Impact of Time on Thrombolysis in Cerebral Infarction Score Results.

PURPOSE: Extended thrombolysis in cerebral infarction (eTICI) score results of 2b or higher are known to be predictors for favorable outcome after acute stroke. Additionally, time is a major factor influencing outcome after ischemic stroke. Until today only little is known about the impact of time on angiographic results regarding the outcome after mechanical thrombectomy; however, this impact might be of interest if an initially unfavorable angiographic result has to be improved. METHODS: Retrospective study of 164 patients with large vessel occlusion of the anterior circulation treated by mechanical thrombectomy. Multiple logistic regression analysis of relevant periprocedural and procedural times in respect to the probability of achieving functional independence at 90 days in respect to different eTICI results was performed to build a time and TICI score-dependent model for outcome prediction in which the influence of time was assumed to be steady among the TICI grades. RESULTS: The probability of achieving a favorable outcome is significantly different between eTICI2b-50, 67, TICI2c and TICI3 results (p < 0.001). The odds for achieving a favorable outcome decrease over time and differ for each TICI category and time point. The individual odds for each patient, time point and TICI grade can be calculated based on this model. CONCLUSION: The impact of periprocedural and procedural times and eTICI reperfusion results adds a new dimension to the decision-making process in patients with primary unfavorable angiographic results.

Evaluation of carbapenem-resistant Enterobacteriaceae in an Italian setting: report from the trench.

The spread of carbapenem resistant Enterobacteriaceae (CRE) has recently become a matter of concern in public health, mainly due to the wide distribution of carbapenemase genes. Italy is a country considered endemic for the spread of blaKPC Klebsiella pneumoniae (KP). The aim of this study was to depict the epidemiological trend of CRE in one Italian hospital over a long period (3 years surveillance, from May 2011 to April 2014). Based on defined MIC cut-off for specific carbapenems, 164 strains isolated from 146 different patients were analyzed both phenotypically and genotypically to establish the resistance genes. Molecular typing was performed using the RAPD technique. 77 strains were demonstrated to harbor the blaKPC gene (73 KP, 4 Escherichia coli - EC), 51 strains the blaVIM gene (44 KP, 3 EC, 2 Enterobacter cloacae and 2 Klebsiella oxytoca), 8 the blaNDM gene (3 KP, 4 EC and one Providencia stuartii), 3 the blaOXA-48 gene (2 KP, 1 EC), whereas 25 out of the 164 isolates (of different genera and species) had a negative multiplex-PCR amplification for all the targets tested. 39 out of the 164 strains analyzed (23.8%) revealed discrepancies between the MICs obtained with automated instrument and gradient MICs of more than two logs of difference; the broth microdilution provided a better agreement with the results obtained with the gradient MIC. The use of RAPD allowed to distinguish different clusters, closely related, both for blaKPC and for blaVIM KP.

p38MAPK inhibition: a new combined approach to reduce neuroblastoma resistance under etoposide treatment.

Neuroblastoma (NB) is the second most common solid pediatric tumor and is characterized by clinical and biological heterogeneity, and stage-IV of the disease represents 50% of all cases. Considering the limited success of present chemotherapy treatment, it has become necessary to find new and effective therapies. In this context, our approach consists of identifying and targeting key molecular pathways associated with NB chemoresistance. This study has been carried out on three stage-IV NB cell lines with different status of MYCN amplification. Cells were exposed to a standard chemotherapy agent, namely etoposide, either alone or in combination with particular drugs, which target intracellular signaling pathways. Etoposide alone induced a concentration-dependent reduction of cell viability and, at very high doses, totally counteracted cell tumorigenicity and neurosphere formation. In addition, etoposide activated p38 mitogen-activated protein kinase (MAPK), AKT and c-Jun N-terminal kinase. Pre-treatment with SB203580, a p38MAPK inhibitor, dramatically sensibilized NB cells to etoposide, strongly reducing the dosage needed to inhibit tumorigenicity and neurosphere formation. Importantly, SB203580-etoposide cotreatment also reduced cell migration and invasion by affecting cyclooxygenase-2, intercellular adhesion molecule-1, C-X-C chemokine receptor-4 and matrix metalloprotease-9. Collectively, our results suggest that p38MAPK inhibition, in combination with standard chemotherapy, could represent an effective strategy to counteract NB resistance in stage-IV patients.

