Acute interstitial nephritis: clinical features and response to corticosteroid therapy.

BACKGROUND: Acute interstitial nephritis (AIN) is a recognized cause of reversible acute renal failure characterized by the presence of an interstitial inflammatory cell infiltrate. METHODS: In order to evaluate the clinical characteristics and management of this disorder, we performed a retrospective study of all cases of AIN found by reviewing 2598 native renal biopsies received at our institution over a 12 year period. Presenting clinical, laboratory and histological features were identified, as was clinical outcome with specific regard to corticosteroid therapy response. RESULTS: AIN was found in 2.6% of native biopsies, and 10.3% of all biopsies performed in the setting of acute renal failure during the period analysed (n = 60). The incidence of AIN increased progressively over the period observed from 1 to 4% per annum. AIN was drug related in 92% of cases and appeared to be idiopathic in the remainder. The presenting symptoms included oliguria (51%), arthralgia (45%), fever (30%), rash (21%) and loin pain (21%). Median serum creatinine at presentation was 670 micromol/l [interquartile range (IQR) 431-1031] and 58% of cases required acute renal replacement therapy. Corticosteroid therapy was administered in 60% of cases. Serum creatinine at baseline was similar in the corticosteroid-treated and conservatively managed groups; 700 micromol/l (IQR 449-1031) vs 545 micromol/l (IQR 339-1110) P = 0.4. In this, the largest retrospective series to date, we did not detect a statistically significant difference in outcome, as determined by serum creatinine, between those patients who received corticosteroid therapy and those who did not, at 1, 6 and 12 months following presentation. CONCLUSION: The results of this study do not support the routine administration of corticosteroid therapy in the management of AIN.     

The role of charge and multiple faces of the CD8 alpha/alpha homodimer in binding to major histocompatibility complex class I molecules: support for a bivalent model.

The CD8 dimer interacts with the alpha 3 domain of major histocompatibility complex class I molecules through two immunoglobulin variable-like domains. In this study a crystal structure-informed mutational analysis has been performed to identify amino acids in the CD8 alpha/alpha homodimer that are likely to be involved in binding to class I. Several key residues are situated on the top face of the dimer within loops analogous to the complementarity-determining regions (CDRs) of immunoglobulin. In addition, other important amino acids are located in the A and B beta-strands on the sides of the dimer. The potential involvement of amino acids on both the top and the side faces of the molecule is consistent with a bivalent model for the interaction between a single CD8 alpha/alpha homodimer and two class I molecules and may have important implications for signal transduction in class I-expressing cells. This study also demonstrates a role for the positive surface potential of CD8 in class I binding and complements previous work demonstrating the importance of a negatively charged loop on the alpha 3 domain of class I for CD8 alpha/alpha-class I interaction. We propose a model whereby residues located on the CDR-like loops of the CD8 homodimer interact with the alpha 3 domain of MHC class I while amino acids on the side of the molecule containing the A and B beta-strands contact the alpha 2 domain of class I.     

Sleep patterns and stability in perimenopausal women

Women between the ages of 40 and 59 years were classified as pre-, peri-, and postmenopausal, with and without hot flash symptoms, for comparison of somnographic sleep variables. Few differences in sleep variables were noted between the groups. However, peri- and postmenopausal women experiencing hot flashes (symptomatic) tended to have lower sleep efficiencies than those not experiencing hot flashes. As well, rapid-eye-movement (REM) latency was longer (p less than 0.05) in the symptomatic women (means = 94.2 min) than in the nonsymptomatic women (means = 71.4 min). Although an age difference existed between the menopausal status groups, it was less than a decade and a main group effect for sleep efficiency and REM latency was seen while controlling for age and/or depression.     

