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Biomedical subjects

D Berkowitz

Publications and source records attributed to D Berkowitz.

At least 37 records · Page 2Linked to original sources

Effect of gamma-hydroxybutyrate on pain, fatigue, and the alpha sleep anomaly in patients with fibromyalgia. Preliminary report.

OBJECTIVE: To evaluate the effects of using a gamma-hydroxybutyrate (GHB) administered in divided doses at night in 11 patients previously diagnosed with fibromyalgia (FM). METHODS: Subjects completed daily diaries assessing their pain and fatigue levels and slept in the sleep laboratory before and one month after initiating GHB treatment. Polysomnographic recordings were evaluated for sleep stages, sleep efficiency and the presence of the alpha anomaly in non-REM sleep. RESULTS: There was a significant improvement in both fatigue and pain, with an increase in slow wave sleep and a decrease in the severity of the alpha anomaly. CONCLUSION: Further controlled studies are needed to characterize the clinical improvement and the polysomnographic changes we observed.

Adult↗

Progressive familial intrahepatic cholestasis among the Arab population in Israel.

BACKGROUND: Progressive familial intrahepatic cholestasis, which constitutes a heterogeneous group of imperfectly delineated syndromes and appears to be inherited as an autosomal recessive condition, has not been hitherto reported from the Middle East, in spite of the high rate of consanguineous marriage in this region. METHODS: Sixteen affected children from six Israeli Arab families were evaluated over 30 years. All were born to consanguineous parents. RESULTS: Jaundice appeared during the first 3 weeks of life in 15 babies. When first referred, 10 had hepatomegaly and nine had splenomegaly. A progression toward cirrhosis was the rule. Serum levels of conjugated bilirubin, liver enzymes, and alkaline phosphatase were raised; gamma-glutamyl transpeptidase levels were normal in all three infants in whom it was examined, but elevated in two siblings of another family at ages 2 and 3 years. No abnormal bile acids were detected in the serum and urine of patients. Histologic examination of the liver showed giant-cell transformation, paucity of intrahepatic bile ducts, cholestasis, fibrosis, or cirrhosis. The pattern of liver pathology differed at times among affected members within the same family. Therapeutic trials with phenobarbital, cholestyramine, or ursodeoxycholic acid were ineffective. Survival of the patients was from 5 to 18 months in four families; in the other two families, three children received liver transplants, and one is awaiting liver transplantation. CONCLUSIONS: Progressive familial intrahepatic cholestasis should be included in the differential diagnosis of infants with cholestatic jaundice of unknown etiology, especially those born to consanguineous Arab parents.

Arabs↗

Adaptive response of the enterohepatic circulation of bile acids to extrahepatic cholestasis.

Experimental cholestasis induced by ligation of the common bile duct results in morphological and functional changes in the rat hepatocyte. The aim of this study was to evaluate the adaptive response of the transport process involved in the enterohepatic circulation of bile salts to obstructive cholestasis. Male Sprague-dawley rats with common bile duct ligation were killed after 48 and 72 hours. Portal and systemic blood and duodenal aspirates were collected. Taurocholate transport was measured in isolated ileal brush border (BBM) and liver basolateral membranes (BLM). Drastic reduction in intraluminal bile salt concentrations in ligated rats accompanied decreases in saturable taurocholate uptake by ileal BBMs. Kinetic analysis indicated that the decrease was attributable to reduction in transporter density and alteration in affinity for the substrate, both of which accentuated with increase in postligation time. In contrast, despite 20-fold higher portal venous bile salt concentrations, taurocholate uptake by hepatic sinusoidal membrane was lower in rats. Kinetic analysis and immunoblots developed using polyclonal antisera to the liver BLM bile acid transporter demonstrated a gradual decrease in transporter density with increase in postligation time accompanied by reduced taurocholate uptake by basolateral membrane. These results further support the concept that the ileal brush border membrane transporter is regulated by the availability of the substrate, whereas regulation of the bile salt transport across the liver BLM is independent of portal venous bile acid concentration.

Adaptation, Physiological↗

Role of the beta 3-adrenergic receptor locus in obesity and noninsulin-dependent diabetes among members of Caucasian families with a diabetic sibling pair.

Obesity and insulin resistance are important risk factors for the development of noninsulin-dependent diabetes (NIDDM) and are prevalent among predisposed first degree relatives of diabetic individuals. Recent molecular screening and analysis of a common missense mutation of the beta 3-adrenergic receptor gene suggested this locus as a strong candidate for increased obesity, earlier age of diabetes onset, and insulin resistance. To test the hypothesis that the beta 3-adrenergic receptor locus affects diabetes susceptibility, obesity as measured by body mass index, and components of the insulin resistance syndrome, we examined the role of this region in families ascertained for two or more NIDDM siblings. Linkage analysis was conducted using both parametric and nonparametric analyses, including multipoint sibling pair analysis. We found no evidence for linkage to NIDDM as a dichotomous trait and no evidence for linkage to body mass index, waist/hip ratio, insulin levels, or glucose levels as quantitative traits or to reported age of onset among NIDDM individuals. The Trp64 Arg missense mutation was present in 11% of the population. The mutation was not associated with NIDDM, and Arg64 carriers did not have earlier NIDDM onset, higher body mass index, or higher waist/hip ratio than Trp64 homozygotes. Among relatives, Arg64 carriers had significantly lower fasting glucose levels and lower waist/hip ratios than Trp64 homozygotes, but no characteristics of the insulin resistance syndrome. We conclude that the beta 3-adrenergic receptor locus does not play an important role in NIDDM susceptibility or in the insulin resistance syndrome among members of families with a strong predisposition to NIDDM.