Cirugía conservadora en el cáncer de riñón (II): resutados de la enuclación in situ / Copnservative surgery of renal tumor (II): results of tumoral enucleation in situ

Elñ incremento sostenido en el diagnóstico de tumores incidentales de riñón por elempleo extendido de métodos ecográficos y tomográficos, el que aquellos resulten de tamaño relativamente pequeño y que este hecho se relacione con menor agresidad biológica ha llevado a una ampliación de las indicaciones de la cirugía conservadora. La misma se aplicó con técnica de enucleación en 19 pacientes. Cinco de ellos reconocieron indicación imperativa por tumores bilaterales o por tratarse de tumores en riñón único; en los restantes la indicación fue electiva, con tumores unilaterales con riñón contralateral sano. Luego de un tiempo medio de seguimiento de 22,5 meses, 2 pacientes con indicación imperativa mostraron progresión local y a distancia, respectivamente, en tanto que no se detectó recidiva local ni metástasis a distancia en ninguno de los 14 casos de indicación electiva. La incidencia de recidivas parece guardar relación con el grado histológico, el estadio y el tamaño del tumor. El empleo de cirugía conservadora en caos de tumores unilaterales con contralateral sano presupone una cuidadosa slección de los pacientes que serán sometidos a la misma(AU)

Cirugía conservadora en el cáncer de riñón (II): resutados de la enuclación in situ / Copnservative surgery of renal tumor (II): results of tumoral enucleation in situ

Elñ incremento sostenido en el diagnóstico de tumores incidentales de riñón por elempleo extendido de métodos ecográficos y tomográficos, el que aquellos resulten de tamaño relativamente pequeño y que este hecho se relacione con menor agresidad biológica ha llevado a una ampliación de las indicaciones de la cirugía conservadora. La misma se aplicó con técnica de enucleación en 19 pacientes. Cinco de ellos reconocieron indicación imperativa por tumores bilaterales o por tratarse de tumores en riñón único; en los restantes la indicación fue electiva, con tumores unilaterales con riñón contralateral sano. Luego de un tiempo medio de seguimiento de 22,5 meses, 2 pacientes con indicación imperativa mostraron progresión local y a distancia, respectivamente, en tanto que no se detectó recidiva local ni metástasis a distancia en ninguno de los 14 casos de indicación electiva. La incidencia de recidivas parece guardar relación con el grado histológico, el estadio y el tamaño del tumor. El empleo de cirugía conservadora en caos de tumores unilaterales con contralateral sano presupone una cuidadosa slección de los pacientes que serán sometidos a la misma

Cirugía conservadora en el cáncer de riñón (I): resultados de la enucleación tumoral ex vivo / Conservative surgery of renal tumor (I): results of tumoral enucleation "ex vivo"

La cirugía de los tumores de riñón con conservación de órgano reconoce, además de sus indicaciones precisas en casos de monorrenos anatómicos o funcionales o de un tumor bilateral, aplicaciones optativas en pacientes con riñón contralateral sano. Las principales objeciones a esta postura residen en las posibilidades de dejar lesiones residuales por inuficiente exéresis del tumor o por multicentricidad del mismo. La enucleación tumoral es una de las técnicas utilizadas en la cirugía conservadora y con objetivo de establecer sus posibilidades la misma fuie practicada en 26 especímenes de nefrectomía radical por cáncer renal. Los tumores de hasta 4 cm de diámetro no mostraron tumor residual en el lecho ni tumores multicéntricos, en tanto que los de mayor diámetro presentaron estas lesiones en proporción creciente en relación con el tamaño tumoral. Los resultados obtenidos sugieren que la enucleación puede ser utilizada razonablemente en tumores renales menores de 4 cm de diámetro(AU)

Cirugía conservadora en el cáncer de riñón (I): resultados de la enucleación tumoral ex vivo / Conservative surgery of renal tumor (I): results of tumoral enucleation \"ex vivo\"

La cirugía de los tumores de riñón con conservación de órgano reconoce, además de sus indicaciones precisas en casos de monorrenos anatómicos o funcionales o de un tumor bilateral, aplicaciones optativas en pacientes con riñón contralateral sano. Las principales objeciones a esta postura residen en las posibilidades de dejar lesiones residuales por inuficiente exéresis del tumor o por multicentricidad del mismo. La enucleación tumoral es una de las técnicas utilizadas en la cirugía conservadora y con objetivo de establecer sus posibilidades la misma fuie practicada en 26 especímenes de nefrectomía radical por cáncer renal. Los tumores de hasta 4 cm de diámetro no mostraron tumor residual en el lecho ni tumores multicéntricos, en tanto que los de mayor diámetro presentaron estas lesiones en proporción creciente en relación con el tamaño tumoral. Los resultados obtenidos sugieren que la enucleación puede ser utilizada razonablemente en tumores renales menores de 4 cm de diámetro

Effects of pyridostigmine and naloxone on the abnormal TSH response to TRH during starvation in humans.

