Abnormal twenty-four hour pattern of pulsatile luteinizing hormone secretion and the response to naloxone in women with hyperprolactinaemic amenorrhoea

OBJECTIVE: Hyperprolactinaemic amenorrhoea is associated with disturbances of pulsatile gonadotrophin secretion. The underlying mechanism remains unclear and the aim of this study was to investigate the 24-hour secretory pattern of gonadotrophins in women with hyperprolactinaemic amenorrhoea. The effect of opioid blockade using naloxone infusion on LH secretory pattern was also studied. DESIGN: The secretory patterns of LH, FSH, PRL and their responses to naloxone infusion were studied by serial blood samples collected at 10-minute intervals for 24 hours. On the following day, naloxone was infused at a dose of 1.6 mg per hour for 4 hours. PATIENTS: Eight women with hyperprolactinaemic amenorrhoea, two women hyperprolactinaemic but with normal ovarian cycles, and nine control subjects in the early follicular phase of menstrual cycle. MEASUREMENTS: Concentrations of LH, FSH and PRL were measured in plasma samples obtained at 10-minute intervals for 24 hours. In one woman, concentrations of urinary oestrone glucuronide were measured daily during treatment with pulsatile GnRH. RESULTS: The number of LH pulses per 24 hours was significantly fewer in women with hyperprolactinaemic amenorrhoea than in those with hyperprolactinaemia with normal cycles or control subjects (mean +/- SEM 4.5 +/- 2.4 vs 13.5 +/- 2.5 vs 17.3 +/- 0.8, P < 0.001). The magnitude of each episode of secretion was significantly higher in the hyperprolactinaemic amenorrhoeic women (P < 0.05) so the overall mean concentrations of LH throughout the 24-hour period was similar in the three groups (5.2 +/- 1.1, 4.8 +/- 0.8 and 5.2 +/- 0.4 U/l respectively). In women with hyperprolactinaemic amenorrhoea there was no significant change in the pattern of LH secretion during sleep in contrast to the control women in whom there was a slowing in the LH pulse frequency during the night. There was no significant change in the mean concentrations of LH, FSH and PRL during the naloxone infusion. There were also no significant changes in the LH pulse frequency in response to naloxone infusion when compared with an equivalent period of time in the previous 24 hours. In one hyperprolactinaemic amenorrhoeic woman, follicular development, ovulation and pregnancy were induced when gonadotrophin releasing hormone (GnRH) was infused in a pulsatile manner at a dose of 5 micrograms every 90 minutes. CONCLUSIONS: The suppression of normal ovarian cycles in women with hyperprolactinaemic amenorrhoea is due to a significant reduction in frequency of LH (GnRH) secretion which is not due to an increase in hypothalamic opioid activity. As normal ovarian cycles can occur or be induced by exogenous GnRH in hyperprolactinaemia, it is unlikely that a high level of prolactin by itself inhibits follicular development and ovulation.     

The anterior pituitary response to a gonadotropin-releasing hormone challenge test in normal older reproductive-age women

OBJECTIVE: To assess the pituitary responsiveness to GnRH stimulation of premenopausal women relative to age. DESIGN: Older and younger reproductive-age women underwent the GnRH stimulation test in the early follicular phase of the menstrual cycle. SETTING: Female subjects in an academic research environment. PATIENTS: Women aged 21 to 44 years consisting of normal volunteers and infertility patients. INTERVENTIONS: Gonadotropin-releasing hormone was administered intravenously between days 2 and 4 of the menstrual cycle. Blood samples were collected from -20 minutes before to 120 minutes after administration. MAIN OUTCOME MEASURE: Luteinizing hormone, FSH, inhibin, and E2 levels. RESULTS: No significant difference in baseline values existed between older and younger women with regard to LH, inhibin, and E2, but basal FSH levels were higher in older women. A significantly diminished percent of LH and percent FSH change above baseline occurred 30 minutes after GnRH administration in the older women compared with younger women. No change in inhibin or E2 levels could be detected during the sampling period. CONCLUSIONS: The present study demonstrates marked attenuation of the acute pituitary LH response (sensitivity) to GnRH stimulation in older women when compared with a younger cohort.     

