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Biomedical subjects

M Horowitz

Publications and source records attributed to M Horowitz.

At least 217 records · Page 12Linked to original sources
PubMed1997

Effects of small intestinal nutrient infusion on appetite and pyloric motility are modified by age.

The mechanisms responsible for the reduction in appetite and slowing of gastric emptying in older persons are unknown. The aims of this study were to evaluate the effects of aging on small intestinal regulation of appetite and pyloric motility. Eight healthy older (age 65-75 yr) and seven healthy young (age 20-34 yr) male subjects received isocaloric (2.9 kcal/min) intraduodenal infusions of lipid and glucose for 120 min, each on separate days. During the intraduodenal infusions, perceptions of hunger, desire to eat, and fullness were assessed by visual analog scales. Pyloric motility (isolated pyloric pressure waves and tonic pyloric pressure) was measured by manometry during the intraduodenal lipid infusion. On each day, after completion of the intraduodenal nutrient infusion the subject was offered a buffet meal and food intake was quantified. Before intraduodenal nutrient infusions, sensations of hunger (P < 0.01) and desire to eat (P < 0.05) were less in the older compared with the young subjects. In the young, intraduodenal lipid suppressed hunger to a greater extent than intraduodenal glucose (P < 0.05). In older persons, neither intraduodenal nutrient infusion suppressed hunger. Intraduodenal lipid and glucose increased fullness in both age groups (P < 0.05 for both), with no significant difference between the two nutrients. There was no significant difference in food intake from the buffet meal between the elderly and young subjects. Intraduodenal lipid infusion stimulated phasic pyloric pressure waves in both age groups (P < 0.01 for both), and this response was greater (P < 0.05) in older persons. There was an increase (P < 0.01) in tonic pyloric pressure during intraduodenal lipid infusion that was not significantly different between the two age groups. We conclude that the effect of small intestinal lipid infusion on hunger is attenuated, and the stimulation of phasic pyloric pressure waves increased in healthy older persons compared with healthy young males. Increased feedback from small intestinal nutrients does not appear to be responsible for the physiological anorexia of aging.

Adult↗
PubMed1997

Blood glucose concentration influences postprandial fullness in IDDM.

OBJECTIVE: Upper gastrointestinal (GI) symptoms and delayed gastric emptying both occur frequently in patients with long-standing IDDM, but the relationship between them is relatively weak. Recent studies in normal subjects have indicated that blood glucose concentration may increase the perception of sensations arising from the upper GI tract. The purpose of this study was to examine the relationships among postprandial fullness, the rate of gastric emptying, and blood glucose concentration in IDDM patients. RESEARCH DESIGN AND METHODS: We studied measurements of gastric emptying, blood glucose concentrations, cardiovascular autonomic nerve function, upper GI symptoms, and postprandial hunger and fullness in 40 IDDM patients (16 men, 24 women). ages 19-63 years. Gastric emptying of solids and liquids was measured scintigraphically, upper GI symptoms were measured by questionnaire immediately before ingestion of the test meal, and fullness and hunger were measured by visual analog scales every 15 min. Blood glucose concentrations were measured at -5, 30, 60, 90, and 120 min. RESULTS: Solid gastric emptying was delayed in 58% of the patients, and both solid and liquid gastric emptying were slower (P < 0.05) in women than in men. The score for upper GI symptoms was not significantly related to gastric emptying. In contrast, postprandial fullness, but not hunger, was related to the amount of solid (r = 0.36, P < 0.05) but not liquid in the stomach. Both before (r = 0.39, P < 0.05) and after (r = 0.47, P < 0.01) the meal, fullness was related to blood glucose concentration. Postprandial fullness was also related to autonomic nerve dysfunction (r = 0.39, P < 0.05). Multiple regression analysis confirmed that blood glucose concentration, the rate of solid gastric emptying, and autonomic nerve dysfunction were independent determinants of postprandial fullness, together accounting for 47% of the variance. CONCLUSIONS: These observations demonstrated that, in IDDM, postprandial fullness is influenced by blood glucose concentration, the rate of solid gastric emptying, and autonomic nerve function.

Adult↗
PubMed1997

Effects of fractionated abdominal irradiation on small intestinal motility--studies in a novel in vitro animal model.

