Clinical value of microalbuminuria in hypertension

Microalbuminuria (MA) is a well recognized marker of cardiovascular complications in hypertension, but whether MA can predict adverse outcome in this clinical condition is still a subject for debate. The fact that in hypertensive cohorts those patients who showed an increase in albumin excretion rate also manifested an increased incidence of morbid events indicates that the presence of MA in hypertension may carry an increased cardiovascular risk. However, the prognostic significance of MA remains controversial because no results of prospective studies performed in hypertensive subjects without diabetes mellitus are available. Several factors can affect the prevalence of MA in hypertension, including severity of the disease, selection procedures, concomitant risk factors, degree of obesity, age, and sex distribution. This accounts for the large differences in the prevalence of MA that can be found in the literature, with prevalence rates going from a low of 4.7% to a high of 40%. There is still conflict over whether MA in hypertension is due to increased intraglomerular pressure or to glomerular damage. The data from the literature suggest that in subjects with mild hypertension the main determinant of albumin excretion rate is the haemodynamic load. In subjects with more severe hypertension and hypertensive complications, the augmented urinary albumin leak is probably the consequence of a systemic microvascular disturbance which involves the glomeruli. In this respect, the insulin resistance state often associated to high blood pressure appears as one of the main pathogenetic factors. Whether management of hypertensive populations may be improved by monitoring of albumin excretion rate and whether antihypertensive drugs which are more effective in decreasing urinary albumin can be more beneficial in patients with MA remains to be determined.     

AMPA receptor potentiation can prevent ethanol-induced intoxication.

We present a substantial series of behavioral and imaging experiments, which demonstrate, for the first time, that increasing AMPA receptor-mediated neurotransmission via administration of potent and selective biarylsulfonamide AMPA potentiators LY404187 and LY451395 reverses the central effects of an acutely intoxicating dose of ethanol in the rat. Using pharmacological magnetic resonance imaging (phMRI), we observed that LY404187 attenuated ethanol-induced reductions in blood oxygenation level dependent (BOLD) in the anesthetized rat brain. A similar attenuation was apparent when measuring local cerebral glucose utilization (LCGU) via C14-2-deoxyglucose autoradiography in freely moving conscious rats. Both LY404187 and LY451395 significantly and dose-dependently reversed ethanol-induced deficits in both motor coordination and disruptions in an operant task where animals were trained to press a lever for food reward. Both prophylactic and acute intervention treatment with LY404187 reversed ethanol-induced deficits in motor coordination. Given that LY451395 and related AMPA receptor potentiators/ampakines are tolerated in both healthy volunteers and elderly patients, these data suggest that such compounds may form a potential management strategy for acute alcohol intoxication.     

Comparative evaluation of cytotoxicity and phototoxicity of mono and diacylglycerol amino acid-based surfactants

Extensive efforts have been made, recently, to find surfactants with lower irritancy potential than those presently commercially employed in pharmaceutical and cosmetic preparations. Cytotoxic and phototoxic effects of novel mono and diacylglycerol amino acid-based surfactants (glutamic acid, or arginine) were evaluated.All tested surfactants showed a clear concentration–response relationship to two immortalized cell lines, murine fibroblast cell line, 3T3, and one human keratinocyte cell line, HaCaT, demonstrated by and decrease of NR uptake. Concentrations resulting in 50% inhibition of NR uptake (IC₅₀) range from 30 to 300 μg mL⁻¹.The potential phototoxicity which could result in irritant products, was determined by modulated cytotoxicity via the resazurin reduction to resorufin and neutral red uptake (NRU) endpoints. Surfactants with two chains showed, in general, less cytotoxic but higher phototoxic effect than surfactants with only one chain.     

PCR colorimetric dot-blot assay and clinical pretest probability for diagnosis of Pulmonary Tuberculosis in Smear-Negative patients

Background  

Smear-negative pulmonary tuberculosis (SNPTB) accounts for 30% of Pulmonary Tuberculosis (PTB) cases reported annually in developing nations. Polymerase chain reaction (PCR) may provide an alternative for the rapid detection of Mycobacterium tuberculosis (MTB); however little data are available regarding the clinical utility of PCR in SNPTB, in a setting with a high burden of TB/HIV co-infection.     

Drug utilization and cost in a Medicaid population: A simulation study of community vs. mail order pharmacy

Background  

Outpatient drugs are dispensed through both community and mail order pharmacies. There is no empirical evidence that substitution of community pharmacy with mail order reduces overall drug expenditures. The need for evaluating the potential effects on utilization and costs of the possible extension of mail order services in Medicaid provides the rationale for conducting this study. This study compares drug utilization and drug product cost in community vs. mail order pharmacy dispensing services in a Medicaid population.     

