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Biomedical subjects

J M Kuhn

Publications and source records attributed to J M Kuhn.

At least 19 recordsLinked to original sources
PubMed1992

Effects of the new somatostatin analogue (BIM 23014) on blood glucose homeostasis in normal men.

Changes in blood glucose homeostasis induced by the new somatostatin analogue BIM 23014 (BIM) were studied. Eight normal men (study 1) received either vehicle or 1000, 2000 and 3000 micrograms BIM as a 24 h s.c. infusion. Blood glucose, plasma insulin, C-peptide, glucagon and growth hormone (GH) were measured before treatment and then hourly for 24 h. In five normal men (study 2) an oral glucose tolerance test (OGTT) was performed during vehicle infusion and then on days 1 and 7 of a continuous s.c. infusion of 2000 micrograms BIM daily for 7 days. The same biological parameters as in study 1 were measured before OGTT and then twice-hourly for 5 h. Dose-dependent and transient glucose intolerance was observed in the first half of study 1. Except for glucagon, BIM significantly (P < 0.01) reduced plasma insulin, C-peptide and GH levels. In study 2 BIM infusion induced glucose intolerance and a drop in plasma insulin and C-peptide on day 1 which disappeared on day 7 of infusion. Higher on day 7 than on day 1, plasma GH secretion was significantly (P < 0.01) reduced throughout BIM infusion. In contrast plasma glucagon levels were not modified at any time. Side-effects were abdominal cramps and diarrhoea which were observed in most subjects when increasing BIM daily dose. In conclusion, BIM infusion induced transient changes in glucose homeostasis and insulin secretion in normal men. By contrast, plasma GH levels remained reduced throughout the treatment. BIM appears to be a useful tool to selectively inhibit GH secretion.

Adult↗
PubMed1992

[Influence of dose and modalities of administration of BIM 23014 on growth hormone secretion in patients with acromegaly].

Somatostatin analogs, with prolonged half-lives have been proposed for the treatment of acromegalics. The aim of the study was to evaluate the short term efficacy of different doses and modalities of administration of the new somatostatin analog, BIM 23014 (BIM), on GH secretion in acromegalics. Ten acromegalics, with evolutive disease, who previously had had transsphenoidal surgery (and pituitary radiotherapy in 8) were evaluated in a three step study. The first part included four patients who received in a random order either vehicle or 500, 1000 and 1500 micrograms BIM for a day as a continuous s.c. infusion using programmable pumps at one-week interval for 24 hours to measure plasma GH levels. The second part included six patients who received in a random order either vehicle or 1500 micrograms/24h BIM as 500 micrograms x 3 s.c. injections, 750 micrograms x 2 s.c. injections and a continuous s.c. infusion using programmable pumps at one-week interval. During each period of the study blood was sampled at 4 hour intervals for 24 hours in order to measure plasma GH and BIM levels by radioimmunoassays. The third part of the study included the same 6 patients as the second part, who received 30 mg IM of a long acting formulation of BIM. Blood was sampled before and thereafter on days 1, 3, 6, 9, 12, 15, 18 and 21 following the injection for measurement of plasma GH and BIM levels. In first group 500 micrograms BIM slightly decreased plasma GH levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Acromegaly↗
PubMed1991

Total and ultrafiltrable plasma magnesium in hyper- and hypoparathyroidism, and in calcium-related metabolic disorders.

Serum total, ultrafiltrable and protein-bound magnesium, and urinary fractional excretion of magnesium were studied in patients with primary hyperparathyroidism (before and after surgery) and in patients with hyperparathyroidism, malignant hypercalcemia and chronic renal failure with or without hemodialysis. Whereas serum total Mg was unchanged in patients with primary hyperparathyroidism, the ultrafiltrable magnesium concentration was higher than in the control group and higher before than after surgery. The total and the ultrafiltrable magnesium concentrations were highly correlated in the overall patients with Ca-related metabolic disorders, suggesting that renal function had no influence on the relation between these two parameters. Moreover, in malignant hypercalcemia, our results suggested that PTH-like peptides might be less effective than PTH in renal handling of Mg as previously described for Ca.

