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Biomedical subjects

David Bernstein

Publications and source records attributed to David Bernstein.

25 records · Page 2Linked to original sources

A review of the influence of particle size, puff volume, and inhalation pattern on the deposition of cigarette smoke particles in the respiratory tract.

Ventilation of the cigarette was designed to allow dilution of the cigarette smoke and thereby reduce the dose delivered to the smoker. Following the toxicological principle of dose response, a lower concentration of cigarette smoke should be associated with a lower toxicological response. However, there have been many studies reporting on the phenomenon of compensation whereby the smoker increases puff volume and/or frequency in order to obtain higher volumes of smoke This article reviews studies of the particle size of cigarette smoke and examines, based on available literature, the associated differences in the tobacco smoke and smoking behavior and their relationship to deposition patterns in the lung. The data available indicate that particle size of the cigarette smoke does not significantly change as a function of cigarette type or smoking behavior. The cigarette smoke particle size is in the same range as the minimum deposition particle size in the lung. While varying concentrations of particles are taken into the mouth, the subsequent inhalation pattern has been reported as remaining constant and also does not appear to change significantly under different smoking types and conditions. The dynamics of what happens to the smoke in the short time it is retained in the mouth have not been studied, and this perhaps should be the subject of future investigations. The current data therefore suggest that the particle deposition pattern of the smoke within the lung would not change significantly if compensation occurs.

Humans↗

Aberrant extracellular and dendritic cell (DC) surface expression of heat shock protein (hsp)70 in the rheumatoid joint: possible mechanisms of hsp/DC-mediated cross-priming.

We describe, in rheumatoid arthritis (RA), abnormalities in the expression and distribution of heat shock protein (hsp) and dendritic cells (DCs) that are conducive to cross-priming and DC cross-talk. As detected by ELISA, inducible (i)hsp70 was dramatically increased in RA synovial fluid (RASF) vs normal human and RA sera and osteoarthritis and gout synovial fluid. Immunoblot analysis of fresh RASF cells revealed marked increases in ihsp70 and activation of its transcription factor heat shock factor-1, compared with fresh normal peripheral blood cells. Flow cytometry and microscopy demonstrated high levels of ihsp70 on the surface of RASF myeloid DCs (but not normal myeloid DCs) that occurred concurrently with hspRs (CD91/CD14). ihsp70 present in RASF exhibited chaperoning potential, as indicated by the capture of ihsp70 present in RASF on the surface of normal DCs. Binding was partially competitively inhibited by excess alpha(2)-macroglobulin, indicating that hspRs in addition to CD91 participate in the capture process. These data indicate that ihsp70 may chaperone autologous Ags into immature RASF DCs via hspRs, and that cross-talk between DCs coexpressing hsp/hspRs reflects a disease process in RA. The induction of surface ihsp70 on normal cells after sublethal heat stress and the release of ihsp70 from normal DCs after inflammatory stress also suggest that the pattern of ihsp70 expression in RASF occurs in response to sustained stress.

Active Transport, Cell Nucleus↗

Impaired IRS-1/PI3-kinase signaling in patients with HCV: a mechanism for increased prevalence of type 2 diabetes.

Patients with hepatitis C virus (HCV) infection have a greater risk of developing type 2 diabetes mellitus. However, the mechanism of this association is unclear. In this study, we examined the potential defects in upstream insulin signaling pathways in liver specimens obtained from nonobese/nondiabetic subjects with HCV infection. Fasting liver biopsy specimens were obtained from 42 HCV-infected subjects and 10 non-HCV-infected subjects matched for age and body mass index. Liver tissues were exposed to insulin and examined for the contents and phosphorylation/activation status of the upstream insulin signaling molecules by immunoprecipitation and Western blot analysis. HCV infection resulted in a trend toward a 2-fold to 3-fold increase in insulin receptor (IR) and insulin receptor substrate (IRS)-1 contents when compared with non-HCV. In contrast, insulin-stimulated IRS-1 tyrosine phosphorylation was decreased by 2-fold in HCV-infected subjects compared with non-HCV-infected subjects (P <.05). The observed reductions in IRS-1 tyrosine phosphorylation were accompanied by a 3.4-fold decrease in IRS-1/p85 phosphatidylinositol 3-kinase (PI3-kinase) association and a 2.5-fold decrease in IRS-1-associated PI3-kinase enzymatic activity (P <.05 vs. non-HCV). This was accompanied by a marked reduction in insulin-stimulated Akt phosphorylation without any alterations in mitogen-activated protein kinase (MAPK) phosphorylation. Cellular contents of the hepatic p85 subunit of PI3-kinase were comparable between HCV-infected and non-HCV-infected subjects. In conclusion, we found that (1). HCV infection leads to a postreceptor defect in IRS-1 association with the IR and (2). insulin signaling defects in hepatic IRS-1 tyrosine phosphorylation and PI3-kinase association/activation may contribute to insulin resistance, which leads to the development of type 2 diabetes mellitus in patients with HCV infection.

