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Biomedical subjects

Y Naveh

Publications and source records attributed to Y Naveh.

At least 19 recordsLinked to original sources

Effect of histamine H2 receptor antagonists on the secretion of cerebrospinal fluid in the cat.

Following a recent report that epithelial cells of the choroid plexus possess histamine H2 receptors, the effect of cimetidine and ranitidine, histamine H2 receptor antagonists, on the secretion and electrolyte content of CSF was examined. Fifty cats were divided into one control (n = 6) and six experimental groups. CSF was collected by puncture of the cisterna magna following pentobarbital anesthesia, and its volume, concentrations of Na+, K+, Cl-, and pH were determined. Cimetidine or ranitidine (50, 20, or 10 mg/kg) was injected intravenously 2 h after the start of the test, and their concentrations were measured in hourly blood samples and in 30-min aliquots of CSF in the 50 mg/kg experimental groups. Whereas the secretion of CSF did not change over 6 h in the control group, it decreased significantly by 30-60 min after injection of cimetidine or ranitidine and remained low for the following 6 1/2 h in all experimental groups except the 10-mg ranitidine group. Peak cimetidine and ranitidine concentrations in CSF in the 50-mg experimental groups were noted 60 and 90 min, respectively, after intravenous injection. CSF electrolyte concentrations and pH did not change during the test in any group. We conclude that intravenous cimetidine or ranitidine can significantly reduce CSF secretion in the cat, possibly by competitive inhibition of the histamine effect on H2 receptors located on the choroid plexus epithelial cell, or by a direct effect on the capillaries of the choroid plexus.

Animals

[Autoimmune enteropathy causing protracted diarrhea].

A 3-month old female infant was transferred from another hospital where she had been hospitalized from the age of 1 month for protracted secretory diarrhea. The diarrhea had begun at birth and was unresponsive to various therapeutic formulas and to total parenteral nutrition (TPN). The parents were consanguineous. There were 6 normal siblings, while 3 siblings had died in infancy, including a sister who had succumbed to protracted diarrhea at the age of 6 months. In our patient duodenal biopsy showed flattening of villi and proliferation of mononuclear cells in the lamina propria. Specific circulating IgG antibodies against gut epithelium were found, as well as thyroglobulin antibodies. Repeated trials of oral feeding were unsuccessful and TPN was required for 8 months. Complications included septicemia, osteomyelitis and acute renal failure. Therapeutic trials with intravenous hydrocortisone, zinc sulphate and metronidazole were unsuccessful and the infant died at the age of 11 months. Intestinal tissue taken postmortem showed nearly absolute flattening of intestinal villi. This is the first report in Israel of intractable infantile diarrhea due to autoantibodies to intestinal epithelium.

Autoantibodies

Effect of zinc-deficient diet of varying duration on intestinal disaccharidase activity in the rat.

To determine whether zinc has a specific role on weight gain and intestinal disaccharidase activity, 42 male Sprague-Dawley rats were assigned to one of seven groups (n = 6 each). These were a baseline control group (0) that was killed to analyze initial intestinal disaccharidase (sucrase and maltase) activity, a second group (A) fed a zinc-deficient diet for 1 week, a third group (B) pair-fed control for A, a fourth group (C) fed a zinc-deficient diet for 2 weeks, a fifth group (D) pair-fed control for C, a sixth group (E) fed a zinc-deficient diet for 3 weeks, and a seventh group (F) pair-fed control for E. All experimental groups received distilled deionized drinking water, whereas control groups received zinc-enriched (25 micrograms of zinc/ml) distilled deionized water. Water was given ad libitum. After killing, the mucosa of the proximal half of the small intestine was analyzed for protein and disaccharidase activity, and liver, kidney, and heart were analyzed for zinc concentration. Protein content and disaccharidase activity of the jejunal mucosa in the experiment and control groups did not differ significantly. However, animals on the zinc-deficient diet demonstrated mildly depressed growth rates that were proportional to the duration of the experiment, and significantly lower zinc concentration in the kidney in the experimental groups. The data indicate that administration of a zinc-deficient diet for up to 3 weeks did not result in significant changes in intestinal mucosa protein content or in disaccharidase activity.

Animals

Clinical zinc deficiency during zinc-supplemented formula.

A 2 1/2-month old preterm infant had failure to gain weight with high caloric intake, and had generalized persistent dermatitis and mild diarrhea. The patient was being fed zinc-supplemented cow's-milk-based formula (Osterfeed). High caloric intake of 8 weeks' and topical treatment of 11 weeks' duration were futile. A thorough investigation revealed low serum zinc concentration. Administration of zinc sulfate 150 mg/day resulted in brisk weight gain and complete clearing of skin lesions. The infant maintained normal levels of zinc 4 months after zinc therapy was discontinued, while being fed unmodified cow's milk and a diet of corn flour. The probability that zinc-supplemented formulas do not meet the high zinc requirements of premature infants is raised. The importance of plasma or serum zinc examination in preterm infants with slow growth velocity or failure to gain weight despite adequate caloric intake, with or without skin lesions and diarrhea, is emphasized.

