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Biomedical subjects

A Rubinstein

Publications and source records attributed to A Rubinstein.

At least 55 records · Page 3Linked to original sources
PubMed1999

Magnesium for the treatment of nocturnal leg cramps: a crossover randomized trial.

BACKGROUND: Nocturnal leg cramps are a common health problem in the ambulatory setting. Our objective was to evaluate the efficacy of magnesium in the treatment of nocturnal leg cramps. METHODS: Our study was a crossover randomized double-blind placebo-controlled trial. We included patients from a large university-based ambulatory clinic in Buenos Aires, Argentina, with at least 6 cramps during the previous month. A total of 93 subjects took part in a 4-week washout period with placebo. Those who were still eligible (n = 45) were randomized to receive either (1) an oral dose of 900 mg magnesium citrate twice daily for 1 month, followed by a matching placebo for 1 month, or (2) the placebo first, followed by magnesium. Both groups had a 4-week washout period with placebo between each treatment month. Forty-two patients completed the 4-month study. The main outcome was the number of nocturnal leg cramps, and the secondary outcomes were duration, severity, and sleep disorders caused by those cramps. RESULTS: There were no significant differences between magnesium and placebo in any of the evaluated outcomes. The mean number of cramps was 11.1 (standard deviation [SD] +/- 7.3) for placebo versus 11.8 (SD +/- 7.6) for magnesium (P = .59). We observed a significant period-effect bias: All patients improved over time regardless of the treatment sequence they received. CONCLUSIONS: Magnesium was not effective for the treatment of nocturnal leg cramps. The period-effect bias probably occurred because of a combination of the natural history of this condition, a regression to the mean, and a true placebo effect.

Adult↗
PubMed1998

Fluctuations of lipid and lipoprotein levels in hyperlipidemic postmenopausal women receiving hormone replacement therapy.

BACKGROUND: Fluctuations in lipid and lipoprotein levels are encountered quite often in hyperlipidemic patients. We examined the possibility that lipid and lipoprotein levels fluctuate due to the different effects of estrogen and progestogen in postmenopausal hyperlipidemic women receiving combined hormonal replacement therapy. METHODS: In an open-label study conducted during 3 consecutive hormonal cycles (3 months), levels of fasting total cholesterol, triglycerides, and low (LDLC)- and high-density lipoprotein cholesterol (HDLC) were determined in 36 postmenopausal hyperlipidemic women on day 13 of conjugated equine estrogen (1.25 mg/d) therapy and on day 25 after 12 days of receiving estrogen plus medroxyprogesterone acetate (5 mg/d). RESULTS: While receiving estrogen and combined therapies, means +/- SD total cholesterol levels increased from 6.50 +/- 0.97 mmol/L (251 +/- 37 mg/dL) to 6.88 +/- 1.42 mmol/L (266 +/- 54 mg/dL) (P<.001); LDLC levels, from 4.05 +/- 1.14 mmol/L (156 +/- 44 mg/dL) to 4.62 +/- 1.36 mmol/L (178 +/- 52 mg/dL) (P<.001). Mean +/- SD HDLC cholesterol levels decreased from 1.44 +/- 0.32 mmol/L (55 +/- 12 mg/dL) to 1.29 +/- 0.28 mmol/L (50 +/- 10 mg/dL) (P<.001); triglyceride levels, from 2.23 +/- 1.03 mmol/L (197 +/- 91 mg/dL) to 2.06 +/- 1.04 mmol/L (182 +/- 92 mg/dL) (P<.001). CONCLUSIONS: Hyperlipidemic postmenopausal women receiving combined sequential estrogen and progestogen replacement therapy demonstrate very significant fluctuations in their lipid and lipoprotein levels. These fluctuations depend on the hormonal phase, ie, estrogen alone or combined with progestogen.

Estrogen Replacement Therapy↗
PubMed1998

The influence of pregnancy on human immunodeficiency virus type 1 infection: antepartum and postpartum changes in human immunodeficiency virus type 1 viral load.

