Molecular characterization of serotype III group B-streptococcus isolates causing neonatal meningitis

We studied a collection of 110 serotype III group B streptococcus (GBS) isolates causing neonatal meningitis, by means of both pulsed-field gel electrophoresis (PFGE) with SmaI and Southern hybridization with probes for genes potentially associated with virulence (neuA, cpsA, scpB, and hylB and, for mobile genetic elements [MGEs], GBSi1 and IS1548), in comparison with 44 serotype III GBS isolates colonizing healthy neonates. Using polymerase chain reaction, we assessed both the insertion of MGEs downstream of the scpB gene and the insertion of IS1548 within the hylB gene. PFGE clustered the isolates into 3 main groups. One PFGE group accounted for 80% of typeable cerebrospinal fluid (CSF) isolates, versus 24% of colonization isolates (P=1.8 x 10-9). GBSi1 was found in 67% of CSF isolates and in only 23% of colonization isolates (P=5.3 x 10-7). A 15-kbp SmaI restriction-DNA fragment bearing the neuA gene was significantly associated with CSF isolates (P=1.1 x 10-11).     

The effects of small-dose ketamine on morphine consumption in surgical intensive care unit patients after major abdominal surgery

In a randomized, double-blinded study, we evaluated the analgesic effect of ketamine in the management of pain in a surgical intensive care unit after major abdominal surgery. Patients received morphine patient-controlled analgesia with either placebo (Group M) or ketamine (Group K). Morphine was administered with initial loading doses of 2 mg until the visual analog scale (VAS) score was <30 and thereafter with bolus doses of 1 mg and a lockout time of 7 min. Ketamine was administered with an initial bolus of 0.5 mg/kg followed by a perfusion of 2 micro g x kg(-1) x min(-1) during the first 24 h and 1 micro g x kg(-1) x min(-1) during the following 24 h. The 4-h cumulative morphine doses were measured over 48 h. The VAS scores at rest and at mobilization were measured every 4 h during 48 h. A total of 101 patients were enrolled, and 93 were analyzed (41 in Group K and 52 in Group M). VAS scores at rest and at mobilization were similar. The cumulative consumption of morphine was significantly smaller in Group K (P < 0.05). We concluded that small doses of ketamine were a valuable adjunct to opioids in surgical intensive care unit patients after major abdominal surgery.     

Reduced activation of phosphatidylinositol-3 kinase and increased serine 636 phosphorylation of insulin receptor substrate-1 in primary culture of skeletal muscle cells from patients with type 2 diabetes

To understand better the defects in the proximal steps of insulin signaling during type 2 diabetes, we used differentiated human skeletal muscle cells in primary culture. When compared with cells from control subjects, myotubes established from patients with type 2 diabetes presented the same defects as those previously evidenced in vivo in muscle biopsies, including defective stimulation of phosphatidylinositol (PI) 3-kinase activity, decreased association of PI 3-kinase with insulin receptor substrate (IRS)-1 and reduced IRS-1 tyrosine phosphorylation during insulin stimulation. In contrast to IRS-1, the signaling through IRS-2 was not altered. Investigating the causes of the reduced tyrosine phosphorylation of IRS-1, we found a more than twofold increase in the basal phosphorylation of IRS-1 on serine 636 in myotubes from patients with diabetes. Concomitantly, there was a higher basal mitogen-activated protein kinase (MAPK) activity in these cells, and inhibition of the MAPKs with PD98059 strongly reduced the level of serine 636 phosphorylation. These results suggest that IRS-1 phosphorylation on serine 636 might be involved in the reduced phosphorylation of IRS-1 on tyrosine and in the subsequent alteration of insulin-induced PI 3-kinase activation. Moreover, increased MAPK activity seems to play a role in the phosphorylation of IRS-1 on serine residue in human muscle cells.     

Early use of the pulmonary artery catheter and outcomes in patients with shock and acute respiratory distress syndrome: a randomized controlled trial

