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Biomedical subjects

J Frick

Publications and source records attributed to J Frick.

At least 37 records · Page 2Linked to original sources

ICln: a chloride channel paramount for cell volume regulation.

Cell volume regulation is a ubiquitous cell regulatory mechanism based on meticulously controlled ion transport mechanisms. Keeping the absolute volume constant seems to be of the highest priority for most cells and is achieved at the expense of altered intracellular ion concentrations. We have been able to demonstrate that ICln, a chloride channel cloned from epithelial cells, is paramount for the ability of swollen cells to regulate their volume back to that under resting conditions. A unique feature of ICln is the distinct sensitivity of these channels for nucleotides and nucleoside analogues added to the extracellular fluid. In addition, cromolyn sodium and nedocromil sodium, drugs used by patients with asthma, are able to impede the function of these channels.

Animals

Five-year results of a phase II study with low-dose bacille Calmette-Guerin therapy in high-risk superficial bladder cancer.

OBJECTIVES: Numerous studies have shown bacille Calmette-Guérin (BCG) to be an effective prophylactic and therapeutic agent for superficial transitional cell carcinoma of the bladder. The high-grade T1 lesion treated by transurethral resection alone is reported to progress to muscle invasion in 30% to 50% of the patients. Until now, optimal treatment schedule and optimal dose have not been defined. As suggested by Pagano's group, we used BCG in a lower dose than hitherto usual in our high-risk cancer patients. METHODS: Five years ago, we treated 32 Stage T1 cancer patients who were described as at high risk based on the criteria of histologic grade 3 in 21 patients, grade 2, but multiple in 11 patients, and with carcinoma in situ in 17 patients. Follow-up ranged from 51 to 63 months, with a mean of 57 months. We used BCG strain Pasteur Paris 75 mg weekly for 6 weeks and then maintenance therapy monthly for the first year and every 3 months for the second year. Complete remission was defined as negative cystoscopy, biopsy, and cytology. RESULTS: After a single 6-week course of BCG, 25 patients had negative cytology and biopsy findings after 3 months; 2 other patients needed a second 6-week cycle of BCG, for an overall response rate of 80%. Five patients underwent cystectomy because of multiple recurrences and tumor progression. After 2 years of follow-up, but under continuing maintenance therapy, 3 additional patients had tumor recurrences and also underwent cystectomy. Now, after 5 years' follow-up, the overall progression rate to cystectomy was 25% (8 of 32 patients), but none of the patients had progression to metastasis. Treatment-related toxicity did not appear to be lower at a lower dose of BCG. CONCLUSIONS: Low-dose BCG therapy is also an effective treatment in high-risk T1 bladder cancer (especially with maintenance therapy and short-term evaluations of the patients always by the same controlling physician) to prevent progression and recurrence and to preserve bladder function.

Aged

Low-dose bacille Calmette-Guérin (BCG) therapy in superficial high-risk bladder cancer: a phase II study with the BCG strain Connaught Canada.

OBJECTIVE: To evaluate low-dose bacille Calmette-Guérin (BCG) therapy, with the Connaught Canada strain, in patients with superficial transitional cell carcinoma (STCC) of the urinary bladder. PATIENTS AND METHODS: Between September 1990 and December 1992 25 patients were entered into a phase II study to evaluate the feasibility, response and toxicity of BCG immunotherapy for patients with high-risk STCC. Therapy consisted of six, weekly instillations of 27 mg (3 x 10(8) colony-forming units) of the BCG strain Connaught Canada. Maintenance therapy was administered monthly for 1 year with the same dosage. RESULTS: Of 25 eligible patients, 84% had complete responses after the initial cycle with low-dose BCG and had stable disease. Four patients had no response, three of whom subsequently underwent radical cystectomy. The mean length of follow-up was 30.8 months (25-36). Toxicity included profound local reactions such as severe dysuria, frequency and gross haematuria. No systemic infections, except fever, were seen; none of the patients needed isoniazid. All reactions were treated symptomatically. CONCLUSIONS: The results of this study suggest that low-dose BCG with the strain Connaught Canada can be successfully used in the treatment of patients with high-risk STCC. Toxicity was not reduced substantially by the lower dosage of BCG used.