Adult↗

Modern health care depends on technology, Part 2.

The first article in this series presented the principles and vocabulary of technology assessment and described the process used at St. Luke's, a tertiary care hospital in Bethlehem, Pennsylvania. This second article will describe the resources needed to support a technology assessment program. Technology planning, acquisition, and management will also be discussed. Historically, the health care marketplace has welcomed new technologies. In a future in which providers will be accountable for the outcomes of the care they provide, the ability to evaluate new and existing technologies will be essential for success.

Databases, Factual↗

Binding affinity and site selectivity of daunomycin analogues.

We have tested a series of daunomycin analogues for binding affinity to a group of oligonucleotides that contain binding sites specific for daunomycin and that were previously screened for relative binding affinity for daunomycin. The series of drugs differed from daunomycin in the sugar moiety, including substitution of a hydroxyl group for the charged amino group and replacement of the 2'-OH by an iodo substituent. Data were analyzed by Scatchard plots and association constants were estimated from the gamma-intercept at saturating levels of oligonucleotide. Because of the solubility problems associated with these compounds, Scatchard plots could not be extended to high levels of binding. A second method of analysis of the fluorescence data confirmed the semiquantitative association constants obtained from the intercepts of the Scatchard plots. The association constants were in the range of 10(5)-10(7) M-1. When compared with daunomycin, the compounds with hydroxyl substituted for the amino group in the sugar ring generally bound less well to the oligonucleotides, by factors of up to several hundred. Much of the binding lost upon removal of the charged amino group was restored, however, with compounds containing an iodo substituent on the sugar ring. Changing the iodo-substituted sugar from the natural L-form to the D-form diminished binding by 6-50-fold, depending on sequence. This result implies a stereospecific interaction of the natural sugar with the DNA chain. A positively cooperative curve was observed in the Scatchard plot for the D-form sugar.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Positioning and securement of riders and their mobility aids in transit vehicles: an analytical review.

Individuals are transported daily in transit vehicles while seated on their mobility aids. Although federal standards exist to regulate this practice, controversy exists over whether the regulations are effective or practical. This article describes an objective and analytical review of information available in several areas relevant to positioning and securing riders and their mobility aids in transit vehicles. The objective of the study was to present the current status of knowledge and to identify gaps in knowledge and related problems. As a result, recommendations are provided on future research needs and options for improvement of policy.

Accidents, Traffic↗

Effect of fasting on the enterohepatic circulation of bile acids in rats.

Fasting Sprague-Dawley rats for 72 h resulted in inhibition of bile salt synthesis, reduced bile flow and bile salt secretion rate, and reduced duodenal and portal venous bile acid concentrations. The initial rate of ileal brush border membrane (BBM) taurocholate (TC) uptake was markedly reduced in the fasted group (45% of control). TC uptake by BBM was saturable, with similar maximal transport velocity for the fasted rats and controls (1.69 +/- 0.06 and 1.62 +/- 0.017 nmol.mg protein-1.min-1, respectively) but higher Michaelis-Menten constant for fasted rats than for controls (96.9 +/- 20.0 and 54.9 +/- 10.2 microM, respectively). Hepatic basolateral membrane (BLM) TC uptake was enhanced by 65% in fasted animals. Transport kinetics in BLM had a similar Michaelis-Menten constant for fasted rats and controls (31.6 +/- 8.2 and 27.3 +/- 4.7 microM, respectively), and maximal transport velocity was higher for fasted rats than for controls (1.84 +/- 0.017 and 1.11 +/- 0.014 nmol.mg protein-1.min-1). The cholesterol-to-phospholipid ratio and fluorescence anisotropy in BLM of fasted rats decreased, and the cholesterol-to-phospholipid ratio and fluorescence anisotropy increased in ileal BBM. Alterations in the enterohepatic circulation of bile acids with fasting may alter expression of transport proteins for bile salts by direct effects on synthesis or indirectly through membrane lipid compositional changes.

Animals↗

Fasting enhances taurine transport by rat liver plasma membrane vesicles.

