Imipenem/cilastatin therapy of infections in cancer patients

Imipenem/cilastatin was administered during 153 febrile episodes occurring in cancer patients and the response rate was 68%. Considering only documented infections the response rate was 71%. Patients who received imipenem as initial therapy had a higher response rate than patients who received it after failing other antibiotics (77% versus 68%). The overall response rates for septicemias and pneumonias were 75% and 58%. Among the 57 gram-negative infections 77% responded, but the response rate was substantially higher if imipenem was used as initial therapy (94% versus 69%). The poorest response rate was observed when imipenem was given as secondary therapy for Pseudomonas infections (50%), but most of these patients had failed to respond to other appropriate antibiotics. The only serious side effect was seizures which occurred in ten patients, although eight of them had other predisposing factors. Imipenem appears to be a useful antibiotic for treatment of infections, even in neutropenic cancer patients.     

Hospital acquired native valve endocarditis caused by Acinetobacter calcoaceticus and treated with imipenem/cilastin

A case of hospital acquired endocarditis due to Acinetobacter calcoaceticus in a severely burned patient is presented. Both aortic and mitral native valves were affected and the organism was resistant to most antimicrobial agents.     

Predicting medical students' intentions to take up rural practice after graduation

Objectives Using a novel longitudinal tracking project, this study develops and evaluates the performance of a predictive model and index of rural medical practice intention based on the characteristics of incoming medical students. Methods Medical school entry survey data were obtained from the Medical Schools Outcome Database (MSOD) project implemented in all Australian and New Zealand medical schools and coordinated through Medical Deans Australia and New Zealand, the representative body for the Deans of 18 Australian and two New Zealand medical schools and faculties. The medical school commencement survey collects data on students’ education and family background, including rural upbringing, personal circumstances and scholarships, and on their practice intentions in terms of location and specialty. The MSOD will also allow tracking of medical graduates after graduation. Logistic regression modelling was used to develop a predictive model of rural practice intention. Split‐sample validation was used to gain some insight into the stability of performance of the model. Results Response rates to the MSOD survey exceeded 90% on average. The model findings confirm and extend previous research examining the association of medical student characteristics with intention to take up rural medical practice. The statistically significant independent factors in the model included students’ rural backgrounds, financial arrangements and intentions regarding specialist versus generalist practice upon graduation. Model performance was good, with an area under the receiver‐operator characteristics curve of 0.86, and reproducible, with an area in a validation sample of 0.83. Conclusions The model and related index provide important insights into individual factors associated with rural practice intention among students commencing medical studies. The model can also provide a means for optimising the use of scarce medical programme resources, thereby helping to improve the supply of rural medical practitioners. This study illustrates the power and potential of a robust, consistent, systematic longitudinal tracking project.     

All-cause and cardiovascular mortality in diabetic subjects increases significantly with reduced estimated glomerular filtration rate (eGFR): 10 years' data from the South Tees Diabetes Mortality study.

AIMS: To investigate the association between estimated glomerular filtration rate (eGFR) and total and cardiovascular mortality in a population-based cohort of diabetic subjects. METHODS: A longitudinal study using a population-based district diabetes register comprising 3288 subjects in South Tees, UK. The eGFR was calculated using the Modification of Diet in Renal Disease (MDRD) study equation. Patients were stratified by baseline eGFR into five stages as per the National Kidney Foundation guidelines: Stage 1, eGFR > 90; Stage 2, eGFR 60-89; Stage 3, eGFR 30-59; Stage 4, eGFR 15-29; and Stage 5, eGFR < 15 ml/min per 1.73 m(2). Main outcome was all-cause and cardiovascular mortality between 1 January 1994 and 31 July 2004. RESULTS: At baseline, mean age (58.4 years) differed between groups. Persons with lower eGFR were older (P < 0.001). Thirty-six percent (n = 1193, males 56%) had died by 10 years (cardiovascular cause in 60%). Median follow-up was 10.5 years amounting to 28 342 person years. Stages 4 and 5 (eGFR 相似文献   

Adherence to treatment in patients with epilepsy: associations with seizure control and illness beliefs.

