RESUMO
PURPOSE: Hyperhomocysteinemia is a known cardiovascular risk factor and a key player in the inflammatory activation of autoimmune diseases. Hashimoto's thyroiditis (HT) is the leading cause of hypothyroidism which, in itself, has been associated with a significant raise of homocysteine (Hcy) levels and increased cardiovascular risk. Our aim was to assess the impact of HT on Hcy levels in patients with acute hypothyroidism. METHODS: We prospectively enrolled 121 patients (mean age: 46 years, F/M = 102/19) with acute post-surgical hypothyroidism. Based on the presence of anti-thyroid antibodies and the histological description of an inflammatory infiltrate, 26 and 95 patients were classified as HT and non-HT, respectively. Several parameters including thyroid-stimulating hormone (TSH), levels of serum free T3 and free T4, weight, glucose levels, total cholesterol, creatinine, vitamin B12, ferritin and erythrocyte sedimentation rate were obtained from all patients and correlated with Hcy levels. RESULTS: Median Hcy level in the whole cohort was 16.8 µmol/L (normal values: < 12 µmol/l). Among all parameters analysed, only Hcy levels were significantly different between HT and non-HT patients (median Hcy = 19.7 vs 16.2 µmol/L, respectively; p = 0.018, Mann-Whitney U test). Analysis of covariance showed the presence of HT to be the strongest predictor of Hcy levels (coefficient = 0.25534, p = 0.001). Serum TSH was not significantly associated with Hcy levels (p = 0.943). CONCLUSION: In patients with iatrogenic hypothyroidism, those with HT have significantly higher Hcy levels than those without HT. The increase of Hcy levels appears to be mainly determined by the HT-related immune-inflammatory condition.
Assuntos
Autoimunidade , Hiper-Homocisteinemia/etiologia , Hipotireoidismo/complicações , Glândula Tireoide/imunologia , Doença Aguda , Adulto , Feminino , Doença de Hashimoto/complicações , Doença de Hashimoto/epidemiologia , Doença de Hashimoto/imunologia , Doença de Hashimoto/cirurgia , Humanos , Hiper-Homocisteinemia/epidemiologia , Hiper-Homocisteinemia/imunologia , Hipotireoidismo/epidemiologia , Hipotireoidismo/imunologia , Doença Iatrogênica/epidemiologia , Radioisótopos do Iodo/uso terapêutico , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Glândula Tireoide/efeitos da radiaçãoRESUMO
INTRODUCTION AND OBJECTIVES: Subjects with severe acquired brain injury (sABI) require long-term mechanical ventilation and, as a consequence, the tracheostomy tube stays in place for a long time. In this observational study, we investigated to what extent the identification of late tracheostomy complications by flexible bronchoscopy (FBS) might guide clinicians in the treatment of tracheal lesions throughout the weaning process and lead to successful decannulation. SUBJECTS AND METHODS: One hundred and ninety-four subjects with sABI admitted to our rehabilitation unit were enrolled in the study. All subjects received FBS and tracheal lesions were treated either by choosing a more suitable tracheostomy tube, or by laser therapy, or by steroid therapy, or by a combination of the above treatments. RESULTS: Overall, 122 subjects (63%) were decannulated successfully. Our subjects received 495 FBSs (2.55 per subject) and as many as 270 late tracheostomy complications were identified. At least one complication was found in 160 subjects (82%). In only 11 subjects, late tracheostomy complications did not respond to the treatment and were the cause of decannulation failure. CONCLUSIONS: In conclusion, in sABI patients FBS is able to guide successful tracheostomy weaning in the presence of late tracheostomy complications that could get in the way decannulation.
Assuntos
Lesões Encefálicas , Traqueostomia , Humanos , Broncoscopia , Remoção de Dispositivo , Respiração Artificial , Complicações Pós-Operatórias , Lesões Encefálicas/reabilitaçãoRESUMO
The work presented here was developed in the framework of the SENTINEL Project and is devoted to the analysis of dental radiology dosimetric data. The procedure of data processing allows the analysis of some important aspects related to the protection of the patient and the staff because of the position of the operators near the patient and their exposure to the radiation scattered by the patient. Dental radiology data was collected in an Italian hospital. Following the Italian quality assurance (QA) protocols and suggestions by the leaders of the SENTINEL Project, X-ray equipment performances have been analysed in terms of: kVp accuracy, exposure time accuracy and precision, tube output, dose reproducibility and linearity, beam collimation, artefacts and light tightness. Referring to these parameters the physical quality index (QI) was analysed. In a single numerical value between 0 and 1, QI summarises the results of quality tests for radiological devices. The actual impact of such a figure (as suggested by international QA protocols or as adopted by local QA routine) on the policy of machine maintenance and replacement is discussed.
