Isotonic saline in elderly men: an open-labelled controlled infusion study of electrolyte balance, urine flow and kidney function.

Isotonic saline is a widely-used infusion fluid, although the associated chloride load may cause metabolic acidosis and impair kidney function in young, healthy volunteers. We wished to examine whether these effects also occurred in the elderly, and conducted a crossover study in 13 men with a mean age of 73 years (range 66-84), who each received intravenous infusions of 1.5 l of Ringer's acetate and of isotonic saline. Isotonic saline induced mild changes in plasma sodium (mean +1.5 mmol.l(-1) ), plasma chloride (+3 mmol.l(-1) ) and standard bicarbonate (-2 mmol.l(-1) ). Three hours after starting the infusions, 68% of the Ringer's acetate and 30% of the infused saline had been excreted (p < 0.01). The glomerular filtration rate increased in response to both fluids, but more after the Ringer's acetate (p < 0.03). Pre-infusion fluid retention, as evidenced by high urinary osmolality (> 700 mOsmol.kg(-1) ) and/or creatinine (> 7 mmol.l(-1) ), was a strong factor governing the responses to both fluid loads.

Double-blind randomized study of symptoms associated with absorption of glycine 1.5% or mannitol 3% during transurethral resection of the prostate.

PURPOSE: We studied which irrigating fluid, glycine 1.5% or mannitol 3%, is associated with the most favorable adverse effects profile when absorbed by the patient during transurethral resection of the prostate. MATERIALS AND METHODS: Irrigating fluid bags containing mannitol 3% or glycine 1.5%, both with added ethanol 1% as an indicator of fluid absorption, were used in a randomized double-blind fashion during 394 transurethral prostatic resections. The incidence of 13 symptoms was studied in 52 patients (13%) who absorbed more than 500 ml. fluid. RESULTS: The incidence of circulatory symptoms did not differ between the fluids but the risk of neurological symptoms, such as nausea, after transurethral prostatic resection was 4.8 times higher when glycine 1.5% was absorbed (p <0.04). An increase of 1,000 ml. in the volume of irrigant absorbed increased the overall risk for circulatory symptoms by a factor of 3.4 (p <0.03) and the risk of neurological symptoms by a factor of 4.4 (p <0.02). CONCLUSIONS: Absorption of mannitol 3% during transurethral prostatic resection is associated with fewer neurological symptoms than glycine 1.5%.

Prostate-specific antigen (PSA), PSA density and age-adjusted PSA reference values in screening for prostate cancer--a study of a randomly selected population of 2,400 men.

Prostate cancer screening with DRE, TRUS, and PSA testing was offered to 2,400 randomly selected men 55-70 years old. Among 1,782 examined, 65 (3.6%) men with prostate cancer were diagnosed. The PSA results were correlated to the diagnosis, the men's age, and the prostate volume. Least square regression analysis was used to calculate the 95% upper confidence intervals for PSA in each year of age in men without prostate cancer. The PPV was calculated for: (i) PSA > 4 ng/ml, (ii) PSAD > 0.15, (iii) PSAD > 0.20 and (iv) age-adjusted PSA reference values. A significant correlation was found between PSA and prostate volume, between PSA and age, and between the prostate volume and age. The calculated annual growth of the prostate was 1.6% and the annual increase in PSA was 2.4%. The age-adjusted upper PSA reference values for the three age categories studied (55-59, 60-64 and 65-70 years) were 5.2, 5.8, and 6.7 ng/ml, respectively. The PPVs for PSA > 4 ng/ml, PSAD > 0.15, PSAD > 0.20, and the age-adjusted PSA reference values were 17%, 14%, 22%, and 27%, respectively. Age-adjusted PSA or PSAD may increase the PPV compared to PSA > 4 ng/ml. The detection rate is, however, inadequate. A PSA cut-off at 4 ng/ml could therefore be maintained in men 55-70 years old. The median PSA values and median prostate volumes calculated for men with benign findings may serve as a reference in future studies.

