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Biomedical subjects

M Horowitz

Publications and source records attributed to M Horowitz.

At least 325 records · Page 18Linked to original sources
PubMed1993

Gastrointestinal function in chronic radiation enteritis--effects of loperamide-N-oxide.

The effects of loperamide-N-oxide, a new peripheral opiate agonist precursor, on gastrointestinal function were evaluated in 18 patients with diarrhoea caused by chronic radiation enteritis. Each patient was given, in double-blind randomised order, loperamide-N-oxide (3 mg orally twice daily) and placebo for 14 days, separated by a washout period of 14 days. Gastrointestinal symptoms; absorption of bile acid, vitamin B12, lactose, and fat; gastric emptying; small intestinal and whole gut transit; and intestinal permeability were measured during placebo and loperamide-N-oxide phases. Data were compared with those obtained in 18 normal subjects. In the patients, in addition to an increased frequency of bowel actions (p < 0.001), there was reduced bile acid absorption, (p < 0.001) a higher prevalence of lactose malabsorption (p < 0.05) associated with a reduced dietary intake of dairy products (p < 0.02), and faster small intestinal (p < 0.001) and whole gut transit (p < 0.05) when compared with the normal subjects. There was no significant difference in gastric emptying between the two groups. Treatment with loperamide-N-oxide was associated with a reduced frequency of bowel actions (p < 0.001), slower small intestinal (p < 0.001), and total gut transit (p < 0.01), more rapid gastric emptying (p < 0.01), improved absorption of bile acid (p < 0.01), and increased permeability to 51Cr EDTA (p < 0.01). These observations indicate that: (1) diarrhoea caused by chronic radiation enteritis is associated with more rapid intestinal transit and a high prevalence of bile acid and lactose malabsorption, and (2) loperamide-N-oxide slows small intestinal transit, increases bile acid absorption, and is effective in the treatment of diarrhoea associated with chronic radiation enteritis.

Adult↗
PubMed1993

Dual effects of cisapride on gastric emptying and antropyloroduodenal motility.

There is little information about the effects of cisapride on human antropyloroduodenal motility, despite its documented efficacy for increasing the rate of gastric emptying in patients with gastroparesis. Cisapride has been reported to have little effect on gastric emptying in normal subjects. Antral, pyloric, and duodenal pressures were recorded simultaneously with gastric emptying in 20 healthy volunteers. Thirty minutes after the solid component of the meal had started to empty from the stomach, each subject received either 10 mg cisapride i.v. (11 subjects) or intravenous saline (9 subjects). Intravenous saline had no effect on either motility or gastric emptying. In contrast, cisapride administration was associated with a dual effect on motility, with initial suppression of antral pressure waves (P < 0.05) followed by stimulation of associated antropyloroduodenal pressure waves (P < 0.01). Gastric emptying slowed in the first 30 min after cisapride (P < 0.05), and this was followed by more rapid gastric emptying (P < 0.01). The amount of the meal emptied in the 60 min after cisapride correlated with the number of associated antroduodenal pressure waves (r = 0.75, P < 0.001) but not with the number of antral waves (r = 0.42, NS). These results indicate that cisapride in a dose of 10 mg i.v. has dual effects on gastric emptying and gastric motility. The stimulation of associated antral pressure waves is a plausible mechanism for the efficacy of cisapride in the treatment of gastroparesis.

Adolescent↗
PubMed1993

Heat acclimation improves cardiac mechanics and metabolic performance during ischemia and reperfusion.

Cardiac mechanics and metabolic performance were studied in isolated perfused hearts of heat-acclimated (AC) rats (at 34 degrees C for 1 mo) and their age-matched controls (C). Diastolic and systolic pressures, coronary flow, and the appearance of ischemic contracture (IC) were measured during progressive graded ischemia, total ischemia (TI), and reperfusion. ATP, phosphocreatine, and intracellular pH were measured during TI and reperfusion with the use of 31P-nuclear magnetic resonance spectroscopy. Systolic pressure was greater in AC hearts than in C hearts (P < 0.0001). During 50% of perfusion pressure 15 and 46% of AC and C hearts, respectively, showed IC (P < 0.001). During 25% of perfusion pressure 85% of the hearts in both groups developed IC. The onset of IC in AC hearts was delayed compared with in C hearts. On reperfusion 93 and 66% of AC and C hearts, respectively, resumed contraction. Recovery of diastolic pressure was 78 and 36% for the AC and C hearts, respectively (P < 0.05). During TI ATP declined by 0.94 and 1.20 mumol/min in AC and C hearts, respectively, resulting in 21 +/- 2.8% preservation of the ATP pool in AC hearts after 30 min of TI (P < 0.001). The AC group also showed a delayed decline in intracellular pH (P < 0.001). The data suggest beneficial effects of heat acclimation on the heart, which were exhibited by greater pressure generation and by the emergence of protecting features during ischemia and reperfusion, possibly via energy-sparing mechanisms.

