bluuebunny/crossref_metadata_2025_split huggingface dataset:
BROMOCRIPTINE TREATMENT OF OLIGOSPERMIA: A DOUBLE BLIND STUDY
Authors: HOVATTA O. , KOSKIMIES A. I. , RANTA T. , STENMAN U.‐H. , SEPPÄLÄ M. 
Published: March 2008

SUMMARYA double blind controlled study of bromocriptine treatment of oligospermia was carried out. Out of fifty‐one men who originally volunteered to the study there were forty who took the drug for 12 weeks as requested. All the partners of these men had failed to conceive, and in each case the pretreatment sperm count had been below 40 million/ml on two or several occasions. The pretreatment serum prolactin concentrations were similar in patients given bromocriptine (N = 20) and placebo (N = 20). There were three men in either group whose pretreatment serum prolactin concentration was in excess of 30 μg/l, the highest value being 96 μg/l. While bromocriptine effectively decreased the serum prolactin concentration, it had no significant effect over placebo on sperm volume, motility and morphology. In the bromocriptine group, sperm count increased to or above 40 million/ml in five out of twenty men, while in the placebo group this occurred in nine out of twenty patients. The plasma testosterone and dihydro‐testosterone levels increased slightly during treatment in both groups, but no significant difference was observed between bromocriptine and placebo treated patients. One wife of a bromocriptine‐treated man and two wives of placebo‐treated men became pregnant during treatment. In this study bromocriptine was no more effective than placebo in the treatment of oligospermia.
HETEROGENEITY IN ADRENAL STEROIDOGENESIS IN NORMAL MEN AND WOMEN
Authors: CHILD D. F. , BU'LOCK D. E. , HILLIER V. F. , ANDERSON D. C. 
Published: March 2008

SUMMARYAdrenal steroidogenesis has been studied in vivo in normal men and women. Serum levels of nine steroids on the biosynthetic pathway (the Δ5 3‐β‐hydroxy‐steroids, pregnenolone (Pe), 17α‐hydroxypregnenolone (17Pe), dehydroepian‐drosterone (DHEA), androstenediol (Adiol), and their Δ4 3‐keto counterparts, progesterone (Po), 17α‐hydroxyprogesterone (17Po), androstenedione (Adione), and testosterone (T)) as well as cortisol were measured during adrenal suppression and stimulation. This study demonstrates a marked heterogeneity in adrenal steroid responses between different subjects in the normal population. Thus, in three subjects ACTH stimulation from a dexamethasone‐sup‐pressed state resulted in a far greater increment of 17Po than in the other nineteen normal subjects. These three individuals (designated Type 2 res‐ponders) may have a partial deficiency of 21‐hydroxylase activity. In the remaining nineteen subjects (designated as Type 1 responders) the women had a greater increment of Adiol (P<0.05) and a lower increment of Po (P<0.01) than the men, suggesting that adrenal 3‐β‐hydroxysteroid dehydrogenase/isomerase activity may be slightly lower in women than men.
ADRENAL STEROIDOGENESIS IN HETEROZYGOTES FOR 21‐HYDROXYLASE DEFICIENCY
Authors: CHILD D. F. , BU'LOCK D. E. , ANDERSON D. C. 
Published: March 2008

