Torben B. Kjaer

Prostatic tissue and fluid concentrations of trimethoprim and sulfamethoxazole experimental and clinical studies

The concentrations of trimethoprim and sulfamethoxazole were determined in prostatic fluid and tissue of the dog after constant intravenous infusion. Concentrations of trimethoprim in both prostatic fluid and tissue exceeded the simultaneous serum concentrations, whereas the sulfamethoxazole prostatic fluid and tissue concentrations were much lower than the simultaneous serum concentrations. Prostatic tissue obtained from patients undergoing transurethral resection of the prostate also contained trimethoprim in higher but sulfamethoxazole in lower concentrations than the simultaneous serum concentrations after oral administration of these drugs preoperatively. In a patient with urinary diversion, trimethoprim was found in prostatic fluid in concentrations as high as forty-four times the simultaneous serum concentrations whereas sulfamethoxazole was found in concentrations representing only a fraction of the simultaneous serum concentrations. These findings lend support to the use of trimethoprim in the treatment of bacterial prostatitis.

Treatment of complicated urinary tract infections. Comparative study of sisomicin and gentamicin.

The efficacy and safety of the two aminoglycoside antibiotics, sisomicin and gentamicin, were investigated in a prospective randomized study of 100 elderly male patients with complicated urinary tract infections. Both drugs were administered intramuscularly, sisomicin twice daily and gentamicin three times daily according to body weight. All bacteria isolated from the urine were sensitive to both antibiotics by disk sensitivity method. Seventy per cent of the patients treated with sisomicn and 63 per cent of those treated with gentamicin were cured of infection. There was no apparent toxicity noted from either drug. The twice daily sisomicin administration appeared to be as effective and safe as the three times daily administration of gentamicin in the treatment of complicated urinary tract infections.

Antimicrobial agents in prostatic fluid and tissue

SummaryLipid solubility and a basic pKa are the necessary requirements for the secretion of antibacterial agents into the prostatic fluid in dogs in concentrations exceeding the simultaneous serum concentrations. Protein binding appears to be of less importance. This was demonstrated in constant infusion experiments in dogs. Ampicillin concentrations in prostatic fluid in a patient with urinary diversion were found to be much higher following oral administration of the lipid-soluble hetacillin ester than following administration of ampicillin. This had also previously been found to be true in prostatic fluid and tissue of dogs. The prostatic tissue ampicillin concentrations in humans were not found to be increased following hetacillin ester administration, possibly because the drug was washed out of the tissue during surgery. The importance of the basic pKa is shown in constant infusion experiments in dogs with trimethoprim, erythromycin and rosamicin, all 3 lipid-soluble antibiotics having a high pKa and all being found to concentrate in prostatic fluid and tissue of dogs.ZusammenfassungFettlöslichkeit und ein basisches pKa sind die notwendigen Voraussetzungen für die Sekretion von antimikrobiellen Substanzen in das Prostatasekret von Hunden in Konzentrationen, die die gleichzeitige Serumkonzentration überschreiten. Eiweißbindung scheint weniger wichtig zu sein. Dies wurde in Dauerinfusionsexperimenten bei Hunden demonstriert. Ampicillin-Konzentrationen im Prostatasekret eines Patienten mit einer künstlichen Harnableitung waren viel höher nach oraler Verabreichung des lipidlöslichen Hetacillin-Esters als nach Verabreichung von Ampicillin. Dies wurde schon früher in Prostatasekret und -gewebe von Hunden festgestellt. Die Ampicillin-Konzentrationen im Prostatagewebe von Menschen wurden nach Hetacillin-Ester-Verabreichung nicht erhöht festgestellt, möglicherweise, weil das Antibiotikum während der Operation aus dem Gewebe gespült wurde. Die Wichtigkeit des basischen pKa wird in Dauerinfusionsexperimenten mit Hunden mit Trimethoprim, Erythromycin und Rosamicin gezeigt. Alle drei lipidlöslichen Antibiotika haben ein hohes pKa, und es wurde festgestellt, daß alle in Prostatasekret und -gewebe von Hunden konzentriert werden.