Dihydrotestosterone and testosterone levels in men screened for prostate cancer: a study of a randomized population.

OBJECTIVE: To investigate the possible relationship between serum levels of prostate specific antigen (PSA), dihydrotestosterone (DHT), testosterone, sexual-hormone binding globulin (SHBG) and tumour stage, grade and ploidy in 65 cases of prostate cancer diagnosed in a screening study compared to 130 controls from the same population. PATIENTS, SUBJECTS AND METHODS: From a population of 26,602 men between the ages of 55 and 70 years, 2400 were selected randomly and invited to undergo screening for prostate cancer using a digital rectal examination, transrectal ultrasonography and PSA analysis. Among the 1782 attendees, 65 cases of prostate cancer were diagnosed. Each case was matched with two control subjects of similar age and prostate volume from the screening population. Frozen serum samples were analysed for PSA, DHT, testosterone and SHBG, and compared to the diagnosis and tumour stage, grade and ploidy. Comparisons between these variables, and multivariate and regression analyses were performed. RESULTS: There were significant differences in PSA level with all variables except tumour ploidy. DHT levels were slightly lower in patients with prostate cancer but the difference was not statistically significant. There was a trend towards lower DHT values in more advanced tumours and the difference for T-stages was close to statistical significance (P = 0.059). Testosterone levels were lower in patients with cancer than in the control group, but the differences were not significant. There was no correlation between testosterone levels, tumour stage and ploidy, but the differences in testosterone level in tumours of a low grade of differentiation compared to those with intermediate and high grade was nearly significant (P = 0.058). The testosterone/DHT ratio tended to be higher in patients with more advanced tumours. SHBG levels were lower in patients with cancer than in controls but the differences were not statistically significant. There were no systematic variations of tumour stage, grade and ploidy. Multivariate analysis showed that if the PSA level was known, then DHT, testosterone or SHBG added no further information concerning diagnosis, stage, grade or ploidy. Regression analysis on T-stage, PSA level and DHT showed an inverse linear relationship between PSA and DHT for stage T-3 (P = 0.035), but there was no relationship between PSA and testosterone. CONCLUSION: PSA was of value in discriminating between cases and controls and between various tumour stages and grades, but no statistically significant correlation was found for ploidy. If PSA level was known, no other variable added information in individual cases. Within a group, DHT levels tended to be lower among cases and in those with more advanced tumours. There was an inverse relationship between tumour volume, as defined by PSA level, and 5 alpha-reductase activity, as defined by DHT level, and the testosterone/DHT ratio. This trend was most obvious with T-stage. No systematic variation were found in the levels of testosterone or SHBG.

Cost-effectiveness analysis in early detection of prostate cancer: an evaluation of six screening strategies in a randomly selected population of 2,400 men.

Based on the findings in an early detection study for prostate cancer [Gustafsson et al.: J Urol 148:1827-1831, 1992] using digital rectal examination (DRE), transrectal ultrasound (TRUS), and prostate-specific antigen (PSA), a cost-effectiveness analysis was performed based on 6 screening strategies, namely: 1) DRE of all individuals; 2) TRUS of all individuals; 3) DRE, TRUS, and PSA analysis followed by reexamination of individuals with PSAs > or = 7 ng/ml; 4) DRE of individuals with PSAs of > or = 4 ng/ml; 5) TRUS of individuals with PSAs of > or = 4 ng/ml; 6) DRE and PSA analysis followed by TRUS on individuals with PSAs > or = 4 ng/ml. The detection rates of prostate cancer using these 6 strategies were 2.4%, 3.3%, 3.6%, 2.0%, 2.6%, and 3.2%, respectively. Except for costs per detected cancer, costs were also calculated per detected small cancer (< or = 1.5 cm) and per detected cancer treated for cure. The cost calculations were based on total costs, i.e., direct plus indirect costs. When the 6 strategies were compared, taking into account the detection rate of cancers treated for cure and cost-effectiveness with respect to cancers treated for cure, strategies 1), 2), 3), and 4) were ruled out as less favorable than the remaining 2 strategies. TRUS of individuals with PSAs > or = 4 ng/ml (strategy 5) was the most cost-effective strategy and detected 80% of the cancers actually treated for cure. Screening with DRE and PSA analysis followed by TRUS of individuals with PSAs > or = 4 ng/ml (strategy 6) had a somewhat lower cost-effectiveness, but detected 90% of the cancers treated for cure.