Assuntos
Diagnóstico por Imagem/instrumentação , Diagnóstico por Imagem/normas , Proteção Radiológica/normas , Radiografia Dentária/métodos , Serviço Hospitalar de Radiologia/normas , Radiometria/métodos , Humanos , Garantia da Qualidade dos Cuidados de Saúde , Controle de Qualidade , Radiografia Dentária/instrumentação , Radiometria/normasRESUMO
Recent advances in semiconductor pixel detectors and read-out electronics allowed to build the first prototypes of single photon-counting imaging systems that represent the last frontier of digital radiography. Among the advantages with respect to commercially available digital imaging systems, there are direct conversion of photon energy into electrical charge and the effective rejection of electronic noise by means of a thresholding process. These features allow the photon-counting systems to achieve high imaging performances in terms of spatial and contrast resolution. Moreover, the now available deep integration techniques allow the reduction of the pixel size and the improvement of the functionality of the single cell and the read-out speed so as to cope with the high fluxes found in diagnostic radiology. In particular, the single photon-counting system presented in this paper is based on a 300-microm thick silicon pixel detector bump-bonded to the Medipix2 read-out chip to form an assembly of 256 x 256 square pixels at a pitch of 55 microm. Each cell comprises a low-noise preamplifier, two pulse height discriminators and a 14-bit counter. The maximum counting rate per pixel is 1 MHz. The chip can operate in two modalities: it records the events with energy above a threshold (single mode) or between two energy thresholds (window mode). Exploiting this latter feature, a possible application of such a system as a fast spectrometer is presented to study the energy spectrum of diagnostic beams produced by X-ray tubes.
Assuntos
Diagnóstico por Imagem , Aumento da Imagem/métodos , Processamento de Imagem Assistida por Computador/instrumentação , Processamento de Imagem Assistida por Computador/métodos , Fótons , Tomografia Computadorizada por Raios X/métodos , Humanos , Aumento da Imagem/instrumentação , Intensificação de Imagem Radiográfica/instrumentação , Intensificação de Imagem Radiográfica/métodos , Radiometria , Tomografia Computadorizada por Raios X/instrumentaçãoRESUMO
In human blood, breakdown of gastrin-releasing peptide and other bombesin-related peptides occurs in less than 15 min. This quick enzymatic cleavage might impair the diagnostic use of labelled bombesin (BN). 99mTc-labelled bombesin (99mTc BN1) was injected intravenously and dynamic uptake data were acquired for diagnosing 26 cancers of different origin: 15 breast, 3 prostate, 5 colo-rectal, 1 pancreas, 2 small cell lung cancers and 1 gastrinoma. Background subtracted tumour uptake data were plotted against time and fitted with known mathematical functions. Twenty-three out of 26 cancers showed rapid increase of radioactivity followed by a radioactivity plateau, with some oscillations around the average plateau value. The time to 80% of max activity (T80) was the reference parameter to measure and to compare the uptake speeds. The slowest T80 was 7 min in one T1b breast cancer, gastrinoma reached T80 in 5 min and node-positive prostate cancers in 2 min. N+ breast cancers showed T80 at 3.62 +/- 0.75 min, N- breast cancers at 5.5 +/- 0.88 min (p < 0.02). When all the tumours were considered, N+ tumours showed T80 at 2.68 +/- 1.03 min and N- cancers at 5.5 +/- 0.82 min. In all the cancer types, the uptake of 99mTc BN was faster than 10 min. This result shows the ability of 99mTc BN to image tumours. The faster uptake by N+ versus N- cancers probably depends on the higher blood flow in N+ cancers.
