Nilutamide pneumonitis: a report on eight patients.

BACKGROUND: Nilutamide is a new, specific synthetic antiandrogen, released in several countries for the treatment of metastatic carcinoma of the prostate. Eight patients at the University Medical Centre at Dijon and affiliated referring hospitals developed reversible pulmonary opacities and respiratory symptoms while taking the drug. METHODS: Records of eight patients who developed new, otherwise unexplained chest opacities while taking nilutamide were reviewed. In each patient a careful aetiological search was made for other environmental or endogenous causes. Six patients underwent bronchoalveolar lavage, and lavage fluid was cultured. Corticosteroids were not given, unless gas exchange was compromised (two patients). RESULTS: The eight patients (all male) had had carcinoma of the prostate diagnosed on average 10.2 months earlier. All had improved with nilutamide, with a dramatic decrease of prostate specific antigen levels. Seven had received nilutamide at the recommended dosage of 150 mg/day, and one had received twice that amount. Treatment had lasted on average 113 (range 10-225) days, and the mean cumulated exposure was 21.8 (3-38) grams. The chest radiographs showed bilateral infiltrates, with no consistent topographic predilection. A restrictive lung defect was present in six patients and hypoxia in all (mean arterial oxygen tension (PaO2) 6.6 kPa). Bronchoalveolar lavage showed lymphocytosis in four patients and neutrophilia in two. The outcome was favourable in all patients after they had stopped nilutamide only (five patients), with corticosteroids (two patients) or a simple reduction of nilutamide from 300 to 150 mg/day (one patient). Recovery was associated with improvement of pulmonary function and PaO2. CONCLUSION: Nilutamide is associated with interstitial pneumonitis in about 1% of patients and appears reversible.     

Systemic injection of products of activated neutrophils and H2O2 in myeloperoxidase-immunized rats leads to necrotizing vasculitis in the lungs and gut.

The strong association of anti-neutrophil cytoplasmic antibodies with various forms of systemic vasculitis suggests a role for these autoantibodies in the pathophysiology of systemic vasculitis. In the present study, we tested the hypothesis that release of neutrophil lysosomal enzymes in the presence of an anti-myeloperoxidase (anti-MPO) immune response may underlie the development of systemic vasculitis. Brown Norway rats were immunized with MPO in complete Freund's adjuvant or complete Freund's adjuvant alone. Two weeks after immunization, rats bad developed antibodies to human and rat MPO as measured by enzyme-linked immunosorbent assay. Next, rats were intravenously infused with 400 micrograms of a human neutrophil lysosomal extract containing 200 micrograms of MPO followed by 0.5 ml of a 1 mmol/L solution of H2O2 through a cannula inserted into the right jugular vein. Rats were sacrificed at 4 hours, 24 hours, 7 days, or 14 days, and several organs (lungs, heart, liver, spleen, gut, and kidneys) were examined for vasculitic lesions and inflammatory cell infiltrates. Macroscopically, patchy hemorrhagic spots were observed in the lungs and gut of MPO-immunized rats at days 7 and 14 after systemic infection of the neutrophil lysosomal extract and H2O2. Such changes were not observed at earlier time points or in control immunized rats. Histologically, the lungs of MPO-immunized rats sacrificed at days 7 and 14 showed patchy inflammatory cell infiltrates associated with vasculitis, granuloma formation, giant cells, and foci of hemorrhage. At 14 days, early signs of fibrosis were found with deposition of collagen and proliferation of fibroblasts. Furthermore, a prominent leukocytoclastic vasculitis was found in the small intestine of these rats characterized by fibrinoid necrosis and an extensive neutrophilic infiltrate. No inflammatory changes were found in the other organs studied (heart, liver, spleen, and kidneys). Control immunized rats, sacrificed at days 7 and 14 showed only some small foci of inflammatory infiltrates in the lungs whereas no inflammatory changes were found in the gastrointestinal tract. These studies show that release of products from activated neutrophils in the presence of anti-MPO autoantibodies may be relevant to the pathogenesis of anti-MPO-associated vasculitides.     

