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Biomedical subjects

A Rubinstein

Publications and source records attributed to A Rubinstein.

At least 91 records · Page 5Linked to original sources

The long-term effect of early telephone intervention on hearing aid success.

The purpose of the study was to determine if subjects who were contacted by telephone periodically during the first 3 months following hearing-aid dispensing would report greater satisfaction, more frequent hearing aid use, and fewer complaints at one year postdispensing than subjects who were not contacted frequently. Subjects were 55 hearing-impaired adults who purchased aids, 27 of whom were contacted periodically by phone. Results revealed that frequent telephone contact in the period soon after dispensing does not appear to be an effective mass management tool in this population, although its value cannot be ruled out for some types of clients.

Aged↗

IgE levels in pediatric HIV-1 infection.

BACKGROUND: Atopic symptoms such as sinusitis, eczema, and wheezing are common in human immunodeficiency virus (HIV)-infected children. OBJECTIVE: To determine whether IgE levels are increased in HIV-seropositive children, and to determine whether there is a relationship between IgE, stage of disease, and atopic symptoms. METHODS: Levels of serum IgE and parameters of HIV infection, including absolute CD4 and CD8 T lymphocyte counts, and serum levels of neopterin, beta 2 microglobulin and HIV P24 antigen were measured. Clinical parameters including stage of disease, opportunistic infections, and atopic symptoms were recorded. RESULTS: IgE was increased prior to 1 year of age and mean levels remained elevated through age 6 years but regressed to the normal mean in children ages 7 to 9. There was a strong association between increased IgE and the presence of secondary disseminated or systemic diseases including pulmonary lymphoid hyperplasia, Pneumocystis carinii pneumonia, or disseminated cytomegalovirus infection. There was no correlation between CD4 levels and IgE levels (r = .03). The relationship between IgE and serum P24 antigen, beta 2 microglobulin, and neopterin levels was also analyzed. A weak positive correlation was found only with serum p24 antigen levels (r = .24). Atopic symptoms were found in a subpopulation of these children, with wheezing occurring in 27% of all patients, atopic dermatitis in 5%, drug reactions in 7% and sinusitis in 8% but IgE levels were not significantly elevated in patients with atopic symptoms. CONCLUSIONS: These findings demonstrate that serum IgE is increased in children very early after HIV infection and that IgE levels increase in association with HIV-associated systemic disease. Increased IgE is not associated with atopic symptoms in children.

Biomarkers↗

Improved brain delivery and in vitro activity of zidovudine through the use of a redox chemical delivery system.

OBJECTIVE: Improved therapy for AIDS dementia and related encephalopathies may be achieved through enhanced delivery of effective antiretroviral agents to the central nervous system (CNS). DESIGN: A novel chemical delivery system (CDS) was used, which utilized redox trapping of drugs in the brain. This study was aimed at defining the pharmacokinetics of a zidovudine (ZDV)-CDS as well as establishing its in vitro antiviral efficacy against HIV in both lymphocytes and in a neural cell line. RESULTS: ZDV-CDS administered parenterally to rats produced significantly higher brain levels of ZDV [area under the curve (AUC), 425 micrograms x min/g] than equimolar ZDV (AUC, 13.5 micrograms x min/g). Native ZDV uptake was minimal after 1 h when analyzed in CEM lymphocytes and in SKNMC neuroblastoma cell line. By contrast, marked uptake of ZDV-CDS was followed by biochemical conversion of ZDV-CDS to its main metabolites (ZDV-CDS quaternary salt, ZDV-Q+, and native ZDV). These improved uptake profiles were associated with greater in vitro virucidal effect. ZDV-CDS at 0.5 microM was 80% more effective than ZDV in suppressing p24 production in a lymphocyte culture infected with 6000 median tissue culture infective doses (TCID50) of the HIV N1T strain and 50% more effective at 0.05 microM. Furthermore, syncytia formation was completely suppressed at a ZDV-CDS dose of 0.5 microM (600 TCID50) but native ZDV at the same dose was ineffective. Finally, while ZDV (at 0.5 microM) is not active in reducing viral replication in an SKNMC neural cell line, the ZDV-CDS complex significantly suppressed p24 synthesis. CONCLUSION: The ZDV-CDS complex is capable of delivering higher ZDV doses to lymphocytes and neural cells, with improved antiretroviral activity.