Body Weight

Immunological investigations in 2 families with progressive diaphyseal dysplasia.

Immunological studies were done in members of 2 families with progressive diaphyseal dysplasia. In one family 10 patients and 5 healthy consanguineous relatives were studied, and in the second family one patient and 4 healthy consanguineous relatives were investigated. Evaluation included serum immunoglobulin and complement levels, peripheral blood mononuclear cell subpopulations and lymphocyte stimulation by mitogens. Immunoglobulin and complement levels were normal. All patients had markedly elevated proportions of OKM1 positive mononuclear cells and some of the healthy consanguineous relatives also exhibited the same abnormality. Proliferative responses of lymphocytes to phytomitogens were generally normal. This abnormality of mononuclear cell subset seems to serve as a marker of the disease and may reflect immune mechanisms involved in this disorder.

Adolescent

Renin-angiotensin system in dogs following chronic bile-duct ligation. Relation to vascular reactivity.

The pressor response to angiotensin II, blood volume, angiotensin II in arterial blood, renin substrate, renin concentration, renin activity and aldosterone in venous blood, liver function tests, kidney function tests, glucose, sodium, potassium, plasma osmolality and complete blood count were examined before and 1, 2, 3 and 5 weeks after ligation of bile ducts in nine conscious trained dogs. The pressor response to angiotensin II was markedly suppressed after bile-duct ligation, especially at 1-3 weeks postoperation. A maximal decrease in plasma renin substrate, and maximal increases in plasma renin concentration, plasma renin activity and aldosterone were noted at 1 week postoperatively. Plasma angiotensin II levels were elevated at 1 and 5 weeks postoperatively but were near normal 2 weeks postoperatively despite suppression of the angiotensin II pressor response. Endogenous levels did not correlate with suppression of the pressor response to exogenous angiotensin II.

Aldosterone

Site of zinc absorption in dog small intestine.

An in vivo intestinal perfusion technique was used to study the absorption of zinc from the duodenum, proximal jejunum and distal ileum of six dogs (group 1). Net absorption of zinc from the duodenum before and after ligation of the common bile duct averaged 596 and 574 ng.min-1.cm-1, respectively. Zinc absorption was greater (P less than 0.01) from the duodenum than from the jejunum (251 ng.min-1.cm-1) or ileum (404 ng.min-1.cm-1). Four other dogs (group 2) experienced perfusion of approximately equal segments of the duodenum (in two animals the common bile duct was ligated, and in another two it was not), proximal jejunum and distal ileum for 4 h. No change in absorption of zinc with time was noted, nor was any difference in absorption by the duodenum with and without ligation of the common bile duct observed. The data indicate that the duodenum has the greatest capacity for zinc absorption, followed by the distal ileum and proximal jejunum, and that pancreatic secretions do not appear to be necessary for adequate zinc absorption in the dog duodenum.

Animals

Effect of cimetidine on tissue distribution of some trace elements and minerals in the rat.

Cimetidine is a histamine H2-receptor antagonist that is used in the treatment of patients with gastric and duodenal ulcers and other hypersecretory conditions. This drug has a structure that suggests that it could act as a chelating agent. To examine its effects on trace metal and mineral metabolism, 38 weanling male Sprague-Dawley rats were assigned to one of five treatment groups. These were a high dose [(HD) 1750 mg/(kg X d)] group, HD pair-fed control (HDPF) group, intermediate dose [(ID) 875 mg/(kg X d)] group, ID pair-fed (IDPF) group and low dose [(LD) 87.5 mg/kg X d)] group. In a separate experiment, 20 female Sprague-Dawley rats were assigned to one of two treatment groups: a high dose cimetidine group [(HDFem) 1750 mg/kg X d)] and a pair-fed control group (PFFem). Cimetidine was administered intragastrically four times per week for 5 wk. Significant differences (P less than 0.05) found among groups for the male rats studied included higher plasma copper in the HD and the ID groups, higher plasma sodium, liver copper, heart calcium and heart zinc in the HD group and a lower percentage of fecal excretion of all the divalent metals studied in the HD and the ID groups than in their pair-fed controls. Pathologic examination of the liver revealed extensive fatty infiltration of liver cells, liver cell necrosis and disrupture of liver lobular architecture in the HD group. Cimetidine-dosed females had higher zinc in heart and plasma, higher copper in heart, kidney, liver, jejunum, ileum and uterus, higher manganese in stomach and ileum, lower iron in kidney and liver, lower kidney calcium and higher stomach calcium and lower liver magnesium compared with their pair-fed controls. Levels of liver and kidney metallothionein in the two groups were comparable. Male and female rats receiving high dose cimetidine experienced significant changes in tissue concentrations of some of the trace metals and minerals studied.

Animals

Progressive diaphyseal dysplasia (Camurati-Engelmann): radiographic follow-up and CT findings.

