Distribution of HIV type 1 (HIV-1) in blood components: detection and significance of high levels of HIV-1 associated with platelets

BACKGROUND: Although inactivation of enveloped viruses transmitted by plasma derivatives has been successful, no methods for virus inactivation or removal have been established for platelet concentrates or red cell (RBC) components. Relatively little is known regarding the extent or significance of virus interactions with the cellular constituents in these components. STUDY DESIGN AND METHODS: Units of whole blood were collected from six HIV type 1 (HIV-1)-positive, asymptomatic individuals and separated into peripheral blood mononuclear cells (PBMNCs), cell-free plasma, white cell-reduced platelet concentrate, and white cell-reduced RBCs. DNA and RNA polymerase chain reaction and virus culture methods were used to study the compartmentalization of HIV-1 immediately after component preparation and after storage. RESULTS: As expected, HIV DNA and infectious virus were detected in fresh blood and in PBMNCs, and virion-associated RNA was detected in fresh plasma from all six donors. The levels of viral nucleic acids in these preparations remained relatively stable with 4 degrees C storage, whereas infectivity of PBMNCs was rapidly lost. Washed RBCs tested negative for HIV in all assays at all time points. Platelets retained high levels of HIV RNA (but not infectivity) after extensive washing, as well as after storage at 4 and 22 degrees C. High-level platelet-associated HIV-1 was also demonstrated in samples collected during early seroconversion. Periseroconversion and postseroconversion levels of platelet-associated HIV-1 correlated with the level of plasma viremia and with the rate of progression to AIDS. Cell-free virus from donor plasma and tissue culture fluid rapidly and firmly attached to platelets from noninfected donors. Infectivity of tissue culture virus bound to platelets was demonstrated in vitro. CONCLUSION: Significant levels of HIV-1 are associated with platelets during all stages of infection. Platelet-associated HIV could either mediate virus clearance or facilitate virus dissemination and expanded tropism. Finally, virus inactivation research must address virus associations with platelets.     

Small-dose hyperbaric versus plain bupivacaine during spinal anesthesia for cesarean section

In a double-blind, randomized trial, 98 parturients undergoing cesarean section received either hyperbaric or plain bupivacaine 6.6 mg combined with sufentanil 3.3 microg as part of a combined spinal-epidural procedure. To prevent hypotension, 1000 mL of lactated Ringer's solution, 500 mL of hydroxyethyl starch 6%, and ephedrine 5 mg were administered i.v. The height of the block was equal in both groups, but more patients in the plain group had blocks that were either too high or too low (P < 0.01). The number of patients requiring epidural supplementation was equal in both groups. Strict criteria were used to treat hypotension. The overall incidence of systolic blood pressure (<90 mm Hg) was 13%, whereas it was more pronounced in the plain group (21% vs 6% in the hyperbaric group, P < 0.05), which required more ephedrine (P < 0.05) and in which a greater incidence of nausea was noticed (P < 0.05). We conclude that the use of a small dose of intrathecal bupivacaine combined with sufentanil plus our described preloading regimen resulted in a lower incidence of hypotension. Further, we conclude that the use of hyperbaric bupivacaine in this manner provides a more reliable block and a lower incidence of hypotension than plain bupivacaine. Implications: A small dose of hyperbaric bupivacaine 0.5% combined with sufentanil used intrathecally during cesarean section offered a more reliable cephalad spread of the spinal block than the glucose-free combination, which was reflected in a lower incidence of hypotension and nausea.     

Is nondipping in 24 h ambulatory blood pressure related to cognitive dysfunction?

OBJECTIVE: Associations between the outcome of 24 h ambulatory monitoring and cognitive performance were studied in order to evaluate the potential relevance of ambulant blood pressure status to brain function. It was hypothesized that a small daytime-night-time difference in mean blood pressure (nondipping) is associated with reduced cognitive performance, in line with studies in hypertensive subjects that have reported associations between nondipping and target-organ damage. METHODS: The study followed a cross-sectional design and was part of a larger research programme on determinants of cognitive aging (Maastricht Aging Study, MAAS). A group of 115 community residents aged 28-82 years was recruited from a general practice population and screened for cardiovascular events and medication use. All underwent 24 h blood pressure monitoring. Cognitive performance was measured with tests of verbal memory, attention, simple speed and information processing speed. RESULTS: Mean daytime or night-time levels of both systolic and diastolic blood pressure were unrelated to cognitive outcome, when age, sex and educational level were controlled for. Differences between mean daytime and night-time blood pressure (based on both narrow and wide measurement intervals for day and night-time periods) were positively associated with memory function (5-9% of additional variance explained) and one sporadic positive association was found on the sensorimotor speed score (4%). Nondippers (n=15) showed lower levels of both memory and sensorimotor speed scores. CONCLUSIONS: Ambulatory blood pressure status was not associated with cognitive performance. A reduced nocturnal blood pressure drop was associated with quite specific cognitive deficits, but the underlying mechanism remains to be determined.     

