Biomedical subjects
Publications and source records attributed to J Frick.
We treated 15 patients with all sonographic criteria of a simple testicular cyst. Of the patients 6 were operated on and the diagnosis was confirmed histologically, while 9 did not undergo an operation but are under close observation (mean surveillance 11 months). All patients are without any detectable malignancy. The possibility of a surveillance strategy in simple intratesticular cysts is discussed.
STUDY OBJECTIVE: 1) to investigate serum levels of tumor necrosis factor-alpha in patients treated with recombinant interferon-gamma and 2) to relate changes in TNF serum levels to other biological responses observed during treatment with interferon gamma (IFN-gamma). PATIENTS: Five patients suffering from metastasizing renal cell carcinoma. INTERVENTION: Each patient received three treatment cycles of 10 micrograms, 100 micrograms and 500 micrograms IFN-gamma applied three times at weekly intervals. The treatment cycles were separated by a therapy free interval of two weeks. The order of dose levels was randomly assigned to each patient. MEASUREMENTS AND MAIN RESULTS: Tumor necrosis factor alpha (TNF-alpha), IFN-gamma and neopterin serum levels, monocyte counts in the peripheral blood and body temperature were measured immediately before and 4, 24, 48, 72, and 168 h after each application of IFN-gamma. Results indicated that elevated serum levels of TNF-alpha are induced by 100 micrograms and 500 micrograms IFN-gamma. Repeated application of the same dose led to downregulation of TNF release into the serum. Changes in TNF serum levels did not correlate with the magnitude of febrile reactions, neopterin production or IFN-gamma serum levels.
The use of alkali citrates for preventing the recurrence of calcium oxalate stones was investigated in two trials. In trial I, alkali citrates were given continuously for 18 months to 8 patients who had shown a tendency to recurrent stone formation. In trial II, 12 similar patients were given intermittent therapy for 12 months. The expected changes in urine chemistry were checked at intervals of 3 months. Recurrent stone formation (2 episodes) was observed in only 1 patient (in trial II) during alkali citrate administration; before therapy this patient had suffered an average of 10 attacks of stone formation annually. In the light of the experience gained in these trials, continuous administration of alkali citrates is recommended; the duration of treatment should be tailored to individual needs, but it should not be prolonged indefinitely. Besides having well-attested effectivity of stone prevention, this mode of therapy carries a relatively low incidence of side effects.
From 114 patients treated with local radiotherapy after nephrectomy up to now 46 patients are alive. 59 patients died; 55 patients died because of the tumor, 4 patients died because of other genesis. At 4 patients, who are alive, a secondary therapy because of pulmonary metastasis was performed. Three times a solitary metastasis of the lung was removed surgically. One female patient came into a CR under therapy with Gestagen (Depo Provera). Three patients (2.6%) died because of a local recidive. There was no change of survival rates and local recidive rates compared to surgery alone.
Ninety-one patients with metastatic colorectal cancer were treated with continuous ambulatory 5-fluorouracil (5FU) infusion 250-300 mg/m2/day through a chronic indwelling central venous catheter. Twenty-six of the 91 patients (29%) had received previous bolus 5FU. Fifty-eight of the 91 patients (64%) had two or more sites of disease, and 74 of 91 patients (81%) had liver metastases. Results were complete remission in 5 of 91 (6%), partial remission in 25 of 91 (27%), stable disease in 33 of 91 (36%), and progressive disease in 28 of 91 (31%), for an overall response rate of 30 of 91 (33%); median duration of response was 7 months. Twenty-six of 65 previously untreated patients (40%) experienced objective response. Median survival from initiation of treatment for all patients was 11 months. Forty-one percent of patients experienced no significant toxicity and were able to continue therapy without treatment interruption. Toxicities necessitating treatment interruption included stomatitis in 35 patients (39%), hand-foot syndrome in 33 patients (36%), and diarrhea in 10 patients (11%). No significant myelosuppression or serious catheter-related complications were encountered. We conclude that continuous systemic venous infusion of 5FU produces a higher response rate than traditional bolus 5FU schedules, with apparent enhancement of survival and easily managed toxicity.
We present the ultrasonic diagnoses and treatment of 44 patients with blunt scrotal trauma (rupture of the testis, hematocele, intratesticular hematoma and hematoma of the scrotal layers). Purely intratesticular hematoma without any other accompanying injury also can be detected sonographically. When massive scrotal swelling is present ultrasound is valuable to determine the status of the underlying testis even if discrete fracture planes of the tunica cannot always be detected. To achieve best long-term results early surgical intervention should be performed in cases of rupture of the testicle and hematocele, while hematoma of the scrotal layers and purely intratesticular hematoma can be treated conservatively.
Because of the atypical symptomatology, which can mimic an EPH-gestosis, the physiological elevation of serum aldosterone in the third trimester and restricted diagnostic possibilities, the diagnosis of primary hyperaldosteronism during pregnancy is difficult. A case of an adrenal adenoma during pregnancy is reported.