Hepatic taurine stores are maintained by biosynthesis from the sulfur-containing amino acids, methionine and cysteine, and by uptake via a Na(+)- and Cl(-)-dependent transport system, which is specific for beta-amino acids. We hypothesized that liver stores of taurine are maintained by enhanced hepatic transport during fasting when dietary sources for taurine and its precursors are diminished. Liver plasma membrane vesicles, enriched for the basolateral domain, were prepared from adult male rats fasted for 72 h and from control rats. The maximum velocity for Na(+)-dependent taurine uptake was twofold greater for the fasted group compared with the control group (0.87 +/- 0.09 vs. 0.31 +/- 0.03 nmol.mg protein-1.min-1). The apparent Michaelis constant for taurine was also greater for fasted compared with control (154.0 +/- 0.5 vs. 80.0 +/- 2.0 microM). gamma-Aminobutyric acid, but not alanine or glutamine, abolished the effect of fasting on hepatic taurine transport. To determine the effect of fasting independent of changes in the lipid microenvironment, taurine uptake was measured in proteoliposomes reconstituted by inserting detergent-solubilized membrane proteins into asolectin vesicles. Taurine uptake by proteoliposomes reconstituted from membranes prepared from the fasted group was significantly greater than from the control group. We conclude that Na(+)-dependent taurine transport is enhanced in liver plasma membranes prepared from fasted rats. Our findings imply that enhanced taurine uptake with fasting is due to either an increased number of functional carriers or activation of existing transporters.

Alanine↗

Localization of mRNA for three distinct alpha 1-adrenergic receptor subtypes in human tissues: implications for human alpha-adrenergic physiology.

alpha 1-Adrenergic receptors (alpha 1ARs) are virtually ubiquitous in human tissues and mediate important physiological functions as diverse as smooth muscle contraction, glycogenolysis, and myocardial inotropy. At least three alpha 1AR subtypes (alpha 1A/D, alpha 1B, and alpha 1C) have been described using molecular and pharmacological techniques. The identification of species heterogeneity (rat versus rabbit) in alpha 1AR subtype distribution has made it imperative to determine the distribution of alpha 1AR subtypes in human tissues. Accordingly, RNA extracted from human tissues was analyzed using RNase protection assays to determine alpha 1AR subtype expression. Of the cloned alpha 1ARs, alpha 1CAR mRNA predominates in many human tissues (heart, liver, cerebellum, and cerebral cortex), in contrast to its restricted distribution in both rats and rabbits. alpha (1B)AR mRNA is present in highest concentrations in human spleen, kidney, and fetal brain. alpha 1A/DAR mRNA is present in highest concentrations in human aorta and cerebral cortex. Hence, alpha 1AR subtype mRNA distribution is tissue selective and differs from that reported for rats and rabbits. These results have potentially significant implications for understanding human adrenergic physiology and are important for the rational development of alpha 1AR subtype-selective drugs.

Adrenal Glands↗

In vitro fertilization and embryo transfer for the treatment of infertility associated with polycystic ovary syndrome.

OBJECTIVE: To examine the outcome of treatment with IVF-ET of women with polycystic ovarian syndrome (PCOS) who failed to conceive on conventional treatment. DESIGN: Retrospective analysis with an age-matched control group. SETTING: University hospital infertility clinic and IVF unit. PATIENTS. INTERVENTIONS: Sixty-eight women with PCOS who had failed to conceive on treatment with clomiphene citrate and during six ovulatory cycles on gonadotropins underwent 208 cycles of IVF-ET. An age-matched group of 68 women with a tubal mechanical factor who received 143 treatment cycles during the same period served as controls. MAIN OUTCOME MEASURES: Cumulative conception rates, the cumulative livebirth rates, and IVF-ET data were compared between the two groups. Results of treatment with and without GnRH agonist (GnRH-a) within the groups were also compared. RESULTS: A comparison of PCOS and mechanical factor (control) groups showed almost identical results at 6 months for cumulative conception rate (82% versus 85%) and cumulative livebirth rate (69% versus 65%). Significantly more oocytes were retrieved but a smaller percentage fertilized in PCOS, and the pregnancy rate per ET did not differ between the two groups (23% versus 26%). Treatment with GnRH-a and gonadotropins as opposed to gonadotropins alone improved the cumulative conception rate, miscarriage rate, and cumulative livebirth rate in the PCOS but not in the control group and improved fertilization rates in both groups. CONCLUSIONS: For patients with PCOS who fail to conceive with gonadotropin treatment, IVF-ET is a successful treatment alternative, producing results equal to those for women with a mechanical tubal factor. Better results were achieved with GnRH-a in women with PCOS but made no difference to those with a mechanical tubal factor compared with treatment with gonadotropins alone.

Adult↗

Idiopathic infantile hypercalcemia: rapid response to treatment with calcitonin.

We report on a 7-week-old infant with idiopathic hypercalcemia, hypercalciuria and nephrocalcinosis. At the time of admission, serum concentrations of parathyroid hormone and 1,25(OH)2D3 were found to be inadequately high, and those of calcitonin and 24,25(OH)2D3 too low, relative to the hypercalcemia. Treatment with calcitonin normalized serum calcium concentrations within 4 days, and a 3-week course of thiazides combined with a decreased dietary calcium:phosphorus ratio corrected the hypercalciuria. A repeat profile of the calcium-regulating hormones done at the age of 5.5 months was normal. Based on the clinical course and the hormonal profiles, we hypothesize that the idiopathic infantile hypercalcemia in this patient could have resulted from a generalized maturational delay of calcium homeostasis. Treatment with calcitonin, therefore, seems to be the most appropriate way to control the hypercalcemia.

24,25-Dihydroxyvitamin D 3↗