Bone mineral density and vertebral fractures and their relationship with pulmonary dysfunction in patients with chronic obstructive pulmonary disease.

To evaluate bone mineral density (BMD) and morphometric vertebral fractures (MVF) in chronic obstructive pulmonary disease (COPD) patients in comparison with two control groups. BMD was lower in the disease group (DG) and was associated with the worst disease severity and prognosis. The prevalence of MVF was high and greater in the DG than in the control groups. INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is associated with osteoporosis and vertebral fractures. It is still unclear whether the presence of fractures and changes in bone mineral density (BMD) are associated with disease severity and prognosis. The aim of this study was to evaluate BMD and morphometric vertebral fractures (MVF) in COPD patients in comparison with two control groups and to correlate these parameters with indices of COPD severity (VEF1 and GOLD) and prognosis (BODE). METHODS: This was a cross-sectional study in COPD patients (disease group, DG) who underwent BMD and vertebral fracture assessment (VFA). Two control groups were used: smokers without COPD (smoker group, SG) and healthy never-smoker individuals (never-smoker group, NSG). RESULTS: The DG comprised 121 patients (65 women, mean age 67.9 ± 8.6 years). Altered BMD was observed in 88.4% of the patients in the DG, which was more prevalent when compared with the control groups (p < 0.001). The BMD values were lower in the DG than in the control groups (p < 0.05). BMD was associated with the worst disease severity and prognosis (p < 0.05). The prevalence of MVF was high (57.8%) and greater than that in the SG (23.8%) and the NSG (14.8%; p < 0.001). The prevalence of fractures was not associated with disease severity and prognosis. CONCLUSIONS: COPD patients have a higher prevalence of MVF and low BMD, and the latter was associated with the severity and poor prognosis of the disease.

A randomized, parallel group, double-blind, multicentre study comparing the efficacy and safety of Avandamet (rosiglitazone/metformin) and metformin on long-term glycaemic control and bone mineral density after 80 weeks of treatment in drug-naïve type 2 diabetes mellitus patients.

AIM: The purpose of this study was to evaluate if superior glycaemic control could be achieved with Avandamet® (rosiglitazone/metformin/AVM) compared with metformin (MET) monotherapy, and if glycaemic effects attained with AVM are durable over 18 months of treatment. Bone mineral density (BMD) and bone biomarkers were evaluated in a subgroup of patients. METHODS: This was a phase IV, randomized, double-blind, multi-centre study in 688, drug naÏve, male and female patients who had an established clinical diagnosis of type 2 diabetes mellitus (T2DM). Patients were randomized in a 1 : 1 ratio either to AVM or MET. RESULTS: As initial therapy in patients with T2DM, AVM was superior to MET in achieving statistically significant reductions in glycated haemoglobin (HbA1c) (p < 0.0001) and fasting plasma glucose (FPG) (p < 0.001), with more patients reaching recommended HbA1c and FPG targets for intensive glycaemic control. The glycaemic effects attained with AVM compared to MET monotherapy were durable over 18 months of treatment. In the bone substudy, AVM was associated with a significantly lower BMD in comparison with MET at week 80 in the lumbar spine and total hip (p < 0.0012 and p = 0.0005, respectively). Between-treatment differences were not statistically significant for distal one-third of radius BMD, femoral neck BMD or total BMD. CONCLUSION: Superior glycaemic control was achieved with AVM compared with MET monotherapy. The superior glycaemic effects were shown to be durable over 18 months of treatment. AVM was associated with a significantly reduced BMD in comparison with MET at week 80 in the lumbar spine and total hip.

Eficácia da suplementação oral com 1, 3-1, 6 betaglucano proveniente de Saccharomyces cerevisiae no controle da mastite bovina / [Efficiency of oral supplementation of 1. 3-1. 6 beta-glucan from saccharomyces cerevisiae on the control of bovine mastitis]

