Pineal gland, F.S.H., and breast-cancer aetiology.
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Biomedical subjects
Publications and source records attributed to L Wide.
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Various conditions for the dissociation of highly purified human pituitary thyrotropin into subunits have been investigated. Dissociation on a preparative scale was accomplished by treatment with 1 M propionic acid at 32 degrees C for 16 h. The isolation of one alpha and two beta subunits was achieved by hydrophobic interaction chromatography on pentyl-Sepharose-4B. Radioimmunological technique was utilized to classify the subunits in accordance with current nomenclature and also to express their activities. The activities of the subunits overlapped insignificantly (less than or equal to 0.3%) and their content of intact thyrotropin was negligible (less than 0.05%). The characterization of the subunits included determination of their amino acid compositions. Analytical polyacrylamide gel electrophoresis of the subunits at acid and alkaline pH values revealed heterogeneity. By free-zone electrophoresis at alkaline pH it was possible to isolate four discrete iso-forms of both the alpha and the beta subunit. All these eight individual subunits had activities consistent with those of their immediate precursor fractions. Isolation of electrophoretically homogeneous thyrotropin subunits has not been reported previously.
Seventeen term pregnancies occurred in 14 amenorrhoeic women with hyperprolactinaemia and radiological evidence of pituitary tumour. The abortion rate was high (32%). All but one of the term pregnancies occurred after ovulation-inducing treatment with human gonadotrophins and bromocriptine (four and 12 pregnancies respectively). Two of the 14 women had visual complications during pregnancy, but neither had serious residual visual impairment. Two patients had possible pituitary enlargement during pregnancy.Bromocriptine may be the most suitable primary treatment for many infertile women with prolactin-secreting tumours. Tumour complications during pregnancy are a definite risk, but most pregnancies went uneventfully to term. Patients with pituitary tumour should be carefully evaluated before starting ovulation-inducing treatment with bromocriptine alone, and they should be told of the possible risks and of the advantages and disadvantages of pretreatment with irradiation or surgery. Patients should be carefully monitored during pregnancy and have their visual fields checked frequently. If visual complications due to tumour enlargement occur during a pregnancy, reinstituting bromocriptine may be the treatment of choice. If this fails, other forms of treatment such as induction of labour, high-dose corticosteroid treatment, pituitary implantation of yttrium-90, or surgery may be effective.
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A nulliparous woman with 12 years of amenorrhea, galactorrhea, and hyperprolactinemia and radiologic evidence of a pituitary macroadenoma was treated with large doses of bromocriptine. During treatment the greatly increased prolactin levels normalized and ovulatory menstrual cycles were regained after 48 weeks of treatment. A transsphenoidal surgical exploration of the pituitary fossa was performed after 27 months of treatment. The findings at surgery suggested that regression of the pituitary adenoma had occurred during the prolonged treatment with bromocriptine. After discontinuation of the therapy, the patient continued to ovulate and subsequently conceived.
Eight patients representing five different, probably hereditary neurological syndromes with oligophrenia and hypogonadism as the common features have been examined clinically and endocrinologically. Two sisters suffered from polyneuropathy, one male from ataxia, one male from spastic tetraplegia, two sisters and a brother from myopathy and one male patient from epilepsy and polyneuropathy. The latter patient was diagnosed as having an acute intermittent porphyria. All the patients had degenerative neurological disorders. The karyotypes were normal. The patients all had signs of hypogonadism. Four male patients had marked testicular atrophy but otherwise normal external genitalia. The testosterone levels in the blood were normal or slightly decreased. Three of the females had their menarche at a normal age but a very early menopause. The fourth female has never menstruated. The four females had normal breasts and body hair. All patients had high basal luteinizing hormone (LH) and follicle-stimulating hormone levels and the response to i.v. LH-releasing hormone was exaggerated. The prolactin values were normal. None of the examined patients had any signs of thyroid or adrenal insufficiency and the sella turcica was normal. A possible etiology to their hypergonadotropic hypogonadism is discussed.
Serum ferritin estimation has been shown to be a reliable test to reveal iron deficiency. Such estimations have been made in groups of male blood donors with a varying number of previous phlebotomies and a mean interval between donations of 9.9 +/- 1.7 SD weeks. It was found that the mean ferritin level was significantly (p less than 0.001) lower in the blood donors than in nondonors. After 6-8 phlebotomies it was about 40% lower. Subnormal ferritin values were found in 10% of the donors, almost exclusively among those who had taken less than 1,000 mg of iron supplementation since the last donation. It is concluded that with a donation interval of about 10 weeks, there is a considerable risk for iron deficiency after about 6 donations. This risk is far less if more than 1,000 mg of iron supplementation is taken between phlebotomies. A role for serum ferritin estimation in monitoring donation intervals and/or iron therapy is suggested.
An intravenous luteinizing hormone-releasing hormone (LRH) test was performed in 287 women with amenorrhoea. Prolactin, progesterone and oestrogens in serum were also measured. Twenty-four women with premature ovarian failure and 9 with gonadal dysgenesis had raised basal follicle-stimulating hormone (FSH) levels. Neither the basal luteinizing hormone (LH) level nor the gonadotrophin responses after LRH gave a better separation of this group of women with irreversible ovarian failure. Measurement of prolactin levels were valuable in that 15 of 42 patients with hyperprolactinaemia had a radiologically abnormal pituitary fossa, whereas pituitary fossa abnormalities were found in only 11 of 245 normoprolactinaemic women. It was thought that 181 women had functional amenorrhoea; 54 per cent of these women had developed amenorrhoea in relation to weight loss and 32 per cent in relation to discontinuation of oral contraceptives. A strong correlation was found between the body weight and the basal gonadotrophin levels. The basal LH levels were correlated with serum oestrogen levels, the basal FSH level and the LH response to LRH. Most of the patients with low basal LH values had developed amenorrhoea in relation to self-imposed weight-loss. The responses to LRH were often impaired in the underweight patients but became normal after weight gain. The polycystic ovary syndrome (PCO) could not be diagnosed by measuring either basal or LRH-stimulated gonatrophin levels. Single FSH and prolactin determinations in serum seemed to be the only indispensible hormone assays in the routine clinical evaluation of amenorrhoea.
