P. O. Madsen

Radical prostatectomy versus expectant primary treatment in stages I and II prostatic cancer : a fifteen-year follow-up

A fifteen-year follow-up of a prospective, randomized study comparing placebo with radical prostatectomy as the primary treatment of early prostatic cancer is presented. A total of 111 patients with clinical Stage I or II prostatic cancer, normal acid phosphatase levels, and negative findings on skeletal x-ray film were evaluable. Thirty Stage I patients and 20 Stage II patients received placebo only; 31 Stage I and 30 Stage II patients underwent radical prostatectomy. The survival status for 95 patients (86%) was established at the fifteen-year follow-up. No significant differences in crude survival occurred in either stage or in both stages combined. Moreover, the survival curves closely followed reference curves based on expected U.S. mortality for men of comparable ages and races. A statistically significant association between a high Gleason histologic score and poor survival was established. In this study, initial treatment with radical prostatectomy did not yield longer survival than initial placebo treatment alone. However, the findings should be interpreted with caution, since sample size was small and staging procedure was simplified.

Spontaneous uroflowmetry in prostatism

Uroflowmetry is a valuable urodynamic screening procedure in selecting patients with prostatism for surgery. A prospective study was undertaken in which patients were selected for transurethral resection of the prostate by means of nonurodynamic data only. All patients underwent extensive urodynamic testing. Fifty-three patients were studied preoperatively, while 38 were examined at three months and 22 at twelve months postoperatively. A weak correlation was noted between maximum flow rate and symptom scores, pressure variables, and minimum urethral resistance. However, classification of patients by groups of high, medium, and low maximum flow rates did not identify groups of patients with less favorable outcome of surgery, i.e., patients with higher flow rates did as well as those with lower flow rates. A clear role for spontaneous uroflowmetry could not be identified in the preoperative evaluation of patients with prostatism.

Pharmacokinetics of cefuroxime in normal and impaired renal function: comparison of high-pressure liquid chromatography and microbiological assays.

The pharmacokinetics of cefuroxime were studied after a single dose of 750 mg was given intravenously to each of 21 male volunteers grouped according to their creatinine clearances; these clearances were 60 to 120, 20 to 59, and less than 20 ml/min per 1.73 m,2 respectively, for groups 1 (12 subjects), 2 (4 subjects), and 3 (5 subjects). Cefuroxime obeyed two-compartment model kinetics in all three groups. Initial serum levels of cefuroxime were approximately 130 microgram/ml in group 1 and 2 and 80 microgram/ml in group 3. the levels then declined rapidly for 0.5 to 1 h after injection. After that time, cefuroxime levels declined more slowly, and the elimination rate became monoexponential. The mean serum half-lives for cefuroxime in groups 2, 2, and 3 were 1.7, 2.4, and 17.6 h, respectively. Mean cefuroxime levels in serum were greater than 8 microgram/ml for 3 h in group 1, for 6 h in group 2, and for 30 h in group 3. Cumulative 24-h urinary excretion accounted for essentially 100% of the dose in group 1 and 2, and for 40% in group 3. Urine levels exceeded the minimal inhibitory concentration for susceptible organisms for more than 12 h in all groups. Cefuroxime distribution characteristics were independent of renal function. In patients with creatinine clearances less than 20 ml/min per 1.73 m2, doses of cefuroxime needs to be reduced. A microbiological disk diffusion assay and a high-pressure liquid chromatography assay for cefuroxime yielded statistically identical results, except for serum levels in uremic patients (group 3).

Pharmacokinetics of piperacillin in subjects with various degrees of renal function.