A mastite bovina, uma das principais doenças do rebanho leiteiro, caracteriza-se por um processo inflamatório no úbere. A inviabilidade econômica, o impacto ambiental negativo e os resíduos antimicrobianos têm estimulado a pesquisa de outros tratamentos alternativos para a prevenção e o tratamento de doenças na bovinocultura leiteira. O betaglucano é um agente imunomodulador com potencial ação preventiva para doenças infecciosas, inclusive a mastite. Este estudo teve como objetivo avaliar a eficácia do uso do betaglucano, por meio de administração oral, em animais em lactação. Foram utilizadas 20 vacas lactantes, distribuídas em dois grupos, um controle e um tratamento, com 10 animais em cada grupo. O grupo tratamento recebeu 5g/dia, durante 60 dias, de 1,3-1,6 betaglucano isolado da parede celular de Saccharomyces cerevisiae diluído em ração após a ordenha, enquanto o grupo controle recebia somente a ração. Foram realizados os testes de California Mastitis Test (CMT), contagem de células somáticas (CCS), produção de leite e percentual de gordura e proteína no leite. Não houve diferença estatisticamente significativa entre os grupos quanto à CCS, ao CMT, à composição do leite ou produção. Não se observou, portanto, eficácia do uso do betaglucano purificado, administrado por via oral, no controle e na prevenção da mastite em vacas leiteiras, quando comparadas com o grupo controle. Atribuem-se esses resultados, principalmente, à degradação ruminal do produto testado. Sugerem-se, portanto, mais pesquisas utilizando o 1,3-1,6 betaglucano purificado de parede de S. cerevisiae por outras vias de administração, tais como intramamária e subcutânea.(AU)

Bovine mastitis, one of the main diseases of dairy herds, is characterized by an inflammatory process in the udder. The economic and environmental impacts, as well as the residues of antimicrobial drugs have stimulated the research of novel alternative treatments for the prevention and treatment of diseases in dairy production cows. The beta-glucan is an immunomodulator agent, with potential preventive action for infectious diseases, including mastitis. This study aimed to assess the effectiveness of orally administered beta-glucan in lactating cows. 20 lactating cows were used, distributed into two groups, one control and one treatment, with 10 cows in each group. The treatment group received 5g of 1.3-1.6 betaglucan daily for 60 days, isolated from the cell-wall of Saccharomyces cerevisiae diluted into a grain meal, whereas the animals in the control group received only the ration. The California Mastitis Test (CMT), Somatic Cells Counting (SCC), daily production and assessments of fat and protein content in milk were done. There was no statistically significant difference between the groups concerning subclinical mastitis detected by CMT, SCC, milk production and composition regarding protein and fat content. It was not observed, therefore, the effectiveness of the use of purified beta-glucan orally administered on the control or prevention of mastitis in dairy cows. The results are attributed to the ruminal degradation of the product tested. It is, therefore, suggested that more research should be conducted using the 1.3-1.6 beta-glucan purified from the cell wall of S. cerevisiae by other administration means and ruminal protection technologies for the isolated beta-glucan.(AU)

Ca+2 dependence of gonadotropin-releasing hormone-stimulated luteinizing hormone secretion: in vitro studies using continuously perifused dispersed rat anterior pituitary cells.

A continuously perifused dispersed rat anterior pituitary cell system was used to determine the importance of calcium (Ca+2) on the release of LH by GnRH. In response to continuous exposure to 10 nM GnRH, LH was released in a biphasic fashion; arbitrarily, phase I was defined as being the LH released during the initial 40 min and phase II as the subsequent release. Withdrawal of Ca+2 from the perifusion medium during phases I or II of LH release led to a rapid inhibition of the LH secretion. Cells were exposed to GnRH for 2.5 min, washed with medium for 30 min, and then reexposed to GnRH for 30 min. This sequence was repeated 1 h later under identical conditions in the presence of a Ca+2 blocking agent; D600 (20 or 100 microM). D600 inhibited both the 2.5- and the 30-min GnRH-stimulated LH release. The results were expressed as the ratio obtained by dividing the total LH released during the second GnRH exposure (either 2.5 or 30 min) by the total LH released during the respective initial GnRH exposure of same duration. For the cells perifused with 20 microM D600 the ratios +/- SE (D600 vs. control) were 0.48 +/- 0.06 vs. 1.28 +/- 0.13 (P = 0.0001) and 0.29 +/- 0.05 vs. 1.01 +/- 0.08 (P less than or equal to 0.0001) for the 2.5- and 30-min exposures, respectively. For the cells perifused with 100 microM D600 the ratios +/- SE (D600 vs. control) were 0.18 +/- 0.05 vs. 1.28 +/- 0.13 (P less than or equal to 0.00001) and 0.12 +/- 0.03 vs. 1.01 +/- 0.08 (P = 0.002) for the 2.5- and 30-min exposures, respectively, revealing an even more profound inhibitory effect of D600 on GnRH stimulated LH secretion. Our data both confirm previous reports that Ca+2 is involved in LH release and demonstrate that Ca+2 is an essential requirement during both phases of GnRH-stimulated LH release in perifused dispersed rat anterior pituitary cells.