Psychological reactions in men screened for prostate cancer.

OBJECTIVE: To investigate the possible negative psychological impact of screening for prostate cancer with special focus on the impact of false positive and true positive test results. SUBJECTS AND METHODS: As part of an early detection study for prostate cancer psychological and psychophysiological reactions to various phases of the diagnostic procedures were examined in 2400 randomly selected men divided into various groups. Their psychophysiological reactions were assessed by measurements of serum cortisol and their psychological reactions by questionnaires directed at determining emotional states and sleep disturbance. In a stratified sample of the population (100 men) measurements were made at the time of the screening examination and again 2 weeks later. In patients undergoing biopsy (307 men) measurements were made 2 weeks after screening, but before they were informed of the biopsy results, and again 4 and 16 weeks after screening. RESULTS: Serum cortisol levels at the screening examination were higher than corresponding levels of a comparable sample of Swedish men during normal daily activity, indicating that an invitation to examination for prostate cancer per se might create emotional stress. Two weeks after the screening the elevated levels had decreased to normal. The highest cortisol levels were found in men who had undergone biopsy, immediately before they were informed of the results 2 weeks after screening. After they were informed, cortisol levels fell, regardless of the results of the biopsy. The patterns of emotional state and sleep disturbance were similar except that sleep disturbance was delayed. CONCLUSION: In screening programmes for prostate cancer it is important to define clearly the high-risk groups to minimize the risk of adverse psychological reactions in those subjects with a low risk of having the disease. The results also emphasize the need to reduce the number of false positive results by choosing diagnostic tests of high specificity. The interval between a test and informing the subject of the results should be minimized to decrease the duration of the increased emotional stress.

Diagnostic methods in the detection of prostate cancer: a study of a randomly selected population of 2,400 men.

We investigated the value of digital rectal examination, transrectal ultrasonography and prostatic specific antigen (PSA) analysis as aids in general clinical practice and in the early detection of prostate cancer. Of a randomly selected population of 2,400 men 55 to 70 years old who were offered examination with digital rectal examination, transrectal ultrasound and PSA analysis, 1,782 (74%) accepted and prostate cancer was detected in 65 (3.6%). When the transrectal ultrasound results were also considered the detection rate of digital rectal examination (2.3%) was increased by 50% and the number of stage T2A or less tumors was doubled. At reexamination due to markedly high PSA values (7 micrograms/l. or more) only a few additional cancers (5%) were detected. However, it is noteworthy that 80% of the detected cancers were found among the subgroup with abnormal PSA values (4 micrograms/l. or more) and comprising 17% of the study population, which suggests the possibility of selecting a risk group at mass screening. Moreover, the positive predictive value increased from 4% (when only digital rectal examination was positive) to 71% for the combination of positive digital rectal examination, positive transrectal ultrasound and an increased PSA concentration (that is 7 micrograms/l. or greater).

Prognostic significance of mucosal aneuploidy in stage Ta/T1 grade 3 carcinoma of the bladder.

