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Biomedical subjects

M Horowitz

Publications and source records attributed to M Horowitz.

At least 109 records · Page 6Linked to original sources
PubMed1999

Heat stress induces ultrastructural changes in cutaneous capillary wall of heat-acclimated rock pigeon.

In heat-acclimated rock pigeons, cutaneous water evaporation is the major cooling mechanism when exposed at rest to an extremely hot environment of 50-60 degrees C. This evaporative pathway is also activated in room temperature by a beta-adrenergic antagonist (propranolol) or an alpha-adrenergic agonist (clonidine) and inhibited by a beta-adrenergic agonist (isoproterenol). In contrast, neither heat exposure nor drug administration activates cutaneous evaporation in cold-acclimated pigeons. To elucidate the mechanisms underlying this phenomenon, we studied the role of the ultrastructure and permeability of the cutaneous vasculature. During both heat stress and the administration of propranolol and clonidine, we observed increased capillary fenestration and endothelial gaps. Similarly, propranolol increased the extravasation of Evans blue-labeled albumin in the skin tissue. We concluded that heat acclimation reinforces a mechanism by which the activation of adrenergic signal transduction pathways alters microvessel permeability during heat stress. Consequently the flux of plasma proteins and water into the interstitial space is accelerated, providing an interstitial source of water for sustained cutaneous evaporative cooling.

Acclimatization↗
PubMed1999

The physiological strain index applied to heat-stressed rats.

A physiological strain index (PSI) based on heart rate (HR) and rectal temperature (Tre) was recently suggested to evaluate exercise-heat stress in humans. The purpose of this study was to adjust PSI for rats and to evaluate this index at different levels of heat acclimation and training. The corrections of HR and Tre to modify the index for rats are as follows: PSI = 5 (Tre t - Tre 0). (41.5 - Tre 0)-1 + 5 (HRt - HR0). (550 - HR0)-1, where HRt and Tre t are simultaneous measurements taken at any time during the exposure and HR0 and Tre 0 are the initial measurements. The adjusted PSI was applied to five groups (n = 11-14 per group) of acclimated rats (control and 2, 5, 10, and 30 days) exposed for 70 min to a hot climate [40 degrees C, 20% relative humidity (RH)]. A separate database representing two groups of acclimated or trained rats was also used and involved 20 min of low-intensity exercise (O2 consumption approximately 50 ml. min-1. kg-1) at three different climates: normothermic (24 degrees C, 40% RH), hot-wet (35 degrees C, 70% RH), and hot-dry (40 degrees C, 20% RH). In normothermia, rats also performed moderate exercise (O2 consumption approximately 60 ml. min-1. kg-1). The adjusted PSI differentiated among acclimation levels and significantly discriminated among all exposures during low-intensity exercise (P < 0.05). Furthermore, this index was able to assess the individual roles played by heat acclimation and exercise training.

Acclimatization↗
PubMed1999

Effect of heat acclimation and heat shock on oscillations of carbamyl-choline-evoked Ca2+ signal in HSY cell line.

We studied effects of heat acclimation (HA) and acute heat stress (HS) on Ca2+ signal oscillations following supramaximal carbamyl-choline (CCh) stimulation, using HSY cell line as a model. In the control cells, oscillations decreased their amplitude with time. HS alone did not change either oscillation amplitude or frequency, although calcium release to the cytosol upon CCh stimulation was faster. HA increased maximal oscillation amplitude only. There was no change in basal cytosolic calcium level and peak evoked signal in all experimental conditions. Collectively, the data suggest that HA affects the oscillation profile. Changes in the oscillation profile did not correlate with changes in the resting and evoked Ca2+ signal, which suggests that the oscillations are a separate target for heat acclimation.

Acclimatization↗
PubMed1999

Hyperglycemia attenuates the gastrokinetic effect of erythromycin and affects the perception of postprandial hunger in normal subjects.