Acclimatization↗
PubMed1993

Isolated horizontal supranuclear gaze palsy as a marker of severe systemic involvement in Gaucher's disease.

Type 3 neuronopathic Gaucher's disease (GD3) is phenotypically heterogeneous. In many GD3 patients, progressive myoclonus and dementia dominate the illness, with death secondary to progressive CNS disease. We have designated this group as GD3a. We studied 14 children with Gaucher's disease, isolated horizontal supranuclear gaze palsy, and aggressive systemic disease, and designated this group as GD3b. In comparison with 13 children with type 1 non-neuronopathic Gaucher's disease, the GD3b children presented earlier, and were shorter, underweight, and more prone to cardiopulmonary, hepatic, and skeletal complications. One-half of the children died in childhood or adolescence of systemic complications. Patients with at least one copy of the mutation that causes substitution of asparagine for serine at amino acid 370 of glucocerebrosidase did not develop neurologic signs. Patients homoallelic for the mutation causing substitution of leucine for proline at position 444 had severe systemic disease; neurologic signs were frequently, but not invariably, present. Early diagnosis and timely enzyme replacement therapy promise to improve the prognosis in GD3b.

Adolescent↗
PubMed1993

Relationships between metacarpal morphometry, forearm and vertebral bone density and fractures in post-menopausal women.

The relationships between metacarpal morphometric, vertebral and forearm density measurements and the prevalence of vertebral and peripheral fractures were examined in 239 postmenopausal women (median age 63, range 32-84 years). Metacarpal cortical area/total area ratio (CA/TA) was measured with needle calipers, forearm mineral density (FMD) by single photon absorptiometry and vertebral mineral density (VMD) by single energy quantitative computed tomography. Of the 239 subjects 97 had not suffered any fractures, 44 had at least one previous vertebral fracture but no peripheral fractures, 41 had a history of peripheral fracture but no vertebral fracture and 57 had suffered both peripheral and vertebral fractures. There were significant correlations between a single measurement of CA/TA and both FMD (r = 0.65, p < 0.001) and VMD (r = 0.41, p < 0.001). Similar correlations existed between the mean of multiple measurements of CA/TA and both FMD and VMD. CA/TA (p < 0.001), FMD (p < 0.001) and VMD (p < 0.001) were reduced in subjects who had suffered fractures, when compared with the no fracture group. The percentage of cases in each of the four fracture groups (vertebral fracture only, peripheral fracture only, peripheral and vertebral fracture, peripheral or vertebral fracture) misclassified with reference to the no fracture group were similar with CA/TA, FMD or VMD measurements. We suggest that metacarpal morphometry, which is widely available at relatively low cost, yields cross-sectional information about bone density and fracture risk, comparable with that obtained by forearm and vertebral densitometry.

Absorptiometry, Photon↗
PubMed1993

Strategic planning applied to quality in asthma management for children.

This strategic plan translates the HCHP vision statement into a working plan for one major clinical condition--asthma in children. It is a working plan for clinicians and managers across specialties and levels. The results of the projects will improve in a measurable way significant clinical practice and outcomes, in keeping with the FY 1993 strategic goals.

Asthma↗
PubMed1993

Prevalence of nine mutations among Jewish and non-Jewish Gaucher disease patients.

The frequency of nine different mutated alleles known to occur in the glucocerebrosidase gene was determined in 247 Gaucher patients, of whom 176 were of Jewish extraction, 2 were Jewish with one converted parent, and 69 were of non-Jewish origin. DNA was prepared from peripheral blood, active glucocerebrosidase sequences were amplified by using the PCR technique, and the mutations were identified by using the allele-specific oligonucleotide hybridization method. The N37OS mutation appeared in 69.77% of the mutated alleles in Jewish patients and in 22.86% of the mutated alleles in non-Jews. The 84GG mutation, which has not been found so far among non-Jewish patients, existed in 10.17% of the disease alleles among Jewish patients. The IVS + 1 mutation constituted 2.26% of the disease alleles among Jewish patients and 1.43% among the non-Jewish patients. RecTL, a complex allele containing four single-base-pair changes, occurred in 2.26% of the alleles in Jewish patients and was found in two (1.43%) of the patients of non-Jewish extraction. Another complex allele, designated "RecNciI" and containing three single-point mutations, appeared in 7.8% of alleles of non-Jewish patients and in only two (0.56%) of the Jewish families. The prevalence of the L444P mutation among non-Jewish Gaucher patients was 31.43%, while its prevalence among Jewish patients was only 4.24%. The prevalence of two other point mutations--D409H and R463C--was 5.00% and 3.57%, respectively, among non-Jewish patients and was not found among the Jewish Gaucher patient population. The prevalence of the R496H mutation, found so far only among Jewish patients, was 1.13%. The results presented demonstrate that seven mutations identify 90.40% of the mutations among Jewish patients and that these seven mutations allow diagnosis of only 73.52% of the non-Jewish patients. Identification of additional mutant alleles will enhance the accuracy of carrier detection.