BACKGROUND: Starvation is associated with a blunted TSH response to thyrotropin-releasing hormone (TRH) (peak minus baseline < 5 mIU/L), despite basal TSH and thyroid hormone levels within the normal range. In light of the inhibitory effect of somatostatin on TSH secretion, we examined whether this condition is caused by an increased hypothalamic somatostatinergic tone in starving subjects. The possible involvement of endogenous opioids in the mechanism underlying the abnormal TSH response to TRH was also evaluated. METHODS: The TSH response to TRH (25 micrograms in an intravenous bolus), serum total and free T4 and T3 levels, and 24-hour urinary-free cortisol levels were measured in 28 normal men (age 27-35 years) within 10% of their ideal body weight. They were randomly divided into 4 groups of 7. In 21 subjects (groups 1, 2, and 3), TRH tests were performed after an overnight (8 hours) fast, placebo administrations (control test), and after prolonged (56 hours) starvation. TRH tests after prolonged starvation were performed either after placebos (in all subjects) or the administration of pyridostigmine (180 mg orally) (in 7 subjects, group 1); naloxone (0.8 mg in an i.v. bolus injection) (in 7 subjects, group 2); or the combination of pyridostigmine and naloxone (in 7 subjects, group 3). The remaining 7 subjects (group 4) were tested at weekly intervals with TRH plus placebo, TRH plus naloxone, TRH plus pyridostigmine, and TRH plus naloxone plus pyridostigmine after a fasting period of 8 hours. RESULTS: In all subjects of groups 1, 2, and 3, TRH-induced TSH rise was significantly lower after prolonged starvation than after overnight fast. Neither pyridostigmine nor naloxone, given alone, changed the basal levels of TSH and the TSH response to TRH after prolonged starvation. In contrast, the concomitant administration of naloxone and pyridostigmine significantly enhanced the TRH-induced TSH rise. After overnight fasting, naloxone administration in group 4 subjects did not change the TSH response to TRH, whereas pyridostigmine significantly enhanced the TSH response to TRH. When naloxone was given together with pyridostigmine and TRH the TSH response was similar to that observed in the TRH plus pyridostigmine test. CONCLUSIONS: These data indicate that naloxone-sensitive endogenous opioids exert an inhibitory effect on the cholinergic stimulatory control of TSH secretion during prolonged starvation. This suggests that an enhanced hypothalamic somatostatinergic activity is involved in the mechanism underlying the reduced TSH response to TRH.

D-dimer after delivery in uncomplicated pregnancies.

UNLABELLED: D-dimer is now widely used as a coagulation marker. During pregnancy the D-dimer level increases until term even in uncomplicated pregnancies. The aim of the study was to establish the D-dimer immediately after delivery in uncomplicated pregnancies. A rapid immunoturbidimetric assay for D-dimer determination was employed in 100 consecutive deliveries. D-dimer level increased significantly in all women after delivery (increase from 1 to more than 10 times over the normal range). CONCLUSION: An increase in fibrinolysis is associated with pregnancy and delivery, and D-dimer level must be interpreted only in association with other clinical, laboratory and instrumental methods when pathological conditions (e.g. pulmonary embolism, deep vein thrombosis or disseminated coagulation) are suspected.

Stimulation of ACTH and GH release by angiotensin II in normal men is mediated by the AT1 receptor subtype.

This study was performed in order to determine whether the stimulatory effect of plasma angiotensin II (ANG II) on Adrenocorticotropic hormone (ACTH) and growth hormone (GH) secretion in humans is mediated by AT1 subtype receptors. For this purpose, the effects of the administration of the AT1 receptor antagonist, losartan (50 mg p.o.) or a placebo on the ACTH and GH responses to ANG II (i.v. infusion for 60 min of successively increasing doses (4, 8 and 16 ng/kg/min); each dose for 20 min) were evaluated in eight normal men. ANG II infusion induced significant increases in both serum ACTH and GH levels (mean peaks were 1.6- and four-times higher than baseline, respectively). The ACTH response to ANG II was completely abolished by pretreatment with losartan. Also, the ANG II-induced GH rise was reduced by administration of losartan, but the GH response was still significantly higher than the basal value (mean peak was twice as high as the baseline). These data provide evidence of AT1 receptor involvement in mediation of the ANG-II stimulating effect on ACTH and GH secretion.

