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E Graff

Publications and source records attributed to E Graff.

At least 37 records · Page 2Linked to original sources
PubMed1996

Effect of the somatostatin analogue octreotide on experimental pancreatitis in rats.

Somatostatin and its analogue octreotide have a profound inhibitory effect on the endocrine and exocrine secretions of the pancreas, stomach, and small intestine. Previous studies have been inconclusive about the possible therapeutic effect of somatostatin and its analogues in the treatment of pancreatitis. This study assessed the effect of the long acting somatostatin analogue, octreotide, in two models of experimental pancreatitis in rats. Necrotizing pancreatitis was induced by pancreatic injection of 5 ml taurocholate, 5% in male Wistar rats. In a second model mild edematous pancreatitis was induced by intravenous injection of caerulein at a supramaximal dose, 6 micrograms/kg/hr, for 5 hr. Compared to untreated rats, treatment with octreotide either prior to or following the induction of necrotizing pancreatitis resulted in less hypocalcemia (P < 0.05) and acidosis (P < 0.05), and prevented the increase in pancreatic weight (P < 0.05). Amylase levels remained high. After 20 days, there was less pancreatic damage, lower mortality rates (P < 0.05), and increase in body weight (P < 0.05). In the model of milder pancreatitis, octreotide treatment attenuated the increase in pancreatic weight (P < 0.05) and pathological damage (P < 0.05). We concluded that the somatostatin analogue octreotide has a beneficial effect in the treatment of experimental acute pancreatitis.

Acute Disease↗
PubMed1996

Fibrinogen is a predictor of mortality in coronary heart disease patients. The Bezafibrate Infarction Prevention (BIP) Study Group.

Results of epidemiological studies have indicated that fibrinogen is an important primary cardiovascular risk factor. The role of fibrinogen as a predictor of mortality in coronary heart disease (CHD) patients is unclear. We investigated the association between fibrinogen and mortality in a large cohort of CHD patients screened for participation in a secondary prevention clinical trial. Of the total investigated, 3092 men who were not included in the trial and for whom vital status was known were followed up for a mean period of 3.2 years. In 54.4% of the 111 men who died, mortality was attributed to CHD. Mean baseline plasma fibrinogen levels were 29.4 mg/dL higher in patients who died than in the survivors. All-cause and CHD mortality rates increased with increasing fibrinogen levels. This relationship was also demonstrated within categories of the primary variables predicting mortality in these patients. The contribution of fibrinogen to CHD and all-cause mortality was assessed by multivariate analysis adjusting for age, CHD severity, and comorbidity. Risk of CHD and all-cause mortality for patients in the highest fibrinogen tertile were 1.67 and 1.75, respectively, relative to patients in the lowest tertile, and an increase of about 1 SD of plasma fibrinogen level (75 mg/dL) was found to increase risk of CHD and all-cause mortality 29% and 31%, respectively. These results indicate clearly that fibrinogen level is associated with significantly increased mortality in CHD patients. Implementation of a standardized measuring method is required to allow assessment of risk in CHD patients on the basis of fibrinogen levels.

Aged↗
PubMed1996

The effect of estrogen replacement therapy on plasma serotonin and catecholamines of postmenopausal women.

We examined the effect of estrogen replacement therapy (ERT) on plasma serotonin (5HT) and norepinephrine (NE) and their correlation with serum estradiol, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in 12 postmenopausal women. Plasma 5HT and NE, estrogen, progesterone, LH and FSH were examined every 4 days for 2 consecutive months (before and during ERT). Serotonin values were low (32.29 +/- 38.36 nmol/l) and showed an intrinsic spontaneous cyclicity with a nadir every 10-11 days. Plasma NE was similar to that observed during the follicular phase of the ovulatory cycle (1,216.8 +/- 503.4 pmol/l) and showed no cyclicity. ERT significantly increased mean (+/- SD) serum estrogen values (from 95.40 +/- 73.31 to 390.72 +/- 347.17 pmol/l, P = 0.0001), significantly decreased serum FSH (from 84.04 +/- 14.97 to 52.97 +/- 20.74 mIU/ml, P = 0.0001) and LH (from 35.35 +/- 13.82 mIU/ml to 29.69 +/- 16.46 mIU/ml, P = 0.03). Plasma 5HT levels showed a tendency to rise under the influence of ERT, but this increase was not statistically significant. Plasma NE decreased significantly from 1,216.8 +/- 503.4 to 994.1 +/- 353.89 pmol/l, P <0.05. In conclusion, plasma serotonin in postmenopausal women has a 10-11 day cycle and is significantly lower than in the follicular phase of ovulating women. Plasma NE shows no cyclicity and is significantly decreased by ERT.