Gastroscopy with gastric biopsy in 50 patients with carcinoma of the stomach radiologically probable or certain (author''s transl)

The varied etiology of pure mitral regurgitation is demonstrated in this clinicopathological study, comprising 59 surgically treated cases with this condition. One third of the cases was of rheumatic origin, one fifth had ischemic heart disease, another fifth floppy valves and one eighth an isolated rupture of the chordae with necrosis of the chord matrix. To our knowledge the histopathological findings in the last group have not been described before. Congenital mitral regurgitation, bacterial endocarditis and cardiomyopathy were rare causes of mitral regurgitation. Differences between the groups were observed in the sex ratio, duration of history, auscultatory findings ECG signs, compliance of the left ventricle and in the morphological findings.     

Retinoid X receptor expression in the normal pituitary and clinically ''non-functioning'' pituitary tumours

Nasal chondromesenchymal hamartoma is the suggested appellation for a tumefactive process of the nasal passages and contiguous paranasal sinuses in seven children with a detectable mass in the nose. With the exception of one patient who was 7 years of age at diagnosis, the others were 3 months of age or less upon recognition of the mass. Two children were diagnosed in the first 2 weeks of life. Imaging studies showed a complex solid and cystic mass or masses filling the nasal cavity and extending into the ethmoid sinuses in most cases. Erosion of the surrounding bone, including the cribriform plate, resulted in an intracranial component in the four cases. Surgical resection was the treatment of choice despite its technical difficulties that often necessitated a combined intranasal and intracranial approach. Residual disease with continued growth in one case was the clinical outcome in two children, and the remaining five patients have not experienced any further difficulties. The piecemeal fragments of tissue disclosed a collage of histologic features, but the basic morphologic elements were well-demarcated nodules of cartilage with some variation in the cellular density and maturation of the chondrocytes, a myxoid to spindle cell stroma, focal osteoclastlike giant cells in the stroma, and erythrocyte-filled spaces resembling those of the aneurysmal bone cyst. Two of the tumors were less polymorphous or complex in their spectrum of histologic features. These nasal masses have similarities to the so-called chest wall hamartoma or mesenchymal hamartoma of the chest wall in terms of the clinical presentation in infancy and the basic cartilaginous character of both entities. There is a degree of presumption in the designation of these nasal and chest wall tumors as hamartomas because the pathogenesis has not been established for either entity.     

Changes in pituitary and ovarian hormones following injection of ultra low dose LH-RH in normal and amenorrhoeic women

The results of the ultra low doses of synthetic LH-RH, 1.56, 3.125 and 6.25 mug, are presented in 8 normal women during the first week of the menstrual cycle and 14 patients with secondary amenorrhoea. Seven of these patients had "stress" amenorrhoea, and 7 had preceeding oligomenorrhoea. There was no significant difference between the mean basal gonadotrophin levels in the normal volunteers and those patients with secondary amenorrhoea. There was no significant difference in basal gonadotrophin levels or the response to LH-RH, between the two groups of amenorrhoea, stress and previous oligomenorrhoea. Basal FSH and oestradiol levels do not appear to influence the response to LH-RH. However, those patients with secondary amenorrhoea and a low basal LH (5 patients) had a significantly higher response to LH-RH at 1.56 and 3.125 mug than the amenorrhoeic patients with normal basal LH levels. Two patients with stress amenorrhoea and weight loss had an exaggerated response to LH-RH. The significance of this is discussed.     

Compartmental analysis of colonic transit reveals abnormalities in constipated patients with normal transit