OBJECTIVE: The major aims of this study were to determine in normal subjects whether the effects of erythromycin on gastric emptying, postprandial hunger, and fullness are modified by the blood glucose concentration. RESEARCH DESIGN AND METHODS: A total of 10 normal subjects (aged 20-39 years) underwent concurrent measurements of gastric emptying, blood glucose, hunger, and fullness on four separate occasions: twice during euglycemia (approximately 4 mmol/l) and twice during hyperglycemia (approximately 15 mmol/l). Either erythromycin (3 mg/kg) or saline (0.9%) was administered intravenously immediately before ingestion of a radioisotopically labeled solid meal. RESULTS: Gastric emptying was slower (P < 0.0001) during hyperglycemia when compared with euglycemia after both erythromycin and saline administration. During hyperglycemia, erythromycin reduced the lag phase (77.8 +/- 12.6 vs. 20.3 +/- 7.3 min; P < 0.05) but had no effect on the postlag emptying rate (0.32 +/- 0.077% per min vs. 0.24% per min). Hunger decreased (P < 0.001) and fullness increased (P < 0.001) after the meal. Postprandial hunger was less during hyperglycemia after saline infusion (P < 0.05) but not after erythromycin. Hunger was greater after erythromycin during both hyperglycemia and euglycemia (P < 0.05). CONCLUSIONS: At a blood glucose concentration of approximately 15 mmol/l, 1) gastric emptying of a solid meal is slower, when compared with euglycemia, even after administration of erythromycin; 2) the effect of erythromycin on gastric emptying of a solid meal is attenuated; and 3) the perception of postprandial hunger is reduced.

Adult↗
PubMed1999

Natural history of diabetic gastroparesis.

OBJECTIVE: The major aim of this study was to evaluate the prognosis of diabetic gastroparesis. RESEARCH DESIGN AND METHODS: Between 1984 and 1989, 86 outpatients with diabetes (66 type 1, 20 type 2; 40 male, 46 female) underwent assessment of solid and liquid gastric emptying and esophageal transit (by scintigraphy), gastrointestinal symptoms (by questionnaire), autonomic nerve function (by cardiovascular reflex tests), and glycemic control (by HbAlc and blood glucose concentrations during gastric emptying measurement). These patients were followed up in 1998. RESULTS: Of the 86 patients, solid gastric emptying (percentage of retention at 100 min) was delayed in 48 (56%) patients and liquid emptying (50% emptying time) was delayed in 24 (28%) patients. At follow-up in 1998, 62 patients were known to be alive, 21 had died, and 3 were lost to follow-up. In the group who had died, duration of diabetes (P = 0.048), score for autonomic neuropathy (P = 0.046), and esophageal transit (P = 0.032) were greater than in those patients who were alive, but there were no differences in gastric emptying between the two groups. Of the 83 patients who could be followed up, 32 of the 45 patients (71%) with delayed solid emptying and 18 of the 24 patients (75%) with delay in liquid emptying were alive. After adjustment for the effects of other factors that showed a relationship with the risk of dying, there was no significant relationship between either gastric emptying or esophageal transit and death. CONCLUSIONS: In this relatively large cohort of outpatients with diabetes, there was no evidence that gastroparesis was associated with a poor prognosis.

Adolescent↗
PubMed1999

Vesicoureteral reflux in infants with prenatal hydronephrosis confirmed at birth: racial differences.

PURPOSE: We compared the incidence of vesicoureteral reflux in black and nonblack patients in whom prenatal hydronephrosis was confirmed postnatally. MATERIALS AND METHODS: We reviewed the records of 58 black and 51 nonblack patients with confirmed hydronephrosis who underwent voiding cystourethrography. RESULTS: Reflux was present in 9 cases (8.3%). The prevalence of reflux in black and nonblack patients was 0 and 17.6%, respectively. CONCLUSIONS: The absence of vesicoureteral reflux in black infants with prenatal hydronephrosis and the 17.6% incidence in nonblack infants suggest that voiding cystourethrography should not be routinely performed in the black population, although it should continue to be done on a routine basis in the nonblack population.

