Early alcoholic liver injury: Activation of lipocytes in acinar zone 3 and correlation to degree of collagen formation in the disse space

Acinar zone 3 areas in liver biopsy specimens from 23 alcoholics and 47 non-alcoholics were investigated by light microscopy and transmission electron microscopy to asses fibrosis in the perisinusoidal space and to evaluate the role of the lipocytes. Quantitative analysis by light microscopy on toluidine blue-stained sections showed a significant reduction in number of lipocytes--median values of 2.7 and 1.2 lipocytes per 100 hepatocytes in biopsies from chronic alcoholics showing no or varying degrees of zone 3 fibrosis, respectively, as compared to 3.6 lipocytes per 100 hepatocytes in non-alcoholic livers. By transmission electron microscopy, the reduction in number of lipocytes was related to a corresponding increase in number of cells rich in rough endoplasmic reticulum and microfilaments (activated lipocytes). The occurrence of activated cells was significantly correlated to fibrosis of the perisinusoidal space. Activation of lipocytes and collagenization of the perisinusoidal space appeared before light microscopic evidence of fibrosis and were topographically not related to Mallory bodies or alcoholic hepatitis.     

The effect of solvent/detergent-treated plasma on red cells stored in vitro

BACKGROUND: The potential use of solvent/detergent-treated plasma (S/D plasma) in transfusion practice raises concerns about the cytolytic effects that any residual solvent and detergent in the virally inactivated blood component might have on units of red cells in vitro, if the two components are mixed during preparation. STUDY DESIGN AND METHODS: S/D plasma was mixed with variously processed units of stored red cells, in vitro, to evaluate the effect the residual solvent and detergent would have on cell membrane integrity. A paired protocol design was used in which half-units of red cells were exposed to S/D plasma (test), and the matched half-units were exposed to either the supernatant additive solution from the original red cell unit or standard fresh-frozen plasma (FFP) (control). After incubation for up to 5 days, the units were evaluated for evidence of hemolysis or changes in other red cell storage assays. RESULTS: This study showed that, for fresh additive solution red cells (AS-1), the 5-day storage plasma hemoglobin levels were comparable in the red cells exposed to S/D plasma (21 mg/dL) and in the paired half-units stored in the original AS-1 supernatant (31 mg/dL) (p > 0.05). Similar findings were recorded for stored AS-1 red cells (S/D plasma; 111 mg/dL vs. AS-1 supernatant, 147 mg/dL; p > 0.05); stored CPDA-1 red cells (S/D plasma, 133 mg/dL vs. FFP, 103 mg/dL; p > 0.05); frozen red cells (S/D plasma, 28 mg/dL vs. FFP, 18 mg/dL; p > 0.017); and stored irradiated AS-1 red cells (S/D plasma, 608 mg/dL vs. AS-1 supernatant, 726 mg/dL; p > 0.05). Comparable results were found for other assays, including levels of plasma potassium, osmotic fragility, and red cell antigen titer. CONCLUSION: These data show that S/D plasma does not induce red cell lysis even after 5 days of in vitro storage. These results are consistent with previous findings by this laboratory that platelets are not harmed by storage in S/D plasma. Red cells resuspended in S/D plasma and stored for up to 5 days maintain in vitro storage characteristics that are acceptable for the use of the cells in clinical transfusion practice.     

The efficacy of behavioral interventions in reducing HIV risk sex behaviors and incident sexually transmitted disease in black and Hispanic sexually transmitted disease clinic patients in the United States: a meta-analytic review

OBJECTIVES: Interventions targeting sexually transmitted disease (STD) clinic patients provide an important opportunity to modify high-risk sex behaviors related to HIV/STD transmission. Identifying efficacious interventions for blacks and Hispanics is urgently needed because these 2 groups are disproportionately affected by the HIV/STD epidemics. GOAL: This meta-analysis evaluates the efficacy of behavioral interventions in reducing unprotected sex and incident STD among black and Hispanic STD clinic patients. STUDY DESIGN: Comprehensive searches, including electronic databases (1988-2004), hand searches of journals (January 2004 to June 2005), reference lists of articles, and contacts with researchers, identified 18 randomized, controlled trials meeting the selection criteria. RESULTS: Interventions significantly reduced unprotected sex (odds ratio [OR] = 0.77; 95% confidence interval [CI] = 0.68-0.87; 14 trials; N = 11,590) and incident STD (OR = 0.85; 95% CI = 0.73-0.998; 13 trials; N = 16,172). CONCLUSIONS: Behavioral interventions provide an efficacious means of HIV/STD prevention for blacks and Hispanics who attend STD clinics.     

Menkes X linked disease: heterozygous phenotype in uncloned fibroblast cultures.

The 64Cu incorporation into uncloned fibroblast cultures from 16 Menkes disease mothers and 19 first and second degree female relatives was examined. The mean incorporation for the Menkes disease mothers (36.2 +/- 3.6 SEM) differed significantly from that of 25 normal subjects (21.7 +/- 0.9 SEM) suggesting the presence of a significant proportion of mutant cells. In addition, the results suggested a heterozygous state in a number of the female relatives. Uncloned fibroblast cultures from four Menkes disease heterozygotes showed increasingly abnormal copper uptake values after repeated freezing procedures. Manipulation of tissue cultures may help to identify a number of female carriers.     