Previous studies had concluded that the treadmill velocity-endurance time hyperbolic relationship for runs could be accuratly approached with a regression at condition that bouts of exercise duration were included between 2 and 12 min. This regression allows to calculate the critical speed (CS) defined as the slope of the regression of work (distance) on time to exhaustion, the anaerobic running capacity (ARC) being the intercept of this line (Monod & Scherrer, 1965). The purpose of this investigation was to give practical indication concerning the choice of the velocities in reference to the maximal aerobic speed (MAS i.e. the minimum speed which elicits VO2max). Subjects were fourteen elite male long-distance runners (27 +/- 3 years old; VO2max = 74.9 +/- 2.9 ml.kg-1.min-1, MAS = 22.4 +/- 0.8 km.h-1, CS = 19.3 +/- 0.7 km.h-1 and 86.2 +/- 1.5% MAS). tlim 100 values (321 +/- 83 s) were negatively correlated with MAS (r = -0.538, p < 0.05) and with CS (km.h-1) (r = -0.644, p < 0.01). tlim 90 (1015 +/- 266 s) was positively correlated with CS when expressed in % MAS (r = 0.645, p < 0.01) and not when expressed in km.h-1 (r = -0.095, P > 0.05). tlim 105 (176 +/- 40 s) only was correlated with ARC (r = 0.526, p < 0.05). These data demonstrate that running time to exhaustion at 100 and 105% of MAS in a homogeneous elite male long-distance runners group is inversely related to MAS. Moreover, tlim 90 is positively correlated with CS (%MAS) but neither with tlim 100 and 105 nor with maximal aerobic speed. So from a practical point of view, the velocities chosen to determine the critical speed, would be closed to the maximal aerobic speed (time to exhaustion around 6 min), taking into account that the tlim 105 is correlated with the anaerobic capacity, whereas tlim 90 is correlated with the critical speed.     

CT appearance of the normal and abnormal breast with mammographic correlation

Mammography is the preferred technique to evaluate the breast but computed tomography (CT) performed for extramammary disease often images breast tissue. We reviewed studies of patients who underwent both CT and mammography to identify abnormalities that were visible with both techniques. The CT appearance of the normal breast, breast cancer, and several other abnormalities is demonstrated in this study. CT may occasionally allow for a precise diagnosis of a previously unsuspected breast lesion but a mammogram is usually required.     

Luteinizing hormone response to gonadotrophin-releasing hormone in normal women undergoing ovulation induction with urinary or recombinant follicle stimulating hormone

Oestradiol enhances pituitary sensitivity to gonadotrophin-releasing hormone (GnRH) in normal women, while in women undergoing ovulation induction the putative factor gonadotrophin surge attenuating factor (GnSAF) attenuates the response of luteinizing hormone (LH) to GnRH. To study the relationships between oestradiol and GnSAF during ovulation induction, 15 normally ovulating women were investigated in an untreated spontaneous cycle (control, first cycle), in a cycle treated with daily i.m. injections of 225 IU urinary follicle-stimulating hormone (FSH) (Metrodin HP, uFSH cycle) and in a cycle treated with daily s.c. injections of 225 IU recombinant FSH (Gonal-F, rFSH cycle). Treatment with FSH started on cycle day 2. The women during the second and third cycle were allocated to the two treatments in an alternate way. One woman who became pregnant during the first treatment cycle (rFSH) was excluded from the study. In all cycles, an i.v. injection of 10 microg GnRH was given to the women (n = 14) daily from days 2-7 as well as from the day on which the leading follicle was 14 mm in diameter (day V) until mid-cycle (n = 7). The response of LH to GnRH at 30 min (deltaLH), representing pituitary sensitivity, was calculated. In the spontaneous (control) cycles, deltaLH values increased significantly only during the late follicular phase, i.e. from day V to mid-cycle, at which time they were correlated significantly with serum oestradiol values (r = 0.554, P < 0.01). Initially during the early follicular phase in the uFSH and the rFSH cycles, deltaLH values showed a significant decline which was not related to oestradiol (increased GnSAF bioactivity). Then, deltaLH values increased significantly on cycle day 7 and further on day v with no change thereafter up to mid-cycle. On these two days, deltaLH values were correlated significantly with serum oestradiol values (r = 0.587 and r = 0.652 respectively, P < 0.05). During the pre-ovulatory period, deltaLH values in the FSH cycles were significantly lower than in the spontaneous cycles. Significantly higher serum FSH values were achieved during treatment with uFSH than rFSH. However, serum values of oestradiol, immunoreactive inhibin, and deltaLH as well as the number of follicles > or = 12 mm in diameter did not differ significantly between the two FSH preparations. These results suggest that in women undergoing ovulation induction with FSH, oestradiol enhances pituitary sensitivity to GnRH, while GnSAF exerts antagonistic effects. The rFSH used in this study (Gonal-F) was at least as effective as the uFSH preparation (Metrodin-HP) in inducing multiple follicular maturation in normally cycling women.     

