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It is known that efferent sympathetic nerves reinnervate the kidney following renal denervation (DNX). As there is evidence for lack of cardiac sensory reinnervation following heart transplantation, it has been thought that renal sensory nerves do not reinnervate following renal DNX. This absence of renal sensory reinnervation has been suggested to contribute to the chronic blood pressure reduction (3 years) in humans following renal DNX. However, whether renal sensory reinnervation occurs following acute renal DNX has not been thoroughly examined. Therefore, we assessed renal sensory innervation at multiple time points from 4 days to 12 wks following unilateral surgical DNX + application of phenol to the renal artery in normal Sprague Dawley rats. The contralateral innervated (INN) kidney served as control. Sensory innervation was determined as optical density (ImageJ) of the sensory nerves identified by immunohistochemistry using antibodies against the neuropeptides substance P and calcitonin-gene-related peptide (CGRP) in the renal pelvic wall, as it is a major site of renal sensory innervation. In INN kidneys, optical density of the sensory nerve fibers in the renal pelvic wall was unchanged over the 4 days - 12 wk period (n=17). In DNX kidneys, optical density of the substance P/CGRP containing sensory nerves was 3%, 30%, 50 % and 100% of the control contralateral INN kidney at 4 days, 2 wks, 4 wks and 12 wks, respectively, after DNX. Linear regression of optical density (DNX/INN) versus time yielded similar intercept and slope values for the substance P and CGRP containing sensory nerves (R2 = 0.82 and 0.77, respectively, P<0.001 for both).Conclusion: in normal rats, sensory reinnervation of the renal pelvic wall is complete at 12 wks following acute surgical renal DNX. [ABSTRACT FROM AUTHOR]

Background: Each year, some 18,000 Dutch residents, most of them elderly, suffer a hip fracture. These patients constitute a major, and increasing, healthcare problem with high mortality. In an ageing population, not only the incidence of hip fractures will increase but also comorbidity. Comorbidity is a major cause of high mortality. The physiologic and operative severity score for the enumeration of mortality and morbidity (POSSUM) system predicts mortality and morbidity in surgical patients using physiologic and operative factors., Methods: For 272 consecutive patients who were treated in our hospital for hip fractures, all complications were registered, and orthopedic POSSUM was performed. Total survival was registered with a mean follow-up of 58 months. Discriminating performance of POSSUM was estimated using receiver-operating curves. After validation, patients were divided into three equal large groups, termed low-risk group, intermediate-risk group, and high-risk group. Kaplan-Meier survival curves were made of each group., Results: Orthopedic POSSUM performed well in predicting mortality with an area under the curve of 0.83 (95% confidence interval 0.76-0.89) and morbidity with an area under the curve of 0.83 (95% confidence interval 0.76-0.90). Three groups that composed of 92 (low risk), 93 (intermediate risk), and 87 (high risk) patients differed significantly in inhospital mortality, all complications, severe complications, and total survival., Conclusion: This study has shown that the orthopedic POSSUM is an excellent predictor of inhospital mortality and long-term survival in patients suffering from hip fractures. It is a reasonable predictor of severe postoperative complications. The orthopedic POSSUM is a useful risk stratification and audit tool.

Objective: Epstein-Barr virus (EBV)-positive lymphomas in HIV carriers are paralleled by elevated EBV-DNA loads in the circulation. Approximately 20% of asymptomatic HIV carriers also show elevated circulating EBV-DNA loads. We aimed to characterize the nature of this EBV DNA and to determine the transcriptional phenotype of EBV in blood, in relation to serological parameters., Design: A total of 197 random asymptomatic HIV carriers, representing 2% of the Dutch HIV-positive population, were sampled for blood, peripheral blood mononuclear cells and plasma. In addition, 39 EBV-DNA carriers were sampled twice, with a 5-year interval., Methods: EBV-DNA loads were determined by LightCycler-based real-time polymerase chain reaction (PCR). EBV transcription was studied by nucleic acid sequence-based amplification and reverse transcriptase PCR. IgA and IgG antibodies to EBV antigens EBNA1 and VCA-p18 were quantified by synthetic peptide-based enzyme-linked immunosorbent assay., Results: : Elevated EBV-DNA loads were found in whole blood of 19.3% of the tested HIV population, which were persistent in 82%. Plasma samples were EBV-DNA negative and circulating EBV DNA could be attributed to the B-cell compartment. Transcription of only LMP2 and (non-translated) transcripts from the BamHI-A region of the EBV genome was found, whereas EBNA1, LMP1 and lytic EBV transcripts were absent despite high cellular EBV-DNA loads. IgA-reactivity to VCA-p18 was seen in 69%. IgG to VCA-p18 was significantly higher in high EBV-DNA load carriers., Conclusion: Asymptomatic HIV carriers show aberrant EBV persistence in the circulation, characterized by elevated, B-cell-associated EBV-DNA loads. EBV transcription is restricted, arguing for EBV gene shutdown in circulating EBV-carrying B cells. Increased IgA and IgG reactive to VCA-p18 is indicative of increased lytic EBV replication, possibly occurring at mucosal lymphoid sites but not in the circulation.

We studied the dynamics of CD4 cell counts after the interruption of virologically successful highly active antiretroviral therapy (HAART) in 139 patients. Changes in CD4 cell counts during HAART interruption followed a biphasic pattern: an initial rapid decline during the first month followed by a slow decrease. During 48 weeks of follow-up mean CD4 cell counts remained just above the mean pre-HAART level. This limits the feasibility of structured treatment interruptions for patients with low nadir CD4 cell counts.

An HIV-infected male patient experienced photophobia after a change in dosing regimen that resulted in substantially higher indinavir plasma levels as compared with a reference population. High indinavir levels were suspected to be the cause of photophobia in this patient.

The objective of this study was to evaluate plasma concentrations of nonnucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs) within several dosing schemes in a cohort of HIV-infected patients in routine clinical practice and to find possible explanations for subtherapeutic plasma concentrations. Patients were included if a PI or NNRTI was part of their antiretroviral regimen, at least one plasma concentration was obtained, and a complete medication overview from community pharmacy records was available. The study period was from January 1998 to September 2001. Each plasma concentration was related to median plasma concentrations of a pharmacokinetic reference curve, yielding a concentration ratio (CR). A cutoff CR was defined for each antiretroviral drug per specific regimen, discriminating between >or=therapeutic and subtherapeutic concentrations. For the patients with subtherapeutic concentrations, it was sorted out whether drug interactions, adverse events and self-reported symptoms, or nonadherence could be the cause of the lower than expected plasma concentration. Ninety-seven HIV-infected patients fulfilled the criteria. During the defined period, 1145 plasma concentrations were available (median, 11; interquartile range, 8-14). Three hundred fourteen (27.4%) plasma concentrations were classified subtherapeutic. Drug interactions (2; 0.6%), adverse events and self-reported symptoms (67; 21.3%), and nonadherence (14; 4.5%) could only partly explain the subtherapeutic drug levels. Consequently, a large number of the subtherapeutic plasma concentrations (73.6%) remained inexplicable. A high number of subtherapeutic plasma concentrations were observed. No clear causes were found; thus, corrective measures will be difficult to employ. Therefore, therapeutic drug monitoring (TDM) must maintain its crucial place in routine clinical care to be able to identify patients who need extra attention so that therapeutic plasma concentrations are achieved.