Perioperative N-acetylcysteine to prevent renal dysfunction in high-risk patients undergoing cabg surgery: a randomized controlled trial

Context  Renal dysfunction is a complication of coronary artery bypass graft (CABG) surgery performed with cardiopulmonary bypass (CPB) that is associated with increased morbidity and mortality. N-acetylcysteine, an antioxidant and vasodilator, counteracts renal ischemia and hypoxia. Objective  To determine whether perioperative intravenous (IV) N-acetylcysteine preserves renal function in high-risk patients undergoing CABG surgery with CPB compared with placebo. Design, Setting, and Patients  Randomized, quadruple blind, placebo-controlled trial (October 2003-September 2004) in operating rooms and general intensive care units (ICUs) of 2 Ontario tertiary care centers. The 295 patients required elective or urgent CABG and had at least 1 of the following: preexisting renal dysfunction, at least 70 years old, diabetes mellitus, impaired left ventricular function, or undergoing concomitant valve or redo surgery. Interventions  Patients received 4 (2 intraoperative and 2 postoperative) doses of IV N-acetylcysteine (600 mg) (n = 148) or placebo (n = 147) over 24 hours. Main Outcome Measures  The primary outcome was the proportion of patients developing postoperative renal dysfunction, defined by an increase in serum creatinine level greater than 0.5 mg/dL (44 µmol/L) or a 25% increase from baseline within the first 5 postoperative days. Secondary outcomes included postoperative interventions and complications, the requirement for renal replacement therapy (RRT), adverse events, hospital mortality, and ICU and hospital length of stay. Results  There was no difference in the proportion of patients with postoperative renal dysfunction (29.7% vs 29.0%, P = .89; relative risk [RR], 1.03 [95% confidence interval {CI}, 0.72-1.46]) in the N-acetylcysteine and placebo groups, respectively. We noted nonsignificant differences in postoperative interventions and complications, the need for RRT (0.7% vs 2.1%; P = .37), total (6.1% vs 9.6%; P = .26) and serious adverse events, hospital mortality (3.4% vs 2.7%; P>.99), and ICU and hospital length of stay between the N-acetylcysteine and placebo groups. A post hoc subgroup analysis of patients (baseline creatinine level >1.4 mg/dL [120 µmol/L]) showed a nonsignificant trend toward fewer patients experiencing postoperative renal dysfunction in the N-acetylcysteine group compared with the placebo group (25.0% vs 37.1%; P = .29). Conclusions  N-acetylcysteine did not prevent postoperative renal dysfunction, interventions, complications, or mortality in high-risk patients undergoing CABG surgery with CPB. Further research is required to identify CABG patients at risk for postoperative renal events, valid markers of renal dysfunction, and to establish renal thresholds associated with important clinical outcomes.      

Hormonal contraceptive use and the effectiveness of highly active antiretroviral therapy

The role of hormonal contraceptive use in the effectiveness of highly active antiretroviral therapy (HAART) was examined among participants in the Women's Interagency HIV Study who were followed from HAART initiation to 2001. Propensity score selection was used to match 77 hormonal contraceptive users with 77 nonusers on age, race, and pre-HAART CD4-positive T-lymphocyte (CD4+ cell) count and viral load. The authors compared hormonal contraceptive users and nonusers with regard to the CD4+ cell count and viral load responses to HAART upon initiation. Proportional hazards analyses were used to assess the effect of hormonal contraceptive use on times to increases in CD4+ cell count of 50 cells/mm(3) and 100 cells/mm(3) and achievement of an undetectable viral load. There were no statistically significant differences in CD4+ cell counts and log viral load responses by hormone use after HAART initiation, except in log viral load at the third visit after initiation (p = 0.047). Time-dependent hormonal contraceptive use was not a statistically significant predictor of achieving increases in CD4+ cell count of 50 cells/mm(3) and 100 cells/mm(3) or an undetectable viral load (p = 0.517, p = 0.751, and p = 0.218, respectively) after HAART initiation. In conclusion, the authors did not find substantial evidence that use of hormonal contraceptives strongly affected responses to HAART.     

Chiral Signatures of α-Hexachlorocyclohexane in Surface Water, Porewater, and Sediment System

No abstract available.     