Human pancreatic growth hormone-releasing factor-40 (hpGRF-40) allows stimulation of GH release by TRH.

The effects of synthetic hpGRF-40 on GH release from continuously perifused male rat anterior pituitary cells were studied. Pulses (2.5 min) of hpGRF-40 stimulated GH release in a log-linear dose response relationship: concentrations of 0.03, 0.1, 0.3, 1, 3, 10, 30 and 100 nM given in a random order elicited a GH response above baseline of 1.2 +/- 0.3, 2.4 +/- 0.4, 2.8 +/- 0.2, 4.3 +/- 0.2, 6.2 +/- 0.7, 7.0 +/- 1.0, 8.7 +/- 1.7, and 10.8 +/- 0.8 micrograms/10(7) cells (mean +/- SEM; n = 3; r = 0.93), respectively. During a 5-h hpGRF-40 infusion, GH stimulation peaked within 5 min and waned to near baseline by the end of the fifth h. The integrated GH responses to 0.03, 0.1 and 0.3 nM hpGRF-40 were 37.6 +/- 7.4, 52.9 +/- 8.5, and 66.15 +/- 8.2 micrograms/10(7) (mean +/- SEM; n = 3; r = 0.72), respectively. The interaction of TRH and hpGRF-40 in the control of GH secretion was studied to investigate the mechanism of the "paradoxical" TRH stimulation of GH release associated with GH excess states in humans. Dispersed cells were perifused with either 100 nM TRH for 0.5 h, 5 nM hpGRF-40 for 4 h, or 5 nM hpGRF-40 for 4 h, to which a 0.5 h pulse of TRH was added at 2 h. GH levels did not change significantly in the presence of TRH alone. When TRH was added to the ongoing hpGRF-40 perifusion, GH release increased from 1.4 +/- 0.06 to 4.0 +/- 1.0 micrograms/min.10(7) cells (n = 4; P = 0.03). Thus, dispersed pituitary cells are highly sensitive to very low concentrations of hpGRF-40 administered as both an acute pulse and as a tonic infusion. When the cells are exposed to a maximal concentration of hpGRF-40 (i.e. 5 nM), TRH becomes a secretagogue at the pituitary level, thus suggesting the site and mechanism of the "paradoxical" GH response to TRH observed in some acromegalics.

The self-priming effect of gonadotropin-releasing hormone on luteinizing hormone release: observations using rat anterior pituitary fragments and dispersed cells continuously perifused in parallel.

To study in vitro the self-priming effect of GnRH on LH release, rat anterior pituitaries were prepared either as fragments or dispersed cells and continuously perifused in parallel chambers. The experimental groups consisted of rats killed at 0800 h on diestrus day 1, diestrus day 2, proestrus or estrus, or at 1400 h on proestrus. To insure truly independent observations, each experimental preparation was tested on three occasions. After basal LH release had stabilized, the tissue preparations were exposed to 10 nM GnRH as two 30-min challenges separated by 1 h. LH secretory rates (nanograms per min/pituitary for fragments; nanograms per min/10(7) cells for dispersed cells) were calculated 1) for basal release (during the 20-min period immediately preceding each GnRH challenge), 2) in response to GnRH, and 3) as the sum of basal and GnRH-stimulated release. Comparison of the two preparations revealed that basal and GnRH-stimulated LH release by pituitary fragments was more variable than LH release by dispersed cells. In addition, while dispersed cells responded promptly to the addition/withdrawal of stimuli, fragments did so more gradually. With respect to GnRH self-priming, the second mean secretory rate for basal LH release by fragments (range, 28.8-46.5) was significantly (0.1 greater than P greater than 0.01) higher than the first rate (range, 14.4-22.0) on diestrus day 1, diestrus day 2, proestrus at 0800 h, and estrus. With dispersed cells, the first and second basal rates were similar to each other on diestrus day 1 and estrus, but on diestrus day 2 and on proestrus at 0800 and 1400 h, the second basal rate (range, 36.8-93) was significantly (P less than 0.001) higher than the first range (range, 17.7-31.7). When fragments received GnRH, the second mean secretory rate (range, 35.2-64.2) was significantly (0.1 greater than P greater than 0.03) higher than the first rate (range, 13.4-34.1) on diestrus day 2 and proestrus at 0800 h. With dispersed cells, the mean secretory rate in response to the second GnRH challenge was higher only on diestrus day 2 (37.0 +/- 4.1 vs. 60.3 +/- 3.8; P less than 0.05). When considered as the total of basal plus GnRH-stimulated LH release, the second secretory rate by fragments (range, 54.5 - 110.8) was significantly (0.1 greater than P greater than 0.02) higher than the first rate (range, 27.9 - 51.4) on diestrus day 1, diestrus day 2, and proestrus at 0800 h.(ABSTRACT TRUNCATED AT 400 WORDS)

