bluuebunny/crossref_metadata_2025_split huggingface dataset:
ON THE USE OF A NEW SOMATOSTATIN ANALOGUE IN THE TREATMENT OF HYPOGLYCAEMIA IN PATIENTS WITH INSULINOMA
Authors: VERSCHOOR L. , UITTERLINDEN P. , LAMBERTS S. W. J. , DEL POZO E. 
Published: March 2008

SUMMARYA novel potent analogue of somatostatin, the octapepide SMS 201–995 was tested as a therapeutic manoeuvre to prevent hypoglycaemia in patients with insulinoma. We investigated the acute effects of a single 50 μg dose of the analogue administered s.c. in three patients, comparing the results in two of them with those obtained after administration of saline (control) and native somatostatin. In addition two patients were treated for up to 5 d with two or three daily s.c. injections (daily dose of analogue ranging from 100 to 300 μg). In two of the three patients SMS 201–995 suppressed circulating insulin levels by more than 50% and increased plasma glucose to hyperglycaemic levels for 6–8 h after a single injection. No undesirable effects of the administration of the analogue were observed. As opposed to insulin suppression obtained with native somatostatin, no rebound increase in insulin levels was observed after administration of the analogue. We conclude that SMS 201–995 prevented hypoglycaemia in two out of three patients with insulinoma. The advantage of s.c. administration, the long duration of action and the absence of a rebound phenomenon give this analogue a place in the pre‐operative management of patients with insulinoma.
EVIDENCE FOR SEROTONINERGIC SYSTEM INVOLVEMENT IN OPIOID CONTROL OF LUTEINIZING HORMONE SECRETION IN MAN
Authors: FORESTA C. , MIONI R. , SCANDELLARI C. 
Published: March 2008

SUMMARYEndogenous opioid peptides tonically inhibit LH by acting on hypothalamic mechanisms which regulate LHRH secretion. Opiates increase hypothalamic serotonin turnover but the involvement of the serotoninergic system in the opioid mechanisms regulating LH secretion in man is not clear at present. This study was designed to evaluate whether the tonic inhibitory effect on LH secretion induced by opiates involves the serotoninergic system. We have studied 10 healthy young men (aged 20–28 years). Five subjects were infused with naloxone (10 mg/h for 3 h) before and 120 min after fenfluramine administration (60 mg orally) on two different occasions. In five other subjects naloxone was infused before and after metergoline pretreatment (8 mg on first and second day and 4 mg on the third day, orally, at 0 time of naloxone infusion). After fenfluramine, naloxone infusion failed to induce any increase in LH plasma levels; metergoline pretreatment significantly enhanced the nalox‐one‐induced LH increase. These data suggest that in man a hypothalamic serotoninergic system may be involved in the opioid mechanisms regulating LH secretion.
CHARACTERISTICS OF PATIENTS WITH NORMAL T3 AND T4 AND A LOW TSH RESPONSE TO TRH
Authors: BOUTIN J. M. , MATTE R. , D'AMOUR P. , GILBERT F. , HAVRANKOVA J. , BÉLANGER R. , CHARTRAND R. , ZAKARIJA M. 
Published: March 2008

SUMMARYThe nature of the thyroid disorder presented by patients with normal T4 and T3 but blunted TSH response to TRH has not been clarified. In this study, we compared thyroid function tests in 16 such patients with those of 14 controls and 10 hyperthyroid patients. Basal total T4, free T4. total T3, iodine uptake and cholesterol of the study group were similar to controls but significantly (P < 0.001) lower than in hyperthyroid patients, except for cholesterol which was higher. In contrast, the basal TSH, increase in TSH after TRH stimulation, and decrease of T4 during T3 suppression tests were similar to data obtained in hyperthyroid patients but significantly (P < 0001) lower than in controls. Pulse rate was mid‐way between the control and the hyperthyroid group. Thyroid stimulating antibody (TSAb) was measured with human thyroid cells in culture; the assay was positive in four subjects in the 16‐patient group and in all hyperthyroid patients tested. TSH stimulation test showed a hyporesponse in iodine uptake in the four patients with positive TSAb (26±29%), as well as in hyperthyroid patients (6+5%). However, there was a hyper‐response to TSH (213 ± 52%) in the remaining 12 patients in the group, none of whom had TSAb. Thus TSAb is not seen as responsible for the thyroid disorder in the majority of patients with normal T3 and T4 and absent or blunted TSH response to TRH; surprisingly, most of these patients have thyroid hypersensitivity to TSH. These two characteristics, absence of TSAb and hypersensitivity to TSH, delineate a thyroid disorder clearly different from Graves' disease.
COMPLEMENT COMPONENT C9 IN GRAVES' DISEASE
Authors: OLEESKY D. A. , RATANACHAIYAVONG S. , LUDGATE M. , MORGAN B. P. , CAMPBELL A. K. , MCGREGOR A. M. 
Published: March 2008