Disordered small intestinal motility occurs frequently during acute radiation enteritis. However, the characteristics and time course of the motor dysfunction are poorly defined. These parameters were assessed in a novel animal model of radiation enteritis. Ileal pressures were recorded in vitro with perfused micromanometric catheter using an arterially perfused ileal loop in 22 ferrets following fractionated abdominal irradiation (9 doses 2.50 Gy thrice weekly for 3 weeks). Tissue damage was graded histologically. Studies were performed 3 to 29 days after irradiation. Tissue from 7 control animals was also studied. All treated animals developed diarrhoea. Histology showed changes consistent with mild to moderate radiation enteritis. Following irradiation, there was an initial increase in frequency followed by a non-significant reduction in the frequency, but not the amplitude of ileal pressure waves. The frequency of pressure waves showed an inverse relationship with time after radiation (r = -0.634, p < 0.002). There was no relationship between motility and histology. We conclude that abdominal irradiation is associated with a time-dependent reduction in ileal motility which does not correlate with light microscopic changes.

Animals↗
PubMed1997

Does electrothrombosis occur immediately after embolization of an aneurysm with Guglielmi detachable coils?

Current options for treating cerebral aneurysms include surgical clipping and placement of Guglielmi detachable coils (GDCs). The latter system is reported to induce acute aneurysmal occlusion by a mechanism of electrothrombosis. We report our observations in the case of a ruptured aneurysm treated with GDCs and then surgically exposed 2 hours later. The lack of thrombus within the aneurysm and around the coils led us to question the mechanism of action of GDCs.

Aneurysm, Ruptured↗
PubMed1997

Periurethral collagen injection for the treatment of urinary incontinence in children.

PURPOSE: We assessed the efficacy and safety of periurethral collagen injection for urinary incontinence in children with neurogenic bladder dysfunction. MATERIALS AND METHODS: We treated 11 children (mean age 10.6 years) who had incontinence and neurogenic bladder dysfunction with periurethral injections of glutaraldehyde cross-linked collagen. All patients were on anticholinergics and all but 1 were on clean intermittent catheterization preoperatively. Four patients had previously undergone augmentation cystoplasty. All patients were assessed before and after injection with a subjective continence scale and multichannel urodynamics. Followup ranged from 4 to 20 months from the last injection. RESULTS: Mean group Valsalva leak point pressure was 34.5 cm. water. Four of the 11 patients had an identifiable detrusor leak point pressure. Overall success rate was 55% with 4 patients dry and 2 improved. Success correlated with a minimum increase in Valsalva leak point pressure of 20 to 25 cm. water to greater than 60 cm. water. Three patients had no demonstrable Valsalva leak point pressure after injection. All 5 patients in whom treatment failed had no change in Valsalva leak point pressure, including 2 with small capacity, poorly compliant bladders preoperatively. Because they had a component of sphincteric insufficiency, they underwent injection in the hope of increasing capacity with increased continence. In 3 patients Valsalva leak point pressure was greater than 50 cm. water. Detrusor leak point pressure developed in 3 patients postoperatively, including 1 with significantly increased Valsalva leak point pressure. One patient with significantly increased Valsalva leak point pressure had urethral hypermobility postoperatively. Of the 3 patients who subsequently underwent augmentation cystoplasty 1 is now dry, 1 is wet and 1 died of complications unrelated to urological disease. Patients underwent 1 to 4 procedures (mean 2.5). CONCLUSIONS: Periurethral collagen injection may be effective for urinary incontinence in patients who have adequate capacity with good compliance and low Valsalva leak point pressure. When there is no response to repeat injections or a transient response, one should consider the possibility of bladder decompensation.

Adolescent↗
PubMed1996

A retrospective study of the effects of pelvic irradiation for gynecological cancer on anorectal function.

