Embryonic cerebellar granule cells are resistant to necrosis induced by homocysteine

Hyperhomocysteinemia is a risk factor for a range of neurodegenerative conditions, yet its effects in the developing nervous system have been poorly elucidated. We studied the in vitro response of cerebellar granule neurons (CGCs) to homocysteine. We have shown that embryonic CGCs are resistant to homocysteine-induced neurotoxicity, whilst postnatal CGCs are not. This is the first demonstration of a neuronal population undergoing a developmental switch in their response to homocysteine. Greater understanding of this change may have important implications for both neurodegenerative conditions and neurodevelopmental disorders.     

Multiphasic helical CT diagnosis of early medullary and papillary necrosis

PURPOSE: The feasibility of identifying early manifestations of renal papillary necrosis (RPN) and medullary necrosis (RMN) on multiphasic helical CT, leading to prompt treatment for the causative conditions, and its impact on reducing the incidence of late-stage RML and RPN, was investigated. PATIENTS AND METHODS: Sixty-eight patients (35 male, 33 female) aged 19 to 88 years were examined by multiphasic helical CT for complaints of microscopic hematuria (N=49), macroscopic hematuria (N=2), bacteriuria (N=45), pyuria (N=10), fever (N=15), and flank pain (N=27). Preenhancement, arterial corticomedullary, parenchymal, and excretory phase scans generated 1.25 to 7-mm-thick slices. Follow-up CTs were performed at 1 month (N=62) and 3 months (N=58). RESULTS: While the attenuation coefficients of areas suspect for RMN and RPN were similar on preenhancement CT, they differed substantially on the arterial corticomedullary phase (lesions 55 HU mean; normal medulla 120 HU mean) and parenchymal phase (lesions 58 HU mean, normal medulla 210 HU mean). Investigation for predisposing conditions identified diabetes in 18 patients, upper urinary-tract infections in 48, sickle-cell disease or trait in 17, urinary obstruction in 7, and cirrhosis of the liver in 1. On follow-up examinations, enhancement had normalized in 26 compromised areas of 14 patients at 1 month, and 47 areas (23 patients) at 3 months, remained stationary in 28 patients at 1 month and 9 at 3 months, and progressed in 20 at 1 and 26 at 3 months (P<0.001; Fisher's exact test). Patients (N=35) treated for underlying conditions causing ischemia showed reperfusion in 12 cases at 1 month and 20 at 3 months, while of the untreated patients (N=10), none showed reperfusion, and all lesions increased in size. CONCLUSIONS: Multiphasic helical CT is recommended for identification of RMN and RPN at a stage when effective treatment of underlying causative conditions can arrest or reverse the process of devascularization and prevent loss of medullary tissue.     

Multiphasic helical CT criteria for differentiation of recurrent neoplasm and desmoplastic reaction after laparoscopic resection of renal mass lesions

BACKGROUND AND PURPOSE: Differentiation of recurrent neoplasm and desmoplastic reaction following laparoscopic resection of renal mass lesions poses a problem. The usefulness of multiphasic helical CT-generated criteria based on enhancement and morphologic characteristics was investigated. PATIENTS AND METHODS: The findings in 5 female and 12 male patients aged 29 to 68 years having renal-cell carcinoma (11-38 mm; N = 15) or solitary angiomyolipomas (N = 2) treated by laparoscopic resection (N = 15) or open segmental surgery (N = 2) were analyzed. Multiphasic helical CT was performed in the preenhancement, arterial corticomedullary, parenchymal, and excretory phases generating 2.5- to 7-mm slices. RESULTS: Both recurrent neoplasms showed median postcontrast enhancement of 119 HU in the arterial corticomedullary phase; the median enhancement of desmoplastic masses was 48 HU. In the parenchymal and excretory phase, recurrent neoplasms showed progressive loss of enhancement, whereas desmoplastic lesions sustained enhancement at about the same level. Recurrent neoplasms presented a defined mass with characteristic spiculation, whereas desmoplastic reaction was characterized by an ill-defined mass with spidery projections extending to abutting fat and residual fascial planes. On 2- to 3-month follow-up scans, recurrent neoplasms showed progressive increases in size and desmoplastic reaction a sharp decrease. CONCLUSION: Enhancement of the mass at the operative site on arterial corticomedullary-phase CT to >90 HU strongly suggests recurrent renal-cell carcinoma, while progressive decrease in size on 1- to 3-month follow-up CT suggests a desmoplastic reaction.     

