of mental disorders among physicians is a complicated problem. In western countries alcohol and drug abuse are the main mental problems of physicians, and programs of early treatment help them keep their practices without their harming their patients. We describe the activities of the Israel Committee for Psychiatric Examination of Physicians in 1989-93, when 115 physicians were examined. Addiction to alcohol or drugs was rare, but mental illness was detected in 50% of those examined. The results indicated that the committee acted therapeutically, dictating mental treatment and following up on it. Due to this policy, in most cases physicians were enabled and allowed to continue their practices. The results emphasize the need for occupational mental health facilities for physicians and other medical professionals.

Adult↗
PubMed1995

Brief report: circadian melatonin, thyroid-stimulating hormone, prolactin, and cortisol levels in serum of young adults with autism.

An abnormal circadian pattern of melatonin was found in a group of young adults with an extreme autism syndrome. Although not out of phase, the serum melatonin levels differed from normal in amplitude and mesor. Marginal changes in diurnal rhythms of serum TSH and possibly prolactin were also recorded. Subjects with seizures tended to have an abnormal pattern of melatonin correlated with EEG changes. In others, a parallel was evidenced between thyroid function and impairment in verbal communication. There appears to be a tendency for various types of neuroendocrinological abnormalities in autistics, and melatonin, as well as possibly TSH and perhaps prolactin, could serve as biochemical variables of the biological parameters of the disease.

Adolescent↗