PURPOSE: To evaluate the prevalence of anorectal dysfunction following therapeutic pelvic irradiation. METHODS AND MATERIALS: Anorectal function was evaluated in 15 randomly selected patients (aged 47-84 years) who had received pelvic irradiation for treatment of carcinoma of the uterine body and cervix 5 and 10 years earlier. The following parameters were assessed in each patient: (a) anorectal symptoms (questionnaire), (b) anorectal pressures at rest and in response to rectal distension, voluntary squeeze, and increases in intraabdominal pressure (multiport anorectal manometry with concurrent electromyography of the anal sphincters), (c) rectal sensation (rectal balloon distension) and, (d) anal sphincteric morphology (ultrasound). Results were compared with those obtained in nine female control subjects. RESULTS: Ten of the 15 patients had urgency of defecation and 4 also suffered fecal incontinence. Basal anorectal pressures measured just proximal to the anal canal (p = 0.05) and anorectal pressures generated in response to voluntary squeeze measured at the anal canal were less (p < 0.01) in the patients. The fall in anal pressures in response to rectal distension was greater in the patients (p < 0.05) and the desire to defecate occurred at lower rectal volumes (p < 0.05). The slope of the pressure/volume relationship in response to rectal distension was greater (p < 0.05) in the patients, suggestive of a reduction in rectal compliance. In 14 of the 15 patients at least one parameter of anorectal motor function was outside the control range. There was no difference in the thickness of the anal sphincters between the two groups. CONCLUSION: Abnormal anorectal function occurs frequently following pelvic irradiation for gynecological malignant diseases and is characterized by multiple dysfunctions including weakness of the external anal sphincter, stiffness of the rectal wall, and a consequent increase in rectal sensitivity.

Adult↗
PubMed1996

Overexpression of human glucocerebrosidase containing different-sized leaders.

Gaucher disease results from impaired activity of the lysosomal enzyme glucocerebrosidase. Aiming at overexpressing the human glucocerebrosidase and testing the efficiency of the two in-frame ATGs of its gene in directing synthesis of an active enzyme, it was coupled to the T7 RNA polymerase promoter in a vaccinia virus-derived expression vector (pTM-1). cDNAs containing either one or both ATGs of the glucocerebrosidase mRNA were linked to the T7 polymerase promoter. Recombinant viruses were produced and used for infecting human cells in tissue culture. The results demonstrated that both ATGs directed translation of active glucocerebrosidase, resulting in a 10-fold increase in enzymic activity. Most of the protein remained sensitive to endoglycosidase H. The active enzyme represented a small fraction of the expressed glucocerebrosidase. The recombinant enzyme had the same Km and optimal pH towards the artificial substrate 4-methylumbelliferyl glucopyranoside as the authentic endogenous human enzyme. Measurements of intracellular enzymic activity directed by the cDNAs with either one or both ATGs in cells loaded with a fluorescent glucosylceramide demonstrated a 30% increase in activity directed by the cDNAs containing the first ATG over that containing the second ATG. This indicates that the protein synthesized from the first ATG, with a 38 amino acid leader, is translocated through the endoplasmic reticulum more readily than its counterpart directed by the second ATG, with a 19 amino acid leader. The elevation in glucocerebrosidase activity and the reproducibility of the data leads us to propose the use of the vaccinia virus-derived expression system as a tool for studying glucocerebrosidase mutants in Gaucher disease.

Bacteriophage T7↗
PubMed1996

Regional bone mineral density interrelationships in normal and osteoporotic postmenopausal women.

We describe a prospective study in which bone mineral density (BMD) was measured in total body and regions, proximal femur, lumbar spine, and forearm in 84 apparently normal postmenopausal women with normal spinal radiographs and in 47 women with 1-10 wedged or compressed vertebrae. There was a history of peripheral fracture in 35 of the 84 controls and 30 of the 47 osteoporotics (p < 0.02) but there was no association between vertebral fracture and wrist fracture. At all sites and regions, the differences in BMD between the "normal"and "osteoporotic" women was highly significant and all but "ribs" and "arms" remained significant after correction for menopausal age. In the whole set, and in both subgroups, the coefficients of correlation between sites and regions were all highly significant (p < 0.001). Nonetheless, some sites discriminated better between the two groups than others. Standardized odds ratios (OR) for vertebral fracture versus no-fracture were calculated by logistic regression and expressed as the rise in OR for each standard deviation (SD) fall in bone density. This ratio was greatest (3.4) in "pelvis" and weakest (1.7) in "ribs" but all were statistically significant. Geometric mean regression equations were calculated for all the 78 possible pairs of sites and regions in the 84 normal subjects and the deviations of the osteoporotic women from these normal slopes calculated. In most pairs of sites and regions, the vertebral fracture cases were scattered around the normal group's slope but fell lower down on both axes. The bone deficits in the osteoporotics compared with young normal women ranged from -14% in "head" to -40% in Ward's triangle and the T-scores ranged from -1.9 in "ribs" to -3.9 in the forearm. Sensitivity ranged from 17% in "ribs" to 36.2% in Ward's triangle. Specificity varied between 88 and 94% and the percent correctly classified ranged from 62.6% in "ribs" to 72.5% in Ward's triangle. We conclude that primary postmenopausal osteoporosis affects the entire skeleton but that some sites discriminate better between vertebral fracture and nonfracture cases regardless of whether they represent cortical or trabecular bone.