Adult↗

Efficacy and safety of desloratadine 5 mg once daily in the treatment of chronic idiopathic urticaria: a double-blind, randomized, placebo-controlled trial.

BACKGROUND: Chronic idiopathic urticaria (CIU) has a major impact on patient well-being. Antihistamines are the first-line treatment for CIU; however, some cause sedation. OBJECTIVE: Our purpose was to study the efficacy and safety of desloratadine, 5 mg, a new H(1)-receptor antagonist, in patients with moderate to severe CIU. METHODS: This study was a randomized, double-blind, placebo-controlled, parallel-group, multicenter trial of 6 weeks' duration. RESULTS: Compared with placebo, desloratadine significantly improved the total CIU symptom score as well as pruritus, the number of hives, and the size of the largest hive. Overall therapeutic response and global CIU status improved significantly with desloratadine; interference with sleep was reduced and the performance of daily activities improved. Statistically and clinically significant improvements were seen within the first 24 hours of treatment and were sustained throughout the full duration of the study. The incidence of adverse events, including somnolence, was similar in the desloratadine and placebo groups. CONCLUSION: Desloratadine is a well-tolerated and effective treatment of CIU.

Administration, Oral↗

Relationship of health-related quality of life to treatment adherence and sustained response in chronic hepatitis C patients.

Interferon therapy may exacerbate health-related quality of life (HRQL) deficits associated with hepatitis C virus (HCV) early in the course of therapy. Treatment with polyethylene glycol-modified interferon (peginterferon) alfa-2a (40 kd) provides improved sustained response over interferon alfa-2a, but its effect on HRQL is unknown. The objective of this study was to (1) evaluate the effect of sustained virologic response on HRQL in patients with HCV and (2) determine whether impairment of HRQL during treatment contributes to early treatment discontinuation. Data consisted of a pooled secondary analysis of patients (n = 1,441) across 3 international, multicenter, open-label, randomized studies that compared peginterferon alfa-2a (40 kd) with interferon alfa-2a. ANCOVA was used to examine the effect of sustained virologic response on HRQL. Repeated-measures mixed-models ANCOVA was used to compare Fatigue Severity Scale (FSS) and SF-36 scores during treatment by treatment group. Logistic regression analysis was used to examine the association between changes at baseline in on-treatment HRQL and early treatment discontinuation. Sustained virologic response was associated with marked improvements from baseline to end of follow-up in all subjects, including patients with cirrhosis. During treatment, patients receiving peginterferon alfa-2a (40 kd) had statistically significantly better scores on both the SF-36 and FSS. Baseline to 24-week changes in fatigue and SF-36 mental and physical summary scores significantly predicted treatment discontinuation. In conclusion, sustained virologic response is associated with improvements in quality of life in patients with or without advanced liver disease. This parameter may be an important consideration in maximizing treatment adherence.

Adult↗

Total extraperitoneal preperitoneal laparoscopic hernia repair using spinal anesthesia.

BACKGROUND: Laparoscopic herniorrhaphy is a well-debated approach to inguinal hernia repair. Multiple technical and outcome variables have been compared with those of traditional open inguinal hernia repairs. One of these variables is the choice of anesthesia. To date, no reports describe the use of spinal anesthesia for laparoscopic hernia repairs. We present herein a review of our experience with spinal anesthesia for the total extraperitoneal preperitoneal laparoscopic hernia repair (TEP). METHODS: We prospectively reviewed 30 patients undergoing TEP while under spinal anesthesia. Methods of anesthesia, surgical procedure, operative and anesthesia delivery times, as well as outcomes were reviewed. Patients were followed up over a 2-year period. Short- and long-term results of the surgical procedure and anesthesia delivered were noted. RESULTS: All patients underwent successful laparoscopic hernia repair while under spinal anesthesia without conversion to general anesthesia. Forty-four hernias were repaired in 30 patients. Short- and long-term follow-up (2 years) revealed no significant untoward affects from the spinal anesthesia in this series of patients. Aside from inguinodynia in 3 patients in the short-term, no other short-term or long-term untoward sequelae occurred. CONCLUSIONS: Spinal anesthesia is a feasible, and in our experience, the preferable method of anesthesia for total extraperitoneal laparoscopic hernia repair.

Anesthesia, Spinal↗