Behavioral and neuropsychological foundations of olfactory fear conditioning

Pavlovian fear conditioning procedures have been a fruitful means of exploring the neural substrates of associative learning. There is now substantial evidence suggesting that many aspects of conditioned fear depend critically upon the integrity of the amygdala and the perirhinal cortex. Recent studies in our laboratory examining the contributions of these areas to olfactory and contextual fear conditioning are reviewed; collectively the results of these studies suggest that the amygdala participates critically in the acquisition and expression of fear conditioned to both an olfactory conditioned stimulus (CS) and to the training context, while the perirhinal cortex contributes to olfactory, but not contextual, fear conditioning. Moreover, it appears that perirhinal cortex may play a prominent role in recognition of the CS following conditioning. These results are discussed in light of the extent to which they replicate and extend previous research examining the contributions of these areas to fear conditioned to auditory and visual CSs.     

Pathology and Pathogenesis of Ovine Pulmonary Adenocarcinoma

Ovine pulmonary adenocarcinoma (OPA), also known as jaagsiekte, is a transmissible lung tumour of sheep caused by jaagsiekte sheep retrovirus (JSRV). JSRV induces neoplastic transformation of alveolar and bronchiolar secretory epithelial cells and the resulting tumours can grow to occupy a significant portion of the lung. Tumour growth is frequently accompanied by the overproduction of fluid in the lung, which further compromises normal respiration. The period between infection and the appearance of clinical signs may be several months or years and many JSRV-infected sheep do not exhibit clinical signs at all during their lifespan. This allows the spread of OPA into new flocks through contact with infected but apparently normal animals. OPA was first described in the early 19th century; however, it has still not been possible to devise effective methods for controlling its spread and it remains an important problem in most countries where sheep are farmed. This is due in part to the absence of an immunological response to JSRV in infected animals, which has hindered the development of serological diagnostic tests and vaccines. In addition to its veterinary importance, OPA is regarded as a potential large animal model for human lung adenocarcinoma and this has stimulated research into the pathogenesis of the ovine disease. This work has produced some significant results, including the finding that one of the JSRV structural proteins is directly involved in oncogenesis. The recent advances in understanding JSRV and the pathogenesis of OPA should lead to novel strategies for diagnosis and control of this disease and for its exploitation as a comparative model for human lung cancer.     

Guidelines for prevention of hospital acquired infections

These guidelines, written for clinicians, contains evidence-based recommendations for the prevention of hospital acquired infections Hospital acquired infections are a major cause of mortality and morbidity and provide challenge to clinicians. Measures of infection control include identifying patients at risk of nosocomial infections, observing hand hygiene, following standard precautions to reduce transmission and strategies to reduce VAP, CR-BSI, CAUTI. Environmental factors and architectural lay out also need to be emphasized upon. Infection prevention in special subsets of patients - burns patients, include identifying sources of organism, identification of organisms, isolation if required, antibiotic prophylaxis to be used selectively, early removal of necrotic tissue, prevention of tetanus, early nutrition and surveillance. Immunodeficient and Transplant recipients are at a higher risk of opportunistic infections. The post tranplant timetable is divided into three time periods for determining risk of infections. Room ventilation, cleaning and decontamination, protective clothing with care regarding food requires special consideration. Monitoring and Surveillance are prioritized depending upon the needs. Designated infection control teams should supervise the process and help in collection and compilation of data. Antibiotic Stewardship Recommendations include constituting a team, close coordination between teams, audit, formulary restriction, de-escalation, optimizing dosing, active use of information technology among other measure. The recommendations in these guidelines are intended to support, and not replace, good clinical judgment. The recommendations are rated by a letter that indicates the strength of the recommendation and a Roman numeral that indicates the quality of evidence supporting the recommendation, so that readers can ascertain how best to apply the recommendations in their practice environments.     