Administration, Intravesical

The effect of active immunization against gonadotropin-releasing hormone on the ultrastructure of the rat ventral prostate.

To evaluate the effects of active immunization against gonadotropin-releasing hormone (GnRH) on the ultrastructure of the rat ventral prostate, male Sprague-Dawley rats received three consecutive intramuscular injections of 10 micrograms/100 g body weight (D-Lys6)-GnRH-diphtheria toxoid conjugate (GnRH-DT vaccine). Following immunization, test animals developed sufficiently high antibody titres to block the pituitary gonadal axis. Consequently testosterone values dropped to the levels in castrates. This therapy leads to atrophy of the prostate. Following immunization a strong immunological response, indicating the presence of considerable amounts of a GnRH-like peptide, was observed in the ventral prostates as early as 14 days after the first injection of GnRH-DT. Immunoneutralisation of GnRH-like activity may contribute to the effects observed.

Animals

Diagnostic problems of urine cytology on initial follow-up after intravesical immunotherapy with Calmette-Guérin bacillus for superficial bladder cancer.

After transurethral resection or biopsy, patients with recurrent bladder cancer or in situ carcinoma were given topical immunotherapy with low-dose Calmette-Guérin bacillus (BCG). In the recurrence-free interval they were treated with BCG monthly for 1 year and then every 3 months for the next year. Cytological analysis was always performed concomitant with the administration of immunotherapy. In order to evaluate the therapeutic success, cystoscopy and biopsy were performed after the first cycle of BCG and then every 3 months. At the start of topical therapy with BCG, a great increase in the number of inflammatory cells was seen. In urothelial cells the nuclei were enlarged; they were hyperchromatic with sometimes increased and prominent nucleoli, anisocaryosis and a distorted nucleus-plasma ratio. These cytological findings were also made 1 year after initial therapy and slowly diminished in the 2nd year during immunotherapy at 3-month intervals. The accuracy of urine cytology for carcinoma in situ is 80%. Interpretation of cytology in the recurrence-free interval was impaired. When doubtful, the recurrence of a carcinoma in situ under maintenance therapy with BCG must be proved by biopsy.

Administration, Intravesical

Mediastinal tumor and Klinefelter's syndrome.

Klinefelter's syndrome with karyotype 47,XXY in patients with primary extragonadal germ cell tumors rarely occurs. The endocrinology of Klinefelter's syndrome is changed; elevated beta-human choriomic gonadotropin levels are present. Chemotherapy and thoracic surgery brought complete remission in a patient with lung metastases.

Adolescent

LHRH and cryptorchidism.

This paper is a historic review of two studies of the treatment of cryptorchidism. One was concluded 20 years ago with native LHRH, while the other took place 14 years ago and involved one of the potent LHRH analogues. The first study was initiated at the end of 1971-at a time when the different modes of action of the decapeptide were by far not evaluated to the full extent they are now-and included ten prepubertal boys with undescended testes aged five to ten years. The treatment consisted of intramuscular application of 20 micrograms LHRH once daily for three weeks. Additionally, three boys, five, seven and nine years of age, also presenting undescended testes underwent an LHRH test with intravenous bolus application of 200 micrograms. In all three subjects, a 2.5-fold increase in plasma testosterone was observed 20 min after the bolus. The treatment group showed neither a rise in LH nor in testosterone at the end of therapy. Testicular descent was achieved in six out of six boys with bilateral and in 2/4 with unilateral undescended testes. These good results might be based on the fact that six boys had retractile rather than actually undescended testes. In the second study started in 1978, 18 boys, three to 12 years of age with either unilateral or bilateral cryptorchidism, were treated with a synthetic LHRH analogue ("D-Leu 6, Des-Gly-10 LHRH ethylamide") applied intranasally. The peptide prepared in an aqueous solution was administered in the form of nose drops.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Intranasal

[Endocrinology and fertility in stage I testicular tumor].