SUMMARYC9, the terminal component of complement, is the key part of the membrane attack complex formed as a result of complement activation; it has also been reported to be an acute phase protein. Its potential role in Graves' disease has been studied by measuring plasma C9 concentrations using an automated two‐site immunoradiometric assay employing monoclonal antibodies, whose binding to thyroid tissue has also been investigated. The plasma C9 concentration in patients with hyperthyroid Graves' disease (86.3 ± 21.6 mg/L mean±SD; n= 49) was significantly increased (P < 0.001) compared with normal subjects (60.4 ± 13.4 mg/l; n= 48). In contrast, the plasma concentration of C‐reactive protein, a marker of the acute phase response, was not significantly different between the two groups. The plasma C9 concentration in patients with hyperthyroid Graves' disease decreased significantly (P < 0.01) after treatment with antithyroid drugs (carbimazole or methimazole; n= 14), but not after radioactive iodine (131I) treatment (n = 18). Immunohistochemical staining demonstrated that monoclonal antibody to C9 bound to the basement membranes of thyroid follicular cells of Graves' thyroid tissue but not to normal thyroid tissue. Radiolabeled monoclonal antibody to C9 bound to membrane fragments prepared from thyroid glands from two patients with Graves' disease. We conclude that C9, and by implication the membrane attack complex, may be involved in the pathogenesis of Graves' disease.
THE EFFECT OF PULSATILE FOLLICLE STIMULATING HORMONE ON THE. ENDOGENOUS LUTEINIZING HORMONE SURGE IN WOMEN
Authors: MESSINIS I. E. , TEMPLETON A. 
Published: March 2008

SUMMARYThe effect of pulsatile administration of ‘pure’ FSH on the endogenous LH surge was investigated in 10 infertile but otherwise normal women. In each woman the LH surge in the spontaneous cycle preceding the treatment cycle was characterized in blood samples taken every 6 h. FSH was injected s.c. via a pump (28 IU every 3 h) starting on cycle day 2. Only five of the FSH‐treated women displayed an endogenous LH surge, and this was markedly attenuated in four of them. The LH surge occurred significantly earlier in the FSH‐treated than in the corresponding spontaneous cycle (cycle day 10.2 ± 0.5 vs 13.6 ± 0.8 mean‐± SEM, P < 005), although it tended to occur later in the FSH‐treated cycles with a higher total follicular fluid volume of follicles 12–15 mm in diameter. This volume was even greater in the FSH‐treated cycles without an endogenous LH surge. Serum progesterone levels increased significantly in all five FSH‐treated cycles after the onset of the LH surge and ovulation was confirmed by ultrasound in four of them. These results suggest that the LH surge during superovulation induction with pulsatile FSH in normally cycling women is a variable event. We postulate that unknown inhibitory substances secreted be small growing follicles antagonize the positive feedback effect of E2 on LH secretion.
EFFECTS OF MEDROXYPROGESTERONE ACETATE IN WOMEN WITH POLYCYSTIC OVARY SYNDROME
Authors: PETSOS P. , RATCLIFFE WENDY A. , ANDERSON D. C. 
Published: March 2008

SUMMARYLH levels are inappropriately elevated in women with polycystic ovary syndrome (PCO). Regardless of whether this LH elevation is primary or secondary it may be involved in the establishment of chronic anovulation. We have therefore tried selectively to suppress LH by giving medroxyprogesterone acetate (MPA) 5 mg twice daily for 14 d to 13 women with PCO (14 studies) and have examined their pituitary and ovarian response to assess whether follicular development and ovulation would be triggered post‐treatment as a result of secretion of endogenous gonadotropins in a more nearly physiological ratio. Blood samples were obtained before and two to three times weekly during and after treatment for 35–50 d. In two of these cycles MPA was started fortuitously during the luteal phase of a spontaneous cycle. In the remainder, three patterns of response were seen. In 9 cycles, after an initial rise, there was a progressive fall in gonadotropin levels, LH (mean 48% of basal) more than FSH (mean 68% of basal); after MPA was stopped FSH levels recovered more rapidly than LH. In two cycles (one subject) MPA administration was associated with a progressive rise in serum oestradiol and progesterone. In a further cycle, treatment was also accompanied by an oestradiol rise and was followed by establishment of regular ovulatory cycles. The observed differential suppressive effect on LH and FSH levels suggests that MPA might be of therapeutic value if followed by treatment with anti‐oestrogens or exogenous gonadotrophins in PCO.
RESPONSE TO NEUROTRANSMITTER MODULATING DRUGS IN PATIENTS WITH CUSHING'S DISEASE
Authors: KOPPESCHAAR H. P. F. , CROUGHS R. J. M. , THIJSSEN J. H. H. , SCHWARZ F. 
Published: March 2008

