Biomedical subjects
Publications and source records attributed to J Frick.
58 patients with a purely intratesticular lesion were investigated with scrotal ultrasound. A pathognomonic echo pattern could be found for simple parenchymal cysts and hemangiomas only. The nature of all other lesions (chronic orchitis, hematoma, epidemoid cyst, testicular necrosis, abscess and tuberculosis) could not be defined solely on sonographic grounds.
ESWL is a non invasive method for treatment of renal and ureteral stones. This method offers the advantage that all radiopositive renal stones irrespectively of their actual location in the collecting system and the free parts of the ureter can be localized and treated. Between March 1985 and December 1986 in 14 children, aged 2 to 14 years, with renal and ureteral calculi this method was performed. Further should be referred to the fact that two children with complete staghorn calculi were successfully treated by ESWL monotherapy. There was no morbidity and no undue side effects. 12/14 children (= 85%) were free of stones within the first three months following ESWL.
UNLABELLED: Twenty-five patients with refractory, metastatic carcinoma of the breast were treated with continuous ambulatory 5-fluorouracil (5 FU) infusion (200 to 300 mg/m2/day) through a chronic indwelling central venous catheter. All patients had had extensive previous treatment, including hormonal therapy in 20/25 patients (80%), radiation therapy in 18/25 patients (72%), and an average of 4.6 previous chemotherapy drugs per patient (range 1-10). Twenty-three of 25 patients (92%) had had previous bolus 5 FU. Seventeen of 25 patients (68%) had two or more metastatic sites of involvement and 17/25 patients (68%) had visceral involvement. RESULTS: complete remission-1/25 (4%), partial remission-7/25 (28%), stable disease-6/25 (24%), and progressive disease-11/25 (44%), for an overall response rate of 8/25 (32%). Median duration of response was 6 months. Toxicities included hand-foot syndrome, mucositis, diarrhea, and nausea and vomiting, and required treatment interruption and/or dose attenuation in 9/25 patients (36%). No myelosuppression or serious catheter-related problems were seen. We conclude that continuous 5 FU infusion is a potentially effective salvage treatment that may provide meaningful palliation in some patients with carcinoma of the breast, in spite of extensive previous treatment.
Considering rIFN-gamma as a potent biological response modifier (BRM), we started an open phase II trial with rIFN-gamma in patients with advanced renal cell carcinoma (RCC). For optimization of the dose and schedule of rIFN-gamma, two biochemical serum markers, neopterin and beta-2 microglobulin, were chosen to monitor the biological response. In order to test the magnitude and kinetics of rIFN-gamma-induced neopterin and beta-2 microglobulin release in the serum, rIFN-gamma was administered thrice at three different dose levels in a randomly assigned order (0.01; 0.1; 0.5 mg). Neopterin and beta-2 microglobulin were assessed by means of commercially available radioimmunoassays. The results revealed: 1) strong, reproducible and dose-dependent increments of both markers after the first injection 2) downregulation of the magnitude of neopterin responses with repeated injections at each of the three dose levels tested, and 3) a dose-dependent downregulation of the magnitude of beta-2 microglobulin responses and of serum baseline values at the highest dose level tested. From these data, we conclude that both the dose and schedule might be of importance for optimization of biological responses to exogenously applied rIFN-gamma.
Between 1 January 1983 and 31 January 1986, 18 patients with distal hypospadias underwent corrective surgery using the MAGPI technique. The age of the young patients varied from 2 months to 12 years. Indication for an operation was mandatory by the presence of meatal stenosis (3 patients), which included the correction of the glans as well as the resection of the foreskin at the same time, or in case of the other children at the request of the parents who wished to prevent social discrimination. 12 patients were operated on using the simple MAGPI technique, whereas 6 underwent an operation extended by the rotation flap technique according to Byars. 16 of the 18 small patients showed excellent results regarding function (miction) as well as cosmetics. In 2 patients the cosmetic results were not entirely satisfactory although their parents were content with the outcome of the operation.
