Relationships among lactate concentration, blood flow and histopathologic profiles in rat C6 glioma

Increased capacity for glycolytic metabolism is a well-known characteristic of neoplastic cells. Because lactic acid is the end product of glycolysis, in vivo MRS measurements of tumor lactate concentration ([lac]t) may provide valuable information about tumor metabolism, which will aid the development of therapies and the clinical diagnosis and treatment of tumors. In the present study, several hemodynamic and histologic parameters were evaluated with respect to their influence on [lac]t. Pronounced differences in [lac]t in two distinct populations of tumors suggested a putative perfusion threshold. Above this threshold, [lac]t was independent of hemodynamic and histologic factors including tumor blood flow (measured using MRS and the method of D2O washout), extent of necrosis and inflammatory cell infiltrate. Thus, for most tumors, [lac]t was not determined by any one single factor such as hypoxia, venous clearance, glucose supply, extent of necrosis or degree of inflammatory cell infiltrate. Rather, [lac]t may be equilibrated, at least in part, by an interplay of forces involving hemodynamics and substrate supply. In general, the data are consistent with the hypothesis that elevated lactate in most tumors is related to the high glycolytic activity of adequately perfused, viable neoplastic cells.     

Platelet prostanoid receptors

Prostaglandins (PGs) and thromboxanes are important modulators of platelet activation, and there is strong evidence to support the existence of distinct thromboxane, prostacyclin, PGD2 and PGE2 receptors on the platelet plasma membrane. In this review, each of these platelet prostanoid receptors is discussed in detail, with respect to their receptor pharmacology, molecular biology and signal transduction, and as to any therapeutic implications of the development of specific agonists and/or antagonists. In addition, it considers the possibility that there are separate vascular receptors for 8-epi PGF2 alpha, which are not present on the platelet.     

Molecular characterization of erythrocyte glucose-6-phosphate dehydrogenase deficiency in Al-Ain District, United Arab Emirates

Operational skills involved in controlling a motor vehicle were measured in two groups of very healthy elderly drivers and a young control group to test the hypothesis that there are age-related declines in operational performance that may influence driver safety. An actual behind-the-wheel, standardized road test was employed using a motor vehicle equipped with sensors to record speed, braking activity, and lane position, as well as direction and magnitude of front-wheel and eye-movement excursions. The data from these sensors were used as dependent measures of operational performance. Older drivers made fewer steering and eye-movement excursions and drifted across the center line more frequently than the young control group. Younger drivers drove significantly faster and executed more braking applications than did their older counterparts. The motor-vehicle operational performance of older healthy drivers was related to visual-spatial attentional declines and the useful field of vision associated with the normal aging process.     

Complications of care in a pediatric intensive care unit: a prospective study

OBJECTIVES: (a) To examine the frequency, type, and severity of complications occurring in a pediatric intensive care unit; (b) to identify populations at risk; and (c) to study the impact of complications on morbidity and mortality. DESIGN: Prospective survey. SETTING: Pediatric intensive care unit (PICU) of a university-affiliated hospital. PATIENTS: 1035 consecutive admissions over an 18-month period. RESULTS: 115 complications occurred during 83 (8.0%) admissions, for 2.7 complications per 100 PICU-days; 48 (42%) complications were major, 45 (39%) moderate, and 22 (19%) minor. Sixty complications (52%) were ventilator-related, 14 were drug-related, 13 procedure-related, 24 infectious, and 22 involved invasive devices (18 vascular catheters). Human error was involved in 41 (36%) cases, 21 of which were major (18%). Treatments included reintubation < 24 h (28), intravenous antimicrobials (24), and invasive bedside procedures (14). Cardiopulmonary resuscitation was required in 6 patients. Thirteen patients with complications died (15.7%); 2 deaths were directly due to complications. Patients with complications were younger, had longer lengths of stay, and had a higher mortality. Length of stay was a positive risk factor for complication risk (odds ratio = 1.09, 95% confidence interval: 1.05 to 1.13; p = 0.0001); other patient characteristics had no predictive effect. Kaplan-Meier estimates showed that the most severe complications occurred early in the PICU stay. The best indicators of patient mortality were number of complications (odds ratio = 2.96, 95% confidence interval 1.72 to 5.08; p = 0.0001), and mortality risk derived from the Pediatric Risk of Mortality Score (odds ratio = 1.08, 95% confidence interval 1.06 to 1.10; p = 0.0001). Mortality was correlated with increasing severity of complications. CONCLUSION: Complications have a significant impact on patient care. Patients may be at increased risk earlier in their PICU course, when the number of interventions may be greatest. Complications may increase patient mortality and predict patient death better than other patient variables.     