OBJECTIVE: Our objective was to examine the influence of pregnancy on human immunodeficiency virus type 1 viral load by measuring human immunodeficiency virus type 1 ribonucleic acid levels during pregnancy and post partum. STUDY DESIGN: One or more plasma or serum specimens obtained before and during the third trimester, and at 2, 12, and 24 months post partum were available for 160 human immunodeficiency virus type 1-seropositive women enrolled in the Mothers and Infants Cohort Study between January 1986 and January 1991. All specimens were frozen and stored at -70 degrees C until analyzed in batch for human immunodeficiency virus type 1 ribonucleic acid by polymerase chain reaction. A multivariate longitudinal random effects model was developed to examine changes in human immunodeficiency virus type 1 ribonucleic acid levels over time. RESULTS: Overall, human immunodeficiency virus type 1 ribonucleic acid levels rose significantly during the study period, particularly during the second year post partum (mean, 0.09 log per year; 95% confidence interval, 0.03 to 0.15 logs per year; p = 0.005). However, the mean slope during pregnancy was not significantly different from zero (p = 0.65). CONCLUSION: Pregnancy had little immediate effect on human immunodeficiency virus type 1 viral load in most human immunodeficiency virus type 1-seropositive women.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Migration of adhesive and nonadhesive particles in the rat intestine under altered mucus secretion conditions.

The migration rate of adhesive (polycarbophil) and nonadhesive (Eudragit RL-100) particles was studied in the small and large intestine of the anesthetized rat under altered mucus secretion conditions accomplished by cholinergic stimulation (a previously developed in situ model which distinctly accounts for the effect of regional changes in mucus turnover rate on mucoadhesion in the digestive tube of the rat). It was found that in the proximal jejunum the relative recovery time (RRT) of adhesive particles, but not nonadhesive particles, was decreased by carbachol stimulation. However, adhesive particles agglomerated a short while after their administration into this organ. In the colon RRT of both adhesive and nonadhesive particles decreased in a similar manner as the mucus secretion increased. It is concluded that, in the rat, interactions between intestinal mucus layer and adhesive and nonadhesive particles are similar. The corresponding similarity in the intestinal transit time for both types of particles raises doubts about the advantage of nonspecific adherence in the design of oral prolonged-release dosage forms.

Adhesives↗
PubMed1998

Low swelling, crosslinked guar and its potential use as colon-specific drug carrier.

PURPOSE: (a) To reduce the swelling properties of guar gum (GG) by crosslinking it with glutaraldehyde (GA), while maintaining its degradation properties in the presence of typical colonic enzymes, (b) to characterize the modified GG and to examine its degradation properties in vitro and in vivo, and (c) to assess, by drug probes with different water solubilities, the potential of the crosslinked GG to serve as a colon-specific drug carrier. METHODS: GG was crosslinked with increasing amounts of GA under acidic conditions to obtain different products with increasing crosslinking densities. These products were characterized by measuring (a) their swelling properties in simulated gastric and intestinal fluids, (b) their crosslinking densities, (c) the release kinetics of three different drugs: sodium salicylate (SS), indomethacin (Indo) and budesonide (Bud) from the crosslinked products into buffer solutions, with or without a mixture of galactomannanase and alpha-galactosidase, and (d) their in vivo degradation in the cecum of conscious rats with and without antibiotic treatment. RESULTS: Significant reduction in GG swelling properties, in both simulated gastric and intestinal fluids, was accomplished by its crosslinking with GA. The crosslinking density of the modified GG products was GA concentration-dependent. The release of SS from crosslinked GG discs was completed within 120 minutes. During the same period of time and for more than 10 hours the release of Indo and Bud was negligible. The release rate of the latter two drugs was enhanced when galactomannanase and alpha-galactosidase were added to the dissolution media. Discs made of the crosslinked GG were implanted in the cecum of rats and their degradation was assessed after 4 days. The extent of degradation was dependent on the amount of GA used for the crosslinking. After 4 days the same discs were recovered intact from rats exposed to antibiotic treatment and from simulated gastric and intestinal fluids. CONCLUSIONS: Reducing the enormous swelling of GG by crosslinking it with GA resulted in a biodegradable hydrogel which was able to retain poorly water soluble drugs, such as Indo and BUD, but not highly water soluble drugs, such as SS, in artificial gastrointestinal fluids. A variety of hydrogels with increasing crosslinking densities were produced and tested for their potential use as colon-specific drug platforms in vitro and in vivo. Their performance did not depend on creating physical barriers by means of compression.