The clinical spectrum of epidermolysis bullosa simplex

As part of the U.K. National Epidermolysis Bullosa Register, we have systematically recorded clinical information on 130 (77%) of the 168 known Scottish epidermolysis bullosa simplex (EBS) sufferers. Three subtypes of EBS were recognized: Dowling–Meara (EBS‐DM), Weber–Cockayne (EBS‐WC) and Köbner (EBS‐Kb), seen in 5%, 42% and 53% of patients, respectively. As there is considerable overlap between EBS‐WC and EBS‐Kb, with both phenotypes frequently seen within the same pedigree, EBS‐WC is best regarded as a milder variant of EBS‐Kb rather than a separate disorder. Improvement with age is common in all variants of EBS, but is not invariable. Pain due to acral blistering in EBS‐Kb/EBS‐WC has a more marked impact on life‐style than the blisters of EBS‐DM. Oral blistering, nail involvement and aplasia cutis congenita occur in all EBS subtypes and laryngeal involvement is a feature of EBS‐DM. Seasonal variation is not seen in EBS‐DM but is common in EBS‐Kb/EBS‐WC.     

Uptake and release of [3H]dopamine by the median eminence: evidence for presynaptic dopaminergic receptors and for dopaminergic feedback inhibition

The accumulation and release of [3H]dopamine by the median eminence in vitro was studied after treatments with different pharmacological agents, to determine whether such a procedure would be useful for measuring neuronal activity in the tuberoinfundibular dopaminergic system. The accumulation of [3H]dopamine was temperature, time, and sodium dependent, and reduced by unlabelled dopamine and by a potent dopamine uptake blocker, nomifensine. The outflow of tritium was studied after blocking the oxidative deamination of dopamine by nialamide. The outflow of tritium was elicited consistently by biphasic square wave electrical pulses and by high molarity potassium ions. The response to electrical stimulation was dependent largely on calcium and partially on sodium. The response to high molarity potassium ions was reduced in the absence of calcium ions. The response to electrical stimulation was increased by nomifensine and by a dopaminergic antagonist, haloperidol, and was reduced by dopamine and by a dopaminergic agonist, piribedil. The inhibitory action of dopamine was antagonized by haloperidol. These results indicate the existence of uptake and release mechanisms in the tuberoinfundibular dopamine neurons, and suggest that dopamine may inhibit its own release via dopaminergic receptors. This in vitro method may be useful for measuring dopamine uptake and release by tuberoinfundibular dopaminergic neurons.     

Effects of LSD on the responses of single units in cat visual cortex

Summary The effects of intravenous doses (200 g) of LSD on the activity of single neurones in the primary visual cortex have been studied in cats anaesthetized with urethane. Cells were stimulated with a bright bar of light moved over the receptive field, and orientation tuning was assessed quantitatively before and after administration of the drug. Changes in neuronal activity were compared with those observed in a control sample of cells recorded when the cats were given no drug. LSD increased the responsiveness of some cells to visual stimuli and decreased that of others, but some cells were not affected. The changes in responsiveness were dose dependent; the larger doses of the drug (expressed in g/kg body weight) tended to depress the responses and the smaller doses to enhance them. The effects appeared earlier in complex cells than in simple cells. Changes in spontaneous activity, direction selectivity and orientational properties were found in some cells.     

Systematic review with meta-analysis: Stress-management interventions for patients with irritable bowel syndrome

Irritable bowel syndrome (IBS) is a common chronic gastrointestinal disorder of unknown pathological origin that is associated with psychological distress and reduced health-related quality of life (HRQoL). We investigated the effects of stress-management for adults with IBS on typical symptoms, HRQoL and mental health. With predefined criteria (patients: adults with IBS; intervention: stress-management; control: care as usual or waitlist; outcome: patient-relevant; study-type: controlled trials), we registered the study with PROSPERO (168030) and searched the main medical databases. Two researchers independently reviewed the publications and assessed the risk of bias using the Scottish Intercollegiate Guidelines Network checklist. We performed meta-analysis with homogeneous trials of acceptable quality. After screening 6656 publications, ten suitable randomized trials of acceptable (n = 5) or low methodological quality (n = 5) involving 587 patients were identified. Our meta-analysis showed no effect of stress-management on IBS severity 1–2 months after the intervention (Hedges' g = −0.23, 95%-CI = −0.84 to −0.38, I² = 86.1%), and after 3–12 months (Hedges' g = −0.77, 95%-CI = −1.77 to −0.23, I² = 93.3%). One trial found a short-term reduction of symptoms, and one trial found symptom relief in the long-term (at 6 months). One of two studies that examined HRQoL found an improvement (after 2 months). One of two studies that examined depression and anxiety found a reduction of these symptoms (after 3 weeks). Stress-management may be beneficial for patients with IBS regarding the short-term reduction of bowel and mental health symptoms, whereas long-term benefits are unclear. Good quality RCTs with more than 6 months follow-up are needed.     

Inhalant allergen sensitization is an independent risk factor for the development of angioedema

Background/objective

The etiology and risk factors for angioedema remain poorly understood with causative triggers often going undiagnosed despite repeated reactions. The purpose of this study was to determine the relationship between inhalant allergen sensitization and angioedema.