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Biomedical subjects

M Horowitz

Publications and source records attributed to M Horowitz.

At least 361 records · Page 20Linked to original sources

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

Adjuvant chemotherapy of high-grade osteosarcoma of the extremity. Updated results of the Multi-Institutional Osteosarcoma Study.

The Multi-Institutional Osteosarcoma Study (MIOS) was designed to determine whether intensive multiagent adjuvant chemotherapy improves the outcome of patients with nonmetastatic high-grade osteosarcoma of the extremity as compared with concurrent controls. After definitive surgery of the primary tumor, patients were randomly assigned to immediate adjuvant chemotherapy or to observation without adjuvant treatment. Updated results of this trial indicate that the projected six-year event-free survival for the control group is 11% compared to 61% for the chemotherapy group (p less than 0.001). Similar results were observed in patients who declined randomization but who were followed according to the treatment arms of the protocol. When randomized and nonrandomized patients are pooled according to assigned treatment, a survival advantage favoring those patients treated with immediate adjuvant chemotherapy is apparent. An analysis of prognostic factors among patients receiving immediate adjuvant chemotherapy reveals that elevation of the serum lactic dehydrogenase at diagnosis is the factor most predictive of adverse outcome. Location of the primary site in the tibia confers a favorable prognosis. The authors conclude that the natural history of high-grade osteosarcoma of the extremity has not changed over the past two decades. The administration of immediate adjuvant chemotherapy has a significant favorable impact on event-free survival and should be recommended for all such patients.

Adult↗

Gaucher disease: heterologous expression of two alleles associated with neuronopathic phenotypes.

To investigate the molecular basis for the distinct neuronopathic phenotypes of Gaucher disease, acid beta-glucosidases expressed from mutant DNAs in Gaucher disease type 2 (acute) and type 3 (subacute) patients were characterized in fibroblasts and with the baculovirus expression system in insect cells. Expression of the mutant DNA encoding a proline-for-leucine substitution at amino acid 444 (L444P) resulted in a catalytically defective, unstable acid beta-glucosidase in either fibroblasts from L444P/L444P homozygotes or in insect cells. This mutation was found to be homoallelic in subacute neuronopathic (type 3) Gaucher disease. In comparison, expression of the mutant cDNA encoding an arginine-for-proline substitution at amino acid 415 (P415R) resulted in an inactive and unstable protein in insect cells. This allele was found only in a type 2 patient with the L444P/P415R genotype. The substantial variation in the type 3 phenotype (L444P homozygotes) suggests the complex nature of the molecular basis of phenotypic variation in Gaucher disease. Yet, the association of neuronopathic phenotypes with alleles producing severely compromised (L444P) or functionally null (P415R) enzymes indicates that the effective level of residual activity at the lysosome is likely to be a major determinant of the severity of Gaucher disease.

Acute Disease↗

Effects of three different calcium preparations on urinary calcium and hydroxyproline excretion in postmenopausal osteoporotic women.

Some authors have claimed that 'solubilized' calcium preparations are better absorbed than calcium carbonate, while others have reported that all forms are equally well absorbed. We measured radiocalcium absorption in 35 postmenopausal osteoporotic women and then gave them on three successive evenings, in random order, three different proprietary calcium preparations (Sandocal containing 1 g of effervescent calcium, Calsup containing 1 g of calcium as the carbonate, and Caltrate containing 1.2 g of calcium as the carbonate). The daily urinary calcium excretion rose significantly and similarly on all three supplements and was greater in the high calcium absorbers than the low calcium absorbers. The fasting urinary hydroxyproline excretion was significantly decreased the morning after administration of each preparation, and one-way analysis of variance showed no significant difference between the days of administration or the type of supplement. The decrease was greater for high absorbers than for low absorbers on all three supplements but the differences did not reach statistical significance. By 36 hours after the last calcium supplement the urinary hydroxyproline had returned to baseline. The response of hydroxyproline excretion (and by implication bone resorption) appears to be rapid in onset and short lived. Strict compliance is therefore important in patients on calcium therapy.

Absorption↗