Follicle-stimulating hormone-secreting pituitary tumor with concomitant elevation of serum alpha-subunit levels.

Hypersecretion of FSH and alpha-subunit was documented in a man with a pituitary adenoma that was previously diagnosed on clinical grounds as nonfunctioning who had been treated by transsphenoidal surgery and postoperative irradiation. Postoperatively, the patient had high serum FSH levels and normal serum, LH levels. Ten years after the surgery, immunostaining of the tumor revealed the presence of beta FSH, beta LH, and beta TSH in the cytoplasm of scattered adenoma cells, although not always in the same cells. LH levels were elevated during the middle portion of the 12 yr that this patient was followed. However, as LH immunoreactivity was shown (in specimens recently drawn) to be largely due to cross-reactivity in the alpha-subunit RIA, the high LH values may represent high alpha-subunit levels. The elevated FSH levels and alpha-subunit concentrations did not rise after GnRH administration. Thus, during the course of 12 yr, this patient's tumor hypersecreted FSH and alpha-subunit and possibly LH. The evolution of these events may represent the natural history of the tumor or the effects of the therapeutic modalities used. We conclude that adult men with pituitary tumors and complaints of hypogonadism should be evaluated for a FSH-secreting tumor.

Divergent influences of calcium ions on releasing factor-stimulated anterior pituitary hormone secretion in normal man.

To investigate the influence of calcium ions on the secretion of anterior pituitary hormones in response to stimulation by exogenous hypothalmic releasing factors in man, we measured serum concentrations of pituitary hormones serially during a continuous infusion of combined TRH (2 micrograms/min) and GnRH (1 microgram/min), with concomitant iv saline or calcium administration. Compared to saline, calcium administration was associated with a significant increase in GnRH-TRH-stimulated LH and FSH release and a corresponding rise in serum testosterone concentrations. The effect of calcium ions on gonadotropin secretion was specific, because releasing factor-stimulated secretion of TSH and PRL was suppressed by hypercalcemia. Serum concentrations of GH were not significantly altered under these conditions. In summary, the present results provide the first in vivo evidence that acute infusion of calcium ions augments GnRH-TRH-stimulated secretion of LH and FSH, with an accompanying increase in serum testosterone levels. In contrast, hypercalcemia did not alter serum GH concentrations, and it suppressed GnRH-TRH-stimulated release of PRL and TSH. We conclude that calcium ions can selectively influence releasing factor-stimulated secretion of certain anterior pituitary hormones in man.

Divergent influences of the structurally dissimilar calcium entry blockers, diltiazem and verapamil, on thyrotropin- and gonadotropin-releasing hormone-stimulated anterior pituitary hormone secretion in man.

We have tested the influence of a new calcium ion channel antagonist, diltiazem, on hypothalamic releasing hormone-stimulated secretion of LH and other anterior pituitary hormones in man. To this end, six normal men received a continuous infusion of GnRH (1 microgram/min) and TRH (2 micrograms/min) for 3 h under three different experimental conditions: 1) saline (control) infusion; 2) iv diltiazem (0.3 mg/kg bolus dose, and 0.002 mg/kg . min) infusion for 4 h beginning 1 h before releasing hormone injection; and 3) oral diltiazem (60 mg, every 6 h) administration for 1 week before pituitary stimulation. Blood was sampled at 10-min intervals for the subsequent immunoassay of LH, FSH, TSH, PRL, and GH concentrations and at hourly intervals for the assay of plasma diltiazem concentrations by high performance liquid chromatography. Despite sustained plasma diltiazem concentrations of 80-120 ng/ml during either iv or oral drug administration, the GnRH/TRH-stimulated release of LH, FSH, TSH, and PRL or the basal secretion of GH did not differ significantly from that during saline infusion. In contrast, when these subjects underwent the same infusion schedule using a structurally dissimilar calcium influx blocker, verapamil (5-mg bolus dose and 15 mg/h, continuous infusion), there was significant suppression of the delayed component of GnRH/TRH-stimulated LH release, with simultaneous enhancement of PRL secretion. We conclude that exogenously stimulated anterior pituitary hormone secretion in man exhibits differential susceptibility to the structurally discrete calcium entry blockers diltiazem and verapamil. Moreover, the differential influence of these two calcium ion channel antagonists on gonadotropes is distinct from that described in cardiac and smooth muscle cells.