Increased expression of CD80, CD86 and CD70 on T cells from HIV-infected individuals upon activation in vitro: regulation by CD4+ T cells

T cells express CD28 and CD27 which transduce co-stimulatory signals after interaction with their ligands on antigen-presenting cells (APC). These ligands, CD80, CD86 and CD70, are also expressed to some extent on activated T cells. Here, we show that in human immunodeficiency virus (HIV)-infected individuals, CD28 and CD27 expression is decreased on CD8+ T cells. On the other hand, T cell stimulation in vitro induced high CD80, CD86 and CD70 expression on T cells from HIV-infected individuals. It appeared that an inverted CD4:CD8 T cell ratio could explain this enhanced expression of co-stimulatory ligands. Indeed, high expression levels of CD80, CD86 and CD70 were found on activated CD8+ T cells from HIV- individuals cultured in the absence of CD4+ T cells. Addition of CD4+ T cells prevented this up-regulation. However, in HIV-infected individuals, addition of excess autologous or healthy control CD4+ T cells did not completely counteract up-regulation of co-stimulatory ligand expression on CD8+ T cells. Thus, to some extent, CD8+ T cells in HIV-infected individuals appeared to be refractory to CD4+ T cell-mediated regulation of ligand expression in vitro. Activated T cells from HIV-infected individuals and activated CD8+ T cells from healthy controls were able to act as accessory cells in CD3-induced T cell proliferation, which was dependent on cell-cell contact. Thus, we showed that T cells from HIV-infected individuals express enhanced levels of co-stimulatory ligands upon activation, which provides them with accessory cell properties. Enhanced stimulatory potential of these nonprofessional APC may contribute to persistently high levels of immune activation in HIV infection related to disease progression.     

Targeted overexpression of protein kinase C beta2 isoform in myocardium causes cardiomyopathy

Increased cardiovascular mortality occurs in diabetic patients with or without coronary artery disease and is attributed to the presence of diabetic cardiomyopathy. One potential mechanism is hyperglycemia that has been reported to activate protein kinase C (PKC), preferentially the beta isoform, which has been associated with the development of micro- and macrovascular pathologies in diabetes mellitus. To establish that the activation of the PKCbeta isoform can cause cardiac dysfunctions, we have established lines of transgenic mice with the specific overexpression of PKCbeta2 isoform in the myocardium. These mice overexpressed the PKCbeta2 isoform transgene by 2- to 10-fold as measured by mRNA, and proteins exhibited left ventricular hypertrophy, cardiac myocyte necrosis, multifocal fibrosis, and decreased left ventricular performance without vascular lesions. The severity of the phenotypes exhibited gene dose-dependence. Up-regulation of mRNAs for fetal type myosin heavy chain, atrial natriuretic factor, c-fos, transforming growth factor, and collagens was also observed. Moreover, treatment with a PKCbeta-specific inhibitor resulted in functional and histological improvement. These findings have firmly established that the activation of the PKCbeta2 isoform can cause specific cardiac cellular and functional changes leading to cardiomyopathy of diabetic or nondiabetic etiology.     

AIDS; new developments. I. HIV tests: time for a more active policy

Until recently, an HIV test was of limited importance for persons who had been at risk for HIV as effective drugs were not available. With the advent of a new generation of antiretroviral drugs with beneficial effect after early treatment, knowledge of the HIV serostatus has become of more importance to asymptomatic persons. There is no need for a mass screening campaign however, as there is no cure as yet.     

Putative liver progenitor cells: conditions for long-term survival in culture

BACKGROUND AND OBJECTIVES: We operated on three patients with leiomyosarcoma of the inferior vena cava. METHODS: Complete excision was possible in all three patients. RESULTS: One patient developed widespread metastasis at 23 months, one patient is alive with no evidence of disease at 70 months, and one patient is alive at 15 months. The third patient had subcutaneous and pulmonary metastases at the time of presentation, which are radiologically nondetectable at present following postoperative chemotherapy. CONCLUSIONS: The clinicopathologic features, prognostic factors, and treatment of 130 cases found in a comprehensive literature search and our three cases are reported.