Assuntos
Bombesina/análogos & derivados , Neoplasias/diagnóstico por imagem , Neoplasias/metabolismo , Compostos de Organotecnécio , Neoplasias da Mama/irrigação sanguínea , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/metabolismo , Carcinoma de Células Pequenas/irrigação sanguínea , Carcinoma de Células Pequenas/diagnóstico por imagem , Carcinoma de Células Pequenas/metabolismo , Neoplasias do Colo/irrigação sanguínea , Neoplasias do Colo/diagnóstico por imagem , Neoplasias do Colo/metabolismo , Feminino , Gastrinoma/irrigação sanguínea , Gastrinoma/diagnóstico por imagem , Gastrinoma/metabolismo , Humanos , Cinética , Neoplasias Pulmonares/irrigação sanguínea , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/metabolismo , Masculino , Estadiamento de Neoplasias , Neoplasias/irrigação sanguínea , Neoplasias Pancreáticas/irrigação sanguínea , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/metabolismo , Neoplasias da Próstata/irrigação sanguínea , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/metabolismo , Cintilografia , Compostos Radiofarmacêuticos , Receptores da Bombesina/metabolismo , Neoplasias Retais/irrigação sanguínea , Neoplasias Retais/diagnóstico por imagem , Neoplasias Retais/metabolismo , Fluxo Sanguíneo RegionalRESUMO
Recent studies in the rat have shown that intracerebroventricular administration of CRH inhibited spontaneous pulsatile GH secretion and prevented GH-releasing hormone (GHRH)-induced GH release. We have studied the effect of CRH on GHRH-induced GH release in man. In the first study, CRH was injected iv at three different doses (100, 50, or 25 micrograms) at 0800 h together with 50 micrograms GHRH in six men and six women. In a second study, 100 micrograms CRH were given iv at 0800 h, 1 h before the administration of 50 micrograms GHRH in five men and five women. Each subject demonstrated a normal GH response after the administration of 50 micrograms GHRH plus saline. All doses of CRH administered simultaneously with GHRH significantly inhibited GHRH-induced GH release in women [peak value +/- SE after GHRH plus saline, 28.9 +/- 2.9 micrograms/L; after GHRH plus 100 micrograms CRH, 9.9 +/- 0.7 micrograms/L (P less than 0.001); after GHRH plus 50 micrograms CRH, 8.7 +/- 0.8 micrograms/L (P less than 0.001); after GHRH plus 25 microgram CRH, 9.5 +/- 1.6 microgram/L (P less than 0.001]). In contrast, in men, while a dose of 100 micrograms CRH was capable of suppressing GHRH-induced GH secretion (peak value +/- SE, 8.1 +/- 0.6 vs. 20 +/- 2.9 micrograms/L; P less than 0.001), no inhibition was observed after 50- and 25-micrograms doses. When 100 micrograms CRH were injected 1 h before the administration of 50 micrograms GHRH, it strongly inhibited GHRH-induced GH secretion in both men (peak value +/- SE, 6.2 +/- 2.8 vs. 24.6 +/- 5.9 micrograms/L; P less than 0.02) and women (peak value +/- SE, 14.2 +/- 4.5 vs. 37.8 +/- 6.7 micrograms/L; P less than 0.005), and this inhibition lasted up to 2 h post-CRH administration. These results demonstrate that CRH is capable of inhibiting GHRH-induced GH release in both men and women. Furthermore, the findings suggest that a sexual dimorphism in the neuroregulation of GH secretion may be present in man. In view of the inhibitory action of CRH on GH secretion, simultaneous administration of CRH and GHRH for testing should be avoided in clinical practice.
Assuntos
Hormônio Liberador da Corticotropina/farmacologia , Hormônio Liberador de Hormônio do Crescimento/farmacologia , Hormônio do Crescimento/sangue , Adulto , Hormônio Liberador da Corticotropina/administração & dosagem , Feminino , Hormônio do Crescimento/metabolismo , Hormônio Liberador de Hormônio do Crescimento/antagonistas & inibidores , Humanos , Hidrocortisona/sangue , Masculino , Ciclo Menstrual/efeitos dos fármacosRESUMO
Nutritional status and metabolic fuels are factors involved in the regulation of GH secretion and GH responses to GHRH. The effects of feeding on GHRH-induced GH release were studied in 13 normal women, 14 obese women, and 9 women with anorexia nervosa. GHRH-(1-44) (50 micrograms, iv) was administered at 0900 h after an overnight fast or at 1300 h after a normal meal at 0800 h, and at the same times 45 min after a 800-Cal meal on different days. The mean peak plasma GH responses to GHRH administered before a meal at 0900 h were 52.8 +/- 5.6 (+/- SE) micrograms/L in normal women, 8.2 +/- 1.3 micrograms/L in obese women, and 53.2 +/- 7.7 micrograms/L in anorexic women. When GHRH was administered before a meal at 1300 h, the mean peak plasma GH levels were lower than those at 0900 h; this reduction was -64.2% in normal women, -64.9% in obese women, and -55.8% in women with anorexia nervosa. After feeding, the plasma GH responses to GHRH were blunted in normal women at 0900 h (-60.9%) and 1300 h (-34.6%) compared with the fasting peak responses. In obese women the plasma GH response to GHRH after feeding was increased compared with that when these women had fasted (+60% at 0900 h and +406.9% at 1300 h). Finally, differential effects of feeding were present in anorexic women; the response was lower at 0900 h (-46.4%) and greater at 1300 h (+50.8%). We conclude that there is an ultradian variation in GHRH-stimulated GH secretion and that the responses differ according to nutritional status and body weight.