Acquired Immunodeficiency Syndrome↗

Safety and immunogenicity of a V3 loop synthetic peptide conjugated to purified protein derivative in HIV-seronegative volunteers.

OBJECTIVES: To develop a peptide-based model for a preventive vaccine for HIV-1 infection. DESIGN: Phase I trial in HIV-1-seronegative volunteers. PARTICIPANTS: Adult healthy subjects HIV-1-antibody-seronegative in an enzyme-linked immunosorbent assay, screened for tuberculin [purified protein derivative (PPD)] reactivity with 2 tuberculin units PPD-administered intradermally. INTERVENTIONS: Submicrogram doses of a PPD conjugate with a peptide of the primary neutralizing domain (PND) of HIV-1MN (PPD-MN-PND) were administered intradermally to tuberculin skin-test-positive and -negative volunteers. RESULTS: Antibodies to the MN-PND were measured after two immunizations in 10 out of 11 PPD skin-test-positive volunteers. After the fourth immunization high-affinity antibodies were detected, which persisted for over 1 year. High titers of MN-PND-specific immunoglobulin (Ig) G and IgA were detected in the serum and saliva of all volunteers tested. Serum antibodies were cross-reactive with PND peptide from some other HIV-1 strains but neutralized only the HIV-1MN prototype. Human leukocyte antigen (HLA)-B7-restricted MN-PND-specific cytotoxic T lymphocytes (CTL) were also detected. CONCLUSIONS: The PPD-MN-PND vaccine at submicrogram doses is safe and immunogenic in PPD skin-test-positive healthy adult volunteers. Long lasting humoral immune responses in the serum and saliva were possibly accompanied by HLA-B7-restricted CTL responses. This is a vaccine prototype that can be rapidly and inexpensively modified to include other peptide epitopes. It is especially suitable for use in a worldwide multibillion Bacillus Calmette-Guérin (BCG)-primed or tuberculosis-exposed population at risk for HIV-1 infection.

AIDS Vaccines↗

Cerebral toxoplasmosis in childhood and adult HIV infection treated with 1-4 hydroxynaphthoquinone and rapid desensitization with pyrimethamine.

BACKGROUND: We describe a child and an adult infected with the human immunodeficiency virus (HIV) who developed cerebral lesions consistent with toxoplasmosis. A biopsy in the child and IgG ELISA in both patients confirmed the diagnosis of Toxoplasma gondii. The patients were initially treated with pyrimethamine, however, computerized tomography studies (CT scan) revealed progression of a left frontal and temporoparietal lesion. Therapy in the child was changed to pyrimethamine, clindamycin, and azithromycin. Repeat CT scan showed further disease progression and therapy was changed to high-dose pyrimethamine (3 mg/kg/d) and azithromycin. A subsequent CT scan disclosed further radiologic progression with increasing edema. The adult patient developed a maculopapular rash during attempted treatment with pyrimethamine. METHODS: Introduction of 2 (trans-4[4 chlorophenol] cyclohexy[3-hydroxy-1, 4 naphthoquinone] (HNPQ) an experimental antiparasitic compound previously used only in adult HIV clinical trials, was instituted in the child and rapid oral desensitization to pyrimethamine was initiated in the adult patient. RESULTS: HNPQ resulted in resolution of the cerebral lesion in the child and rapid oral desensitization to pyrimethamine produced an excellent clinical response in the adult. To our knowledge, these are the first cases of childhood and adult cerebral toxoplasmosis treated successfully with HNPQ and rapid oral desensitization to pyrimethamine. CONCLUSION: HNPQ and pyrimethamine desensitization should be considered as alternate modes of therapy in patients who become intolerant or fail to respond to traditional therapy for toxoplasmosis.

