Cardiac morphology and left ventricular function in normotensive morbidly obese patients with and without congestive heart failure, and effect of weight loss

BACKGROUND: Prevention of hypothermia during abdominal surgery by insulating or heat-transferring methods has been the subject of numerous investigations. This study approaches the problem from a less discussed point of view, i.e. the effect of different surgical techniques on body temperature changes. METHODS: Body temperature was measured at 3 core and 6 skin points in 40 patients scheduled for cholecystectomy through open laparotomy or laparoscopy with pneumoperitoneum created and maintained with unwarmed carbon dioxide (CO2) insufflation. End-tidal CO2 was kept constant by adjustments of respiratory frequency. Anaesthesia, intravenous infusions, and draping of the patients were standardized. RESULTS: During the first 1 h of anaesthesia core temperatures decreased approximately by 0.7 degrees C and distal skin temperatures increased by 7 degrees C in both groups. At the end of surgery heat balance was similar in both groups. An increase of 2.5 1.min-1 in respiratory minute volume was needed to control end-tidal CO2 levels in the laparoscopy group during pneumoperitoneum which was maintained with a CO2 flow of 1.2 1.min-1 through the abdominal cavity. CONCLUSION: Laparoscopic technique with unwarmed carbon dioxide insufflation does not offer any advantage in terms of body temperature changes when compared to open surgery.     

Cytotoxicity of polycyclic aromatic hydrocarbon o-quinones in rat and human hepatoma cells

A novel pathway of polycyclic aromatic hydrocarbon (PAH) metabolism involves the oxidation of non-K-region trans-dihydrodiols by dihydrodiol dehydrogenase (DD) to yield PAH o-quinones whose cytotoxicity and genotoxicity are unknown. The cytotoxicity of several PAH o-quinones derived from this reaction [naphthalene-1,2-dione (NPQ), benzo[a]pyrene-7,8-dione (BPQ), and 7,12-dimethylbenz[a]anthracene-3,4-dione (DMBAQ)] was examined in rat (H-4IIe) and human (Hep-G2) hepatoma cells which are known to express DD. 2-Methylnaphthalene-1,4-dione (menadione), a known cytotoxic p-quinone, was used as a positive control. Hepatoma cells (1 x 10(6) cells/mL) were exposed to PAH o-quinones (1-100 microM) for 0-4 h, and cell viability and survival were measured and related to O2.- production and changes in redox potential [GSSG/GSH and NAD(P)+/NAD(P)H]. Three different modes of cytotoxicity were observed: (1) NPQ (no bay region) and DMBAQ (methylated bay region) were as cytotoxic as menadione in reducing cell survival but had less effect on cell viability. These o-quinones adversely affected GSH levels and the redox state of the cell and caused an increase in the production of O2.- in cell suspensions. This cytotoxicity was not enhanced by dicoumarol (10 microM), a DT-diaphorase inhibitor, implying that this enzyme is unable to prevent these PAH o-quinones from entering one-electron redox-cycles. (2) BPQ (bay region only) was the least cytotoxic of the PAH o-quinones studied. BPQ decreased cell viability (< 40% at 20 microM) but did not adversely affect cell survival or the redox state of the cell.(ABSTRACT TRUNCATED AT 250 WORDS)     

Absence of detectable human herpesvirus 8 in the semen of human immunodeficiency virus-infected men without Kaposi's sarcoma

The prevalence of human herpesvirus 8 (HHV-8)/Kaposi's sarcoma (KS)-associated herpesvirus was investigated in the semen of 99 human immunodeficiency virus (HIV)-infected men (median CD4 cell count, 357/mm3) by use of a polymerase chain reaction (PCR) assay capable of detecting <10 copies of HHV-8 DNA. Of the subjects, 95 (96%) self-identified as men who have sex with men (MSM), and 3 had a history of clinical KS. Seminal cell specimens were negative for HHV-8 in 98 subjects. None of the 26 without KS (27.1% of 96 tested) who were seropositive for HHV-8 by IFA for latency-associated nuclear antigens had HHV-8 detected in their semen. The only subject with any evidence for seminal HHV-8 DNA was seropositive for HHV-8 and had active KS. HHV-8 was detected in 10 (10.4%) of 96 peripheral blood mononuclear cell specimens. The prevalence of HHV-8 DNA by PCR in semen of HIV-infected MSM without KS is low.     

