Epithelial‐microbial crosstalk in polymeric Ig receptor deficient mice

Innate and adaptive mucosal defense mechanisms ensure a homeostatic relationship with the large and complex mutualistic gut microbiota. Dimeric IgA and pentameric IgM are transported across the intestinal epithelium via the epithelial polymeric Ig receptor (pIgR) and provide a significant portion of the first line of natural or adaptive antibody‐mediated immune defense of the intestinal mucosa. We found that colonic epithelial cells from pIgR KO mice differentially expressed (more than twofold change) more than 200 genes compared with cells from WT mice, and upregulated the expression of antimicrobial peptides in a commensal‐dependent manner. Detailed profiling of microbial communities based on 16S rRNA genes revealed differences in the commensal microbiota between pIgR KO and WT mice. Furthermore, we found that pIgR KO mice showed increased susceptibility to dextran sulfate sodium‐induced colitis, and that this was driven by their conventional intestinal microbiota. Thus, in the absence of pIgR, the stability of the commensal microbiota is disturbed, gut homeostasis is compromised, and the outcome of colitis is significantly worsened.     

Combined effects of irritants and allergens. Synergistic effects of nickel and sodium lauryl sulfate in nickel- sensitized individuals

Knowledge of the combined effects of irritants and allergens is of interest with respect to accurate risk assessment. The threshold for elicitation of allergic contact dermatitis in previously sensitized individuals may theoretically be markedly influenced by the simultaneous presence of irritants and allergens. Combined exposures have, however, only been studied infrequently. In the present study, the combined effect of an irritant and an allergen was evaluated in a dose-response designed experimental study. 20 nickel-sensitized subjects were exposed to patch testing with varying concentrations of NiCl2 (nickel chloride) and sodium lauryl sulfate (SLS) alone and in combination. Evaluation of skin reactions was performed by colorimetry, measurement of transepidermal water loss and clinical evaluation, and the data were analyzed by logistic dose-response models. A synergistic effect was found of combined exposure to NiCl2 and SLS, as compared to each of the substances applied separately, as evaluated by colorimetry and clinical scoring. This means that the effect produced by the combined exposure was substantially greater than the effect produced by either of the substances alone. A synergistic effect of combined exposure on skin barrier impairment was not found, since the barrier function is significantly influenced by SLS-exposure only and not by NiCl2. Concentration limits are used by industry and government agencies to protect consumers. The present results clearly illustrate that elicitation thresholds and concentration limits may be influenced considerably by combined exposure to allergens and irritants.     

Impact of gender on the risk of AIDS-defining illnesses and mortality in Danish HIV-1-infected patients: A nationwide cohort study

Abstract Background: Gender differences in the risk of AIDS-defining illness (ADI) and mortality have been reported in the HIV-1-infected (HIV-positive) population, with conflicting findings. We aimed to assess the impact of gender on the risk of ADI and death in HIV-positive patients infected sexually. Methods: This was a population-based, nationwide cohort study of incident Danish HIV-positive individuals infected by sexual contact. Outcomes were progression to AIDS and death. We used Cox proportional hazards models and Poisson regression analyses to calculate the risk of progression to AIDS and mortality rate ratios (MRR) between risk groups and compared these with the general Danish population. Results: We identified 587 heterosexually infected women, 583 men who have sex with women (MSW), and 1089 men who have sex with men (MSM). The total follow-up time was 13,708 person-y. At the time of HIV diagnosis MSM had a lower prevalence of AIDS compared to MSW. Women and MSW presented more often with tuberculosis and less often with AIDS-defining cancers compared to MSM. In the adjusted analyses we observed no differences in progression to AIDS. In the adjusted analyses of risk of death, there were no differences between the 3 risk groups, although we saw a trend towards a higher risk of death in older MSW. MSM had a lower risk of death compared to the background population than women and MSW. Conclusions: In the Danish HIV population, gender has no major impact on progression to AIDS or mortality. Differences in these factors between women, MSW, and MSM are mainly due to confounding from race and CD4 + cell count at diagnosis.     

Multilevel analysis of couple congruence on pain, interference, and disability

Couple congruence on ratings of pain severity and disability were examined using hierarchical linear modeling. Older community Individuals with Chronic Pain (ICPs) and their spouses completed the Multidimensional Pain Inventory (pain severity, interference, negative spouse responses to pain), Sickness Impact Profile (physical disability, psychosocial disability), and the Mood and Anxiety Symptom Questionnaire (psychological distress). Both spouses reported on ICPs' pain and disability as well as their own psychological distress. Spousal incongruence was observed on interference and physical disability such that ICPs reported greater disability than their spouses reported for them. No significant incongruence was observed in pain severity or psychosocial disability. Predictors of couples' mean ratings of pain and disability were identified. Specifically, couples in which the ICP was female reported higher couples' ratings of pain severity and interference. ICP distress was related to higher couples' ratings of all pain and disability variables whereas spouse distress was related to higher psychosocial disability ratings. ICPs' perceptions of negative spouse responses were also positively associated with couples' ratings of physical and psychosocial disability. In terms of congruence, ICP distress was associated with incongruence on interference, physical disability, and psychosocial disability whereas spouse distress predicted incongruence on pain severity, and interference. This study suggests that understanding couples' pain outcome ratings involves an awareness of factors that might influence their perceptions and behaviors.     

Percutaneous nephrolithotripsy under assisted local anaesthesia for high risk patients: Is it effective?