Different effects of naloxone on the growth hormone response to melatonin and pyridostigmine in normal men.

The effect of melatonin (MEL) (12 mg orally), pyridostigmine (60 mg orally), the combination of MEL and pyridostigmine, or placebo on growth hormone (GH) secretion was tested in seven normal men. In addition, MEL tests and pyridostigmine tests were repeated after pretreatment with naloxone (1.2-mg bolus followed by intravenous [i.v.] infusion of 1.6 mg/h for 3 hours). Serum GH levels increased fivefold after MEL and sixfold after pyridostigmine administration. The concomitant administration of MEL did not change the GH response to pyridostigmine. In the presence of naloxone, the GH response to MEL was completely abolished, whereas naloxone did not modify the pyridostigmine-induced GH increase. These data suggest that MEL and pyridostigmine stimulate GH secretion through a common mechanism, which is probably represented by the inhibition of somatostatin activity. However, in contrast to pyridostigmine, the action of MEL appears to be exerted through a naloxone-sensitive opioid mediation.

Different effects of pyridostigmine on the thyrotropin response to thyrotropin-releasing hormone in endogenous depression and subclinical thyrotoxicosis.

Primary organic disorders of the thyroid gland must be excluded in interpreting the thyrotropin (TSH)-releasing hormone (TRH) test in affective disease. Both endogenous depression and subclinical thyrotoxicosis are frequently associated with low basal TSH levels and a blunted (<5 mIU/L) TSH response to TRH despite thyroid hormone levels within the normal range. The present study was performed to establish whether a reduction of the hypothalamic somatostatinergic tone by treatment with the acetylcholinesterase inhibitor pyridostigmine before TRH might be useful to distinguish endocrine from affective diseases. Twelve male depressed patients (aged 41.4 +/- 3.1 years) and 12 men (aged 43.4 +/- 4.1 years) with subclinical thyrotoxicosis because of autonomous thyroid nodules were selected according to the presence of a low basal TSH level and a blunted TSH response to 200 microg TRH intravenously (IV) (TSH increment was <5 mIU/L at 30 minutes [peak] after TRH) but thyroid hormone levels within the normal range. All patients were tested again with TRH 60 minutes after treatment with 180 mg pyridostigmine orally. Eleven normal men served as controls. Basal TSH levels were 0.2 +/- 0.2 mIU/L (mean +/- SE) in depression and 0.1 +/- 0.2 in subclinical thyrotoxicosis (normal controls, 1.4 +/- 0.3). In both groups, the mean peak response to TRH was significantly higher than baseline; however, according to selection, the TSH increase was less than 5 mIU/L. Pyridostigmine did not change basal TSH levels in any group, but significantly enhanced the TRH-induced TSH increase in normal controls and in depressed subjects (TSH increment became >7 mIU/L in all depressed subjects). In contrast, no significant change in the TSH response to TRH was observed in subclinical thyrotoxicosis after pyridostigmine treatment. Basal and TRH- and pyridostigmine + TRH-induced TSH levels were significantly higher in the normal controls than in the other groups. These data show a cholinergic involvement in the blunted TSH response to TRH in patients with endogenous depression, but not in subjects with subclinical thyrotoxicosis, suggesting that these diseases could be separated on the basis of the pyridostigmine + TRH-induced TSH response test.

Abnormal effect of cigarette smoking on pituitary hormone secretions in insulin-dependent diabetes mellitus.