Effects of methyltestosterone on insulin secretion and sensitivity in women

The frequent coexistence of hyperandrogenism and insulin resistance is well established; however, whether a cause and effect relationship exists remains to be established. In this study we tested the hypothesis that short-term androgen administered to women would induce insulin resistance. To test this hypothesis, regularly menstruating, nonobese women were studied before and during methyltestosterone administration (5 mg tid for 10-12 days) by the hyperglycemic (n=8) and euglycemic, hyperinsulinemic (n=7) clamp techniques. Short-term methyltestosterone administration had no significant effects on the fasting levels of glucose, insulin, c-peptide, glucagon, or glucose turnover. During the hyperglycemic clamp studies, the mean glucose level during the final hour was 203+/-2 and 201+/-1 mg/dL in the methyltestosterone and control studies, respectively. The insulin response to this hyperglycemic challenge was slightly but not significantly greater during methyltestosterone treatment (first phase 59+/-8 vs. 50+/-8 microU/mL in controls; second phase 74+/-9 vs. 67+/-9 microU/mL in controls; total insulin response 133+/-16 vs. 117+/-15 microU/mL in controls). In spite of this, glucose uptake was reduced from the control study value of 10.96+/-1.11 to 7.3+/-0.70 mg/kg/min by methyltestosterone (P < 0.05). The ratio of glucose uptake per unit of insulin was also significantly reduced from a control study value of 14.3+/-1.4 to 9.4+/-1.3 mg/kg/min per microU/mL x 100 during methyltestosterone administration. In the euglycemic hyperinsulinemic clamp studies, insulin was infused at rates of 0.25 and 1.0 mU/kg/min to achieve insulin levels of approximately 25 and 68 microU/mL, respectively. During low-dose insulin infusion, rates of endogenous hepatic glucose production were equivalently suppressed from basal values of 2.37+/-0.29 and 2.40+/-0.27 mg/kg/min to 0.88+/-0.25 and 0.77+/-0.26 mg/kg/min in the methyltestesterone and control studies respectively. Whole body glucose uptake during low-dose insulin infusion was minimally affected. During the high-dose insulin infusion, endogenous hepatic glucose production was nearly totally suppressed in both groups. However, whole body glucose uptake was reduced from the control value of 6.11+/-0.49 mg/kg/min to 4.93+/-0.44 mg/kg/min during methyltestosterone administration (P < 0.05). Our data demonstrate that androgen excess leads to the development of insulin resistance during both hyperglycemic and euglycemic hyperinsulinemia. These findings provide direct evidence for a relationship between hyperandrogenemia and insulin resistance, and its associated risk factors for cardiovascular disease.     

Skinfold thickness measurements are better predictors of body fat percentage than body mass index in male Spanish children and adolescents

OBJECTIVES: Risk factors for increased blood lead concentration (BPb) has been investigated. However, the effect of sibship and Chinese herbal medicine on BPb has not been systematically studied. In this study BPb data from voluntary testing was used to determine if Chinese herbal medicine and sibship were associated with BPb. METHODS: 319 children aged 1-7 were tested for BPb. Meanwhile, parents were interviewed to obtain information including consumption of Chinese herbal medicine, living environment, lifestyle, and sibship of the children tested. RESULTS: The mean (SD) BPb of 319 preschool children was 4.4 (2.4) micrograms/dl. The consumption of Ba-baw-san (a Chinese herbal medicine) was significantly associated with increased BPb in children (p = 0.038). Further multivariate regression analysis of BPb in 50 pairs of siblings showed the factors of being brothers explained 75% of variation for BPb, and being sisters and brother-sister explained 51% and 41% of variation respectively. CONCLUSION: Chinese herbal medicine and children's play patterns within the family expressed in different types of sibship are the main determinants of low concentrations of BPb in preschool children of Taiwan.     