Thirteen patients with metastatic colorectal adenocarcinoma underwent treatment with continuous ambulatory 5-fluorouracil (5-FU) infusion 300 mg/m2/day and intermittent bolus methotrexate (MTX) (200 mg/m2) with calcium leucovorin (LCV) 10 mg/m2 orally every 6 h X four to eight doses given 24 h after MTX. Although MTX administration was planned every 14 days, the average time between treatments exceeded 19 days (range 14-42) because of excessive toxicity. All patients experienced toxicity at some time in their treatment course, requiring interruption of 5-FU infusion in 12 of 13 patients. Significant toxicities included stomatitis (13 of 13 patients), hand-foot syndrome (8 of 13 patients), and diarrhea (3 of 13 patients). Toxicity did not appear to be minimized by attenuation of MTX and/or 5-FU dosage or by increasing the dose and/or duration of LCV. At this dosage schedule the addition of MTX/LCV to 5-FU infusion results in excessive and unacceptable toxicity and does not appear to improve treatment results.
At least three species of tissue kallikrein-like antigens are present in human seminal plasma which differ in their molecular masses and enzymatic activities. At least one of these species is a genuine tissue kallikrein as judged by the criteria of molecular mass, immunoreactivity, inhibition by aprotinin and non-inhibition by soybean trypsin inhibitor, and the ability to release kallidin from kininogen. The prostatic gland was identified as the origin of the seminal fluid tissue kallikrein first by indirect studies and then by demonstrating the presence of immunoreactive tissue kallikrein both in prostatic tissue and secretion.
The investigations were carried out with partially purified angiotensin converting enzyme (E.C.3.4.15.1) from human seminal plasma and from human blood plasma. The Km-constants for angiotensin converting enzyme (ACE) from both sources, estimated by the use of synthetic substrates, were in the same order. The catalytic properties of the enzymes were characterized by a series of known peptidase inhibitors. The male antifertility drug gossypol (1,1',6,6',7,7'-hexahydroxy-3,3'-dimethyl-5,5'-bis-isopropyl-(2,2' -naphthalene)--8,8'-dicarboxaldehyde) was identified as a potent ACE-inhibitor. The inhibitory constants of several kinins and other biologically active peptides were determined. Any regulatory influence of the peptides investigated on the ACE-activity in vivo is not probably. The inhibitor of Zn-containing metalloproteases 2-(N-hydroxycarboxamido)-4-methylpentanoyl-L-alanylglycin e amide) (Zinkov) selectively inhibited ACE from blood plasma, whereas ACE from seminal plasma was not influenced. In seminal plasma the majority of the enzyme is associated with macromolecular structures, identified as membrane vesicles. These vesicles contain also other enzymatic activities usually detectable in seminal plasma. In the male genital tract ACE is synthesized in the prostate, epididymis and testis. As our data indicate ACE seems not to be involved in the regulation of sperm motility.
The present study examines the ultrastructure of ejaculated spermatoza from bonnet monkey, Macaca radiata under normal conditions, with gossypol treatment and during recovery from such treatment. Monkeys were fed orally with gossypol acetic acid (GAA) for 3 months (4 mg/monkey/5 days a week). Semen samples collected by electro-ejaculation, and the spermatozoa were examined using both light and electron microscopy. The degree of motility was also noted by Kalla et al. Ejaculated spermatoza were immotile 90 days after GAA treatment, but little evidence for any abnormality in the spermatozoa could be seen by light microscopy. Some ultrastructural changes were observed, but not to the extent previously reported in spermatozoa of Macaca fascicularis. After termination of treatment, semen samples were obtained every 5th day until sperm count and motility recovered to the normal level. After 90 days only a small proportion of spermatozoa showed abnormal structure. We conclude that in a subhuman animal model gossypol induced effects on sperm motility and morphology are reversible.
In this study we investigated the effect of low and high dosages of a potent LHRH agonist on the pituitary-gonadal axis with special consideration to the effect on the tubular compartment of the testis. Included were 3 treatment groups: the probands in Group I were treated with 3 X 50 micrograms HOE 766/week intranasally for 5 months; in Group II with 3 X 100 micrograms HOE 766 intranasally/day for 6 months and in Group III with 3 X 200 micrograms HOE 766 intranasally plus 5 mg fluoxymesterone orally/day for 5 months. With the low dose (Group I) no changes in the seminal parameters measured could be observed whereas LH and FSH levels increased in plasma, testosterone showed no change compared to pretreatment values. When high dosages/day of a potent LHRH agonist were administered without androgen replacement (Group II) pronounced decrease of LH and FSH took place, the testosterone plasma levels approached the female range. Spermatogenesis was arrested. The agonist plus androgen replacement (Group III) counteracted the suppression of spermatogenesis.