Sixteen patients with progressive diaphyseal dysplasia (PDD) and aged six months to 76 years were examined. Fourteen cases were hereditary, two were not. The progression of the radiologic manifestations in 13 patients who were followed up from 1 to 32 years and the computed tomography (CT) scans from five patients were obtained. The progression of PDD was slow and unpredictable, from minimal endosteal thickening of the mid-diaphyses in one pair of long bones to severe sclerosis of long bones, skull, and vertebrae. The severity of the osseous changes was not age dependent. A six-stage system was used to grade the severity of involvement and progression of PDD. CT scans demonstrated muscle mass that was preserved and showed the distribution of the osteosclerotic process, which was irregular and inhomogeneous. CT scanning was advantageous over plain radiography in this respect. Endosteal involvement was more extensive than periosteal thickening. CT scans also showed a distinct pattern of vertebral sclerosis that was confined to the posterior areas of the vertebral body and arches. In light of the paucity of characteristic clinical signs of PDD, the recognition of the radiologic features is mandatory for the diagnosis of this disease.

Camurati-Engelmann Syndrome

Effect of selenium and molybdenum on methylbenzylnitrosamine-induced esophageal lesions and tissue trace metals in the rat.

Thirty-six weanling male Sprague-Dawley rats were randomly assigned to one of four treatment groups: SE rats received 4.0 ppm selenium as sodium selenite in drinking water containing 1% sucrose; 15MO rats received 15 ppm molybdenum as sodium molybdate in the drinking water; 45MO rats received 45 ppm molybdenum in their water; and CON rats received distilled-deionized water containing only 1% sucrose. The esophageal carcinogen methylbenzylnitrosamine (MBN) was administered intragastrically in 10% ethanol twice per week for 5 wk at a dose of 2.5 mg/kg. MBN dosing was followed by a 12-wk period for tumor promotion. After this, heart, lungs, liver, spleen, kidneys, testes, tibia, muscle, brain and esophagus were excised. The esophagus was examined for MBN-induced lesions using dissecting and light microscopes and a portion was analyzed for Se. All other tissues were analyzed for Cu, Zn, Fe and Mn; some were also analyzed for Se and Mo. Most rats had precancerous lesions, and all rats had papillomas. There were no significant differences among the four treatment groups in the incidence and number per rat of precancerous lesions or gross papillomas. The SE group had significantly fewer carcinomas per rat than the other groups. The SE rats exhibited a number of significant differences in tissue trace element concentrations; in particular, they had higher Fe concentrations in heart, kidney and spleen than the other rats. The SE rats also had significantly greater urinary excretion of Mn and Fe, and excretion of the latter elements was significantly correlated with that of selenium.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance

Progressive diaphyseal dysplasia: evaluation of corticosteroid therapy.

Progressive diaphyseal dysplasia is characterized clinically by crippling leg pain, fatigue, headache, poor appetite, muscle weakness, and waddling gait. Twelve affected patients, aged 2 years 4 months to 40 years, were treated with intermittent courses of low doses of prednisone given in a single dose on alternate mornings for periods ranging from 6 months to 10 years. The average initial dose of prednisone was 0.6 mg/kg/d, and average maintenance dose was 0.3 mg/kg/d. Relief of all crippling symptoms was achieved in all patients. No untoward serious side effects have been observed, and the growth of children was not slowed. However, corticosteroid therapy should be restricted to patients suffering from crippling pain. The mechanism through which steroids act remains undefined.

Adolescent

Muscle involvement in progressive diaphyseal dysplasia.

Muscle involvement in progressive diaphyseal dysplasia was evaluated in five children, of whom four were members of one family. Age range was 2 to 10 years 9 months, and mean age was 5.5 years. Evaluation included serum enzymes, electromyography, and muscle biopsy examined by light and electron microscopy. Serum enzymes were usually noncontributory. Electromyography revealed "myopathic pattern" in four of the five patients. Muscle biopsy specimens were taken from three of the five children, including two patients from one family, of whom one had normal electromyography, and one sporadic case. Examination of the biopsy specimens by light microscope was generally not useful, whereas electron microscopic examination revealed myopathic and vascular changes consisting of atrophy of isolated muscle fibers, accumulation of endomysial collagen fibrils, and thickening of the perivascular basement membrane. The main contribution of this study is to describe electron microscopic vascular changes in muscles that appear to be similar in familial and sporadic cases of progressive diaphyseal dysplasia.

Aspartate Aminotransferases

Neurological sequelae of septic meningitis. A follow-up study of 65 children.

Seventy-two children who survived septic meningitis were reevaluated after 3 to 11 years. Thirty-four (52%) of 65 children were found to have neurological sequelae. Of the 34, 15 had major sequelae and 19 showed evidence of only minimal brain dysfunction--namely, hyperkinetic behavior, organic learning disturbances and minor motor disabilities. Acute-phase findings that were significantly associated with the rate of neurological sequelae were age, time between onset and admission, seizures, spinal fluid glucose level and the number of polymorphonuclear cells. In view of the high frequency of late neurological sequelae, it is advisable that children who survive septic meningitis have long-term follow-up in order to detect evidence of minimal brain dysfunction. An early diagnosis will help in proper management.

Adolescent