1141154113Expression of natural cytotoxicity receptors in peripheral blood NK cell subsets of women with recurrent spontaneous abortions (RSA) or implantation failures

Aim:  To determine if IgA is required for protection against Chlamydia infection in the male reproductive tract (MRT).
Materials and Methods:  Male polyimmunoglobulin receptor knockout mice (PIgR^-/-) and wild-type C57BL/6 (WT) mice were immunised intranasally with chlamydial major outer membrane protein (MOMP) and cholera toxin (CT). MOMP-specific IgG and IgA in serum and prostatic fluids were measured by ELISA. Serum and PF were also assayed for inhibition of in vitro chlamydial infection. Immunized WT and PIgR^-/- mice were challenged by direct inoculation of C. muridarum into the meatus urethra. Four weeks post challenge Chlamydia levels in the penile urethra, epididymis and testis were determined by PCR.
Results:  Equivalent levels of IgG were found in the serum of both WT and PIgR^-/- mice however IgA in serum of PIgR^-/- mice was 19- to 20-fold higher than in WT animals consistent with the lack of the PIgR IgA transport molecule. IgA levels were significantly lower in PIgR^-/- PF compared to WT PF after both immunization and infection. Only PF from WT but not PIgR^-/- animals was able to inhibit in vitro chlamydial infection. Following challenge significantly higher levels of Chlamydia were recovered from the MRT of PIgR^-/- mice compared to WT animals.
Conclusions:  Male mice lacking a functional PIgR were unable to clear a genital tract Chlamydia infection despite high levels of serum IgA. These data show that mucosal IgA plays a major role in preventing chlamydial infection of the male genital tract and suggest that immunization strategies to protect males should target a strong mucosal IgA response.     

Unusual Renal Manifestations in a Girl with Hyperthyroidism

A 16-year-girl, a known case of hyperthyroidism since last 6 months, presented to the emergency with complaints of acute gastroenteritis of 5 days duration. At admission the child was found to be hypovolemic with acidotic breathing, which was thought to be due to dehydration. However, despite fluid correction she remained acidotic. A diagnosis of distal renal tubular acidosis (RTA) was suspected when her renal scan, for the cause of metabolic acidosis, revealed nephrocalcinosis. This was later confirmed by relevant investigations. She was started on treatment for distal RTA on which she symptomatically improved. The association of distal RTA and thyroid disorders is rarely reported in children. Till date there is only one report of distal RTA and hypothyroidism, but none with hyperthyroidism in this age group. The authors chose to report this case to highlight the fact that one should have a high index of suspicion for renal tubular disorders in children with thyroid hormone abnormalities, as these are treatable conditions if diagnosed early.     

Human immune response to outer membrane protein CD of Moraxella catarrhalis in adults with chronic obstructive pulmonary disease

Moraxella catarrhalis is a common cause of lower respiratory tract infection in adults with chronic obstructive pulmonary disease (COPD). The antibody response to outer membrane protein (OMP) CD, a highly conserved surface protein of M. catarrhalis under consideration as a vaccine antigen, was studied in adults with COPD following 40 episodes of infection or colonization. Following infection or colonization, 9 of 40 patients developed new serum immunoglobulin G (IgG) to OMP CD, as measured by enzyme-linked immunosorbent assay. Adsorption assays revealed that a proportion of the serum IgG was directed toward surface-exposed epitopes on OMP CD in six of the nine patients who developed new IgG to OMP CD. Immunoblot assays with fusion peptide constructs indicated that the new antibodies that developed after infection or colonization recognized conformational epitopes, particularly in the carboxy region of the protein. Three of 28 patients developed new mucosal IgA to OMP CD in sputum supernatants. This study establishes that OMP CD is a target of a systemic and mucosal immune response following infection and colonization in some patients with COPD.     

Differential dissociation of G protein heterotrimers

Signalling by heterotrimeric G proteins is often isoform-specific, meaning certain effectors are regulated exclusively by one family of heterotrimers. For example, in excitable cells inwardly rectifying potassium (GIRK) channels are activated by Gβγ dimers derived specifically from G_i/o heterotrimers. Since all active heterotrimers are thought to dissociate and release free Gβγ dimers, it is unclear why these channels respond primarily to dimers released by G_i/o heterotrimers. We reconstituted GIRK channel activation in cells where we could quantify heterotrimer expression at the plasma membrane, GIRK channel activation, and heterotrimer dissociation. We find that G_oA heterotrimers are more effective activators of GIRK channels than G_s heterotrimers when comparable amounts of each are available. We also find that active G_oA heterotrimers dissociate more readily than active G_s heterotrimers. Differential dissociation may thus provide a simple explanation for Gα-specific activation of GIRK channels and other Gβγ-sensitive effectors.     