In a prospective series of 71 patients with newly detected grade 3, stages Ta and T1 bladder carcinoma tumor characteristics, including the results of deoxyribonucleic acid (DNA) analysis as well as morphological and DNA characteristics of the grossly normal urothelium, were investigated and related to progression-free survival. The mean duration of followup was 57 months, with a minimum of 24 months. Of the 71 patients 24 underwent primary cystectomy, and 47 were conservatively treated with transurethral resection alone, or followed by instillation therapy or irradiation therapy. Of the cystectomy and conservatively treated patients 2 (8%) and 16 (34%), respectively, died of bladder carcinoma. Among the 47 conservatively treated patients tumor progression could not be predicted by the initial characteristics of tumor stage, papillary or nonpapillary growth, tumor multiplicity, tumor size, existence of 1 or multiple aneuploid cell populations, S phase value, carcinoma in situ and atypia or aneuploidy in the mucosal biopsies. Neither was progression predicted by the recurrence rate during year 1 of observation. However, a change to or persistent mucosal aneuploidy and a change to or persistent morphological abnormality of the mucosa during year 1 of observation were predictive for tumor progression (p = 0.001 and 0.045, respectively). When compared in stepwise regression analysis (Cox's proportional hazard model), DNA aneuploidy in the mucosa at 12 months after diagnosis was a highly significant predictor, whereas morphology added no further prognostic information. Therefore, progression is related to gross chromosomal abnormalities of the mucosa. High risk patients can be identified by evaluation of the grossly normal mucosa, which should be done as part of the initial diagnosis and during followup in conservatively treated patients with stages Ta and T1, grade 3 bladder carcinoma.

Male and female sexual function and activity following ileal conduit urinary diversion.

A group of 66 patients (40 males, 26 females) underwent an ileal conduit urinary diversion because of bladder cancer (44 patients) or incontinence/bladder dysfunction (22). They were questioned about pre- and post-operative sexual function and activity and it was found that 90% of the males (26/29) who were sexually active before surgery lost the ability to achieve erection following radical cystectomy. Although they were unable to achieve penile erection, 41% were able to experience orgasm by means of masturbation. Five of the 29 males received penile implants. Five of the 6 females treated by cystectomy, who were sexually active before the operation, reported either a decrease or cessation of sexual activity (i.e. coitus) post-operatively. The main problems were a decrease in sexual desire, dyspareunia and vaginal dryness. One women reported the inability to experience orgasm after surgery. Compared with women with bladder cancer, those with incontinence/bladder dysfunction were more likely to have an active sexual life after urostomy surgery. Seven females in this group, of whom 4 were sexually inactive before surgery, increased their sexual activity after the operation. For these women the conduit operation removed the need to use incontinence pads or indwelling catheters.

[A study on prostatic cancer. The patient can decide himself: medical or surgical treatment]. / Studie om prostatacancer. Patienten kan få bestämma själv: medicinsk eller kirurgisk behandling.

In a multicentre study, 101 consecutive patients with advanced prostate cancer were offered the choice of orchiectomy or treatment with an LHRH analogue. Together with the cancer diagnosis the patients were given verbal information about the treatment alternatives, and detailed written information to peruse at home. One week later the patients informed the attending physicians of their choice. Information as to the reasons for the patients' choice, and their views on their choice after the start of treatment were elicited by questionnaire. Of the 101 patients, 48 chose orchiectomy, and 48 treatment with an LHRH analogue, five patients being excluded owing to their inability to decide. Mean age was about 73 years in both treatment groups, and about two thirds of each group lived with a partner. The level of education was higher among those who chose medical treatment. The predominant reasons for the choice of treatment were as follows: Orchiectomy, simpler (31 per cent), troublesome having to have monthly injections (19 per cent), simple to perform (15 per cent); medical treatment, possibility of change in treatment (27 per cent), simpler (17 per cent), fear of surgery (15 per cent). Most patients in both groups had no difficulty deciding, chose quickly, felt sure about their choice, appreciated the opportunity of choosing, and had discussed their choice with their partners or intimates. Three months after the start of treatment, almost all patients were still satisfied with their choice, and had no wish to change their choice even if that were possible.(ABSTRACT TRUNCATED AT 250 WORDS)

Preventable sudden death in patients receiving angiotensin converting enzyme inhibitors and loop/potassium sparing diuretic combinations.