Intranasal administration of human pancreatic tumor GH-releasing factor-40 stimulates GH release in normal men.

Human pancreatic tumor GH releasing factor-40 (hpGRF-40) selectively stimulates GH secretion in normal men and in some adult patients with GH deficiency. As the latter finding suggests that some children with GH deficiency may benefit from therapy with hpGRF-40 or an analogue, we investigated the effect of hpGRF-40 administered intranasally on GH release. Six normal men were given hpGRF-40 (30 ug/kg; test day) or an equivalent volume of vehicle alone (control day) at 0900 h. Immunoreactive GH was measured in serum obtained at intervals between 0800-1200 h. Mean (+/- SEM) integrated serum levels of GH (ng/ml/h) prior to and following administration of vehicle were not different (1.27 +/- 0.57 vs 0.87 +/- 0.28; p = 0.54). However, following hpGRF-40 administration, GH levels increased significantly (0.53 +/- 0.03 vs 2.88 +/- 0.75; p = 0.022). Peak levels of serum GH were detected within 30 min following hpGRF-40. Except for mild burning of the nasal mucosa reported by one subject, no side effects were noted. We conclude that, if hpGRF-40 or an analogue is shown to be useful in the treatment of some children with GH deficiency, the intranasal route of administration may be utilized and will be more acceptable for chronic therapy than intravenous, intramuscular, or subcutaneous injection.

Stimulation of growth hormone (GH) and somatomedin C in idiopathic GH-deficient subjects by intermittent pulsatile administration of synthetic human pancreatic tumor GH-releasing factor.

After initial challenges with vehicle alone and then 10 micrograms/kg human pancreatic tumor GH-releasing factor (hpGRF)-40, six adult subjects who had presented in childhood with idiopathic GH deficiency were given 0.33 micrograms/kg hpGRF-40, iv, every 3 h for 5 days. Serum GH levels were monitored daily for 90 min after the 0800 h doses of 0.33 micrograms/kg hpGRF-40, and serum somatomedin C was measured at 0800 and 2000 h. In addition, plasma levels of cholesterol, high density lipoprotein cholesterol, and triglycerides were measured daily at 0800 h. Three hours after the last 0.33 micrograms/kg dose, all subjects were rechallenged with 10 micrograms/kg hpGRF-40. In response to the initial 10 micrograms/kg challenge with hpGRF-40, and although serum GH levels rose in two of six subjects, the mean maximum GH level achieved was no different from that after treatment with vehicle alone. Within 12 h after initiation of the intermittent administration of hpGRF-40, mean +/- SEM serum somatomedin C had risen by 0.1 +/- 0.05 U/ml, and at the end of the 5-day period, had increased from 0.24 +/- 0.07 to 0.78 +/- 0.32 U/ml. In response to the second challenge with 10 micrograms/kg hpGRF-40, serum GH levels rose in three of the four subjects who initially failed to respond or had a less than 1 ng/ml GH response. The increase in serum GH was greater in one of the two subjects who had responded to the first dose. In addition, unlike the first dose, the mean maximal serum GH level achieved in response to the second 10 micrograms/kg dose of hpGRF-40 was higher than that in response to vehicle (P = 0.031). Although there was no statistically significant change during the 5-day period, in plasma cholesterol, high density lipoprotein cholesterol, or triglycerides, the latter exhibited a trend toward increased levels. Our preliminary data show that 5 days of intermittent hpGRF-40 administration augment GH secretion in some adults with GH deficiency, suggesting that somatotropes are present in idiopathic GH deficiency and may be primed by hpGRF-40. The rise in serum somatomedin C to normal levels after multiple injections of hpGRF-40 is encouraging, since circulating levels of somatomedin C may be more important than the increase in immunoreactive GH levels as an index of response for induction of linear growth. The demonstration of biological effects of hpGRF-40 in all six subjects without any serious adverse effects suggests that hpGRF-40 has promise in the treatment of GH deficiency.