Administration, Oral↗
PubMed1998

Receptor-mediated maternofetal transfer of immunoglobulins. Inhibition of transport of anti-HIV-1 immunoglobulin by generic immunoglobulins in the in vitro perfused placenta.

OBJECTIVES: The passage of immunoglobulin G (IgG) across the placenta is thought to involve Fc' receptors on the syncytiotrophoblast. To confirm the receptor dependency of this process we have studied the changes in the tissue content and transfer kinetics of immunoglobulins and hyperimmune serum to HIV (HIVIG) during in vitro dual placental perfusion. METHODS: Isolated lobules of term placentae from normal pregnancies were perfused in a model of maternal and fetal circulation. The perfused tissue was compared to fresh tissue samples from the same placenta for the content of IgG, IgG subclasses, IgM, cytokeratin, human placental lactogen and SP1 antigen by immunohistochemistry and by protein elution. RESULTS: The immunoglobulin staining faded by an average of 40% during the 1st hour of perfusion. In contrast, staining for cytokeratin, human placental lactogen and SP1 remained unchanged. During a 4-hour recycling of endogenous immunoglobulins in the maternal circulation, IgG and HIVIG crossed to the fetal side in a steady rate. The transport of HIVIG could be inhibited by preperfusion with an intravenous gammaglobulin preparation (IVIG). DISCUSSION: The transfer of IgG across the placenta occurs in a steady state rate consistent with a receptor-mediated mechanism. Furthermore, inhibition of HIVIG maternofetal transfer by IVIG further establishes the receptor-mediated transfer of immunoglobulins through the placenta.

Female↗
PubMed1998

Hepatitis C virus infection in the mothers and infants cohort study.

OBJECTIVES: To estimate the hepatitis C virus (HCV) vertical transmission rate, the effect of potential risk factors, and the pattern of HCV antibody response and viremia in HCV-infected infants. STUDY DESIGN: The Mothers and Infants Cohort Study enrolled both human immunodeficiency virus (HIV)-seropositive and HIV-seronegative pregnant women at five obstetric clinics in New York City in a prospective cohort study between January 1986 and January 1991. HCV-infected mothers and their 122 offspring were followed-up for a minimum of 12 months for evidence of HCV infection as determined by persistent HCV antibodies or detection of HCV RNA by reverse transcription polymerase chain reaction. Comparisons among groups for categorical variables were performed using the Fisher's exact test. RESULTS: Seven (6%; 95% confidence interval, 2%-11%) of the 122 infants were HCV-infected. There was a tendency for increased risk of transmission with maternal viral and obstetrical factors, such as coinfection with HIV (7% vs 4%), high HIV viral load (13% vs 6%), HCV viremia (8% vs 3%), vaginal delivery (6% vs 0%), and female gender of offspring (8% vs 3%), although none of the associations reached statistical significance. After loss of maternal antibody, HCV antibody seroconversion occurred at a mean age of 26 months in 3 HIV-coinfected infants compared with 7 months of age in 4 HCV-infected HIV-uninfected infants. Serial samples showed that HCV RNA persisted in 6 infants for at least 18 to 54 months. CONCLUSIONS: Our study is in accordance with other studies that have shown low overall HCV vertical transmission risk and a trend toward higher risk with maternal risk factors such as HIV-coinfection or HCV viremia. A delay in infant HCV antibody response may be associated with HIV coinfection although larger studies are needed to confirm these findings.

