Compressibility effects on outflows in a two-fluid system. 1. Line source in cylindrical geometry

A two-dimensional line source outflow is considered, in which the evolution of a sharp interface separating an incompressible fluid from a bounding weakly compressible gas is analysed. Linear theory is applied, assuming that anisotropies in the source outflow are small, to develop an approximate solution for the interfacial evolution. The simplest solutions to the governing linearised equations require the presence of a high-order velocity singularity at the location of the line source. A spectral method is also developed to capture the nonlinear behaviour of the flow; after some finite time, curvature singularities are found to develop on the interface. Comparisons are made between the stability of the interface and its analogue which separates two incompressible fluids. It is found that when the bounding fluid is weakly compressible rather than incompressible, the stability of the interface is significantly increased.     

The Role of α1-Adrenoceptor Antagonists in the Treatment of Prostate and Other Cancers

This review evaluates the role of α-adrenoceptor antagonists as a potential treatment of prostate cancer (PCa). Cochrane, Google Scholar and Pubmed were accessed to retrieve sixty-two articles for analysis. In vitro studies demonstrate that doxazosin, prazosin and terazosin (quinazoline α-antagonists) induce apoptosis, decrease cell growth, and proliferation in PC-3, LNCaP and DU-145 cell lines. Similarly, the piperazine based naftopidil induced cell cycle arrest and death in LNCaP-E9 cell lines. In contrast, sulphonamide based tamsulosin did not exhibit these effects. In vivo data was consistent with in vitro findings as the quinazoline based α-antagonists prevented angiogenesis and decreased tumour mass in mice models of PCa. Mechanistically the cytotoxic and antitumor effects of the α-antagonists appear largely independent of α 1-blockade. The proposed targets include: VEGF, EGFR, HER2/Neu, caspase 8/3, topoisomerase 1 and other mitochondrial apoptotic inducing factors. These cytotoxic effects could not be evaluated in human studies as prospective trial data is lacking. However, retrospective studies show a decreased incidence of PCa in males exposed to α-antagonists. As human data evaluating the use of α-antagonists as treatments are lacking; well designed, prospective clinical trials are needed to conclusively demonstrate the anticancer properties of quinazoline based α-antagonists in PCa and other cancers.     

A line vortex in a two-fluid system

This paper considers the classical problem of a line vortex in planar flow of a fluid. However, an interface is present at some finite radius from the line vortex, and beyond that is a second fluid of different density. The interface is therefore subject to shearing-type instabilities and may overturn as time progresses. A linearized inviscid theory is developed and reveals unstable behaviours, dependent on the parameters in the system. The non-linear inviscid problem is solved by a spectral method, and high-frequency modes are regularized by a type of filtering. In addition, a Boussinesq viscous model is presented and allows the overturning interface to fold. Results are discussed and compared with the predictions of the inviscid theory.     

Analysis of 59 cases of non-traumatic sudden death in various neurological diseases]

Sudden death is a common complication of myocardial infarction, necrotic pancreatitis and other diseases. Physicians usually neglect the possibility of neurological disorders. 59 cases of sudden death among 314 autopsied cases with neurological diseases were analyzed. The most frequent cause of neurological sudden death was cerebrovascular disease (CVD). It was present in 53 (89.9%) cases. 48 of them had hemorrhagic CVD. 37 of these 48 cases were due to hypothalamic lesions. In 37 cases general autopsy was performed; pathological abnormalities of heart, lungs, stomach etc, were found in 28 of them. In conclusion, the size and location of the lesion correlated with the prognosis of the disease. Concomitant multiple organ damage may deteriorate the lesion. Awareness of sudden death resulting from CVD may elevate the rate of correct diagnosis.     