Postoperative mortality after nontraumatic lower extremity amputation in patients with renal insufficiency

Mortality rates after lower extremity amputation are extremely high among dialysis patients. However, the impact of milder degrees of renal insufficiency on death rates after lower extremity amputation has not been carefully examined. In this study, the authors used data from the Department of Veterans Affairs' National Surgical Quality Improvement Program (NSQIP) to measure the association between renal dysfunction and 30-d mortality after nontraumatic amputation adjusted for confounders. The study population consisted of 16,994 patients undergoing their first NSQIP recorded amputation from January 1, 1994 through September 30, 2001. Thirty-five percent of all cohort patients had at least moderate renal insufficiency, and 52% of all postoperative deaths occurred in this group. Postoperative mortality was 9% in patients with moderate renal insufficiency, 15% in patients with severe renal insufficiency, and 16% in dialysis patients, compared with 6% in patients with normal or mildly reduced renal function. Renal insufficiency remained associated with death after adjustment for confounders (adjusted odds ratio [OR] 3.36, 95% confidence interval [CI] 2.75 to 4.10 [dialysis patients]; OR 2.54, CI 2.06 to 3.14 [severe renal insufficiency]; and OR 1.52, CI 1.32 to 1.76 [moderate renal insufficiency]). In conclusion, even moderate renal insufficiency is independently associated with postoperative death after lower extremity amputation. This finding highlights the need for a targeted approach to improving the care of patients with renal insufficiency undergoing lower extremity amputation.     

Nutritional indicators, peripheral blood lymphocyte subsets and survival in an institutionalised elderly population

The objectives of this study were to determine the percentage and absolute counts of the peripheral blood lymphocyte subsets, and to examine the relationship between lymphocyte subsets and nutritional status, and total mortality in an institutionalised elderly population. Design The study had a cross-sectional and observational design. The sample of 115 permanent elderly residents was drawn from large geriatric institution in Melbourne, Australia. The main outcome measures were as follows: (i) percentages and absolute counts of lymphocyte subsets, (ii) association between biochemical indices of nutritional status (ferritin, iron and zinc) and peripheral blood lymphocyte subsets, (iii) total mortality during a 22-month period in relation to baseline lymphocyte subset counts. Women had higher absolute counts of various lymphocyte subsets than men. Positive correlations of serum ferritin with the number of CD8 (T-suppressor cell) and of serum iron with CD56 (natural killer, NK cells) were observed in men. In women, serum zinc was positively correlated with the absolute counts of CD3 (total T-cells), CD4 (T-helper cell) and CD19 (total B-cell). The analysis of survival data after 22 months showed that the mean number of CD4 cells of non-survivors (524 +/-292 x10(6)cells/L) was significantly lower than that of survivors (759+/-292 x 10(6) cells/L). The biochemical indicators of iron and zinc status partly account for variations in lymphocyte subset counts, consistent with known effects of iron overload and of zinc deficiency on immunocompetence. The number of CD4 T-cells may be useful in the prediction of total mortality in an institutionalised elderly population.     

Extended spectrum beta-lactamase producing organisms at the University Hospital of the West Indies

Extended spectrum beta-lactamases (ESBL) represent a major group of beta-lactamases that have the ability to inactivate beta-lactam antibiotics containing an oxyimino group such as third generation cephalosporins and monobactams. These enzymes are produced by gram negative organisms, especially members of the Enterobacteriaceae family such as Klebsiella pneumoniae and Escherichia coli. The prevalence of these organisms varies widely internationally, as well as within the same country. This is the first study on ESBL production in K pneumoniae and E coli at the University Hospital of the West Indies, a tertiary care hospital in Jamaica. Two-hundred and sixty-four isolates of K pneumoniae and 300 isolates of E coli were collected over the study period January 2002 to December 2002. Forty-eight (18.2%) K pneumoniae isolates were confirmed to be ESBL producers, while there was no ESBL producing E coli. Infections with ESBL producing organisms can pose a therapeutic challenge, leading to treatment failure if the wrong class of antibiotics is used. With increasing resistance to all classes of antibiotics, there is a narrowing of available treatment options. It is very important that these organisms be monitored and antibiotic policies as well as infection control policies be in place to curtail their spread.     

