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I Zahavi

Publications and source records attributed to I Zahavi.

At least 37 records · Page 2Linked to original sources

Ketotifen is protective against indomethacin-induced intestinal ulceration in the rat.

Ketotifen is an anti-allergic agent that was recently shown to prevent experimental gastric and colonic mucosal injury. We studied the effect of ketotifen on indomethacin-induced small intestinal ulceration in the rat. Ulceration was produced by s.c. injection of 30 mg/kg indomethacin, 30 min after refeeding 24 h fasted rats. Total ulcer area (mm2), prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) were measured 24 h after indomethacin administration. Study groups received ketotifen 100 micrograms/ 100 g body weight 30 min before and 5 h after indomethacin administration, either i.p. or orally. There were 7-9 animals in each group. Ulcer area was significantly reduced by oral administration of ketotifen from 229 +/- 26 to 146 +/- 28 mm2. PGE2 level was reduced by ketotifen from 505 +/- 73 to 228 +/- 68 ng/mg protein, and LTB4 was reduced from 289 +/- 68 to 59 +/- 26 ng/mg protein. Intraperitoneal administration of ketotifen had no effect on any of the measured parameters. Ketotifen had a definite protective effect on small intestinal mucosa in the rat, which was accompanied by a reduction of mucosal inflammatory mediators. Ketotifen may have a role in the prevention or treatment of small intestinal damage induced by nonsteroidal anti-inflammatory drugs.

Administration, Oral↗

Haemodialysis arteriovenous access--a prospective haemodynamic evaluation.

BACKGROUND: Factors affecting cardiac function in dialysis patients include arterial blood pressure, anaemia, intravascular volume, and the arteriovenous (a-v) access. Cardiac failure has been directly attributed to dialysis a-v access in several cases. The contribution of the a-v access to cardiac performance has been tested, in the past, by a short manual compression on the fistula, but this technique has obvious limitations. METHODS: The present study examined prospectively the effect of dialysis a-v access on both cardiac function and various hormonal responses. Ten patients (age, mean +/- SD, 59.6 +/- 12.3) with end-stage renal failure being prepared for chronic dialysis therapy were included. All patients underwent an echocardiographic study before and 2 weeks after the creation of the a-v access. Plasma atrial natriuretic peptide (ANP), plasma renin activity (PRA), and plasma aldosterone were measured at the same time periods. RESULTS: Following the creation of the a-v fistula or graft, shortening fraction increased by 15.8 +/- 6.3% (P < 0.01), stroke volume increased by 21.9 +/- 5.3% (P < 0.01), ejection fraction increased by 10.6 +/- 4.5% (P < 0.02), cardiac output increased by 19.0 +/- 6.9% (P < 0.02), and cardiac index increased by 18.3 +/- 7.1% (P = 0.05). Systemic vascular resistance decreased by 23.5 +/- 7.1% (P < 0.01). There was no change in blood pressure, heart rate, weight, haemoglobin or serum creatinine. ANP increased by 83.7 +/- 17.0% following the a-v access operation (P < 0.001), PRA decreased by 41.2 +/- 10.0% (P < 0.05), and plasma aldosterone did not change. None of the patients developed overt high-output cardiac failure. CONCLUSIONS: This study shows that at least in the short term following the creation of a dialysis a-v access, a mild state of volume overload develops, which is offset by the ¿unloading' effect of the decreased peripheral vascular resistance; the latter is probably mediated by secretion of ANP in response to atrial stretching.

Adult↗

Plasma fibrinogen in Israeli Moslem and Jewish school-children: distribution and relation to other cardiovascular risk factors. The Petah Tikva project.

Plasma fibrinogen levels were measured in 1,175 Israeli schoolchildren, aged 9-18 years, originating from diverse ethnic groups. The Moslem children displayed striking differences in levels and age-patterns of fibrinogen compared to Jewish children. Lower mean plasma fibrinogen levels in boys aged 9-10, 13-14 and 16-18 were observed among Moslem boys, compared to their Jewish counterparts born in Israel. Moslem girls showed lower levels of fibrinogen than Jewish Israeli girls at ages 9-10 and 16-18. While the Jewish children displayed an age-associated fibrinogen pattern comparable at the three age groups, the levels for Moslem children increased pre-puberty and decreased post-puberty, peaking at 13-14 years. No significant difference in mean plasma fibrinogen was found between sexes within ethnic groups. A number of statistically significant but low correlations (-0.32 to 0.24) were found between plasma fibrinogen and high density lipoprotein cholesterol (HDL-C) as a percentage of total cholesterol, triglycerides, blood glucose, uric acid, blood pressure, Quetelet index and sports activity. The difference between fibrinogen levels might point to a possible ethnicity risk factor explanation rather than environmentally acquired factors.