Aged↗
PubMed1995

Decreased dopamine uptake into platelet storage granules in Gilles de la Tourette disease.

The movement disorder of Gilles de la Tourette (GdlT) disease may reflect hyperactivity of the basal ganglionic dopamine system. Since platelets have been suggested as peripheral models for the study of catecholamine neurons, we developed a method to measure the uptake of [3H]-DA into platelet storage granules (PSG). In the present report, PSG were incubated with [3H] DA, and Vmax and Km values were calculated by linear regression analysis (Lineweaver Burke plot). The uptake of DA (0.5-5 microM) by PSG from 18 GdlT patients was significantly lower (p < .0001) compared to 15 controls (Vmax mean +/- SD, 107.5 +/- 42.5 and 265.3 +/- 66.5 fmole/mg protein resp.). The decrease of DA uptake in GdlT may reflect compensatory presynaptic changes that reduce DA activity.

Adolescent↗
PubMed1995

Tel Aviv-Heidelberg three-generation offspring study: genetic determinants of apolipoprotein A1 and apolipoprotein B.

The contribution of major gene and multifactorial effects on variation of plasma apolipoproteins A1 and B has been tested in a large sample of population-based Israeli pedigrees. Our most parsimonious and best fitting model for both apolipoproteins is consistent with Mendelian transmissibility, with significant contribution of major genes (with 2 alleles recessive and dominant within each locus) and polygenes, but neglects effects of common sib environment as well as related intergeneration differences in polygenic effects. Total genetic effects explain 71 and 58% of phenotypic variance of APO-A1 and APO-B levels. The major genes account for about 44 and 32% of the variance in APO-A1 and APO-B, respectively, and the frequency of the recessive alleles determining the high level of apolipoproteins under the study in the Israeli population is in the vicinity of 40% at each locus.

Apolipoprotein A-I↗
PubMed1995

Glanzmann's thrombasthenia associated with deletion-insertion and alternative splicing in the glycoprotein IIb gene.

Glanzmann's thrombasthenia is a bleeding disorder characterized by a decrease or absence of the functional platelet membrane glycoprotein (GP) complex, GPIIb/IIIa (alpha IIb beta 3). We describe a new deletion-insertion mutation in the GPIIb gene causing type I Glanzmann's thrombasthenia in two siblings of a consanguineous Iranian-Jewish family. The proband's platelets bound more antibodies against the vitronectin receptor-alpha V beta 3 than normal platelets, suggesting a normal GPIIIa (beta 3) gene and a defect in the GPIIb gene. Sequencing of amplified cDNA and genomic DNA fragments showed a 6-bp deletion and 31-bp insertion in exon 25 of the GPIIb gene. The predominant platelet GPIIb mRNA of the proband was a product of the splicing of exon 24 to a cryptic AG acceptor site in the insertion and encoded for deletion of amino acids Leu817-Asn826 and insertion of eight different amino acids. Cotransfection of COS-7 cells with expression vectors containing wild-type GPIIIa cDNA and the mutated GPIIb cDNA failed to produce detectable amounts of GPIIb/IIIa on the surface of the cells. Allele-specific restriction analysis of genomic DNA of family members showed homozygosity for the mutation in the affected siblings, heterozygosity in the parents, and homozygosity for the normal allele in an unaffected sibling. The observed mutation is in a region that is conserved from rodents to humans and has been suggested to be involved in the interaction between GPIIb and GPIIIa when these GPs are complexed in solution.

Adult↗
PubMed1995

Plasma fibrinogen levels and their correlates in 6457 coronary heart disease patients. The Bezafibrate Infarction Prevention (BIP) Study.

The association between fibrinogen measured in healthy individuals and subsequent development of ischemic heart disease is well established, but studies reporting fibrinogen levels in coronary heart disease patients are scarce. Plasma fibrinogen was determined for 5729 men and 728 women (aged 45 to 74) with established coronary heart disease, screened for participation in the Bezafibrate Infarction Prevention study, with the following lipid profile at the time of the first screening visit: total serum cholesterol < or = 270 mg/dl, high density lipoprotein cholesterol < or = 45 mg/dl and triglyceride < or = 300 mg/dl. Increased age was associated with augmented plasma fibrinogen values. Age-adjusted fibrinogen levels were higher in women than in men. A direct association was found between mean fibrinogen levels and low density lipoprotein cholesterol. On the other hand, the correlation with high density lipoprotein cholesterol was inverse. Fibrinogen was also associated with body mass index, behavioral variables and severity of coronary heart disease. In a multivariable linear regression analysis performed, risk factors considered explained merely 6 and 4% of fibrinogen variation for men and women, respectively. Therefore, most of the fibrinogen level variability in coronary heart disease patients is accounted for by factors that remain to be established by further research.