Hypoesthesia after anterior cruciate ligament reconstruction: The relationship between proprioception and vibration perception deficits in individuals greater than one year post-surgery

Background

While surgical reconstruction restores mechanical stability following anterior cruciate ligament (ACL) rupture, many experience early-onset osteoarthritis despite surgery. Neurophysiological changes are hypothesized to contribute to knee osteoarthritis progression. Proprioceptive deficits have been reported following ACL injury/reconstruction; however, vibration perception threshold (VPT) has been less studied. This study explored relationships between pain, VPT, proprioception, function, and strength following ACL-reconstruction.

Predictive value of early HCV RNA quantitation for sustained response in nonresponders receiving daily interferon and ribavirin therapy

The prognostic value of early hepatitis C virus (HCV)-RNA load was evaluated among nonresponder patients to previous interferon (IFN) therapy treated with daily IFN and ribavirin. One hundred-six nonresponders (83 men), mean age 44.8 +/- 11 years, were treated with IFN-alpha 2b 3 MU/day for 24 weeks, followed by 3 MU x 3/week for 24 weeks plus ribavirin 1-1.2 g/day for 48 weeks. HCV RNA was quantified by Versant HCV RNA 3.0 assay (Bayer). The predictive values of the baseline and the change in viral load at week 1, 4, and 12 for sustained virological responses were analyzed using receiver operating characteristic (ROC) curves, as well as predictive values of >2 log(10) drop from baseline by weeks 1, 4, and 12 in combination with undetectable HCV RNA for sustained virological response. Thirty-two patients (30.2%) were sustained virological responders. The highest area under the curve was obtained at week 4. The unquantifiable HCV RNA level, in combination with at least a 2 log(10) drop in viral load by week 4 and week 12, had a negative predictive value of 96% and 97%, respectively. Nonresponse can be predicted as early as week 4 or week 12 in nonresponders treated with daily IFN and ribavirin.     

Carpal tunnel release by the Agee endoscopic technique. Results at 4 year follow-up

Ninety-five hands (86 patients) were treated by endoscopic carpal tunnel release using the technique of Agee. They were the first ones operated on by the senior author (GF) using this technique. The patients were interviewed at a mean follow-up of 4.5 years: 72% of hands were free of symptoms and 94% were described by the patients as functionally normal. Seventeen hands (out of 27) with residual or recurrent symptoms were examined. Nine hands (nine patients) were only partially improved (mean 6.7 on a 10 point scale) and in eight hands (seven patients), some symptoms had recurred after a mean delay of 3.8 years. It was possible to find a second pathology in most of these cases. It is necessary to inform the patient before operation that incomplete relief or recurrence of symptoms can occur after endoscopic carpal tunnel release, as with conventional release.     

Indications and results of skin flaps in painful digital neuroma

Of the many procedures for treating painful neuromas, resection and proximal translocation are the most usual techniques, but these can decrease distal sensibility increasing deafferentation pain. In cases of intricate pain (nociception plus deafferentation), certain types of flaps allow the treatment of both components of the pain. We have used 30 such flaps in 28 patients: local flaps (exchange, advancement or lasso island flaps) and distant flaps (free "custom-made" toe flaps). The results of the different techniques provides 86.6% excellent or good results.     

Murine Typhus,Reunion, France, 2011–2013

Murine typhus case was initially identified in Reunion, France, in 2012 in a tourist. Our investigation confirmed 8 autochthonous cases that occurred during January 2011–January 2013 in Reunion. Murine typhus should be considered in local patients and in travelers returning from Reunion who have fevers of unknown origin.     

Plasmocytose sanguine et dengue : une anomalie biologique sous-estimée ?

Introduction

A significant peripheral blood plasmacytosis is a rare finding associated with viral infections. We reported five consecutive cases of dengue virus infection, with circulating plasma cells.

Case reports

Three women and two men, aged 26 to 75 years, had returned from French West Indies less than one week before the onset of the symptoms (mean: 2.5 days). The transient blood plasmacytosis was variable in intensity (0.1 to 0.8 G/L) with a maximal level between the fourth and the seventh day following the onset of the symptoms, and was associated in four patients, with activated lymphocytes and lympho-plasma cells.

Conclusion

Reactive plasmacytosis during dengue fever is common and probably underestimated because it is transient and only identified by careful microscopic examination of a blood smear. Plasmacytosis could be explained by the intensity of the immunological response and the production of large amount of interleukins.