The object of this study was to investigate the effects of different single doses of recombinant interferon-gamma (rIFN-gamma) on white blood cell counts, differential blood counts, and the relative composition of T-cell subsets in the peripheral blood of cancer patients. Sixteen patients suffering from metastasizing renal cell carcinoma received 10, 100, or 500 micrograms of rIFN-gamma three times at weekly intervals. After a therapy-free interval of 2 weeks, the next dose level was applied. The order of dose levels was assigned randomly to each patient. White blood cells, differential blood counts, and the number of Leu1, Leu3, Leu2a, Leu7, and HLA DR+ cells were measured immediately before and at 4, 24, 48, 72, 96, and 168 h after the administration of single doses of rIFN-gamma. Results indicated that white blood cells were transiently removed from the blood circulation after administration of IFN-gamma. Monocytes, HLA DR+ cells, and Leu7+ cells were reduced to below 50% of pretreatment values 4 h after application of the cytokine. CD8+ cells and granulocyte counts declined to approximately 70% of pretreatment values 24 h after IFN therapy. The preferential reduction of CD8+ lymphocytes resulted in a temporary increase of the T4/T8 ratio in these patients.
The activity of angiotensin converting enzyme (ACE) was assessed in human body fluids (serum, seminal plasma, prostatic secretions), in tissue extracts of the testis, epididymis, prostate and skeletal muscle, in split ejaculates and in seminal plasma obtained from patients before and after vasectomy. To ensure the specificity of the results the dependence of ACE activity on specific inhibitors was evaluated. Enzyme activity found in tissues of the male genital tract was considerably higher than that in serum and other tissues. ACE in human seminal plasma is synthesized by the testis, epididymis and prostate in different amounts.
Pulsatile administration of LHRH can drive the pituitary to secrete LH and FSH in a pattern that closely mimics the physiological pattern of the hypothalamic-pituitary-gonadal axis. As there is evidence that infertility in some men is due to dysfunction of this axis, 14 men with reported infertility of more than 2 years duration were treated by long-term pulsatile LHRH therapy. They were 24-42 years of age, with variable degrees of oligozoospermia, elevated FSH levels but normal LH and testosterone levels. The number of endogenous LH pulses/24 h was less than eight in all 14 subjects. The degree of testicular damage was assessed semi-thin sections prepared from biopsies of both testes. Scores for spermatogonia per seminiferous tubule (SPT) were calculated from the actual number of Ad-spermatogonia/tubule. Patients were grouped according to sperm density and SPT score (groups I-III). Pulsatile LHRH therapy was administered by means of a portable infusion pump; 4 micrograms LHRH were administered subcutaneously every 120 min for a period of 6 months. This treatment restored the normal pattern of LH secretion to 12 LH pulses/24 h in all patients. A statistically significant decrease of mean FSH levels to normal, and an increase of mean LH levels was observed in most of the 14 patients. Testosterone values did not change in any group. Marked improvement of the sperm count was observed in eight out of 14 patients (groups I and II) and three pregnancies were reported during the treatment periods. These results suggest that some states of male infertility are due to hormonal dysregulation and that these patients may benefit from pulsatile LHRH therapy.
We tested the clinical efficacy of a biologically active dose (BAD) of interferon (IFN)-gamma for treatment of progressive renal cell carcinoma (RCC). Twenty-two RCC patients with disease progression subsequent to nephrectomy were entered on a phase II clinical trial. During an initial dose-finding phase, biochemical responses to repeated once-weekly subcutaneous injections of 10, 100, or 500 micrograms of recombinant IFN-gamma were tested in 16 patients. Results indicated that 100 micrograms IFN-gamma applied once weekly was biologically active with induction of serum beta 2-microglobulin and neopterin. Such a dose induced a nearly maximum response of both markers lasting more than 4 days. This dose was also associated with minimal side effects. A dose of 100 micrograms IFN-gamma given once weekly was, therefore, subsequently given weekly for long-term treatment. During a median time of therapy of 10 months (range, 2 to 32 months) two complete (CR; 20+, 20+ months) and four partial tumor responses (PR; 6+, 7+, 8+, 24+ months) were seen (30% CR plus PR; 95% confidence limits, 12% to 54%) among 20 patients evaluable for response. Patients with refractory disease had significantly lower IFN-gamma-induced increments of serum beta 2-microglobulin than those who achieved clinical remission or stable disease.
This study is part of a series designed to identify the smallest effective gossypol dose for male fertility control. Three men, aged 31-35 years, were administered gossypol, 10 mg/day, orally for 3 months. Urinalysis and assays for plasma hormone values, including cortisol, beta 2-microglobulin, potassium, and BUN, showed no changes during treatment. Forward sperm motility, however, was severely affected by the end of the treatment period (less than 4% forward motility). Sperm density also showed a marked decrease. The subjects developed no undue side effects.
