Control of feeding and sexual behaviors by neuropeptide Y: physiological implications

Recent evidence suggests that a variety of hypothalamic neuropeptides may mediate interneuronal communication to coordinate diverse neuroendocrine and behavioral functions. In this work, we describe the effects of neuropeptide Y (NPY) on feeding and sexual behaviors. We observed that central administration of bolus NPY stimulated a robust, dose-related feeding response in satiated male and female rats. Continuous NPY receptor activation also evoked dose-related, intermittent feeding in a manner normally observed during nocturnal feeding. It appears that the paraventricular nucleus in the hypothalamus may be the primary site of NPY action because the anticipated reciprocal changes in NPY concentrations, in response to food deprivation followed by ad libitum food intake, occurred only in this site. Additional findings revealed that NPY-induced feeding may follow either substantial reduction or complete restraint of an inhibitory influence on feeding mediated by alpha 2-adrenoreceptor systems in satiated rats. Further, NPY was found to suppress male and female sexual behaviors. The suppressive effects on sexual behavior were apparent prior to or at the time of the onset of feeding after NPY administration. These observations may provide a neurochemical basis for clinical and animal studies on disorders of feeding associated with diminished reproductive functions.     

Atrial natriuretic peptide levels in the prediction of congestive heart failure risk in frail elderly.

OBJECTIVE--To develop a noninvasive clinical predictive model for acute congestive heart failure (CHF) in a frail elderly cohort using bedside clinical assessment (medical history and physical examination) and venous atrial natriuretic peptide (ANP) levels. DESIGN--One-year prospective blinded cohort study. SETTING--Life care facility. PARTICIPANTS--Three hundred thirty-one frail, elderly volunteers free of acute illness at study entry (mean +/- SD age, 88 +/- 7 years; 23% male, 77% female). MAIN OUTCOME MEASURE--Clinical episodes of CHF with confirmation of acute pulmonary edema by chest roentgenogram. RESULTS--Fifteen percent of the elderly cohort developed at least one episode of CHF during the 1-year follow-up period. Those developing CHF had significantly higher mean +/- SE ANP values at study entry: 493 +/- 55 vs 207 +/- 15 pmol/L. The risk for development of CHF rose progressively with increasing ANP levels at study entry. In multivariate analysis, only two independent variables significantly predicted CHF: ANP value greater than 200 pmol/L (adjusted odds ratio [OR], 7.9; 95% confidence interval [CI], 3.2 to 19.2) and history of CHF in the previous year (adjusted OR, 7.0; 95% CI, 2.9 to 17). Stratifying the cohort by these two variables results in three CHF risk groups: 55% of the population at 3% annual risk of CHF, 37% of the population at 20% to 24% annual risk of CHF, and 8% of the population at 66% annual risk of CHF. CONCLUSIONS--This simple clinical prediction model identifies elderly subjects at risk for CHF and allows appropriate focusing of medical resources for prevention, early detection, and treatment of this highly morbid clinical syndrome.     

Benign ovarian cysts in England and Wales and in the United States.

OBJECTIVE: To compare the rates of hospital admission for management of ovarian cysts in England and Wales and the United States between 1972 and 1974 and 1984 and 1986; and to determine whether these rates are related to rates of early diagnosis of ovarian cancer. DESIGN: Analysis of published and unpublished hospital discharge data based on national samples, the Hospital In-patient Enquiry (HIPE), a 10% hospital discharge sample for England and Wales, and the National Hospital Discharge Survey (NHDs), a 5% sample for the United States. MAIN OUTCOME MEASURES: Age-specific discharge rates for primary and secondary diagnoses of ovarian cyst or benign ovarian tumour. RESULTS: There was an age-adjusted increase in discharge rates of about 8% in both countries; discharge rates in the United States were approximately double those in England and Wales in both time periods. There was no difference in the rates of early diagnosis of ovarian cancer. CONCLUSIONS: Ovarian cysts are a common cause of hospital admission in both countries. The higher rates in the United States are not associated with earlier diagnosis of ovarian cancer.     

Surgical aspects of chronic peritoneal dialysis in the neonate and infant under 1 year of age.