Age Factors↗
PubMed1995

Asymptomatic hyperglycemia in coronary heart disease: frequency and associated lipid and lipoprotein levels in the bezafibrate infarction prevention (BIP) register. The BIP Study Group.

BACKGROUND: The lipid profile of patients with type-II diabetes is characterized by low levels of high-density lipoprotein cholesterol, hypertriglyceridemia, and increased levels of lipoprotein (a), all of which may affect the prognosis in patients with atherosclerotic cardiovascular disease. This study aimed to assess the prevalence of asymptomatic hyperglycemia and the associated lipid profile in a large group of patients with documented coronary heart disease. METHODS: From February 1990 to October 1992, 14,326 patients aged 45-74 years with documented coronary heart disease (a history of myocardial infarction or angina pectoris) were screened for inclusion in a secondary prevention study using bezafibrate retard. All screened patients underwent a medical examination and a blood test after fasting for 14 h. Asymptomatic hyperglycemia was defined as a fasting blood glucose level of 140 mg/dl or above in patients with no previous history of diabetes mellitus. RESULTS: The prevalence of asymptomatic hyperglycemia was 4%, with no differences between the sexes or age groups. Total cholesterol and triglyceride levels were significantly higher and the high-density lipoprotein cholesterol level significantly lower in asymptomatic hyperglycemic than in normoglycemic patients. After multiple adjustments, the relative risk of death was 1.75 and 1.71 in patients with diabetes or asymptomatic hyperglycemia compared with those with no glycemic disorders. CONCLUSION: Asymptomatic hyperglycemia was detected in 4% of patients with ischemic heart disease. The lipid profile in these 4% resembles that of patients with confirmed diabetes, and their morbidity and mortality may therefore be higher than that of normoglycemic patients. Repeated assessment of glucose levels in patients with coronary heart disease is mandatory.

Aged↗
PubMed1993

Rationale and design of a secondary prevention trial of increasing serum high-density lipoprotein cholesterol and reducing triglycerides in patients with clinically manifest atherosclerotic heart disease (the Bezafibrate Infarction Prevention Trial).

Controlled clinical trials have demonstrated the efficacy of reducing the blood levels of low-density lipoprotein cholesterol in reducing the incidence of coronary artery disease in hypercholesterolemic middle-aged men. However, a similar reversibility of the risk of coronary artery disease has not been demonstrated for high-density lipoprotein cholesterol elevation and triglyceride reduction. Therefore, the effect of administering 400 mg of bezafibrate retard daily versus placebo (double blind) to patients with myocardial infarction preceding randomization by 6 months to 5 years, or a clinically manifest anginal syndrome documented by objective evidence of dynamic myocardial ischemia, or both, is being investigated. Three thousand subjects (aged 45 to 74 years) are being enrolled from 19 cardiac departments in Israel, with total serum cholesterol between 180 and 250 mg/dl, high-density lipoprotein cholesterol < or = 45 mg/dl and triglycerides < or = 300 mg/dl. In addition, low-density lipoprotein cholesterol concentrations are required to be < or = 180 mg/dl (< or = 160 mg/dl for patients aged < 50 years). Patients needing lipid-modifying therapy, exhibiting > or = 1 prespecified exclusion criterion or not giving informed consent, or a combination, are not randomized. The primary end points for evaluating efficacy are the incidence of fatal and nonfatal myocardial infarction, and sudden death. The hypothesized effect of bezafibrate administration under the aforementioned protocol is to reduce an estimated cumulative end point event incidence of > or = 15% by 20 to 25% over an average follow-up period of 6.25 years, through early 1998, when the last patient recruited will have completed 5 years.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1993

[3H] dopamine uptake by platelet storage granules in Parkinson's disease.

[3H] Dopamine (DA) uptake by platelet storage granules was determined in 10 never-treated patients with Parkinson's disease (PD) (in 6 of them, also after 6 months of levodopa treatment), in 18 long-term levodopa-treated patients and in 15 age-matched normal controls. Maximum velocity (Vmax) of DA uptake was significantly lower in the group of never-treated PD subjects compared to healthy controls (P < 0.001) and also lower compared to the PD long-term treated patients (P < 0.025). The Vmax of PD never-treated changed after submitting the patients to 6 months treatment (P < 0.025) and became similar to the Vmax in the treated group. The apparent Michaelis constant (Km) of DA uptake in PD never-treated was also significantly different from controls (P < 0.005) and also different (but not significantly) from PD "long-term" treated patients. Decreased DA uptake by platelet storage granules in PD may reflect a generalized defect of dopaminergic cells with an impairment in the vesicularization of DA which may contribute to the symptomatology of this motor disease.