Absorptiometry, Photon↗
PubMed1996

The glucocerebrosidase D409H mutation in Gaucher disease.

Gaucher disease, resulting from the decreased activity of the lysosomal enzyme glucocerebrosidase, is the most prevalent sphingolipid storage disease. Due to considerable heterogeneity of phenotypic expression, it has been subdivided into the nonneurological type 1 disease, and types 2 and 3, the neurological types. We describe homozygosity for the D409H mutation within the glucocerebrosidase gene associated with a unique form of type 3 Gaucher disease. Twelve patients, originating from three Arab sibships, were found to be homozygous for the D409H mutation. They all presented with oculomotor apraxia and a progressive cardiac valve defect with minimal organomegaly. When expressed in human cells in tissue culture, using the T7/EMC/vaccinia virus hybrid expression system, we were able to demonstrate that the mRNA carrying the D409H mutation was less stable than the normal counterpart. Pulse-chase experiments demonstrated that the mutated protein exhibited lower stability than the normal counterpart. Its activity toward the artificial substrate 4-methyl umbelliferyl glucopyranoside was similar to that of the mutated enzymes carrying the N370S or the L444P mutations. However, in loading experiments using lissamine-rhodamine conjugated glucosyl ceramide as a substrate, the recombinant mutated protein carrying the D409H mutation exhibited 28.63 +/- 6.05% of the activity exhibited by the normal enzyme. L444P and N370S mutations exhibited 51.90 +/- 7.16 and 115.75 +/- 12.64% of normal enzyme activity, respectively. Loading of cells homozygous for the D409H mutation demonstrated 10. 05% of the activity shown by normal cells. L444P and N370S homozygous cells demonstrated 25.3 and 98.5% of foreskin fibroblast glucocerebrosidase activity, respectively. We demonstrate that homozygosity for the D409H mutation is a unique case of a peculiar phenotype associated with a specific intracellular glucocerebrosidase activity.

DNA, Complementary↗
PubMed1996

Purification and characterization of plasma vitamin D binding protein from the snapping turtle, Chelydra serpentina.

Vitamin D binding protein (DBP) was isolated from the plasma of the snapping turtle, Chelydra serpentina (mixed sex adult), and compared with the previously characterized dual function binding plasma protein that binds both thyroxine (T4) and vitamin D (tsTDBP) in an emydid turtle, Trachemys scripta. Purification of Chelydra serpentina DBP (csDBP) was accomplished by ion exchange chromatography, preparative polyacrylamide gel electrophoresis, and reverse-phase high-performance liquid chromatography. Estimates of increased purification (ca. 71-fold), recovery (ca. 1.5%), and corresponding plasma concentration (ca. 0.6 mg/ml) are confounded by interference with other proteins. A protein was identified that showed the same high affinity for 25-OH-cholecalciferol (vitamin D3) as the tsTDBP, and the two exhibited similar heat resistances in binding. The csDBP and tsTDBP had similar molecular weights by SDS-PAGE (ca. 58 kDa), showed immunological cross reactivity, and differed by only three residues, representing conservative substitutions, in the 30 NH2-terminal amino acid sequence. A slightly lesser homology (up to 89% similarity based on conservative substitutions) was seen with three mammalian DBPs. However, unlike tsTDBP, the DBP from the snapper did not bind T4. These data support the view that the DBP of emydid turtles secondarily evolved a second T4 binding site, and this is probably independent of the D3 binding domain.

Amino Acid Sequence↗
PubMed1996

The effect of short-term dietary supplementation with glucose on gastric emptying of glucose and fructose and oral glucose tolerance in normal subjects.