Down-regulation of specific antigen-driven cytokine production in a population with endemic Schistosoma japonicum infection

Schistosome antigen-driven cytokine responses and antischistosome antibody levels of residents of a Schistosoma japonicum endemic island in Poyang Lake, Jiangxi Province were studied before and 45 days after treatment with praziquantel. IL-4, IL-5, IL-10 and INF-gamma were all detected in the supernatants of whole-blood cultures after stimulation with schistosome soluble egg antigen (SEA) and soluble worm antigen preparation (SWAP). The percentages of subjects producing detectable amounts of each cytokine assayed were higher in the group who were negative by stool examination at the start of the study than in those who were initially stool positive. After praziquantel treatment the percentages of subjects producing both type I and type II cytokines increased. This suggests that the production of both types of cytokine was down-regulated in the presence of live, egg-laying S. japonicum adult worms but that this was reversible by treatment. In contrast, the antibody studies showed higher levels of SWAP and SEA-specific antibodies (IgE, total IgG, IgG4, IgM) in subjects who were originally stool-positive than in those who were stool-negative. After treatment specific IgE responses were elevated, but total IgG and IgG4 anti-SEA and IgM anti-SWAP antibody levels all fell significantly.     

High-dose etoposide and cyclophosphamide without bone marrow transplantation for resistant hematologic malignancy

Seventy-five patients with resistant acute leukemia or lymphoma received high-dose cyclophosphamide and etoposide to explore the activity of this combination in resistant hematologic malignancies, and to determine the maximum doses of these drugs that can be combined without bone marrow transplantation. Etoposide was administered over 29 to 69 hours by continuous infusion corresponding to total doses of 1.8 g/m2 to 4.8 g/m2. Cyclophosphamide, 50 mg/kg/d, was administered on 3 or 4 consecutive days total 150 to 200 mg/kg ideal body weight). At all dose levels myelosuppression was severe but reversible. Mucosal toxicity was dose-limiting with the maximum tolerated dose level combining etoposide 4.2 g/m2 with cyclophosphamide 200 mg/kg. Continuous etoposide infusion produced stable plasma levels that were lower than would be achieved after administration by short intravenous infusion, and this could explain our ability to escalate etoposide above the previously reported maximum tolerated dose. There were 28 complete (35%) and 12 partial (16%) responses. Median duration of complete response (CR) was 3.5 months (range 1.1 to 20+). Seventeen of 40 patients (42%) with acute myelogenous leukemia (AML) achieved CR, including 6 of 20 (30%) with high-dose cytosine arabinoside resistance. We conclude that bone marrow transplantation is not required after maximum tolerated doses of etoposide and cyclophosphamide. This regimen is active in resistant hematologic neoplasms, and the occurrence of CR in patients with high-dose cytosine arabinoside-resistant AML indicates a lack of complete cross-resistance between these regimens.     

Cystic fibrosis and the phenotypic expression of autosomal dominant polycystic kidney disease

Recent experiments in cultured cyst epithelial cells from kidneys of patients with autosomal dominant polycystic kidney disease (ADPKD) have shown that the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) is present in the apical surface of these cells and mediates chloride (Cl-) and fluid secretion in vitro. To determine whether the presence of CF with the expression of mutated CFTR proteins modifies cyst formation in ADPKD, we studied a large family with both inherited diseases. ADPKD in this family is linked to PKD1. The family is composed of 26 members; 11 members with ADPKD, 4 members with CF, and 2 members with both diseases. Renal volumes measured by computerized tomography (CT), calculated creatinine clearances, and other clinical parameters in the family members with ADPKD and CF were compared with those in the family members with ADPKD alone, as well as to a large population of patients with ADPKD. The patients with CF and ADPKD, but not the CF heterozygote carriers with ADPKD, had less severe polycystic kidney and liver disease, as indicated by normal renal function; smaller renal volume, even when corrected for height and body surface area; and the absence of hypertension and liver cysts. These observations suggest that the coexistence of CF may reduce the severity of ADPKD.