Since 1982 eight patients under 1 year of age with end-stage renal failure have been treated by chronic peritoneal dialysis (CPD) following insertion of an abdominal Tenckhoff catheter. We routinely perform a partial omentectomy now, and in males undertake bilateral exploration of the groins at the time of catheter insertion, with herniotomy or ligation of the patent processus vaginalis as required. Up to January 1990, 19 straight double-cuff catheters had been inserted with a total follow-up of 244.5 patient months. The median age at the initial catheter insertion was 14.6 weeks (range, 2 days to 11 months) and the median weight was 3.89 kg (range, 2.2 to 5.5). Peritonitis was the most common complication, with 46 episodes, representing one episode of peritonitis per 5.3 patient months on dialysis. The frequency of peritonitis has decreased in the last 6 months since all patients have been dialysed by two caregivers. The present rate of peritonitis is 1 episode per 10 patient months on dialysis. One patient has died of septicemia secondary to associated congenital abnormalities, one patient has regained renal function, and two patients have been transplanted, one successfully. Five patients are currently dialysing via their abdominal Tenckhoff catheters and awaiting transplantation. We conclude that neonates and infants under 1 year of age can be treated satisfactorily by CPD to enable successful preparation for transplantation later in childhood.     

In vitro bone-cell response to a capacitively coupled electrical field. The role of field strength, pulse pattern, and duty cycle.

Newborn rat calvarial bone cells were grown to confluence and subjected to a matrix of sine wave 60-kHz capacitively coupled electrical signals of various field strengths, pulse-burst patterns, and duty cycles. Both [3H] thymidine incorporation into DNA and alkaline phosphatase activity were evaluated in field strengths ranging from 0.0001 to 20 mV/cm, with pulse-burst patterns ranging from continuous to 5 milliseconds ON/495 milliseconds OFF, with daily duty cycles ranging from 0.25% to 25%. A significant increase in proliferation occurred in field strengths of 0.1, 1, and 20 mV/cm when the signal was applied continuously for six hours. Significant proliferation also occurred when the 20-mV/cm field was pulsed for six hours at 5 milliseconds ON/495 milliseconds OFF and at 5 milliseconds ON/245 milliseconds OFF. No change in alkaline phosphatase activity occurred in the 20-mV/cm field with any signal. At 1 mV/cm, there was a significant decrease in alkaline phosphatase activity in the continuous signal and in the 5 milliseconds ON/62 milliseconds OFF signal; in the lower fields evaluated, there was an actual decrease in alkaline phosphatase activity with some of the signals. The field strength plays a dominant role in determining the bone-cell's proliferative response, and to a lesser extent the alkaline phosphatase activity response, to a capacitively coupled electric field. The pulse configuration and the duty cycle are also important, but only if the proper field strength is being applied to the cell.     

Adenylate cyclase activity as a predictor of thyroid tumor aggressiveness

Prior studies in our laboratory have shown that human thyroid neoplasms have a greater adenylate cyclase activity in response to thyroid stimulating hormone (TSH) than does the adjacent histologically normal thyroid tissue. However, there is little information relating activity of the TSH receptor-adenylate cyclase system to the type of thyroid neoplasm. Thyroid tissue from 67 patients was divided by clinical and histological criteria into 6 categories: normal (59), benign tumors (20), stage 1 carcinoma—intrathyroidal involvement only (25), stage 2 carcinomaregional lymph node involvement (6), stage 3 and 4 carcinoma—tissue invasion or distant metastasis (11), and medullary carcinoma (3). Adenylate cyclase activity in an 8,000 x g thyroid membrane preparation was determined in the basal state and when maximally stimulated with 300 mU/ml TSH. The cyclase responsiveness was the ratio of TSH stimulated adenylate cyclase activity compared to basal adenylate cyclase activity. The cyclase responsiveness by category is: normal, 2.8±0.2 (mean ± SEM); benign, 17.9±2.4; stage 1 carcinoma, 9.2±1.9; stage 2 carcinoma, 4.0±1.0; stage 3 and 4 carcinoma, 1.6±0.4; and medullary carcinoma, 1.05±0.04 (for the neoplasms,p <0.02 by ANOVA). Tumor stage was the only correlate with this trend as other prognostic risk factors (age, sex, a history of neck irradiation, or papillary versus follicular histology) showed no difference in cyclase responsiveness. These studies demonstrate a consistent inverse correlation between adenylate cyclase responsiveness and tumor stage or aggressiveness. Cyclase responsiveness appears to have clinical application for predicting which thyroid tumors will behave aggressively.

