Age, comorbidity and hypertensive co-medication do not affect cardiovascular tolerability of 10 mg alfuzosin once daily.

PURPOSE: We assessed in real-life practice the impact of age, cardiovascular comorbidity and co-medication on the tolerability and efficacy of 10 mg alfuzosin OD in men with lower urinary tract symptoms suggestive of benign prostatic obstruction. MATERIALS AND METHODS: A total of 6,523 men with a mean age of 64.7 years were enrolled in a 6-month open label study of 10 mg alfuzosin OD. They were stratified by age quartile (younger than 60, 60 to 64, 65 to 70 and older than 70 years), comorbidity (hypertension, ischemic heart disease and diabetes) and antihypertensive co-medication (diuretics, beta-blockers, angiotensin converting enzyme inhibitors, angiotensin II inhibitors and calcium channel antagonists). RESULTS: Alfuzosin was effective and well tolerated. Despite an increased prevalence of cardiovascular comorbidity and antihypertensive co-medication with age changes in blood pressure did not significantly differ among age groups. In controls, ie those with no cardiovascular comorbidity or co-medication, alfuzosin produced minimal decreases in sitting systolic (mean -2.6 to -2.8 mm Hg) and diastolic (mean -1.7 to -1.8 mm Hg) blood pressure. In men with cardiovascular comorbidity mean decreases in systolic (-3.5 to 5.8 mm Hg) and diastolic (-2.0 to -3.3 mm Hg) blood pressure remained marginal. Of the 6,523 exposed patients 19.3% withdrew from the study, mainly for adverse events (6.4%) or a lack of efficacy (5.3%), while 229 (3.5%) experienced serious adverse events and 1,558 (23.9%) reported at least 1 treatment emergent adverse event. The most commonly reported adverse event was dizziness/postural dizziness (4.8%). Hypotension/postural hypotension was uncommon (0.7%). Age, cardiovascular comorbidity and antihypertensive co-medication had no impact on the safety profile of 10 mg alfuzosin OD. CONCLUSIONS: Alfuzosin (10 mg) OD is effective and well tolerated, and it has marginal effects on blood pressure, including in elderly patients and those with hypertension, ischemic heart disease or diabetes and those receiving antihypertensive agents.

Experimental evaluation of furosemide renography in unobstructed and partially obstructed upper urinary tracts in pigs.

To evaluate the reliability and the constancy of the furosemide renography an experimental evaluation of the test has been performed. A standardized unilateral partial proximal ureteral obstruction was applied to 11 pigs. Preoperatively and again weekly in the three weeks following obstruction a furosemide renogram (FR) was done. The furosemide renography was a very constant parameter in the unobstructed kidney (85%) and in the partly obstructed kidney (85%). A type I FR pattern (O'Reilly classification) was an exact indicator of an unobstructed pelvis. After partial ureteral obstruction, an immediate change in the FR pattern was seen either into type II or type IIIa renography. In this experimental study furosemide renography was found to be a reliable tool in the differentiation between the unobstructed normal renal pelves and the partly obstructed dilated renal pelves.

O-linked mucin-type glycoproteins in normal and malignant colon mucosa: lack of T-antigen expression and accumulation of Tn and sialosyl-Tn antigens in carcinomas.