Angiotensin-converting-enzyme inhibitors are frequently used in conjunction with diuretics in the treatment of congestive cardiac failure. We report two cases in which use of a proprietary combination diuretic containing a loop diuretic and potassium sparing agent with an angiotensin converting enzyme inhibitor was associated with hyperkalaemic cardiac arrest. Successful resuscitation from the arrest permitted elucidation of its mechanism. We believe that this outcome has not previously been reported, and emphasise the importance of electrolyte monitoring in patients receiving angiotensin converting enzyme inhibitors particularly if prescribed in addition to fixed combination proprietary diuretics.

Deoxyribonucleic acid profile and tumor progression in primary carcinoma in situ of the bladder: a study of 63 patients with grade 3 lesions.

In 63 patients with primary grade 3 carcinoma in situ of the bladder flow cytometric deoxyribonucleic acid (DNA) analysis was performed at diagnosis and during an average followup of 63 months. The results of DNA measurements were related to disease progression, that is invasive tumor and/or metastatic disease. The DNA histograms were classified as diploid (2 patients) or aneuploid (61). A total of 3 categories of aneuploid tumors with different prognostic significance could be defined: 1) carcinoma in situ with 1 aneuploid cell population at diagnosis and with no change to multiple aneuploid cell populations throughout observation, 2) carcinoma in situ with 1 aneuploid cell population at diagnosis but with a later change to multiple aneuploid cell populations and 3) carcinoma in situ with multiple aneuploid cell populations already at diagnosis. At 5 years the progression-free survival for the 3 categories was 94%, 43% and 20%, respectively. Over-all, of the patients with multiple aneuploid cell populations (categories 2 and 3) 76% had progression, in contrast to 19% of those in category 1 (p less than 0.0005). In category 2 development of multiple aneuploid cell populations preceded progression in 8 of 11 progressive cases by an average of 20 months. Therefore, the occurrence of multiple aneuploid cell populations must be considered as a sign of high aggressiveness. We conclude that flow cytometric DNA analysis is a potent predictor of prognosis in cases of primary carcinoma in situ of the bladder.

Psychosocial adjustment and general state of health in patients with ileal conduit urinary diversion.

The psychosocial adjustment and general state of health were investigated in 66 patients (40 males, 26 females) who had been subjected to an ileal conduit urinary diversion on account of bladder cancer (44 patients) or incontinence or bladder dysfunction (22 patients). Seventy per cent of the patients reported unchanged, overall, social activity (OSA) after the operation. Twenty per cent reported less and 10% more activity. Bladder-cancer patients were more likely to curtail their social activities compared with the patients with incontinence or bladder dysfunction. Appliance-related problems were mentioned by half of the patients who reported decreased OSA. One-third of the patients considered accidental leakage or fear of such leakage as the most negative aspect of surgery. Factors related to an altered body image were the most common negative aspect reported by females. Despite psychosocial problems, the majority of the patients (80%) considered their health to be good. Males, individuals working full-time and patients with unchanged OSA scored higher on a Health Index, i.e. considered themselves healthier than the rest of the patients.

Comparative histopathology and deoxyribonucleic acid flow cytometry of random mucosal biopsies in untreated bladder carcinoma.

In a study of 290 patients with untreated carcinoma of the bladder, histopathological studies of random mucosal biopsies were compared with the results of deoxyribonucleic acid (DNA) flow cytometry. By histopathology the findings were classified as severe atypia corresponding to primary grade 3 carcinoma in situ, atypia not fulfilling the criteria for carcinoma in situ and no atypia. The DNA histograms were classified as diploid or aneuploid. Aneuploid cell populations in mucosal biopsies were found mainly in cases with aneuploid tumors of grade 3. Of the biopsies classified as concomitant carcinoma in situ 76% were aneuploid. In biopsies exhibiting less severe or no atypia aneuploidy was found in 41 and 10%, respectively. For these 3 morphological categories the distributions of the aneuploid cell populations were similar irrespective of the histopathological findings and they were also the same as that found in primary carcinoma in situ. We concluded that gross chromosomal aberrations may appear at an early stage of the tumor development and before changes recognizable by morphology. The similarity of the DNA profiles of the aneuploid cell populations, regardless of morphological findings, indicates that apart from gross chromosomal aberrations changes of the phenotype are necessary for the expression of morphological changes.