Scanning electron microscopy of normal and malignant human urothelium.

Scanning electron microscopy (SEM) was used to evaluate and compare normal bladder mucosa to tumor epithelium as well as to normal-appearing mucosa in patients with diagnosed bladder tumor. Bladder urothelium adjacent to tumors exhibits a characteristic pattern of fine structural relief which is distinct from normal uroepithelium. These changes in microcontour may be guides to the identification of early malignancy, and thus the technique will be helpful in deciding how aggressive the treatment of bladder tumor should be.

Effect of estramustine phosphate on plasma testosterone during treatment of carcinoma of prostate

Estramustine phosphate administered orally at 900 mg. daily depressed plasma testosterone levels in 10 consecutive patients who had previously been treated with estrogen hormones and/or orchiectomy and who were all in relapse from carcinoma of the prostate. Approximately one half of the patients responded to the treatment clinically. The decrease in plasma testosterone did not correlate with the clinical response. The clinical effect of estramustine phosphate may be due to decreased plasma testosterone levels, inhibiton of 5-alpha reductase activity, and a local cytotoxic effect.

Treatment of complicated urinary tract infections with sisomicin a comparison of once daily and twice daily dosage forms

SummaryIn the first part of this study the efficacy and tolerance of the new aminoglycoside antibiotic sisomicin administered intramuscularly 1 mg/kg body weight every 12 hrs was studied in the treatment of complicated urinary tract infections in 25 elderly male patients. The antibiotic was found to be well tolerated and effective, eradicating urinary tract infections caused by sensitive micro-organisms. In the second part of this study sisomicin administered intramuscularly once daily (75 or 100 mg) or twice daily (50 or 75 mg every 12 hr) according to body weight was evaluated in the treatment of complicated urinary tract infections in 24 elderly male patients randomized in two equal groups according to the dosage regimen. No significant difference in the tolerance and efficacy was found between the two groups. The cure rate in all 49 patients, defined as having a negative urine culture one week following treatment, was 75%. The sisomicin urine concentrations from 6 to 12 and even 12 to 24 hrs following the intramuscular injection was many times higher than the minimum inhibitory concentration for most gram-negative organisms commonly found in urinary tract infections. This probably explains the efficacy of the single daily dosage regimen which therefore can be recommended as effective and safe in the treatment of complicated urinary tract infections.ZusammenfassungDer erste Teil der Studie umfaßt die Überprüfun von Wirkung und Verträglichkeit von 1 mg/kg KG Sisomicin intramuskulär zweimal täglich verabreicht, bei komplizierten Harnwegsinfektionen von 25 älteren Männern. Das Antibiotikum wurde gut vertragen und beseitigte Harnwegsinfektionen durch empfindliche Keime. Im zweiten Teil der Studie wurde Sisomicin intramuskulär einmal täglich (75 mg oder 100 mg) bzw. zweimal täglich (50 mg oder 75 mg alle 12 Std.) entsprechend dem Körpergewicht bei 24 älteren Männern angewendet. Die Zuteilung zu den beiden Dosierungsgruppen erfolgte über eine Randomliste. Keine signifikanten Unterschiede in Wirkung oder Verträglichkeit fanden sich zwischen den beiden Dosierungsgruppen. Die Heilungsquote bei allen 49 Patienten, definiert durch eine negative Harnkultur eine Woche nach Ende der Behandlung, betrug 75 %. Die Harnkonzentrationen des Siomicin 6 bis 12 und sogar 12 bis 24 Std. nach der intramuskulären Injektion waren vielfach höher als die minimale Hemmkonzentration für die meisten gramnegativen Keime, die üblicherweise bei Harnwegsinfektionen gefunden werden. Das dürfte die Wirkung der einmal täglichen Dosierung-erklären, die deshalb als sicher und wirksam bei komplizierten Harnwegsinfektionen empfohlen werden kann.