Black People↗
PubMed1999

The effects of season and alcohol intake on mineral metabolism in men.

We have examined the relationship between self-reported alcohol intake (SRAI), season and mineral metabolism in a series of 96 men aged 32 to 78 years of age. Alcohol intake was reported as between 0 and 50 oz/week. SRAI correlated positively with liver function tests, including serum bilirubin, alkaline phosphatase, and AST initially and at 6 months. In addition, SRAI correlated with serum calcium, testosterone, estradiol, and immunoreactive parathyroid hormone (iPTH) as well as urinary calcium [per 100 mg of creatinine (Cr)], and pyridinoline crosslinks (DPC) (per 100 mg of Cr). We have divided the participants into two groups on the basis of their reported alcohol intake. Individuals with none-to-moderate intake had <8.4 oz/week of ethanol. Those with moderate or heavier intake had 8.4 oz or more of ethanol/week. Individuals with none-to-moderate SRAI had a significant seasonal increase in iPTH, osteocalcin, urine DPC/100 mg of Cr and a decrease in distal forearm bone mineral density, 25 hydroxyvitamin D (250HD), and urinary calcium/100 mg of Cr. Individuals with moderate or heavier SRAI only had significant seasonal decrease in 250HD. We have concluded that alcohol intake decreases seasonal change in serum iPTH. The biological effects of such alterations in parathyroid hormone levels include decreased seasonal loss of bone mineral density.

Adult↗
PubMed1999

Gastric emptying in diabetes mellitus: relationship to blood-glucose control.

The application of novel investigative techniques has established that disordered gastric motility is a frequent complication of diabetes mellitus. Thus, gastric emptying of solid or nutrient liquid meals is abnormal in 30% to 50% of randomly selected outpatients with long-standing type 1 or type 2 diabetes. Delayed gastric emptying occurs more frequently than rapid emptying. There is increasing evidence that disordered gastric motility has a major impact on the management of patients with diabetes mellitus by leading to gastrointestinal symptoms and poor glycemic control. Although both gastroparesis and upper gastrointestinal symptoms have been attributed to irreversible autonomic damage, it is now clear that acute changes in the blood-glucose concentration have a major effect on both gastrointestinal motor function and the perception of sensations arising in the gut. For example, there is an inverse relationship between the rate of gastric emptying and the blood-glucose concentration, so that gastric emptying is slower during hyperglycemia and accelerated during hypoglycemia. This article reviews some issues in the etiology, diagnosis, and management of problems associated with gastric emptying in elderly persons with diabetes mellitus.

Aged↗
PubMed1999

Emotional control theory and the concept of defense: A teaching document.

Defensiveness in intrapsychic and interpersonal activities is a generally accepted concept among psychodynamic theorists, but a theoretically grounded classification of emotional control processes is needed. As a result of intensive case-by-case clinical and empirical studies, such a system was assembled. The system is organized by three major categories of processes that can regulate emotions. These are sets of mental operations that control 1) content of thought and communications, 2) form of thought and communications, and 3) person schemas that organize beliefs and interpersonal expressions. Each category of defensive control processes is linked to observable outcomes at intrapsychic and interpersonal levels. This classification system can be used to formulate how patterns of avoidance and distortion are formed.(The Journal of Psychotherapy Practice and Research 1999; 8:213-224)

Adult↗
PubMed1999

The adolescent varicocele I: left testicular hypertrophy following varicocelectomy.

