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Premenopausal women are much less prone to develop cardiovascular disease than men of similar age, but this advantage no longer applies after menopause. We previously found that male mice have a significantly higher rate of cardiac rupture than females during the acute phase of myocardial infarction (MI); however, the effects of sexual hormones on chronic remodeling are unknown. We hypothesized that estrogen (E) may protect the heart from chronic remodeling and deterioration of function post-MI, whereas testosterone (T) may have adverse effects. Mice (4 wk old) of both genders were divided into four groups: female groups consisted of 1) sham ovariectomy (S-Ovx) + placebo (P) (S-Ovx + P), 2) S-Ovx + T, 3) Ovx + P, and 4) Ovx + T; and male groups consisted of 1) sham castration (S-Cas)+ P (S-Cas + P), 2) S-Cas + 17[beta]-estradiol (E), 3) Cas + P, and 4) Cas + E. MI was induced 6 wk later. Echocardiography was performed to assess cardiac function and left ventricular dimensions (LVD). Myocyte cross-sectional area (MCSA) was measured at the end of the study. In females, both testosterone and ovariectomy decreased ejection fraction (EF) and increased LVD, and when combined they aggravated cardiac function and remodeling further. Testosterone significantly increased MCSA. In males, castration or estrogen increased EF and reduced LVD, whereas castration significantly reduced MCSA. Our data suggest that estrogen prevents deterioration of cardiac function and remodeling after MI, but testosterone worsens cardiac dysfunction and remodeling and has a pronounced effect when estrogen levels are reduced. sexual hormones; cardiac dysfunction

Researchers used meta-analysis to evaluate 127 studies on community-acquired pneumonia (CAP) covering 33,148 patients that were published from 1966 to 1995. The overall mortality rate was 13.7%, but rates in individual studies ranged from 5.1% in hospitalized and ambulatory patients to 36.5% in an intensive care unit. Eleven factors were found to predict mortality and included male sex, chest pain, hypothermia, hypotension and pulmonary infiltrate. Most of these factors are known at the time of admission and could be used to predict mortality. Mortality was also associated with the type of bacterium involved, being highest in patients infected with Pseudomonas, Klebsiella, E. coli and Staphylococcus aureus. Only one-third of the studies reported any other complications of CAP and less than 10% reported on functional outcomes such as return to work or regular activities., Objective. - To systematically review the medical literature on the prognosis and outcomes of patients with community-acquired pneumonia (CAP). Data Sources. - A MEDLINE literature search of English-language articles involving human subjects and manual reviews of article bibliographies were used to identify studies of prognosis in CAP. Study Selection. - Review of 4573 citations revealed 122 articles (127 unique study cohorts) that reported medical outcomes in adults with CAP. Data Extraction. - Qualitative assessments of studies' patient populations, designs, and patient outcomes were performed. Summary univariate odds ratios (ORs) and rate differences (RDs) and their associated 95% confidence intervals (CIs) were computed to estimate a summary effect size for the association of prognostic factors and mortality. Data Synthesis. - The overall mortality for the 33 148 patients in all 127 study cohorts was 13.7%, ranging from 5.1 % for the 2097 hospitalized and ambulatory patients (in six study cohorts) to 36.5% for the 788 intensive care unit patients (in 13 cohorts). Mortality varied by pneumonia etiology, ranging from less than 2% to greater than 30%. Eleven prognostic factors were significantly associated with, mortality using both summary ORs and RDs: male sex (OR=1.3; 95% CI, 1.2 to 1.4), pleuritic chest pain (OR=0.5; 95% CI, 0.3 to 0.8), hypothermia (OR=5.0; 95% CI, 2.4 to 10.4), systolic hypotension (OR=4.8; 95% CI, 2.8 to 8.3), tachypnea (OR=2.9; 95% CI, 1.7 to 4.9), diabetes mellitus (OR=1.3; 95% CI, 1.1 to 1.5), neoplastic disease (OR=2.8; 95% CI, 2.4 to 3. 1), neurologic disease (OR=4.6; 95% CI, 2.3 to 8.9), bacteremia (QR=2.8; 95% CI, 2.3 to 3.6), leukopenia (OR=2.5; 95% CI, 1.6 to 3.7), and multilobar radiographic pulmonary infiltrate (OR=3.1; 95% CI, 1.9 to 5.1). Assessments of other clinically relevant medical outcomes such as morbid complications (41 cohorts), symptoms resolution (seven cohorts), return to work or usual activities (five cohorts), or functional status (one cohort) were infrequently performed. Conclusions. - Mortality for patients hospitalized with CAP was high and was associated with characteristics of the study cohort, pneumonia etiology, and a variety of prognostic factors. Generalization of these findings to all patients with CAP should be made with caution because of insufficient published information on medical outcomes other than mortality in ambulatory patients.