A preliminary analysis of binge episodes: comparison of a treatment-seeking sample of Black and White women

OBJECTIVE: This study sought to examine differences in the nutritional composition of binges, both qualitatively and quantitatively, between participants with binge eating disorder (BED) and bulimia nervosa (BN) taken from a sample of treatment-seeking Black and White women. Overall qualitative and quantitative differences between diagnostic categories, regardless of ethnicity, were also explored. METHOD: Patients seeking treatment for eating disorders were assessed on binge content. Black (n=26) and White (n=26) participants were matched on age and body mass index (BMI). RESULTS: The binges of individuals with BN were lower in percent protein, but higher in calories, carbohydrates, and sugar, than those individuals with BED. However, there was little difference as a function of ethnicity between treatment-seeking Black and White women. DISCUSSION: Preliminary data suggest that health professionals are faced with similar binge eating pathology, regardless of ethnicity, despite, probably, etiologic variation. The importance of the role of ethnicity in the expression of eating disorders is discussed.     

Framing the doctor-patient relationship in chronic illness: a comparative study of general practitioners' accounts

How family doctors conceptualise chronic illness in the consultation has important implications for both the delivery of medical care, and its experience by patients. In this paper, we present the results of a re-analysis of qualitative data collected in a series of studies of British family doctors between 1995 and 2001, to explore the ways in which the legitimacy and authority of medical knowledge and practice are organised and worked out in relation to three kinds of chronic illness (menorrhagia; depression; and chronic low back pain/medically unexplained symptoms). We present a comparative analysis of (a). the moral evaluation of the patient (and judgements about the legitimacy of symptom presentation); (b). the possibilities of disposal; and (c). doctors' empathic responses to the patient, in each of these clinical cases. Our analysis defines some of the fundamental conditions through which general practitioners frame their relationships with patients presenting complex but sometimes diffuse combinations of 'social', 'psychological' and 'medical' symptoms. These are fundamental to, yet barely touched by, the increasingly voluminous literature on how doctors should interact with patients. Moving beyond the individual studies from which our data are drawn, we have outlined some of the highly complex and demanding features of what is often seen as routine and unrewarding medical work, and some of the key requirements for the local negotiation of patients' problems and their meanings (for both patients and doctors) in everyday general practice.     

Assessment of patient management skills and clinical skills of practising doctors using computer-based case simulations and standardised patients

CONTEXT: Standardised assessments of practising doctors are receiving growing support, but theoretical and logistical issues pose serious obstacles. OBJECTIVES: To obtain reference performance levels from experienced doctors on computer-based case simulation (CCS) and standardised patient-based (SP) methods, and to evaluate the utility of these methods in diagnostic assessment. SETTING AND PARTICIPANTS: The study was carried out at a military tertiary care facility and involved 54 residents and credentialed staff from the emergency medicine, general surgery and internal medicine departments. MAIN OUTCOME MEASURES: Doctors completed 8 CCS and 8 SP cases targeted at doctors entering the profession. Standardised patient performances were compared to archived Year 4 medical student data. RESULTS: While staff doctors and residents performed well on both CCS and SP cases, a wide range of scores was exhibited on all cases. There were no significant differences between the scores of participants from differing specialties or of varying experience. Among participants who completed both CCS and SP testing (n = 44), a moderate positive correlation between CCS and SP checklist scores was observed. There was a negative correlation between doctor experience and SP checklist scores. Whereas the time students spent with SPs varied little with clinical task, doctors appeared to spend more time on communication/counselling cases than on cases involving acute/chronic medical problems. CONCLUSION: Computer-based case simulations and standardised patient-based assessments may be useful as part of a multimodal programme to evaluate practising doctors. Additional study is needed on SP standard setting and scoring methods. Establishing empirical likelihoods for a range of performances on assessments of this character should receive priority.