ObjectivesThe aim of the present study is to evaluate the feasibility and safety of performing PNL under local anesthesia in a selected group of patients who are at high risk for general anesthesia.Patients and methodsForty seven patients underwent PNL under local anesthesia. There were 38 males and 9 females with a mean age of 62 years. All patients were at medical high-risk for general anesthesia, with an American Society of Anesthesiologists (ASA) score of 3. The indications for local anesthesia in this study were obstructed single functioning kidney with azotemia in 29 patients, hepatic insufficiency in 8 patients, cardiac problems in 7 patients and 3 patients had hepatocellular carcinoma. The mean stone size was 2.7 cm (range 2–3.1 cm). Local infiltration with 10–20 cc of 2% lidocaine at the site of puncture was used in all cases. Narcotics were given 30 min prior to the procedure and medazolam was given intraoperatively upon demand. Utrasound guided puncture was performed in all cases and tract dilatation was then done under fluoroscopy using high pressure balloon catheter in 35 and Alken's metal dilators in 12 cases. Stones were then retrieved after disintegration in the same cession in 33 patients, while the other 14 patients underwent staged PNL, where a 12 Fr. nephrostomy tube was placed in the first stage, followed by tract dilatation and stone retrieval one week later.ResultsOut of 47 patients included, 44 had successful PNL either one stage (30 patients) or two stages (14 patients). Only 3 patients could not tolerate pain and the procedure was terminated after placement of nephrostomy tube and stone retrieval was completed later under general anesthesia.ConclusionOur results demonstrated that PNL under local anesthesia with narcotics and sedatives seems to be a satisfying solution for the treatment of a selected group of patients with renal pelvic stones and who have high anesthetic risk. However, additional studies with different groups of patients are required to validate our results.     

Complications attributable to rotavirus-induced diarrhoea in a Swedish paediatric population: report from an 11-year surveillance

The aim of this retrospective observational study was to evaluate age, length of hospital stay and development of complications in children hospitalized with community- or nosocomially- acquired rotavirus gastroenteritis (RV GE). In total, medical records of 984 children with RV GE were analysed retrospectively. The median age was 13.8 months (3 weeks to 99 months) in children with community acquired RV GE (n=723) and 9.0 months (range 3 weeks to 82 months) in children with nosocomially acquired RV GE (n=261). During this 11-y surveillance, only 2 children were admitted twice for a RV GE, suggesting development of subsequent protective immunity against severe rotavirus gastroenteritis after the first episode. Complications occurred in 16.5% of the children with community acquired RV GE and only in 1.9% of the nosocomially acquired RV GE. Identified complications in children with community acquired RV GE were: severe dehydration resulting in intensive care (1.7%), death (0.1%), hypertonic dehydration (9.1%), seizures (4.0%) and encephalitis with abnormal EEG (1.7%). The median age of children in need of intensive care was 9.1 months and in those developing hypertonic dehydration 10.8 months, both significantly lower than in children with no complications (p<0.05). Interestingly, the age of children developing seizures and signs of encephalitis was significantly higher than in children with no complications (p<0.01).     

Decreased expression of phospholipase C-beta 2 isozyme in human platelets with impaired function

Platelets from a patient with a mild inherited bleeding disorder and abnormal platelet aggregation and secretion show reduced generation of inositol 1,4,5-trisphosphate, mobilization of intracellular Ca2+, and phosphorylation of pleckstrin in response to several G protein mediated agonists, suggesting a possible defect at the level of phospholipase C (PLC) activation (see accompanying report). A procedure was developed that allows quantitation of platelet PLC isozymes. After fractionation of platelet extracts by high-performance liquid chromatography, 7 out of 10 known PLC isoforms were detected by immunoblot analysis. The amount of these isoforms in normal platelets decreased in the order PLC- gamma 2 > PLC-beta 2 > PLC-beta 3 > PLC-beta 1 > PLC-gamma 1 > PLC- delta 1 > PLC-beta 4. Compared with normal platelets, platelets from the patient contained approximately one-third the amount of PLC-beta 2, whereas PLC-beta 4 was increased threefold. These results suggest that the impaired platelet function in the patient in response to multiple G protein mediated agonists is attributable to a deficiency of PLC-beta 2. They document for the first time a specific PLC isozyme deficiency in human platelets and provide an unique opportunity to understand the role of different PLC isozymes in normal platelet function.     

Possible effect of secretor locus on plasma concentration of factor VIII and von Willebrand factor

A significant fraction (30%) of the genetically determined variance in plasma concentration of the von Willebrand factor antigen (vWf:Ag) has been shown to be related to ABH determinants. Individuals with blood group O, who have the highest amounts of blood group H substance, have the lowest concentration of vWf:Ag. The Lewis substances, Le(a) and Le(b), are biochemically closely related to the ABH substances as both can be produced from the same precursor substance. We studied the effect of the presence of the Lewis antigens on the plasma concentration of vWf:Ag and factor VIII antigen (VIII:Ag) in 323 individuals of different ABO groups from a series of twins and in 58 blood donors of blood group O. Among persons belonging to blood group O, those with the Le(a) antigen had a higher concentration of both vWf:Ag and VIII:Ag than individuals lacking Le(a). Le(a+b-) people are nonsecretors and Le(a-b+) people are secretors of ABH substance. Thus, the lowest concentration of vWf:Ag and VIII:Ag was found in group O secretors. The effect is most likely due to an effect of the secretor locus. This finding may be of importance for the detection of carriers of hemophilia A and for the diagnosis of type I von Willebrand disease.