Recent observations indicate that gastric emptying may be influenced by patterns of previous nutrient intake. The aims of this study were to determine the effects of a high glucose diet on gastric emptying of glucose and fructose, and the impact of any changes in gastric emptying on plasma concentrations of glucose, insulin and gastric inhibitory polypeptide in response to glucose and fructose loads. Gastric emptying of glucose and fructose (both 75 g dissolved in 350 ml water) were measured in seven normal volunteers on separate days while each was on a "standard' diet and an identical diet supplemented with 440 g/day of glucose for 4-7 days. Venous blood samples for measurement of plasma glucose, insulin and gastric inhibitory polypeptide levels were taken immediately before and for 180 min after ingestion of glucose and fructose loads. Dietary glucose supplementation accelerated gastric emptying of glucose (50% emptying time 82 +/- 8 vs 106 +/- 10 min, p = 0.004) and fructose (73 +/- 9 vs 106 +/- 9 min, p = 0.001). After ingestion of glucose, plasma concentrations of insulin (p < 0.05) and gastric inhibitory polypeptide (p < 0.05) were higher during the glucose-supplemented diet. In contrast, plasma glucose concentrations at 60 min and 75 min were lower (p < 0.05) on the glucose-supplemented diet. We conclude that short-term supplementation of the diet with glucose accelerates gastric emptying of glucose and fructose, presumably as a result of reduced feedback inhibition of gastric emptying from small intestinal luminal receptors. More rapid gastric emptying of glucose has a significant impact on glucose tolerance.

Adult↗
PubMed1996

The effect of acute hyperglycaemia on small intestinal motility in normal subjects.

The effects of hyperglycaemia on postprandial small intestinal motor activity are unclear. Duodenal and jejunal pressures and duodeno-caecal transit were measured in eight healthy male volunteers during euglycaemia (blood glucose 4-6 mmol/l) and hyperglycaemia (blood glucose 12-15 mmol/l). Duodenal and jejunal pressures were recorded with a manometric assembly during intraduodenal infusion of 100 ml nutrient liquid comprising 14% protein, 31.5% fat and 54.5% carbohydrate together with 15 glactulose. Duodeno-caecal transit was determined by a breath hydrogen technique. The number of duodenal (p < 0.05) and jejunal (p < 0.01) pressure waves, excluding phase III episodes was reduced during hyperglycaemia compared to euglycaemia Hyperglycaemia was associated with earlier onset of phase III activity (30 +/- 12 vs 132 +/- 20 min; p < 0.05) Duodeno-caecal transit was slower during hyperglycaemia when compared to euglycaemia (114 +/- 17 vs 49 +/- 6 min, p < 0.01). We conclude that induced hyperglycaemia has major effects on postprandial small intestinal motility. The reduction in duodenal and jejunal motor activity is likely to explain the retardation of small intestinal transit during hyperglycaemia.

Acute Disease↗
PubMed1996

Endourologic removal of upper airway foreign objects: case report.

The authors report on removal of upper airway foreign bodies using endourology baskets and stone graspers in a patient who did not respond to standard upper airway management. The procedure was safe and effective with localization and successful removal of most of the stone burden.

Bronchi↗
PubMed1996

Intracavernous carotid artery aneurysms: the possible importance of angiographic dural waisting. A case report.

BACKGROUND: Cavernous carotid aneurysms are generally benign entities. Certain indications exist for their treatment, however, including transient ischemic events, subarachnoid hemorrhage or risk of subarachnoid hemorrhage, epistaxis or its risk, ophthalmoplegia, pain, and progressive visual loss. We feel certain angiographic features may indicate a greater likelihood that cavernous carotid aneurysms extend into the subarachnoid space, thus making their rupture a life-threatening event. METHODS: A case report of an intracavernous carotid aneurysm, which at surgery extended into the subarachnoid space, is described. RESULTS: In this particular case, deformation of the aneurysm (waisting) as seen at angiography was in retrospect an indication that the cavernous carotid aneurysm extended into the subarachnoid space, either through the dural ring or through the eroded dural roof of the cavernous sinus. This finding was verified at surgery when the lesion was explored and trapped. CONCLUSION: Angiographic waisting of a cavernous carotid aneurysm may indicate that the aneurysm extends into the subarachnoid space. Such extension means that rupture would be a life-threatening event. While deformation of the aneurysm may be secondary to compression against the optic nerve or anterior clinoid process with an intact layer of dura overlying the aneurysm, the neurosurgeon confronted with such findings should analyze such lesions carefully and consider surgical exploration.