This study was undertaken to determine the effects of gossypol alone and gossypol in combination with prostaglandin and aspirin. Rats were administered gossypol (40 mg/kg/day), gossypol and prostaglandin (PGF2 alpha-2 mg/kg/day), gossypol and aspirin (300 mg/kg) for 4 weeks. A marked effect of the gossypol-prostaglandin combination was observed on sperm motility and spermatogenesis. The effect of the gossypol-aspirin combination was less pronounced. The ratio of body weight to testicular and epididymal weights between the different groups showed no marked difference. No effect of drug treatment on plasma testosterone, LH and FSH was observed. The data presented in this paper suggest that prostaglandin plays an important role in the antifertility effects of gossypol.
We report on 18 patients, aged 43-77 years, with clinical stage-C adenocarcinoma of the prostate, primarily treated by pelvic lymphadenectomy and 125I-seed implantation. After lymphadenectomy, the staging assessment differed from the preoperative diagnosis as follows: 4 patients were classified as stage C; 6 as D1, and 8 as D2 (distant nodal metastases). The 4 patients, classified postoperatively as stage C, received no further treatment. 11 patients with a postoperative classification of stage D had additional external beam radiation to the pelvic and paraaortic lymph nodes with shielding of the implanted prostatic region. In addition, 8 of these 11 patients had hormonal therapy. The remaining 3 patients have been treated by combining interstitial irradiation with preoperative external beam radiotherapy; postoperative irradiation was supplemented when the lymph nodes were positive.
The effectiveness of a ten-day course of either oral bacitracin or oral vancomycin hydrochloride for treatment of Clostridium difficile-induced antibiotic-associated diarrhea was compared in a randomized double-blind study. Bacitracin was as effective as vancomycin in resolving diarrhea; most patients responded within five days of therapy with either drug. Three patients receiving bacitracin worsened during therapy; two of these were considered treatment failures. Neither C difficile nor its toxin was detected in stool samples collected on the final day of therapy in 71% of patients (10/14) receiving vancomycin and in 30% (3/10) receiving bacitracin. Five patients receiving bacitracin and three receiving vancomycin had at least one recurrence. Low but nontoxic concentrations of bacitracin were detected in serum samples collected from 11 patients. Oral bacitracin at this dosage level was as effective as vancomycin in resolving the symptoms of C difficile-induced antibiotic-associated diarrhea in most patients but was less effective in eradicating C difficile and its toxin from patients' stools.
To determine how the androgen binding protein in human testes (hABP) is related to the serum protein, testosterone-estradiol binding globulin (hTeBG), both proteins were isolated and compared. The hABP in extracts of human testes was composed of two molecular species based on concanavalin A (ConA)-Sepharose chromatography. Form I hABP did not interact with ConA while Form II hABP bound to ConA and eluted with alpha-methylmannoside. Form I and Form II hABP from five batches of testes were then purified approximately 30,500- and 30,000-fold to apparent homogeneity by high-performance liquid chromatography and compared with hTeBG isolated from human pregnancy serum. Fractionation of both forms of hABP and hTeBG by polyacrylamide gel electrophoresis in the absence of sodium dodecyl sulfate suggested that the native forms of these proteins were indistinguishable. However, analysis of the purified proteins on sodium dodecyl sulfate-containing polyacrylamide gels indicated that all three were dimers and that each was composed of monomers of at least two sizes which were not present in equimolar concentrations. Two distinctive monomers or protomers of each protein were designated as heavy (H) and light (L) according to their electrophoretic mobilities on sodium dodecyl sulfate-polyacrylamide gels. The H and L protomers of Form I hABP showed apparent molecular weights of 55,000 and 52,000, respectively, in all preparations and were usually present in a 4:5 ratio (H:L). The two components of Form II hABP had apparent molecular weights of 53,000 and 48,000, respectively, and existed in a ratio of approximately 20:1. These two components could not be distinguished in some preparations where Form II hABP migrated as a broad band rather than as distinct protomers. By contrast, hTeBG, which was similar to Form II hABP with respect to ConA binding, always exhibited discrete H and L protomers in a 10:1 ratio. Photolysis of these highly purified proteins with delta 6-[3H]testosterone resulted in specific covalent labeling of their binding sites, confirming that the products identified by silver staining and immunoblotting were indeed steroid binding proteins. The H and L protomers of Form I hABP and hTeBG were separated and examined by peptide mapping using Staphylococcus aureus protease V8 and chymotrypsin. The comparison of the respective fragmentation patterns of protomers indicated that Form I hABP and hTeBG contained distinctive peptides.(ABSTRACT TRUNCATED AT 400 WORDS)
