The hyperpolarization-activated cyclic nucleotide-gated HCN2 channel transports ammonium in the distal nephron

Recent studies have identified Rhesus proteins as important molecules for ammonia transport in acid-secreting intercalated cells in the distal nephron. Here, we provide evidence for an additional molecule that can mediate NH3/NH4 excretion, the subtype 2 of the hyperpolarization-activated cyclic nucleotide-gated channel family (HCN2), in collecting ducts in rat renal cortex and medulla. Chronic metabolic acidosis in rats did not alter HCN2 protein expression but downregulated the relative abundance of HCN2 mRNA. Its cDNA was identical to the homolog from the brain and the protein was post-translationally modified by N-type glycosylation. Electrophysiological recordings in Xenopus oocytes injected with HCN2 cRNA found that potassium was transported better than ammonium, each of which was transported significantly better than sodium, criteria that are compatible with a role for HCN2 in ammonium transport. In microperfused rat outer medullary collecting duct segments, the initial rate of acidification, upon exposure to a basolateral ammonium chloride pulse, was higher in intercalated than in principal cells. A specific inhibitor of HCN2 (ZD7288) decreased acidification only in intercalated cells from control rats. In rats with chronic metabolic acidosis, the rate of acidification doubled in both intercalated and principal cells; however, ZD7288 had no significant inhibitory effect. Thus, HCN2 is a basolateral ammonium transport pathway of intercalated cells and may contribute to the renal regulation of body pH under basal conditions.     

Norovirus outbreak associated with person-to-person transmission, U.S. Air Force Academy, July 2011

In July 2011, the U.S. Air Force School of Aerospace Medicine (USAFSAM) Epidemiology Consult Service investigated an ongoing outbreak of acute gastrointestinal (GI) illness--characterized by vomiting, nausea, diarrhea, and stomach cramps--that affected cadets and support personnel at a field training location at the U.S. Air Force Academy. Six outbreak-related stool specimens were confirmed by RT-PCR to be infected with norovirus, genogroup I. Overall, 290 cases (suspected and confirmed) of norovirus-related GI illness were recorded; the estimated attack rate among 1,359 cadets was 18%. The investigation suggested that norovirus was introduced into the field dining facility by one or more food service workers, possibly transmitted via common use serving utensils, and then further spread among cadets by person-to-person contact. Numbers of new cases sharply declined after ill cadets were segregated in separate tents for convalescence, and after all cadets moved from field billets (i.e., tents) to dormitories after completing the field training.     

Relationship of sociodemographic variables with outcomes after cataract surgery

Purpose

The objective of this study is to analyse the relationship between sociodemographic characteristics of patients undergoing cataract extraction and their outcomes.

Methods

The method comprised a prospective cohort study of patients recruited from 17 hospitals of different areas of Spain. Data gathered before surgery included sociodemographic variables, visual acuity, and visual function (using the Visual Function Index-14). After surgery, we assessed visual acuity and visual function at 6 weeks and at 3 months, respectively. Multivariate multilevel analysis was performed to assess the relationship of sociodemographic variables with changes in visual acuity and function, analysing whether improvements surpassed the minimal clinically important differences (MCIDs).

Results

Multivariate analysis showed that for visual acuity, (i) older men had a lower odds ratio (OR) of surpassing the MCID (OR: 65–75 years, 0.64; >75 years, 0.51); (ii) those with primary (1.65) or secondary (1.41) education had higher ORs than those with no formal education; and (iii) those living in a residential home had a lower OR than men living alone (0.36). In women, we found that the higher the educational level, the greater the improvement in visual acuity (primary, 1.41; secondary, 1.76), whereas socially dependent women (0.70) were less likely to exceed the MCID. With regards to predictors related to achievement of an MCID in visual function, only dependency was associated with more improvement in men (OR: 1.39), whereas in women the educational level was the only predictor (primary: 0.72; secondary: 0.61).

Conclusions

This study found that patients with certain sociodemographic characteristics were less likely to experience an MCID in visual acuity or visual function after cataract surgery.     

Rituximab in the treatment of acute cellular rejection of renal allograft with CD20-positive clusters in the infiltrate

A 31-year-old woman with nephronophthisis received a cadaveric kidney transplant, and was immunosuppressed with cyclosporine, azathioprine and steroids. Twelve days after transplant a biopsy showed acute rejection with vascular damage. She was treated with 3 pulses of methylprednisolone and change of immunosuppression to mycophenolate mofetil and tacrolimus, without improving graft function. At day 21, a second biopsy showed accentuation of interstitial and vascular rejection. Antibody-mediated rejection was suspected and plasmapheresis and rituximab were prescribed. Graft function improved rapidly. Staining for C4d was negative and there were no circulating antibodies against the donor. In the interstitial infiltrate there were clusters of B lymphocytes that accounted for 40% of cells, which was thought to be an ominous sign, as it has been associated with poor graft outcome. Acute T-cell-mediated rejection grade III (Banff 07) was diagnosed. Thirty-nine months after transplant her kidney function is stable with no other complication. This clinical case generates the hypothesis that rituximab may have a beneficial role in the therapy of acute cellular rejection when there are clusters of B lymphocytes in the infiltrate and a good response has not been obtained to conventional anti-rejection therapy.     

Single-port surgery: laboratory experience with the daVinci single-site platform

Background and Objectives:

The purpose of this study was to evaluate the feasibility and validity of a dedicated da Vinci single-port platform in the porcine model in the performance of gynecologic surgery.

Methods:

This pilot study was conducted in 4 female pigs. All pigs had a general anesthetic and were placed in the supine and flank position. A 2-cm umbilical incision was made, through which a robotic single-port device was placed and pneumoperitoneum obtained. A data set was collected for each procedure and included port placement time, docking time, operative time, blood loss, and complications. Operative times were compared between cases and procedures by use of the Student t test.

Results:

A total of 28 surgical procedures (8 oophorectomies, 4 hysterectomies, 8 pelvic lymph node dissections, 4 aorto-caval nodal dissections, 2 bladder repairs, 1 uterine horn anastomosis, and 1 radical cystectomy) were performed. There was no statistically significant difference in operating times for symmetrical procedures among animals (P=0.3215).

Conclusions:

This animal study demonstrates that single-port robotic surgery using a dedicated single-site platform allows performing technically challenging procedures within acceptable operative times and without complications or insertion of additional trocars.     

Clinical utility of viscoelastic testing (TEG and ROTEM analyzers) in the management of old and new therapies for hemophilia

Hemophilia A and B are rare inherited bleeding disorders resulting from deficiency of coagulation factors VIII and IX respectively. In the past few decades, the field of hemophilia has witnessed pivotal management challenges and therapeutic advances. Routine coagulation and factor assays, while useful in the classification of severity and treatment monitoring in hemophilia patients, have been shown to be of limited use in managing clinical presentations and outcomes. This prompted the investigation of viscoelastic studies in hemophilia care, which have established their utility in various bleeding and thrombotic states. In this review, we will discuss and critically assess the current literature highlighting the use of viscoelastic studies in various aspects of hemophilia including the determination of clinical phenotype, management of patients with inhibitors, perioperative management, and monitoring of novel agents.