Determinants of survival and left ventricular performance after mitral valve replacement. Department of Veterans Affairs Cooperative Study on Valvular Heart Disease

To determine how survival and clinical status were related to left ventricular (LV) size and systolic function after mitral valve replacement, 104 patients (48 mitral regurgitation [MR], 33 mitral stenosis [MS], and 23 MS/MR) with isolated mitral valve replacement were evaluated before and after surgery. Preoperative hemodynamic abnormalities by cardiac catheterization were improved 6 months after surgery in all three patient groups. The patients with MR exhibited reductions in LV end-diastolic volume index (EDVI) (117 +/- 51 to 89 +/- 27 ml/m2, p less than 0.001) and ejection fraction (EF) (0.56 +/- 0.15 to 0.45 +/- 0.13, p less than 0.001); however, the ratio of forward stroke volume to end-diastolic volume increased (0.32 +/- 0.21 to 0.45 +/- 0.17, p less than 0.001) because of the elimination of regurgitant volume. Survival analysis revealed that mortality was significantly higher in MS or MS/MR patients with postoperative EDVI more than 101 ml/m2 (p less than 0.001 and p less than 0.042, respectively) and in MR patients with postoperative EF less than or equal to 0.50 (p less than 0.031). Also, the majority of patients with MR or MS/MR and postoperative EDVI more than 101 ml/m2 and EF less than or equal to 0.50 were in New York Heart Association class III or IV. Multivariate logistic regression analysis in the patients with MR revealed that the strongest predictor of postoperative EF was preoperative EF (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Oral metoprolol therapy in dilated cardiomyopathy: hemodynamic evidence for improved diastolic function accompanying amelioration of symptoms

Twenty patients with dilated cardiomyopathy (11 males and 9 females) aged from 14 to 54 (37.3 +/- 10.5) years were treated orally with metoprolol (dose 37.5 mg-100 mg/day, mean 91 +/- 18.6 mg/day) after a baseline hemodynamic study. On follow-up, all patients showed improvement in symptomatic status by at least one NYHA class within 2 to 4 weeks of the initiation of therapy. Repeat right heart study and left ventricular angiography (venous digital subtraction angiography) afer 3 to 6 months of treatment in 10 patients showed a fall in the mean pulmonary arterial wedge pressure from 24.4 +/- 9.6 to 12.8 +/- 7.7 mm Hg (P = 0.025), right ventricular end-diastolic pressure from 8.8 +/- 4.7 mm Hg to 4.5 +/- 1.9 mm Hg (P = 0.025) and mean pulmonary arterial pressure from 34.2 +/- 12.4 mm Hg to 25.9 +/- 10.9 mm Hg (P less than 0.01). There was no significant change in the left ventricular ejection fraction (18.7 +/- 1.6% vs. 22 +/- 0.48%, P = NS) or cardiac index (2.2 +/- 0.48 l/m/m2 to 2.12 +/- 0.68 l/m/m2, P = NS). These hemodynamic results indicate that the improvement in symptoms and congestive cardiac failure produced by treatment with metoprolol in patients having dilated cardiomyopathy is related to improvement in diastolic function of the myocardium.     

Comparison of Tc-99m MAA Planar Versus SPECT/CT Imaging for Lung Shunt Fraction Evaluation Prior to Y-90 Radioembolization: Are We Overestimating Lung Shunt Fraction?

CardioVascular and Interventional Radiology - To compare lung shunt fraction (LSF) prior to Y-90 radioembolization calculated using planar imaging versus SPECT/CT in patients with hepatocellular...     

Thirty-Day Readmission After Laparoscopic Sleeve Gastrectomy—a Predictable Event?

Background

Thirty-day readmission post-bariatric surgery is used as a metric for surgical quality and patient care. We sought to examine factors driving 30-day readmissions after laparoscopic sleeve gastrectomy (LSG).

Methods

We reviewed 1257 LSG performed between March 2012 and June 2014. Readmitted and nonreadmitted patients were compared in their demographics, medical histories, and index hospitalizations. Multivariable regression was used to identify risk factors for readmission.

Results

Forty-five (3.6 %) patients required 30-day readmissions. Forty-seven percent were readmitted with malaise (emesis, dehydration, abdominal pain) and 42 % with technical complications (leak, bleed, mesenteric vein thrombosis). Factors independently associated with 30-day readmission include index admission length of stay (LOS) ≥3 days (OR 2.54, CI?=?[1.19, 5.40]), intraoperative drain placement (OR 3.11, CI?=?[1.58, 6.13]), postoperative complications (OR 8.21, CI?=?[2.33, 28.97]), and pain at discharge (OR?8.49, CI?=?[2.37, 30.44]). Patients requiring 30-day readmissions were 72 times more likely to have additional readmissions by 6 months (OR?72.4, CI?=?[15.8, 330.5]).

Conclusions

The 30-day readmission rate after LSG is 3.6 %, with near equal contributions from malaise and technical complications. LOS, postoperative complications, drain placement, and pain score can aid in identifying patients at increased risk for 30-day readmissions. Patients should be educated on postoperative hydration and pain management, so readmissions can be limited to technical complications requiring acute inpatient management.