Biomedical subjects
Publications and source records attributed to T C Gasser.
Intracavernous self-injection with vasoactive drugs is a new treatment for impotence. Although few reports of side effects have been published complications such as priapism and fibrosis of the spongy tissue are of concern. We report a case of penile fibrosis after intracavernous self-injection of a combination of phentolamine and papaverine.
To evaluate the efficacy and safety of intracavernous self-injection of phentolamine and papaverine for the treatment of impotence, 30 patients were enrolled in a prospective, randomized, double-blind, placebo-controlled cross-over study of papaverine and phentolamine versus normal saline. A total of 29 patients completed the study. The phentolamine plus papaverine combination resulted in erection in 24 patients (82.8 per cent) and no erection occurred after injection of saline. Of the patients 12 (41.4 per cent) experienced technical difficulties with the injection. Ecchymosis of the penis at the site of injection was common and 1 patient experienced priapism that resolved spontaneously. No other side effects occurred. Intracavernous self-injection with phentolamine and papaverine appears to be a safe and effective treatment of impotence but long-term effects must be determined.
The pharmacokinetics of ciprofloxacin following single oral doses of 500 and 750 mg in 32 patients with various degrees of renal function impairment were investigated in an open, randomized crossover fashion. Ciprofloxacin was administered after overnight fasting; the washout time between the two doses was 1 week. Serum and urine samples were collected serially between 0 and 24 h and subjected to bioassay and high-performance liquid chromatography. Pharmacokinetic parameters were analyzed, assuming an open two-compartment model with first-order input and elimination. A distinct difference was observed in pharmacokinetic parameters between patients with impaired renal function (creatinine clearance, less than 50 ml/min per 1.73 m2) and those with normal renal function (creatinine clearance, greater than or equal to 50 ml/min per 1.73 m2). For the former group, the area under the curve of serum concentration versus time was doubled, the renal clearance of ciprofloxacin was cut to one-fourth, the total and nonrenal ciprofloxacin clearance was reduced by 50%, and the elimination half-life was prolonged by a factor of approximately 1.7. The correlation between renal drug clearance and creatinine clearance was highly significant (r = 0.890; P less than 0.001). On the basis of these findings, it appears that a 50% dose reduction of ciprofloxacin in patients with impaired renal function (creatinine clearance, less than 50 ml/min per 1.73 m2) may be indicated to achieve concentrations in serum similar to those observed in normal individuals. As the concentration of ciprofloxacin in urine after 24 h remained above the MIC for most urinary pathogens, this drug appears to be of potential benefit for the treatment of urinary tract infections in patients with impaired renal function.
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.
Thirty-seven patients with prostatism and an estimated prostatic weight of less than or equal to 20 g were randomly allocated to transurethral incision or resection of the prostate. Both procedures had an 85% success rate as judged by patients' personal evaluation. At 3 and 12 months follow-up a significant and identical improvement was noted in symptom score and uroflowmetry in the two groups. Postoperative catheterization time and hospital stay was only half as long in the incision group as in the resection group. No patients became impotent as a consequence of the procedures. Frequency of retrograde ejaculation was 28% in the incision group versus 100% in resected patients. Incision of the prostate is easy to perform and seems to be followed by less severe complications. It has a high patient acceptability and may cut the cost of transurethral surgery.
Transurethral incision of the prostate under local anaesthesia was performed in 27 patients with symptoms of infravesical obstruction and an estimated prostatic weight of 20 g or less. Local anaesthesia (lidocaine 1%) was infiltrated transurethrally under the urethral prostatic mucosa using a special needle adaptable to the resectoscope. Pain control, assessed with a scoring system, was judged as good or very good by the majority of patients (25) and fair by the remaining 2 patients. No patient required conversion to another type of anaesthesia. The results of surgery as estimated by symptom score, uroflowmetry, and patients' personal evaluation were good. Transurethral incision of the prostate can be satisfactorily performed under local anaesthesia; this may be especially applicable to high-risk surgical patients. Incision of the prostate in the treatment of benign prostatic hyperplasia may be performed as an outpatient procedure in selected cases.
