Predictive factors of acute urinary morbidity after iodine-125 brachytherapy for localised prostate cancer: a phase 2 study.

PURPOSE: To analyse predictive factors of acute urinary morbidity after transperineal permanent prostate brachytherapy. METHODS AND MATERIALS: Sixty patients treated in a phase 2 study with iodine-125 brachytherapy (9/1998 to 2/2000) for localised prostate adenocarcinoma were analysed after at least 1-year follow-up. Prescribed dose was 144 Gy and all patients had a pre-planning and a post-implant dosimetry. Urinary morbidity was evaluated prospectively using the Radiation Therapy Oncology Group (RTOG) scale. We examined the relationship between pre-implant ultrasound prostate volume, post-implant CT-scan prostate volume, neoadjuvant hormonotherapy, total number of needles and seeds, post-implant dosimetry variables, first 30 vs. last 30 treated patients and post-implant urinary morbidity. RESULTS: All patients experienced some degree of urinary distress symptoms after treatment. Symptoms were generally mild grade 1 in 56% and grade 2 in 10% lasting less than 6 months. Eight patients (13%) required bladder catheter for acute urinary obstruction. At 1-year follow-up, nine patients (15%) complained from persistent dysuria requiring in three cases endoscopic prostate resection. The percentage of urethra volume receiving 216 Gy (cut-off 40%) and the pre-implant prostate volume (cut-off 31 ml) were the only statistically significant predictor of grade 2-3 or persistent urinary morbidity on multivariate analysis. CONCLUSION: Our short-term data suggest that both pre-implant prostate volume value and post-implant V.U. 150 value might be predictors for urinary morbidity after prostate brachytherapy.     

Comprehensive PKD1 and PKD2 Mutation Analysis in Prenatal Autosomal Dominant Polycystic Kidney Disease

Prenatal forms of autosomal dominant polycystic kidney disease (ADPKD) are rare but can be recurrent in some families, suggesting a common genetic modifying background. Few patients have been reported carrying, in addition to the familial mutation, variation(s) in polycystic kidney disease 1 (PKD1) or HNF1 homeobox B (HNF1B), inherited from the unaffected parent, or biallelic polycystic kidney and hepatic disease 1 (PKHD1) mutations. To assess the frequency of additional variations in PKD1, PKD2, HNF1B, and PKHD1 associated with the familial PKD mutation in early ADPKD, these four genes were screened in 42 patients with early ADPKD in 41 families. Two patients were associated with de novo PKD1 mutations. Forty patients occurred in 39 families with known ADPKD and were associated with PKD1 mutation in 36 families and with PKD2 mutation in two families (no mutation identified in one family). Additional PKD variation(s) (inherited from the unaffected parent when tested) were identified in 15 of 42 patients (37.2%), whereas these variations were observed in 25 of 174 (14.4%, P=0.001) patients with adult ADPKD. No HNF1B variations or PKHD1 biallelic mutations were identified. These results suggest that, at least in some patients, the severity of the cystic disease is inversely correlated with the level of polycystin 1 function.     

Intracellular calcium variations evoked by mechanical stimulation of mammalian isolated vestibular type I hair cells

The variations of intracellular free calcium concentration ([Ca²⁺]_i) were recorded on-line from guinea-pig isolated vestibular sensory cells using a fura-2 fast fluorescent photometry system, during mechanical displacements of the hair bundle. Repetitive displacements of the hair bundle towards the kinocilium (positive stimulation 7°, 300 ms, 2Hz for 10 s), revealed [Ca²⁺]_i variations detectable only in the cuticular plate. [Ca²⁺]_i increased from 105 to 145 nM. Single mechanical displacements of the hair bundle (7°, 200 ms, 0.5Hz) evoked increases of [Ca²⁺]_ifrom 50±23 nM to 139±79 (n=12). In the opposite direction, the mechanical stimulations (8°, 400ms, 0.5Hz) evoked a decrease of [Ca²⁺]_i from 68±17 nM to 37±12 nM (n= 8). The variations of [Ca²⁺]_i detected in the cuticular plate during positive displacements of the hair bundle were reversibly abolished in the presence of 100 M gentamicin and they could not be evoked in 0.1 mM calcium in the external medium. From these experiments, it has been concluded that the [Ca²⁺]_i variations recorded in the cuticular plate were due to a limited entry of calcium ions through transduction channels localized in the hair bundle. The typical kinetics of variations of [Ca²⁺]_i evoked during positive displacements of the hair bundle should account for the presence of strong calcium regulation systems in the hair bundle and cuticular plate.     