Polymorphisms of the p53 gene in women with ovarian or endometrial carcinoma

The mechanisms underlying macrovascular complications in NIDDM are partially understood. In addition to increased prevalence and severity of systemic cardiovascular risk factors, local alterations of arterial wall and hemodynamics may play a role. Atherosclerotic lesions usually lie in regions of low wall shear stress. We therefore investigated the wall shear stress--that is, the frictional force acting tangentially to the endothelial surface--in the common carotid artery of diabetic and control subjects. Enrolled were 18 male NIDDM subjects and 18 age-matched control subjects. None of the participants were hypertensive, hyperlipidemic, or a cigarette smoker. Common carotid wall shear stress was calculated according to the following equation: blood viscosity x blood velocity/internal diameter. Blood viscosity was measured by use of a cone/plate viscometer. Blood velocity and internal diameter were measured by high-resolution echo-Doppler. Wall shear stress was significantly lower in NIDDM subjects than in control subjects (mean wall shear stress: 9.7 +/- 2.4 vs. 11.7 +/- 2.6 dynes/cm2, P < or = 0.005). Six diabetic participants had a plaque in one carotid tree and no lesions in the contralateral carotid. Among these subjects, mean wall shear stress was significantly lower in the side with lesion (8.1 +/- 1.6 vs. 10.5 +/- 2.4 dynes/cm2, P < or = 0.02). These findings suggest that diabetes is associated with a more atherosclerosis-prone carotid hemodynamic profile, which might represent an additional factor contributing to the increased prevalence and severity of carotid atherosclerosis in diabetic patients compared with general population.     

Menstrual abnormalities in women with Cushing's disease are correlated with hypercortisolemia rather than raised circulating androgen levels

Menstrual irregularity is a common complaint at presentation in women with Cushing's syndrome, although the etiology has been little studied. We have assessed 45 female patients (median age, 32 yr; range, 16-41 yr) with newly diagnosed pituitary-dependent Cushing's syndrome. Patients were subdivided into 4 groups according to the duration of their menstrual cycle: normal cycles (NC; 26-30 days), oligomenorrhea (OL; 31-120 days), amenorrhea (AM; > 120 days), and polymenorrhea (PM; < 26 days). Blood was taken at 0900 h for measurement of LH, FSH, PRL, testosterone, androstenedione, dehydroepiandrosterone sulfate, estradiol (E2), sex hormone-binding globulin (SHBG), and ACTH; cortisol was sampled at 0900, 1800, and 2400 h. The LH and FSH responses to 100 micrograms GnRH were analyzed in 23 patients. Statistical analysis was performed using the nonparametric Mann-Whitney U and Spearman tests. Only 9 patients had NC (20%), 14 had OL (31.1%), 15 had AM (33.3%), and 4 had PM (8.8%), whereas 3 had variable cycles (6.7%). By group, AM patients had lower serum E2 levels (median, 110 pmol/L) than OL patients (225 pmol/L; P < 0.05) or NC patients (279 pmol/L; P < 0.05), and higher serum cortisol levels at 0900 h (800 vs. 602 and 580 nmol/L, respectively; P < 0.05) and 1800 h (816 vs. 557 and 523 nmol/L, respectively; P < 0.05) and higher mean values from 6 samples obtained through the day (753 vs. 491 and 459 nmol/L, respectively; P < 0.05). For the whole group of patients there was a negative correlation between serum E2 and cortisol at 0900 h (r = -0.50; P < 0.01) and 1800 h (r = -0.56; P < 0.01) and with mean cortisol (r = -0.46; P < 0.05). No significant correlation was found between any serum androgen and E2 or cortisol. The LH response to GnRH was normal in 43.5% of the patients, exaggerated in 52.1%, and decreased in 4.4%, but there were no significant differences among the menstrual groups. No differences were found in any other parameter. In summary, in our study 80% of patients with Cushing's syndrome had menstrual irregularity, and this was most closely related to serum cortisol rather than to circulating androgens. Patients with AM had higher levels of cortisol and lower levels of E2, while the GnRH response was either normal or exaggerated. Our data suggest that the menstrual irregularity in Cushing's disease appears to be the result of hypercortisolemic inhibition of gonadotropin release acting at a hypothalamic level, rather than raised circulating androgen levels.     