AIDS-Related Opportunistic Infections↗

Lipoprotein profile changes during intense training of Israeli military recruits.

The effect of prolonged strenuous military training on serum lipoproteins was studied in 73 new recruits. Dietary intake, body weight, and average energy expenditure were recorded, and blood samples collected at three time periods before training began (time 0), and after 6 and 12 wk of intense physical activity (times I and II, respectively). There was a significant increase in high density lipoprotein (HDL) cholesterol and a decrease in low density lipoprotein (LDL) cholesterol accompanying an increase of duration and intensity of exercise. HDL increased from 40.5 +/- 7.7 mg.dl-1 at time 0 to 44.5 +/- 9.4 mg.dl-1 at time I and to 52.8 +/- 8.7 mg.dl-1 at time II, and each mean P-value for increases in HDL from time 0-I, I-II, and 0-II were P < 0.0001). For LDL cholesterol, the mean decreases were -1.1, -6.1, and -7.3 mg.dl-1, respectively (P = 0.003 from I-II, and 0.01 from 0-II). These changes did not correlate with weight loss, reduced energy, or fat intake. We conclude that intense physical activity is associated with beneficial changes in the lipoprotein profile in new military recruits during a training period extending over 12 wk.

Adolescent↗

Serum lipids and restenosis after successful percutaneous transluminal coronary angioplasty. Ichilov Magnesium Study Group.

The effects of plasma lipids on the clinical and angiographic parameters of 134 patients, in whom coronary angioplasty was performed in 157 vessels, were prospectively examined. During a 6-month follow-up, restenosis was detected angiographically in 39 patients (29%; 45 vessels). None of the clinical, biochemical, or angiographic variables examined was predictive of stenosis and the tendency of a vessel to restenose was not patient-dependent but rather lesion-related. However, restenosis developed in 31 of 102 vessels (30%) in patients with high-density lipoprotein (HDL) cholesterol < or = 40 mg/dl, compared with restenosis in 10 of 55 vessels (19%) in patients with HDL cholesterol > 40 mg/dl (p = 0.092). No significant differences were observed when restenosis rates were compared in patients with total cholesterol levels > 250 mg/dl or < 250 mg/dl; no differences were seen in low-density lipoprotein (LDL) cholesterol levels when comparing patients with > 160 mg/dl and < 160 mg/dl. In 117 patients (132 vessels), complete serial blood specimens were obtained until the concluding angiography at 6 months. During follow-up, both groups (those with and without restenosis) had almost similar findings. Triglycerides decreased equally in both groups, and total cholesterol increased mildly in those who had restenosis; HDL and LDL cholesterol levels increased significantly in each group. No significant differences were observed with respect to extent of these changes between the groups. Thus, although lipid levels at the time of angioplasty and at 6 months follow-up were not found to predict the occurrence of restenosis, the association of low high-density lipoprotein levels and the tendency for restenosis should not be overlooked.

Angioplasty, Balloon, Coronary↗

Disseminated human immunodeficiency virus 1 (HIV-1) infection in SCID-hu mice after peripheral inoculation with HIV-1.