Aged↗
PubMed1993

Food preferences, body weight, and platelet-poor plasma serotonin and catecholamines.

The possible relationship between body weight, food preferences, and plasma neurotransmitters was investigated in 96 healthy volunteers. The volunteers were divided into groups according to sex, body mass index, and food preferences. In all groups fasting platelet-poor plasma (PPP) norepinephrine and serotonin (5-HT) were examined. PPP-5-HT was low in obese individuals (mean +/- SD: 51.7 +/- 34.6 nmol/L) in comparison with lean individuals (94.31 +/- 85.2 nmol/L; P < 0.01), in lean male carbohydrate cravers (22.7 +/- 16.4 nmol/L) in comparison with protein cravers (132.9 +/- 80.6 nmol/L; P < 0.005) and noncravers (64.7 +/- 51.7 nmol/L; P < 0.05), and in obese male carbohydrate cravers (34 +/- 22.7 nmol/L) in comparison with obese male protein cravers (98.8 +/- 28.4 nmol/L; P < 0.001). In conclusion, PPP-5-HT might be seen as a peripheral indicator of processes linked with food consumption and food preferences.

Adult↗
PubMed1993

The Gulf War and diabetes mellitus.

The Gulf war was a traumatic and stressful event for the inhabitants of Tel-Aviv and vicinity. The entire population changed its way-of-life. In order to evaluate the influence of the war stress on glucose control, we reviewed the charts of all diabetic patients attending the outpatient clinics at the Tel-Aviv Medical Centre, whose weight and glycated haemoglobin was determined between 15.1.91 and 2.5.91 (the war period), with comparative measurements within 4 1/2 months both before and after these dates. Sixty-six patients with non-insulin dependent diabetes mellitus (NIDDM) and 16 with insulin-dependent diabetes mellitus (IDDM) were examined. During the war, their glycated haemoglobin increased by 10.1 to 10.9% and from 9.6 to 10.2%, respectively. Weight increased from 76.1 to 77.5 kg in the NIDDM and from 63.2 to 64.7 kg in the IDDM patients. Both measurements returned to baseline after the war. No correlation was found between the changes in glycated haemoglobin and weight.

Adult↗
PubMed1993

Broad bean (Vicia faba) consumption and Parkinson's disease.

In 1913, Guggenheim identified L-DOPA in the seedlings, pods, and beans of the broad bean, Vicia faba (VF). Since then, anecdotal cases of symptomatic improvement after VF consumption have been described in patients with PD. In the present study, five healthy volunteers and six PD patients (mean age, 63.5 years; mean disease duration, 13 years; stage III, Hoehn-Yahr scale) ate 250 g cooked VF after 12 hours off medication. Blood samples for L-DOPA measurements (by HPLC-ED) were obtained before eating VF and every 30 minutes, for 4 hours. During this period, a substantial clinical improvement was noted and three patients also showed severe dyskinesias. High plasma L-DOPA values were also measured (Cmax 0.66 to 1.20 micrograms/ml; AUC 1.82 to 4.12 micrograms/ml/H). In addition, their clinical performance and plasma L-DOPA levels were compared to those found after 125 mg L-DOPA + 12.5 mg carbidopa ingested on another day. These data show that VF ingestion produces a substantial increase in L-DOPA plasma levels, which correlates with a substantial improvement in motor performance. Our findings may have implications for the treatment of PD, especially in patients with mild symptoms.

Carbidopa↗
PubMed1992

Decreased (3H) quinuclidinyl benzilate binding to lymphocytes in Gilles de la Tourette syndrome.

In spite of an unknown pathophysiology, it has been suggested that central dopaminergic hyperactivity exists in Gilles de la Tourette syndrome (TS). Cholinergic influences have also been postulated as a dopaminergic-cholinergic balance seems to be important in other movement disorders. If TS is due to alterations of cholinergic activity, this may also be expressed at postsynaptic levels. Recently, we showed that circulating lymphocytes may serve as useful peripheral markers reflecting induced alterations or inherent changes in muscarinic receptors in the central nervous system (CNS). In the present study, we compared the muscarinic binding characteristics in peripheral lymphocytes as measured by (3H) quinuclidinyl benzilate [(3H)-QNB] in 27 unmedicated TS patients, against 22 healthy (age and gender-matched) controls. B(max) and Kd values were determined using Lineweaver-Burke plots. The mean B(max) values in nontreated TS patients was markedly and significantly lower than in controls (10.59 +/- 8.4 versus 40.16 +/- 9.2 fmole/10(6) cells, p less than 10(-6), while Kd values were similar in both groups. Our findings suggest that changes in cholinergic receptors may play a role in the pathophysiology of Tourette syndrome.

