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Biomedical subjects

J Happ

Publications and source records attributed to J Happ.

At least 37 records · Page 2Linked to original sources

[Clinical evaluation of the tumor marker CA 19-9 in comparison with carcinoembryonic antigen (CEA) in surgical pre- and postoperative diagnosis].

A new tumor marker (CA 19-9) was investigated. CA 19-9 is a tumor-associated antigen which is detected by a monoclonal antibody. CA 19-9 (CIS-Centocor) was compared simultaneously with CEA (carcinoembryonic antigen) in 347 patients. 123 patients with gastrointestinal tumors showed a sensitivity of 31% for CA 19-9 (CEA 49%), combination increased sensitivity to 58%. The highest sensitivity was found in pancreas carcinoma (CA 19-9 75%, CEA 66%, combination 92%); it was lower in gastric, colon, and oesophagus carcinomas. In relapsed colorectal carcinomas sensitivity was 53% (CEA 78%, combination 85%). In cases of relapse, tumor markers may become positive even if they were not detectable before resection of the primary tumor. Specificity for CA 19-9 was 100% (CEA 84%) compared to a group of non-malignant diseases including patients with inflammations and patients with nicotin abuse (n = 102). Because of its high specificity and superior sensitivity to CEA in pancreas carcinomas CA 19-9 should be determined in primary and relapse diagnosis in combination with CEA.

Antigens, Neoplasm↗

Pulsatile gonadotropin-releasing hormone therapy in male patients with Kallmann's syndrome or constitutional delay of puberty.

The response to low-dose pulsatile gonadotropin-releasing hormone (GnRH) therapy was tested in three hypogonadotropic hypogonadal male patients and a boy with delayed puberty showing different luteinizing hormone responses (delta LH) to test doses of 25 micrograms GnRH intravenously before treatment. Four male patients, 16 to 20 years of age, three with Kallmann's syndrome and one with idiopathic delay of puberty, received 2 micrograms GnRH subcutaneously every 2 1/2 hours for 3 months by the use of the Zyklomat pump (Ferring GmbH, Kiel, FRG). In two patients with Kallmann's syndrome and decreased delta LH, serum testosterone did not increase during treatment, even after increasing the dosage and changing the route of administration (4 micrograms subcutaneously or 8 micrograms intravenously every 2 1/2 hours for 4 weeks with every dosage). The third patient with Kallmann's syndrome and the boy with delayed puberty, both with normal delta LH, presented normal serum testosterone after 3 months of subcutaneous low-dose treatment. The different responses to a GnRH test dose corresponding to the response to pulsatile GnRH therapy probably reflect different degrees of maturation of the pituitary gonadotrophs.

Eunuchism↗

Thallium-201 scintigraphy in the diagnosis of pheochromocytoma.

6 patients were studied by 201Tl scintigraphy; 1 of them suffered from a benign, and another from a malignant adrenal pheochromocytoma. 1 patient had a hormonal inactive adrenal tumor, 3 others multiple organ metastases of malignant pheochromocytomas. At the same time, 3 of the patients were studied by 131I-metaiodobenzylguanidine (131I-MIBG) scintigraphy. Using different techniques like kinetic studies, whole-body scan or a 201Tl-99m-Tc difference scan, benign and malignant pheochromocytoma tissues could be localized by 201Tl scintigraphy. Benign and malignant pheochromocytomas showed different kinetics of 201Tl. In 2 patients with multiple organ metastases of malignant pheochromocytomas, the metastases were partly imaged by 131I-MIBG, the others by 201Tl.

3-Iodobenzylguanidine↗

[99mTc uptake and TSH receptor autoantibodies--comparative study in Basedow's disease and other thyroid diseases].

In 255 patients (normals: group I, n = 30; nontoxic goitres: group II, n = 134; toxic goitres without ophthalmopathy: group III, n = 63; Graves' disease: group IV, n = 28) a TSH-receptor-autoantibody-assay (TRAK assay) for detection of thyrotropin-binding inhibiting antibodies (TBIAb) was tested and 99mTcO4-uptake (TcTU) was measured. Normal TcTU (range: 1.5-5.5%) and normal TRAK values (normal limit: F less than 11%) were only found in group I. An increased TcTU was found in group II in 22.4% (increased TRAK values only in 2.2%). In group III an increased TcTU was measured in 34.9% of the patients (all with normal TRAK titers). The stimulation of the TSH-receptor in immunogenic hyperthyroidism by TBIAb could be demonstrated by increased TRAK values in 71.4% of the patients with Graves' disease. In correlation, TcTU was also increased in 82.1% of the patients in group IV. As the measurement of TcTU can be helpful in differential diagnosis, the functional imaging with gamma camera and computer is today a conditio sine qua non, especially in suspected hyperthyroidism.