The expression of carbohydrate core-structures on O-linked glycoproteins was examined in fetal (n = 6), infantile (n = 2), normal adult (n = 15), and malignant (n = 22) colorectal tissue by means of monoclonal antibodies (MAbs) specific for Tn (GalNAc alpha 1-O-R), sialosyl-Tn (NeuAc alpha 2-6GalNAc alpha 1-O-R), and T (Gal beta 1-3GalNAc alpha 1-O-R) antigens. Immunolabelling of solubilized malignant tissue, separated by SDS-PAGE, showed expression of Tn and sialosyl-Tn antigens on 3 molecules of similar mw (230, 210, and 170 kDa), whereas no T antigens could be detected. Immunohistochemical techniques showed that fetal colon mucosa expressed Tn antigens but no sialosyl-Tn antigens. Infantile colon mucosa, however, expressed Tn as well as sialosyl-Tn antigens, and normal adult colon mucosa cells expressed no Tn antigens but sialosyl-Tn in 2 out of 6 biopsies from cecum, which indicates occurrence post partum of alpha-6-NeuAc-transferase. Endothelium in normal adult mucosa showed expression of both Tn and sialosyl-Tn antigens; 82% of carcinoma tissue sections expressed Tn antigens, and 73% expressed sialosyl-Tn antigens in mucin or cytoplasm, or on luminal cell membranes. T antigens could be detected neither in normal mucosa cells at any stage of development, nor in carcinomas. The possibility exists that this could be due to masking of T antigen. Mucin-type blood-group A antigens which contain an internal T-disaccharide were demonstrated in 4 out of 4 A1 tumors by means of MAb HH5. However, urea-containing SDS-PAGE analysis demonstrated an HH5 binding to molecules different from those binding anti-Tn. In remote morphologically normal and abnormal crypts in colons from carcinoma patients, both Tn and sialosyl-Tn antigens were expressed in secreted mucin in 40% of the cases. The data indicate an expression of O-linked Tn and sialosyl-Tn core structures in fetal and infantile colon and in colorectal carcinomas.

The impact of unilateral ureteral obstruction on pelvic and parenchymal transit times in the pig kidney.

In 10 female pigs a partial unilateral ureteral obstruction was investigated for 3 weeks. The pigs were monitored with 131I-iodo-hippuran scintigraphies before obstruction and once a week during the course of obstruction. Parenchymal and pelvic mean transit times were calculated by deconvolution analysis. Before the pigs were killed, pelvic pressure and volume were measured. During the course of obstruction there was a slight, but significant (P less than or equal to 0.05) difference in renographical split function between the 2 sides. Parenchymal transit times increased moderately ipsilaterally during the 1st and 2nd week after obstruction and a significant difference (P less than 0.02) appeared in the 2nd week compared to the contralateral side, which was unchanged during the course of obstruction. Pelvic transit times increased steadily ipsilaterally during the course of obstruction and the opposite took place contralaterally. A fair correlation (r = 0.65) was found between parenchymal transit time and pelvic baseline pressure. Pelvic transit times were prolonged at any time after obstruction and significantly correlated to the presence of obstruction. The study suggests that interpretation of the obstructed renogram will encounter analysis of both parenchymal and pelvic transit times in cases where renal function is moderately reduced.

Urinary cytology in the detection of bladder tumours. Influence of concomitant urothelial atypia.

The role of urinary cytology in detection and follow-up of urinary bladder tumours is still evolving. However, considerable variations in the accuracy of detecting bladder tumours exist in published work on the subject. In this study the influence of concomitant urothelial atypia on urinary cytology was investigated. Further, the correlation of grading between cytology and tumour histology was examined, and finally the role of urinary cytology as a prognostic factor was investigated. 102 comparative studies of simultaneously achieved precystoscopic voided urine samples, tumour histology and 8 pre-selected site biopsies were available from patients having a Ta, T1 or T2 bladder tumour. The overall numbers of positive cytology were found to be 64%, but correcting for false positives caused by concomitant urothelial atypia the numbers were reduced to 55% (p less than 0.01). A considerable higher ability to detect high-grade than low-grade tumours was found. Correlation between grading of tumour histology and cytology was found to be only 50%. Patients were followed for 3 years. From the results of pre-cystoscopic cytology it was possible to define a low-risk group and a high-risk group. Patients with negative cytology had very low risk of future invasive tumour recurrence whereas all patients with grade III-IV cytologic changes were found to harbour either a grade III tumour or carcinoma in situ, both conditions predictive of aggressive tumour course.

Transabdominal ultrasonography plus urine cytology in control of benign bladder tumours.

Transabdominal ultrasonography can detect bladder tumours down to 5 mm in diameter, and in combination with urine cytology it is a potential alternative to cystoscopy for control of bladder tumour patients. This modality was compared with cystoscopy in 260 investigations on patients with previous non-invasive tumours. Of 153 negative ultrasonographies 55 (21%) were false negative, overlooking 15 tumours above 5 mm (including 5 flat papillomatous areas), 30 tumours 5 mm or less and 10 flat dysplastic lesions (diagnostic sensitivity 64%). In 14 of the false negative ultrasonographies urine cytology was abnormal, increasing the combined diagnostic sensitivity to 73%. Most overlooked tumours above 5 mm were in bladder neck, anterior wall and dome. Of 89 positive ultrasonographies 15 were false positive (diagnostic specificity 83%). Two patients developed invasive tumours in the study period. One was detected by ultrasound and urine cytology, the other - a flat muscle invasive tumour - was not. Ultrasonography plus urine cytology is only acceptable for control of patients with very little risk of invasive and few non-invasive recurrences, i.e. patients with previous Ta, grade I or II transitional cell tumours and no recurrences after 1 or 2 control cystoscopies.

