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Biomedical subjects

A Rubinstein

Publications and source records attributed to A Rubinstein.

At least 37 records · Page 2Linked to original sources
PubMed2000

Anticipatory strategy training: implications for the postlingually hearing-impaired adult.

The present study was designed to determine if speech recognition performance will improve after subjects prepare for an unfamiliar communication situation as opposed to a familiar one. Forty-five normal-hearing subjects were divided into three groups: one trained using a well-known fairytale, one trained using an obscure fable, and one without training. Post-training, all groups performed similarly when tested on the familiar tale. When test material involved the unfamiliar fable, only the group trained on that material obtained significantly better scores than the other groups. Results support teaching clients that increasing their knowledge of upcoming unfamiliar events can improve subsequent speech recognition.

Adult↗
PubMed2000

Drug targeting by surface cationization.

Cationization of drug products and carriers involves a direct modification or attachment of conveying or accompanying components, either of which cause a charge modification. Cationization of macromolecules such as proteins and nucleotides and particulate drug carriers generally enhances their cellular uptake by endocytosis. The most common use of cationization today is in gene delivery. This is undertaken by either employing cationic polymers or entraping nucleotides in cationic carriers such as cationic liposomes. Cationized delivery systems are also used to overcome biological barriers and are suggested for drug targeting, in a nonspecific manner, to a variety of body organs, including brain, eyes, nose, and inflamed intestinal epithelium. Protein cationization is also suggested both for tumor immunotherapy and as a diagnostic tool in cancer therapy. Cationization has proven itself to be a straightforward tool for targeting to cells, tissues, and selected organs. This article reviews the extensive range of applications of cationization for improving drug and gene delivery and summarizes major technologies employed for that purpose.

Animals↗
PubMed1999

Immunologic responses of HIV-1-infected study subjects to immunization with a mixture of peptide protein derivative-V3 loop peptide conjugates.

V3 loop peptide sequences from several HIV-1 strains were covalently linked to purified protein derivative (PPD) of Mycobacterium tuberculosis. A mixture of PPD conjugates of V3 loop peptides from six different strains of HIV-1 induced a stronger antibody response than a single V3 peptide-conjugate administered to guinea pigs and humans. Sera from animals immunized with a PPD-six peptide-PPD conjugate neutralized multiple primary-isolate strains of HIV-1. Potent immune responses were noted only when animals were primed with bacillus Calmette-Guerin (BCG), PPD was covalently bound to the peptides, and PPD was used as the carrier protein. Based on these animal studies, an immunogen consisting of PPD-conjugated V3 loop peptides from five HIV-1 strains was tested in 7 HIV-1 seropositive PPD skin test positive study subjects. Vaccinees exhibited over time a uniform increase in neutralizing antibodies for both laboratory adapted and primary isolates of HIV-1, including strains from multiple clades. In 3 patients with baseline viral loads between 8000 and 12,000 RNA copies/ml, the viral load declined in 2 patients to <400 copies/ml and in 1 patient to 1200 copies/ml without concurrent administration of highly active antiretroviral therapy (HAART).

AIDS Vaccines↗
PubMed1999

Hormone replacement therapy enhances postprandial lipid metabolism in postmenopausal women.

Postmenopausal estrogen therapy reduces cardiovascular morbidity and mortality, except in women with advanced coronary disease. This beneficial effect is partly attributed to a reduction of fasting plasma total and low-density lipoprotein cholesterol (LDL-C) and an elevation of plasma high-density lipoprotein cholesterol (HDL-C) concentrations. Since postprandial lipemia seems to play a role in the pathogenesis of coronary artery disease, we evaluated the effect of hormone replacement therapy (HRT) on postprandial lipoprotein metabolism in 14 normolipemic postmenopausal women. A vitamin A fat-loading test before and after three cycles of treatment with a sequential combination of conjugated equine estrogen (CEE) and medroxyprogesterone acetate (MPA) was used to label chylomicrons and chylomicron remnants with retinyl palmitate (RP), and RP clearance was assessed over an 8-hour period postprandially. Following 3 months of HRT, fasting total cholesterol and LDL-C levels were reduced 9.8% (P = .049) and 16.5% (P = .023), respectively. Fasting HDL-C levels increased 18.9% (P = .001). Fasting triglycerides (TGs) increased, but not significantly. Postprandial integrated plasma TGs did not change significantly. The integrated RP levels in whole plasma and chylomicron (Svedberg flotation units [Sf] > 1,000) and nonchylomicron (Sf < 1,000) fractions were reduced 58% (P = .043), 78% (P = .041), and 75% (P = .001), respectively, after hormonal treatment. Enhanced clearance of chylomicrons and chylomicron remnants by HRT may contribute to the protective effect of estrogens against cardiovascular disease in normolipemic postmenopausal women.

