Search PubMed⌕ Search

Biomedical subjects

M Horowitz

Publications and source records attributed to M Horowitz.

At least 379 records · Page 21Linked to original sources

Effect of salt restriction on urine hydroxyproline excretion in postmenopausal women.

Fasting calcium and hydroxyproline excretion are related to fasting sodium excretion in postmenopausal women. We postulate that calcium excretion is sodium dependent and that hydroxyproline excretion is calcium dependent. Therefore, we sought to lower urinary hydroxyproline, which is a marker of bone resorption, by lowering urinary sodium. Fasting urine samples were obtained from 59 postmenopausal women before and after 2 to 7 days of dietary salt restriction. The urinary sodium-to-creatinine ratio fell from 16 to 7; calcium to creatinine, 0.30 to 0.26; and hydroxyproline to creatinine, 18.2 to 16.8. In the 28 subjects with starting sodium-to-creatinine ratios greater than 15, the hydroxyproline-to-creatinine ratio fell from 19.6 to 16.3. Salt restriction may be one way of reducing bone resorption in postmenopausal women, particularly in those whose sodium intake is high.

Aged↗

Use of technetium-99m(V)thiocyanate to measure gastric emptying of fat.

Technetium-99m(V)thiocyanate was evaluated as a radio-pharmaceutical for measuring gastric emptying of fat. Olive oil was labeled with 99mTc(V)thiocyanate by direct extraction from acidic thiocyanate solution. After incubation with dilute HCl (pH 1.4) at 37 degrees C for 3 hr, approximately 5% of the total radioactivity eluted into the aqueous phase. When incubated with human gastric juice (pH 1.8 and 2.2), approximately 8% of the activity was detected in the aqueous phase at 3 hr. Scintigraphic studies performed in two rabbits showed that olive oil labeled with 99mTc(V)thiocyanate emptied slowly from the stomach, with a gastric half-emptying time (T50) of more than 3 hr. A low-nutrient soup labeled with 113mIn-DTPA and mixed with 99mTc(V)thiocyanate labeled oil was consumed by six human volunteers. The oil emptied much more slowly (p less than 0.02) (median T50 = 198 min) than the aqueous component (median T50 = 30 min). These observations indicate that 99mTc(V)thiocyanate is a suitable pharmaceutical to measure gastric emptying of extracellular fat.

Adult↗

Prevalent and rare mutations among Gaucher patients.

Sequence analysis of gcs cDNA (encoding glucocerebrosidase) or genomic fragments originated from Gaucher patients revealed novel mutations. Two rare mutations were found in a type-2 non-Jewish Gaucher patient: a G----A transition (Gly325----Arg) at nucleotide (nt) 5306 of the active gene and a T----G transversion (Cys342----Gly) at nt 5357. These mutations were not found in any other patient. A G----C transversion (Asp409----His) at nt 5957 was identified in two non-Jewish patients, and was designated TL. Two recombinant alleles were found. One recombinant allele designated recTL contained four single-nt mutations. These mutations included: (1) a G----C transversion at nt 5957 (Asp409----His) (the TL mutation); (2) a T----C transition at nt 6433 (Leu444----Pro) creating a new NciI site (NciI mutation); (3) a G----C transversion at nt 6468 (Ala456----Pro; 456 mutation); and (4) a G----C transversion at amino acid (aa) 460 (nt 6482), not associated with any aa change. Sequence analysis indicated that at least part of exon 9, intron 9 and exon 10 of the recombinant gene derived from the pseudogene. The other recombinant gene, designated recNciI, contained a mutation at aa 444 (NciI mutation), and mutations 456 and 460 described above; at least exon 10 of this gene originated from the pseudogene. We hypothesize that the presence of the pseudogene close to the active gene causes transfer of mutations into the active gene via gene conversion or nonhomologous recombination, thus accounting for the high frequency of mutations observed in the gcs gene.

Alleles↗

Mutation analysis of an Ashkenazi Jewish family with Gaucher disease in three successive generations.