Effects of human pancreatic growth hormone-releasing factor-40 on serum growth hormone, prolactin, luteinizing hormone, follicle-stimulating hormone, and somatomedin-C concentrations in normal women throughout the menstrual cycle.

Human pancreatic tumor GH-releasing factor-40 (hpGRF-40) selectively stimulates GH secretion in normal men and in some adults with GH deficiency. To study its effects in women, we administered hpGRF-40 (3.33 micrograms/kg) or an equivalent volume of vehicle as an iv bolus at 0900 h to 10 normal women during the early follicular, late follicular, and midluteal phases of the menstrual cycle. Serum concentrations of GH, PRL, LH, and FSH were measured at intervals between 0800-1100 h. Serum somatomedin-C concentrations were measured before and 24 h after the administration of vehicle of hpGRF-40. Within 1-3 min after the injection of hpGRF-40 all women described warmth localized to the head and neck and exhibited facial flushing. No changes in pulse rate or blood pressure were noted. When expressed as change from baseline and compared to control values, peak levels of serum GH (nanograms per ml; mean +/- SEM) were higher after hpGRF-40 treatment during the early follicular (5.4 +/- 3.2 vs. 34.9 +/- 8.3; control vs. test day; P = 0.011), late follicular (5.6 +/- 1.5 vs. 25.2 +/- 6.8; P = 0.014), and luteal (0.8 +/- 1.0 vs. 32.7 +/- 12.8; P = 0.033) phases of the menstrual cycle. Similarly, integrated serum GH levels (nanograms per ml/h) were higher after hpGRF-40 administration during the early follicular (0.72 vs. 16.1; P = 0.011), late follicular (0.83 vs. 9.9; P = 0.037), and luteal (-1.54 vs. 17.0; P = 0.036) phases of the cycle. When the increases in serum GH after hpGRF-40 treatment were compared among the phases of the menstrual cycle, however, no differences were found. Serum somatomedin-C values 24 h after hpGRF-40 treatment were higher than those 24 h after vehicle at all stages of the menstrual cycle. hpGRF-40 did not stimulate the release of PRL, LH, or FSH. We conclude that hpGRF-40 stimulates the release of GH, but that in response to the dose used, hpGRF-40-stimulated GH release does not vary during the menstrual cycle.

Effects of intravenous, subcutaneous, and intranasal administration of growth hormone (GH)-releasing hormone-40 on serum GH concentrations in normal men.

In addition to stimulating GH release in normal subjects, GH-releasing hormone-40 (GHRH-40) stimulates GH secretion in some adults and children with GH deficiency. Recognizing that GHRH-40 may have potential as a therapeutic agent for the treatment of GH deficiency, we examined the effects of iv, sc, and intranasal (in) GHRH-40 administration on GH secretion and measured the plasma levels of immunoreactive GHRH achieved after the administration of the peptide via these different routes. Normal men were given vehicle or GHRH-40 iv (0.003, 0.01, 0.03, and 0.1 micrograms/kg; n = 10), sc (1, 3.3, and 10 micrograms/kg; n = 8), or in (3, 10, 30, and 100 micrograms/kg; n = 5). No subject had any symptoms after administration of vehicle or GHRH-40. During the 2-h period after iv administration of GHRH-40, the maximal increment in serum GH levels above basal (nanograms per ml; mean +/- SD) after the 0.1 micrograms/kg dose was 15.5 +/- 10.4 compared to 2.4 +/- 4.1 after vehicle (P = 0.0017). During the 3-h period after sc administration, when compared to the maximal increment in serum GH above basal after vehicle alone (10.2 +/- 12.9), the maximal increments above basal in serum GH were increased after both the 3.3 micrograms/kg (26.2 +/- 23.1; P = 0.022) and 10 micrograms/kg (63.6 +/- 53.5; P = 0.0003) doses. During the 3-h period after in administration, when compared to the maximal increment in serum GH above basal after vehicle alone (2.8 +/- 6.4), the maximal increments above basal in GH were higher after both the 30 micrograms/kg (18.5 +/- 10.4; P = 0.0053) and 100 micrograms/kg (21.7 +/- 8.1; P = 0.0028) doses. In addition, significant dose-response relationships were documented between the maximal increments above basal in serum GH and GHRH-40 administered by all routes. The mean (+/- SEM) peak plasma level of IR-GHRH (nanograms per ml) achieved after administration of 10 micrograms/kg GHRH-40, iv, as reported previously (66.6 +/- 17.6), was approximately 60- and 500-fold higher than the mean levels in the current study after administration of the same dose sc (1.11 +/- 0.39) or in (0.14 +/- 0.02), respectively. In summary, although GHRH-40 stimulates GH release when administered iv, sc, or in, significantly higher doses were required using the sc and in routes to achieve responses comparable to those obtained with iv administration.