Crossed Ectopia of Seminal Vesicles, Renal Aplasia and Ectopic Ureter

A unique case of left ureteral opening into a seminal vesicle, ipsilateral renal hyperplasia and crossed ectopia of the seminal vesicles is reported. This 24-year-old white man underwent a nephroureterectomy for relief of symptoms of lower urinary tract infection. The embryological development of this abnormality is discussed briefly.

A Comparative Study of Ticarcillin and Gentamicin in the Treatment of Complicated Urinary Tract Infections

Ticarcillin is a semisynthetic penicillin for parenteral use with an antibacterial spectrum similar to that of carbenicillin but better in vitro activity against Pseudomonas aeruginosa.

Sisomicin treatment of complicated urinary tract infections

The purpose of this presentation is twofold: firstly, to present our experience with sisomicin in the treatment of complicated urinary tract infections; secondly, to summarize the results of our clinical trials with this antibiotic in patients with normal and impaired renal function, with particular reference to the determination of dosage and dosage intervals in cases of impaired renal function. We first treated 36 male patients (average age 71 years) with complicated urinary tract infection, but with normal renal function. These were divided into three groups of 12 each, with one group receiving sisomicin 0.5 mg/kg every eight hours, while the other two received 0.75 mg/kg and 1 mg/kg respectively every eight hours. Each group was treated for a total of seven days. Defining cure as a negative urine culture two to three weeks after cessation of antibiotic therapy, we obtained a cure rate of 50, 75 and 58% for the three respective groups. Sisomicin was well tolerated locally and systemically. In our second clinical trial we treated 29 males, all with complicated urinary tract infections, and again divided the patients into three groups, but this time according to renal function. Patients in Group A had a serum creatinine of 1.4 mg/ 100 ml, with an average creatinine clearance of 82 ml/min. Group B had a serum creatinine of 1.5 to 2.5 rag/100 ml and an average creatinine clearance of 34 mI/min, and Group C had a serum creatinine of 2.5 mg/100 ml and an average clearance of 18 ml/min. All patients received 1 mg/kg of sisomicin intravenously (IV) the first day, followed by 1 mg/kg intramuscularly (IM) every eight hours (Group A), every 12 hours (Group B) and every 24 hours (Group C) for seven days. Again sisomicin was well tolerated. It was equally effective in patients with normal and impaired renal function and a cure rate of 56% was obtained. The sisomicin urine concentrations up to 24 hours following a single IV injection in all three groups of patients were many times higher than the MIC values for most gram-negative organisms found in urinary tract infections. There was a good correlation between the sisomicin serum half-life and the serum creatinine level. The dosage intervals for administration of sisomicin in patients with normal renal function should be approximately eight hours, increased in azotemic patients by multiplying this interval by the serum creatinine (in rag/100 ml) or, if the dosage interval is kept unchanged, by dividing the dosage by the serum creatinine. Thus, a patient with a serum creatinine of 3 rag/100 ml would require 1 mg/kg every 24 hours. Since we found high sisomicin concentrations in the urine 8 to 16 and even 16 to 24 hours following IM administration, we proceeded to our next study in which we compared two groups of patients, again with complicated urinary tract infections, using two different dosages of sisomicin. One group received 75 mg of sisomicin every 12 hours, the other 100 mg every 24 hours. The cure rate, defined as a negative urine culture one week after treatment, was 75 % in both groups. In our last study we compared sisomicin with gentamicin in a prospective, randomized study of 100 patients with complicated urinary tract infections. Sisomicin (75 mg IM) was administered every 12 hours for seven days and gentamicin (80 mg IM), every 8 hours for seven days. Both groups were comparable in terms of age, other demographic factors, the urinary tract pathology and causative bacteria.

The Excretion of Hetacillin Methoxymethyl Ester (BL-P1761) into the Prostatic Fluid of the Dog

The lipid-soluble methoxymethyl ester of hetacillin was found to penetrate well into the prostatic fluid of dogs. The prostatic fluid ampicillin concentrations following intravenous infusion of the ester were approximately 15 times higher than following intravenous infusion of ampicillin in equivalent amounts and were approximately 1/2 of the simultaneous blood concentrations. The bactericidal effect of the prostatic fluid following hetacillin ester administration is demonstrated in vitro.