Seven members of an Ashkenazi Jewish family with Gaucher disease in 3 successive generations were tested for the presence of the 2 common mutations known to occur in the glucocerebrosidase gene. Genomic DNA from blood or skin fibroblasts of relatives was amplified by using the PCR technique and individual mutations identified by oligonucleotides specific to the mutated sequences. Four individuals were homozygous for a mutation at amino acid 370 (370 mutation) known to occur only in type 1 disease. The other 3 affected relatives were compound heterozygotes for this mutation and for a mutation at amino acid 444 (NciI mutation) which, in the homozygous state, is associated with neurological disease. Clinical severity was more marked in the compound heterozygotes than in the homozygotes. Since the mutation is present in Ashkenazim, molecular diagnosis in families which carry the NciI mutation should prove useful in assessing their risk of the neurologic forms of Gaucher disease.

Adult↗

Hyperglycaemia slows gastric emptying in type 1 (insulin-dependent) diabetes mellitus.

In 10 patients with Type 1 (insulin-dependent) diabetes mellitus gastric emptying of a digestible solid and liquid meal was measured during euglycaemia (blood glucose concentration 4-8 mmol/l) and during hyperglycaemia (blood glucose concentration 16-20 mmol/l). Gastric emptying was studied with a scintigraphic technique and blood glucose concentrations were stabilised using a modified glucose clamp. Patients were also evaluated for gastrointestinal symptoms, autonomic nerve function and glycaemic control. When compared to euglycaemia, the duration of the lag phase before any of the solid meal emptied from the stomach (p = 0.032), the percentage of the solid meal remaining in the stomach at 100 min (p = 0.032) and the 50% emptying time for the solid meal (p = 0.032) increased during hyperglycaemia. The 50% emptying time for the liquid meal (p = 0.042) was also prolonged during the period of hyperglycaemia. These results demonstrate that the rate of gastric emptying in Type 1 diabetes is affected by the blood glucose concentration.

Adult↗

Malabsorption of calcium in corticosteroid-induced osteoporosis.

We have examined the relation between radiocalcium absorption and serum 1,25-dihydroxyvitamin D [1,25(OH)2D3] levels in a set of 60 postmenopausal women on corticosteroid therapy (29 with and 31 without vertebral compression fractures) and compared these results with those from 31 normal postmenopausal women age-matched with the "normal" corticosteroid-treated women. Radiocalcium absorption was a function of serum 1,25(OH)2D3 in both corticosteroid-treated groups and in the set as a whole, but the impaired calcium absorption in the corticosteroid-treated patients with osteoporosis was not accounted for by their slightly reduced serum 1,25(OH)2D3 levels. This apparent resistance to the intestinal action of 1,25(OH)2D3 was quantified by a Z score which expresses, in standard deviation units, the difference between the measured calcium absorption and that predicted from the 1,25(OH)2D3 level. The Z score was significantly reduced in the osteoporotic group. Vertebral mineral density (VMD) was measured by quantitative computed tomography in 43 of the corticosteroid-treated cases and in all the normal postmenopausal women; analysis by VMD yielded similar conclusions.

Adrenal Cortex Hormones↗

The effect of terminal ileal triglyceride infusion on gastroduodenal motility and the intragastric distribution of a solid meal.

The infusion of triglyceride emulsions into the terminal ileum in concentrations that approximate those found in malabsorption results in the slowing of gastric emptying. The aim of this study was to characterize the changes in gastroduodenal motility responsible for this effect. Antropyloroduodenal pressures in 8 healthy volunteers were recorded with a manometric assembly incorporating a sleeve sensor across the pylorus and side holes in the antrum and duodenum. Each subject ingested a 100-g, 99m Tc-labeled solid meal; when approximately 25% of the meal had emptied from the stomach, a triglyceride emulsion (20% Intralipid) was infused into the terminal ileum at 1 ml/min for 45 min. Gastric emptying slowed markedly 15-30 min after the start of the lipid infusion (p = 0.01), and there was retrograde movement of the solid meal from the distal to the proximal portion of the stomach. During lipid infusion, there was a decrease in antral (p = 0.01), duodenal (p less than 0.05), and propagated antropyloroduodenal pressure waves (p less than 0.05) and an increase in isolated pyloric pressure waves (p less than 0.05). The rate of gastric emptying correlated with antral pressure waves (r = 0.92, p less than 0.001), duodenal pressure waves (r = 0.80, p less than 0.01), and propagated pressure waves (r = 0.88, p = 0.0025) and correlated inversely with the number of isolated pyloric pressure waves (r = -0.60, p = 0.05). The changes in antral, pyloric, and duodenal motility and the intragastric redistribution of a solid meal associated with ileal lipid infusion are likely to contribute to the delay in gastric emptying caused by this stimulus.