SUMMARYAdrenal steroidogenesis has been studied in vivo in eight obligate heterozygotes (six men and two women) for 21‐hydroxylase deficiency and the results compared with twenty‐one normal subjects. Serum levels of nine steroids on the biosynthetic pathway (the Δ53β‐hydroxysteroids, pregnenolone (Pe), 17α‐hyd‐roxypregnenolone (17Pe), dehydroepiandrosterone (DHEA), androstenediol (Adiol), and their Δ4 3‐keto counterparts, progesterone (Po), 17α‐hydroxypro‐gesterone (17Po), androstenedione (Adione), testosterone (T)) as well as corti‐sol were measured following ACTH stimulation from a dexamethasone‐sup‐pressed state. There was evidence of reduced 21‐hydroxylase activity in the heterozygotes when the results were compared with the usual pattern of response seen in nineteen of twenty‐two normal subjects. Thus the increment at 1 h for 17α‐hydroxyprogesterone was greater in all the heterozygotes and three of them (one man, two women) also had a greater increment for progesterone. 17,20 desmolase activity may also be reduced in the heterozygotes for they had a lower increment than normal of dehydroepiandrosterone and androstenediol. The results were complicated by the finding that three additional subjects in the normal population tested have much greater 17Po and Po responses than the majority and clearly form a separate population. Our data suggest that there is a common variant within the normal population which may result from the heterozygous state of 21‐hydroxylase deficiency; alternatively other forms of 21‐hydroxylase may exist with reduced activity that even in the homozygous state may not produce clinical disease.
RADIOIMMUNOASSAY OF PLASMA 18‐HYDROXY‐ll‐DEOXYCORTICOSTERONE AND ITS RESPONSE TO ACTH
Authors: MAY C. N. , LEWIS P. S. , HORTH C. E. 
Published: March 2008

SUMMARYA radioimmunoassay for the measurement of 18‐OH‐DOC in plasma was developed using an antiserum raised against the γ‐lactone derivative. The steroids with the greatest degree of cross reaction were 18‐OH‐corticosterone‐γ‐lactone and aldosterone‐γ‐lactone which showed cross‐reactivities of 1.96% and 0.47% respectively. These and other interfering steroids were eliminated by chromatography of the extracts on columns of Sephadex LH‐20. The lowest limit of detection of 18‐OH‐DOC in 1 ml of plasma corresponded to 33 pmol ‐1. The intra‐assay precision was 9.7, 4.8 and 2.6% at 102.0, 316.1 and 1144.0 pmol 1‐1 respectively and the interassay precision was 15.3 and 5.4% at 71.3 and 404.7 pmol l‐1 respectively. The amount of 18‐OH‐DOC measured (y) which showed a high degree of correlation (r = 0.999) with the amount added (x) to plasma in the range 240–1920 pmol 1‐1 could be predicted from the linear least squares equation y = 1.006x + 31.3. The concentration of 18‐OH‐DOC in ten normal subjects was 172.1 ± 39.1 pmol l‐1 at 09.00 h, 100.9 ± 16 9 pmol l‐1 at 12.00 h and 95.8 ± 33.3 pmol l‐1 at 16.30 h. Plasma 18‐OH‐DOC and cortisol levels were measured after various intravenous doses of ACTH in three patients with essential hypertension. Lower doses of ACTH caused similar percentage increases in both hormones but higher doses caused considerably greater increases in 18‐OH‐DOC. These results confirm the ACTH dependancy of 18‐OH‐DOC secretion.
GLUCAGON METABOLISM IN NORMAL SUBJECTS AND IN CIRRHOTIC PATIENTS BEFORE AND AFTER PORTASYSTEMIC VENOUS SHUNT SURGERY*
Authors: ALFORD F. P. , DUDLEY F. J. , CHISHOLM D. J. , FINDLAY D. M. 
Published: March 2008