Base Sequence↗
PubMed1993

Adult-type Gaucher disease in children: genetics, clinical features and enzyme replacement therapy.

Clinical manifestations of type 1 (Adult) Gaucher disease usually start in childhood. However, most of the previously published data describe the features of this disorder in adults. We present the clinical and genetic characteristics of 34 children and adolescents with type 1 Gaucher disease evaluated in our clinic during the past two years. Patients were aged 2-18 years; 18 were boys and 16 girls. The majority presented before the age of 10. Growth retardation appeared as a prominent feature, with 26% in or below the third percentile in weight, and 30% so in height, especially in the youngest age group (2-5 years). Anaemia and thrombocytopenia occurred in 80% and 60% of the children, respectively. Hepatosplenomegaly was noted in all the children; only 3 were splenectomized. Skeletal involvement was evident on X-rays in 90% of the patients, but only 50% complained of bone pains. Three patients had severe bone disease, with avascular necrosis of the hip joint. Mutation analysis at the DNA level revealed the 1226/1226 genotype in 12 (35%) patients and 1226/84GG in 13 (38%). Correlation was found between the genotypes and the severity of the disease, including growth retardation. A positive response was documented in all 9 patients who completed 12 months of the recently-introduced enzyme replacement therapy for Gaucher disease.

Adolescent↗
PubMed1993

The effect of heat load and dehydration on hypertonic saline solution treatment of controlled hemorrhagic shock.

Small volume hypertonic saline solution has been suggested for initial effective resuscitation of hemorrhagic shock. The effect of hypertonic saline solution in controlled hemorrhagic shock was studied in rats subjected to dehydration or heat, or both. The rats were randomly divided into four groups--group 1 (n = 19), normal rats; group 2 (n = 21), water deprivation for 12 hours; group 3 (n = 20), heating at 37 degrees C. for five hours, and group 4 (n = 19), water deprivation for 12 hours and heating at 37 degrees C. for five hours. Controlled hemorrhagic shock was induced in all rats by arterial bleeding of 15 milliliters per kilogram and the rats were divided into three treatment subgroups--group a was untreated, group b was treated with 5 milliliters per kilogram 0.9 percent NaCl and group c was treated with 5 milliliters per kilogram 7.5 percent NaCl. Arterial bleeding of 15 milliliters per kilogram in group 1 resulted in decrease in mean arterial pressure (MAP) to 44 +/- 2 millimeters of mercury (p < 0.001) and pulse rate to 280 +/- 13 per minute (p < 0.01). A similar decrease in MAP and pulse rate was observed in all four groups. Infusion of hypertonic solution (HTS) in group 1c was followed by an increase in MAP to 89.0 +/- 9.7 milliliters of mercury (p < 0.01) in 15 minutes. This was significantly higher than infusion of normal saline solution in group 1b (p < 0.01) or untreated group 1a (p < 0.01). This difference remained significant also after 45 minutes from infusion (p < 0.05 and p < 0.05, respectively). The increase in MAP in response to HTS in group 1c after 15 minutes was significantly higher than the rise in groups 2c (p < 0.05), 3c (p < 0.05) and 4c (p < 0.05). This difference in response to HTS remained significant 45 minutes from infusion in groups 3c (p < 0.05) and 4c (p < 0.05), but not in dehydrated rats in group 2c. Arterial bleeding did not alter serum sodium significantly in all four groups. Infusion of HTS in group 1c was followed by an increase in serum sodium from 149.1 +/- 1.4 to 161.1 +/- 2.4 milliequivalent per liter (p < 0.001), while infusion of HTS in group 4c, where serum sodium was initially elevated to 157.1 +/- 3.0 milliequivalent per liter, did not further elevate the serum sodium level.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1993

Murine prosaposin: expression in the reproductive system of a gene implicated in human genetic diseases.