Chylomicrons↗
PubMed1999

Changes in immune activation markers during pregnancy and postpartum.

Changes in CD4 + cell levels and other immune parameters have been reported to occur during pregnancy but the timing of these alterations and their relationship to changes in immune function have not been well characterized. In addition, the influence of sociodemographic, obstetric, and other covariates on these relationships is largely unknown. We measured three immune activation markers, soluble interleukin-2 receptor (sIL-2Ralpha), soluble CD8 antigen (sCD8), and neopterin during pregnancy and postpartum in 170 HIV-1-seronegative women enrolled in the Mothers and Infants Cohort Study. Ante-partum and postpartum changes in these markers were examined using multivariable longitudinal random effects models. Neopterin levels began to rise well before delivery and were in decline by 2 months postpartum. sIL-2Ralpha and sCD8 levels increased at or near delivery and peaked by 2 months postpartum. After adjustment for other variables, the peak in sIL-2Ralpha was greater among women with pre-term than full-term deliveries (P = 0.05). All three markers were higher in whites than non-whites and in 'hard' drug users than non-users (P < or = 0.001 for each). After adjustment for these and other variables, hepatitis C virus (HCV) seropositivity was associated with higher levels of sCD8 and neopterin (P < or = 0.001 for each) but not sIL-2Ralpha (P = 0.27). These longitudinal data indicate that a state of broad immune activation develops at or near delivery. A number of maternal variables appear to influence the magnitude of these changes.

Adult↗
PubMed1999

Differences in the reducing power along the rat GI tract: lower antioxidant capacity of the colon.

The ability of the gastrointestinal (GI) tract, as well as other tissues, to cope with reactive oxygen species (ROS) efflux in pathological events is determined partly by epithelial antioxidant levels. These levels are comprised of tissue antioxidant enzymes and low molecular weight antioxidants (LMWA). While glutathione levels and the activity of enzymatic antioxidants along the GI tract have been studied, the contribution of the overall LMWA to the total antioxidant capacity has not yet been determined. In this study the overall antioxidant activity in the mucosa/submucosa and muscularis/serosa of various sections along the small intestine and colon of the rat was evaluated by determining the reducing power, which reflects the total antioxidant activity derived from LMWA, using cyclic voltammetry. The activity of the antioxidant enzymes superoxide dismutase (SOD) and catalase was also measured. The reducing power (total antioxidant activity) was higher in the mucosa/submucosa of the small intestine as compared to the mucosa/submucosa of the colon. Similarly, catalase and SOD activity in the mucosa/submucosa of the small intestine was significantly higher than in the mucosa/submucosa of the colon. Differences were also observed in the reducing power and SOD activity in the muscularis/serosa of the rat small intestine as compared to the colon. The low antioxidant capacity in the colon may facilitate reactive oxygen species (ROS)-mediated injury and lead to inflammatory diseases such as ulcerative colitis, specifically in the colon.

Animals↗
PubMed1999

Development and psychometric testing of a quality of recovery score after general anesthesia and surgery in adults.

UNLABELLED: A variety of methods have been used to quantify aspects of recovery after anesthesia. Most are narrowly focused, are not patient-rated, and have not been validated. We therefore set out to develop a patient-rated quality of recovery score. We constructed a 61-item questionnaire that asked individuals (patients and relatives, medical and nursing staff; total n = 136) to rate various postoperative items describing features a patient may experience postoperatively. The most highly ranked items were included in a final nine-point index score, which we called the "QoR Score." We then studied two cohorts of surgical patients (n = 449). There was good convergent validity between the QoR Score and the visual analog scale score (rho = 0.55, P < 0.0001). Discriminant construct validity was supported by comparing resultant QoR Scores in patients undergoing day-stay, minor, and major surgery (P = 0.008), as well as a negative correlation with duration of hospital stay (rho = -0.20, P < 0.0001), and, using multivariate regression, demonstrating a significant negative relationship between QoR Score and female gender (P = 0.048) and older age (P = 0.041). There was also good interrater agreement (rho = 0.55, P < 0.0001), test-retest reliability (median rho = 0.61, P < 0.0001), and internal consistency (alpha = 0.57 and 0.90, P < 0.0001). There was a significant difference between the groups of patients recovering from major and minor surgery (P < 0.001). This study demonstrates that the QoR Score has good validity, reliability, and clinical acceptability in patients undergoing many types of surgery. IMPLICATIONS: We set out to develop a patient-rated quality of recovery score (QoR) that could be used both as a measure of outcome in perioperative trials and for clinical audit. We first surveyed patients and staff to identify important aspects of recovery, then developed a nine-point QoR Score. This was then compared with other measures of postoperative outcome. We found that the QoR Score is a useful measure of recovery after anesthesia and surgery.

