Mycobacterial Infections After Renal Transplantation

Mycobacterial infections occurred in 11 of 633 (1.7 per cent)recipients of successful renal transplants. There were no casesof tuberculosis in patients receiving chemoprophylaxis, butamongst those who did not receive prophylaxis disease occurredin six of the 27 (22 per cent) high-risk patients. The majorcause of morbidity during treatment was renal allograft rejection,largely due to reduction in immunosuppressive drug therapy.     

Hepatitis C virus among blood donors: follow-up study

BACKGROUND: The exact significance of antibodies to hepatitis C virus (HCV) in blood donors remains unknown. Confirmatory tests of anti-HCV- reactive serum and HCV RNA by polymerase chain reaction (PCR) are used to refute a large proportion of false-positive results. STUDY DESIGN AND METHODS: Ninety-two blood donors who were anti-HCV reactive in a first-generation enzyme-linked immunosorbent assay (ELISA) were reevaluated 10 months later with a second-generation ELISA (ELISA-2) as well as with second-generation recombinant immunoblot assay (RIBA-2) and by PCR. RESULTS: Twenty-five (43.9%) of the 57 ELISA-2-positive donors were confirmed as positive by RIBA-2; of these, 84 percent were HCV RNA positive in PCR. Of the 57 who were still anti-HCV positive, 46 were followed up and tested again in the same manner 2 years after the first screening. At that time, the pattern was little changed: 94 percent of RIBA-2- and PCR-positive donors remained positive. Of RIBA-2- and PCR-positive blood donors, 62 percent had abnormal alanine aminotransferase levels in at least one of the three evaluations. Among the anti-HCV-positive donors confirmed by RIBA-2, 60 percent, versus 12.6 percent in the control group, had a significantly (p < 0.001) more frequent risk factor for HCV infection, due to parenteral exposure to blood. CONCLUSION: These data confirm a good correlation between RIBA-2 reactivity and the detection of HCV RNA in a population of anti-HCV- positive blood donors.     

Fluoxetine in orthostatic hypotension of Parkinson's disease: A clinical and experimental pilot study

Summary— Recent clinical studies have reported a beneficial effect of fluoxetine, a serotonin reuptake inhibitor, in patients with severe refractory orthostatic hypotension. The present study was undertaken to investigate the effect of fluoxetine in orthostatic hypotension occurring during Parkinson's disease on both blood pressure values and number of clinical symptoms during orthostatic procedure evaluated using a validated clinical rating scale. In a pilot study performed in fourteen patients with idiopathic Parkinson's disease plus orthostatic hypotension, fluoxetine hydrochloride (20 mg orally daily during one month) significantly reduced the fall in systolic blood pressure [-33 ± 21 (SD) mmHg before fluoxetine vs -22 ± 19 mmHg after fluoxetine, P = 0.03] elicited by standing without modifying heart rate. The drug also significantly reduced the number of postural symptoms occurring during the orthostatic procedure [2.9 ± 1.5 (SD) before fluoxetine vs 1.2 ± 1.3 after fluoxetine, P = 0.006]. A similar pattern of response was obtained in an experimental model of neurogenic orthostatic hypotension obtained in chronically sino-aortic denervated dogs submitted to an 80° head-up tilt test procedure under chloralose anaesthesia. Fluoxetine did not change plasma noradrenaline levels. This pilot study suggests a slight but clinically significant effect of fluoxetine on both hemodynamic parameters and clinical symptoms in parkinsonian patients suffering from orthostatic hypotension.     