Autoantibodies↗

[Pregnancy and hyperprolactinemia].

After endocrinological and radiological evaluation of a hyperprolactinemia 13 patients became pregnant under bromocriptine therapy. In two of these patients a selective adenomectomy was performed by the transphenoidal route because of a prolactin (PRL) secreting adenoma. In 12 patients the pregnancy was not complicated. The serum PRL levels were different but mostly in a normal range. The control of x-ray and visual field in patients with a rapid increase of the PRL levels did not result in a tumor recurrence. After a normal course of the serum PRL concentrations one patient with a microadenoma developed suddenly a chiasma syndrome in the 31th week of gestation. The further evaluation resulted in a pituitary tumor with suprasellar extension. The discrepancy between the radiological result and the normal serum PRL levels was explained by a hemorrhage into the adenoma. After the operation the chiasma syndrome was reversible within a short period. Altogether, the course of the pregnancies was not complicated. We did not see fetal malformations. Post partum the sella x-ray of all patients did not reveal any significant changes so far.

Adenoma↗

[Diagnosis of the site of insulinomas: percutaneous transhepatic portal vein catheterisations with selective blood sampling for hormone determination (author's transl)].

Percutaneous transhepatic portal vein catheterisation with blood sampling from the various areas of drainage, especially the pancreatic veins, was undertaken in seven patients with insulinoma to diagnose its site. In six patients measurement of serum-insulin levels revealed an abrupt rise in the vascular area later found to drain the area of the insulinoma. Insulin measurement in one patient with insulinoma in the head of the pancreas falsely indicated an islet-cell tumour in the region of the tail of the pancreas. C-peptide concentration in serum followed the concentration of insulin, but did not show such a marked rise. The method of percutaneous transhepatic portal vein catheterisation with selective blood sampling for the measurement of hormonal concentration was superior to ultrasound, computer tomography or coeliacography for determining the site of the tumour.

Adenoma, Islet Cell↗

Endocrine studies with a gonadotropin-releasing hormone analogue to achieve withdrawal of testosterone in prostate carcinoma patients.

This investigation on 12 well-defined patients with untreated, advanced prostatic adenocarcinoma establishes the gonadotropin-releasing hormone analogue [D-Ser(But)6](1-9)-nonapeptide-ethylamide (Hoe 766) as an effective, safe and non-toxic form of medical castration. Hoe 766 was given either as subcutaneous injections of 2 x 200 micrograms/day over 14 days and pernasal application (3 x 400 micrograms/day) thereafter, or as subcutaneous injections of 3 x 1,000 micrograms/day over 6 days and pernasal application thereafter in the dosage mentioned above. Both dose regimens were equally effective: pituitary overstimulation between days 3 and 6 with a rise of serum HL and testosterone; pituitary and testicular desensitization with LH and testosterone decline between days 6 and 14; medical castration with average serum testosterone levels maintained around 0.5 ng/ml for up to 12 weeks. Except for transient hot flashes in 4 patients, no clinical or laboratory side effects were observed. It is concluded from this study that the gonadotropin-releasing hormone analogue. Hoe 766, is a valuable alternative to conventional contrasexual measures for prostate cancer palliation. To improve the patient's compliance, however, the smallest single pernasal dosage effective for maintenance of down-regulation and steroidogenic arrest has still to be determined.

Adenocarcinoma↗

[Effect of calcium dobesilate on permeation of plasma proteins in diabetic patients].

The effect of six months of treatment with 750 mg calcium dobesilate on sedimentation rate blood count, cholesterol, triglycerides, platelet aggregation factor, total protein, electrophoretic distribution of serum protein concentrations, and kinetics of intravenous albumin marked with 131I was established in 35 diabetics with a mean duration of diabetes of 9.8 years. There was significant intravascular retention of 131I albumin and significant increase of serum albumin, beta-globulins and total protein after treatment. The other parameters remained unchanged. The results are interpreted as evidence of lowering of the increased transcapillary permeability within the vascular system seen in diabetics.

Aged↗

Treatment of delayed puberty by intranasal application of gonadotropin-releasing hormone (GnRH).