SUMMARYThe effect of portasystemic shunt surgery on basal immunoreactive glucagon (IRG) levels, metabolic clearance rate (MCR) and t ½ for glucagon decay, and basal systemic delivery rate (BSDR) of glucagon was investigated in paired studies in ten cirrhotic subjects. The degree of hepatocellular dysfunction and extent of portasystemic venous shunting was also recorded. Basal IRG levels were highest in the post‐shunt (meanSEM, 382 ± 73 pg/ml) as compared to the pre‐shunt (213±27 pg/ml; P<0.05) cirrhotic and control (53 ± 13 pg/ml; P<0.005) groups. The MCR of glucagon was similar in control (13.±1.3 ml/kg/min) and pre‐shunt cirrhotic patients (13‐3±1.7 ml/kg/min) but was significantly (P<0.02) decreased in the post‐shunt cirrhotics (7.6±1.3 ml/kg/min). The ½for glucagon decay was similar in the control and cirrhotic groups. The BSDR, an estimate of pancreatic A cell secretion, was increased four‐fold (P<0.01) in the pre‐shunt (3042±454 pg/kg/min) and post‐shunt (2518±535 pg/kg/min) cirrhotic groups, as compared to controls (750±244 pg/kg/min). It is concluded that (a) in the presence of cirrhosis, the magnitude of portasystemic shunting is important in determining the degree of hyperglucagonaemia; (b) in preshunt cirrhotics raised basal IRG levels are principally due to A cell hypersecretion of glucagon whereas in post‐shunt cirrhotics raised IRG levels reflect both A cell hypersecretion and delayed clearance of glucagon; and (c) acute shunting of splanchnic venous blood away from the liver reduces the clearance of glucagon, suggesting that, in man, the liver contributes to the clearance of circulating glucagon.
IMMUNOLOGICAL AND GENETIC MARKERS IN A FAMILY WITH HASHIMOTO'S DISEASE
Authors: GORDIN A. , MÄENPÄÄ J. , MÄKINEN TUULIKKI , TÖTTERMAN T. H. , TIILIKAINEN ANJA 
Published: March 2008

SUMMARYA family with Hashimoto's disease in three generations is described. Seven persons (all female) had Hashimoto's disease and four of them were initially hypothyroid. Hashimoto's disease was the only thyroid disorder occurring in this family; no other autoimmune disease was observed. Circulating thyroid antibodies were detected in all seven subjects with overt thyroiditis in this family. Thyroid antibodies were also detected in low titres in about half of the healthy relatives. Evidence of thyroid antigen‐directed cell‐mediated immunity was demonstrated using the leucocyte migration inhibition test in four out of seven subjects with thyroiditis and also in about half of the relatives without clinical thyroid disease. The relative number of thyroglobulin‐binding circulating lymphocytes was elevated in six subjects with Hashimoto's disease. Again, the percentage of such cells was also increased in about half of the‘healthy’relatives. Thyroid‐stimulating immunoglobulins were detected by the radio receptor assay in three of the seven subjects with Hashimoto's disease and in four out of thirteen relatives without overt signs of thyroiditis. In conclusion, all subjects with Hashimoto's disease carried immunological markers of autoimmune thyroid disease in the circulation. In addition, most of the‘healthy’relatives were also positive for some or all of the markers sought in this study. The expression of these markers thus seems to be variable. No clear‐cut conclusion could be drawn regarding the inheritance of these markers. H LA genotypes were assayed for thirty‐five specificities of A, B and C loci and five of the D loci. There was no correlation between any individual antigen or HLA haplotype and overt Hashimoto's disease in this family.
EFFECTS OF RADIOIODINE ON THYROTROPHIN BINDING INHIBITING IMMUNOGLOBULINS IN GRAVES’DISEASE
Authors: McGregor A. M. , PETERSEN M. M. , CAPIFERRI R. , EVERED D. C. , REES SMITH B. , HALL R. 
Published: March 2008

SUMMARYWe have studied the effects of 131I therapy on thyrotrophin binding inhibiting immunoglobulins (TBII) in fifty‐five patients with Graves’disease and five patients with toxic multinodular goitre (MNG). A group of forty patients with Graves’disease and four patients with toxic MNG were treated with drugs and acted as controls. In 78% of patients treated with 131I there was a marked increase in the serum TBII activity during the 3 months following therapy, whereas drug‐treated patients showed a decrease (77%) or no change in TBII activity over the same period. TBII activity was not detectable in patients with toxic MNG before or after drug or 131I therapy. Consideration of the mechanisms involved in the changes in serum TBII activity after 131I treatment or during drug treatment provide insight into the basic defects responsible for the development of hyperthyroid Graves’disease and suggest that both the thyroid and immune system are involved.
THYROID FUNCTION, IODINE NUTRITION AND FETAL BRAIN DEVELOPMENT
Authors: HETZEL BASIL S. , HAY IAN D. 
Published: March 2008