Adult↗
PubMed1991

Effect of the new dopaminergic agonist CV 205-502 on plasma prolactin levels and tumour size in bromocriptine-resistant prolactinomas.

Bromocriptine is currently and successfully used for the treatment of pituitary prolactinomas. However, bromocriptine appears unable to normalize plasma prolactin levels in about 10% and to reduce tumour size in one-third of cases. The lack of normalization of plasma prolactin levels in spite of a daily dose of bromocriptine equal to or higher than 15 mg suggests a bromocriptine resistance. We compared the long-term effects of bromocriptine and CV 205-502 (a non-ergot derivative D2 dopamine agonist) on plasma prolactin levels and tumour size in seven bromocriptine-resistant prolactinomas. Bromocriptine reduced significantly (P less than 0.001) plasma prolactin levels (from 2307 +/- 518 to 568 +/- 279 micrograms/l) (conversion to Sl units: 1 microgram/l = 20 mU/l). Visual field defects observed in five patients improved in four. However, CT scan analysis showed a decrease in tumour size in only three patients. Except for transient and minor side-effects at the beginning of the treatment, CV 205-502 was well tolerated in five of seven patients. In the remaining two patients nausea and vertigo occurred with high dosages of CV 205-502 and it was necessary to reduce the daily dose. CV 205-502 lowered plasma prolactin to levels similar to those obtained after bromocriptine therapy in four cases. In the three remaining patients, CV 205-502 was more potent than bromocriptine as demonstrated by the further 90% reduction in plasma levels obtained in one case and by the normalization of plasma prolactin levels in the two other cases. One woman became pregnant during CV 205-502 treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

[Somatostatin analogs in oncology].

Somatostatin octapeptide analogues have a longer half-life and are more potent than natural somatostatin (SS-14). Somatostatin analogues are presently approved for the treatment of gastrointestinal (GI) endocrine cancers such as carcinoids, vipomas and glucagonomas. They are also effective in the treatment of inoperable or relapsing acromegaly. Although symptomatic relief is marked and rapidly induced, the inhibitory effect on tumor growth is modest. However, prolonged stabilizations are frequent. Somatostatin analogues may have wider therapeutic indications. Somatostatin octapeptide analogues are also known to interact with growth factors such as epidermal growth factor and insulin-like growth factor, and have shown cytostatic activity in vitro and in vivo in various experimental models of breast, prostate, lung and GI cancers. Neuroendocrine tumors often express somatostatin receptors. Labelled analogues may be useful for tumor assessment and for the prediction of tumor response to therapy. The role of somatostatin analogues in the treatment of the most frequent cancers is currently under investigation.

Adenoma↗
PubMed1990

[Dynamics of gonadotropin secretion in oligospermia with isolated elevation of follicle stimulating hormone (FSH)].

The mechanism of oligospermia with high level of follicle stimulating hormone (FSH) and normal levels of luteinizing hormone (LH) and testosterone is subject to controversy: pituitary origin with slowing down of LH pulses, or primary gonadal deficiency? We studied 23 men presenting with this hormonal profile. Compared with a control population, these men had decreased mean testosteronaemia, increased mean LH level, both at baseline and under LHRH, and increased area under the LH pulsatility curve. A positive correlation was found between LH and FSH plasma levels. These data are in favour of a primary gonadal deficiency, and we therefore expected to find an increased frequency and amplitude of LH pulses. In fact, the frequency was normal and the amplitude increased in one half of these men, while the frequency was reduced and the amplitude also increased in the other half. There was no difference in plasma FSH levels between these two groups. Pulsed administration of LHRH restored physiological stimulation, but it did not result in normalisation of the FSH/LH ratio and cannot be regarded as a suitable treatment. It would therefore seem that the mechanism of oligospermia with isolated high FSH level is an abnormal feedback of gonadal peptides and steroids.

Adult↗
PubMed1990

[Endocrine consequences of corticotherapy. Weaning from long-term corticotherapy].