The pharmacokinetics of piperacillin were examined after single intravenous doses to three groups of male patients with creatinine clearances of greater than or equal to 60 (group I), greater than or equal to 20 but less than 60 (group II), and less than 20 (group III) ml/min per 1.73 m2. Each of 32 patients received either 1 or 4 g of piperacillin as a bolus injection. Three patients received both doses. After a rapid 0.5- to 1-h distribution phase, antibiotic levels in serum declined monoexponentially. After the 1-g dose, mean peak piperacillin levels in serum were 60, 103, and 67 micrograms/ml and the beta phase elimination half-lives were 1.0, 1.6, and 3.9 h in groups I, II, and III, respectively. After the 4-g dose, the respective mean peak piperacillin levels in serum were 329, 232, and 262 micrograms/ml and beta phase half-lives were 1.4, 2.3, and 2.6 h in the three groups. There was no clear evidence of significant dose-dependent effects on any pharmacokinetic parameters in any of the groups. Piperacillin levels in urine were far higher than those in serum, generally exceeding the minimal inhibitory concentrations for susceptible organisms during the 24 h after both the 1- and the 4-g dose. Piperacillin dosage modification is required only in patients with severe renal impairment.

Fleroxacin (Ro 23-6240) Distribution in Canine Prostatic Tissue and Fluids

The distribution of fleroxacin (Ro 23-6240) in canine prostatic tissue and fluids was investigated under steady-state conditions during intravenous infusion. Mean ratios of fleroxacin concentration in tissue and fluids over concentration in plasma were 1.57 +/- 0.25 for prostatic tissue, 1.12 +/- 0.28 for prostatic secretion, and 0.93 +/- 0.14 for prostatic interstitial fluid. These levels and concentrations in urine were several times higher than the MIC for most pathogens that cause chronic bacterial prostatitis and urinary tract infection. The MICs for several isolates of Escherichia coli were only slightly affected by canine prostatic secretion, human prostatic tissue extract, and human urine. Clinical trials with fleroxacin appear justified for chronic bacterial prostatitis and urinary tract infection.

Chronic bacterial prostatitis: theoretical and experimental considerations.

SummaryThe results of the treatment of chronic bacterial prostatitis are disappointing. The current status of antimicrobial and immunological research is described. While both a local and systemic antibody response is demonstrated in acute bacterial prostatis, only a local antibody production is found in chronic bacterial prostatitis. This response as reflected in the expressed prostatic secretion is specific for the infecting organism and immunoglobulin A is the major antibody class involved. Drug penetration into the prostate has mainly been studied in dogs and the ideal drug appears to be a lipid-soluble base which will concentrate in the slightly acidic prostatic secretion because of ion-trapping. However, these results are not directly applicable to humans because of the slight alkalinity of human prostatic secretion, the localization of the chronic inflammatory process in the interstitium, and the evidence of an active secretory mechanism for trimethoprim. The clinical consequences of these findings are discussed in relation to several recent studies and the treatment with lipid-soluble bases with a low plasma protein binding over extended periods is recommended.

Urodynamics of the lower urinary tract

SummaryThe principles and techniques of uroflowmetry, cystometry, pressure-flow studies and urethral pressure profilometry are reviewed. The interpretation of urodynamic tests depends on the methodology used and whether the patients usual voiding symptoms during the examination. The more complicated urodynamic tests may require computer assistance both for data storage but also for test interpretation. One of the main challenge in future urodynamic is to transform these tests to clinical usable tools.

Comparison of concentrations of rifampin and a new rifamycin derivative, DL 473, in canine bone.

Constant-infusion experiments were performed in 14 dogs to determine the penetration into bone of rifampin and a new C-3 substituted rifamycin, DL 473. The drugs were assayed in cortical bone and medulla from tibia-femur and cortical and cancellous bone from rib. After identical dosage, the concentrations of DL 473 appeared to be higher, except in the medulla, although the serum concentrations of rifampin were almost twice as high as those for DL 473. The concentrations of both drugs in all bone areas were several times higher than their minimum inhibitory concentrations against pathogenic Staphylococcus aureus.

Rosamicin in Urethral and Vaginal Secretions and Tissues in Dogs and Rats

In animal studies we investigated the distribution of rosamicin in plasma and urethral and vaginal tissues in rats as well as in urethral and vaginal secretions in dogs. We found concentration ratios between urethral secretion and plasma of 1.9 and between vaginal secretion and plasma of 2.4. The rosamicin concentrations in urethral and vaginal tissue significantly exceeded the levels of all other tissues investigated. Because rosamicin could be valuable for the treatment of bacterial urethritis and the colonization of the vaginal introitus with fecal bacteria in women, it should be investigated clinically in this respect.