Feasibility of azithromycin prophylaxis during a pertussis outbreak among healthcare workers in a university hospital in Paris.

The objective of the present study was to evaluate the feasibility of azithromycin prophylaxis with respect to tolerability and compliance during a pertussis outbreak among healthcare workers in a university hospital ward. Compliance with the prophylaxis regimen was 89%; compliance was 75% from intent-to-treat perspective. The rate of adverse events was 33%. Female sex was associated with reporting of adverse events. Nonstudents and healthcare workers who reported adverse events were less compliant with the prophylaxis regimen.     

community-acquired infection with healthcare-associated methicillin-resistant Staphylococcus aureus: the role of home nursing care.

OBJECTIVE: To better understand the role of indirect transmission in community-acquired infection with methicillin-resistant Staphylococcus aureus (MRSA). DESIGN: Prospective case-control study. SETTING: A French teaching hospital. PATIENTS: A total of 198 case patients and 198 control patients with MRSA or methicillin-susceptible S. aureus infection diagnosed between April 2002 and July 2003. RESULTS: Multivariate analysis showed a highly significant independent link between MRSA infection at admission and prior receipt of home nursing care (odds ratio [OR], 3.7; P<.001). Other independent risk factors were prior hospitalization (OR, 3.8; P<.001), transfer from another institution (OR, 2.3; P=.008), and age older than 65 years (OR, 1.6; P=.04). Prior home nursing care showed a frequency dose-response relationship. Eleven MRSA-infected patients had had home nursing procedures but no hospital stay in the previous 3 years. These patients' MRSA strains were related to the prevalent MRSA clone currently spreading in French hospitals. CONCLUSION: Home nursing care appears to be an independent risk factor for MRSA acquisition in the community. The reservoir probably consists of MRSA carriers discharged from the hospital. Community nurses seem to be a potential vector.     

Antimycobacterial calixarenes enhance innate defense mechanisms in murine macrophages and induce control of Mycobacterium tuberculosis infection in mice

Tuberculosis remains the leading cause of death among infectious diseases, accounting for more than two million deaths annually. The incidence of the disease is increasing globally, partially because of the resurgence of drug-resistant strains of Mycobacterium tuberculosis. Calixarenes are macrocyclic oligomers, some of which are able to modify the growth of M. tuberculosis in infected cells. Most experimental work has been carried out with Macrocyclon, also known as HOC 12.5EO. In this study, we demonstrate that Macrocyclon is effective in controlling M. tuberculosis infections, and we provide evidence that its effect is partially mediated by an l-arginine-dependent mechanism of macrophage activation that involves the activity of the inducible nitric oxide synthase. We also show that Macrocyclon is effective in athymic and major histocompatibility complex class II-/- mice and synthesized a number of structurally related calixarenes expressing significant antimycobacterial activity.     

Neurotoxicity and neuroprotection, two aspects of microglial activation in human immunodeficiency virus (HIV) infection

Microglial cells and macrophages are the only cells within the central nervous system, in which productive HIV infection has been unquestionably demonstrated. Those cells play a key role in the origin of the neuronal dysfunction underlying HIV-related cognitive disorders. The neurotoxicity of the cells is both direct, related to HIV proteins, and indirect, through the release by activated macrophages and microglial cells (AMM) of multiple neurotoxic factors. The mechanisms of neuronal damage, the final irreversible stage of which is neuronal apoptosis, are only partly understood but appear to involve oxidative stress and glutamate-receptor mediated toxicity. On the other hand, recent experimental in vitro and in vivo studies, and neuropathological studies in HIV infected patients at different stages of the disease, tend to show that AMM express excitatory amino acid transporters (EAAT) suggesting that in addition to their neurotoxic properties, they also have a neuroprotective role by clearing extra-cellular glutamate and producing antioxidant glutathione. This neuroprotective role could counteract, at least in the early stages of the disease, the neurotoxicity of AMM explaining the discrepancy between the conspicuous microglial activation at that stage and the absence of cognitive disorder, neuronal loss and neuronal apoptosis. It could also explain the regression of the cognitive disorders in some patients who received highly active antiretroviral treatment.     

Calpastatin overexpression in the skeletal muscle of mice prevents clenbuterol-induced muscle hypertrophy and phenotypic shift

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