Adult↗

Gastroduodenal motility during the delayed gastric emptying induced by cold stress.

We have assessed the changes in gastroduodenal motility responsible for the delay in gastric emptying produced by cold stress. Antropyloroduodenal pressures were recorded in 7 healthy volunteers, concurrent with scintigraphic measurement of gastric emptying. The manometric assembly incorporated a sleeve sensor located across the pylorus and side holes in the antrum and the duodenum. When approximately 25% of a 100-g 99m Tc-labeled ground beef burger had emptied from the stomach, a standardized cold pressor test was applied. This consisted of 60-s immersions of the left hand in iced water (4 degrees C), with 15-s rest periods between immersions, for up to 20 min. Cold stress was associated with slowed emptying from the total stomach (median, 17% before stress vs. 2% during stress; p less than 0.01) and the proximal stomach (9% before vs. 3% during; p less than 0.01). Retrograde movement of the solid meal from the distal to the proximal stomach was observed in 4 subjects. Cold stress increased the number of isolated pyloric pressure waves (p less than 0.05), and decreased the number of antral (p less than 0.01) and propagated antropyloroduodenal pressure waves (p less than 0.05). Phase 3-like duodenal activity occurred in 2 subjects during the first 5 min of stress; otherwise there was a reduction in the number of duodenal pressure waves during stress (p less than 0.05). Basal pyloric pressure was not elevate before, during, or after stress. We conclude that in addition to the previously reported antral inhibition, cold stress is associated with changes in pyloric and duodenal motility and, in some subjects, in the intragastric distribution of food. These modifications in gastroduodenal motility are likely to contribute to the delay in gastric emptying produced by this stimulus.

Adolescent↗

Calcium and calcitriol therapy in osteoporotic postmenopausal women with impaired calcium absorption.

The effects of oral calcitriol (0.25 and 0.50 micrograms/d), together with calcium (1 g/d), on calcium absorption and bone resorption were measured in postmenopausal osteoporotic women with calcium malabsorption. Radiocalcium absorption was significantly improved and urinary hydroxyproline/creatinine excretion significantly reduced on both doses, but the higher dose caused an unacceptable incidence of hypercalcemia. In 49 patients treated for an average of 15 months with the lower dose, there was a nonsignificant gain in forearm bone mass of 0.4 +/- 0.3 mg/cm/mo (approximately 1/2% per annum) compared with a significant decrease in 17 untreated patients of 3.8 +/- 1.3 mg/cm/mo (approximately 5% per annum).

Absorption↗

Relationship between plasma calcium fractions, other bone-related variables, and serum follicle-stimulating hormone levels in premenopausal, perimenopausal, and postmenopausal women.

The study comprises 186 untreated normal premenopausal, perimenopausal, and postmenopausal women in whom we measured serum follicle-stimulating hormone and a number of bone-related plasma and urinary variables. The calcium fractions in the plasma were calculated from the total calcium, albumin, globulin, anion gap, and bicarbonate concentrations. With a level of follicle-stimulating hormone within the reference range (up to 20 U/L) to define the premenopausal state, we confirmed previously reported menopausal rises in plasma calcium, phosphate, alkaline phosphatase, and bicarbonate, and in urinary calcium and hydroxyproline. However, inspection of the data, and t testing at different follicle-stimulating hormone criteria showed that these changes in bone-related variables did not generally occur until the level of follicle-stimulating hormone exceeded approximately 50 U/L. The plasma alkaline phosphatase level rose earlier than the other variables and was significantly elevated in subjects with follicle-stimulating hormone values above 30 U/L. The rise in plasma calcium was mainly a result of a rise in the ultrafiltrable fraction, which in turn was accounted for by rises in the ionized and complexed fractions, of which the complexed fraction was the most significant and proportionately the largest. The rise in the complexed fraction was accounted for by the increase in plasma bicarbonate.