Adolescent↗
PubMed1999

Efficacy and safety of cerivastatin for type 2 diabetes and hypercholesterolaemia. Hyperlipidaemia in Diabetes Mellitus investigators.

BACKGROUND: The prevalence of coronary heart disease (CHD) is markedly increased in diabetic patients compared with non-diabetic individuals, and its prognosis is less good. Serum total and low-density lipoprotein (LDL) cholesterol concentrations have been shown to be powerful predictors of CHD morbidity and mortality in patients with type 2 diabetes. The available data suggest that the target cholesterol concentration in patients with diabetes should be similar to that in non-diabetic individuals with a previous myocardial infarction. This led us to investigate the efficacy, tolerability and safety of a new, highly potent statin, cerivastatin, in diabetic hyperlipidaemia. METHODS: This was a multinational, multicentre, double-blind, randomized study in type 2 diabetic patients with hypercholesterolaemia (LDL cholesterol >3.35 mmol/l; triglycerides <4.56 mmol/l). Eligible patients were randomly assigned to groups to receive cerivastatin 0.1 mg or 0.3 mg or placebo in a ratio of 2:2:1 for 12 weeks. They were monitored in the clinic every 4 weeks. RESULTS: Of the 453 patients screened, 265 were allocated to the study groups. Fifty-one received placebo and 107 patients were assigned to each active treatment group (0.1 mg and 0.3 mg cerivastatin). At the close of the study, total cholesterol had decreased by 13.7% and 23.5%, LDL cholesterol decreased by 20.2% and 33.8%, and triglyceride concentrations decreased by 3.9% and 12.3% in the cerivastatin 0.1 mg and 0.3 mg groups, respectively. There was no significant difference between the groups in haemoglobin A1c, adverse events or increases in liver and muscle enzymes during the study period. CONCLUSIONS: Hypercholesterolaemic patients with type 2 diabetes had a significant reduction in LDL cholesterol and total cholesterol concentrations after cerivastatin treatment once daily. The dose of 0.3 mg cerivastatin is effective in diabetic hypercholesterolaemia, with co-reduction of triglyceride concentrations. The effect of cerivastatin on coronary morbidity and mortality is currently being investigated in clinical trials.

Adult↗
PubMed1999

Thyroxine replacement therapy enhances clearance of chylomicron remnants in patients with hypothyroidism.

To further confirm the benefit of replacement therapy in terms of risk for coronary artery disease, we evaluated the effect of T4 on postprandial lipoproteins in patients with hypothyroidism. Nine normolipidemic patients (aged 62.75+/-7.6 yr) with TSH of 32.2+/-13.2 mU/L and free T4 of 0.66+/-0.17 ng/mL were treated with T4 (50-100 microg/day) for at least 4 months. The behavior of postprandial lipoproteins was assessed before and during treatment by determining retinyl palmitate levels in the total plasma, chylomicrons (Sf >1000) and chylomicron remnants (Sf <1000) fractions for 8 h after a mixed meal plus vitamin A. During T4 treatment, serum levels of TSH and FT4 were 4.4+/-4.9 mU/L and 1.2+/-0.34 ng/mL (P = 0.001 and P = 0.002), respectively. Fasting low density lipoprotein cholesterol decreased from 166+/-35 to 135+/-23 mg/dL (P = 0.035). Retinyl palmitate (RP) levels in the chylomicron remnant fraction was reduced significantly during therapy from 6948+/-2790 to 5174+/-2401 microg/L x h (area under the curve +/-SD; P = 0.014). Total plasma RP and chylomicron RP remained unchanged. We conclude that T4 enhances the clearance of chylomicron remnants in normolipidemic patients with hypothyroidism.

Cholesterol, HDL↗
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↗