Onset Patterns Prior to 36 Months in Autism Spectrum Disorders

The present study investigated differences among children with three different patterns of autism symptom onset: regression, plateau, and no loss and no plateau. Cross-sectional data were collected from parents of children aged 3–17 years with an autism spectrum disorder (n = 2,720) who were recruited through a US-based online research database. Parental report of developmental characteristics was assessed through a parent questionnaire, and current autism symptoms were measured via the Social Responsiveness Scale and Social Communication Questionnaire. Multivariate analyses indicated that children with regression had a distinct developmental pattern marked by less delayed early development. However, following regression, these children evinced elevated autism symptom scores and an increased risk for poorer outcomes when compared with the other onset groups.     

Antibiotics are associated with lower relapse rates in outpatients with acute exacerbations of COPD

BACKGROUND: COPD is a complex disease with exacerbations characterized by worsening of symptoms resulting in deteriorating lung function. STUDY OBJECTIVE: To assess predictive factors of relapse for patients with acute exacerbations of COPD (AECB). DESIGN: Retrospective cohort analysis of visits for AECB. SETTING: Veterans Affairs Medical Center. PATIENTS: Three hundred sixty-two visits (173 patients) with documented COPD treated as outpatients for AECB. MEASUREMENTS: Severity of underlying COPD, severity of AECB, comorbid conditions, therapy, and relapse rates (return visit within 14 days with persistent or worsening symptoms). RESULTS: Each visit was analyzed individually (referred to as a patient-visit). One group received antibiotics (270 patient-visits), and the second group (92 patient-visits) did not. Both groups had similar demographics and severity of underlying COPD. The overall relapse rate was 22%. The majority of patient-visits (95%) with severe symptoms at presentation were prescribed antibiotics vs only 40% of those with mild symptoms. Twenty-nine of 92 patient-visits (32%) were followed by relapse in the group that was not given antibiotics, whereas only 50 of 270 (19%) treated with antibiotics relapsed (p < 0.001). Those treated with amoxicillin had an even higher relapse rate (20 of 37 patient-visits, or 54%) than those who did not receive antibiotics (p = 0.006). CONCLUSIONS: Relapse from AECB was not related to the severity of underlying disease or to the severity of the acute exacerbation. Patients treated with antibiotics had significantly lower relapse rates than those who did not receive antibiotics. However, the specific choice of antibiotic is important because those treated with amoxicillin had the highest relapse rates of all groups.     

Inhibition of cytochrome P450 2E1 by propofol in human and porcine liver microsomes

While almost anesthetics are metabolized by the cytochrome P450 (CYP) 3A4, some major volatile ones such as halothane and sevoflurane are metabolized by CYP2E1 in humans. To determine whether 2,6-diisopropylphenol (propofol), a widely used intravenous anesthetic agent, known to inhibit CYP3A4 and CYP1A2, also inhibits CYP2E1, 6-OH hydroxylation of chlorzoxazone, a prototypical CYP2E1 substrate, was estimated using two pools of human microsomes and one pool of porcine microsomes from seven livers. Basal human enzyme activities were characterized by a V(max) of 1426+/-230 and 288+/-29 pmol min(-1)mg(-1) protein and a K(m) of 122+/-47 and 149+/-42 microM, while the corresponding porcine activities were associated with a V(max) of 352+/-42 pmol min(-1)mg(-1) protein and a K(m) of 167+/-38 microM. A competitive inhibition of CYP2E1 by propofol was observed with low inhibition constants in the therapeutic range in both porcine (19 microM) and human (48 microM) liver microsomes. These in vitro results suggest that propofol could have a protective effect on toxic metabolite activation of compounds catalyzed by CYP2E1.     

Optimizing care for African-American HIV-positive patients

The African-American community has been disproportionately affected HIV/AIDS, as noted by higher reported rates of HIV infection, higher proportion of AIDS cases, and more deaths caused by complications of AIDS than whites and other ethnic groups. In addition, epidemiologic trends suggest that African Americans with HIV infection are more often diagnosed later in the course of HIV disease than whites. Numerous reasons account for this disparity, including the lack of perception of risk and knowledge about HIV transmission as well as a delays in HIV testing and diagnosis in the African-American community. Understanding the important considerations in the management of HIV infection in the African-American patient may create awareness among health care professionals and broaden the knowledge of HIV-infected patients within the African-American community.     