Ultrasound transmission speed and ultrasound bone profile score (UBPS) of the phalanges in normal women and women with osteoporosis

The distal metaphysis of the first phalanx of the fingers II-V is, like the vertebral body, a useful site for the measurement of mineralisation and structure of the bone because of the simultaneous presence of compact and trabecular bone. With an ultrasound device (DBM sonic 1200, IGEA, Italy), we measured the adSOS (the amplitude dependent speed of sound) and the UBPS (ultrasound bone profile score), a score which is calculated from the graphic traces of the receiving probe with an expert system which uses fuzzy-logic at phalanges II-IV, as well as bone mineral density (BMD) at lumbar spine using dual X-ray absorptiometry (DXA). Precision of the measurements was as follows: adSOS: short-time-CV% = 0.576, long-time-CV% = 1.1, SCV% = 5.9, RMSSD% = 1.825. UBPS: short-time CV% = 5.95. There was no correlation between adSOS or UBPS and lumbar BMD (DXA). There was a significant positive correlation between adSOS and UBPS, r = 0.804 (p<0.00001). The validity of adSOS and UBPS was examined in 25 young and healthy women (mean age: 33.4 year), 15 postmenopausal healthy women (mean age: 58.5 years), 17 women with osteopenia, (mean age: 52.4 years), as defined by a t-score between -1 to -2.5 SD as lumbar BMD (DXA), and 20 women with osteoporosis and vertebral fractures (mean age: 61.4 years). We compared the healthy postmenopausal women and the women with osteoporotic vertebral fractures, the z-score of the adSOS was below minus 1.5 SD and UBPS was below 40, sensitivity was 0.7 for adSOS, and 0.85 for UBPS, with a specificity 0.97 for adSOS, and of 0.93 for UBPS; positive predictive value: adSOS: 0.93, UBPS: 0.85. AdSOS declined with age (r= 0.694, p=0.021); the UBPS was not age dependent (r=-0.15, p = n.s.). The ROC-curve shows a value of 0.96 for adSOS and 0.94 for UBPS. AdSOS and UBPS could discriminate well between the healthy controls and the women with osteopenia or vertebral fractures (p<0.00001). These results show that adSOS and UBPS are precise parameters to be measured at the phalanges. The detection level of pathological changes in osteoporosis are similar between adSOS and lumbar BMD (DXA) and improved by using the UBPS. This might be explained by the influence of structural changes in bone on UBPS, rather than change in bone mineral alone. Prospective studies have to clarify the role of adSOS and UBPS in fracture prediction.     

Body composition in normal black women: the four-compartment model

The four-compartment model of body composition was studied in 112 healthy black women to develop normative data to be used to assess deviations in illness. Each compartment was measured by an independent method: tritiated water dilution, prompt-gamma neutron activation analysis (for nitrogen), inelastic neutron scattering (for carbon) and dual energy x-ray absorptiometry (for calcium). The mean age of the population was 43.2 years. Race was self-declared. The mean values for the four compartments were [kg SE] protein: 9.6 (0.07); mineral 3.0 (0.03); fat 24.2 (0.70); and water 33.1 (0.29). Each of the compartments changed significantly with age (P < .0001). There were declines in total body water, mineral, and protein, whereas fat increased linearly with age. Linear regressions performed on pre- and postmenopausal women showed a significant difference only for the mineral compartment. Various models were fit to the data to adjust for body size and age. The equation y = age + height + weight fits the data as well as the other models. Equations and graphs were developed to assess each compartment using this linear model and may be used to assess the body composition status of healthy and ill black women. Although black women tended to be heavier than white women, after controlling for differences in body weight (and age) black women had a greater mass of protein, mineral, and water and a similar fat store. These differences, while statistically significant, were not of great magnitude. This was a cross-sectional study and suspected trends with aging must be confirmed by a longitudinal study.     