Adolescent↗

The choleretic effect of nonsteroidal anti-inflammatory drugs in total parenteral nutrition-associated cholestasis.

Cholestasis is a frequent problem in patients on total parenteral nutrition (TPN) therapy. Nonsteroidal anti-inflammatory drugs (NSAIDs), especially aspirin, cause choleresis in animals. We studied the effect of aspirin on bile flow and bile salt secretion in TPN-associated cholestasis in rats. Four groups of 6-10 animals each received either 154 mM NaCl (saline) or 2.5% amino acid solution (TRAVASOL, Travenol, Israel) and 10% glucose i.v. (TPN) for 3 h. During the second and third hours, taurocholate, the main bile salt in rats, was infused at a rate of 10 micromol/min per kg to prevent bile salt pool depletion. Aspirin, one of the main NSAIDs, was infused during the last 2 h into animals with or without TPN treatment at a rate of 100 mg/kg. Bile was directly collected from the common bile duct for 3 h. Rats given TPN showed a significant reduction in bile flow and bile salt secretion rate compared to control groups: 20.89 vs. 29.60 microl/min per kg (P <0.02) and 0.37 vs. 0.65 micromol/min per kg (P <0.0001), respectively. Aspirin had a significant choleretic effect and was able to overcome the bile flow and bile salt secretion rate reduction caused by TPN; 33.07 vs. 20.89 microl/min per kg (P <0.002) and 0.66 vs. 0.37 micromol/min per kg (P <0.0001), respectively. These results may have clinical implications for TPN-associated cholestasis.

Amino Acids↗

Oxygen radical scavengers are protective against indomethacin-induced intestinal ulceration in the rat.

Nonsteroidal antiinflammatory drugs (NSAIDs) are widely used and may cause small intestinal inflammation and damage. Reactive oxygen metabolites are involved in various gastrointestinal inflammatory processes, but there is little information about their role in small intestinal mucosal damage induced by NSAIDs. We studied the effect of the oxygen radical scavengers superoxide dismutase (SOD), catalase (CAT), and allopurinol (ALLO) on indomethacin (INDO)-induced intestinal ulceration in the rat. Ulceration was produced by s.c. injection of 30 mg/kg of INDO 30 min after refeeding 24 h-fasted rats. Total ulcer area was measured 24 h after INDO administration. Study groups each consisted of eight animals which received either i.p. CAT, SOD, or both together, at a dosage of 5,000 U/kg each. All drugs were divided into five doses, given once an hour over a 4-h period, starting at the time of INDO injection. Another group received 100 mg/kg ALLO in two doses. Total ulcer area was reduced by SOD from 228 +/- 12 (sq mm, mean +/- SEM) to 153 +/- 12 (p < 0.001), by CAT to 179 +/- 13 (p < 0.01), and by both together to 95 +/- 5 (p < 0.0001). ALLO administration reduced the total ulcer area to 176 +/- 7 (p < 0.003). The protective effect of oxyradical scavengers supports the hypothesis that oxygen radicals are involved in the pathogenesis of INDO-induced small intestinal ulceration in the rat.

Allopurinol↗

Therapeutic effect of colloid bismuth subcitrate in experimental colitis in the rat.

Colloid bismuth subcitrate (CBS) has a protective effect on ulcerated gastric and duodenal mucosa. To investigate its effect on large intestinal mucosal injury, we used acetic acid-induced colitis in the rat. Colitis was produced in male Wistar rats by rectal instillation of 1 ml of 10% acetic acid followed immediately by 1.5 ml of NaCl 0.9% (saline) enema. 1.5 ml of saline containing 240 mg of CBS or saline alone were then administered rectally every 24 h for 5 days. Another group of animals received CBS only. On the sixth day the distal colon was examined macroscopically and histologically using a 0 (normal) to 3 (necrosis) score. Prostaglandin E2 (PGE2) was measured by RIA (ng/mg protein). CBS significantly reduced both macroscopic and microscopic scores from 2.09 to 1.25 (p < 0.02) and from 2.4 to 1.08 (p < 0.02) respectively. It also induced a significant reduction in PGE2 from 1.6 to 0.57 (p < 0.004) in the inflamed colonic mucosa. The significant protective effect of topical CBS, which is accompanied by a reduction of PGE2, indicates that CBS may have a role in the treatment of colitis.

Acetates↗

Celiac disease associated with systemic lupus erythematosus.

Celiac disease in children has been occasionally reported to be associated with various disorders such as arthritis, cutaneous vasculitis and diabetes mellitus. We report on a 12-year-old girl with celiac disease, diagnosed at 1 year of age, who developed systemic lupus erythematosus. This association has not yet been reported in children.