SUMMARYThe clinical effects of congenital hypothyroidism on brain function have been well documented and the need for early diagnosis and treatment established. This is now possible through neonatal screening. Improved results may be expected but there is evidence of prenatal effects. More evidence of the effects of fetal hypothyroidism on brain development is required in order to determine the need for antenatal diagnosis. Experimental studies indicate significant effects of hypothyroidism on fetal brain development in the monkey and the sheep during the third trimester. In the rat, significant effects, particularly on the cerebellum, can be shown in the first 3 weeks postnatally, a period corresponding to the third trimester of the human pregnancy. Retardation of cerebellar nerve cell migration, differentiation, growth and arborization have all been demonstrated, together with persistence of the external granular zone and DNA polymerase activity. Such effects provide an explanation for the common occurrence of ataxia and nystagmus in congenital hypothyroidism. Severe iodine deficiency with an intake less than 20 μg per day and high goitre prevalence in endemic goitre areas is associated with the condition of endemic cretinism characterised in its fully developed form by mental deficiency, deaf mutism, spastic diplegia and squint with absence of clinical hypothyroidism. This condition does not respond to replacement therapy with thyroid hormones. Correction of the iodine deficiency prior to pregnancy will prevent the condition, but correction of the iodine deficiency in the latter half of pregnancy will not. This indicates the necessity of iodine for fetal brain development in man. Experimental studies in the guinea pig and sheep indicate an effect of severe iodine deficiency on brain growth early in pregnancy at the time of neuroblast multiplication. Such an early effect could provide an explanation for the irreversibility of the effects of severe iodine deficiency on brain development in man. The role of maternal and fetal hypothyroidism and iodine deficiency itself in these effects has still to be defined. It may be concluded that the relation
SERUM PREGNENOLONE, PROGESTERONE, 17α‐HYDROXYPROGESTERONE, ANDROSTENEDIONE, TESTOSTERONE, 5α‐DIHYDROTESTOSTERONE AND ANDROSTERONE DURING PUBERTY IN BOYS
Authors: PAKARINEN A. , HAMMOND G. L. , VIHKO R. 
Published: March 2008

SUMMARYWe have determined the concentrations of pregnenolone, progesterone, 17α‐hydroxyprogesterone, androstenedione, testosterone, 5α‐dihydrotestosler‐one and androsterone in serum samples collected from a total of seventy‐nine boys who were 8–18 years of age at the time the first blood samples were drawn. Additional samples were drawn from sixty‐six and forty‐four of these boys after 1 and 2 year intervals, respectively. The first increases in serum steroid concentrations were those of androstenedione and androsterone, thus supporting the hypothesis that an early activation of the adrenal cortex is the first hormonal change in puberty. This increase in serum androstenedione occurred 2 years earlier than the first significant increase in serum testosterone, which took place by 13 5 years, after the first signs of external genital development, but in concert with the onset of pubic hair growth. The serum concentrations of 5α‐dihydrotestosterone were closely related to those of testosterone, but the relative increases were smaller, the consequence of which is a decrease in the ratio of 5α‐dihydrotestosterone: testosterone throughout puberty. The main increase in serum androsterone tends to take place after that of 5α‐dihydrotestosterone and testosterone. In comparison with the four androgens, the serum concentrations of their C21precursors correlated rather poorly with the physical signs of advancing puberty. As in the case of androstenedione, the concentrations of pregnenolone and 17α‐hydroxyprogesterone were relatively high in the youngest age groups, which probably also reflects an early adrenal activation. In contrast to testosterone, the major increases in precursor steroids occur at a relatively late stage of puberty. It seems likely therefore that a major qualitative shift in the testicular secretion of steroids occurs during puberty in boys.
FAILURE OF NALOXONE TO ALTER GROWTH HORMONE AND PROLACTIN LEVELS IN ACROMEGALIC AND IN HYPERPROLACTINAEMIC PATIENTS
Authors: BLANKSTEIN J. , REYES F. , WINTER J. , FAIMAN C. 
Published: March 2008