Expression of the prosaposin gene, implicated in human genetic diseases, was studied in the mouse by Northern blot analysis and in situ hybridization. Using a cloned mouse prosaposin cDNA as a probe, we observed high expression of the prosaposin gene in the adult and embryonic nervous and reproductive systems while lower levels of prosaposin mRNA were detected in the heart, kidneys, liver, adrenals and lymphoid organs. Ubiquitous low level of prosaposin mRNA were detected by in situ hybridization in 12.5 days-old embryos. However, high expression was restricted to the hindbrain, the dorsal ganglia and to the genital ridge, the primordium for both male and female gonads. RNA transcription in the testis was detected in Sertoli cells, Leydig cells and peritubular cells but not in germ cells of adult mice. Similar observations were obtained with the atrichosis mutant mouse known to lack normal germ cells, indicating that prosaposin gene expression was not dependent on the presence of germ cells in the testis. Prosaposin was found to be expressed in the mature female gonads at various stages of the corpus luteum development. These results strongly suggest that prosaposin may play an important role in the reproductive system as well as the nervous system.

Animals↗
PubMed1993

Effects of erythromycin on gastric emptying, alcohol absorption and small intestinal transit in normal subjects.

The effects of erythromycin on gastric emptying and intragastric distribution of a mixed solid/liquid meal, alcohol absorption and small intestinal transit were examined in eight male volunteers. Each subject received, in double-blind randomized order, either erythromycin as the lactobionate (3 mg.kg-1 i.v. over 20 min) or saline immediately before the consumption of a radioisotopically labeled test meal, which consisted of 330 g minced beef and 400 ml of orange juice containing ethanol (0.5 g.kg-1 body weight) and 10 g lactulose. Erythromycin increased the rate of total stomach emptying and proximal stomach emptying of both the solid and liquid components of the meal (p < 0.001), but slowed small intestinal transit (p < 0.01). Peak blood alcohol concentrations (p < 0.01) were higher after erythromycin, with a mean increase of 40%. There was a significant inverse relationship between peak blood alcohol concentrations and the 50% emptying time for the liquid component of the meal after saline (r = -0.70, p < 0.05), but not after erythromycin (r = -0.57, p < 0.1). The total area under the venous blood alcohol concentration time curve (i.e., total absorption) was greater (p < 0.01) after erythromycin. These results suggest that: faster emptying from the proximal stomach contributes to more rapid gastric emptying induced by erythromycin, erythromycin retards small intestinal transit and that erythromycin increases the total amount of alcohol absorbed as well as the rate of alcohol absorption. These latter effects are likely to reflect more rapid delivery of alcohol to the small intestine and reduced metabolism of alcohol by the gastric mucosa.

Adult↗
PubMed1992

Systemic lupus erythematosus patients with central nervous system involvement show autoantibodies to a 50-kD neuronal membrane protein.

An antibody was detected in the sera from patients with systemic lupus erythematosus (SLE) and central nervous system (CNS) involvement that reacted with a 50-kD antigen in the plasma membrane of brain synaptic terminals. The 50-kD antigen was solubilized with Triton X-100 from preparations enriched with synaptic plasma membranes, and was partially purified by molecular sieve filtration column chromatography. The sera of 19 of 20 CNS-SLE patients showed strong to moderate immunoreactivity with the 50-kD protein in Western blots. Immunoreactivity with the 50-kD protein was also detected in the cerebrospinal fluid of CNS-SLE patients. Control sera from healthy individuals did not react with the 50-kD protein. Low to background reactivity was detected in 35% of a group of SLE patients without CNS manifestations, and in 3% of patients displaying other connective tissue diseases. A total of 100 individuals were tested in this study. Purified autoantibodies to the 50-kD protein from CNS-SLE patients were used for immunofluorescent labeling of neuroblastoma cells. The immunofluorescent staining revealed a distinct macular distribution pattern on the surface of the cell membrane. Taken together, the data suggest that the 50-kD protein may be an important target for autoantibodies, preponderantly found in CNS-SLE patients, and that the antigen may play a role in the pathogenesis of some neurological manifestations in SLE.

Adolescent↗
PubMed1992

Hemopoietic functions of marrow-derived osteogenic cells.