Assuntos
Anorexia Nervosa/fisiopatologia , Ritmo Circadiano , Hormônio Liberador de Hormônio do Crescimento/farmacologia , Hormônio do Crescimento/sangue , Obesidade/fisiopatologia , Adulto , Anorexia Nervosa/sangue , Glicemia/metabolismo , Ácidos Graxos não Esterificados/sangue , Feminino , Alimentos , Humanos , Estado Nutricional , Obesidade/sangueRESUMO
We studied the inhibitory effect of exogenous CRH on pulsatile gonadotropin secretion and the role of endogenous opioid peptides in this phenomenon in normal women. To do so, we infused human CRH (100 micrograms/h for 3 h) into 15 normal women during the midluteal phase of their menstrual cycle and studied its effect on both basal (10 women) and GnRH-stimulated (5 women) plasma gonadotropin levels. CRH infusion induced a significant decrease in plasma LH and FSH levels in all women. The decline in plasma LH (62%) was greater than that in FSH (36%). Plasma LH and FSH concentrations returned to basal levels within 30 min after the end of the CRH infusion. CRH infusion did not alter the gonadotropin response to GnRH. We also infused naloxone plus CRH in the 10 women who had received CRH alone during the midluteal phase of a different cycle. Addition of naloxone to CRH (5 women) reversed the LH and FSH inhibition when naloxone was started 1 h after the start of the CRH infusion. When naloxone was started 1 h before CRH infusion (5 women), plasma LH and FSH concentrations did not change. Plasma cortisol increased similarly during both the CRH and CRH plus naloxone infusions; the mean cortisol levels at the end of the CRH and CRH plus naloxone infusions were 497 +/- 40 (+/- SE) and 484 +/- 41 nmol/L, respectively, compared to 240 +/- 14 nmol/L after saline infusion (P less than 0.001). These results demonstrate that in normal women during the midluteal phase of the menstrual cycle, CRH inhibits the secretion of both LH and FSH. The CRH-induced inhibition of gonadotropin secretion is primarily mediated by endogenous opioid peptides, and this effect is not dependent on glucocorticoid levels. We suggest that the disruptive effect of stress on reproductive function in the women could be, at least in part, dependent on decreased gonadotropin secretion induced by elevated endogenous CRH levels.
Assuntos
Hormônio Liberador da Corticotropina/farmacologia , Hormônio Foliculoestimulante/antagonistas & inibidores , Hormônio Luteinizante/antagonistas & inibidores , Naloxona/farmacologia , Adulto , Hormônio Liberador da Corticotropina/antagonistas & inibidores , Endorfinas/fisiologia , Feminino , Hormônio Foliculoestimulante/metabolismo , Humanos , Hidrocortisona/sangue , Hidrocortisona/metabolismo , Infusões Intravenosas , Hormônio Luteinizante/metabolismo , Ciclo Menstrual/efeitos dos fármacosRESUMO
Sex differences in the neuroregulation of GH secretion are not now known in humans. To investigate whether activation of cholinergic tone by pyridostigmine could cause a sex-related difference in the pituitary responsiveness to GH-releasing hormone (GHRH), we have studied the GH response to GHRH in 16 normal subjects (8 men and 8 women) tested after oral placebo or different doses of pyridostigmine (30, 60, and 120 mg). Each subject presented a normal response after iv administration of 50 micrograms GHRH and placebo. In men each dose of pyridostigmine induced a significant increase in the GH response to GHRH, as assessed by both the maximal GH peak and the area under GH curve. In women, on the contrary, the GH response to GHRH was not potentiated by pretreatment with pyridostigmine at any given dose. Only five female subjects were tested with 120 mg pyridostigmine because of the severe side-effects of the drug at this dosage. Our present data strongly suggest that in humans there is a sex-related difference in the neuroregulation of GH secretion and this is probably expressed through a different cholinergic tone.
