Lipid mediators of inflammation in obesity-related glomerulopathy.

The interplay between chronic kidney disease (CKD) and obesity represents the convergence of two of the most common contemporary clinical issues, and is of particular interest and significance in the context of the burden presented by each at present, and the dismal projections associated with both of these conditions for the future. That obesity leads to CKD through its association with other risks, such as hypertension, type 2 diabetes mellitus and atherosclerosis, is well established; however, it is likely that obesity itself is an independent risk factor for the development of CKD. The aetiology of this obesity-related glomerulopathy (ORG) is not clear, but it appears to be strongly influenced by chronic inflammation, manifest as a disturbance of the balance between pro-inflammatory and pro-resolving lipid mediators, adipokines and mononuclear cells. This review examines the association between obesity and CKD, the role of inflammation therein, and the potential for pro-resolving lipid mediators to restore homoeostasis and offer therapeutic potential in ORG.

First UK case report of kidney transplantation from an HIV-infected deceased donor to two HIV-infected recipients.

Kidney transplantation is now considered the treatment of choice for many human immunodeficiency virus (HIV)-infected patients with end-stage renal disease (ESRD). Graft survival rates using HIV-negative donors and carefully selected HIV-positive ESRD patients are similar to those observed in HIV-uninfected kidney transplant recipients. To address the relative shortfall in donated organs it has been proposed that organs from HIV-infected deceased donors might be allocated to HIV-infected patients on the transplant waiting list. Preliminary experience in South Africa reports promising short-term outcomes in a small number of HIV-infected recipients of kidney transplants from HIV-infected donors. We sought to replicate this experience in the UK by accepting kidney offers from HIV infected deceased donors for patients with HIV-infection on the kidney transplant waiting list. Here we report the UK's first cases of kidney transplantation between HIV-positive donors and recipients.

Short communication: Investigation of incident HIV infections among U.S. army soldiers deployed to Afghanistan and Iraq, 2001-2007.

The U.S. Army initiated an investigation in response to observations of a possible increase in HIV incidence among soldiers deployed to combat. Human immunodeficiency virus (HIV)-infected U.S. Army soldiers are not eligible to deploy. Combat presents a health hazard to HIV-infected soldiers and they pose a threat to the safety of the battlefield blood supply and their contacts. All soldiers are routinely screened for HIV every 2 years and those who deploy are also screened both prior to and after deployment. Seroconversion rates were estimated for all soldiers who deployed to Afghanistan or Iraq in the period 2001-2007 and all active duty soldiers who did not. Seroconverters with an estimated date of infection, based on calculation of the midpoint between the last seronegative and first seropositive test date, that was either before or during deployment were eligible for inclusion. Confidential interviews and medical record reviews were conducted to determine the most likely time, geographic location, and mode of infection. Reposed predeployment samples were tested for HIV ribonucleic acid. The HIV seroconversion rate among all soldiers who deployed was less than the rate among those who did not deploy: 1.04 and 1.42 per 10,000 person-years, respectively. Among 48 cases, most were determined to have been infected in the United States or Germany and prior to deployment (n=20, 42%) or during rest and relaxation leave (n=13, 27%). Seven seronegative acute infections were identified in the predeployment period. Subtype was determined for 40 individuals; all were subtype B infections. All were acquired through sexual contact. These findings can inform development of preventive interventions and refinement of existing screening policy to further reduce HIV-infected deployed soldier person time.

The accuracy of physicians' perceptions of patients' suffering: findings from two teaching hospitals.

PURPOSE: How accurately physicians perceive patient suffering remains unclear. The authors sought to quantitatively compare physicians' estimates of their patients' suffering with the patients' ratings of their own suffering, using a paired survey. METHOD: Six major domains of suffering (DOSs) were derived from narrative descriptions of suffering by physicians and patients in a preliminary multicenter pilot study. From September 2005 through July 2006 at two teaching hospitals in Washington, DC, and Bethesda, Maryland, before a clinical encounter between a patient and physician, patients rated the impact of each of these DOSs on their overall suffering. After the same encounter, physicians rated the same DOSs according to their perception of suffering experienced by that patient. Patient responses were compared with physician responses using the Wilcoxon signed ranks and Spearman correlation tests. RESULTS: Two hundred twenty-seven adult patients and their treating physicians completed the survey. Cooperation rates among patients and physicians were 94% and 97%, respectively. For two of the six DOSs (pain and physically nonpainful symptoms), there was no significant difference between the physicians' estimates of suffering and the patients' ratings of the DOS. For the remaining four DOSs (communication, emotional factors, loss, and systems factors), there was significant disagreement between the physicians' estimates and the actual suffering of the patients (P < .01). When all six DOSs were combined to ascertain how well perceptions of overall suffering correlated, significant discordance was also observed between physicians' perceptions and patients' descriptions (P < .001). CONCLUSIONS: This study suggests that the physicians who participated might need more training in the recognition of patient suffering. Because these physicians were trained in medical schools across the country, the deficiencies noted here may not be limited to only the physicians in this study. More studies of physicians' ability to detect and manage suffering are needed, especially at nonteaching hospitals.

Behavioral synergism between D(1) and D(2) dopamine receptors in mice does not depend on gap junctions.

Activation of the D(1) and D(2) classes of dopamine receptor in the striatum synergistically promotes motor stereotypy. The mechanism of D(1)/D(2) receptor interaction remains unclear. To investigate the involvement of electrical synaptic transmission in this phenomenon, genetic inactivation of the neuronal gap junction (GJ) protein connexin 36 and pharmacological blockade of GJs were utilized. Stereotyped motor behavior was quantified after selective activation of D(1) receptors, D(2) receptors, or both receptors. These patterns of activation were produced by injection of the agonist apomorphine (3.0 mg/kg) 30 min after either the D(2) antagonist eticlopride (0.3 mg/kg), the D(1) antagonist SCH 23390 (0.1 mg/kg) or vehicle, respectively. Mixed background C57/BL6-129SvEv mice homozygous or heterozygous for the connexin 36 "knockout" allele displayed potent synergistic interaction between D(1) and D(2) receptor activation, and did not differ significantly from wild-type mice on any measure. All genotypes demonstrated long-lasting stereotypic sniffing, chewing, and/or licking after simultaneous activation of D(1) and D(2) receptors, effects that were absent following selective D(1) or D(2) activation. Swiss-Webster mice treated with the GJ blockers carbenoxolone (35 mg/kg), octanol (350 mg/kg) or mefloquine (50 mg/kg) also demonstrated the normal synergistic interaction between D(1) and D(2) receptors, although these drugs did block the grooming stimulated by selective D(1) receptor activation, independently of D(2) receptors. While D(1) receptor-stimulated grooming depends on GJs composed of connexins or possibly pannexins, the synergistic interaction of D(1) and D(2) receptors in control of stereotypy does not involve GJs.