Aged↗
PubMed1996

Vitamin D receptor genotypes are related to bone size and bone density in men.

Three restriction fragment length polymorphisms in the vitamin D receptor gene have been associated with a low bone density in twin and female population studies, but no studies have been conducted exclusively in men. We studied 146 normal men aged 20-83 years. Bone density was measured in the spine, hip, whole body and forearm, and the Bsm polymorphism for the vitamin D receptor was detected by the polymerase chain reaction. Men with genotype BB tended to have a lower bone density at all but one site than the other genotypes. In the men < or = 50 years of age bone density in the forearm was 7% lower in the BB than the Bb and bb groups (P = 0.030) but bone mineral content did not differ between the groups. Bone area was greater in the BB genotype at all sites. This was statistically significant in the forearm (P = 0.026). We conclude that BB genotype is associated with lower bone density in men, which may be due to larger bone size rather than reduced bone mass.

Absorptiometry, Photon↗
PubMed1996

Comparative urodynamic findings after primary valve ablation, vesicostomy or proximal diversion.

PURPOSE: There is little known about the effect of urinary diversion on the bladder of children with posterior urethral valves. There is a fear that diversion may result in contracted noncompliant bladders. We wished to compare urodynamic parameters in patients who underwent primary ablation of posterior urethral valves and in those who underwent diversion in the form of vesicostomy or pyelostomy. MATERIALS AND METHODS: Urodynamics were done in 32 boys with a history of posterior urethral valves divided into 3 groups based on initial treatment: 1) transurethral valve ablation; 2) cutaneous vesicostomy, subsequent closure and valve ablation, and 3) proximal cutaneous pyelostomy, subsequent reconstitution and valve ablation. RESULTS: Patients who underwent initial diversion with vesicostomy or pyelostomy had bladders with larger functional capacity, better compliance and less instability. Chronic renal failure developed in 25% of the patients who underwent primary valve ablation and 33% of those who underwent diversion. Average period of diversion in vesicostomy and pyelostomy patients was 25 months. CONCLUSIONS: Based on our findings temporary diversion does not seem to damage bladders. On the contrary, placing a damaged bladder at rest may help to improve bladder function. Bladder function following reconstitution correlated poorly with ultimate outcome and progression to renal failure. While we do not recommend temporary diversion as the treatment of choice for patients with posterior urethral valves, we believe that when chosen as treatment, it can be safely performed with little risk of further damage to the bladder.

Adolescent↗
PubMed1996

A new technique for assessing detrusor leak point pressure in patients with spina bifida.

PURPOSE: We report a new modification of the technique used to measure detrusor leak point pressure in patients with myelodysplasia and discuss its clinical implications. MATERIALS AND METHODS: We assessed detrusor leak point pressure during standard multichannel urodynamics in 77 patients with spina bifida. At leakage and in the absence of a detrusor contraction detrusor pressure is noted and the catheter is removed. With the cessation of leakage the catheter is reinserted and detrusor pressure is again noted. This cycle is repeated several times and the average difference is noted. In 23 patients there was no identifiable detrusor leak point pressure. The remaining 54 patients with a detrusor leak point pressure are included in this report. Also reviewed were renal ultrasound studies and voiding cystourethrograms for each patient. RESULTS: Three groups of patients were identified: 1 (20 patients)-detrusor leak point pressure greater than 40 and less than 40 cm. water with the catheter in and out, respectively; 2 (29)-detrusor leak point pressure consistently less than 40 cm. water with the catheter in and out, and 3 (5)-detrusor leak point pressure consistently greater than 40 cm. water with the catheter in and out. There was a 5% incidence of upper tract changes in group 1 and a 40% incidence in group 3. All patients in group 2 had normal upper tracts. CONCLUSIONS: A difference in upper tract changes was noted between groups 1 and 3, although in both groups detrusor leak point pressure was greater than 40 cm. water using standard measurement techniques and similar rates of upper tract changes would have been expected. Our modification may be a more accurate measurement of detrusor leak point pressure. It provides a better means of identifying patients at increased risk for renal deterioration and assessing outlet resistance.

Child↗