Assuntos
Hormônio Liberador de Hormônio do Crescimento/farmacologia , Hormônio do Crescimento/metabolismo , Brometo de Piridostigmina/farmacologia , Caracteres Sexuais , Adulto , Sinergismo Farmacológico , Feminino , Humanos , Masculino , Brometo de Piridostigmina/administração & dosagem , Brometo de Piridostigmina/efeitos adversosRESUMO
UNLABELLED: This study evaluates the short- and long-term therapeutic efficacy of 186Re-1,1-hydroxyethylidene diphosphonate (HEDP) in the palliation of painful bone metastases and the influence of variables before therapy in determining the characteristics of pain palliation. METHODS: Sixty patients with painful bone metastases from different tumor types were treated with 1406 MBq 186Re-HEDP. After treatment, the patients were followed up clinically at weekly intervals for the first month and monthly thereafter up to 1 y, until death or pain relapse. Pain response was graded as complete, partial, minimal, or absent using the Wisconsin test scoring system. Duration of pain relief, performance status, tumor markers, serum alkaline phosphatase levels, hematologic toxicity, and metastatic bone progression were also evaluated. RESULTS: Overall, 80% of individuals experienced prompt relief of pain, with 31% complete, 34% partial, and 15% minimal responses. Transient World Health Organization grade 1-2 hematologic toxicity was apparent, with a decrease in the mean platelet (32%) and mean leukocyte (18%) counts at 3 and 4 wk, respectively. The degree of pain response did not correlate with any pretreatment variable. The duration of pain relief ranged from 3 wk to 12 mo and correlated positively with the degree of response (P = 0.02) and negatively with pretreatment scintigraphic scores and alkaline phosphatase levels (P = 0.02). CONCLUSION: 186Re-HEDP is effective for fast palliation of painful bone metastases from various tumors. The effect tends to last longer if patients are treated early in the course of their disease.
Assuntos
Neoplasias Ósseas/radioterapia , Neoplasias Ósseas/secundário , Ácido Etidrônico/uso terapêutico , Compostos Organometálicos/uso terapêutico , Dor Intratável/radioterapia , Cuidados Paliativos , Radioisótopos/uso terapêutico , Idoso , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias da Mama/fisiopatologia , Feminino , Seguimentos , Humanos , Masculino , Neoplasias da Próstata/fisiopatologia , Cintilografia , Fatores de TempoRESUMO
UNLABELLED: Presurgical neoadjuvant chemotherapy (PSNC) is the treatment of choice for patients with locally advanced breast carcinoma (LABC). Accurate assessment of tumor response is important in planning subsequent treatments. Conventional response assessment by mammography and clinical evaluation is not fully reliable. This study evaluates the diagnostic yield of serial 99mTc-MIBI scintigraphy in the assessment of LABC response to PSNC. METHODS: Twenty-nine patients affected by LABC underwent clinical, mammographic and 99mTc-MIBI scintigraphy before and after 3 cycles of FEC (500 mg/m2 5-fluorouracil, 50 mg/m2 epirubicin and 400 mg/m2 cyclophosphamide) on Days 1 and 8. Surgery was planned for 15 days after the third cycle of chemotherapy. Pathological status was obtained after surgery in all patients. RESULTS: Sensitivities (i.e., true-positive ratios) for a correct prediction of tumor presence after PSNC were 65% for scintigraphy, 35% for clinical evaluation and 69% for mammography. Specificities (i.e., true-negative ratios) for a correct prediction of tumor absence after PSNC were 100% for scintigraphy, 67% for clinical evaluation and 33% for mammography. Technetium-99m-MIBI uptake in this series did not correlate with P-170 expression, proliferating cell nuclear antigen, Her-2/neu oncogene protein, antihuman endothelial cell CD31 antigen and estrogenic and progestinic receptor status. CONCLUSION: Technetium-99m-MIBI scintigraphy is effective in monitoring the response to PSNC in LABC patients. Its diagnostic yield is clearly superior to clinical evaluation alone. Scintigraphy performs as does mammography in patients with negative response, but it is clearly superior in patients with positive response.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/diagnóstico por imagem , Compostos Radiofarmacêuticos , Tecnécio Tc 99m Sestamibi , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/cirurgia , Quimioterapia Adjuvante , Ciclofosfamida/administração & dosagem , Epirubicina/administração & dosagem , Feminino , Fluoruracila/administração & dosagem , Humanos , Cintilografia , Sensibilidade e Especificidade , EstereoisomerismoRESUMO