Human pancreatic tumor growth hormone-releasing factor: dose-response relationships in normal man.

Human pancreatic GRF (hpGRF-40; 1 microgram/kg, iv) selectively stimulates GH release in normal men (9). We now report the effects of graded doses of hpGRF-40 on GH release in 12 normal men. Mean peak increments in serum GH after vehicle and the various doses of hpGRF-40 were 1.13, 11.40, 14.60, 17.01, 14.45, and 15.60 ng/ml after vehicle and 0.1, 0.33, 1.0, 3.3, and 10 micrograms/kg hpGRF-40 (iv bolus), respectively. Peak values were observed 30-60 min after hpGRF-40 treatment. There was considerable variability of responsiveness among individual subjects, and no dose-response relationship between the doses and maximal GH values was found. However, the higher doses of 3.3 and 10.0 micrograms/kg resulted in a more prolonged and biphasic pattern of GH release. A side effect of facial flushing of less than 5-min duration occurred in 4 or 6 subjects who received 3.3 micrograms/kg and in all 5 who received 10 micrograms/kg of hpGRF-40. No changes in serum glucose, LH, TSH, PRL, plasma cortisol, or 8 enteropancreatic hormones occurred after hpGRF-40 treatment. There were small increases in serum somatomedin C levels 24 h after the administration of various doses of hpGRF-40 in 11 of 13 studies. Plasma immunoreactive GRF levels measured 5 min after injection were 0.09, 2.0, 4.9, 23.9, and 66.6 ng/ml after 0.1, 0.33, 1.0, 3.3, and 10 micrograms/kg hpGRF-40, respectively. Serum GH responses after insulin-induced hypoglycemia were compared to GH responses after hpGRF-40. Comparable peak GH stimulation occurred with both provocative tests. Mean +/- SEM peak GH was 20.2 +/- 1.0 ng/ml after insulin and 20.9 +/- 3.2 after hpGRF-40 treatment. hpGRF-40 selectively stimulates GH release in normal men over a dose range of 0.1-10 micrograms/kg and is an effective probe to investigate the dynamics of GH release.

Mesulergine, a new dopamine agonist: effects on anterior pituitary function and kinetics.

We investigated the effects of single doses of mesulergine on basal and thyrotropin-releasing hormone (TRH)-stimulated serum levels of several anterior pituitary hormones in healthy men and defined its kinetics. We also compared the effects on serum prolactin (PRL) levels of three doses (0.1, 0.35, and 0.5 mg) of mesulergine to those in response to 2.5 mg bromocriptine. Secretory rates of PRL before the first dose of TRH were not affected by any dose of mesulergine or bromocriptine. TRH-stimulated PRL secretion was not altered by 0.1 mg mesulergine but was blunted by both the 0.35- and 0.5-mg doses at 10 A.M. and 1 P.M. Bromocriptine inhibited TRH-stimulated PRL secretion at 10 A.M. and 8 P.M. When analyzed as the 8 A.M. to 8 P.M. and the 8 P.M. to 9 A.M. (day 2) intervals, PRL secretion was not changed by 0.1 or 0.35 mg mesulergine but was suppressed during both periods by the 0.5-mg dose. A dose-response relationship was evident, however, between mesulergine and PRL secretion during both the 8 A.M. to 8 P.M. (R2 = 0.27) and the 8 P.M. to 9 A.M. (day 2; R2 = 0.18) intervals. Bromocriptine lowered PRL secretion during both intervals. Secretory rates of growth hormone during these intervals were not affected by 0.1 mg or 0.35 mg mesulergine but were increased during both intervals by the 0.5-mg dose. Neither the secretory rates of thyrotropin in response to TRH nor those of cortisol, luteinizing hormone, or follicle-stimulating hormone were changed by 0.1 or 0.35 mg mesulergine.(ABSTRACT TRUNCATED AT 250 WORDS)

Congenital dislocation of the hip in boys.