Gefitinib induction of in vivo detectable signals by Bcl-2/Bcl-xL modulation of inositol trisphosphate receptor type 3

PURPOSE: To test whether epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) induce detectable signals in tumor cells and whether such signals may reveal alterations of the apoptotic program. EXPERIMENTAL DESIGN: Tumor cells were treated with gefitinib or erlotinib and tested for their ability to accumulate 99mTc-Sestamibi, a radiolabeled lipophilic cation that localizes in mitochondria. Then we tested whether Bcl-2 and Bcl-xL alter the pattern of drug-dependent tracer accumulation while reducing tumor cell sensitivity to EGFR TKIs. The mechanism underlying the pattern of tracer accumulation was elucidated. Finally, imaging studies were done in animal models and lung cancer patients before and after treatment with EGFR TKIs using single-photon emission computed tomography and 99mTc-Sestamibi. RESULTS: Gefitinib increases accumulation of 99mTc-Sestamibi in Bcl-2-overexpressing cells and enhances the physical interaction of phosphorylated Bcl-2 with inositol trisphosphate receptor type 3 (IP3R3). Consequently, a relative increase of cytosolic and mitochondrial calcium levels occurs. Similarly, lung cancer cells showed an increase of tracer uptake and an enhanced interaction of Bcl-xL with IP3R3 on exposure to erlotinib concentrations achievable in plasma. The occurrence of these interactions was associated with an enhanced EGFR TKI-induced apoptosis resistance. Posttreatment imaging studies in nude mice bearing control and Bcl-2-overexpressing breast carcinomas showed a high tumor uptake of the tracer whereas baseline studies failed to visualize tumors. Similarly, an enhancement of tracer uptake could be detected in patients with lung cancer treated with erlotinib. CONCLUSION: EGFR TKIs generate detectable signals by Bcl-2/Bcl-xL modulation of IP3R3 in tumor cells.     

Surgical site infections at the National Cancer Institute in Mexico: a case-control study

OBJECTIVES: To quantify the surgical infection rate and to identify risk factors associated with surgical site infection. METHODS: We conducted a case-control study of all surgical patients between January 1, 1993, and June 30, 1994. The frequency of surgical site infection per 100 surgeries was calculated. The odds ratio (OR) was estimated by using logistic regression analysis. SETTING: A 130-bed tertiary-care teaching hospital for adult patients with cancer. RESULTS: The study followed 3372 surgeries. Three hundred thirteen patients had a surgical site infection (rate per 100 surgeries: 9. 30). The risk factors associated with surgical site infection were diabetes mellitus (OR = 2.5, 95% confidence interval [CI] = 1.27-4. 91), obesity (OR = 1.76, 95% CI = 1.14-2.7), presence of surgical drains for >5 and <16 days (OR = 1.84, 95% CI = 1.02-3.31), and presence of surgical drains for >/=16 days (OR = 2.14, 95% CI = 1. 0-4.6). The bacteria most frequently isolated were Escherichia coli 38 (21.8% of the total of microorganisms found), Pseudomonas sp 22 (12.6%), Staphylococcus aureus 16 (9.2%), and coagulase-negative Staphylococcus 25 (13.6%). The coexistence of other nosocomial infections was greater among the cases (OR = 1.8, 95% CI = 1.1-3.1) than in the control group. CONCLUSIONS: The surgical site infection rate in our hospital is slightly higher than the rates reported for general hospitals. The risk factors associated with surgical site infection are similar to those previously reported. Diabetes mellitus, obesity, and prolonged presence of a surgical drain increased the risk of infection.     

Bacterial infection in cirrhotic patients and its relationship with alcohol

OBJECTIVE: Infections are regarded as a major complication and an important cause of death in cirrhotics. Alcohol is a predisposing factor to infections in such patients. This study was undertaken to compare the frequency and evolution of bacterial infection among alcoholic and nonalcoholic cirrhotics. METHODS: To observe this relationship, we retrospectively studied a cohort of 382 cirrhotic inpatients, 201 of whom were alcoholic (alcohol intake > or =80 g/day for > or =10 yr) and 181 of whom were nonalcoholic. RESULTS: A total of 128 (33.5%) patients presented with infection upon hospitalization, 78 of whom were alcoholic and 50 of whom were nonalcoholic (p = 0.02). A total of 157 cases of infection were diagnosed, with spontaneous bacterial peritonitis as the most prevalent one (54.1%), followed by pneumonia (18.5%), infection of the soft parts (10.8%), and urinary tract infection (7.0%). Infection and deaths were more frequent in patients with Child-Pugh C than in those with Child-Pugh A/B (p = 0.003, p = 0.0002 respectively). Alcoholic patients with Child-Pugh A/B were more susceptible to infection compared to nonalcoholic patients (p = 0.02), although no difference was noted as to the number of deaths (p = 0.1). With regard to patients with Child-Pugh C, no statistical difference was found in the infections or deaths among alcoholics and nonalcoholics (p = 0.8, p = 0.8). CONCLUSIONS: Our findings suggest that, despite the fact that bacterial infections are more common in cirrhotic alcoholics, its seems that the mortality rate is associated more with the severity than with the etiology of the hepatic disease.