SUMMARYWe designed a systematic study of patients with Cushing's disease to compare the results of acute experiments with cyproheptadine, sodium valproate and bromocriptine with the results of chronic treatment with sodium valproate. In 13 patients the plasma Cortisol response to single doses of 2.5 mg bromocriptine, 6 mg cyproheptadine and 300 mg sodium valproate was assessed over 4.8 h. All patients were then treated with sodium valproate 200 mg three times a day for a period of 3 months. Subjects were classified as responders when there was a reduction in plasma Cortisol by at least 50% below the basal level in two consecutive plasma samples during one of these tests, and/or clinical remission and normalization of Cortisol production rate during sodium valproate treatment. Four patients responded significantly to at least one of the agents (group I) and 9 did not (group II). In group I three patients were bromocriptine responsive and one of these responded also to cyproheptadine; in this patient both sodium valproate and cyproheptadine were able to induce a remission during chronic treatment. In the one patient of the responder group who was bromocriptine insensitive, sodium valproate treatment also induced a remission. In two patients of the responder group sodium valproate treatment was ineffective. However, in both patients chronic treatment with bromocriptine induced a marked clinical improvement associated with a decrease of Cortisol production rate. There was no difference between the groups in sex, age, clinical presentation, duration or severity of hypercortisolism. In one patient in group I a macroadenoma with suprasellar extension was present, while a microadenoma was detected in four patients in group II. There was no difference in the sensitivity of Cortisol secretion to the suppressive effect of overnight or 5 h infusion of dexamethasone between the two groups, and PRL levels were normal in all. These data show that responsiveness of patients with Cushing's disease to neurotransmitter modulating drugs is not associated by specific clinical or biochemical characteristics. Bromocriptine tests most reliably predict the chances for successful medical treatment. However, non‐responsiveness to acute administration of neurotransmitter modulating drugs does not exclude with certainty their usefulness during chronic treatment.
RAPID IMPROVEMENT IN VISUAL FIELD DEFECTS FOLLOWING BROMOCRIPTINE TREATMENT OF PATIENTS WITH NON‐FUNCTIONING PITUITARY ADENOMAS
Authors: D'EMDEN M. C. , HARRISON L. C. 
Published: March 2008

SUMMARYThe role of bromocriptine in the treatment of non‐functioning pituitary tumours is not yet defined. Patients with these tumours who present with visual field defects usually undergo immediate surgery. Three consecutive patients are reported: each had rapid improvement in their visual field defects following bromocriptine 7.5 mg/d before surgery. Histological and immunohistochemical examination confirmed that their tumours were non‐functioning chromophobe adenomas. Their responses indicate that bromocriptine may have a role in the management of some patients with non‐functioning pituitary tumours.
EFFECTS OF SOMATOSTATIN ANALOGUE SMS 201–995 IN NON‐INSULIN‐DEPENDENT DIABETES
Authors: DAVIES R. R. , MILLER MARGARET , TURNER S. J. , WATSON M. , McGILL A. , ØRSKOV H. , ALBERTI K. G. M. M. , JOHNSTON D. G. 
Published: March 2008