Osteoblasts, members of the marrow stromal cellular network, may play an active role in the hemopoietic microenvironment as well as in bone remodeling. In this study, we examined the extent to which marrow-derived osteogenic cells (MBA-15) possess various stromal functions. This marrow stromal-derived cell line was shown by us to exhibit osteoblastic characteristics in culture and to form bone in vivo. These cells are shown here to constitutively produce and secrete cytokines identified as M-CSF, GM-CSF, and IL-6. MBA-15 cells modulate growth of normal and malignant myeloid and lymphoid cells as well as leukemia cell lines in vitro. Cell-cell interactions were studied in co-cultures with adherent MBA-15 cells and the target hemopoietic cells. Growth inhibition effects, observed under various experimental conditions, can be attributed to the presence of different soluble and membrane-bound inhibitory activities produced by MBA-15 cells. Thus, MBA-15 cells spontaneously produce both stimulators and inhibitors that can affect myeloid and lymphoid cell growth. Marrow osteogenic cells may therefore participate in the stromal regulation of hemopoiesis.

Alkaline Phosphatase↗
PubMed1992

Ambiguous genitalia: diagnosis, evaluation, and treatment.

The pediatric radiologist plays a significant role in the evaluation and the treatment of infants with ambiguous genitalia. On the first day of life, an investigation should be initiated that includes studies, in particular a sonogram, to demonstrate the presence or absence of a uterus, and a genitogram to define the presence of a vagina. Once gender assignment has been made, information regarding the size of the vagina and its position in regard to the urogenital sinus becomes essential to the pediatric urologist when planning a course for reconstruction. Herein we break down intersex states into four major categories: female pseudohermaphroditism, male pseudohermaphroditism without müllerian structures, and male hermaphroditism with müllerian structures and true hermaphroditism. The role of the radiologist in each of these states is discussed.

Disorders of Sex Development↗
PubMed1992

Intravenous erythromycin overcomes small intestinal feedback on antral, pyloric, and duodenal motility.

The retardation of gastric emptying caused by intraduodenal lipid is associated with suppression of antral contractions and stimulation of localized pyloric contractions. Similar patterns of motility have been described in patients with gastroparesis. The effect of erythromycin on the antropyloroduodenal motor responses to intraduodenal lipid was investigated. In 17 volunteers an intraduodenal lipid infusion (10% Intralipid) was given at 1 mL/min for 50 minutes. Either erythromycin (3 mg/kg) or saline was administered IV for 15 minutes, beginning 20 minutes after the start of the intraduodenal lipid infusion. Antral, pyloric, and duodenal motility were measured with a sleeve/sidehole manometric assembly. Intraduodenal lipid stimulated localized pyloric contractions. Erythromycin suppressed localized phasic (P less than 0.003) and tonic (P less than 0.002) pyloric pressure waves and stimulated antral (P less than 0.003) and duodenal pressure waves (P less than 0.02). After erythromycin antral pressure waves were usually of high amplitude (greater than 50 mm Hg) and often associated with duodenal pressure waves. It was concluded that erythromycin overcomes the effects of intraduodenal lipid on antral, pyloric, and duodenal motility. These effects probably contribute to the gastrokinetic properties of erythromycin.

Adult↗
PubMed1992

Adaptive changes in the pyloric motor response to intraduodenal dextrose in normal subjects.

Gastric emptying of glucose is faster after dietary supplementation of glucose, suggesting specific adaptation to changes in nutrient intake. In the present study, the effects of a continuous long-term (0-120-minute) and two short-term (0-20- and 80-100-minute) intraduodenal infusions of dextrose (2.4 kcal/min) on antropyloroduodenal motility and blood glucose, plasma gastric inhibitory polypeptide, and insulin concentrations were evaluated in nine volunteers. In four volunteers, an intraduodenal infusion of triglyceride (2.4 kcal/min) was administered immediately after the long-term dextrose infusion. The long-term dextrose infusion initially increased isolated pyloric pressure waves (IPPWs) and basal pyloric pressure (P < 0.05 for both), but after about 30 minutes IPPWs and basal pyloric pressure decreased and returned to baseline within 80 minutes. Each short-term infusion increased IPPWs and basal pyloric pressure (P < 0.05 for both). Antral pressure waves remained suppressed during the long-term dextrose infusion. Intraduodenal triglyceride increased IPPWs and basal pyloric pressure (P < 0.05 for both). The long-term dextrose infusion was associated with a sustained increase, and both short-term dextrose infusions were associated with peaks in glucose, insulin, and gastric inhibitory polypeptide levels. There was no significant relationship between biochemical measurements and antropyloroduodenal motility. It is concluded that specific adaptive changes occur rapidly in the phasic and tonic pyloric motor response, but not the antral motor response, to intraduodenal dextrose.

Adaptation, Physiological↗