Seven male patients between 15(5)/12 and 19(6)/12 years of age with delayed puberty, two of them anosmic, received 200 microgram GnRH nasally (N) six to eight times daily for a period of 3 months, or in one case for 6 months. Changes in basal secretion and responsiveness of the gonadotropins were recorded by serial GnRH tests. Serial measurements of serum testosterone (T) were also done. While serum T, before treatment, was low it prepubertal levels in all patients, basal serum gonadotropins and gonadotropin responsiveness in the GnRH tests were found to be within the adult range in most of the patients. In the two anosmic patients, after 2 to 4 weeks of treatment decreasing gonadotropin responsiveness of GnRH was observed, and no, or only transitory, increases of serum T were found. In another patient, in spite of sustained gonadotropin responsiveness of GnRH throughout the treatment, no increase of serum T was seen which is probably due to additional primary Leydig cell deficiency. In the other four patients increases of serum T were observed which, however, did not reach the middle of the normal adult range. If stimulation of T secretion was achieved a further increase of serum T was observed after termination of the treatment. Thereafter, serum T returned to pretreatment values in one patient or stayed within the normal adult range in two other patients. No significant effects on clinical parameters were found with the GnRH therapy. This is probably due to the short duration of therapy in these patients as well as to the changes in serum T observed during the treatment, which are small in comparison to gonadotropin therapy.

Administration, Intranasal↗

[Endocrinological prediction of the responsiveness of depressive patients to lofepramine (author's transl)].

In a pilot study of 15 depressive patients of the neurotic and endogenous type we could show that some neuroendocrinological parameters are apt to predict the thymoleptic efficacy of lofepramine. These parameters, which were measured with a simple global stimulation test (insulin hypoglycaemia combined with injection of TRH and LHRH), were as follows: high basal blood glucose; high hypoglycaemic blood glucose; high decrease of blood glucose in comparison to the basal level; low basal TSH; low increase of HGH and low increase of cortisol after hypoglycemia. A synopsis of these parameters allowed a correct classification of 14 out of 15 patients according to therapy response and therapy resistance.

Adult↗

[Gonadotropin secretion following pernasal stimulation with synthetic gonadotropin releasing hormone (GnRH) and a highly effective GnRH-analog in healthy men and prepubertal boys].

Potent long acting analogs of GnRH are of great interest especially in view of pernasal (p.n.) treatmen of hypogonadism of hypothalamic origin and of cryptorchidism. To find the necessary p.n. dosage of such a substance, serum LH and FSH were measured in 6 normal adult human males after p.n. application of various doses of D Leu6-des-Gly10-GnRH ethylamide. 50 microgram of the GnRH analog were necessary to obtain increased serum gonadotropins over a period of at least 8 hours. By repeated p.n. application of 200 microgram of synthetic GnRH every 2 hours in 6 normal adult males a considerable increase of serum gonadotropins could be demonstrated as well. Pernasal application of 200 microgram GnRH repeated at an interval of 1 hour in 3 cryptorchid boys produced a distinct increase of the serum gonadotropins. The intraindividual comparison of 200 microgram GnRH and 20 microgram of the GnRH analog in one boy showed equivalent net increases of the gonadotropins. With the analog the gonadotropin increase lasted for about 6 hours.

Administration, Intranasal↗

Changes of serum testosterone and of LH-RH test after treatment of cryptorchidism by intranasal LH-RH.

The aim of the present investigation was to study, in a collaborative double-blind study, the treatment with intranasal LH-RH application of boys aged 1 1/2 to 12 years, who suffered from unilateral or bilateral cryptorchidism. A total of 88 subjects were randomly and blindly allocated to LH-RH and placebo therapy. Before and after 4 weeks of treatment basal testosterone serum levels were estimated and LH-RH tests were performed. Intranasal treatment with LH-RH resulted in partial or complete descents of testes in 23 out of 88 patients, whereas the position of testes remained unchanged in 17 subjects. 42 boys did not respond to placebo therapy, but complete descents were observed in 6 boys of the placebo group. Hormone analysis data of 4 different laboratories were recorded and statistically evaluated. No changes of LH, FSH and testosterone were found in the placebo groups. Only patients of the Frankfurt group responded to LH-RH test with augmented LH release after therapy (P less than 0.05). All patients treated with intranasal LH-RH showed a significant decrease of FSH release after therapy (P less than 0.05 to P less than 0.01). Basal testosterone serum levels were found to be increased after therapy only in the patients treated at Zürich (P less than 0.05). Data of the present study combine to suggest that chronic application of LH-RH may result in an overstimulation phenomenon, and that LH-RH test as well as basal testosterone levels cannot be used as prognostic index of therapy efficacy.