Assessment of bioequivalence after subcutaneous and intramuscular administration of urinary gonadotrophins

The objective was to demonstrate bioequivalence between s.c. and i.m. administration of Humegon (FSH/LH ratio 1:1) and Normegon (FSH/LH ratio 3:1). In two randomized, single-centre, cross-over studies, 18 healthy volunteers on each formulation were assigned to one of the two administration sequences. Subjects were given single doses of one of the above gonadotrophins after endogenous gonadotrophin production had first been suppressed using high-dose oral contraceptive. Subsequently, rate (Cmax, tmax) and extent (AUC) of absorption of follicle stimulating hormone (FSH) and luteinizing hormone (LH) were determined for 14 days. For Cmax and AUC, analysis of variance (ANOVA) was performed on log-transformed data and for tmax ANOVA was performed on ranks. Intramuscular and s.c. injections of Humegon were bioequivalent with respect to the main pharmacokinetic parameters, being AUC and Cmax of FSH absorption. Intramuscular and s.c. injections of Normegon were bioequivalent with respect to the AUC of FSH and not bioequivalent with respect to the Cmax of FSH. For tmax of FSH as well as for most LH variables of both preparations, bioequivalence could not be proven due to the high intra- and interindividual variability and/or concentrations being close to the detection limit. Thus, the main pharmacokinetic FSH variables after i.m. and s.c. administration of Humegon and Normegon were bioequivalent.      

传染性肺结核患者家庭中儿童结核感染发病及预防的研究

目的　分析传染性肺结核患者家庭中的儿童结核感染和发病情况 ,探讨预防儿童发病的有效方案。方法　对与传染性肺结核患者密切接触的儿童进行X线胸透和做结核菌素试验 ;对结核菌素强阳性者给予预防性治疗。结果　与传染性肺结核患者密切接触的儿童感染率为 88 2 %。规则预防治疗组、不规则预防治疗组和不接受预防治疗组的患病率分别为 :8 3%、4 7 6 %、5 8 8%。结论　与传染性肺结核患者密切接触的儿童属于高危人群 ,给予预防性治疗可减少发病。     

Clinicians' perceptions of the problem of antimicrobial resistance in health care facilities

BACKGROUND: Many clinicians do not comply with guidelines regarding antimicrobial resistance (AR). In response, the Centers for Disease Control and Prevention developed a national Campaign to Prevent Antimicrobial Resistance in Healthcare Settings that presents 4 strategies and 12 evidence-based steps. METHODS: To assess clinicians' perceptions of AR, barriers and facilitators to preventing AR, and how best to reach clinicians, a questionnaire and 4 focus groups were conducted after presentation of the Campaign at 4 Pittsburgh Regional Healthcare Initiative hospitals. RESULTS: One hundred seventeen clinicians completed the questionnaire; 28 participated in the focus groups. Clinicians were significantly more likely to perceive that AR was a problem nationally than in their own institution (95% vs 77%; P<.001) or practice (95% vs 65%; P =.002), consistent with focus group results (93% nationally vs 46% institution or practice). The 3 Campaign steps with the most barriers to implementation were "Treat infection, not colonization" (35%), "Stop treatment when infection is cured or unlikely" (35%), and "Practice antimicrobial control" (33%). Clinicians in the focus groups cited the additional barriers of the health care culture, lack of knowledge, and the nursing shortage; facilitators included education, information technology, and consults. Computer programs, posters, and local data were suggested for reaching clinicians about AR. CONCLUSIONS: Clinicians perceive AR to be a complex national problem but less relevant to their own institution or practice. Providing clinicians with information and steps for preventing AR, as in the Campaign, may affect their perceptions of the problem and motivate them to take actions to ensure patient safety.     

Hormone profiling in a novel enteroendocrine cell line pGIP/neo: STC-1

Objective.GIP is a peptide hormone of therapeutic interest in type 2 diabetes and obesity. This study evaluated pGIP/neo STC-1 as a potential K-cell model for studying GIP secretion.Methods.We evaluated cellular storage and medium accumulation of GIP along with other gastrointestinal peptides cholecystokinin (CCK), peptide YY (PYY), obestatin and ghrelin over 72 h and probed possible intracellular signals (PKA, PKC, Ca^2 + and GPCR) involved in peptide hormone synthesis/secretion.Results.Results demonstrate for the first time that pGIP/Neo STC-1 cells produce and secrete 3 to 6 times more GIP than STC-1. The cells clearly retain the ability to synthesize and secrete CCK and PYY but reduced levels indicate a shift towards a predominantly K-cell phenotype. Furthermore, gastric peptides such as obestatin and ghrelin are not produced in either STC-1 or pGIP/Neo STC-1 cells.Discussion.This study demonstrates the potential usefulness of pGIP/Neo cells for studying GIP secretion and further investigations will establish its suitability for investigating hormone release in vitro.