Tuberculosis in Patients Infected with Human Immunodeficiency Virus 1. A Retrospective Multicentre Study of 123 Cases in France

SUMMARY In order to study the epidemiological, clinical, and progressivecharacteristics of TB in HIV-infected individuals, a retrospectivestudy was conducted in nine infectious disease centres of universityhospitals located in the southern half of France. Among the5730 HIV-seropositive in- and out-patients, 123 (2.1 per cent)had TB (121 infections caused by M. tuberculosis, 2 by M. bovis).Tuberculosis was pulmonary in 53 patients (43.1 per cent), extrapulmonaryin 36 patients (29.3 per cent), and combined in 34 patients(27.6 per cent). There was no statistically significant differenceamong these three locations as to the mean CD4 count/mm³ (160±17),the type of antituberculosis therapy, the length of treatment(10.8±0.6 months) and the outcome. Fifty-two (45.2 percent) patients received an initial antituberculosis therapeuticregimen of four drugs: isoniazid, rifampicin, ethambutol, pyrazinamide;54 (46.9 per cent) were started on three drugs: isoniazid, rifampicin,ethambutol; and nine (7.8 per cent) received a two-drug combination:isoniazid, rifampicin. Fourteen of 75 patients subsequentlyreceived secondary preventive therapy. The mean follow-up timewas 252±290 days. Clinical healing was obtained in 57.7per cent of patients. Forty-six patients died, 33 during treatment:23 from AIDS and eight from TB (in the first 3 weeks of treatment).Five patients suffered from relapses due to poor treatment compliance.Patients had a good prognosis if tuberculosis was diagnosedearly.     

Opportunistic infections and organ‐specific diseases in HIV‐1‐infected children: a cohort study (1990–2006)

Objectives

Highly active antiretroviral therapy (HAART) has dramatically changed the natural history of HIV infection in children, but there are few studies in the literature about the incidence of clinical manifestations after HAART in this population, compared with adults. The aim of this study was to describe the influence of the widespread use of HAART on the development of opportunistic infections and organ‐specific diseases in HIV‐infected children.

Methods

An observational study of a cohort of 366 vertically HIV‐infected children followed from 1990 to 2006 was carried out. According to the main antiretroviral protocol used, three calendar periods (CPs) were defined and compared: CP1 (1990–1996: no patients on HAART), CP2 (1997–1999: <60% on HAART) and CP3 (2000–2006: >60% on HAART).

Results

Children experienced a progressive increase in CD4 T cell count (P<0.05) and a decrease in HIV viral load from 1996 onwards (P<0.05). Similarly, rates of death, AIDS, opportunistic infections (bacteraemia, candidosis, cryptosporidiosis and bacterial pneumonia) and organ‐specific diseases (wasting syndrome, thrombocytopenia, cardiomyopathy, lymphoid interstitial pneumonia and HIV‐associated encephalopathy) were lower in CP2 and CP3 than in CP1.

Conclusions

This study provides evidence of improved clinical outcomes in HIV‐infected children over time and shows that mortality, AIDS, opportunistic infections and organ‐specific diseases declined as HAART was progressively instituted in this population.

     

Diagnosis of advanced fibrosis in HIV and hepatitis C virus-coinfected patients via a new noninvasive index: the HGM-3 index

Background

Noninvasive tests are increasingly being used for the assessment of liver fibrosis. We aimed to develop a serum index for the identification of advanced fibrosis (F≥3) in HIV/hepatitis C virus (HCV)‐coinfected patients.

Methods

We carried out a cross‐sectional study on a group of 195 patients comprised of an estimation group (EG; n=127) and a validation group (VG; n=68) who all underwent liver biopsy and had not received previous interferon therapy. Liver fibrosis was estimated using the METAVIR score. We developed a new serum index (HGM‐3) dependent on levels of platelets, alkaline phosphatase, hepatic growth factor, tissue inhibitor of metalloproteinase‐1 and hyaluronic acid.

Results

In the EG, the area under the receiver operating characteristic curve (AUC‐ROC) of HGM‐3 for identification of F≥3 was 0.939 [95% confidence interval (CI) 0.899, 0.979] which was significantly higher than the AUC‐ROC of the HGM‐2, FIB‐4, aspartate aminotransferase to platelet ratio (APRI) and Forns' indexes. With HGM‐3 <0.135 for F<3, 57 patients were correctly identified and two patients were misclassified. We found the presence of F<3 with 96.6% certainty. The negative likelihood ratio (LR) was <0.1 and the diagnostic odds ratio (DOR) was >40. With HGM‐3 >0.570 in the EG for F≥3, 31 patients were correctly identified, and five patients were misclassified. We found the presence of F≥3 with 86.1% certainty. The positive LR was >12 and the DOR was >40. For the VG, the diagnostic accuracy values were similar to the values for the EG.