Leishmune vaccine blocks the transmission of canine visceral leishmaniasis: absence of Leishmania parasites in blood, skin and lymph nodes of vaccinated exposed dogs

Leishmune vaccine is the first licensed vaccine against canine visceral leishmaniasis. It contains the Fucose-Mannose-ligand (FML) antigen of Leishmania donovani. The potential Leishmune vaccine effect on the interruption of the transmission of the disease, was assayed by monitoring, in untreated (n=40) and vaccinated dogs (n=32) of a Brazilian epidemic area: the kala-azar clinical signs, the FML-seropositivity and the Leishmania parasite evidence by immunohistochemistry of skin and PCR for Leishmanial DNA of lymph node and blood samples. On month 11 after vaccination, untreated controls showed: 25% of symptomatic cases, 50% of FML-seropositivity, 56.7% of lymph node PCR, 15.7% of blood PCR and 25% of immunohistochemical positive reactions. The Leishmune-vaccinated dogs showed 100% of seropositivity to FML and a complete absence of clinical signs and of parasites (0%) in skin, lymph node and blood PCR samples (p<0.01). The positivity in FML-ELISA in untreated dogs significantly correlates with the PCR in lymph node samples (p<0.001) and with the increase in number of symptoms (p=0.006) being strong markers of infectiousness. The absence of symptoms and of evidence of Leishmania DNA and parasites in Leishmune-vaccinated animals indicates the non-infectious condition of the Leishmune-vaccinated dogs.     

Differential expression of carbonic anhydrase isoenzymes in various types of anemia

BACKGROUND: The aim of the present study was to determine the concentrations of cytosolic carbonic anhydrase (CA) isoenzymes in erythrocytes of patients with aplastic, autoimmune hemolytic, iron deficiency or beta-thalassemia anemia. METHODS: Western blotting and CA esterase activity analysis were used to analyze cytosolic erythrocyte CA isoenzymes in 118 subjects with various types of anemia and 35 healthy controls. RESULTS: Total CA activity and CAII concentration of anemia patients were significantly higher than that of the control subjects while CAI concentration was significantly lower in patients of autoimmune hemolytic anemia (P<0.01). Compared with controls, CAIII concentration was lower in iron deficiency anemia (P<0.01), but higher in beta-thalassemia anemia (P<0.001). CONCLUSIONS: Carbonic anhydrase isoenzymes may contribute differently to various types of anemia. CAI may be an indicator to differentiate autoimmune hemolytic anemia from other types of anemia. CAII provides the CA activity necessary for maintaining ion transport in erythrocytes while CAIII may play an agent against oxidative damage in iron deficiency and beta-thalassemia anemia.     

Asthma: one hundred years of treatment and onward

There have been four types of drug treatment of asthma that have been used over the past 100 years. Belladonna alkaloids, derived from the thorn-apple plant were used in 1905, and chemically synthesized entities in this class are still in use today. Western medicine began to use adrenergic stimulants approximately 100 years ago, but they were likely used in Asian medicine long before that. Systemic treatment with corticosteroids was introduced into the treatment of asthma in the mid-20th century; inhaled corticosteroids have been in use for over 35 years. The last 40 years have also seen the development of the first targeted asthma treatments: cromones, antileukotrienes, and anti-IgE. As we learn more of the biology of asthma, we anticipate that more effective targeted asthma treatments will be developed.     

Solitary plasmacytoma

A Retrospective Review Is Presented Of Nine Patients Presenting With Solitary Plasmacytoma. Between 1963 And 1980, These Patients Were Treated With Radiation At The Department Of Radiation Oncology, University Of Louisville. Criteria For Admission To This Particular Study Include (1) A Solitary Focus Of Plasmacytoma Proven By Biopsy, (2) Normal Bone Marrow Findings (Less Than 10% Plasma Cells), And (3) No Evidence Of Disseminated Disease. In Six Patients The Primary Site Was Osseous, And In Three Extramedullary, Two Of Which Were Located In The Nasopharynx And Nasal Cavity And The Third In The Stomach. All Of The Extramedullary Plasmacytomas Are Disease Free For Periods Ranging From 4 To 10 Years. Of The Six Patients With Osseous Lesions, Two Developed Multiple Myeloma In 2 And 3 Years, Two Are Ned (No Evidence Of Disorder) After 9 Years, One Died Of Intercurrent Disease, And The Remaining Patient Was Ned For 2 Years, After Which He Was Lost To Follow-Up. These Results Suggest The More Favorable Prognosis Of Extramedullary Plasmacytoma And Support The Theory That The Solitary Plasmacytoma Of Bone And Extramedullary Plasmacytoma Are Distinct Disease Entities.     

PHARMACOLOGIC STUDIES OF 15-METHYL PRO''STAGLANDIN F2a(PGF2a)

Some of the important pharmacologic ac- tions of 15-methyl PGF 2cc are reported in this paper. The potency of subcutaneous 15-methyl PGF 2a in terminating early pregnancy in mice is about 10 times greater than that of PGF 2a This action can be suppressed by simultaneous administration of either megestrol acetate or HCG. 15-methyl PGF2a can also shorten the pseudopregnancy period and inhibit the forma- tion of deciduoma. Experiments on isolated smooth muscles show that the contra.ctile ac- tivity of 15-methyl PGF2a on the uterine muscle is similar to that of PGF2a: . However, contrac- tile activity of 15 methyl-PGF 2a on isolated rat stomach fundus and rabbit jejunum are only 300/o that of PGF2a. Acute toxicity tests on monkeys show no observable toxic reactions after administration of 15-methyl PGF2a at the doses used in this experiment.