OBJECTIVE: This study investigated non-adherence to antiepileptic drug treatment amongst patients with epilepsy in secondary care. The associations between adherence and seizure control, perceptions of illness and medication, anxiety and depression were also examined. METHODS: A cross-sectional study of fifty-four patients with epilepsy were recruited from a hospital epilepsy clinic. RESULTS: Fifty-nine percent were estimated to be non-adherent to medication. There was a negative correlation between adherence and frequency of seizures. Patients with poorly controlled epilepsy were more anxious, and expected a longer duration of their epilepsy. CONCLUSION: Assessment of adherence should be a routine part of management of epilepsy. Further recognition and support should be given to patients who have poor seizure control since they are more likely to be more anxious and have unhelpful illness and treatment beliefs.     

Mycobacterium tuberculosis and Mycobacterium avium inhibit IFN- gamma -induced gene expression by TLR2-dependent and independent pathways.

Mycobacteria-infected macrophages are poor responders to interferon-gamma (IFN-gamma), resulting in decreased expression of IFN-gamma-induced genes. In the present study, we examined the inhibition of IFN-gamma-induced gene expression by Mycobacterium tuberculosis and four different Mycobacterium avium strains in mouse RAW264.7 macrophages. Gamma-irradiated M. tuberculosis inhibited mRNA expression of a panel of six different IFN- gamma-induced genes. All four of the M. avium strains completely inhibited IFN-gamma-induced expression of MHC class II Aalpha and Ebeta mRNA. However, the Mac101 strain, which is serovar 1, inhibited IFN-gamma induction of IFN regulatory factor-1 (IRF-1) and guanylate-binding protein-1 (GBP-1) mRNA to a greater extent than the other M. avium strains, which are serovar 2. In this study, we also show that mycobacteria inhibit gene expression by both toll-like receptor 2 (TLR2)-dependent and independent pathways. The inhibition of IFN-gamma-induced gene expression by M. avium was reduced but not completely blocked in macrophages from TLR2(/) mice. IFN-gamma-induced gene expression was also inhibited by mycobacteria in RAW264.7 cells expressing dominantnegative TLR2 or myeloid differentiation factor 88 (MyD88), further indicating the existence of a pathway independent of TLR2 and MyD88. These data suggest that mycobacteria inhibit IFN-gamma-induced gene expression by multiple pathways involving both TLR2 and non-TLR receptors.     

GLUT1 and GLUT8 in endometrium and endometrial adenocarcinoma.

Glucose is provided to cells by a family of glucose transport facilitators known as GLUTs. These transporters are expressed in a tissue specific manner and are overexpressed in many primary tumors of these tissues. Regulation of glucose transport facilitator expression has been demonstrated in endometrial tissue and endometrial adenocarcinoma. The following experiments were conducted to quantify and localize the expression of GLUT1 and GLUT8 in benign endometrium and compare this expression to endometrial cancer. Endometrial tissue samples were obtained from random hysterectomy specimens of patients with benign indications for surgery and endometrial cancer. Immunoblot and immunolocatization studies were performed using GLUT1 and GLUT8 specific antisera. Endometrial samples from 65 women who had undergone hysterectomy were examined (n=38 benign, n=27 malignant). A 44 and a 35.4 kDa immunoreacive species was demonstrated in endometrium and endometrial cancer for GLUT1 and GLUT8, respectively. Upregulation of GLUT1 expression was demonstrated with increasing grade of tumors (P<0.002). GLUT8 expression was increased in all tumor subtypes compared to atrophic endometrium (P<0.001). Apical localization by GLUT1 and GLUT8 was demonstrated in endometrial glands. GLUT1 and GLUT8 demonstrated diffuse intracellular localization in the cancer subtypes. GLUT1 and GLUT8 are expressed in both human endometrium and endometrial cancer. There appears to be a step-wise progression in GLUT1 and GLUT8 expression as tumor histopathology worsens. GLUT1 and GLUT8 may be important markers in tumor differentiation, as well as providing energy to rapidly dividing tumor cells.