Treatment for infertility and risk of invasive epithelial ovarian cancer

The relationship between the use of fertility drugs and the risk of ovarian cancer was analysed using data from an Italian case-control study. The study comprised 971 women below the age of 75 years with histologically confirmed invasive epithelial ovarian cancer diagnosed within the year before the interview. The controls were 2758 women admitted to the same network of hospitals where the cases of ovarian cancer had been identified. Five cases (0.5%) and 11 controls (0.4%) reported use of fertility drugs. In comparison with women who had never used fertility drugs, the multivariate odds ratio (OR) for women who had taken fertility drugs was 1.1 [95% confidence interval (CI) 0.4-3.3]. The OR were 0.7 (95% CI 0.1-7.9) and 1.0 (95% CI 0.2-3.8) for women who had used fertility drugs for <6 and > or =6 cycles respectively. Considering the 14 cases and 45 controls reporting difficulty in conception, the risk of ovarian cancer was 0.5 (95% CI 0.1-3.6) for women who reported use of fertility drugs. Considering nulliparous women only, the estimated OR of ovarian cancer for any fertility drug use was 0.6 (95% CI 0.1-3.5). Although the present results have limitations in terms of statistical power and available information, they provide reassuring evidence of the absence of a strong association between fertility drugs and subsequent risk of developing epithelial ovarian cancer.     

Experience in organizing surgical care during the combat operations in the Chechen Republic

In the article the final analysis of organization of surgical care during the local military conflict in northern Caucasus was presented. The real possibilities of different medical units such as single medical company and medical squadron of special assignment was described. Also concrete contents of emergency specialized surgical care and its role in improvement of outcomes in patients with combined combat injuries was reflected. Mortality in this patients was decreased from 25.2 to 12.8%. The defects of surgical care were analyzed and the main ways of improvement of surgical care in local military conflict were presented. In the result of using the principle of moving the medical care closer to the wounded in the whole system of consecutive care the mortality was decreased up to 1.3%.     

X-ray photoelectron spectroscopy analysis of whole cells and isolated cell walls of gram-positive bacteria: comparison with biochemical analysis

The surface chemical composition of whole cells and isolated cell walls of four coryneform bacteria and of a Bacillus brevis strain has been determined by X-ray photoelectron spectroscopy (XPS). The XPS data were converted into concentrations of model compounds: peptides, polysaccharides, and hydrocarbonlike compounds. The composition of the surface of B. brevis differed markedly from that of coryneforms: the peptide concentration was about twice higher in the former case, which is attributed to the presence of an S-layer at the cell surface; in contrast, the surface of coryneforms was rich in hydrocarbonlike compounds (about 40%), which was concomitant with a high water contact angle. The peptide surface concentration of the isolated cell walls of the five strains deduced from XPS data fitted well with the total peptide content determined by biochemical analysis, which supports the validity of XPS to determine the overall macromolecular composition of the bacterial cell surface. Compared to biochemical analysis of isolated cell walls, XPS analysis of whole cells provides information which concerns directly the cell surface (2- to 5-nm-thick layer) and is less subject to alteration via losses of cell wall constituents or contamination by intracellular compounds.     

Identification of C1 presympathetic neurons in rat rostral ventrolateral medulla by juxtacellular labeling in vivo

The rostral ventrolateral medulla (RVLM) contains barosensitive, bulbospinal neurons that provide the main supraspinal excitatory input to sympathetic vasomotor preganglionic neurons. However, the phenotype of the critical RVLM cells has not been conclusively determined. The goal of the current study was to identify the proportion of electrophysiologically defined, putative, presympathetic RVLM neurons that are C1 cells. We used a juxtacellular labeling technique to individually fill spontaneously active, barosensitive, bulbospinal RVLM neurons with biotinamide following electrophysiological characterization in chloralose-anesthetized rats. To determine whether these neurons could be classified as C1 cells, the biotinamide-labeled cells were processed for detection of tyrosine hydroxylase. The majority of barosensitive bulbospinal RVLM neurons were tyrosine hydroxylase immunoreactive (TH-ir; 28 of 39). All of the barosensitive bulbospinal RVLM neurons with axonal conduction velocities in the C fiber range (<1 m/second) were TH-ir (n = 16), whereas faster conducting cells (1 to 7 m/second) were either lightly TH-ir (n = 12) or not detectably TH-ir (n = 11). Adjacent respiratory-related RVLM units labeled with biotinamide were not detectably TH-ir (n = 10). To verify that TH-ir cells were indeed adrenergic, a subset of barosensitive bulbospinal cells labeled with biotinamide were examined for phenylethanolamine N-methyltransferase immunoreactivity (PNMT-ir). Three slowly conducting cells had detectable PNMT-ir, and two fast-conducting cells had no detectable PNMT-ir. These results indicate that the majority of bulbospinal RVLM neurons with putative sympathoexcitatory function are C1 cells.     