AIDS Serodiagnosis↗
PubMed1997

Sexual behavior and injection drug use during pregnancy and vertical transmission of HIV-1.

We evaluated maternal sexual behavior and injection drug use practices as possible risk factors for vertical transmission of human immunodeficiency virus type 1 (HIV-1). Data were analyzed from the Mothers and Infants Cohort Study, a prospective study in Brooklyn and the Bronx, New York. A total of 207 mother-infant sets were enrolled between 1986 and 1991 and followed for up to 4 years after the enrollment visit during pregnancy. HIV-1 transmission occurred in 49 of 201 mother-infant sets, yielding an overall transmission rate of 24.4% (95% confidence interval (CI) = 18.7% to 31.0%). Increased frequency of vaginal intercourse after the first trimester of pregnancy was positively associated with vertical transmission of HIV-1 (trend p = 0.03). A lifetime history of injection drug use was not associated with vertical transmission. However, a history of combined cocaine and heroin injection after the first trimester of pregnancy was associated with vertical HIV-1 transmission, particularly among women with CD4+ lymphocyte levels of 20% or higher (risk ratio = 4.0; 95% CI = 2.0 to 8.1). Cocaine and heroin injection drug use after the first trimester accounted for most of the relation between preterm birth and vertical HIV-1 transmission in this cohort. Maternal coinfection with hepatitis C virus or human T-cell lymphotropic virus types I and II could not explain these observations, because coinfection with these viruses had no detectable effect on HIV-1 transmission. These results suggest that maternal sexual behavior and injection drug use practices during the second and third trimester of pregnancy may modify the risk of vertical HIV-1 transmission.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Three-dimensional image reconstruction of large nuclear RNP (lnRNP) particles by automated electron tomography.

Nuclear RNA transcripts of split genes and their splicing products, as well as the general population of nuclear polyadenylated RNA are packaged in multi-component large nuclear ribonucleoprotein (lnRNP) particles. These lnRNP particles, which sediment at the 200 S region in sucrose gradients, contain all U small nuclear RNPs required for precursor messenger RNA (pre-mRNA) splicing and several protein splicing factors, including U2AF and the SR proteins. Electron microscopy of lnRNP particles revealed a large compact structure of 50 nm in diameter. In this study we employed automated computed tomography from electron micrographs for the three-dimensional (3D) image reconstruction of individual lnRNP particles isolated from mammalian cells nuclei and negatively stained. For each particle, a tilt series of 71 images was collected by direct digital recording of the images on a CCD camera attached to a computer controlled TEM facility. The 3D image was reconstructed according to the back projection principle. For rendering, real time display and comparison of the reconstructed particles, interactive computer graphics was employed. The reconstructed 3D images show a compact structure composed of four major subunits connected to each other. Comparison of the reconstructed lnRNP particles revealed morphological similarity of the individual particles, as well as similarity among the sub-structures. Based on these observations we propose a model for the packaging of nuclear pre-mRNAs in lnRNP particles where each substructure represents a functional unit. This model is compatible with the requirements for alternative splicing in multi-intronic pre-mRNAs, and with the fact that the splicing of multi-intronic pre-mRNAs does not occur in a sequential manner.

Animals↗
PubMed1997

The use of scintigraphy to provide "proof of concept" for novel polysaccharide preparations designed for colonic drug delivery.

PURPOSE: The aim of the present study was to provide "proof of concept" data in man for novel polysaccharide preparations designed for colonic drug delivery using gamma scintigraphy. METHODS: Two placebo calcium pectinate matrix tablet formulations were studied: one contained calcium pectinate and pectin (CaP/P) and was designed to rapidly disintegrate in the ascending colon, the other contained calcium pectinate and guar gum (CaP/GG) and was designed to disintegrate more slowly, releasing its contents throughout the ascending and transverse colon. Both formulations were enteric coated in order to protect them from the stomach. Ten healthy volunteers received either a CaP/P or CaP/GG tablet, in a randomised cross-over study. Transit and disintegration of the radiolabelled formulations was followed by gamma scintigraphy. Rat studies were conducted in order to verify that the expected colonic degradation of the polysaccharide formulations was as a consequence of bacterial enzyme attack. RESULTS: The in vivo clinical study confirmed the results obtained in the rat and bench in vitro fermentation models; complete tablet disintegration for Formulation CaP/GG appeared to be slower than that of Formulation CaP/P and the time and the location of complete tablet disintegration was more reproducible with Formulation CaP/P compared to Formulation CaP/GG. CONCLUSIONS: These results provide "proof of concept" data for the use of calcium pectinate preparations for drug delivery to the colon and highlight the value of scintigraphy in focusing the development strategy for colonic targeting preparations.