PURPOSE: Ipsilateral testicular catch-up growth has been reported to occur in approximately 80% of adolescents with varicoceles following unilateral varicocelectomy. We have been observing not only catch-up growth, but hypertrophy (left at least 10% larger than right testicular volume) in some adolescents postoperatively. To our knowledge this phenomenon has not been previously described. We assess the incidence of left testicular hypertrophy following ipsilateral varicocele ligation and whether it is related to age at operation and/or procedure performed. MATERIALS AND METHODS: We reviewed the records of 42 patients who underwent unilateral left varicocelectomy for asymptomatic varicoceles. Testicular volume was determined before and after surgery, and all patients were followed for a minimum of 6 months. Indication for surgery was ipsilateral left testicular hypotrophy in 23 cases, grade 2 to 3 varicocele with palpably softer ipsilateral left testicle in 5, grade 3+ varicoceles in 12, an exaggerated response to gonadotropin-releasing hormone stimulation test in 1 and persistent pain in 1. Average patient age at operation was 14.7 years (range 9 to 22) and average followup was 22 months (range 6 to 84). Patients were stratified according to Palomo versus modified Ivanissevich technique and age at operation. Testes were measured using the Takihara ring orchidometer with relative volume of the left testis expressed as a percentage of the right testis. Results were compared in different age groups as well as by procedure performed to correct the varicocele using chi-square analysis. RESULTS: Left testicular hypertrophy developed in 13 of 32 patients (43.8%) who underwent a Palomo repair and in 3 of the 10 (30%) who underwent a modified Ivanissevich repair. When compared by age at operation, 8 of 20 patients (40%) 14.7 years old or younger had left testicular hypertrophy compared to 8 of 22 (36.4%) older than 14.7 years. Differences between these groups were not statistically significant. CONCLUSIONS: Ipsilateral testicular hypertrophy occurs in a substantial number of adolescents following varicocele ligation. This phenomenon does not seem to be dependent on age at surgery or type of varicocele repair.

Adult↗
PubMed1999

Dantrolene and recovery from heat stroke.

Several authors have shown that dantrolene may be effective in the treatment of heat stroke patients. However, the scant data available are still controversial. The aim of this investigation was to establish an animal experimental model for studying the efficacy of this drug both as a prophylactic agent and as a means of hastening the cooling process after heat stroke. Male albino rats were divided into five groups: Sedentary controls (SC), Sedentary+dantrolene (S+D), Exercise controls (EC), and Exercise+dantrolene (E+D, E+D1). The drug (140 mg x kg(-1) body weight) was administered i.v. either prior to subjection to heat stress (40 degrees C) (S+D, E+D) or upon development of heat stroke syndrome (E+D1). In the S+D group, dantrolene administered prior to heat stress (HS) delayed the development of heat stroke by 70%, although colonic temperature (Tc) at the onset of heat stroke was similar to that in group SC (43.0 +/- 0.1 degrees C and 43.2 +/- 0.4 degrees C for S+D and SC, respectively). In E+D animals, dantrolene shortened exercise endurance in the heat by 17.5%, but concomitantly hindered severe Tc rise (40.9 +/- 0.2 degrees C and 40.0 +/- 0.2 degrees C for EC and E+D, respectively). Administration of dantrolene on the development of heat stroke appeared to improve cooling in the exercise group (0.25 degrees C x min(-1) and 0.18 degrees C x min(-1), for the first 1 5 min of cooling, for E+D1 and EC, respectively). The results suggest that dantrolene is effective as a prophylactic agent in sedentary animals only. It also might have application on development of heat stroke. It is hypothesized that the observed rapid cooling is associated with dantrolene's effect on muscle contraction, thus leading to attenuated heat production and peripheral vascular relaxation.

Analysis of Variance↗
PubMed1998

Nutrition, osteoporosis, and aging.