Long term corticosteroid therapy has multiple effects on the endocrine system. These include adrenocortical suppression in high doses, alteration of gonadotropic and gonadal secretion, slowing down of long bone growth and bone maturation in children, osteoporosis in adults, alteration of the thyrotropic function and changes in thyroxine peripheral metabolism, diabetogenic effect. The list is not exhaustive, and there are more complex effects on the secretion of prolactin, pancreatic peptides, VIP, etc. Because of these various effects, the pros and cons of long term corticosteroid therapy must be carefully weighted, and if it is necessary steroids should be prescribed in such a way as to limit their side-effects: at best one dose taken in the morning every other day, together with the prescription of calcium, of a salt-free diet and, in some cases, of androgens or oestrogens. Weaning must be carried out with caution, to avoid rebound of the disease treated, and with substitution of hydrocortisone when the corticosteroid dosage reaches 5 mg per day of prednisone or equivalent and can be interrupted. The functional soundness or alteration of the corticotropic and adrenal functions must then be evaluated by testing corticotropic and adrenal functions must then be evaluated by testing the adrenocortical response to tetracosactrin, or even better by measuring early morning concentrations of blood cortisol. Depending on the results obtained, hydrocortisone can be withdrawn and limited to episodes of stress, or continued until ACTH and endogenous cortisol levels have returned to normal values.

Adrenal Cortex Hormones↗
PubMed1990

[A hormone assay as a therapeutic choice in male sterility].

In order to study the function of the hypothalamic-pituitary-testicular axis in men referring for severe oligospermia, the hormonal pattern of 57 oligospermic men was compared to those of 19 healthy volunteers. Fourteen patients had plasma gonadotrophin levels in the normal range contrasting with low plasma testosterone (T) levels. An hyperprolactinemia was found in 2 of these men who were treated with bromocriptine. A dramatic increase in sperm count was obtained on month 9 to 12 of the therapy and 5 pregnancies were obtained. Two men with hypogonadotrophic hypogonadism and azoospermia were treated with gonadotrophins. Such a treatment induced a desquamation of immature germinal cells in the sperm on month 6 and the maturation et spermatozoa on month 18. By contrast to the latter patients, 8 men had a decrease in plasma T levels without clinical signs of hypoandrogenism. The spermocytogram showed numerous immature germinal cells. On month 7 of a treatment using gonadotrophins, the sperm count rose and 4 pregnancies were obtained after 3 to 12 months of therapy. In 2 patients an isolated FSH deficiency was suspected on the basis of undetectable FSH levels unresponsive to the infusion of GnRH. These patients were treated with hMG. This treatment induced a sharp increase in sperm count on month 6. Forty-three patients had an increase in either LH and/or FSH: 24 men had plasma testosterone and LH levels in the normal ranges, contrasting with an increase in plasma FSH level. In such men, the mean of testosterone level was significantly (p less than 0.001) lower than in controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Prevention of the transient adverse effects of a gonadotropin-releasing hormone analogue (buserelin) in metastatic prostatic carcinoma by administration of an antiandrogen (nilutamide).

Gonadotropin-releasing hormone (GnRH) analogues administered for the treatment of advanced prostatic cancer induce a transient increase in plasma testosterone levels during the first week of treatment, often with a secondary rise in plasma levels of prostatic acid phosphatase and a flareup of disease. To determine whether the antiandrogen nilutamide (Anandron) blocks these effects, we carried out a multicenter, placebo-controlled study of nilutamide in men with prostatic cancer treated with the GnRH analogue buserelin. Thirty-six men with disseminated prostatic cancer and elevated plasma levels of prostatic acid phosphatase were randomly assigned to two groups. Group 1 included 17 men who received buserelin (500 micrograms daily subcutaneously) and nilutamide (300 mg daily by mouth); group 2 included 19 men treated with buserelin and placebo. Symptoms were assessed, and plasma was collected before treatment, daily for 14 days, and on days 18, 22, and 29 after the initiation of treatment. Bone pain appeared or worsened in 5 of the 17 men in group 1 and in 12 of the 19 men in group 2 (P less than 0.05). Acute urinary obstruction occurred in one man in group 2. Despite similar changes in the plasma testosterone levels in both groups, the median concentration of plasma prostatic acid phosphatase decreased almost immediately in group 1, but increased transiently, then decreased on day 14 in group 2. Median levels of prostate-specific antigen decreased immediately in group 1 and decreased on day 8 in group 2. We conclude that nilutamide can prevent the adverse consequences of the buserelin-induced transient rise in plasma testosterone levels in men with advanced prostate cancer treated with a GnRH analogue.

