Mechanisms of T cell-induced glomerular injury in anti-glomeruler basement membrane (GBM) glomerulonephritis in rats

The effector mechanisms of T cell-dependent acute glomerular injury were studied in autologous phase anti-GBM glomerulonephritis (GN) in rats. Acute proliferative GN was induced in sensitized rats by a subnephritogenic dose of sheep anti-rat GBM antibody. Injury was manifested by proteinuria and glomerular leucocyte infiltration composed predominantly of macrophages but also CD4⁺ and CD8⁺ T cells. T cell depletion, using an anti-CD5 MoAb, demonstrated that glomerular leucocyte infiltration and proteinuria were T cell-dependent. Inhibition of T helper cell function using an anti-CD4 MoAb prevented proteinuria and glomerular macrophage and CD4⁺ T cell influx, but not accumulation of CD8⁺ T cells. Depletion of CD8⁺ T cells also prevented proteinuria and the influx of macrophages and CD8⁺ T cells, but not accumulation of CD4⁺ T cells. Macrophage depletion, using micro-encapsulated clodronate, prevented proteinuria and glomerular macrophage infiltration, but not the accumulation of CD4⁺ or CD8⁺ T cells, indicating that macrophages are the common cellular effectors for both CD4 and CD8 T cell-dependent injury. Evidence for cytotoxic mechanisms of injury (increased numbers of apoptotic cells or accumulation of natural killer (NK) cells in glomeruli) could not be demonstrated. These data suggest that acute glomerular injury in anti-GBM GN is the result of macrophage recruitment, which is dependent on both CD4 and CD8 T cells, and that direct T cell-mediated injury (cellular cytotoxicity) is not involved.     

ORTHOTOPIC BLADDER SUBSTITUTION AFTER RADICAL CYSTECTOMY: 5 YEARS OF EXPERIENCE WITH A NOVEL PERSONAL MODIFICATION OF THE ILEAL S POUCH

PURPOSE: We report a 5-year experience with 52 patients who underwent radical cystoprostatectomy for bladder cancer and orthotopic bladder substitution using a novel personal modification of the S pouch. MATERIALS AND METHODS: From September 1995 to December 1999, 52 men 36 to 72 years old (mean age 63) underwent bladder substitution with an S pouch. They were followed until September 2000. The pouch was constructed with a 36 cm. segment of ileum with the whole length used for the reservoir. The ureters were directly anastomosed with one above the other in the mid segment of the pouch without any antireflux procedure. Complications were documented and classified as early or up to 3 months postoperatively and late, and further subdivided by the relationship to neobladder construction. Continence and voiding pattern were evaluated by personal interview and neobladder function was urodynamically assessed. Mean followup in our patients was 30 months. RESULTS: The most common of the 5 early and 9 late neobladder related complications were persistent urine leakage and reflux, respectively. There was no reflux greater than grade III in the 4 patients with reflux (5 refluxing ureters) and no functional disorders. We observed 12 early and 5 late complications unrelated to the neobladder. Open reoperation was required in 5 cases. Good or satisfactory daytime and nighttime continence was reported by 95% and 88% of our patients, respectively. By year 1 postoperatively 91% of our patients voided at an interval of 3 to 5 hours during the day. Mean maximum neobladder capacity was 672 ml. and mean post-void residual was 30 ml. by year 3 postoperatively. Two patients required self-catheterization once daily and mild hyperchloremia without acidosis developed in 2. CONCLUSIONS: The advantages of our modified S pouch are technical simplicity, substantially shorter operative time and decreased bowel length required. It is associated with an acceptable complication rate and functional parameters with subsequent patient satisfaction and good quality of life.     

Arrhythmogenic Right Ventricular Cardiomyopathy in an Octogenarian Presenting with Ventricular Tachycardia

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is one of the major causes of sudden death. Myocardial atrophy with subsequent fibro‐fatty replacement predominantly affects right ventricular myocardium and results in global and regional dysfunction as well as areas of slow conduction and dispersion of refractoriness, which are prerequisites for reentrant ventricular tachyarrhythmias. ARVC is commonly presented in patients <65 years old. However, few cases of elderly people suffering from this cardiomyopathy have been reported in the literature. We present a case of an 82‐year‐old woman with sustained ventricular tachycardia due to first diagnosed ARVC.     

COMPARATIVE EVALUATION OF THE DIAGNOSTIC PERFORMANCE OF THE BTA STAT TEST, NMP22 AND URINARY BLADDER CANCER ANTIGEN FOR PRIMARY AND RECURRENT BLADDER TUMORS

