Microscopic polyangiitis. A systemic vasculitis with a positive P-ANCA

A young girl presented with a purpuric rash on lower limbs, fever, eosinophilia, peripheral neuropathy and progressive renal insufficiency. She developed vesicles, purpuric macules and papules on the head, several nodules on the palmar sides of hands and lingers, splinter haemorrhages, and a disfiguring, facial oedema. A renal biopsy specimen disclosed a focal and segmental necrotizing glomerulonephritis with crescents. Peripheral ANCA with antimyeloperoxidase specificity [P-ANCA (MPO)] was positive and cytoplasmic ANCA with PR 3 specificity was negative. Treatment with prednisone and cyclophosphamide was started with a good clinical response, stabilization of renal insufficiency and disappearance of P-ANCA (MPO). Our case fulfils the diagnostic criteria for microscopic polyangiitis (microscopic polyarteritis, MPA). namely a segmental necrotizing and crescentic glomerulonephritis associated with extrarenal vasculitis involving small-sized vessels, without granulomas or asthma. This is a rare disease, which has a poor prognosis in the absence of aggressive therapy, and is infrequently reported in dermatological journals.     

Transhepatic removal of obstructed Carey-Coons biliary endoprosthesis

A criticism of the use of an endoprosthesis for relief of biliary obstruction has been the difficulty of removing or exchanging the endoprosthesis if it becomes obstructed. We present a simple method of removal that has been successful in four of five patients who presented with an obstructed endoprosthesis 3-7 months after placement.     

Rifampicin-associated acute renal failure: pathophysiologic, immunologic, and clinical features

A 71-year-old woman was treated for a relapsing pulmonary tuberculosis with reinstitution of rifampicin after a medication-free interval of 2 years. After ingestion of the second dose, she developed severe hemolytic anemia and acute renal failure (ARF) necessitating dialysis. We demonstrated the presence in the patient's serum of rifampicin-dependent immunoglobulin G (IgG) and IgM antibodies, which caused red blood cell lysis through interaction with the I antigen on the erythrocyte surface. A review of the literature yielded 48 cases of rifampicin-associated renal failure. A subgroup of 37 patients could be distinguished, which, analogous to our case, suddenly developed ARF and frequently also developed hemolytic anemia and/or thrombocytopenia during intermittent or interrupted treatment. Regarding the pathogenesis of the ARF, renal biopsy consistently revealed tubular lesions. Although intravascular hemolysis with hemoglobinuria may play a role, it is not uniformly present. Our demonstration of an antibody with anti-I specificity provides a possible explanation. The I antigen is also expressed on tubular epithelium and may, therefore, be the target structure through which rifampicin-antibody complexes lead to tubular cell destruction. The other cases of rifampicin-associated ARF were unrelated to this subgroup: two cases of rapidly progressive glomerulonephritis, five cases of acute interstitial nephritis, and four cases of light chain proteinuria were recorded.     

Measures of cardiac repolarization and body position in infants

Sudden Infant Death Syndrome (SIDS) is the most common cause of death in children between 1 and 6 months of age. Recent data suggest that a prolonged QTc interval on the 12-lead electrocardiogram (ECG) is associated with SIDS. Prone body position during sleep is also known to be a risk factor for SIDS; this has prompted the American Academy of Pediatrics to promote the "Back to Sleep" campaign. We postulated that the QTc interval in infants might change as a function of body position, linking the observations relating body position and QTc interval to SIDS. We recorded ECGs in a group of infants in both the supine and prone position to determine if the QTc interval and QT dispersion differ between the 2 positions. Forty-seven standard 12-lead EGGs and high-amplitude, rapid-sweep 12-lead EGGs were performed on 45 healthy infants (mean age 26 +/- 40 days) in both the supine and prone positions. The infants were asleep in a quiet, restful state. The ECGs were reviewed by 2 investigators blinded to the position of the infants during recording. Measurements included the average QTc interval (using Bazett's correction) and QT dispersion (the difference between the longest and the shortest QT intervals on a standard 12-lead EKG). The study was designed to detect a 3% difference in QTc interval with 80% power and alpha = 0.05. All subjects had telephone or clinical follow-up at 1 year. The average QTc interval was 403 +/- 20 milliseconds (msec) in the supine position and 405 +/- 27 msec in the prone position (p = NS). The QT dispersion was 20 +/- 12 msec in the supine position and 22 +/- 13 msec in the prone position (p = NS). One infant in the study group died of SIDS at the age of 3 months. The EGG of this patient revealed a QTc interval of 382 msec in the supine position and 407 msec in the prone position; the QT dispersion was 34 msec in the supine position and 34 msec in the prone position. We found no difference in QTc interval or QT dispersion as a function of body position in healthy infants resting quietly. Prolongation of the QTc interval is unlikely to explain the increased risk for SIDS associated with prone body position in the general population of healthy infants, unless patients with long QT syndrome are somehow more influenced by body position than normal patients are.     

In vitro effects of fluoroquinolone and aminoglycoside antibiotics on human keratocytes

PURPOSE: The purpose of this study was to assess the cytotoxic effects of the fluoquinolone ofloxacin and the aminoglycoside netilmicin on stromal human keratocytes in vitro. METHODS: Cultured human keratocytes were exposed to various concentrations of ofloxacin or netilmicin (0.16-5.0 mg/mL). Both cell proliferation (MTT assay) and cell morphology (phase-contrast microscopy) were evaluated after 1, 4, 12, and 24 hours of incubation. Measurement of annexin V binding performed in association with the dye exclusion test using propidium iodide (PI) was also performed by FACS analysis after 4 hours of exposure. RESULTS: Both antimicrobials induced dose- and time-dependent morphologic changes in keratocytes, yet the effects of netilmicin were minimal. After 24 hours of exposure, both drugs induced a dose-dependent inhibition of cell proliferation; however, ofloxacin demonstrated significantly more toxic effects than netilmicin (t test for ED50 values, P < 0.0001). Statistical differences between 2 antibiotics start at concentrations above 1.25 mg/mL (ANOVA with post-hoc test, P < 0.01). Expression of the apoptotic marker annexin V was unaffected by antibiotic exposure, whereas the uptake of the necrotic marker PI was increased by ofloxacin (5 mg/mL) but not by netilmicin (ofloxacin versus netilmicin, ANOVA, P < 0.05). CONCLUSIONS: Relative effects of aminoglycosides and fluoroquinolones on stromal keratocytes appear to be different: netilmicin was shown to be significantly less toxic than ofloxacin. This finding is particularly relevant in deciding the optimal antibiotic to be applied in clinical situations in which the epithelium is absent or compromised, as after photorefractive keratectomy, alkali burns, or ulcerative keratitis.