Acid Phosphatase↗
PubMed1989

Comparative assessment of ACTH and lipotropin plasma levels in the diagnosis and follow-up of patients with Cushing's syndrome: a study of 210 cases.

PURPOSE: A series of 210 patients with Cushing's syndrome was evaluated at a single center to assess the relative values of adrenocorticotropic hormone (ACTH) and lipotropin (LPH) plasma levels in the etiologic diagnosis of Cushing's syndrome and in the follow-up of treated Cushing's diseases. PATIENTS AND METHODS: These patients included 149 patients with Cushing's diseases, 20 with adrenal tumors, and 41 with ectopic ACTH/LPH syndromes. Hormone levels were measured before therapy and during the follow-up of treated Cushing's diseases. RESULTS: ACTH and LPH plasma levels were moderately elevated in Cushing's diseases, low or undetectable in adrenal tumors, and highly elevated in ectopic ACTH/LPH syndromes, but the overlap between the three etiologic groups was less for LPH than for ACTH. LPH appeared to be as sensitive as ACTH in evaluating the outcome of trans-sphenoidal surgery and in detecting the occurrence of Nelson's syndrome after bilateral adrenalectomy. CONCLUSION: Therefore, plasma LPH determinations provide a better index than ACTH measurements, probably for technical reasons as well as because of the greater stability of LPH in blood.

ACTH Syndrome, Ectopic↗
PubMed1989

hCG test in gynaecomastia: further study.

In adult men referred with gynaecomastia, the prolonged plasma oestradiol (E2) response to hCG appears to be a useful tool in the diagnosis of feminizing Leydig cell tumour (LCT) of the testis. However, its specificity is uncertain. The hormonal status was therefore studied in 85 men with gynaecomastia including 17 with LCT, 52 with clinically isolated gynaecomastia and 16 hypogonadal men (13 with Klinefelter's syndrome and three with hypogonadotrophic hypogonadism). The data obtained after hCG (5000 IU i.m., n = 85) or GnRH (100 micrograms i.v., n = 70) administration were compared to those of a group of control men. Means of basal gonadotrophin and of gonadotrophin responses to GnRH were similar in LCT and controls but were significantly (P less than 0.001) higher than controls in patients with either Klinefelter's syndrome or isolated gynaecomastia. Half the patients with isolated gynaecomastia had normal gonadotrophin parameters (NGG) while half had significantly (P less than 0.001) higher levels (EGG) than controls, suggesting either primary testicular failure or androgen resistance. The T responses to hCG did not differentiate patients with LCT from either isolated gynaecomastia or controls. A prolonged E2 response (greater than 300 pmol/l on day 3 following hCG) was observed in all patients with LCT, in 10/21 EGG patients and in 3/13 patients with Klinefelter's syndrome. Such a response was observed in only one NGG patient. We conclude that a prolonged E2 response to hCG does not appear to be specific to LCT but that specificity is greatly improved (from 80 to 98%) when the gonadotrophin pattern (basal and/or responses to GnRH) is also taken into account.

Adolescent↗
PubMed1989

[Pituitary adenoma treated with a somatostatin analog].

We studied for over 7 months the use of SMS 201-995, in 1 woman with pituitary adenoma. Eight years after surgical and irradiation therapy, adenoma relapsed with hyperthyroidism (T4 L = 71pmol/l, TSH = 5.3 mU/l, subunit: 309 micrograms/l) and was complicated by meningitis. It was invasive and removed only partly. SMS therapy, 100 micrograms SC q 8 h, allowed partial reduction of clinical hyperthyroidism and decreased TSH and alpha subunit of 47%. Increased dosage and changing route of administration did not increase efficacy. A modest decrease of adenoma was probably caused by several reasons. In summary in an adenoma unusual by the extremely high value of alpha subunit in contrast with modest value of TSH, SMS therapy allowed partial control only.

Adenoma↗