Abstract: Current guidelines for treatment of diabetic ketoacidosis (DKA) recommend administration of an intravenous bolus dose of insulin followed by a continuous infusion. This study was designed to investigate whether the initial bolus dose is of significant benefit to adult patients with DKA and if it is associated with increased complications. This was a non-concurrent, prospective observational cohort study of adult patients who presented with DKA in a 12-month period. Charts were divided into two groups depending on whether they received an initial bolus dose of insulin. Data on glucose levels, anion gap (AG), intravenous fluid administration (IVF), and length of stay (LOS) were collected. Primary outcome was hypoglycemia (need for administration of 50% dextrose). Of 157 charts, 78 received a bolus of insulin and were designated the treatment group, the remaining 79 formed the control group. Groups were similar at baseline and received equivalent IVF and insulin drips. There were no statistically significant differences in the incidence of hypoglycemia (6% vs. 1%, respectively, p = 0.12), rate of change of glucose (60 vs. 56 mg/dL/h, respectively, p = 0.54) or AG (1.9 vs. 1.9 mEq/L/h, respectively, p = 0.66), LOS in the Emergency Department (8 vs. 7 h, respectively, p = 0.37) or hospital (5.6 vs. 5.9 days, p = 0.81). Equivalence testing revealed no clinically relevant differences in IVF change, rate of change of glucose, or AG. Administration of an initial bolus dose of insulin was not associated with significant benefit to patients with DKA and demonstrated equivalent changes in clinically relevant endpoints when compared to patients not administered the bolus. [Copyright &y& Elsevier]

Abstract: Study Objectives: To compare the efficacy of continuous radiofrequency (CRF) thermocoagulation with pulsed radiofrequency (PRF) in the treatment of lumbar facet syndrome. Design: Prospective, randomized, double-blinded study. Setting: Ambulatory pain clinic at a level-I trauma center and teaching institution. Patients: 50 ASA physical status I, II, and III patients, at least 18 years of age, scheduled to undergo CRF or PRF for lumbar back pain. Interventions: Target facet joints were identified with oblique radiographic views. Continuous radiofrequency thermocoagulation was delivered at 80°C for 75 seconds, while PRF was delivered at 42°C with a pulse duration of 20 ms and pulse rate of two Hz for 120 seconds. Measurements: Visual analog scale (VAS) pain assessment and Oswestry Low Back Pain and Disability Questionnaire (OSW) were administered at baseline and then at three months. Comparisons between groups and within groups were made of the relative percentage improvement in VAS and OSW scores. Main Results: No significant differences in the relative percentage improvement were noted between groups in either VAS (P = 0.46) or OSW scores (P = 0.35). Within the PRF group, comparisons of the relative change over time for both VAS (P = 0.21) and OSW scores (P = 0.61) were not significant. However, within the CRF group, VAS (P = 0.02) and OSW scores (P = 0.03) showed significant improvement. Conclusions: Although there was no significant difference between CRF and PRF therapy in long-term outcome in the treatment of lumbar facet syndrome, there was a greater improvement over time noted within the CRF group. [Copyright &y& Elsevier]