Conclusions

HGM‐3 appears to be an accurate noninvasive method for the diagnosis of bridging fibrosis and cirrhosis in HIV/HCV‐coinfected patients.     

p.R254Q mutation in the aquaporin‐2 water channel causing dominant nephrogenic diabetes insipidus is due to a lack of arginine vasopressin‐induced phosphorylation

Vasopressin regulates human water homeostasis by re‐distributing homotetrameric aquaporin‐2 (AQP2) water channels from intracellular vesicles to the apical membrane of renal principal cells, a process in which phosphorylation of AQP2 at S256 by cAMP‐dependent protein kinase A (PKA) is thought to be essential. Dominant nephrogenic diabetes insipidus (NDI), a disease in which the kidney is unable to concentrate urine in response to vasopressin, is caused by AQP2 gene mutations. Here, we investigated a reported patient case of dominant NDI caused by a novel p.R254Q mutation. Expressed in oocytes, AQP2‐p.R254Q appeared to be a functional water channel, but was impaired in its transport to the cell surface to the same degree as AQP2‐p.S256A, which mimics non‐phosphorylated AQP2. In polarized MDCK cells, AQP2‐p.R254Q was retained and was distributed similarly to that of unstimulated wt‐AQP2 or AQP2‐p.S256A. Upon co‐expression, AQP2‐p.R254Q interacted with, and retained wt‐AQP2 in intracellular vesicles. In contrast to wild‐type AQP2, forskolin did not increase AQP2‐p.R254Q phosphorylation at S256 or its translocation to the apical membrane. Mimicking constitutive phosphorylation in AQP2‐p.R254Q with the p.S256D mutation, however, rescued its apical membrane expression. These date indicate that a lack of S256 phosphorylation is the sole cause of dominant NDI here, and thereby, p.R254Q is a loss of function instead of a gain of function mutation in dominant NDI. © 2009 Wiley‐Liss, Inc.     

Factors associated with health care-acquired urinary tract infection

BACKGROUND: Health care-acquired urinary tract infection is common, and the risk factors should be understood by those who manage hospitalized patients and researchers interested in interventions and programs designed to reduce rates. METHODS: We used multivariable logistic regression to identify factors that demonstrated a statistical association with infection. RESULTS: The incidence rate for infection was 1.66%, and risks increased for patients with prolonged length of stay (odd ratio [OR], 5.28; 95% confidence interval [CI]: 2.46-11.34), urinary catheter (OR, 5.16; 95% CI: 2.84-9.36), unresolved spinal injury (OR, 4.07; 95% CI: 1.04-15.92), transfer to/from another hospital (OR, 2.9; 95% CI: 1.39-6.04), some assistance for daily living prior to admission (OR, 2.58; 95% CI: 1.51-4.41), underlying neurologic disease (OR, 2.59; 95% CI: 1.49-4.49), previous stroke (OR, 1.94; 95% CI: 1.03-3.67), and fracture or dislocation on admission (OR, 3.34; 95% CI: 1.75-6.38). Male sex was protective (OR, 0.44; 95% CI: 0.26-0.77). CONCLUSION: Our data describe a general hospital population and therefore have relevance to many hospital-based health care professionals. The statistical model is a good fit to the data and has good predictive power. We identify high-risk groups and confirm the need for good decision making for managing the risks of health care-acquired urinary tract infection. This requires information on the effectiveness of risk-reducing strategies and the changes to economic costs and health benefits that result and the synthesis of these data in appropriately designed economic models.     

LRTOMT: a new tone in understanding the symphony of non-syndromic deafness

Mutations of LRTOMT, a fusion gene with alternative reading frames, cause nonsyndromic deafness in humans
Ahmed et al. (2008)
Nature Genetics 40: 1335–1340.