Amicrobial pustulosis of the folds. A cutaneous manifestation associated with connective tissue disease

Amicrobial pustulosis (AP) is a recently defined entity associated with connective tissue diseases. Few cases have appeared in the literature. We report a case of AP coexisting with a systemic lupus erythematosus-scleroderma overlap syndrome and marked photosensitivity. The patient presented prominent pustular skin lesions and a few discoid lupus ones. No significant differences in the inflammatory infiltrate were found between the two clinical variants. The infiltrate consisted mainly of CD4+ lymphocytes and many neutrophils. CD1a+ dendritic cells were few in both epidermis and dermis. AP introduces a potential source of diagnostic confusion, but increasing experience of this syndrome will improve the awareness and diagnostic potential among dermatologists.     

A prospective 12-year study of subsyndromal and syndromal depressive symptoms in unipolar major depressive disorders

BACKGROUND: Investigations of unipolar major depressive disorder (MDD) have focused primarily on major depressive episode remission/recovery and relapse/recurrence. This is the first prospective, naturalistic, long-term study of the weekly symptomatic course of MDD. METHODS: The weekly depressive symptoms of 431 patients with MDD seeking treatment at 5 academic centers were divided into 4 levels of severity: (1) depressive symptoms at the threshold for MDD; (2) depressive symptoms at the threshold for minor depressive or dysthymic disorder (MinD); (3) subsyndromal or subthreshold depressive symptoms (SSDs), below the thresholds for MinD and MDD; and (4) no depressive symptoms. The percentage of weeks at each level, number of changes in symptom level, and medication status were analyzed overall and for 3 subgroups defined by mood disorder history. RESULTS: Patients were symptomatically ill in 59% of weeks. Symptom levels changed frequently (1.8/y), and 9 of 10 patients spent weeks at 3 or 4 different levels during follow-up. The MinD (27%) and SSD (17%) symptom levels were more common than the MDD (15%) symptom level. Patients with double depression and recurrent depression had more chronic symptoms than patients with their first lifetime major depressive episode (72% and 65%, respectively, vs 46% of follow-up weeks). CONCLUSION: The long-term weekly course of unipolar MDD is dominated by prolonged symptomatic chronicity. Combined MinD and SSD level symptoms were about 3 times more common (43%) than MDD level symptoms (15%). The symptomatic course is dynamic and changeable, and MDD, MinD, and SSD symptom levels commonly alternate over time in the same patients as a symptomatic continuum of illness activity of a single clinical disease.     

Group cognitive-behavioral treatment of binge eating disorder: a comparison of therapist-led versus self-help formats

A new enzymatic assay for selectively measuring conjugated bilirubin concentration in serum with use of bilirubin oxidase (BOD) has been developed. At pH 5.5 BOD can oxidize only conjugated bilirubin in the presence of reagents such as sodium fluoride and N-acetylcysteine which can decrease BOD reactivity to unconjugated bilirubin and bilirubin covalently bound to albumin (delta bilirubin). The resulting decrease in absorbance at 450 nm is linearly related to the concentration of conjugated bilirubin in serum. The BOD in this new assay was confirmed to oxidize conjugated bilirubin, and neither unconjugated nor delta bilirubin, based on both its reactivity to unconjugated bilirubin and HPLC results. This assay was found to give satisfactory results, such as in terms of the range of measurement, the reproducibility of the results, the lack of interference with coexisting substances in serum and the stability of the reagent solutions, in practical applications. The serum conjugated bilirubin concentrations determined using this assay correlate well with those determined by the HPLC analysis. This assay can be used for accurate monitoring of changes in the conjugated bilirubin concentration in patient sera. These findings suggest that the conjugated bilirubin assay is useful for fractional determination of bilirubin in icteric sera.     

Streptococcus mitis cell walls and lipopolysaccharide induce lethality in D-galactosamine-sensitized mice by a tumor necrosis factor-dependent pathway

PURPOSE: To investigate the clonal origin of malignant cells in recurrent superficial bladder cancer. MATERIALS AND METHODS: We compared the protein expression of p53 and retinoblastoma (Rb) by immunohistochemistry using antibody P1801 and PMG3-245, respectively, in 13 patients at the time of primary superficial bladder cancer resection (6 Ta and 7 T1) and their 15 corresponding recurrences of disease. Mutations in p53 and Rb were inferred on the basis of immunoperoxidase staining. RESULTS: At the time of initial tumor resection, a p53 mutation was observed in 5 patients (39%) and an Rb mutation was observed in 3 (23%). The p53/Rb mutation status of recurrent bladder cancers completely matched their corresponding primary bladder cancer. CONCLUSIONS: The chance that recurrent bladder cancer originated from independent clones in this study was extremely small (p < 10(-6)). This result strongly supports the monoclonal origin of recurrent superficial bladder cancer.