A small animal model that could be infected with human immunodeficiency virus 1 (HIV-1) after peripheral inoculation would greatly facilitate the study of the pathophysiology of acute HIV-1 infection. The utility of SCID mice implanted with human fetal thymus and liver (SCID-hu mice) for studying peripheral HIV-1 infection in vivo has been hampered by the requirement for direct intraimplant injection of HIV-1 and the continued restriction of the resultant HIV-1 infection to the human thymus and liver (hu-thy/liv) implant. This may have been due to the very low numbers of human T cells present in the SCID-hu mouse peripheral lymphoid compartment. Since the degree of the peripheral reconstitution of SCID-hu mice with human T cells may be a function of the hu-thy/liv implant size, we increased the quantity of hu-thy/liv tissue implanted under the renal capsule and implanted hu-thy/liv tissue under the capsules of both kidneys. This resulted in SCID-hu mice in which significant numbers of human T cells were detected in the peripheral blood, spleens, and lymph nodes. After intraimplant injection of HIV-1 into these modified SCID-hu mice, significant HIV-1 infection was detected by quantitative coculture not only in the hu-thy/liv implant, but also in the spleen and peripheral blood. This indicated that HIV-1 infection can spread from the thymus to the peripheral lymphoid compartment. More importantly, a similar degree of infection of the hu-thy/liv implant and peripheral lymphoid compartment occurred after peripheral intraperitoneal inoculation with HIV-1. Active viral replication was indicated by the detection of HIV-1 gag DNA, HIV-1 gag RNA, and spliced tat/rev RNA in the hu-thy/liv implants, peripheral blood mononuclear cells (PBMC), spleens, and lymph nodes of these HIV-1-infected SCID-hu mice. As a first step in using our modified SCID-hu mouse model to investigate the pathophysiological consequences of HIV-1 infection, the effect of HIV-1 infection on the expression of human cytokines shown to enhance HIV-1 replication was examined. Significantly more of the HIV-1-infected SCID-hu mice expressed mRNA for human tumor necrosis factors alpha and beta, and interleukin 2 in their spleens, lymph nodes, and PBMC than did uninfected SCID-hu mice. This suggested that HIV-1 infection in vivo can stimulate the expression of cytokine mRNA by human T cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Mucus gel thickness and turnover in the gastrointestinal tract of the rat: response to cholinergic stimulus and implication for mucoadhesion.

The thickness of the mucus gel and its turnover rate were measured in the stomach, proximal jejunum, cecum and proximal colon of the rat, using microscopy and staining techniques. The specific mucus-secretory responses to carbachol-induced cholinergic stimulus in these locations were also studied. The mucus gel was found to be the thinnest (18 +/- 1 microns) in the cecum, and the thickest in the stomach (39 +/- 14 microns). The effect of carbachol on mucus secretion was profound and dose dependent in the stomach, and less profound, although still dose dependent, in the proximal jejunum. The least responsive organs were the cecum and the proximal colon, where no effect was observed after three doses of carbachol. Mucus secretion rate was significantly higher in the jejunum (1.1 +/- 0.5 microgram glucose equivalent min-1 cm-2) than in the colon (0.5 +/- 0.2 microgram glucose equivalent min-1 cm-2). Also, the proximal jejunum was more responsive to the carbachol stimulus (mucus secretion rate of 5.4 +/- 2.2 micrograms glucose equivalent min-1 cm-2 after carbachol treatment) than the colon (mucus secretion rate of 1.0 +/- 0.4 micrograms glucose equivalent min-1 cm-2 after carbachol treatment). In vitro mucoadhesion studies with Polycarbophil disks were performed in the mucosal tissues of the stomach, jejunum, cecum and proximal colon of the rat with and without cholinergic (carbachol) stimulus. The adhesion force in the cecum and the colon was significantly stronger than in the stomach and proximal jejunum when the studies were performed at pH 2.(ABSTRACT TRUNCATED AT 250 WORDS)

Acrylic Resins↗

HIV type 1 infection of human cortical neuronal cells: enhancement by select neuronal growth factors.