Context  Many physicians believe that the pulmonary artery catheter (PAC) is useful for the diagnosis and treatment of cardiopulmonary disturbances; however, observational studies suggest that its use may be harmful. Objective  To determine the effects on outcome of the early use of a PAC in patients with shock mainly of septic origin, acute respiratory distress syndrome (ARDS), or both. Design, Setting, and Patients  A multicenter randomized controlled study of 676 patients aged 18 years or older who fulfilled the standard criteria for shock, ARDS, or both conducted in 36 intensive care units in France from January 30, 1999, to June 29, 2001. Intervention  Patients were randomly assigned to either receive a PAC (n = 335) or not (n = 341). The treatment was left to the discretion of each individual physician. Main Outcome Measures  The primary end point was mortality at 28 days. The principal secondary end points were day 14 and 90 mortality; day 14 organ system, renal support, and vasoactive agents–free days; hospital, intensive care unit, and mechanical ventilation–free days at day 28. Results  The 2 groups were similar at baseline. There were no significant differences in mortality with or without the PAC at day 14: 49.9% vs 51.3% (mortality relative risk [RR], 0.97; 95% confidence interval [CI], 0.84-1.13; P = .70); day 28: 59.4% vs 61.0% (RR, 0.97; 95% CI, 0.86-1.10; P = .67); or day 90: 70.7% vs 72.0% (RR, 0.98; 95% CI, 0.89-1.08; P = .71). At day 14, the mean (SD) number of days free of organ system failures with or without the PAC (2.3 [3.6] vs 2.4 [3.5]), renal support (7.4 [6.0] vs 7.5 [5.9]), and vasoactive agents (3.8 [4.8] vs 3.9 [4.9]) did not differ. At day 28, mean (SD) days in hospital with or without the PAC (0.9 [3.6] vs 0.9 [3.3]), in the intensive care unit (3.4 [6.8] vs 3.3 [6.9]), or mechanical ventilation use (5.2 [8.5] vs 5.0 [8.5]) did not differ. Conclusion  Clinical management involving the early use of a PAC in patients with shock, ARDS, or both did not significantly affect mortality and morbidity.      

Human oligodendrocytes are susceptible to cytolysis by major histocompatibility complex class I-restricted lymphocytes

The majority of human oligodendrocytes in enriched glial cell cultures expresses class I major histocompatibility complex (MHC) antigens. We used a 51Cr release assay to study the susceptibility of oligodendrocyte-enriched glial cells to MHC-restricted and non-restricted immune-mediated cytolysis. Mitogen-activated mononuclear cells induced significant lysis in a lectin-dependent cytotoxicity assay. Mononuclear cells allo-activated in a one-way mixed lymphocyte culture with E- cells from the glial cell donor induced a significantly higher degree of oligodendrocyte cytolysis than mononuclear cells activated with E- cells bearing MHC-class I antigens discordant with the glia. Cytolysis by alloactivated unfractionated lymphocytes and by purified CD8+ lymphocytes was reduced by an anti-class I antibody (W6/32). Our findings suggest that human oligodendrocytes can be susceptible targets for MHC class I-restricted lysis.     

Evaluation of consumer satisfaction using the tetra-class model

BACKGROUND: A number of studies have shown the importance of consumers' satisfaction toward pharmacy services. The measurement of patient satisfaction through different elements of services provided is challenging within the context of a dynamic economic environment. Patient satisfaction is the result of long-term established habits and expectations to the pharmacy as an institution. Few studies to date have attempted to discern whether these changes have led to increased patient satisfaction and loyalty, particularly within developing nations. OBJECTIVES: The objective of this study was to evaluate the elements of the services provided in Bulgarian pharmacies and their contribution to consumer satisfaction using a tetra-class model. Three main hypotheses were tested in pharmacies to validate the model in the case of complex services. Additionally, the contribution of the different service elements to the clients' satisfaction was studied. METHODS: The analysis was based on a survey of customers in central and district pharmacies in Sofia, Bulgaria. The data were analyzed through a correspondence analysis which was applied to the results of the 752 distributed questionnaires. RESULTS: It was observed that different dimensions of the pharmacies contribute uniquely to customer satisfaction, with consumer gender contributing greatly toward satisfaction, with type/location of pharmacy, consumer age, and educational degree also playing a part. The duration of time over which the consumers have been clients at a given pharmacy influences the subsequent service categorization. CONCLUSIONS: This research demonstrated that the tetra-class model is suitable for application in the pharmaceutical sector. The model results could be beneficial for both researchers and pharmacy managers.     

Inflammation and aging: Can endocannabinoids help?

Aging often leads to cognitive decline due to neurodegenerative process in the brain. As people live longer, there exists a growing concern linked to long-term, slowly debilitating diseases, such as Alzheimer's disease for which a cure has not yet been found. Recently, the role of neuroinflammation has attracted attention due to its slow onset, chronic nature and its possible role in the development of many different neurodegenerative diseases. In the future, treatment of chronic neuroinflammation may help counteract aspects of neurodegenerative disease. Our recent studies have focused upon the endocannabinoid system for its unique effects on the expression of neuroinflammation. The basis for the manipulation of the endocannabinoid system in the brain in combination with existing treatments for Alzheimer's disease will be discussed in this review.