Fifty-five boys with seventy-eight congenitally dislocated hips were treated between 1965 and 1990. The patients were divided into three groups according to the initial treatment. Group I included thirty hips (twenty-two boys) that had been treated initially with a Pavlik harness. Two hips (7 per cent) had a successful outcome, and twenty-eight (93 per cent) needed additional methods of treatment. Group II included forty-two hips (twenty-nine boys) that had been treated initially with closed reduction and immobilization in a hip-spica cast. After the closed reduction, twenty-nine hips (69 per cent) were considered stable, although fifteen (52 per cent) of them needed a secondary procedure because of residual subluxation or persistent acetabular dysplasia. Thirteen hips (31 per cent) were considered unstable after the closed reduction and subsequently had an open reduction. Group III included six hips (four boys) that had been treated initially with open reduction. Two of these hips redislocated after the open reduction, and they were reduced with an additional open reduction. A pelvic osteotomy was later performed to treat persistent acetabular dysplasia in these two hips. Two hips that had been treated with an open reduction and concomitant pelvic and femoral procedures did not need additional treatment. This study demonstrates that boys who have congenital dislocation of the hip do not always respond well to treatment and constitute a high-risk group.

Experimental heterotopic bone transplant.

We studied the reaction in rats to implants of heterotopic bone in the paravertebral region, using three types of material: bone preserved in alcohol, homologous bone preserved in alcohol associated with autogenous cancellous bone obtained from the iliac crest of the same animal, and isolated autogenous cancellous bone. Thirty rats were operated on, ten in each group. Some were sacrificed after 6, 14 and 21 days. The excised grafts were histologically studied. Animals in the third group showed new bone formation even in the first days, those in the second group presented less intense bone formation and those in the first group showed only traces of new bone tissue in the third week.

[Colorectal diseases in AIDS patients and endoscopic findings]. / Afecções colorretais em portadores da síndrome da imunodeficiência adquirida e suas manifestações endoscópicas.

In order to establish which are the most frequent endoscopic detectable colorectal disorders in AIDS patients with intestinal complaints we analysed 236 colonoscopies in a series of 186 patients. The colonoscopic procedure was always followed by biopsies, even in the absence of macroscopic lesions. The most frequent diagnosis was colitis due to citomegalovirus infection observed in 64 exams (27.1%) and presented with an inflammatory pattern with ulcers, followed by Cryptosporidium sp., found in 31 exams (13.1%). This infection, conversely, presented as an inflammatory non-ulcerative lesion. Others pathogens found in lower frequency were: Mycobacterium sp., Histoplasma capsulatum, Herpes simplex, Isospora sp., Giardia sp., Candida sp. and Campilobacter sp.. Neoplastic lesions, mostly Kaposy's sarcoma, were detected in 10 of the colonoscopies (4.2%). The most frequent colorectal disorders in AIDS patients detected by endoscopic procedures are citomegalovirus and Cryptosporidium infection. Biopsies are always necessary to confirm the endoscopic diagnosis and to identify the presence of associated pathogens.

[Cerebral toxoplasmosis in a kidney transplant patient. A clinical case and review of the literature]. / Toxoplasmose cerebral em transplantado renal. Caso clínico e revisão da literatura.

Infection caused by Toxoplasma gondii is a frequent event in Portugal. When this occurs in immunocompetent individuals it is rarely a matter of concern; the contrary occurs with immunosuppressed patients or in pregnancy. Transplant patients are treated with immunosuppressive drugs which mainly disturb their mechanisms of cellular immunity, and that opens the way to infections by opportunistic intracellular microorganisms. We recently treated a renal transplant patient who suffered from cerebral toxoplasmosis, and this provided an opportunity for a review of the other 20 patients reported in medical literature to date.

Cerebral toxoplasmosis after renal transplantation. Case report and review.

Infection caused by Toxoplasma gondii is a frequent event in Portugal. When this occurs in immunocompetent individuals, it is rarely a matter of concern; the contrary occurs with immunosuppressed patients or in pregnancy. Transplant patients are treated with immunosuppressive drugs which mainly disturb their mechanisms of cellular immunity, and that opens the way to infections by opportunistic intracellular microorganisms. We recently treated a renal transplant patient who suffered from cerebral toxoplasmosis, and this provided an opportunity for a review of the other 20 patients reported in medical literature to date.