Prognostic significance of normal dobutamine-atropine stress sestamibi scintigraphy in women with chest pain

The high risk of vaso-occlusive events in children younger than 4 years with cyanotic congenital heart disease and polycythaemia has been attributed to increased thromboxane (Tx) A2 formation. In older children with cyanotic congenital heart disease, however, the risk of vaso-occlusive events is much lower. We therefore hypothesized that the formation of TxA2 and prostacyclin is not disturbed in this age group. We measured urinary excretion of stable index metabolites of in vivo TxA2 and prostacyclin formation by gas chromatography-mass spectrometry in nine children (age 5.9-14.4, median 8.7 years) with cyanotic congenital heart disease, and in nine healthy, age-matched control subjects. The patients excreted less 2,3-dinor-TxB2 (systemic TxA2 formation, P = 0.03), 2,3-dinor-6-keto-PGF1 alpha (systemic prostacyclin formation. P = 0.03) and TxB2 (renal TxA2 formation, P = 0.01) than the control subjects. We conclude that in children older than 5 years with cyanotic congenital heart disease, endogenous synthesis of TxA2 and prostacyclin is not stimulated. This result may explain the lower risk of vaso-occlusive events in this age group as compared with younger children. In addition, our results suggest that chronic hypoxaemia may affect the in vivo formation of TxA2 and prostacyclin and the metabolic disposition of TxB2.     

Cystoscopic findings consistent with interstitial cystitis in normal women undergoing tubal ligation

PURPOSE: We test the hypothesis that women without chronic pelvic pain or irritative voiding symptoms do not demonstrate petechial hemorrhages known as glomerulations that are characteristic of patients with interstitial cystitis. MATERIALS AND METHODS: A prospective cohort design was used for examination with cystoscopy and bladder distention of 20 asymptomatic women undergoing tubal ligation. Cystoscopy with the patient under general anesthesia was performed to inspect the bladder mucosa before and after distention at 70 cm. of water pressure for 2 or 6 minutes. Photographs of the right, posterior and left of the bladder surfaces taken before and after the distention were scored on a scale of 1 to 5 using a panel of standards. Five urologists blinded to the source of individual photographs independently evaluated 120 research images interspersed with 46 other pictures from a library containing images from 19 symptomatic patients with and without interstitial cystitis. RESULTS: A total of 20 normal women with a mean age plus or minus standard deviation of 29+/-6 years consented to participate in this trial during laparoscopic tubal ligation. Photographs of bladder sites before and after distention with 890+/-140 ml. were scored as 1.4+/-0.3 (before distention) and 3.1+/-1.1 (after distention) on the scale of 1 to 5. The increase in scores following distention in normal subjects was seen to the same degree and in the same proportion as in patients with symptoms of interstitial cystitis (8 of 19 symptomatic patients in this series met current diagnostic criteria for interstitial cystitis). Slight but significant differences were seen among sites in the bladder but not between 2 and 6-minute distention durations. CONCLUSIONS: Bladder mucosal lesions characteristically associated with irritative voiding symptoms and pelvic pain in patients diagnosed with interstitial cystitis were observed in asymptomatic women.     

Intracranial abnormalities in infants treated with extracorporeal membrane oxygenation: update on sonographic and CT findings

The phylogenetic relationship of the asexual mycorrhizal fungus Cenococcum geophilam Fr. among sexual ascomycetes was examined by phylogenetic analysis of nucleotide sequence data from the nuclear small subunit (18S) ribosomal RNA genie region. A specific focus of this study was to test the hypothesis that the genus Elaphomyces is the closest sexual relative of C. geophilum. Thus nucleotide sequence data of five C. geophilum isolates, three Elaphomyces species, and 44 additional genera of ascomycetes were included in the phylogenetic analyses. The percentage of similarity among the 18S rDNA sequences of the C. geophilum isolates examined was 99.8 to 100%, indicating that C. geophilum is monophyletic. Percent similarity of nucleotide sequence among the three Elaphomyces species was also high and ranged from 99.4 to 99.5%. DNA parsimony and distance analysis of the sequence data separated these 2 genera on distant clades when sequence from 44 additional genera of ascomycetes was included. Parsimony and distance analyses positioned C. geophilum as a basal, intermediate lineage between the two Loculoascomycete orders, the Pleosporales and the Dothidiales, and strongly supported Elaphomyces to be of Plectomycete origin. Among the sexual Ascomycetes examined, which included representative taxa from four classes of filamentous Ascomycetes (Plectomycetes, Pyrenomycetes, Discomycetes, and Loculoascomycetes), no close sexual relative to C. geophilum was identified. At least four independent lineages of mycorrhizal fungi were identified among the ascomycetes examined.