Six healthy male volunteers were given chlorimipramine 25 mg t.i.d. or nortriptyline 25 mg t.i.d. in a randomized order of 7 days. Plasma samples were assayed for TSH, GH and prolactin before and after stimulation with TRH 200 microgram i.v. It was found that the tricyclic antidepressants did not exert any influence on plasma hormonal levels compared with no treatment conditions. Diminished TSH-responses following daily TRH injections were demonstrated in endogenously depressed and chronic schizophrenic patients. A decreased TSH-response was observed in healthy volunteers after a second TRH injection with an interval of 2 days between the TRH injections. A complete restoration of the TSH-response was obtained after an interval of 4 days.
Serum ferritin, transferrin, iron and haptoglobin have been investigated in a longitudinal study in 18 patients hospitalized for various acute infections. Within a couple of days after the onset of an infection, a rise in serum ferritin was seen, the magnitude of which was not dependent on the type of infection (bacterial or viral). The serum ferritin level remained elevated for several weeks in some patients, and 7 out of the 18 patients still had abnormally high values 5 weeks after the onset of illness. The mean curves for serum ferritin and the acute phase reactant haptoglobin were parallel. Possible mechanisms causing the elevation in serum ferritin are discussed.
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Changes in thyroid hormone metabolism induced by surgical trauma were studied by determination of TSH, T3, rT3, T4 and T3-resin uptake before, during and after mastectomy in 20 women and cholecystectomy in 10 women. Pronounced and reciprocal changes, explained by altered peripheral T4 metabolism were found concerning T3 and rT3. The decreased T3 and increased rT3-levels approached or exceeded the limits of the reference range on the first post-operative day. A significant increase in T3-resin uptake and a decrease in serum T4 were already observed during surgery and probably was caused by a decreased protein binding capacity. An increased concentration of TSH in the serum during surgery was followed by a significant post-operative decrease, possibly due to a suppressive effect of endogenous cortisol. No obvious difference in absolute values or the pattern of change was found between the mastectomy and cholecystectomy groups, although a somewhat more pronounced and retarded alteration in rT3 was found after cholecystectomy.
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Acetone-ether extracts of rat, mouse and hamster placentae were fractionated by molecular sieve chromatography on Sephadex G-200. The fractions were tested for immunoreactivity in human chorionic gonadotropin (hCG), hCG-beta-subunit and alpha-subunit radio-immunoassay systems. The elution profiles were compared with those of similar chromatographic studies of a human placental extract and of purified preparations of hCG and its subunits. The results indicate that rodent placentae have a chorionic gonadotropin and that this hormone in the rat, mouse and hamster is structurally similar to hCG with its alpha- and beta-subunits. Extracts of rat and hamster placentae had a gonadotropic activity similar in concentration to that found in normal human placentae at term. Until now, it has been difficult to find an animal model for studying how the production of chorionic gonadotropin is regulated. Our results suggest that rodents may be suitable for such an investigation.
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Eleven patients with active acromegaly were treated with bromocriptine for one year or more. Nine showed significant reduction in plasma growth hormone levels and eight improvement with respect to clinical symptoms. No serious side effects were observed.
A stimulatory luteinizing hormone-releasing hormone (LRH) analogue D-Ser(TBU)6-EA10-LRH was administered subcutaneously once daily in a dose of 5 microgram to four regularly menstruating women. Treatment was instituted within the first three days of the menstrual bleeding and continued for 22--30 days. Ovulation was inhibited in all the women during the treatment cycle. The treatment resulted in disturbances in the pituitary gonadotropin secretion which presumably led to disordered follicular menuration and anovulation. The maximum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) responses to the LRH analogue were obtained during the first few days of treatment. The gonadotropin responses then rapidly decreased during the prolonged treatment. This change in the pituitary responsiveness probably prevented the release of a normal preovulatory LH surge. After the treatment, all the women resumed normal ovulatory menstrual cycles. The results suggest that it might be possible to use stimulatory LRH analogues for birth control.
A stimulatory luteinizing hormone-releasing hormone (LRH) analogue D-Ser (TBU)6-EA10-LRH was administered subcutaneously once daily in a dose of 5/microgram to four regularly menstruating women. Treatment was instituted within the first three days of the menstrual bleeding and continued for 22--30 days. Ovulation was inhibited in all the women during the treatment cycle. The treatment resulted in disturbances in the pituitary gonadotropin secretion which presumably led to disordered follicular maturation and anovulation. The maximum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) responses to the LRH analogue were obtained during the first few days of treatment. The gonadotropin responses then rapidly decreased during the prolonged treatment. This change in the pituitary responsiveness probably prevented the release of a normal preovulatory LH surge. After the treatment, all the women resumed normal ovulatory menstrual cycles. The results suggest that it might be possible to use stimulatory LRH analogues for birth control.