SUMMARYWe examined the effects of high‐dose intravenous naloxone administration in four acromegalic patients (mean serum growth hormone level 72 ng/ml) and in seven hyperprolactinaemic women (mean serum prolactin level 59 ng/ml), in order to assess whether this opiate antagonist would be effective in lowering growth hormone and prolactin levels. No effect was observed. This lack of effect suggests that an opioid pathway is not involved in the maintenance of elevated growth hormone or prolactin secretion in these patients. However, conclusions regarding the possible role of endogenous opioids in regulation of pituitary function in normal individuals cannot be drawn from this study.
METABOLISM OF INTRAVENOUSLY ADMINISTERED CHOLECALCIFEROL IN MAN
Authors: BARRAGRY J. M. , FRANCE M. W. , BOUCHER B. J. , COHEN R. D. 
Published: March 2008

SUMMARYFollowing intravenous injection of (3H) cholecalciferol into healthy subjects the disappearance of label from the plasma was followed by the reappearance (‘rebound’) of (3H) radioactivity associated exclusively with cholecalciferol. Lipoprotein fractionation of plasma revealed an increasing association of label with protein rather than lipoprotein during the rebound phase. We conclude that the rebound of plasma radioactivity reflects the transfer of label from lipoprotein to Vitamin D‐binding globulin in the liver followed by its release into plasma.
EFFECTS OF NORGESTREL AND ETHINYLOESTRADIOL INGESTION ON SERUM LEVELS OF SEX HORMONES AND GONADOTROPHINS IN MEN
Authors: KJELD J. M. , PUAH C. M. , KAUFMAN B. , LOIZOU S. , VLOTIDES J. , GWEE H. M. , KAHN F. , SOOD R. , JOPLIN G. F. 
Published: March 2008

SUMMARYDL‐norgestrel and ethinyloestradiol were ingested separately and in combination by six healthy men. Serum levels of testosterone, 5α‐dihydrotestosterone, oestradiol, FSH, LH and prolactin were measured before (basal), during and after ingestion of the combined drugs. Ethinyloestradiol 50 μg and DL‐norgestrel 500 μg for nine days lowered the levels of testosterone to 8% (1·25 nmol/l = 0·36 ng/ml), 5α‐dihydrotestosterone to 22% (0·39 nmol= 106 pg/ml), oestradiol to 46%(0·025 nmol/l = 6·88 pg/ml), FSH to 31% (0·55 U/l)and LH to 61% (2·37 U/l) of the basal values. All levels had risen on the third day after stopping the drugs and had recovered to pretreatment values within a week. Prolactin values did not show any definite trend of change during the treatment. In three men ethinyloestradiol alone, 50 μg daily for 5 days, reduced serum levels of all three sex hormones to approximately 80% of basal levels and FSH to 70% but left LH and prolactin levels unchanged. In three men DL‐norgestrel alone, 525 ug daily for 4 days, reduced the androgen levels to below 40% of the basal levels, but had little effect on oestradiol levels. FSH, LH and prolactin levels were reduced to 63%, 70% and 65% respectively by the 4 days of DL‐norgestrel treatment. The 26 h effects of DL‐norgestrel were studied in three men who ingested 1050 ug of the drug in one dose. Serum testosterone and 5α‐dihydrotestosterone levels had their greatest depression (30% and 60% respectively) at 12 to 14 h after the ingestion, whereas serum levels of DL‐norgestrel peaked at 2 h after the ingestion. In this study serum FSH levels showed a clear depression in two men but LH and prolactin levels did not change. The results show a powerful effect of DL‐norgestrel in reducing serum androgen levels in men, an effect which may be partly mediated through the concurrent suppression of the pituitary gonadotrophins.
THE CIRCADIAN VARIATION OF IMMUNOREACTIVE LIPOTROPHIN AND ITS RELATIONSHIP TO ACTH AND GROWTH HORMONE IN MAN
Authors: MULLEN P. E. , JEFFCOATE W. J. , LINSELL C. , HOWARD R. , REES LESLEY H. 
Published: March 2008