Administration, Intranasal↗

[Gonadotropin secretion after stimulation with a highly effective analog of the gonadotropin-releasing-hormone (GnRH) in normal adult human males (author's transl)].

Potent long acting anologs of GnRH are of great interest especially in view of treatment of hypothalamic hypogonadotropic hypogonadism and of cryptorchidism. To find necessary parenteral doses of such a substance immunoreactive serum LH and FSH were measured in 4 normal adult human males after s.c. injection of various doses of D-Leu6-des-Gly10-GnRH-EA. 5 microgram of the GnRH anlog were necessary to obtain increased serum gonadotropins over a period of at least 8 h. Comparable maximal levels were seen after i.v. bolus injection of 25 microgram natural GnRH a dose as used in diagnostic routine tests in 3 probands. Comparing the areas under the curves of LH secretion an over 15 times greater effectiveness of the analog was calculated.

Adult↗

Treatment of cryptorchidism with pernasal gonadotropin-releasing hormone therapy.

Twenty-five boys between 1 and 10 years of age with unilateral or bilateral cryptorchidism were treated with 200 microgram of gonadotropin-releasing hormone (GnRH) pernasally six times daily until descensus was completed, or for 10 weeks at most. Complete descent of the tests occurred in 16 patients, usually after 2 to 5 weeks of treatment. No adverse side effects have been observed. Radioimmunologic measurements of serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, and prolactin, carried out before treatment, at the end of treatment, and 6 months after treatment, showed a transitory increase of the LH responsiveness to GnRH in only four of the patients and in the group as a whole a slight but significant decrease of FSH responsiveness. There were no signs of precocious puberty. GnRH antibodies were not found.

Administration, Intranasal↗

Treatment of cryptorchidism with a potent analog of gonadotropin-releasing hormone.

Pernasal therapy of cryptorchidism with D-Leu6-des-Gly10-gonadotropin-releasing hormone ethylamide (D-Leu6-des-Gly10-GnRH-EA), a potent, long-acting GnRH analog, was attempted. Eleven prepubertal cryptorchid boys received between 25 microgram once daily and 25 to 50 microgram twice daily for 5 to 12 weeks. Complete testicular descent was achieved in 4 of the 11 boys. GnRH tests (1.5 microgram/kg intravenously), conducted in six boys before treatment, after 4 weeks of treatment, and in 2 boys 3 months after treatment, did not reveal changes in gonadotropin secretion indicative of precocious puberty or of decreased hypophyseal sensitivity to GnRH. Antibodies to the GnRH analog or to GnRH could not be detected.

Antibody Formation↗

Gonadotropin and testosterone secretion in normal human males after stimulation with gonadotropin-releasing hormone (GnRH) or potent GnRH analogs using different modes of application.

Gonadotropin-releasing hormone (GnRH) and some potent long-acting GnRH analogs, applied by different routes of administration, were tested in six healthy human males. The effects on gonadotropin secretion were compared with the one after intravenous (i.v.) bolus injection of 25 microgram of GnRH. The net increase of luteinizing hormone (deltaLH) in serum produced by 25 microgram of GnRH i.v. was matched by subcutaneous (s.c.) injection of 100 microgram of GnRH, dissolved in 20% gelatin or without gelatin; 5 microgram of D-Ser (TBU)6-des-Gly10-GnRH-ethylamide i.v.; 5 microgram of D-Leu6-des-Gly10-GnRH-ethylamide i.v.; and 50 microgram of D-Trp6-des Gly10-GnRH-ethylamide given pernasally (p.n.). D-Leu6-des-Gly10-GnRH-ethylamide, 50 microgram p.n., produced one-half such increase as did also multiple p.n. administrations of 200 microgram of GnRH every 2 hours. With 100 microgram of GnRH and all analogs, elevation of serum LH lasted for about 7 to 9 hours. The longest elevation was observed with GnRH dissolved in gelatin and with D-Ser (TBU)6-des-Gly10-GnRH-ethylamide, as reflected by the greatest areas under the curves of net increase. The longer the duration of the action of LH secretion, the higher was the observed increase in follicle-stimulating hormone (FSH). Correlation between effect on LH secretion and testosterone secretion was not found. By infusion of 1 microgram/kg/hour od D-Leu6-des-Gly10-GnRH-Ethylamide in two men over a period of 15 hours, a plateau of gonadotropin levels was reached within 7 to 9 hours. These plateau levels, especially of FSH, were higher than after bolus injection or p.n. application.

Administration, Intranasal↗