Pyeloureteral dynamics. Pelvic pressure and kidney function in partial long-term ureteric obstruction.

In 10 pigs with reno-scintigraphically proven normal upper urinary tracts, a standardized partial obstruction of the left ureter was created at the lower kidney pole level. Three weeks later kidney function was scintigraphically reassessed and the pressure flow relationship in the flow range 0-20 ml/min outlined. The partially obstructed pelvic baseline pressure varied from 9.0 to 32.0 cmH2O. During perfusion small increases in pelvic pressure were seen at all flow rates in the individual cases and there was a linear relationship between pressure and flow. Compared to previous results of a similar but acute obstruction the results were identical in pressure ranges and pressure flow profile. This demonstrates, that a longitudinal stability in transport mechanism qualities is present also during the course of obstruction. The pelvic pressure at low flow rates was significantly correlated to kidney function depression, whereas perfusion pressures at high flow rates did not show any correlation, except at 20 ml/min. This clearly indicates, that the pelvic pressure at normal urine flow rate is an important factor in the pathogenesis of obstructive nephropathy.

Pelviometry in the normal and the partially obstructed porcine kidney: recordings before and three weeks after application of ureteral obstruction.

In 11 pigs a standardized proximal ureteric obstruction was applied. The effect of the obstruction was examined three weeks later. In both the normal and the obstructed systems the pressure-volume relationship was exponential. Mean pelvic capacity increased from 6.5 ml. to 44.1 ml. (p less than 0.002). Mean intrapelvic baseline pressure increased from 10.0 to 16.8 cm. H2O (p less than 0.02), and this parameter correlated positively to volume (rS = 0.79 - p less than 0.05). There was a slight decrease in the relative function of the obstructed kidney on renography (from 49% to 39% of the total renal function), but this was not significant. The decrease in function was correlated to the increase in capacity (rS = -0.69 - p less than 0.05). In this series renal deterioration occurred in the hydronephrotic kidneys, and at least in this model of acute ureteral obstruction there was no support for the theory that hydronephrotic transformation is a compensatory mechanism which protects the kidney when the upper urinary tract is obstructed.

Positive urinary cytology after tumor resection: an indicator for concomitant carcinoma in situ.

Concomitant urothelial atypia (grade II atypia or carcinoma in situ) is predictive of new tumor growth after transurethral tumor resection. Concomitant urothelial atypia can be demonstrated by pre-selected site mucosal biopsies. However, a number of patients have new tumors despite normal pre-selected site biopsies. To investigate whether urinary cytology is a better indicator for concomitant urothelial atypia than pre-selected site biopsies, we studied in bladder tumor patients the correlation between the findings of pre-selected site biopsies (8 per patient) at tumor resection and urinary cytology (2 per patient) after successful resection. Concomitant urothelial atypia was demonstrated by biopsies in 52 per cent of the patients, of whom 60 per cent had grade II atypia and 40 per cent had carcinoma in situ. All patients with concomitant carcinoma in situ in biopsies had positive cytology findings. Of the patients with concomitant grade II atypia in biopsies 15 per cent had negative cytology studies. In 48 per cent of the patients no urothelial atypia in pre-selected site biopsies was demonstrable. However, cytology was positive, that is neoplastic cells were present, in 64 per cent of these specimens (19 patients). Of the 19 patients 16 currently have had demonstrable urothelial atypia in pre-selected site mucosal biopsies at a later occasion. We conclude that urinary cytology seems to be a better indicator for the presence of concomitant urothelial atypia than pre-selected site mucosal biopsies and, therefore, it can be used as a screening procedure for patients without demonstrable concomitant carcinoma in situ at tumor resection.