Minimal Acute Rejection after Lung Transplantation: A Risk for Bronchiolitis Obliterans Syndrome

Bronchiolitis obliterans syndrome (BOS) is a major cause of lung allograft dysfunction. Although previous studies have identified mild to severe rejection (grade>or=A2) as a risk factor for BOS, the role of minimal rejection (grade A1) remains unclear. To determine if A1 rejection by itself is a risk factor for BOS, we performed a retrospective cohort study on 228 adult lung transplant recipients over a 7-year period. Cohorts were defined by their most severe rejection episode (none, A1 only, and >or=A2) and analyzed for the subsequent development and progression of BOS using univariate and multivariate time-dependent Cox regression analysis. In the univariate model, the occurrence of isolated minimal rejection was a risk factor for all stages of BOS. Similarly, multivariate models that included HLA mismatch, cytomegalovirus pneumonitis, community acquired viral infection, underlying disease and type of transplant demonstrated that A1 rejection was a distinct risk factor for BOS. Furthermore, the associated risk with A1 rejection was slightly greater than the risk from >or=A2 and treatment of A1 rejection decreased the risk for subsequent BOS stage 1. We conclude that minimal rejection is associated with an increased risk for BOS development and progression that is comparable to A2 rejection.     

Effect of intravenous sedation on the outcome of transvaginal oocyte retrieval: a comparative study of propofol- and methohexital-based techniques

This study retrospectively compares patients who underwent outpatient transvaginal follicle aspiration with either a propofol- or methohexital-based intravenous sedation technique. Data collected from patient charts (n = 212) over a 46-month period were analyzed to determine the effects of each sedation technique on procedure and recovery times, number of retrieved ova, as well as rates of nausea, fertilization, cleavage, pregnancy, and delivery. All patients were included in the study, regardless of age or diagnosis. procedure time was lower in the propofol group (51 t 18 min) than in the methohexital group (61 I 20 min) (p > 0.01). Patients in the methohexital group (139 2 51 min) spent more time in the recovery room than did those in the propofol group (71 ? 34 min) (p > 0.01). The nausea rates were significantly lower in the propofol group compared with the methohexital group (1.9% vs. 14.4%, respectively) (p > 0.02). Fertilization rate in the propofol group was 77.7% and was 62.9% in the methohexital group (p > 0.01). The numbers of retrieved ova and the cleavage rates were similar in both groups. The rate of pregnancy in patients sedated with propofol (46.1%) was higher than the methohexital group (26.9%) (p > 0.02). Delivery rate was 38.5% in the propofol group and 20.6% in the methohexital group (p > 0.02). In summary, propofol intravenous sedation for transvaginal follicle aspiration was associ- ated with an improved outcome. Pregnancy and delivery rates were higher while nausea, an unpleasant side effect, was sharply reduced.     

Determination of hepatitis C virus genotype by Pyrosequencing

A simple sequencing-based assay is described for genotyping of hepatitis C virus (HCV). RT-PCR was employed to amplify a 237-nucleotide-long fragment from the 5' untranslated region (UTR) of the genome using one biotinylated and one normal primer. Subsequent to capture of the PCR products on streptavidin-coated beads, single-stranded DNA separation, and hybridization of sequencing primer, Pyrosequencing was performed. The genotype of 98 samples out of which 77 samples were from American veterans and 21 samples were from Iran was determined. The samples from the American veterans contained six different subtypes, while five subtypes were found in Iranian samples. For rapid population-specific HCV subtyping, a multiplex assay was developed. This study demonstrates the suitability of this technology for low-cost, high throughput and accurate microbial genotyping.     

Humoral immune response to chlamydial genital infection of mice with the agent of mouse pneumonitis.

The objective of this study was to characterize the humoral immune response to chlamydial genital infection of mice with the mouse pneumonitis agent (MoPn). With an enzyme-linked immunoabsorbent assay, immunoglobulin G antibodies to MoPn were first detected in plasma by day 14. Peak plasma antibody concentrations were reached by day 49, and this response did not decline significantly throughout the 300-day monitoring period. Immunoglobulin A against MoPn could first be detected in pooled vaginal washes by day 21 after infection and had reached peak concentrations by day 28, but anti-MoPn immunoglobulin G was not consistently present in secretions. The antibody response in secretions had declined slightly by day 300. Immunoblot analysis revealed that the early phase of the plasma antibody response to MoPn as a result of genital infection was against lipopolysaccharide, the major outer membrane protein, and a 62-kilodalton (kDa) protein. In secretions, early-phase immunoglobulin A antibodies were directed to the major outer membrane protein and lipopolysaccharide. Late reactions to 15-, 22-, and 83-kDa proteins in plasma were noted. Late reactions to the 62-kDa protein in secretions were also noted. The cause of these late responses remains unexplained. When mice were challenged intravaginally with MoPn at 50-day intervals after the primary infection, it was found that mice inoculated on day 100 or after were susceptible to reinfection. Susceptibility could not be related to a decline in the antibody concentration in plasma or secretions or in the antibody response to specific components of MoPn as measured by immunoblot analysis.     

Differential effects of external pH alteration on intracellular pH in rat coronary and cardiac myocytes

Changes in extracellular pH (pH_o) induce changes in the intracellular pH (pH_i) of cardiac myocytes that are slow and attenuated. Little however is known about the effects of changing pH_o on the pH_i of the coronary smooth muscle cells. We have therefore directly compared the effects of altering pH_o on pH_i of both coronary and cardiac myocytes. Carboxy-SNARF was used in single cells to measure pH_i. Alteration of pH_o caused corresponding changes in pH_i that were large (70–80 % of pH_o) and rapid in coronary myocytes compared to cardiac myocytes. In contrast, changes of pH_i produced by weak acids or bases produced similar pH_i responses in both types of cells. It is suggested that the differential effects of pH_o on coronary and cardiac cells may be functionally significant, as it will allow rapid alteration of coronary perfusion to meet tissue needs, while maintaining cardiac output.Supported by the BHF and MRC     

Inducible Nitric Oxide Synthase Does Not Affect Resolution of Murine Chlamydial Genital Tract Infections or Eradication of Chlamydiae in Primary Murine Cell Culture

Mice lacking inducible nitric oxide synthase (iNOS) or treated with iNOS inhibitors resolved chlamydial genital tract infections. Additionally, treatment of primary murine cell cultures with gamma interferon restricted chlamydial growth in the absence of nitric oxide. From these results, iNOS activity is unnecessary for the resolution of chlamydial genital tract infections in mice and inhibition of chlamydial growth in culture.