Neuronal cells in culture respond to neuronal growth factors by secondary cellular pathways similar to those described for activation of lymphocytes and macrophages. In HIV-1-infected T lymphocytes and in macrophages, these pathways were shown to converge on nuclear factors that bind and stimulate the HIV-1 LTR and lead to enhancement of HIV-1 expression. In the current study we have investigated whether the same mechanisms also enhance HIV-1 production by neural cells. We have demonstrated that HIV/N1T replication in HCN-1A cells, a human cortical neuronal cell line, is enhanced threefold by nerve growth factor (NGF) and by fibroblast growth factor (FGF), but not by epidermal growth (EGF) factor, or phorbol ester. HCN-1A cells also responded to HIV/N1T infection with pronounced morphological changes, indicative of a differentiation-like process. The cells diminished in size and small neurites were observed.

Cell Line↗

The effect of telephone intervention on success with amplification.

The purpose of this study was to determine whether periodic clinician-initiated telephone contact would reduce the number of unresolved complaints and increase satisfaction, use, and perceived benefit at 4 mo postfitting. Thirty subjects were contacted at 6, 9, and 12 wk postfitting to address questions and to encourage them to return to the clinic to resolve hearing aid-related problems. A control group of 30 subjects was encouraged to contact the center if problems arose at the time of dispensing only. All subjects were interviewed at 4 mo following receipt of the aids, and were sent the Hearing Handicap Inventory for the Elderly at the same time as well as at the time of dispensing. Results revealed a significant reduction in perceived handicap in general, but no significant difference between groups on measures of satisfaction, use, or benefit. There was no significant difference between groups in the number of unresolved complaints at the time of the interview; however, a trend toward fewer complaints in the experimental group was noted. A significantly greater number of complaints were raised for the first time in the control group than in the experimental group at the time of the interview, indicating that more problems remained unaddressed in the absence of clinician-initiated intervention. Therefore, the continued investigation of aggressive, and efficient, postfitting management schemes is warranted.

Aged↗

Cutaneous blood flow abnormalities in hypertriglyceridemia.

An accelerated atherosclerosis, in particular of the coronary arteries, was documented in hypertriglyceridemia. The objective of the present study was to assess the cutaneous dynamic blood flow in hypertriglyceridemia, utilizing the optical noninvasive method of laser Doppler flowmetry. The cutaneous blood flow on the forearms was measured during the postischemic reactive hyperemia test in treated and non-treated patients with hypertriglyceridemia and healthy control subjects. The subjects were 32 patients with hypertriglyceridemia--15 untreated and 17 following 6-9 months of bezafibrate treatment--and 27 healthy control subjects. In untreated patients with hypertriglyceridemia, the peak flow was significantly lower than in both the treated group (p < 0.005) and control group (p < 0.02). Similarly, the area under the response-time curve of the untreated patients with hypertriglyceridemia was smaller (p < 0.01 and p < 0.05, respectively). These parameters were similar in the treated group and the control group. The reaction was faster in the treated group, as compared to the other two groups (p < 0.001). The control group exhibited a longer time to decay than the treated group (p < 0.01). Postischemic reactive hyperemia tests in patients with hypertriglyceridemia reveal cutaneous microcirculatory changes in the forearm. These changes may arise from several mechanisms, including functional abnormalities of the endothelium or vascular smooth muscle, or structural changes in the blood vessels that limit vasodilatation. These changes are reversible, and corrected when reducing the triglyceride levels, but other abnormalities are then present, suggesting a permanent damage. These dynamic measurements of cutaneous blood flow are sensitive indicators of atherogenesis, and can be employed for the evaluation of microvascular involvement and follow-up of patients with hypertriglyceridemia.

Arteriosclerosis↗

Ferritin levels in pediatric HIV-1 infection.

Ferritin is an acute phase protein which is often elevated in acute and chronic inflammation, as well as in neoplastic disease. In adults with human immunodeficiency virus (HIV) infection, elevated serum ferritin levels indicate advanced or progressive disease. In the present study, ferritin levels were evaluated in 88 HIV-infected children. Ferritin levels greater than 100 ng/ml were found in 93% of patients with advanced disease. Increasing levels always accompanied or closely preceded rapid disease progression. Serum ferritin levels may prove to be a useful marker to monitor disease progression and therapeutic efficacy in HIV-infected children.