Loss of bone is an almost universal accompaniment of aging that proceeds at an average rate of 0.5-1% per annum from midlife onwards. There are at least four nutrients involved in this process: calcium, salt, protein, and vitamin D, at least in women. The pathogenesis of osteoporosis in men is more obscure. Calcium is a positive risk factor because calcium requirement rises at the menopause due to an increase in obligatory calcium loss and a small reduction in calcium absorption that persist to the end of life. A metaanalysis of 20 calcium trials shows that this process can generally be arrested by calcium supplementation, although there is some doubt about its effectiveness in the first few years after menopause. Salt is a negative risk factor because it increases obligatory calcium loss; every 100 mmol of sodium takes 1 mmol of calcium out of the body. Restricting salt intake lowers the rate of bone resorption in postmenopausal women. Protein is another negative risk factor; increasing animal protein intake from 40 to 80 g daily increases urine calcium by about 1 mmol/day. Low protein intakes in third world countries may partially protect against osteoporosis. Vitamin D (sometimes called a nutrient and sometimes a hormone) is important because age-related vitamin D deficiency leads to malabsorption of calcium, accelerated bone loss, and increased risk of hip fracture. Vitamin D supplementation has been shown to retard bone loss and reduce hip fracture incidence in elderly women.

Aged↗
PubMed1998

Neuroprotection against oxidative stress by serum from heat acclimated rats.

Exposure of PC12 cells, to 1% serum derived from normothermic (CON) rats resulted in 79% cell death. Sister cultures treated with 1% serum derived from heat acclimated (ACC) rats, were neuroprotected and expressed a significant reduction in cell death. In PC12 cells exposed to a free radical generator causing an oxidative stress, 90% cell death was measured in CON serum treated cultures, while ACC serum treated cultures were neuroprotected. Xanthine oxidase activity and uric acid (UA) levels were lower in ACC serum compared to CON. Addition of UA to both sera abolished the difference in cell viability, and toxicity of ACC serum reached that of CON. These findings suggest a causal relationship between the lower levels of UA in ACC and the neuroprotective effect observed. The present study proposes heat acclimation as an experimental and/or clinical tool for the achievement of neuroprotection.

Acclimatization↗
PubMed1998

Differential stimulation of c-fos expression in hypothalamic nuclei of the rat brain during short-term heat acclimation and mild dehydration.

Activation of central nervous structures involved in the perception and integration of thermo- and osmoregulatory signals was investigated in the Sabra rat. Male rats were either non-treated (C-E), water-deprived for 24 h (C-D), short-term acclimated to 34 degrees C for two days (STHA-E) or subjected to both stimuli (STHA-D). Immunoreactivity for c-Fos protein (Fos-IR) as marker for neuronal activation was quantified in (extra-)hypothalamic structures: organum vasculosum laminae terminalis (OVLT); subfornical organ (SFO); medial (MPA), ventromedial preoptic (VMPO) and lateral hypothalamic (LHA) areas; median preoptic (MnPO), magnocellular supraoptic (SON) and paraventricular (mPVN) nuclei; limbic lateral septal (LS) and thalamic paraventricular (PV) nuclei. Compared to C-E rats, dehydration markedly increased Fos-IR exclusively in neurons of the OVLT, SFO and MnPO known to be involved in osmoreception, in the mPVN and SON, and to a minor extent in the VMPO. The VMPO, MPA, LHA and LS-important (extra-)hypothalamic sites for the perception and integration within the thermoregulatory control circuit-exhibited intense elevation of Fos-IR upon short-term heat acclimation. Of all (extra-)hypothalamic structures involved in central osmoregulation, only the MnPO revealed heat-induced Fos-IR in numerous cells located preferentially in its rostral component. Thus, the MnPO proved to be activated during both thermal and osmotic stimulations applied separately. Subjected to the combined stress (STHA-D), most brain structures investigated showed striking Fos-IR due to thermally enhanced osmotic stimulation, with additive effects demonstrated in the MnPO. The data support differential central activation of c-fos expression due to thermal or osmotic stimulations, with the MnPO acting as putative integrative center for both autonomic control circuits.

Acclimatization↗
PubMed1998

Unrelated and HLA-nonidentical related donor marrow transplantation for thalassemia and leukemia. A combined report from the Seattle Marrow Transplant Team and the International Bone Marrow Transplant Registry.