The situation of endocrinology and fertility of patients suffering from testicular cancer stage I (Peckham) with good survival rates were evaluated before semicastration. The value of beta-hCG is of great importance. According to this criteria 3 groups were formed. beta-hCG positive tumors, beta-hCG positive tumors out of the blood sample of the vena spermatica after ablation of the testis tumor and beta-hCG negative tumors. The histology is of secondary importance. 54 patients with testicular cancer were evaluated in this study. From 37 patients it was possible to get a spermiogram before semicastration. For the analysis of the spermiogram the values of LH, FSH, Testosterone and E2 are responsible. The values of beta-hCG in the serum from the periphery is of great importance, while a single elevation of beta-hCG in the serum out of the v.spermatica does not change the endocrinology. The question of kryosperm conservation is according to these parameters better evaluable.

Adult

Differences in serum potassium concentrations in normal men in different geographic locations.

Hypokalemia has been associated with the taking of gossypol, a potential oral antifertility drug for men. Because the frequency of this response differed in different parts of the world, this study was done to learn if "normal" serum [K+] also differed. [K+] was measured by flame photometry in serum from apparently normal men from Austria (n = 30), China (53), Brazil (100), the Dominican Republic (38), and the US (103), and in plasma from Nigerian men (82). The mean (SD) for [K+] in Chinese men, 3.82 (0.27) mmol/L, was lower than that in Brazilians [4.06 (0.29) mmol/L], Austrians [4.14 (0.44) mmol/L], Dominicans [4.37 (0.33) mmol/L], or Americans [4.38 (0.37) mmol/L]. Apparently there are regional differences in average serum [K+], with men in China having lower serum [K+] than men elsewhere. This may predispose them to hypokalemia.

Adolescent

Effect of active immunization to luteinizing-hormone-releasing hormone on the fertility and histoarchitecture of the reproductive organs of male rat.

The feasibility of using a vaccine against luteinizing-hormone-releasing factor for suppression of pituitary and gonadal functions has been indicated for some time. Antibody production against this low-molecular-weight, naturally occurring decapeptide, however, requires to be coupled to a carrier protein to enhance its immunogenicity. LHRH was coupled to diphtheria toxoid (DT). Adult male Sprague-Dawley rats with a mean basal body weight of 200 g were immunized with anti-LHRH-DT (20 micrograms/injection/rat) at four-week intervals. An equal number of unexposed animals served as controls. Six animals were killed every two weeks up the end of the week 43. The vaccination schedule did not have any effect on the gain in body weight, nor was any adverse effect of vaccination observed in the course of the investigations. The pituitary, prostate, epididymis, testes, seminal vesicles, adrenal and thyroid were excised for determination of organ weight and histological examination. The adrenal, pituitary and thyroid showed no remarkable weight changes during the observation period, whereas the weights of the reproductive organs demonstrated significant reductions compared to those of the control group. The histopathology revealed marked to significant changes in the gonads and the accessory sex organs including the prostate. A progressive phase of regeneration of spermatogenesis was evident 98 days after vaccination. Total recovery of spermatogenesis was observed 300 days after vaccination. The mating studies showed the return of fertility 300 days after vaccination. The litters borne were normal. Prostate showed recovery after 154 days of vaccination. Our observations lend strong support to the hypothesis that anti-LHRH vaccine can be effectively used on the management of prostate carcinoma. If the vaccination is given together with a suitable dose of long-acting androgen, contained in an adequate delivery system, the regimen may be used for the regulation of male fertility.

Animals

Experiences with extracorporeal shock wave lithotripsy in patients with a solitary kidney.

Between March 1985 and January 1990, 43 patients with stones in solitary kidneys were treated by extracorporeal shockwave lithotripsy (ESWL) in our department. The most common cause of unilateral kidney absence was previously surgical removal of the kidney. The primary treatment modality was ESWL in all patients; the need for auxiliary procedures was higher than in general stone patients. Of the 43 patients 42 were available for control checkups after therapy, and these examinations revealed a stone-free rate of 85.7%. Of the patients 14.3% had asymptomatic lower calix fragments. All our patients showed a successful result 6 months after ESWL therapy. No loss of kidney was observed. Our results indicate that ESWL as an effective and safe method is also the therapy of choice for stone patients with solitary kidneys.

Female