Celiac Disease↗

Upper gastrointestinal endoscopy in the pediatric patient.

During a 4 year period (January 1988 to December 1991), 237 pediatric patients (mean age +/- SD, 9.75 +/- 5.17 years) underwent 289 upper gastrointestinal endoscopies. Premedication was used in only 102 of the endoscopic examinations, mostly in children between 2 and 10 years of age. Patients who were examined without sedation tolerated the procedure well. Abdominal pain was the most frequent indication, accounting for 57.4% of all procedures. Gastritis, esophagitis, duodenitis and duodenal ulcer were the most common endoscopic findings. Seventy-five endoscopies were performed to obtain small bowel biopsies. We found this procedure to be easy and safe and preferable to capsule biopsies. In our experience, upper gastrointestinal endoscopy with or without sedation is a safe and effective diagnostic procedure in the pediatric age group.

Adolescent↗

Total parenteral nutrition-associated cholestasis after selective damage to acinar zone 3 hepatocytes by bromobenzene in the rat.

Total parenteral nutrition is known to cause cholestasis, but the hepatic site of this effect has not been determined. The purpose of our study was to observe the effect of TPN on bile flow and bile salt secretion rate in rats after selective damage to acinar zone 3. Bromobenzene, 3.8 mmol/kg, was injected i.p., and the animals were studied 48 hours later. Experimental groups received either parenteral nutrition or saline for 2 hours. Bromobenzene caused selective damage to acinar zone 3 hepatocytes, and reduced baseline bile flow (23.99 +/- 1.09 vs 37.2 +/- 1.66, mean +/- SEM, microliter/min/kg, p < 0.001). Bromobenzene had no effect on bile salt secretion rate. Total parenteral nutrition decreased bile flow in the bromobenzene treated groups, despite the selective hepatic damage to acinar zone 3 (20.54 +/- 1.07 vs 23.28 +/- 1.63, mean +/- SEM, p < 0.001). Total parenteral nutrition reduced bile salt secretion rate in healthy animals, but this reduction was not seen in bromobenzene treated rats. Our results suggest that bile flow reduction in response to total parenteral nutrition is mediated through an effect on acinar zones 1 and 2, as this reduction is still observed after zone 3 destruction by bromobenzene. Zone 3 hepatocytes may be involved in the effect of parenteral nutrition on bile salt secretion, as the reduction in secretion rate seen in healthy animals was not observed in bromobenzene treated rats.

Analysis of Variance↗

Gastroesophageal dysfunction in Brachmann-de Lange syndrome.

Two children with the Brachmann-de Lange syndrome and severe gastroesophageal reflux are described. Both had esophagitis, recurrent severe anemia, and one had recurrent episodes of aspiration pneumonia and clubbing. Medical treatment failed in both children. One child responded dramatically to surgery, but the other died before surgery could be attempted. Our experience and a review of the literature suggest that early recognition and surgical treatment of gastroesophageal reflux will reduce morbidity and mortality in children with this syndrome.

Child↗

L-dopa is protective against indomethacin-induced small intestinal ulceration in the rat: possible role of an alpha-2-adrenergic mechanism.

Dopaminergic agents ameliorate experimentally induced gastroduodenal mucosal injury, but there is no information about their effect on small intestinal mucosa. We studied the effect of L-dopa and related substances on indomethacin-induced intestinal ulceration in the rat. Ulceration was produced by s.c. injection of 30 mg/kg indomethacin, 30 min after refeeding fasted rats. Total ulcer area was measured 24 hrs after indomethacin administration. L-dopa, 5 mg/kg given in two divided doses 5 h apart, starting 30 minutes before administration of indomethacin, was found to protect the small bowel mucosa against indomethacin- induced damage (ulcer area 122 +/- 5.5 vs 224.2 +/- 5.4 mm2, mean +/- SEM, p less than 0.006). Administration of 5 mg/kg haloperidol, a dopa antagonist, did not abolish the protective effect of L-dopa. On the other hand, yohimbine, an alpha-2-adrenoreceptor antagonist, almost completely abolished the protective effect (180.4 +/- 5.3 vs 122 +/- 5.5, p less than 0.004). Clonidine 20 micrograms/kg, an alpha-2-adrenoreceptor agonist, closely mimicked the protective effect of L-dopa (141.5 +/- 10.9 vs 224.2 +/- 5.4, p less than 0.006). All drugs were give i.p. in two divided doses, at the same schedule as described for L-dopa. The results demonstrate that L-dopa has a protective effect on indomethacin-induced small bowel injury in the rat. The protective effect is probably mediated through stimulation of alpha-2-adrenoreceptors.

Animals↗

Evidence for instability of the autonomic nervous system in patients with migraine headache.