SUMMARYThe 24‐h hormonal and metabolic profiles obtained in five non‐insulin‐dependent diabetics receiving twice daily s.c. injections of the long‐acting somatostatin analogue SMS 201–995 (50 μg) have been compared with those obtained following placebo injection. Injections were given 30 min before breakfast and the evening meal. GH secretion was not suppressed by the analogue administered in this manner. Despite suppression of serum insulin levels following breakfast and the evening meal, blood glucose levels were similar during the two study periods with no evidence of worsening in diabetic control. Prolonged suppression of plasma glucagon levels was observed and the nocturnal elevation in serum TSH levels was abolished. Free T4 levels fell significantly following the analogue but total T3 levels were unaffected. Blood alanine levels were elevated throughout the study period following SMS 201–995 but changes in lactate, pyruvate, glycerol and 3‐hydroxybutyrate were minor. All five subjects suffered gastrointestinal side‐effects. SMS 201–995 (50 μg) given twice daily before meals does not cause a deterioration in metabolic control, does not suppress 24‐h GH secretion and causes significant side‐effects in patients with non‐insulin‐dependent diabetes mellitus.
OVULATORY DISTURBANCES IN PATIENTS WITH LUTEAL INSUFFICIENCY
Authors: HAMILTON C. J. C. M. , EVERS J. L. H. , DE HAAN J. 
Published: March 2008

SUMMARYIn order to study ovulatory disturbances in patients with luteal insufficiency we evaluated 210 cycles of 170 women from infertile couples by ultrasonographic follicle measurements and hormonal determinations. Only cycles with evidence of luteinization were included into the study. Mid‐luteal progesterone (P) levels were determined in relation to the ultrasonographic ovulation time or, where the follicle failed to rupture, in relation to the LH peak. In spontaneous cycles with a mid‐luteal P level below 32 nmol/l (10 ng/ml) a luteinized unruptured follicle (LUF) was found in 71.1 % of cycles, whereas in spontaneous cycles with a mid‐luteal P level above 32 nmol/l only 7.9% cycles exhibited a failure of the follicle to rupture. The same phenomenon was encountered in cycles in which agents had been given to induce ovulation. The incidence of LUF cycles in an average infertility population could be calculated to be as high as 50% if the mid‐luteal P level is below 32 nmol/l and as low as 4% if the mid‐luteal P level is above 32 nmol/l. The geometric mean mid‐luteal P level in spontaneous LUF cycles was 32.5 nmol/l, compared to 55.2 nmol/l in spontaneous ovulatory cycles (P < 0001). We conclude that in patients with luteal insufficiency a high incidence is found of a failure of the follicle to rupture. The entrapment of the oocyte in the unruptured follicle constitutes an important cause of infertility in these patients.
SOMATOMEDIN‐C LEVELS IN TREATED AND UNTREATED PATIENTS WITH ACROMEGALY
Authors: ROELFSEMA F. , FRÖLICH M. , VAN DULKEN H. 
Published: March 2008

SUMMARYWith the aid of a recently developed commercially available radioimmunoassay for Somatomedin‐C (Sm‐C) we measured the Sm‐C levels in 38 controls, 24 untreated acromegalics, 45 inactive acromegalics and five pituitary dwarfs. With the exception of the dwarfs, the age and sex distributions for the various groups were similar. In inactive acromegalics the basal GH level (calculated as the mean of four blood samples taken during the day) was < 5 mU/1; it was depressed to, or less than, 2‐5 mU/1 during the 100 g oral glucose tolerance test. The mean Sm‐C level found for control subjects was 20‐4 ± 5.1 nmol/1 and for untreated patients 85‐6 ± 25‐7 nmol/1 (mean ± SD, P<0.001). The mean Sm‐C level for inactive patients who had undergone surgery and invariably showed a normalized paradoxical reaction to TRH was 18‐2 ± 7‐1 nmol/1 (NS) vs 16.1+8.2 nmol/1 (NS) for those who underwent surgery plus postoperative pituitary radiation therapy. Only one out of 45 inactive acromegalics exhibited an increased Sm‐C level. The Sm‐C levels correlated significantly not only with the log GH levels (r= 0–82) but also with the fasting insulin/glucose ratio the integrated incremental insulin levels, the maximal insulin increase and the integrated glucose levels during the oral glucose tolerance test as well as the 24‐h urinary excretion of calcium and hydroxyproline. The prolactin level did not influence the Sm‐C level; however the Sm‐C levels were lower in inactive patients with an impaired GH release during insulin‐induced hypoglycaemia than in patients with an adequate release (i.e. > 12 mU/1). These results demonstrate that the Sm‐C levels are increased without exception in active acromegaly and normal in inactive patients, so that this measurement can be used for assessment of the activity of the disease.
AMENORRHOEA IN CYSTIC FIBROSIS
Authors: STEAD R. J. , HODSON M. E. , BATTEN J. C. , ADAMS J. , JACOBS H. S. 
Published: March 2008

