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Biomedical subjects

M Horowitz

Publications and source records attributed to M Horowitz.

At least 37 records · Page 2Linked to original sources
PubMed1991

Three unique base pair changes in a family with Gaucher disease.

Single-stranded cDNA was prepared from RNA obtained from a patient with type 1 Gaucher disease. The cDNA was amplified in vitro and analyzed by sequencing. Three base-pair changes were identified which included a G to C transversion at nucleotide 3119 of the active gene (Asp140----His), an A to C transversion at nucleotide 3170 (Lys157----Gln) and a G to A change at nucleotide 5309 (Glu326----Lys). To study the mode of inheritance of the three different base-pair changes, genomic DNA was prepared from blood or skin fibroblasts of several family members. Genomic glucocerebrosidase DNA sequences were amplified and subjected to hybridization with allele-specific oligonucleotides (ASOs). The hybridization profiles demonstrated that two of the base-pair changes originated from the mother and were transmitted to her two affected sons and to a grandchild, while the third base-pair change, originating from the father, was transmitted to his two affected sons, a carrier daughter and a second grandchild. Tests of other patients with Gaucher disease failed to disclose the presence of the three base-changes. This is a unique family with three base-pair changes tightly linked to Gaucher disease.

Base Composition↗
PubMed1991

Calcium absorption in normal and osteoporotic postmenopausal women.

Hourly fractional absorption of radiocalcium (alpha), serum calcitriol, and a number of other variables were measured in 152 normal and 148 osteoporotic postmenopausal women. Alpha, body weight, and serum albumin were all significantly lower in the osteoporotic than in the normal women, and plasma alkaline phosphatase, fasting urinary calcium, sodium, and hydroxyproline were all significantly higher in the osteoporotic than in the normal group. The most significant determinant of alpha in each group was the serum calcitriol concentration, but calcium absorption relative to serum calcitriol was significantly lower in the osteoporotic than in the normal women. The serum calcitriol level was slightly but not significantly lower in the osteoporotic than in the normal group and accounted for only 20% of the difference in alpha between them. The implied "resistance" to calcitriol in the osteoporotic group was significantly related to serum albumin and body weight but independent of age. Urinary hydroxyproline was an inverse function of alpha and a positive function of fasting urinary calcium in the osteoporotic group.

Absorption↗
PubMed1991

Tumors of the central nervous system. Improvement in outcome through a multimodality approach.

More children with CNS tumors will continue to be cured of their neoplasms as a result of improved surgical, radiotherapeutic, and chemotherapeutic intervention. The complex problems seen in these patients mandate their treatment at academic centers actively involved in therapeutic investigations and capable of providing comprehensive multidisciplinary care.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Effect of insulin-induced hypoglycaemia on antral, pyloric and duodenal motility in fasting subjects.

1. Hyperglycaemia alters gastric motility and delays gastric emptying. By contrast, there is little information regarding the effect of sub-normal blood glucose concentrations on gastric and, in particular, pyloric motility, although limited data suggest that hypoglycaemia is associated with accelerated gastric emptying despite an apparently increased basal pyloric pressure. 2. To determine the effects of hypoglycaemia on pyloric motility, we compared the effects of an intravenous injection of insulin (0.15 units/kg) with those of a placebo injection of saline in eight healthy human volunteers during phase I of the interdigestive migrating motor complex. 3. All subjects developed profound hypoglycaemia (mean blood glucose concentration 1.6 mmol/l compared with 4.0 mmol/l in the control group). 4. There was no significant difference in the number of antral (9 versus 7, P = 0.34), pyloric (3 versus 0, P = 0.31) or duodenal (21 versus 13, P = 0.42) pressure waves or in the basal pyloric pressure (0.3 mmHg versus 0.1 mmHg, P = 0.37) in the 45 min after insulin injection (hypoglycaemia) when compared with the 45 min after saline injection (euglycaemia). In both the euglycaemic and hypoglycaemic studies there was a time-dependent increase in the numbers of antral and duodenal waves consistent with the expected changes in the interdigestive migrating motor complex. 5. These results indicate that insulin-induced hypoglycaemia has no significant effect on pyloric motility during phase I of the interdigestive migrating motor complex.

Adolescent↗
PubMed1991

Cross sectional and longitudinal study of bone mineral content of the distal forearm in adult premenopausal women.