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Resumen Estudios previos en nuestro laboratorio han demostrado que los neoplasmas tiroideos humanos poseen una mayor actividad de adenilato ciclasa en respuesta a la administración de hormona estimulante de la tiroides (TSH) que el tejido tiroideo histológicamente normal adyacente. Sin embargo, existe muy poca información sobre la relation de la actividad del sistema receptor de TSH-adenilato ciclasa y el tipo del neoplasma tiroideo. Tejido tiroideo proveniente de 67 pacientes fue dividido mediante criterios chlínicos e histológicos en 6 categorias: normal (59), tumores benignos (20), extensión intratiroidea solamente en estado 1 (25), carcinoma-extensión ganglionar regional en estado 2 (6), carcinoma-invasión tisular o metástasis distantes en estados 3 y 4 (11), y carcinoma medular (3). La actividad de la adenilato ciclasa en una preparación de membrana tiroidea de 8,000 × g fue determinada en el estado basai y en estado de maxima estimulación con 300 mU/ml TSH. El grado de respuesta de la ciclasa fue la tasa de actividad de la adenilato ciclasa estimulada por TSH comparada con la actividad basai de la adenilato ciclasa. El grado de respuesta por categorías fue: normal, 2.8±0.2; tumor benigno, 17.9±2.4; carcinoma estado 1, 9.2±1.9; carcinoma estado 2, 4.0±1.0; carcinoma estados 3 y 4, 1.6±0.4; y carcinoma medular, 1.05±0.04 (para los neoplasmas,p < 0.02 por ANOVA). El estado del tumor apareció como el único factor de correlatión con esta gradación, ya que otros factures de pronóstico (edad, sexo, historia de irradiación cervical, histología papilar versus folicular) no demostraron diferencia en cuanto al grado de respuesta de la ciclasa. Estos estudios demuestran una consistente relación inversa entre el grado de respuesta de la adenilato ciclasa y el estado o agresividad tumoral. El grado de respuesta de la ciclasa parece tener aplicación clínica para predecir qué tumores tiroideos se habrán de comportar en forma agresiva.

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Résumé Les études antérieures provenant de nos laboratoires ont démontré une augmentation de l'activité enzymatique de l'adénylate-cyclase en réponse à la thyroïd stimulating hormone (TSH) dans le tissu thyroïdien humain tumoral, par rapport au tissu thyroïdien adjacent normal. Cependant il existe peu de données concernant l'activité du système récepteur TSH/adénylatecyclase par rapport au type de tumeur de la thyroïde. Les tissus thyroïdiens provenant de 67 patients différents ont été repartis en 6 groupes selon des critères cliniques et histologiques: normal (59), tumeur bénigne (20), cancer stade 1 (intrathyroïdien uniquement) (25), cancer stade 2 (envahissement ganglionnaire régional) (6), cancer stade 3 et 4 (envahissement tissulaire avoisinant ou métastases à distance (11), et cancer médullaire (3). A partir d'une préparation de membrane thyroïdienne centrifugée à 8,000 × g, l'activité de l'adénylate-cyclase a été déterminée en l'état basai et après stimulation maximale par 300 mU/ml de TSH. La réponse enzymatique a été mesurée comme étant le rapport de l'activité stimulée par la TSH/activité basale. Les résultats selon les 6 groupes étaient (moyen±ET): tissu normal, 2.8±0.2; tumeur bénigne, 17.9±2.4; cancer stade 1, 9.2±1.9; cancer stade 2, 4.0±1.0; cancers stade 3 et 4, 1.6±0.4; et cancer médullaire, 1.05±0.04 (p < 0.02 par l'analyse de variance pour les néoplasies). Le stade tumoral était la seule variable corrélée avec l'activité enzymatique. L'activité enzymatique n'était pas corrélée avec l'âge, le sexe, les antécédents d'irradiation cervicale antérieure ou l'histologie (papillaire vs. folliculaire). Ces études montrent un rapport inversement proportionnel entre l'activité d'adénylate-cyclase et le degré d'agressivité tumorale ou le stade. La réponse d l'adénylate-cyclase paraît avoir une application clinique: prévoir quelles tumeurs thyroïdiennes auront une évolution agressive.

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Presented at the International Association of Endocrine Surgeons in Sydney, Australia, September, 1987.

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Supported in part by the Medical Research Service of the Veterans Administration.     

Needle localization biopsy of occult lesions of the breast. Experience in 199 cases

From January 1980 through June 1986, 199 percutaneous needle localizations for clinically occult breast lesions were performed at North Carolina Memorial Hospital. A retrospective analysis of the medical records, mammograms, operative notes, and pathology reports was undertaken to evaluate the success of this procedure. In our series, biopsy was prompted by abnormal calcifications in 27.1% of lesions, occult masses in 37.2%, and by a combination of occult masses and microcalcification in 35.7%. Overall, we had a yield of positive biopsies for cancer of 16.3%, with the yield improving from 12.3% in the earlier years of our study, to 18.7% in the latter years. Of the cancer cases detected, 89.7% were stage I. The localization procedure was successful in 95.9% of the cases. Analysis of our eight failures, along with a review of the literature, shows the major reasons for failure to be incomplete removal of areas with multiple calcifications, dislodgement of the needle, and problems resulting from lack of communication between the radiologist and surgeon. We conclude that the failure rate is low, the yield good, and needle localization a worthwhile procedure for localizing nonpalpable occult lesions.