Macrophage colony-stimulating factor expression and macrophage accumulation in renal allograft rejection

BACKGROUND: Studies of infiltrating cells from acutely rejecting renal allografts show that a high proportion of these cells are macrophages, and early macrophage infiltration is a poor prognostic sign for transplant survival. Macrophage colony-stimulating factor (M-CSF), produced by tubular and mesangial cells, has been associated with macrophage infiltration and proliferation in experimental and human kidney diseases. We investigated the expression of M-CSF in a model of acute rejection. METHODS: Lewis rats underwent bilateral nephrectomies and received an orthotopic Dark Agouti allograft or Lewis isograft. Animals received cyclosporine (10 mg/kg/day) from day 0 to day 3 and were killed at days 4, 8, or 14 after transplantation. Macrophages (ED1+) and T cells (W3-13+) were identified by immunohistochemistry, and M-CSF expression was identified by Northern blotting and in situ hybridization. RESULTS: Isografts had normal renal function without histological evidence of rejection. Allografts exhibited a moderate infiltrate at day 4 but progressed to severe rejection at day 14, with elevated serum creatinine level and severe tubulointerstitial damage. Macrophages and T cells were present in equal proportion in the infiltrate at day 4. At day 14, the number of macrophages increased fivefold (2580/mm2), although T cells were unchanged (380/mm2). Proliferating macrophages (ED1+, BrdU+) increased from day 4 (4%) to day 14 (10%). M-CSF mRNA expression was strongly up-regulated in allografts compared with isografts and normal rat. In situ hybridization demonstrated M-CSF expression by resident and infiltrating cells. Renal tubular expression was minimally increased at day 4 but strongly up-regulated at day 14 (more than 50% of tubules positive), particularly in areas of tubular damage. Tubular M-CSF expression colocalized with areas of intense macrophage infiltration and proliferation. Serial sections with double labeling demonstrated that T cells were the dominant source of M-CSF at day 4, yet later in the rejection (day 14) the predominant sites of production were both renal tubular cells and interstitial macrophages. CONCLUSIONS: Renal production of M-CSF by graft-infiltrating (macrophages and T lymphocytes) and resident (tubular) cells was up-regulated during acute rejection. M-CSF promotes macrophage recruitment and proliferation and may thereby play a pathogenic role in acute rejection. The kinetics of M-CSF production during acute rejection suggest that local macrophage proliferation may be initiated by T cells and perpetuated by both renal tubular and autocrine release.     

Umfrage zur Therapie der tiefen Beinvenenthrombose unter den Mitgliedern der Deutschen Gesellschaft für Gefäßchirurgie

Introduction. In the literature of the past 15 years, deep venous thrombectomy has been rarely described. The only indications reported for thrombectomy seem to be recurrent pulmonary embolisation and phlegmasia coerulea dolens. Many contraindications and severe complications are making decisions concerning thrombolysis very difficult. At present, anticoagulation therapy is preferred over fibrinolysis. There is no conclusive concept for the standardization of treatment for deep venous thrombosis. As a first step towards achieving this, it was necessary to know what therapy is performed in hospitals throughout Germany. Methods. In 1999, we sent letters of enquiry to the members of the “Deutsche Gesellschaft für Gefässchirurgie”. We wrote to 341 members (hospitals), and the information gained by means of a questionnaire was analysed and evaluated. Results. We received answers from 39.9% (n=136) of the members. In all, 69% of the hospitals had an independent vascular department. In 1999, 6,718 patients underwent treatment for deep venous thrombosis, on average, 51 patients per hospital. Overall, 7,665 therapies were performed in one year (15.9% thrombectomy, 18.6% fibrinolysis, and 65.5% only anticoagulation). Only 23.5% of the hospitals had their own data about the outcome of their patients. The patency rate was 71.8% for thrombectomy and 48.9% for fibrinolysis. A severe postthrombotic syndrome was seen in 6.2% after thrombectomy, in 8.1% after fibrinolysis, and in 10.4% after singular anticoagulation. Conclusion. At present, there is still no standardized concept for the treatment of patients with deep venous thrombosis. It seems that there are better results for some indications with thrombectomy than with other methods. For the establishment of a concept of treatment, a prospective randomised study is necessary.