Adult↗

Effect of dexfenfluramine on gastric emptying of a mixed solid-liquid meal in obese subjects.

Recent studies suggest that dexfenfluramine (D-fenfluramine), because of its pure serotonergic effect, may be a more potent anti-obesity agent, associated with fewer side-effects than the racemate DL-fenfluramine. The effect of dexfenfluramine on gastric emptying of a mixed solid and liquid meal was assessed with a double-isotope scintigraphic technique in eleven obese patients. Each subject took a placebo capsule on the morning and evening of the day before, and on the morning of the first gastric emptying measurement. Dexfenfluramine was then taken at a dose of 15 mg twice daily and gastric emptying measurements were performed at 5 and at 29 d after the initiation of active treatment. Dexfenfluramine significantly slowed gastric emptying of the solid meal at both 5 and 29 d when compared with the placebo (P less than 0.05) and also delayed emptying of solid food from the proximal stomach (P less than 0.01), but no significant effect on liquid emptying was observed. No significant side-effects were reported and there was a marginal weight loss (P less than 0.005) during treatment. We conclude that inhibition of gastric emptying may contribute to the efficacy of dexfenfluramine in the treatment of obesity.

Adolescent↗

Perceptual robustness of the nonrelationship between psychopathology and popular responses on the Hand Test and the Rorschach.

A Hand Test Popular response is developed using 106 normal subjects and Rorschach's traditional "one-in-three" criterion. Six popular responses were derived. Neither the newly established Hand Test Popular response nor the Rorschach Popular discriminated psychosis from nonpsychosis, but as expected, Rorschach chi + % and Rorschach WSum6 were significant, and the Hand Test Bizarre (BIZ) score approached significance. Both the Rorschach Popular and the newly developed Hand Test Popular await further elucidation.

Humans↗

Myocardial pathology in rats exposed to prolonged environmental heat.

STUDY OBJECTIVE: The aim was to assess the role of continuously high environmental temperature in the genesis of tropical cardiomyopathies. DESIGN: Rats were kept in a climatic chamber at a constant temperature of 34 degrees C (40% relative humidity) for 1 or 2 months. Controls were kept at 24 degrees C. The hearts, either taken directly from the animals or following Langendorff perfusion, were then examined by light and electron microscopy. EXPERIMENTAL MATERIAL: 69 rats of two different strains, aged about 1 month, were used as the study group. There were 32 suitable controls. MEASUREMENTS AND MAIN RESULTS: The weights of the heated rats and their hearts were lower than controls but the body to heart weight ratio was unchanged. The maximum pressure developed by the left ventricle was higher. With light microscopy, focal necrosis, lymphoid and mast cell infiltrations, fibrosis, and occasional calcifications were seen in most heat exposed rats. With electron microscopy most myocytes appeared normal when taken from whole animals. The additional trauma of heart suspension or hypo-osmolar perfusion caused severe membrane related pathology, while controls remained unaffected. CONCLUSIONS: Prolonged exposure to heat produces focal cellular reactions and disturbance of the myocyte membrane. The pathogenesis of the changes is as yet uncertain. It may be multifactorial and include calcium and/or oxygen derangements mediated by mast cells, catecholamines, hypothyroidism, and heat shock proteins.

Animals↗

Femoral fractures secondary to low velocity missiles: treatment with delayed intramedullary fixation.

The literature is replete with descriptions of the advantages of intramedullary nailing in the treatment of femoral fractures. However, little has been reported about the use of this method in femoral fractures resulting from gunshot wounds. Often, the amount of bony comminution and retained metal fragments have discouraged attempts at operative intervention. We reviewed our experience with 26 patients who had sustained low velocity gunshot fractures of the femur that were treated operatively with intramedullary fixation. After injury, the patients were stabilized in the emergency room and placed in balanced skeletal traction. They also received local wound care. When the patients recovered from associated injuries and the bullet wounds were healing, a delayed closed intramedullary nailing was performed. Nineteen patients were followed to union. Seventeen had fractures that united at an average of 4.5 months. One patient had a delayed union, and one had a nonunion. There were no deep wound infections and no cases of osteomyelitis. Range of motion was within 10 degree of the unaffected side in all but one patient, and there were neither rotatory nor angular deformities.

Adult↗