Dose of hemodialysis and survival: differences by race and sex

CONTEXT: Although blacks receive lower doses of hemodialysis than whites, their survival when receiving dialysis treatment is better than that for whites. Previous studies of the relationship between the dose of dialysis and patient survival have not controlled for differences in patient characteristics. OBJECTIVE: To examine the association of mortality with the dose of hemodialysis for clusters of patients categorized by race and sex. DESIGN: Retrospective analysis of laboratory data and mortality outcomes from 1994, using a national database of hemodialysis patients. PATIENTS: A total of 18144 black and white patients receiving hemodialysis 3 times weekly who either lived the entire year receiving hemodialysis or died. MAIN OUTCOME MEASURES: The fractional reduction of urea in a single dialysis session as the measured hemodialysis dose (urea reduction ratio [URR]) after controlling for race, sex, age, and diabetes mellitus. Mortality was determined by strata of URRs and albumin and creatinine levels. RESULTS: Across all age categories, blacks had lower URRs than whites, and men had lower URRs than women. In an age-adjusted model for evaluating interactions among URRs, race, sex, and diabetes, the association of URR with mortality risk was weak among blacks, particularly black men. After adjustment for age and diabetes, death probability curves were most steep for white women with URR values less than 60%. The death probability curves were least steep for black men. There was no meaningful difference between death probability and albumin or creatinine concentration among the race by sex clusters. CONCLUSION: Using URR, the usual measure of hemodialysis dose, the assumption that the association between dialysis dose and survival is uniform across demographic groups appears incorrect. Comparisons of the quality of dialysis patient care should not rely on URR alone to predict patient survival.     

Single- versus multiple-dose antimicrobial prophylaxis for major surgery: a systematic review

BACKGROUND: Single-dose antimicrobial prophylaxis for major surgery is a widely accepted principle; recommendations have been based on laboratory studies and numerous clinical trials published in the last 25 years. In practice, single-dose prophylaxis has not been universally accepted and multiple-dose regimens are still used in some centres. Moreover, the principle has recently been challenged by the results of an Australian study of vascular surgery. The aim of this current systematic review is to determine the overall efficacy of single versus multiple-dose antimicrobial prophylaxis for major surgery and across surgical disciplines. METHODS: Relevant studies were identified in the medical literature using the MEDLINE database and other search strategies. Trials included in the review were prospective and randomized, had the same antimicrobial in each treatment arm and were published in English. Rates of postoperative surgical site infections (SSI) were extracted, 2 x 2 tables prepared and odds ratios (OR) [with 95% confidence intervals (95% CI)] calculated. Data were then combined using fixed and random effects models to provide an overall figure. In this context, a high value for the combined OR, with 95% CI > 1.0, indicates superiority of multiple-dose regimens and a low OR, with 95% CI < 1.0, suggests the opposite. A combined OR close to 1.0, with narrow 95% CI straddling 1.0, indicates no clear advantage of one regimen over another. Further subgroup analyses were also performed. RESULTS: Combined OR by both fixed (1.06, 95% CI, 0.89-1.25) and random effects (1.04, 95% CI, 0.86-1.25) models indicated no clear advantage of either single or multiple-dose regimens in preventing SSI. Likewise, subgroup analysis showed no statistically significant differences associated with type of antimicrobial used (beta-lactam vs other), blinded wound assessment, length of the multiple-dose arm (> 24 h vs 24 h or less) or type of surgery (obstetric and gynaecological vs other). CONCLUSIONS: Continued use of single-dose antimicrobial prophylaxis for major surgery is recommended. Further studies are required, especially in previously neglected surgical disciplines.     

Specificity of the Speed''s test: arthroscopic technique for evaluating the biceps tendon at the level of the bicipital groove

A historical cohort study was conducted in Misasa town, Tottori prefecture, Japan, where radon spas have been operating for a long time. Misasa town was divided into an elevated radon level area and a control area, with mean indoor radon levels of about 60 and 20 Bq/m3, respectively. In total, 3,083 subjects in the elevated radon level area and 1,248 in the control area, all aged 40 or older on January 1, 1976, were followed up until December 31, 1993, for a mean period of 14 years. The mortality rates from all causes exhibited no difference between the elevated radon level area and the control area for both sexes. No difference was observed in the incidence of all-site cancers (age, period-adjusted rate ratios by Poisson regression, RR = 1.06, 95% confidence interval (CI) 0.79-1.42 for males, RR = 0.90, 95% CI 0.65-1.24 for females), while stomach cancer incidence seemed to decrease for both sexes (RR = 0.70, 95% CI 0.44-1.11 for male, RR = 0.58, 95% CI 0.34-1.00 for female) and lung cancer incidence for males only seemed to increase (RR = 1.65, 95% CI 0.83-3.30 for male, RR = 1.07, 95% CI 0.28-4.14 for female) in the elevated radon level area. Caution is needed in the interpretation of these findings, however, since the individual exposure level was not measured and major confounding factors, such as smoking and diet, could not be controlled in this study.     