Autonomic impairment in migraine is well documented. In order to evaluate the autonomic control in migraine, spectral analysis of heart rate fluctuations was performed on ten migraine patients, drug-free and during the inter-headache phase. They were compared to nine healthy controls and eight tension headache patients. A 24h Holter recording of ECG was performed for each subject. Every half hour, a short ECG subtrace was digitized and submitted to R wave detection, followed by computation of heart rate power spectrum. The spectral analysis of heart rate fluctuations disclosed significant differences between control subjects and patients with migraine. The migraine patients displayed markedly enhanced low frequency fluctuations (below 0.1 sec-1), during day hours (p less than 0.01) and especially at night (p less than 0.0006). In the respiratory frequency band (between 0.2 and 0.4 sec-1) no significant change was observed. Tension headache patients however, resembled the controls in that they did not display enhanced low frequency fluctuations. The enhancement at low frequencies fluctuations only, a frequency range known to be related to vasomotor control, suggests that the migraine patients are characterized by a clear sympathetic instability. This finding supports the hypothesis that migraine is of neural origin and is consistent with the observation of large variations in regional cerebral flow. Spectral analysis of heart rate fluctuations allows us to specify and quantitate this autonomic imbalance and may provide a useful tool for the evaluation of drug therapy in migraine.

Adult↗

Propranolol in the prophylaxis of migraine--evaluation by spectral analysis of beat-to-beat heart rate fluctuations.

Migraine patients seem to suffer from a continuous autonomic imbalance. Sympathetic instability, expressed by enhanced low frequency fluctuations, which exists during the headache free intervals, was observed in our previous study by spectral analysis of heart rate (HR) fluctuations. Propranolol--a beta adrenoceptor antagonist, is widely used in migraine prophylaxis. In order to specify and quantitate propranolol efficacy in migraine, spectral analysis of heart rate fluctuations was performed on 10 migraine patients before and during the treatment with propranolol. They were compared to 10 healthy control patients and 6 migraine patients who were treated for several months with propranolol and then discontinued the medication. The analysis was carried out on a 24h Holter ECG recording, which was performed for each subject during a headache free interval. Short 256 sec subtraces, taken every 30 min from the 24h ECG signal, were submitted to A/D conversion, R wave detection and computation of heart rate power spectrum. Propranolol achieved a marked effect, when comparing the power spectra of HR fluctuations in treated versus untreated migraine patients. A strong reduction (to normal level) in the low frequency HR fluctuations in the range below 0.1 Hz., was apparent in patients treated with propranolol. Subjects who had received propranolol in the past and discontinued the drug, displayed a carry-over effect of reduced fluctuations even 2-3 months after its discontinuation. It seems that the propranolol efficacy in migraine is associated with the mechanism of stabilizing the fluctuations within the frequency band related to sympathetic activity, hereby moderating the vascular instability in migraine.

Adult↗

Inflammatory pseudotumor of the heart with vasculitis and venous thrombosis.

Inflammatory pseudotumor (IPT) is a tumor-like reactive lesion of unknown etiology. An unusual case of intracardiac IPT with multisystemic involvement, including leukocytoclastic vasculitis, polyarthritis, and inferior vena cava thrombosis in a 17-year-old boy is reported. This unique combination may suggest that immune/autoimmune factors are important in the pathogenesis of IPT.

Adolescent↗

Placental ferritin in coeliac disease: relation to clinical stage, origin, and possible role in the pathogenesis of malignancy.

Placental ferritin is a tumour associated antigen present in the serum of patients with active Hodgkin's and non-Hodgkin's lymphoma, and the serum values fall during remission of the disease. There is no correlation between placental and total blood ferritin values. Because of the strong association between coeliac disease and lymphoma, 19 children with active and 25 with inactive coeliac disease were screened for the presence of placental ferritin. Thirty two children with other intestinal disorders served as controls. Placental ferritin was identified by using a monoclonal antibody in an ELISA procedure. The mean (SEM) placental ferritin value in the control serum was 12.6 (2.4) while the values in serum of patients with active and inactive coeliac disease were 117 (22.8) and 43.8 (10.2) U/ml respectively. Patients with active coeliac disease differed significantly from both control subjects (p = 0.0004) and those with inactive disease (p = 0.03). Peripheral blood lymphocytes contained no placental ferritin. It was present, however, in lamina propria lymphocytes of intestinal biopsy specimens from active coeliacs. Placental ferritin was also found in some of the better differentiated malignant cells in two patients with adult onset enteropathy associated lymphoma. Placental ferritin is known to have an immunosuppressive effect, and this may be one of the necessary steps in the development of malignancy associated with coeliac disease. Gluten free diet, by reversing this state, may have a role in the prevention of lymphoma.

Adolescent↗