Four newer quinolones (amifloxacin, ciprofloxacin, enoxacin, norfloxacin) were administered to female dogs by intravenous infusion. Drug concentrations in plasma, urine, and vaginal and urethral secretion were determined by bioassay. All four quinolones penetrated into vaginal and urethral secretion in concentrations several times higher than the MIC against common urinary pathogens, ciprofloxacin and norfloxacin reaching concentrations exceeding the simultaneous plasma concentrations. Because of their favorable antibacterial spectra, new quinolones should be investigated clinically for the treatment of recurrent urinary tract infection and bacterial vaginitis.
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Nosocomial urinary tract infections represent approximately 40 per cent of all nosocomial infections, thereby contributing considerably to secondary bacteremia and sepsis and possibly increased mortality. Urethral catheterization is the single most important predisposing factor in the development of urinary tract infection. Patients at increased risk of nosocomial infectious complications are the elderly, malnourished and debilitated, those with diabetes or prosthetic devices, and those on immunosuppressive therapy. About 75 per cent of nosocomial urinary tract infections are attributable to gram-negative bacteria, a disproportionate number of which when compared with community-acquired infections are caused by Proteus, Klebsiella, and Pseudomonas. There is enough evidence in the literature to support the use of prophylaxis in urologic surgery. Antimicrobial prophylaxis reduces the incidence of postoperative urinary tract infection. It does not seem to reduce the incidence of transient perioperative bacteremia but probably prevents the development of sepsis, thereby reducing the number of serious infective complications, the average hospital stay, and the associated total cost of treatment. To achieve adequate urine, blood, and tissue levels of the antimicrobial agent at the time of surgery, the drug should be given preoperatively. A short perioperative course represents sufficient prophylaxis. Regimens with combinations of beta-lactam and aminoglycoside antibiotics or single use of an extended spectrum beta-lactam antibiotic are acceptable for this purpose.
A study in guinea pigs was performed to investigate the importance of timing, dosage and duration of antimicrobial prophylaxis in urologic surgery. To simulate high-risk conditions, in one group a foreign body was implanted subcutaneously. The prostate and one kidney were cauterized and bacteremia was induced by intravenous injection of an Escherichia coli suspension. Various ciprofloxacin regimens were tested. The results indicate that antimicrobial prophylaxis is beneficial only if administered before or shortly after surgery. Full therapeutic dosage may not be necessary for prophylactic efficacy. Single-dose prophylaxis was as effective as multiple doses. Foreign body infection could be prevented by single-dose prophylaxis.
Prostate cancer (PCa) is the most commonly diagnosed cancer in men as well as the second leading cause of cancer death. Age, family history and race are proved risk factors for developing a PCa. Prostate specific antigen (PSA) in combination with the digital rectal examination (DRE) has proven to be an essential element in early prostate cancer detection. Enthusiasm for using transrectal ultrasound (TRUS) alone to identify early prostate cancer has not been demonstrated with longer follow-up. The major role of TRUS today is to ensure accurate wide-area sampling of prostate tissue in men with PCa suspicion. This is best accomplished by targeted biopsy of TRUS-suspicious lesions and systematic biopsy of areas without hypoechoic lesions. Urologists recommend digital rectal examination and a PSA blood test annually starting at age 50.
Since the introduction of prostate specific antigen (PSA) into widespread use in clinical practice for early detection of prostate cancer (PCa), in combination with digital rectal examination (DRE), there has been a marked increase in the incidence of localized, potentially curable, disease coupled with a simultaneous decline in regional and metastatic prostate cancer in the least years. After the diagnosis of adenocarcinoma of the prostate has been histologically confirmed, an accurate assessment of the stage--or extent--of the disease should be made. We will provide a critical assessment of the currently employed PCa staging modalities. Therapeutic options in locally defined PCa are analyzed. Intracapsular PCa (T1a-T2b N0 M0) is preferably managed by radical prostatectomy, "insignificant" cancers may be treated by watchful waiting. The outcome of irradiation is not as predictable as radical surgery. Neoadjuvant treatment with radical prostatectomy in locally advanced PCa is probably not as efficient as believed; in some instances the value of adjuvant treatment is undecided. As it seems irradiation in conjunction with androgen deprivation can equal efficacy of surgery.