SUMMARYThere is a clear circadian rhythm of plasma immunoreactive LPH in man with the trough occurring between 22.00 h and 03.00 h and the peak between 07.00 h and 08.00 h, immediately after waking. At all times circulating LPH and ACTH levels follow each other closely. However, no correlation was observed between LPH levels and either plasma GH or the stage of sleep.
URINARY FREE CORTISOL EXCRETION IN PATIENTS WITH HYPERSEROTONINAEMIA FROM THE CARCINOID SYNDROME
Authors: FELDMAN JEROME M. 
Published: March 2008

SUMMARYTo determine if patients with chronic hyperserotoninaemia from the carcinoid syndrome have increased basal adrenocortical function, I have determined the urinary free Cortisol excretion of seventeen patients with carcinoid tumours and the carcinoid syndrome, twelve patients with carcinoid tumours without the carcinoid syndrome and seventeen normal subjects. There was no significant difference in the urinary free Cortisol excretion of the patients with carcinoid tumours and the carcinoid syndrome (133±20±0 nmoles/24 h), patients with carcinoid tumours without the carcinoid syndrome (115±29 nmoles/24 h) and the normal subjects (96 ±r 9 nmoles/24 h). There was no correlation between the urinary free Cortisol secretion and urinary 5‐hydroxyindoleacetic acid or serum serotonin concentration in the patients with the carcinoid syndrome. There was a suggestion that patients with 5‐hydroxytryptophan (5‐HTP) secreting carcinoid tumours had higher urinary free Cortisol excretion than patients with predominantly serotonin (5‐HT) secreting carcinoid tumours. This may be due to the fact that the non‐polar 5‐HTP molecule penetrates the blood‐brain barrier more effectively than the polar 5‐HT molecule. 5‐HTP is then converted to 5‐HT within the brain. None of the twenty‐nine patients with carcinoid tumours had clinical or laboratory evidence of the ectopic ACTH syndrome.
THE EFFECTS OF PROLONGED ADMINISTRATION OF D‐SER(TBU) 6‐LH‐RH‐EA10 (HOE 766) IN SUBJECTS WITH HYPOGONADOTROPHIC HYPOGONADISM
Authors: SMITH R. , DONALD R. A. , ESPINER E. A. , STRONACH S. 
Published: March 2008

SUMMARYNine patients with hypogonadotrophic hypogonadism (five due to isolated gonadotrophin deficiency and four due to craniopharyngioma) were treated with daily subcutaneous injections of a long acting LHRH analogue, Hoe 766. Therapy was continued for between 27 and 38 weeks and doses varied between 1–25 and 5 μg per day. At monthly intervals patients were assessed by their LH and FSH response to 100 μg of LHRH and by second hourly sampling for LH, FSH and testosterone for the 24 hours after their Hoe 766 dose. Regardless of the diagnosis or the dose of Hoe 766 the LH response to Hoe 766 and to LHRH deteriorated with increasing duration of therapy. Plasma FSH values became low after only 1 week of therapy and failed to improve. Peak plasma testosterone during therapy correlated with peak plasma LH regardless of the duration of treatment (r = 0±43, P < 0±05, n = 22). Peak plasma LH on LHRH stimulation tests correlated with peak plasma LH on Hoe 766 24 hour studies independently of the length of treatment or the dose of Hoe 766 (r=0±62, P < 0±01, n = 18). In this group of patients peak plasma LH on LHRH stimulation tests did not correlate with basal plasma LH. Throughout the study in all patients testosterone was subnormal at 08.00 h. If testosterone rose after Hoe 766 it did so within the first 12 hours following the injection and had returned to baseline levels by 08.00 h the following day. It is concluded that prolonged daily administration of Hoe 766 within the dose range studied leads to loss of pituitary LH and FSH responses to both Hoe 766 and LHRH. Our results suggest that the loss of LH responsiveness is not due to testosterone feedback inhibition or selective resistance to Hoe 766, but may be explained by depletion of gonadotrophin stores in the pituitary gland.