Living with a urostomy. A follow up with special regard to the peristomal-skin complications, psychosocial and sexual life.

Sixty-six subjected to an ileal conduit urinary diversion on account of bladder cancer (44 patients) or incontinence or bladder dysfunction (22 patients) were investigated. Stoma and skin complications were frequently observed and the patients who practiced inadequate stoma-care routines were more likely to show peristomal-skin complications, compared with the rest of the patients. With the passage of time after surgery, a quarter of the patients obtained full disability pensions. Stoma-related problems were the main causative factor in half of these cases. The majority of the bladder-cancer males reported were more likely to report decreased rather than no sexual activity. Compared with females with bladder cancer, females with the diagnosis of incontinence or bladder dysfunction were more likely to increase their sexual activity after the operation. Bladder-cancer patients more frequently curtailed their social activities, compared with the patients with the diagnosis of incontinence or bladder dysfunction.

Digital rectal examination versus transrectal ultrasound in detection of prostate cancer. Preliminary results from a study of a randomly selected population.

In a study of 2,400 randomly selected men (age 55-70 years) for early detection of prostate cancer the authors have compared the diagnostic value of digital rectal examination (DRE), transrectal ultrasound (TRUS) and prostate specific antigen (PSA). Altogether 62 prostate cancers were detected, corresponding to a detection rate of 3.5% but by use of DRE the detection rate was only 2.3%. The study showed that TRUS added significantly to the detection rate. If radical surgery is restricted to stages T1 and T2A, the combined use of DRE and TRUS detected twice as many cases fit for this treatment than DRE alone. The authors advocate randomized studies for evaluation of early radical treatment of prostate cancer. Before results of such studies have appeared they recommend methodological studies aimed at development and enhancement of the accuracy of the diagnostic tools.

Fine-needle aspiration biopsy with a new automatic fine-needle gun versus histological core in ultrasonically-guided transrectal biopsy for detection of prostate cancer.

In connection with a health control study of 2,400 men for early detection of prostate cancer the authors have compared fine-needle aspiration biopsy using a new automatic fine-needle gun with histological cores obtained by the Biopty gun. Both procedures were ultrasonically guided. Prostate cancer was found in 62 patients and in 46 of these both biopsy methods were used on the same occasion. There was no essential difference in sensitivity between the two methods. The authors recommend fine-needle aspiration biopsy as the primary method but regard the histological core technique as a valuable supplement.

Conventional heparin and semisynthetic heparin analogue (SSHA) alteration of blood coagulation after embolic occlusion of human renal circulation.

Blood coagulation and fibrinolytic variables were measured in a peripheral vein in a study of 21 consecutive patients before and after angio-embolization of renal carcinoma. The first ten patients received conventional heparin, 5000 IU twice daily, and the following eleven a semi-synthetic heparin analogue (SSHA), 50 mg twice daily, for 5 days. The first injection was given 2 hours before embolization and the last injection at least 12 hours before the last blood sampling. Both groups showed increased levels of FPA on day 5-7, indicating that the anticoagulant influence had ceased. F VII levels decreased only in the SSHA group from embolization to day 3, but were increased in both groups on day 5-7. Levels of thrombin-antithrombin complexes (TAT) were significantly increased in the heparin group 2 hours after embolization, indicating that thrombin activity had been formed. The corresponding TAT level in the SSHA group was not significantly increased. The differences could possibly indicate a different mechanism of action on blood coagulation of SSHA as compared with heparin, with involvement of extrinsic pathway and maybe by-passing antithrombin III inhibition.