Solution structure of the motile major sperm protein (MSP) of Ascaris suum - evidence for two manganese binding sites and the possible role of divalent cations in filament formation

The major sperm protein (MSP) of Ascaris suum mediates amoeboid motility by forming an extensive intermeshed system of cytoskeletal filaments analogous to that formed by actin in many other amoeboid cells. MSP is a dimeric molecule that polymerizes to form non-polar filaments constructed from two helical subfilaments that wind round one another. Moreover, MSP filaments can interact with one another to form higher-order assemblies without requiring the range of accessory proteins usually employed in actin-based systems. A knowledge of how MSP polymerizes and forms the hierarchical series of helical MSP macromolecular assemblies is fundamental to understanding locomotion in these cells. Here we describe the solution structure of MSP dimers determined by NMR spectroscopy under conditions where MSP does not polymerize to form filaments. The solution structure is indistinguishable from that observed in putative MSP subfilament helices by X-ray crystallography, indicating that MSP polymerization is not accompanied by a major conformational change. We also show that the rate of MSP polymerization associated with movement of vesicles in an in vitro motility assay is enhanced by the presence of magnesium and manganese ions and use NMR to show that the primary residues that bind these ions are 24-25 and 83-86. These residues are distant from the interface formed between MSP dimers in subfilament helices, and so are probably not involved in this level of polymerization. Instead the manganese and magnesium ion binding appears to be associated with the assembly of subfilaments into filaments and their subsequent aggregation into bundles.     

Infertility update: use of assisted reproductive technology

OBJECTIVE: To describe assisted reproductive technology (ART) and use of medications during these procedures. DATA SOURCES: Recent clinical literature. STUDY SELECTION: Not applicable. DATA EXTRACTION: Not applicable. DATA SYNTHESIS: ARTs are procedures used in treatment of infertility that involve removal of oocytes and their manipulation outside the woman's uterus. The simplest form of ART, in vitro fertilization, involves aspirating eggs from the ovaries, fertilizing them outside the body, and transferring the embryos into the uterus at the four- to eight-cell stage. Experimental regimens for in vitro fertilization include use of various medications (gonadotropin-releasing hormone agonists, human menotropins, follicle-stimulating hormone, growth hormone) at varying points in the menstrual cycle and after introduction of the embryo into the uterus. Human chorionic gonadotropin has been used to increase implantation of embryos during the woman's luteal phase. Gamete intrafallopian transfer (GIFT) involves transfer of oocytes and sperm into the fallopian tubes, where fertilization takes place. This technique has the advantage of causing the zygote to enter the uterus at the time it would during natural conception. Zygote intrafallopian transfer is similar to GIFT, except that fertilization occurs in vitro, with embryos placed in the fallopian tubes at the two-cell stage. Various micromanipulation techniques and innovative sperm aspiration procedures are currently under development. CONCLUSION: Many advancements have been made in ART, and pharmacists who understand these procedures can serve patients by providing medication information in an empathetic and supportive manner.     

IFN-alpha 2B enhances Th1 cytokine responses in bladder cancer patients receiving Mycobacterium bovis bacillus Calmette-Guérin immunotherapy

Combination therapy with intravesical bacillus Calmette-Guérin (BCG) plus IFN-alpha for superficial bladder cancer has been demonstrated to be more effective than either single agent alone in animal studies and of suggested greater efficacy in clinical studies. However, the mechanism by which IFN-alpha enhances BCG-mediated antitumor activity is poorly understood. Using PBMCs from bladder cancer patients, IFN-alpha was found to substantially enhance the efficacy of BCG to induce IFN-gamma production. Among 34 patients tested, 80% showed >4-fold increase. This effect of IFN-alpha was observed in both initial and memory responses to BCG. In addition, IFN-alpha up-regulated BCG-induced IL-12 and TNF-alpha and down-regulated BCG-induced IL-10. Neutralizing endogenous IL-10 or adding exogenous IL-12 provided further synergy for IFN-gamma production. In clinical practice, intravesical IFN-alpha 2B (50 million units (MU)/dose) was observed to accelerate urinary IFN-gamma production to low-dose BCG (one-tenth or one-third of a full dose) in patients treated with combination therapy compared with BCG alone. These results suggest that IFN-alpha is a potent BCG enhancer that polarizes the BCG-induced immune response toward the cellular immune pathway by promoting Th1 cytokine expression and reducing Th2 cytokine expression. This study provides an immunological basis for future rational use of IFN-alpha in conjunction with intravesical BCG for bladder cancer immunotherapy.