Adult↗
PubMed1997

The effect of intestinal bacteria adherence on drug diffusion through solid films under stationary conditions.

PURPOSE: To study the in vitro and in vivo the role of surface bacterial adhesion on the diffusion of model drugs at stationary conditions. METHODS: Salicylic acid (SA) diffusion through ethyl cellulose (EC) films was measured in vitro in side-by-side diffusion cells with and without E. coli of intestinal origin. Insulin (I) release from paper strips coated or uncoated with pectin films, with or without antibiotic treatment, was measured in vivo in conscious rats after cecal implantation by comparing blood glucose levels at Tmax of the pharmacodynamic effect. RESULTS: During five hours of diffusion studies which were performed immediately following incubation of EC films with bacteria, the diffusion rate of SA throughout the films was 2.72-fold lower in the presence of bacteria compared with the diffusion rate in the control studies conducted without bacteria. The mean blood glucose levels dropped in the rat to 40.6 +/- 21.6% of glucose basal levels within 2.4 +/- 1.4 h when uncoated I solid carriers were used. Glucose levels did not change for pectin-coated dosage forms. After antibiotic treatment which prevented the formation of bacterial biofilm on the surface of the I solid dosage forms, blood glucose levels dropped to 22.0 +/- 4.7% and 50.9 +/- 20.5% of glucose basal levels within 7.4 +/- 2.6 h and 1.8 +/- 0.9 h for pectin uncoated or coated dosage forms, respectively. Maximum bacterial adherence occurred at stationary conditions (RPM = 0), while at maximum agitation (200 RPM), almost no adherence occurred. CONCLUSIONS: (a) Bacterial adherence shows down the diffusion rate of SA through EC films; (b) Under stationary conditions bacterial adherence may also interfere with drug release from biodegradable (pectin) films; (c) Successful functioning of biodegradable colon-specific delivery systems depends on agitation and surface friction in the lumen of the colon.

Animals↗
PubMed1997

Influence of other maternal variables on the relationship between maternal virus load and mother-to-infant transmission of human immunodeficiency virus type 1.

To assess the relationship between maternal human immunodeficiency virus (HIV) type 1 RNA level, other important covariates, and mother-to-infant (vertical) transmission of HIV-1, third trimester repository specimens from 160 HIV-1-seropositive women enrolled in the Mothers and Infants Cohort Study between 1986 and 1991 were assayed in batch for HIV-1 RNA. A significant association between peripheral blood HIV-1 RNA level and vertical transmission remained after controlling for CD4 cell level, duration of ruptured membranes, "hard" drug (cocaine and heroin) use, and frequency of sexual activity during pregnancy. However, the association was attenuated among women with advanced HIV infection and those with a high frequency of sexual activity during pregnancy. In these settings, interventions that target risk factors other than virus load may be particularly important for preventing vertical transmission of HIV-1.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Holmium YAG laser-assisted osteotomies in plastic and reconstructive surgery: a preliminary report.

An Omnipulse holmium-yttrium aluminum garnet (YAG) laser was used to assist in the harvesting of outer table or split calvarial bone grafts in cadaver skulls. Two- or 4-mm depth and 0.55-mm width holes in the outer cortex of cadaveric calvarium were formed without apparent gross periosteal or bony injury. Osteotomes were then used to shave or split calvarial grafts by connecting the 2- and 4-mm depth holes, respectively. The procedure was efficient as well as precise. We believe that this method of bone graft harvesting may have the added benefit of safety by decreasing the incidence of inadvertent dural penetration. This study will lead to further analysis of the potential use for additional bony work with the Omnipulse holmium-YAG laser.