UNLABELLED: This study reports on a prototype single-photon emission mammograph (SPEM) dedicated to 99mTc-hexakis-2-methoxyisobutile isonitrile (MIBI) scintimammography. Main technical features are reported together with physical performance. Preliminary patient data are also reported. METHODS: The SPEM detector head is composed of a CsI(T1) scintillating array coupled to a Hamamatsu R3292 position-sensitive photomultiplier tube with crossed-wire anode. The high-resolution collimator is 35-mm thick with a 1.7-mm hole diameter and a 0.2-mm septal thickness. The electronic acquisition system is composed of five integrated cards with computation based on high-speed programmable microprocessors. The readout electronics include correction maps for on-line energy correction and spatial uniformity. The small size of the detector head allows the use of mechanical breast compression to minimize detection distance and tissue scatter. After physical SPEM performance evaluation in vivo scintimammography was performed in 29 patients and was compared with a state-of-the-art Anger camera. RESULTS: The SPEM showed an intrinsic spatial resolution of 2 mm, an energy resolution of 23% FWHM at 122 keV and spatial uniformities of 18% (integral) and 13.5% (differential). The SPEM imaged one 0.4-cm carcinoma missed by the Anger camera and resolved as separate lumps an irregular focal uptake on the Anger camera image. The remaining cases yielded concordant results. CONCLUSION: The SPEM prototype presented in this study shows adequate physical characteristics for 99mTc-MIBI scintimammography.
Assuntos
Mama/diagnóstico por imagem , Compostos Radiofarmacêuticos , Tecnécio Tc 99m Sestamibi , Tomografia Computadorizada de Emissão de Fóton Único/instrumentação , Adulto , Idoso , Neoplasias da Mama/diagnóstico por imagem , Feminino , Câmaras gama , Humanos , Pessoa de Meia-IdadeRESUMO
Previously we observed that prolactin (PRL) is secreted in response to gonadotropin-releasing hormone (GnRH) in normal women during the periovulatory phase of the menstrual cycle. Because sedative drugs affect the neurotransmitters involved in the regulation of PRL secretion, we investigated PRL responsiveness to GnRH in pre- and postmenopausal female subjects during prolonged treatment with benzodiazepines (six-60 months). In both pre-and postmenopausal patients who were not on benzodiazepine treatment, GnRH infusion (0.2 micrograms/min for 3 hr) was ineffective in eliciting a PRL response. In six premenopausal women treated with benzodiazepines, basal PRL concentrations were not influenced by the drug in four subjects (range 4.0-15.7 ng/ml) and were slightly elevated in two subjects (23 and 30 ng/ml). In six treated postmenopausal women, basal PRL concentrations were in the normal range (7.5-11.0 ng/ml). GnRH infusion induced a progressive increase in PRL concentrations which reached a peak at 120 min in the premenopausal subjects (mean % SEM increase: 64 +/- 30.5%) and at 60-90 min in the postmenopausal subjects (mean % increase: 110.6 +/- 34.7%). A saline infusion, performed on a separate day during benzodiazepine treatment as a control, did not influence PRL.
Assuntos
Ansiolíticos/uso terapêutico , Transtornos Mentais/tratamento farmacológico , Hormônios Liberadores de Hormônios Hipofisários , Prolactina/sangue , Distúrbios do Início e da Manutenção do Sono/tratamento farmacológico , Adulto , Benzodiazepinas , Feminino , Humanos , Assistência de Longa Duração , Menopausa/efeitos dos fármacos , Transtornos Mentais/sangue , Pessoa de Meia-Idade , Distúrbios do Início e da Manutenção do Sono/sangueRESUMO
Anorexia nervosa (AN) is frequently associated with anomalies of growth hormone (GH) and prolactin (PRL) secretion. We studied the GH and PRL responses to GHRH1-44 (50 micrograms IV) and the effect of a naloxone infusion (1.6 mg/hr), started 1 hr before GHRH administration, on this response in 12 female patients with AN, aged 15-30 yr, and in seven normal women, aged 19-27 yr, during the follicular phase as controls. In AN, GHRH induced an increase in GH levels similar to that observed in normal subjects. A significant inhibition of the GH response to GHRH was observed during naloxone infusion, similar to the inhibition in normal female subjects during the follicular phase. PRL levels showed a significant increment after GHRH alone and a slight, nonsignificant, PRL increment after GHRH during naloxone infusion in AN patients. In contrast a slight PRL decrease was observed after GHRH, both before and during naloxone infusion, in the normal subjects. Our study demonstrates that endogenous opioids play a role in influencing PRL secretion in patients with AN different from their role in normal subjects.