Luteinizing hormone-releasing hormone (LH-RH) secretion from the hypothalamus follows a rhythmic pattern, inducing pulsatile luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretion from the pituitary gland. Consideration of this physiologic principle led to the introduction of pulsatile LH-RH therapy via infusion pump for the treatment of different forms of hypogonadotropic hypogonadism. We report on 10 male patients, 16 to 28 years of age, suffering from idiopathic hypogonadotropic hypogonadism (IHH) including Kallman's syndrome (n = 2) and delayed puberty (n = 2). All presented with complete eunuchoidism and had undergone no treatment for their conditions during the previous 2 years. LH-RH was administered in subcutaneous pulses of 4 to 16 micrograms, with a portable infusion pump (ZYKLOMAT, Ferring Corp., Kiel, FRG); treatment periods ranged from 6 to 24 months. With therapy, the subjects improved secretion of LH, FSH and testosterone. Testicular volumes and penis size increased; all patients developed normal secondary sexual characteristics. Spermatogenesis was induced in all patients. The time to onset of spermatogenesis ranged from 3 to 15 months. No major side effects were observed, and no patient dropped out of the study. The results indicate that pulsatile LH-RH therapy is an highly effective treatment for IHH and delayed puberty.
To share contraceptive measures between partners is a goal which should be reached in the future. The possibilities on the male side are still limited in comparison with the techniques available for women. During the last 20 years many efforts have been undertaken to study and evaluate possible methods for fertility control in the male, based on interaction with the hormonal axis, sperm maturation and sperm transport. The requirements for such a method in the male are the same as in female: high efficacy, little or almost no side-effects, high practicability and compliance and the possibility for easy reversibility in a high percentage of men. Despite their increasing acceptability worldwide, the existing male methods, condom and vasectomy, do not fully meet these requirements and therefore a search for alternative male methods is warranted. At present, the following medical approaches to male fertility control have been tested or are under consideration: (i) selective inhibition of FSH: antibodies, inhibin; (ii) inhibition of pituitary-gonadal axis: steroids such as testosterone, progestin-testosterone combinations, LHRH analogues with and without testosterone substitution; and (iii) selective inhibition of spermatogenesis by gossypol, a phenolic compound from cotton plant. Whether one of these methods will reach the desired goal for male fertility control has yet to be determined.
The reversibility of the effect of gossypol on testicular histology and fertility was studied in rats. Adult males of proven fertility were treated orally with gossypol acetic acid (15 mg/kg) for 9 or 16 weeks (groups 1 and 2, respectively). Another groups of animals (group 3) was given gossypol (15 mg/kg) for 16 weeks and killed 6 weeks after the end of treatment. Control animals (group 4) were given the vehicle only by oral intubation. In the mating studies, although only 33% of the animals in group 1 were infertile, 100% infertility was observed following 16 weeks of gossypol treatment (group 2). All animals in group 3 regained their fertility 6 weeks after cessation of drug treatment. Damage was observed to 15.7% of the seminiferous tubules after 9 weeks of drug treatment, and to 78% after 16 weeks of treatment. Extensive vacuolization, increased numbers of lipid droplets, degeneration of germ cells, loosening of the epithelium, and a significant decrease in the number of pachytene spermatocytes (stages VII-X) and spermatids (steps 7-10 at stages VII-X) were observed after gossypol treatment. There was a decrease in the diameter of only stage VIII seminiferous tubules after 9 weeks of treatment, whereas a reduction was observed in the tubules of all stages after 16 weeks of gossypol treatment. In the recovery phase, the diameter of seminiferous tubules was similar to that of controls, except for tubules at stage VIII. No change in the area of the lumen of the seminiferous tubules and lipid bodies was observed after 9 weeks of drug treatment, but a marked reduction in the area of the lumen (stages II-X) and an increase in lipid bodies (all stages) was observed after 16 weeks of gossypol treatment. Six weeks after cessation of treatment, the area of the lumen and the number of lipid bodies were comparable to values in controls. A reduction in the area of the epithelium was restricted to just a few stages (VIII-XIV) in treated animals at 9 weeks, whereas after 16 weeks the area of the epithelium was decreased in all tubules. In the recovery phase, except for tubules at stage VIII, the area of the seminiferous epithelium was comparable to that in controls.
In 14 children, aged 2-14 years, extracorporeal shock wave lithotripsy was performed for renal and ureteral calculi. In 12 out of 14 children, including 1 patient with a staghorn calculus, complete stone clearance was achieved within the first 3 months following treatment representing 85%. No undue side effects or complications were encountered in this series.
We investigated the effect of high energy shock waves on human spermatozoa in vitro. Human semen samples of proven motility, kept in polyethylene tubes, were subjected to shock waves (100, 500, and 1,000) using a HM3 Dornier lithotripter. A progressive decrease in the spermatozoa vitality was observed with increasing doses of shock waves. Spermatozoa decapitation became significant with increasing doses of shock waves. A progressive decrease in sperm motility was observed following exposure to shock waves, but these changes were not significant.
Scrotal ultrasound was carried out since 1980 in five centers. 1,971 cases presenting with pathological conditions of scrotal content were reviewed to asses limitations and possibilities of the method. Scrotal sonography was found to be a highly reliable method to distinguish between intra- and extratesticular lesions. The data presented reveal that sonography is not capable of differentiating reliably between benign and malignant lesions. In the decision-making process ultrasound is sometimes of great help to the urologist but surely no substitution for careful examination and history taking.