Bone Transplantation↗
PubMed1997

Suppression of HIV-1 replication by propolis and its immunoregulatory effect.

In the current study we show that propolis, a non-toxic natural bee-hive product, suppresses HIV-1 replication and modulates in vitro immune responses. CEM cells were treated with propolis at nontoxic concentrations prior to or following infection with HIV-1. Propolis abolished syncytium formation at 4.5 micrograms/ml and inhibited it at lower doses in a concentration-dependent manner. Propolis decreased p24 antigen production by as much as 90-100% in a concentration-dependent manner. Furthermore, modulation of peripheral blood mononuclear cells (PBMCs) mitogenic responses upon the addition of propolis was noted, reducing the elevated responses to Concanavalin A (Con A) and enhancing suppressed mitogenic responses to pokeweed mitogen (PWM). In summary, propolis may constitute a non-toxic natural product with both anti HIV-1 and immunoregulatory effects.

Antigens, CD↗
PubMed1996

CD4 confers susceptibility to human immunodeficiency virus type 1 infection in a rat fibroblast cell line.

A new model system is delineated that will enable study of CD4 cofactors and gp120 binding proteins other than CD4. We have previously described a nontransformed rat fibroblast cell line that can efficiently produce HIV-1 upon transfection with an HIV-1 infectious clone, in contrast to other nonhuman mammalian cell lines tested. In the present study we analyzed the susceptibility to HIV-1 infection of Rat2 cells expressing the human CD4 protein. We have used the mammalian expression vector pKS286, in which HIV-1 LTR drives the expression of the CD4 gene. We show that the Rat2 cell line, expressing the human CD4 (Rat2/CD4), is susceptible to fusion with and infection by HIV-1. The virus produced by the Rat2/CD4 cells was infectious. CD4 expression in the Rat2/CD4 was down-regulated over time, similarly to HIV-1 expression in HIV-1-transfected Rat2 cells. Transfection of the Rat2/CD4 cells with a tat expression vector reestablished the CD4 expression on the surface of those cells, as expected. We conclude that the expression of a gp120 binding protein on the Rat2 cells' surface suffices to render the Rat2 cells susceptible to HIV-1 infection.

Animals↗
PubMed1996

Clearance of chylomicron remnants in normolipidaemic patients with coronary artery disease: case control study over three years.

OBJECTIVE: To test the hypothesis that subjects who clear chylomicron remnants slowly from plasma may be at higher risk of coronary artery disease than indicated by their fasting plasma lipid concentrations. DESIGN: Case control study over three years. SETTING: An 800 bed general municipal hospital. SUBJECTS: 85 normolipidaemic patients with coronary artery disease selected prospectively and matched with 85 normolipidaemic subjects with normal coronary arteries on angiography. INTERVENTIONS: All subjects were given a vitamin A fat loading test which specifically labels intestinal lipoproteins with retinyl palmitate. MAIN OUTCOME MEASURE: Postprandial lipoprotein metabolism. RESULTS: The area below the chylomicron remnant retinyl palmitate curve was significantly increased in the coronary artery disease group as compared with the controls (mean 23.4 (SD 15.0) v 15.3 (8.9) mumol/l.h; 95% confidence interval of difference 4.37 to 11.82). CONCLUSION: Normolipidaemic patients with coronary artery disease had significantly higher concentrations of chylomicron remnants in plasma than normolipidaemic subjects with normal coronary vessels. This may explain the mechanism underlying the susceptibility to atherosclerosis of coronary artery disease patients with normal fasting lipid values. As diet and drugs can ameliorate the accumulation of postprandial lipoproteins in plasma, the concentration of chylomicron remnants should be measured in patients at high risk of coronary artery disease.

Adult↗