Assuntos
Anorexia Nervosa/sangue , Hormônio Liberador de Hormônio do Crescimento/farmacologia , Hormônio do Crescimento/sangue , Naloxona/farmacologia , Prolactina/sangue , Adolescente , Adulto , Anorexia Nervosa/fisiopatologia , Endorfinas/fisiologia , Feminino , Fase Folicular/fisiologia , Humanos , Infusões Intravenosas , Naloxona/administração & dosagemRESUMO
The effect of opiate-receptor antagonist naloxone on growth hormone (GH) release after growth hormone-releasing hormone (GHRH) 1-44 administration was investigated in ten normal men and 18 normal women during different phases of their menstrual cycle. Naloxone was infused at a rate of 1.6 mg/h in women and 1.6- and 3.2 mg/h in men, starting one hour before GHRH administration (50 micrograms iv as a bolus). On different day sessions, naloxone, GHRH, or saline were administered as controls. Naloxone infusion reduced the GHRH-induced GH release in normal women. The mean % inhibition of peak GH response was 83% during follicular phase, 46.5% during periovulatory phase, and 77.6% during luteal phase. On the contrary, in normal men, both doses of naloxone infusion were ineffective in blunting the GH response to GHRH. Our studies indicate that naloxone infusion was capable of inhibiting GH release induced by direct stimulation with GHRH in normal women, suggesting an opiate-antagonist action at the anterior pituitary level. The absence of such an effect in normal men strongly indicates a sex dependence of naloxone effects and suggests a role of the sexual steroid environment in opioid modulation of pituitary hormone secretion.
Assuntos
Hormônio Liberador de Hormônio do Crescimento/farmacologia , Hormônio do Crescimento/metabolismo , Naloxona/farmacologia , Caracteres Sexuais , Adulto , Interações Medicamentosas , Feminino , Humanos , Masculino , Fragmentos de Peptídeos/farmacologiaRESUMO
Following the demonstration of a positive prolactin (PRL) response to growth hormone-releasing hormone (GHRH) in acromegalic and anorexic women, we have injected GHRH (50 micrograms intravenously as a bolus) in normal women during various phases of their menstrual cycle in order to establish whether a positive response was present also in normal subjects. Synthetic GHRH 1-44 elicited a significant increase in circulating PRL levels in eight women studied during the periovulatory phase of the menstrual cycle. In contrast, no significant changes in circulating PRL levels after GHRH administration were found in nine women during the midfollicular phase or in five women during the midluteal phase. A temporal correlation between the midcycle gonadotropin peak and the positive response to GHRH has been observed. Synthetic GHRH elicited the expected increase in GH levels during all phases of the cycle studied. Our data demonstrate that GHRH is capable of stimulating a PRL response in normal subjects and raise the possibility that PRL secretion is regulated by several hormones of hypothalamic origin.
Assuntos
Hormônio Liberador de Hormônio do Crescimento/farmacologia , Ciclo Menstrual/efeitos dos fármacos , Prolactina/sangue , Adulto , Feminino , Fase Folicular/efeitos dos fármacos , Hormônio do Crescimento/sangue , Humanos , Fase Luteal/efeitos dos fármacos , Ovulação/efeitos dos fármacosRESUMO
To determine whether corticotropin-releasing hormone (CRH) exerts an inhibitory action on gonadotropin secretion in normal fertile women, the effects of CRH on luteinizing hormone (LH), follicle-stimulating hormone (FSH), and cortisol secretion were studied during the menstrual cycle. CRH had no effect on LH release during the midfollicular phase of the cycle. By contrast, IV injection of 100 micrograms CRH elicited significant decreases in LH concentrations during late follicular (-50%) and midluteal (-52%) phases of the cycle. LH concentrations decreased during the four-hours following injection of CRH and returned to those observed during the control period five hours after injection. Similarly, CRH elicited a significant decrease in FSH secretion during the midluteal phase of the cycle. CRH injection induced an increase in cortisol release during all phases of the cycle. These data demonstrate that exogenous CRH administration results in inhibition of gonadotropin secretion in late follicular and midluteal phases of the cycle. These results suggest that elevated endogenous CRH levels resulting in increased cortisol secretion could contribute to decreased gonadotropin secretion and, thus, disruption of reproductive function during stressful conditions in women.