The range of fat corrected distal forearm mineral content (FMC) (at a site which comprises approximately 75% cortical and 25% trabecular bone) and the effect of aging on FMC were determined in normal premenopausal women. In 106 women (mean age 39; range 18-56) the mean FMC was 1.184 (SD 148) g/cm; fat correction increased this to 1.239 (SD 148) g/cm. There were significant correlations between fat corrected FMC and height, weight and BMI (r greater than 0.16; P less than 0.05). In 43 of these women (mean age 35; range 18-51) repeat measurements of FMC were performed. The last measurement was separated from the first by a mean time interval of 27 +/- 3 months. There was no significant change in uncorrected FMC (baseline 1.185 +/- 0.21 g/cm compared with their final measurement 1.182 +/- .020 g/cm; P = 0.51). Fat-corrected FMC (baseline 1.229 +/- .021 g/cm compared with 1.223 +/- .020 g/cm later) tended to decrease although this change was not significant (P = 0.06). Age ranked cusum analysis demonstrated a non-significant fat-corrected rate of change in FMC of -.3% yr in those over 35 years of age (P less than 0.10). This data suggests that if there is any distal forearm bone loss before the menopause it is negligible.

Adolescent↗
PubMed1991

The effect of short-term dietary supplementation with glucose on gastric emptying in humans.

In order to test whether gastric motility can adapt to changes in nutrient load, gastric emptying of hyperosmotic glucose and protein drinks was measured by applied potential tomography in two groups of ten volunteers following dietary supplementation with 400 g glucose/d for 3 d. The half emptying time for the glucose test meal was significantly faster after the standard diet had been supplemented with glucose compared with the standard diet alone (median and range, 20.7 (4.6-36.8) v. 29.1 (19.8-38.4) min; P less than 0.05), while the emptying of the protein drink (Oxo; Brooke Bond Ltd) was unchanged (median and range, 18.0 (12.5-23.6) v. 16.1 (9.6-22.7) min). These results suggest that rapid and specific adaptation of the small intestinal regulatory mechanisms for gastric emptying of nutrient solutions can occur in response to increases in dietary load. This adaptation may be explained by desensitization of nutrient receptors or by a reduction in the area of receptor field exposed to nutrients caused by increased absorption of glucose in the upper small intestine.

Adult↗
PubMed1991

Relations among autonomic nerve dysfunction, oesophageal motility, and gastric emptying in gastro-oesophageal reflux disease.

Recent studies suggest that vagal nerve dysfunction may be important in the aetiology of gastro-oesophageal reflux disease. Delayed oesophageal transit and slowed gastric emptying occur frequently and may also be of pathogenic importance. In 48 patients with gastro-oesophageal reflux disease we studied the prevalence of and relations between autonomic nerve dysfunction (as assessed by cardiovascular reflex tests) and oesophageal transit, oesophageal motility, gastric emptying, and endoscopic grade of oesophagitis. Of the 48 patients, 21 (44%) had abnormal autonomic nerve function, which was predominantly parasympathetic. Oesophageal transit was delayed in 28% of the patients and gastric emptying of the solid component of the meal was delayed in 46%. Oesophageal transit was significantly (p less than 0.007) slower in patients with abnormal autonomic nerve function. The percentage of synchronous oesophageal contractions was related to the score for autonomic nerve dysfunction (r = 0.40, p less than 0.05). There was no significant relation of autonomic nerve dysfunction to either delayed gastric emptying or endoscopic grade of oesophagitis. We conclude that in gastro-oesophageal reflux disease there is a high prevalence of parasympathetic nerve dysfunction which relates to delayed oesophageal transit and abnormal peristalsis and may therefore be of pathogenic importance.

Adult↗
PubMed1991

Hyperglycaemia stimulates pyloric motility in normal subjects.

The motor correlates of the delay in gastric emptying produced by hyperglycaemia were investigated in 11 healthy volunteers. Fasting gastroduodenal motility was measured during euglycaemia (blood glucose concentration 3-5 mmol/l) and during hyperglycaemia induced by intravenous dextrose (blood glucose concentration 12-16 mmol/l). Antral, pyloric, and proximal duodenal pressures were recorded by a sleeve/sidehole manometric assembly positioned across the pylorus, with the aid of measurements of transmucosal potential difference. During hyperglycaemia there was stimulation of isolated pyloric pressure waves when compared with the euglycaemia period (p less than 0.05). This was associated with inhibition of antral pressure waves (p less than 0.05). In nine of the 11 subjects an episode of duodenal 'phase III like' activity occurred within 15 minutes of the onset of hyperglycaemia. It is proposed that the stimulation of localised pyloric contractions and inhibition of antral contractions contribute to the delayed gastric emptying induced by hyperglycaemia. Abnormal gastric motility in patients with diabetes mellitus may be the result of hyperglycaemia itself, rather than irreversible autonomic neuropathy.