Allogeneic marrow transplantation is curative therapy for thalassemia, but fewer than 30% of patients have an HLA-identical sibling marrow donor. Selection of alternative donors of hematopoietic stem cells (unrelated individuals or HLA-nonidentical family members) has been aided by establishment of world-wide donor registries now exceeding 3.6 million volunteers and by DNA-based HLA typing to more closely match potential donors. Coupled with improved methods to control graft-versus-host disease and prevent fungal and cytomegalovirus infection, remarkable progress has been made in alternative donor transplantation. For patients 50 years of age or younger, with recently diagnosed chronic myelogenous leukemia (CML) in chronic phase, 1- and 5-year survivals after HLA-A, B, DRB1 identical unrelated marrow transplantation in Seattle are 82% and 74%, respectively. These results are essentially identical to outcome in similar patients given HLA-matched sibling allografts. However, the world-wide number of alternative donor transplants for thalassemia remains limited to date: 4 unrelated and 60 HLA-nonidentical related transplants have been reported to the IBMTR since 1969 with actuarial overall survival of 75%. Using the paradigm of CML, it is likely that access to curative therapy of thalassemia will improve with optimal HLA typing and donor selection early in the course of disease.

Bone Marrow Transplantation↗
PubMed1998

Adoptive immunotherapy for leukemia: donor lymphocytes transduced with the herpes simplex thymidine kinase gene for remission induction. HGTRI 0103.

This study will evaluate the safety and efficacy of allogenic donor lymphocyte infusions in patients who have relapsed hematologic malignancies after allogeneic bone marrow transplantation (BMT). Donor lymphocyte transfusions have resulted in the cure of some patients with relapsed leukemia or lymphoproliferative disorder after allogeneic BMT, but has been complicated by the development of graft versus host disease (GvHD). We hypothesize that a retroviral vector containing the Herpes simplex thymidine kinase (HStk) gene will allow for retention of the anti-leukemia response of transfused donor lymphocytes while allowing for the adverse effects of GVHD to be mitigated. Patients with relapsed hematologic malignancies after allogeneic BMT will be infused with ex vivo gene modified donor lymphocytes. The Herpes Simplex thymidine kinase (HStk) gene will be transduced into the cells ex vivo using LTKOSN. 1 vector supernate. Insertion of the HStk gene into lymphocytes confers a sensitivity to the anti-herpes drug ganciclovir (GCV). This selective destruction of donor lymphocytes in situ will be used to abrogate the effect of graft versus host disease, if it develops.

Clinical Protocols↗
PubMed1998

Prevalence of glucocerebrosidase mutations in the Israeli Ashkenazi Jewish population.

Gaucher disease is the most prevalent inherited disease among Ashkenazi Jews. It is very heterogeneous due to a large number of mutations within the glucocerebrosidase gene, whose impaired activity is the cause for this disease. Aiming at determining Gaucher carrier frequency among the Ashkenazi Jewish population in Israel, 1,208 individuals were molecularly diagnosed for six mutations known to occur among Ashkenazi Jewish Gaucher patients, using the newly developed Pronto Gaucher kit. The following mutations were tested: N370S, 84GG, IVS2+1, D409H, L444P, and V394L. Molecular testing of these mutations also allows identification of the recTL allele. The results indicated that Gaucher carrier frequency is 1:17 within the tested population. The prevalence of N370S carriers is 1:17.5. This implies that approximately 1:1225 Ashkenazi Jews will be homozygous for the N370S mutation. Actually, in our study of 1,208 individuals one was found to be homozygous for the N370S mutation. The actual number of known Ashkenazi Jewish Gaucher patients with this genotype is much lower than that expected according to the frequency of the N370S mutation, suggesting a low penetrance of this mutation. Results of loading experiments in cells homozygous for the N370S mutation, as well as cells homozygous for the L444P and the D409H mutations, exemplified this phenomenon.

Cells, Cultured↗