Assuntos
Hormônio Liberador da Corticotropina/farmacologia , Hormônio Foliculoestimulante/metabolismo , Hormônio Luteinizante/metabolismo , Ciclo Menstrual , Adulto , Feminino , Fase Folicular , Humanos , Hidrocortisona/metabolismo , Fase LutealRESUMO
A paradoxical growth hormone (GH) response to thyrotropin-releasing hormone (TRH) has been observed in type 1 diabetic patients and was hypothetically attributed to a reduced hypothalamic somatostatin tone. We have previously reported that corticotropin-releasing hormone (CRH) inhibits GH response to growth hormone-releasing hormone (GHRH) in normal subjects, possibly by an increased release of somatostatin. To study the effect of CRH on anomalous GH response to TRH, we tested with TRH (200 micrograms intravenously [IV]) and CRH (100 micrograms IV) + TRH (200 micrograms IV) 13 patients (six males and seven women) affected by insulin-dependent diabetes mellitus. A paradoxical GH response to TRH was observed in seven of 13 patients, one man and six women. In these subjects, the simultaneous administration of CRH and TRH significantly reduced the GH response to TRH, as assessed by both the maximal GH mean peak +/- SE (2.18 +/- 0.67 v 9.2 +/- 1.26 micrograms/L, P less than 0.005) and the area under the curve (AUC) +/- SE (187 +/- 32 v 567 +/- 35 micrograms.min/L, P less than .001). CRH had no effect on TRH-induced thyroid-stimulating hormone (TSH) release. Our data demonstrate that the paradoxical GH response to TRH in patients with type 1 diabetes mellitus is blocked by CRH administration. This CRH action may be due to an enhanced somatostatin release. Our data also show that exogenous CRH has no effect on TSH response to TRH, thus suggesting the existence of separate pathways in the neuroregulation of GH and TSH secretion.
Assuntos
Hormônio Liberador da Corticotropina/farmacologia , Diabetes Mellitus Tipo 1/sangue , Hormônio do Crescimento/antagonistas & inibidores , Hormônio do Crescimento/sangue , Hormônio Liberador de Tireotropina/farmacologia , Adulto , Hormônio Liberador da Corticotropina/administração & dosagem , Diabetes Mellitus Tipo 1/fisiopatologia , Feminino , Humanos , Injeções Intravenosas , Masculino , Radioimunoensaio , Somatostatina/sangue , Tireotropina/sangue , Hormônio Liberador de Tireotropina/administração & dosagemRESUMO
Cardiotoxicity of high dose rate epirubicin (140-160 mg/m(2) as a bolus every 21 days up to a cumulative dose of 1280 mg/m(2)) was evaluated by angiocardioscintigraphy in 121 patients with advanced neoplastic disease and no preexisting cardiac risk factors. LVEF was measured in each patient before chemotherapy and during the treatment at different epirubicin cumulative dosages. The cases were subdivided into 3 groups: Group A=121 basal studies; Group B=93 studies performed under 800 mg/m(2); Group C=44 studies performed over 800 mg/m(2). A statistically significant decrease of LVEF was observed only at cumulative doses over 800 mg/m(2) (mean LVEF: 53% +/- 11% in Group C vs 64% +/- 7% in Group A). In no case was chemotherapy stopped prematurely and no case of heart failure was observed. A decrease of LVEF 10 units was recorded in 15 patients and 12 of them had been treated with over 800 mg/m(2). No clinical signs of severe cardiac failure were observed in these patients during a follow-up of 5-17 months. In conclusion, epirubicin treatment at high dose rate up to a cumulative dose of 1000 mg/m(2) does not increase the risk of clinically relevant cardiomyopathy and an LVEF decrease of 10 units should not in itself lead to chemotherapy termination in responsive patients.
RESUMO
A 17-year-old boy with polymorphic simple and complex partial seizures is described. Magnetic resonance imaging revealed a unilateral periventricular nodular heterotopia near the occipital ventricular right horn. Interictal and ictal electroencephalographic recordings showed bilateral specific epileptiform anomalies in the occipital region and asynchronous slow waves in frontal areas. Single photon emission computed tomography documented a reduction in regional cerebral blood flow in an area of the left occipital cortex and a symmetric increase in tracer uptake in the frontal lobes. The neuropsychologic assessment revealed a dysfunction of the frontal associative areas. Data collected led the authors to suspect a more diffuse cortical dysfunction than the nodular heterotopia revealed on magnetic resonance imaging.