Adolescent↗
PubMed1991

Gastrointestinal adaptation to diets of differing fat composition in human volunteers.

The effect of a low fat diet (9 MJ) v a high fat diet (19.26 MJ), each consumed separately for four and 14 days, on gastric emptying and mouth to caecum transit time of a high fat test meal and body weight and satiety were examined in groups of 10 and six normal male volunteers. The half time for gastric emptying (t1/2) and the mouth to caecum transit time of a high fat test meal was significantly faster after the high fat diet than the low fat diet when consumed for 14 days (t1/2=98 (80-116) v 147 (88-206) minutes (median (range)), p less than 0.05; mouth to caecum transit time 240 (130-350) v 360 (200-520) minutes, p less than 0.05), but not when consumed for only four days. The mean (SEM) body weight of all subjects significantly increased during the 14 day high fat diet (74.7 (1.3) v 72.7 (1.6) kg, p less than 0.05) but was not influenced during the consumption of the low fat diet. When subjects were given an appetising meal to consume on the day that they had consumed the transit test meal, they ate similar amounts irrespective of their recent dietary history, though the eating rate was significantly slower after the high fat diet (mean (SEM)) 46.7 (1.9) v 71.3 (14.8)/min, p less than 0.05). Maintaining normal subjects on a high or low fat diet for two weeks resulted in a desensitisation or sensitisation respectively of the mechanisms by which nutrients regulate gastrointestinal transit. These findings emphasise the importance of the recent dietary history in the interpretation of gastric emptying and small bowel transit time data.

Adaptation, Physiological↗
PubMed1991

Role of the proximal and distal stomach in mixed solid and liquid meal emptying.

The role of the proximal and distal stomach in the emptying of solids and liquids from the stomach remains unclear. We have used a dual isotope technique to quantify proximal and distal stomach emptying of a solid (100 g of 99mTc labelled liver/ground beef) liquid (either 200 ml of normal saline (eight subjects) or 25% dextrose (seven subjects) labelled with 113mIn-diethylenetriaminepenta-acetic acid) mixed meal. A manometric catheter simultaneously measured antral, pyloric, and duodenal motor activity. The liquid component dispersed rapidly throughout the stomach and emptied after a minimal lag period. The emptying of the 25% dextrose was delayed compared with the saline. This delay was associated with increased retention of the liquid in the distal stomach, a significant increase in localised phasic pyloric contractions, and a suppression of antral contractions. The solid component initially resided wholly within a proximal stomach reservoir area. Solids then redistributed from proximal to distal stomach during the emptying of liquid from the stomach. Dextrose delayed gastric emptying of solids compared with saline by increasing the solid lag period and retention in the proximal stomach. There was no significant difference between saline and dextrose meals in the distal stomach retention of solid or in the linear rate of emptying after the lag period. We conclude that, contrary to general opinion, the proximal stomach plays an important role in the control of gastric emptying of solids while the distal stomach is important in the emptying of nutrient liquids.

Adolescent↗
PubMed1991

Autourethrography.

"Autourethrography," a technique of retrograde urethrography in which the patient injects the contrast material, was used on 22 patients. The results of the study were compared with the results of nonemergency retrograde urethrography performed on 22 patients during an earlier 1-year period. The following observations of the autourethrography group were made. Patient tolerance was enhanced, with less discomfort and anxiety. There was no extravasation of contrast material outside the urethra, compared with extravasation in three of 22 patients (14%) in the control group for whom conventional techniques were used. Retrograde opacification of the posterior urethra was achieved in 20 of 22 patients (91%) in the autourethrography group, compared with 13 of 22 patients (59%) in the control group. Radiation exposure to the examining radiologist was eliminated. Autourethrography is a technique that has important benefits for both the radiologist and the patient.

Adult↗
PubMed1991

Heat stress and thermal dehydration: lactacidemia and plasma volume regulation.