Mechanism-based inactivation of human liver cytochrome P450 2A6 by 8-methoxypsoralen

The P450 2A6 catalyzed 7-hydroxylation of coumarin proceeded with a mean Km of 0.40 (+/-0.13) microM and Vmax of 6.34 nmol/nmol P450/min (36-fold variation) in microsomal preparations from a panel of 12 human livers. Substrate depletion was avoided during the kinetic determinations. 8-Methoxypsoralen (8-MOP) is a potent mechanism-based inactivator of human liver P450 2A6 and reconstituted purified recombinant P450 2A6 based on the following evidence: 1) 8-MOP causes time, concentration, and NADPH-dependent loss of P450 2A6 activity that is not reversed by potassium ferricyanide or extensive dialysis, 2) loss of P450 2A6 activity is associated with a loss of spectrally observable P450, 3) addition of nucleophiles or reactive oxygen scavengers to the incubations does not prevent inactivation of P450 2A6, and 4) 8-MOP-dependent P450 2A6 inactivation is inhibited (concentration dependent) by the addition of a competitive inhibitor (pilocarpine). Inactivation is selective for P450 2A6 at low concentrations of 8-MOP (2.5 microM) after short incubation time periods (3 min) and was characterized by a KI of 0.8 and 1.9 microM in a reconstituted and microsomal system, respectively, and a kinact of 1 min-1 and 2 min-1 in a reconstituted and microsomal system, respectively. A substrate depletion partition ratio of 21 was calculated for the inactivation of recombinant P450 2A6. Potency and selectivity suggest that 8-MOP could be a useful tool in vitro for evaluating P450 2A6 activity in various enzyme preparations.     

Racial differences in incidence, outcome, and quality of life for African-Americans on hemodialysis

African-Americans are the fastest growing racial minority with end-stage renal disease (ESRD) in the United States. Although comprising < 15% of the US population, African-Americans comprise approximately 31% of the ESRD population. African-Americans are approximately 7 years younger than their white counterparts with ESRD. Surprisingly, although African-Americans systematically receive less dialysis than whites, their survival with ESRD is greatly improved. This improved survival with ESRD is accompanied by an improved quality of life for African-Americans. In this review, we will examine the reasons why African-Americans have an excessive incidence of selective diseases that culminate in ESRD. Furthermore, we will judge several hypotheses that may account for the improved survival enjoyed by African-Americans with ESRD. We contend that research targeted to clarify the basis for these differences between African-Americans and whites with ESRD will improve the outcomes for both populations.     

Serum concentrations of soluble adhesion molecules in patients with colorectal cancer

The concentrations of the soluble adhesion molecules E-cadherin, E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were investigated in 48 patients with colorectal cancer before treatment, and their relation to clinical, histological and routine laboratory parameters was examined. Data were collected on tumour stage at presentation, presence and sites of metastatic disease, tumour pathology and results of routine laboratory tests. Serum concentrations of ICAM-1 and VCAM-1 were significantly elevated in the patients with colorectal cancer in comparison with a group of healthy subjects (P < 0.00001). Levels of circulating ICAM-1 and VCAM-1 were increased both in patients with local and those with metastatic disease. Although elevated in some patients soluble E-cadherin and E-selectin concentrations were not significantly elevated compared with the control group (P = 0.71 and P = 0.052 respectively). The levels of circulating ICAM-1 were significantly correlated with those of VCAM-1 and E-selectin. A correlation was also found between the serum concentrations of E-selectin and ICAM-1 and alkaline phosphatase, total white cell count and platelet count. VCAM-1 was positively correlated with age and negatively with degree of tumour differentiation and haemoglobin concentration. The biological implications and possible clinical relevance of these findings are discussed.