SUMMARYMenstrual history in relation to nutritional status and lung function was assessed in 45 adolescent and adult patients with cystic fibrosis (CF). Twenty patients had regular menstrual cycles (of whom six had been pregnant), 12 had primary or secondary amenorrhoea, 11 had irregular cycles and two were pre‐menarcheal. Patients with regular menstruation had a significantly higher body mass index and percentage body fat (estimated from skinfold thickness measurements) than those with amenorrhoea (P<lt;0.001), and also better lung function (P<lt;0.01). A linear discriminant analysis indicated that of the four indices studied percentage body fat was the most important predictor of menstrual function. Ovarian and uterine morphology were studied by ultrasonography in 28 patients and 17 healthy controls. In 10 patients multicystic ovaries were noted. Even in patients with regular cycles uterine size was reduced (P<lt;0.01) and in those with amenorrhoea appeared to be related to thinness. Amenorrhoea in CF is an appropriate adaptive response in preventing pregnancy, but the resultant oestrogen deficiency and psychological effects must be considered.
BROMOCRIPTINE TREATMENT OF WOMEN WITH CLOMIPHENE‐RESISTANT POLYCYSTIC OVARY SYNDROME
Authors: POLSON D. W. , MASON H. D. , FRANKS S. 
Published: March 2008

SUMMARYTwenty‐three patients with polycystic ovary syndrome and anovulatory infertility have been treated with bromocriptine. All had previously failed to respond to clomiphene. Twenty had normal serum prolactin concentrations and, of these, four (20%) developed regular ovulatory cycles. All three women with moderate hyperprolactinaemia ovulated regularly on bromocriptine so that, overall, seven of 23(30%) responded, which was a significantly higher proportion than that observed during a control period of no treatment. A further eight women ovulated at least once during the study period but these occasional ovulations were no more common during bromocriptine than with either clomiphene or no treatment. No suppression of LH was noted except during the luteal phase of ovulatory cycles and there was no change in the pattern of pulsatile release of LH. Testosterone and androstenedione concentrations remained elevated and unchanged. We conclude that bromocriptine may be expected to induce ovulation in hyperprolactinaemic women with polycystic ovary syndrome but that there is no clear indication for its use in clomiphene‐resistant patients with normal serum prolactin concentrations.
AMIODARONE IODINE‐INDUCED HYPOTHYROIDISM: RISK FACTORS AND FOLLOW‐UP IN 28 CASES
Authors: MARTINO E. , AGHINI‐LOMBARDI F. , MARIOTTI S. , BARTALENA L. , LENZIARDI M. , CECCARELLI C. , BAMBINI G. , SAFRAN M. , BRAVERMAN L. E. , PINCHERA A. 
Published: March 2008

SUMMARYAmiodarone, an iodine‐rich drug widely used for the treatment of cardiac tachyarrhythmias, may induce either hyperthyroidism or hypothyroidism. Of 467 patients chronically treated with this drug referred to our institution, amiodarone iodine‐induced hypothyroidism (AIIH) developed in 28 patients (6%). AIIH patients were subdivided into two groups according to the presence (group A) or absence (group B) of underlying thyroid abnormalities. Thyroid autoantibodies were present in 10 of 19 patients from group A and 0 of 9 patients from group B. The thyroid 24‐h radioiodine uptake (RAIU) was evaluated in 15 patients: low values (<4%) were found in three patients and detectable values (7–50%) were observed in 12. Perchlorate discharge tests were positive in all four patients tested. Follow‐up data were available in 20 patients (16 in group A and four in group B). Hypothyroidism was transient in 12 (60%) and persistent for several months after amiodarone withdrawal in eight (40%). While all patients in group B had transient hypothyroidism, 50% of patients with underlying thyroid abnormalities (group A) had persistent hypothyroidism. Thyroid autoantibodies were found in seven of eight patients with persistent hypothyroidism and in only three of 12 patients with transient hypothyroidism. Conversely, seven of 10 patients with positive thyroid autoantibodies had persistent hypothyroidism and 9 of 10 patients with undetectable thyroid autoantibodies had transient hypothyroidism. These data indicate that: (i) AIIH may develop in patients with or without underlying thyroid abnormalities; (ii) RAIU is inappropriately elevated in many patients with AIIH; (iii) intrathyroidal iodine is not organified; (iv) serum thyroid autoantibodies represent a risk factor for the development of AIIH; (v) AIIH spontaneously remits after amiodarone withdrawal in patients without thyroid abnormalities, but may persist in patients with concomitant thyroid disorders, especially those with circulating thyroid autoantibodies.