This investigation was undertaken to study heat stress and dehydration effects on 1) plasma lactic acid (LA) concentration and 2) plasma LA effect on plasma volume conservation during thermal dehydration. Experiments were performed on conscious nonacclimated and heat-acclimated laboratory rats subjected to various levels of heat stress and/or dehydration (37-42 degrees C with and without drinking water). During the exposures, rectal temperature (Tre), plasma LA pyruvic acids, and hematocrit were measured. From these data, excess LA, indicative of anaerobic metabolism, was calculated. In separate experiments, transvascular protein efflux (half time of Evans blue-labeled albumin) was measured before and after plasma LA elevation, either by LA infusion or thermal dehydration. The results show that elevation of plasma LA was associated with a rise in Tre, with accelerated elevation within a Tre range of 41-42 degrees C. LA concentrations were similar for the same Tre in all experimental groups. In nonacclimated rats, this rise was accompanied by a significant rise in excess LA. In acclimated rats, only a minor rise in excess LA was observed. A positive correlation was found between plasma LA elevation and the increase in plasma protein efflux. It is concluded that there is a temperature threshold for the rise in plasma LA. In nonacclimated rats, local hypoxia may contribute to this rise. The data also suggest that, in nonacclimated rats, lactacidemia accelerates plasma protein and fluid loss, leading to circulatory failure during acute thermal dehydration.

Acclimatization↗
PubMed1991

Molecular aspects of Gaucher disease.

Gaucher disease is the most common sphingolipid storage disorder. Due to its high prevalence it may appear with a nonrelated neurological disease and be misinterpreted as Gaucher type 3. A family is described in which 2 Gaucher brothers presented different clinical signs. Molecular analysis has shown that both carried two mutated alleles. One allele had a G to C transversion at nucleotide 3119 of the active gene (Asp140-His) while the other presented two base pair changes, an A to C transversion at nucleotide number 3170 (Lys157-Gly), and a G-A transition at nucleotide number 5309 (Glu324-Lys). Therefore, both presented the same type of Gaucher disease which was accompanied with a nonrelated neurological disease in one of them. Molecular diagnosis of 161 patients has provided a relative abundance of different mutations among Jewish and non-Jewish patients and allowed some genotype-phenotype correlation. Differential expression of the murine glucocerebrosidase activator gene (the prosaposine) has been demonstrated using Northern technique and in situ hybridization. High expression levels were observed in the brain and testes. In the testes the prosaposine expression was confined to the supporting cells. In the female gonad prosaposine expression has also been shown, in the corpus luteum. In a 12 1/2-day-old embryo, prosaposine gene expression was detected mainly in brain stem, in dorsal ganglia and in the genital ridge.

Adolescent↗
PubMed1991

Evidence for a renal calcium leak in postmenopausal women.

We have measured calcium, albumin, globulin, bicarbonate, and anion gap in the plasma; and calcium, sodium, and creatinine in the urine, in 115 premenopausal and 140 postmenopausal normal women after an overnight fast, and calculated the calcium fractions in the plasma and the calcium/and sodium/creatinine ratios in the urine. The total ultrafiltrable calcium was significantly higher in the postmenopausal group, mainly due to their higher complexed calcium fraction, due in turn to their higher bicarbonate and anion gap concentrations. Urinary calcium was also significantly higher in the postmenopausal group even after correcting for sodium. After matching for total calcium and each of the calcium fractions in turn, the urinary calcium remained significantly higher in the post- than in the premenopausal sets even after correction for sodium. The implication is that the rise in urinary calcium at the menopause is due to reduced tubular reabsorption of calcium rather than to an increase in filtered load. We suggest that estrogens promote tubular reabsorption of calcium and that the rise in bone resorption at the menopause could be accounted for, at least in part, by the effect of estrogen deficiency on the kidney.

Acid-Base Equilibrium↗
PubMed1991

Comparative effects of duodenal and ileal intubation on gastric emptying and postprandial antral, pyloric, and duodenal motility.

The influence of gastric and small-intestinal intubation on fed patterns of antropyloroduodenal motility and gastric emptying of a solid meal has been investigated in normal volunteers. In 10 subjects a manometric assembly was passed as far as the fourth part of the duodenum; in 8 other subjects the terminal ileum was intubated; and a further 8 subjects were not intubated. The manometric assemblies were similar, apart from their length, and both incorporated a sleeve/side hole assembly located across the pylorus. All subjects ingested a meal of 100 g 99mTc-labelled liver/ground beef. There was no significant difference in either the lag phase or the linear emptying phase of gastric emptying between the control and duodenal intubation groups. The emptying phase of the test meal, but not the lag phase, was slower (p less than 0.01) in the ileal intubation group than in the non-intubated and duodenal intubation groups. There were fewer (p less than 0.01) antral pressure waves in the ileal than in the duodenal intubation group. We conclude that ileal but not duodenal intubation has an important inhibitory influence on gastric emptying and antral motility.

Adult↗