Bradykinin dilates efferent arterioles via release of efferent arteriole epoxyeicosatrienoic acids when perfused retrograde (no glomerular autacoids). However, when efferent arterioles are perfused orthograde through the glomerulus, bradykinin-induced dilatation is caused by a balance between: (1) the glomerular vasoconstrictor 20-hydroxyeicosatetraenoic acid and vasodilator prostaglandins, and (2) epoxyeicosatrienoic acids from the efferent arteriole and possibly the glomerulus. However, the role of 20-hydroxyeicosatetraenoic acid has only been studied with a cyclooxygenase inhibitor, which may artificially enhance its production by shunting arachidonic acid into the cytochrome P450 pathway. We hypothesized that in the absence of cyclooxygenase inhibition, bradykinin induces release of 20-hydroxyeicosatetraenoic acid from the glomerulus, which blunts the vasodilator effect of bradykinin; and that prostaglandins released from glomeruli in response to bradykinin are generated by cyclooxygenase-1. Rabbit efferent arterioles preconstricted with norepinephrine were perfused orthograde from the end of the afferent arteriole. Bradykinin was added to the perfusate with or without a 20-hydroxyeicosatetraenoic acid antagonist (20-HEDE), epoxyeicosatrienoic acid synthesis inhibitor (MS-PPOH), and/or cyclooxygenase-1 (SC-58560) or cyclooxygenase-2 inhibitor (NS-398). Bradykinin-dependent dilatation was enhanced by 20-HEDE but blunted by MS-PPOH. When the inhibitors were present, bradykinin-induced dilatation was abolished by blockade of cyclooxygenase-1 but not cyclooxygenase-2. We concluded that: (1) in the absence of cyclooxygenase inhibitors, bradykinin causes the release of a glomerular vasoconstrictor (20-hydroxyeicosatetraenoic acid) that antagonizes the vasodilator effect of epoxyeicosatrienoic acids released from the efferent arteriole and perhaps from the glomerulus, and (2) bradykinin-induced vasodilatation is caused by the release of epoxyeicosatrienoic acids from the efferent arteriole and glomerular metabolites of cyclooxygenase-1.

The formation of DNA adducts can lead to DNA replication errors and the potential for carcinogenesis. DNA adducts have been detected in prostate cells, but the distribution of adducts with respect to prostate cancer risk factors and histology is unknown. In a study of 130 Caucasian (n = 61) and African-American (n = 69) men with prostate cancer who underwent radical prostatectomy, we quantified polycyclic aromatic hydrocarbon (PAH)-DNA adducts in prostate tumor and adjacent nontumor cells by immunohistochemistry. A strong correlation between paired adduct levels in the two cell types was observed (r = 0.56; P < 0.0001); however, nontumor cells had a significantly higher level of adducts compared with tumor (0.30 absorbance units +/- 0.05 versus 0.17 absorbance units +/- 0.04; P < 0.0001). Variables significantly associated with PAH-DNA adduct levels in tumor cells included primary Gleason grade, tumor volume, and log-transformed prostate-specific antigen (PSA) at time of diagnosis. Tumors with a primary Gleason grade of 5 had significantly lower PAH-DNA adduct levels than tumor cells with a primary Gleason grade of 3 or 4 (P < 0.0001 for both). Tumors that involved 10% or less of the prostate gland had significantly higher PAH-DNA adduct levels than tumors that involved 15 to 20% of the prostate gland (P = 0.004). PSA levels were inversely associated with PAH-DNA adduct levels in tumor cells (P = 0.009). A similar, albeit less significant, inverse association was observed between PSA and PAH-DNA adduct levels in nontumor cells (P = 0.07). Interestingly, increasing primary Gleason grade was associated with increasing PAH-DNA adduct levels in adjacent nontumor cells (P = 0.008). Our results show that PAH-DNA adducts are present in the prostate but vary with regard to cellular histology. In prostate tumor cells, decreased cellular differentiation and increased tumor proliferation may reduce PAH-DNA adduct levels.

Secreted protein acidic and rich in cysteine (SPARC) has a suppressive effect on U87 glioma cell proliferation when assessed in vitro and in vivo using parental U87T2 and U87T2-derived SPARC-transfected clones. Since SPARCinteracts with extracellular matrix (ECM) proteins, we examined the effect of SPARC secretion on proliferation, morphology, and cell density of glioma cells grown in vitro, in the absence and presence of ECM proteins under standard (10% fetal bovine serum [FBSI) and reduced (0.1% FBS) serum stress conditions. Under standard conditions, MTT (3-(4,5-cimethythiazol-2-yl)-2,5-diphenyltetrazolium bromide) growth curves, morphology, and Western blot analyses demonstrated that SPARC had a suppressive and biphasic effect on growth that was not grossly modulated by the ECMs. The SPARC-induced changes in morphology observed at 24 h were not altered by the presence of ECMs. Under reduced-serum stress conditions, Western blot, morphological, and flow cytometric analyses indicated that the SPARC-induced suppressive growth effects were eliminated when the cells were grown on plastic. However, ECM-specific changes in growth were observed, some of which correlated with secreted SPARC levels. These results indicate that the differential effects of SPARC and ECMs on proliferation are dependent on culture conditions. Since the results obtained under standard conditions agree with our in vivo observations, we conclude that the ability of SPARC to suppress proliferation is regulated to a greater degree by the level of SPARC and that this suppressive effect is not influenced by the presence of any of the ECMs examined.