AIDS-Related Opportunistic Infections↗

Effect of chronic cholesterol loading in the development of acute ischemic renal failure in rats.

The effect of chronic cholesterol loading and lovastatin administration in renal artery clamping acute renal failure in rats is not known. Acute renal failure was induced by 60-min left renal artery clamping immediately after right nephrectomy. The changes in renal function after renal artery clamping in the hyperlipidemic rats were unexpected. The acute renal failure in the cholesterol-loaded groups was less severe than in the nonhyperlipidemic rats. The lovastatin administration had some favorable effect on renal function after ischemia; however, this effect was not additive to the high dietary cholesterol administration. Our results seems to favor the concept that in this special form of experimental renal ischemic acute renal failure, serum cholesterol levels, elevated through diet, may have protective effects with respect to renal tubular lesions during or following the acute ischemic insult.

Acute Kidney Injury↗

A nonparametric analysis of the transmission rate of human immunodeficiency virus from mother to infant.

Infants born to mothers who are infected with the human immunodeficiency virus (HIV) may or may not become infected by perinatal transmission. Unfortunately, passively transferred maternal antibodies make it hard to determine the infant's infection status from HIV antibody testing, because shortly after birth it is not possible to distinguish passively transferred maternal antibodies from antibodies produced by an infected infant. Usually, the infection status is unobservable for each infant, unless the infant reaches the age of 15 months or develops an HIV-related disease such as the acquired immunodeficiency syndrome (AIDS). Traditionally, statistical analyses of the perinatal transmission rate of HIV are based on infants who had been born at least 15 months before the date of analysis. Such analyses can be both inefficient and biased. In this note, we define a mixture model underlying the onset time of AIDS and then obtain the nonparametric maximum likelihood estimators of the HIV transmission rate and of the distribution function of AIDS onset time for infected infants. Nonparametric tests are also derived for detecting differences in HIV transmission rates among different groups of infants. Finally, the methods are applied to the Mothers and Infants Cohort Study in New York City. The transmission rate of HIV from infected mothers to their infants was estimated to be 30.0% with 95% confidence interval (22.3%, 39.1%).

Age of Onset↗

Cigarette smoking, premature rupture of membranes, and vertical transmission of HIV-1 among women with low CD4+ levels.

To examine the possible influence of obstetric factors, substance use during pregnancy, and other maternal factors on the relationship between a low maternal CD4+ level and vertical transmission of human immunodeficiency virus type 1 (HIV-1), data were analyzed from the Mothers and Infants Cohort Study, a prospective cohort followed for up to 4 years between 1986 and 1992 in Brooklyn and the Bronx, New York. The overall transmission rate for the cohort was 25.1% (95% confidence interval (CI) = 19.0-31.3). Prenatal CD4+ lymphocyte measurements were available for 162 HIV-seropositive mothers of infants with known infection outcomes. Among mothers who smoked cigarettes after the first trimester, those whose mean prenatal CD4+ level was < 20% had more than a threefold increased risk of transmitting their infection to their infants [relative risk (RR) = 3.30; 95% CI = 1.46-7.44; p = 0.004]. Among mothers who developed premature rupture of membranes, those with a low CD4+ level had a similarly increased risk of vertical transmission (RR = 4.33; 95% CI = 1.78-10.5; p = 0.003). These relative risks were much higher than those for mothers who did not smoke after the first trimester (RR = 1.14; 95% CI = 0.48-2.70; p = 0.76) or have premature rupture of membranes (RR = 1.29; 95% CI = 0.61-2.74; p = 0.50), indicating that these factors modified the effect of CD4+ level on transmission. Among all mothers without regard to CD4+ level, those who experienced preterm premature rupture of membranes were also at greater risk of transmission (RR = 2.24; 95% CI = 1.07-4.69; p = 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