Adolescent↗
PubMed1992

Dexamethasone suppression of the calcitonin induced beta-endorphin, ACTH and cortisol secretion.

Our previous observations have shown that calcitonin (CT) stimulates beta-endorphin, ACTH, and cortisol secretion. In order to give further information on the supposed hypothalamic pituitary involvement in this effect, we studied the influence of dexamethasone on this stimulative influence of CT. Six healthy women aged 50-65 years were investigated. All the subjects received 100 U CT salmon (Sandoz) i.v. at 0800 (0 time). Plasma beta-endorphin, ACTH, and cortisol were estimated every 30 min from -30 to 120 min by specific radioimmunoassays. The same subjects were evaluated a second time, at the same intervals, when 1 mg dexamethasone was administered per os at 11 PM the previous night and CT i.v. at 0800 the next morning. Beta-endorphin, ACTH, and cortisol levels (mean +/- SEM) rose significantly after 100 U CT from 5.6 +/- 0.17 to 16.75 +/- 1.8 pmol/L (p less than 0.001); from 39.6 +/- 6 to 88.0 +/- 3.1 pg/ml (p less than 0.0001) (from 8.7 +/- 1.3 to 19.4 +/- 0.7 pmol/L); and from 13.1 +/- 1.6 to 23.8 +/- 3.0 micrograms/dl (p less than 0.0001) [374 +/- 45 to 680 +/- 85 nmol/L], respectively. Dexamethasone suppressed almost completely the stimulatory effect of CT beta-endorphin rose from 4.9 +/- 0.12 to 6.3 +/- 1.3 pmol/L (n.s.), ACTH from 38.6 +/- 5.1 to 42.6 +/- 6.2 pg/ml (n.s.) (from 8.5 +/- 1.1 to 9.4 +/- 0.9 pmol/L) and cortisol from 0.88 +/- 0.23 to 0.88 +/- 0.18 microgram/dl (n.s.) (from 25.1 +/- 6.5 to 25.0 +/- 5.1 nmol/L).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed1992

[3H]dopamine uptake by platelet storage granules in schizophrenia.

[3H]Dopamine (DA) uptake by platelet storage granules was determined in 26 schizophrenic male patients, paranoid type (14 acute stage; 12 in remission) and 20 age-matched, normal controls. Maximum velocity (Vmax) of DA uptake was significantly higher in acute patients, than patients in remission or controls (p less than 0.05). The apparent Michaelis constant (Km) of DA uptake in acute patients was also significantly different from chronic patients (p less than 0.05). Preincubation with reserpine (10(-4), 10(-5) M) produced a substantial diminution of DA uptake, while haloperidol (10(-4), 10(-5) M) did not affect the assay. Considering that a DA dysequilibrium in schizophrenia may be expressed not only in the brain, but also in the periphery and that an increased amount of DA accumulated in the vesicles, implies that an increased quantity of catecholamine is available for release, our findings suggest additional evidence for the role of DA overactivity in the pathophysiology of this disorder.

Adult↗
PubMed1992

The influence of meal composition on plasma serotonin and norepinephrine concentrations.

Reports concerning changes in plasma neurotransmitter values that result from dietary manipulations have not been published so far. The influence of various meal compositions on platelet-poor plasma (PPP) serotonin (5-HT) and norepinephrine (NE) levels was investigated. Healthy volunteers were subjected to three test meals: a carbohydrate-rich meal (86% carbohydrates), a protein-rich meal (70% protein), and a fat-rich meal (92% fat). After a carbohydrate-rich meal, PPP 5-HT values increased significantly (4.47-fold, P less than .02), whereas a smaller increase (1.66-fold, P = NS) was observed after a fat-rich meal. These effects on PPP 5-HT values could be correlated with insulin plasma levels. A protein-rich meal significantly reduced (P = 0.0011) PPP 5-HT to 28% of initial values, despite an increase in plasma insulin levels. This study has shown that (1) changes in meal compositions influence PPP 5-HT and, to a lesser extent, NE values; (2) the resulting changes in PPP 5-HT levels parallel those reported for brain neurotransmitters; and (3) these results seem to indicate that PPP 5-HT levels may be a model for brain synthesis and release of 5-HT.

Adult↗