Immunohistochemical expression of muscarinic receptors in the urothelium and suburothelium of neurogenic and idiopathic overactive human bladders, and changes with botulinum neurotoxin administration.

PURPOSE: To investigate the possible associations of urothelial and suburothelial muscarinic receptors with human bladder pathophysiology we examined the immunohistochemical expression of muscarinic receptors types 1, 2 and 3 in the bladder urothelium and suburothelium of patients with neurogenic or idiopathic detrusor overactivity compared with that in controls. We also examined associations with patient quantified symptoms and the effect of intradetrusor botulinum neurotoxin type A treatment. MATERIALS AND METHODS: We obtained bladder biopsies from 36 patients with detrusor overactivity before, and 4 and 16 weeks after treatment with intradetrusor botulinum neurotoxin type A via flexible cystoscopy. Patients with neurogenic detrusor overactivity were injected with 300 U botulinum neurotoxin type A and those with idiopathic detrusor overactivity received 200 U. Control biopsies were taken from 7 patients during investigation for asymptomatic microscopic hematuria. We studied muscarinic receptor immunohistochemical expression using commercial antibodies to muscarinic receptors 1, 2 and 3 with results quantified by image analysis. RESULTS: We noted decreased suburothelial muscarinic receptor immunoreactivity in detrusor overactivity biopsies vs controls, which were significant for muscarinic receptors 1 and 3. After successful botulinum neurotoxin treatment we noted only increased muscarinic receptor 1 and 2 immunoreactivity. Urothelial muscarinic receptor 1 and 3 immunoreactivity was increased after treatment. We identified no substantial urothelial muscarinic receptor 2 immunoreactivity. Receptor levels showed inverse correlations with patient urgency and frequency. CONCLUSIONS: Decreased muscarinic receptor levels in the urothelium and suburothelium of patients with detrusor overactivity were largely restored to control levels after successful treatment with botulinum neurotoxin type A. Correlations of receptor levels with patient symptoms further support a role for urothelial and suburothelial muscarinic receptors in detrusor overactivity in humans.

A pilot study of nuclear instability in archived renal and upper urinary tract tumours with putative ochratoxin aetiology.

DNA ploidy measurement has been applied uniquely to wax-embedded tissue of primary renal cell and metastatic tumours of a key experimental researcher on porcine ochratoxicosis, a control, and four transitional cell carcinomas from cases of Balkan endemic nephropathy. Primary renal tumour was diploid, and hyperdiploid metastasis was within the lower ploidy range for typical renal cell carcinoma. Three Balkan primary tumours showed extensive aneuploidy indicating marked nuclear instability, similar to model rat renal carcinoma caused by ochratoxin A. In contrast, much less nuclear instability in the putative occupational ochratoxicosis case fitted poorly with the ochratoxin A model.

A rare case of renal infarction caused by infective endocarditis.

BACKGROUND: A 29-year-old man presented to the emergency department of a general hospital complaining of sudden onset left loin pain, radiating to the groin, which had started 48 h previously. He described no urological symptoms and had no medical history of note. INVESTIGATIONS: Physical examination, electrocardiography, dipstick testing of urine, radiography of the chest and abdomen, blood tests (white blood cell count and serum urea, creatinine, sodium, potassium and C-reactive protein levels), CT of the renal tract, blood and urine cultures, renal angiography, thromboembolic blood panel, urine and blood tests for illicit drugs, transthoracic echocardiography, transesophageal echocardiography, renal ultrasonography. DIAGNOSIS: Infective endocarditis resulting in thromboembolic unilateral renal infarction. MANAGEMENT: The patient was started on anticoagulation therapy with low-molecular-weight heparin and treated with intravenous gentamicin and benzylpenicillin for 4 weeks. He was seen in an outpatient clinic 4 weeks after discharge, at which time serum urea and creatinine levels and repeat ultrasonography of the renal tract confirmed normal renal function. He will be followed up regularly by cardiologists and urologists, at 6 weeks initially, and every 6 months to 1 year thereafter by his family physician.

A case of scrotal sarcoidosis that mimicked tuberculosis.

BACKGROUND: A 38-year-old man presented with bilateral testicular swelling, night sweats and weight loss with little response to antibiotics. Examination revealed systemic lymphadenopathy and multiple small masses arising from both testes. INVESTIGATIONS: Scrotal ultrasound revealed multiple intratesticular, hypoechoic lesions; chest radiograph and abdominal ultrasound were normal. A CT scan revealed multilevel lymphadenopathies. A Heaf (tuberculin) skin test was negative. Testicular biopsy revealed multiple granulomata, some of which showed patchy central necrosis. DIAGNOSIS: A diagnosis of tuberculosis was initially made. After 3 months of clinical deterioration despite antitubercular drug therapy, however, the diagnosis was changed to sarcoidosis because blood results revealed hypercalcemia, elevated serum angiotensin-converting enzyme, and an elevated erythrocyte sedimentation rate. MANAGEMENT: The patient improved dramatically on corticosteroid therapy, with complete regression of all testicular lesions on imaging after 2 months. Steroids were tapered, then discontinued after 6 months. The patient remained in complete remission, but became oligospermic by the 3 year follow-up.