Mesh inguinal herniorrhaphy: a ten-year review

Inguinal herniorrhaphy remains one of the most common surgical operations, with approximately 10 to 20 per cent performed for recurrence. Reviews by specialized hernia centers show mesh repair has a recurrence rate of 0.2 per cent. Detractors of this repair include increased cost, technical difficulty, and risk for infection. The purpose of this study was to compare mesh versus nonmesh inguinal herniorrhaphy at a large teaching institution. From 1985 to 1994, 892 patients underwent primary repair for inguinal hernia at the Veterans Administration Hospital at Memphis, TN. Patients were stratified by repair [Lichtenstein (Mesh), open anterior (Bassini, Marcy, McVay, and Shouldice), laparoscopic (Lap), and preperitoneal (Post)]. Operative time for Mesh repair (111 +/- 2 minutes) was longer than for Bassini or McVay (91 +/- 2 and 98 +/- 2 minutes; P < 0.05), and Lap repairs were longer than all others (192 +/- 16 minutes; P < 0.05). Hospital stay averaged 2.2 +/- 0.1 days for Mesh versus 2.6 +/- 0.1 days for all repairs combined (P = not significant). Mesh patients developed four wound infections (1.0%), none requiring mesh removal, versus nine infections (1.8%) in other groups (P = not significant). One Mesh patient (0.3%) developed recurrence, compared with 16 (3.5%) with open anterior repair (P < 0.01). Inguinal herniorrhaphy using an open mesh repair technique provides superior recurrence rates without increasing risk for infection, length of stay, or technical difficulty.     

Interaction of the von Willebrand factor with platelets and thrombosis

The human von Willebrand factor (vWf) is a multimeric glycoprotein present in plasma, platelets, endothelial cells and subendothelium and synthesized in endothelial cells and megakaryocytes. vWf plays a pivotal role in the mechanisms of blood clotting and platelet thrombus formation; quantitative and qualitative abnormalities of vWf cause the most common congenital bleeding disorder in man, the von Willebrand disease. vWf stabilizes factor VIII and interacts with subendothelial components and with platelet membrane receptors. The multimeric structure of vWf provides an array of binding sites which allows multivalent interactions with its ligands, thus supporting the formation of stable platelet aggregates at the site of vascular injury, particularly under flow conditions characterized by high shear stress. In the last years, remarkable progress has been made toward understanding the structure of vWf protein and gene, and the elucidation of many structure-function relationships, which may result in improved therapeutic intervention for vWD patients, and in the development of effective strategies for antithrombotic therapy.     

Properties of the regulatory subunit of cAMP-dependent protein kinase type II from human brain

The regulatory subunit type II (RII) of cAMP-dependent protein kinase purified from human brain was represented by two proteins with apparent molecular masses of 51-52 kD and 54 kD. Dephosphorylation of human RII containing 3 mol phosphate/mol protein did not change the electrophoretic pattern. One-dimensional peptide mapping of 51-52 kD and 54 kD proteins after digestion with St. aureus V8 protease evidenced to their being distinct proteins. The data obtained permit to assume that human RII of neural type is represented by two isoforms.     

Homocamptothecins: synthesis and antitumor activity of novel E-ring-modified camptothecin analogues

Homocamptothecin (hCPT), a camptothecin (CPT) analogue with a seven membered beta-hydroxylactone which combines enhanced plasma stability and potent topoisomerase I (Topo I)-mediated activity, is an attractive template for the elaboration of new anticancer agents. Like CPT, hCPT carries an asymmetric tertiary alcohol and displays stereoselective inhibition of Topo I. The preparation and biological screening of racemic hCPT analogues are described. The 10 hCPTs tested were better Topo I inhibitors than CPT. Fluorinated hCPTs 23c, d,f,g were found to have potent cytotoxic activity on A427 and PC-3 tumor cell lines. Their cytotoxicity remained high on the K562adr and MCF7mdr cell lines, which overexpress a functionally active P-glycoprotein. Fluorinated hCPTs were more efficacious in vivo than CPT on HT-29 xenografts. In this model, a tumor growth delay of 25 days was reached with hCPT 23g at a daily dose of 0.32 mg/kg, compared to 4 days with CPT at 0.625 mg/kg. Thus difluorinated hCPT 23g warrants further investigation as a novel Topo I inhibitor with high cytotoxicity toward tumor cells and promising in vivo efficacy.     

Effect of propofol and thiopentone on free radical mediated oxidative stress of the erythrocyte

Propofol has free radical scavenging properties similar to those of recognized phenol-based antioxidants. We have examined these properties in an in vitro model of radical-induced cellular injury, comparing its activity with that of thiopentone (which has also been shown to have radical scavenging activity). Haemolysis of human erythrocytes was induced using the azo compound 2,2'-azo-bis(2-amidinopropane) dihydrochloride (ABAP). This was achieved by incubating a 10% suspension of erythrocytes with ABAP 100 mmol litre-1 at 37 degrees C. For propofol, at concentrations of 12.5, 25 and 50 mumol litre-1, the times to achieve 50% haemolysis were mean 126 (SEM 7) min (95% confidence interval 108-144 min), 150 (8) (129-170) min and 182 (12) (160-180) min, respectively (Intralipid control 107 (7) (90-125) min, ANOVA P < 0.0001). For thiopentone, at concentrations of 62.5, 125 and 250 mumol litre-1, the values were 117 (2) (112-121) min, 126 (3) (119-133) min and 138 (2) (132-144) min, respectively (saline control 109 (2) (104-113) min, ANOVA P < 0.0001). Spectroscopic analysis in the visible and ultraviolet spectra demonstrated a steady increase in the proportion of methaemoglobin during haemolysis, with the highest concentrations in the propofol-containing flasks. The formation of methaemoglobin was preceded by the generation of ferrylhaemoglobin (a Fe4+ haemoglobin species). Further experiments examining oxidation of purified methaemoglobin to ferrylhaemoglobin by hydrogen peroxide suggested that propofol, but not Intralipid or thiopentone, reduced ferrylhaemoglobin back to the met- state, and thereby explained the higher concentrations of methaemoglobin in the propofol-containing erythrocyte suspensions. We conclude that propofol is a more potent free radical scavenger in this model of oxidant stress than thiopentone, and that reduction of high oxidation states of haemoglobin may contribute to such activity.