The urinary neopterin excretion was measured by high-performance liquid chromatography in 417 healthy subjects and in 76 patients with clinically and pathohistologically verified neoplasias of the urinary tract (bladder tumor, carcinoma of the prostate, and renal cell carcinoma). The patients with early tumor stages both with bladder tumor and carcinoma of the prostate had normal urinary neopterin levels, except one patient with bladder tumor who had a value at the upper confidence limit. Of 40 patients with higher stages of bladder tumor and carcinoma of the prostate, 35 had elevated urinary neopterin levels. Two of 10 patients with bladder tumor in stage T3, 1 of 4 patients with carcinoma of the prostate Stage C, and 2 of 15 patients with prostatic cancer Stage D showed normal neopterin levels. The patients with renal cell carcinoma did not demonstrate any definite correlation between tumor stage and urinary neopterin excretion. The current study suggests that the neopterin assay may supplement laboratory measurements in tumors of the urinary tract, providing helpful information regarding case selection for the most convenient therapeutic management and postoperative follow-up.
A double-blind study with Serocytol "Muqueuse urinaire" (immune serum against mucosa of the urinary tract) and Serocytol "S.R.E." (immune serum against reticulo-endothelial system) and placebo was designed for treatment of different bladder diseases (interstitial cystitis sui generis, after radiotherapy and in connection with multiple transurethral resections of bladder tumour, cystitis granularis). Twenty-four patients (17 women and 5 men, aged 41-75, with interstitial cystitis, and 2 women, aged 42 and 75, with cystitis granularis) were included in this study. According to the procedure and after breaking the code 13 patients were treated with Serocytol and 11 patients with the placebo. Nine out of 13 patients who were treated with Serocytol showed an improvement of their condition. In 1 patient the condition was unchanged. Three patients treated with the active compound dropped out of the study during the treatment phase. In one instance the patient did not appear for further check-up; in another the therapy was discontinued after 3 weeks, and in one case a general exanthema occurred. Of the 11 patients treated with placebo, there was an improvement in 2 patients, whereas in 9 cases their status was unchanged. Serocytol and placebo were well tolerated by most of the patients. There were no side effects resulting from the almost daily suppository application over a period of 2 months. No changes in the blood counts, electrolytes, liver and renal function could be found in any of these patients.
Gossypol at a concentration of 10 micrograms/ml has been reported to be a specific inhibitor of DNA synthesis in mammalian cells in vitro. The present study investigates the in vitro effect of different concentrations of gossypol on rat testis tissue. In the presence of gossypol at a concentration of 10 micrograms/ml, DNA - as well as RNA - and protein synthesis were decreased to about 35% of the activity of controls. From these results it can be assumed that in rat testis tissue, gossypol acts as a more general inhibitor of macromolecular synthesis, an effect which may be at some common mechanism such as transport of precursors into the cells rather than a specific effect on the individual processes.
An in vitro study showed that in rat testis gossypol acts as a nonspecific inhibitor of macromolecular synthesis. In this report we describe the in vivo effect of gossypol on DNA, RNA, and protein synthesis in rat testis. Gossypol treatment of rats (20 mg/kg) for 6, 10 and 16 weeks resulted in partial inhibition of macromolecular synthesis. When status of infertility is achieved after 6 weeks, macromolecular synthesis of the spermatogenetic epithelium is not essentially affected by gossypol. In contrast to the previously described DNA strand breaking induction of gossypol in human fibroblasts in vitro, no DNA strand breaking in testes of gossypol-treated rats was found as established by alkaline sucrose gradient centrifugation.