PURPOSE: We compared overall sensitivity and specificity of the urinary bladder cancer antigen enzyme-linked immunosorbent assay (UBC, IDL Biotech, Sollentuna, Sweden), BTA stat test (Bion Diagnostic Sciences, Inc., Redmond, Washington) and NMP22 test kit (Matritech, Newton, Massachusetts), and the differential sensitivity regarding the histological pattern of tumors. MATERIALS AND METHODS: A total of 213 patients with clinical and/or imaging signs of bladder cancer provided a single voided urine sample for the bladder cancer antigen, BTA stat test and NMP22 before cystoscopy. Of these patients 95 were monitored for superficial bladder cancer, while the remaining 118 had no history of bladder cancer. All detected bladder tumors or suspicious lesions were resected transurethrally. A group of 21 age and sex matched healthy volunteers were also evaluated with the same tests. RESULTS: Bladder cancer was confirmed histologically in 118 patients, of whom primary and recurrent tumors were in 68 and 50, respectively. The optimal cutoffs calculated with receiver operating characteristics curves were 8 units per ml. for NMP22 and 12 microg./l. for bladder cancer antigen. Overall sensitivity and specificity were 72.9% and 64.6% for the BTA stat test, 63.5% and 75.0% for NMP22, and 80.5% and 80.2%, respectively, for bladder cancer antigen. Bladder cancer antigen proved significantly more sensitive than NMP22 for detecting bladder cancer (p = 0.001) but not more than the BTA stat test, while the specificity of it was significantly higher than that of the BTA stat test (p = 0.009). Bladder cancer antigen had a sensitivity of 80.7% for stage Ta tumors, which was significantly higher than NMP22 (52.6%, p = 0.001) and the BTA stat test (57.9%, p = 0.01). In grade I tumors the sensitivity of bladder cancer antigen (70%) did not differ significantly than that of the BTA stat test (50%) and NMP22 (50%, p = 0.14). Bladder cancer antigen had the least false-positive results in patients with a history of bladder cancer and negative cystoscopy, and those with urological disease other than bladder cancer. CONCLUSIONS: Our data indicate that bladder cancer antigen may be a more potent diagnostic marker for bladder cancer than NMP22 and the BTA stat test based on the higher sensitivity for detecting low stage and low grade tumors, and the higher specificity. The contribution of these tests for detection of bladder cancer should still be considered adjunctive to cystoscopy.     

Polymorphic Ventricular Tachycardia Induced During Tilt Table Testing in a Patient with Syncope and Probable Dysfunction of the Sinus Node

We present a case of life-threatening arrhythmia occurring during tilt table testing in a 44-year-old man with syncope. Polymorphic ventricular tachycardia occurred while the patient was tilted up under the intravenous infusion of isoproterenol (2 μg/min). No ischemia, QTc prolongation, or electrolyte abnormality preceded this event. The arrhythmia was not induced by programmed ventricular stimulation or exercise testing. Based on electrophysiological and clinical data, the diagnosis of sick sinus syndrome was entertained.     

Effects of ketanserin on epicardial coronary arteries after coronary angioplasty in patients with stable angina

Previous studies have demonstrated the development of vasoconstrictionimmediately after percutanous coronary angioplasty (PTCA), distalto the dilated stenosis, presumably resulting from endothelialinjury. We have investigated the role of 5-HT₂ receptors inmediating vasomotor changes in proximal and distal coronarysegments and coronary stenoses, immediately after successfulPTCA in patients with chronic stable angina. We compared theeffects of the intracoronary infusion of 1 mg ketanserin (5-HT₂receptor antagonist) on proximal and distal coronary arterialsegments immediately after PTCA in both vessels subjected toPTCA and control vessels. Coronary diameters, before and afterangioplasty and after ketanserin administration, of proximaland distal segments and coronary stenoses were measured by computerizedquantitative coronary angiography (CAAS system) in 12 patients(10 male, two female; mean age 54 ±6 years) with stableangina subjected to PTCA. After coronary angioplasty, vasoconstrictionwas observed in the segment distal to the dilated stenosis butnot in the distal segments of control vessels ( – 0.12± 0.04 and – 0.02 ± 0.02 mm respectively,P<0.05). After ketanserin infusion significant dilatationwas found in the distal segments of both PTCA vessels and controlvessels, but the dilatation was greater in the PTCA vessels(P<0.05). No significant changes were found in the proximalsegments of either PTCA or control vessels, or at the PTCA site.In conclusion, the vasoconstriction distal to the site of PTCAis mediated, at least in part, via 5-HT₂ receptors.     

Auditory function in young patients with chronic renal failure

Debate on the relationship between renal insufficiency and hearing loss continues mainly due to the advanced age and the possible accelerated presbycusis of the patients that have been studied in surveys. Hearing acuity was studied in 46 children and adolescents suffering from renal insufficiency. Sensorineural hearing loss (mainly high-frequency) of unknown cause was found in 14 patients (30.4%). Hearing loss was not influenced by the various haematological, biochemical and clinical parameters (type of renal disease, blood pressure, history of ototoxic drugs administration). However, hearing loss seemed to be affected by the method of management of the renal insufficiency (more in the haemodialysis group than in the peritoneal dialysis group). There were no significant changes in audiometric findings before and after haemodialysis.     

Torsion of undescended testis in a man with Down''s syndrome

Undescended testis is one of the most common disorders in Down's syndrome. We present an extremely rare case of torsion of an inguinal undescended testis in a 35-year-old patient with Down's syndrome. Surgical exploration revealed a rotated gangrenous testis, radical orchiectomy was performed, and pathological examination confirmed the diagnosis of testicular torsion.