OBJECTIVE: We observed the effect of smoking two cigarettes on GH, AVP and cortisol secretion in patients with diabetes and normal subjects. DESIGN AND PATIENTS: We tested 10 male smokers with insulin-dependent diabetes mellitus (IDDM) and 10 normal smokers. On a different occasion, normal and diabetic smokers were tested with an insulin (0.15 U/kg body weight) tolerance test (ITT). MEASUREMENTS: Hypoglycaemia-induced hormonal responses in smokers were compared with those observed in 10 diabetic and 10 normal non smokers. RESULTS: All subjects showed similar basal GH, cortisol and AVP levels. In the normal subjects, cigarette smoking induced a significant increase in circulating GH, AVP and cortisol levels, with mean peaks 3.3, 3 and 1.58 times higher than baseline, respectively. Smoking-induced hormonal responses were significantly higher in diabetics (mean peak was 5.2 times higher than baseline for GH, 4.0 for AVP and 1.83 for cortisol). Insulin induced a similar hypoglycaemic nadir in all subjects at 30 minutes, even though the diabetic subjects had a delayed recovery in blood glucose levels. GH and AVP responses to hypoglycaemia were significantly higher in diabetic (mean peaks 11.5 and 3.2 times higher than baseline, respectively) than in normal (mean peaks 7.3 and 1.9) non-smokers, whereas these groups showed similar cortisol responses (mean peak 2.3 times higher than baseline). Smoking did not change any hypoglycaemia-induced hormonal rise in the normal controls, whereas it significantly enhanced GH, AVP and cortisol levels (mean peaks 14.5, 4 and 3.8 times higher than baseline, respectively) in diabetics. CONCLUSIONS: In patients with IDDM, cigarette smoking not only elicits higher GH, AVP and cortisol responses than in normal subjects, but also enhances the counter-regulatory hormone responses to insulin-induced hypoglycaemia. These findings suggest interactions between nicotine inhaled with cigarette smoking and diabetes-induced neuroendocrine alterations.

Significado y conducta frente a márgenes positivos y compromiso ganglionar en pacientes con cáncer de próstata tratados con prostatectomía radical / Significance and management of positive margins and ganclionar involvement en patientes with prostatic cancer treated with radical prostatectomy

La estadificación previa a la prostatectomía radical de 43 pacientes con cáncer prostático clínicamente localizado arrojó porcentajes relativamente elevados de subestratificacion (46 porciento). Catorce pacientes presentaron márgenes positivos de exéresis con invasión a vesículas seminales en 6 de ellos (estadio C). Otros 6 tuvieron compromiso ganglionar microscópico (estadio DI). Diez de los casos con márgenes positivos tuvieron expresión bioquímica (APE>0,2 ng/ml) de enfermedad residual o progresión y uno de ellos, manifestación clínica de progresión local. Diez pacientes de este grupo fueron adecuadamente controlados (16 a 67 meses) con adyuvancia hormonal. Los 6 pacientes con estadio DI se mantienen clínica y bioquímicamente controlados (16 a 67 meses) con la adyuvancia hormonal. Cirugía y bloqueo androgénico total aparece como una alternativa a tener en cuenta en pacientes con estadios C y DI(AU)

Significado y conducta frente a márgenes positivos y compromiso ganglionar en pacientes con cáncer de próstata tratados con prostatectomía radical / Significance and management of positive margins and ganclionar involvement en patientes with prostatic cancer treated with radical prostatectomy

La estadificación previa a la prostatectomía radical de 43 pacientes con cáncer prostático clínicamente localizado arrojó porcentajes relativamente elevados de subestratificacion (46 porciento). Catorce pacientes presentaron márgenes positivos de exéresis con invasión a vesículas seminales en 6 de ellos (estadio C). Otros 6 tuvieron compromiso ganglionar microscópico (estadio DI). Diez de los casos con márgenes positivos tuvieron expresión bioquímica (APE>0,2 ng/ml) de enfermedad residual o progresión y uno de ellos, manifestación clínica de progresión local. Diez pacientes de este grupo fueron adecuadamente controlados (16 a 67 meses) con adyuvancia hormonal. Los 6 pacientes con estadio DI se mantienen clínica y bioquímicamente controlados (16 a 67 meses) con la adyuvancia hormonal. Cirugía y bloqueo androgénico total aparece como una alternativa a tener en cuenta en pacientes con estadios C y DI

Influence of residual C-peptide secretion on the arginine vasopressin response to hypoglycaemia and metoclopramide in insulin-dependent diabetes.

Arginine vasopressin (AVP) hypersecretion in response to metoclopramide or to insulin-induced hypoglycaemia has been described in type I diabetes mellitus. In the present study, we examined whether residual endogenous insulin secretion may play a role in the control of this abnormal AVP secretory pattern. For this purpose, 21 insulin-dependent diabetic men and 10 age- and weight-matched normal men were tested with MCP (20 mg in an i.v. bolus). On a different occasion, subjects were tested with insulin (0.15 IU kg-1). The diabetic patients were subdivided into C-peptide negative patients (CpN, 11 patients without detectable endogenous pancreatic beta cell activity) (group I) and C-peptide positive patients (CpP, 10 patients with residual endogenous insulin secretion) (group II). Experiments started after optimization of the metabolic status of the diabetic men by 3 days of treatment with continuous subcutaneous insulin infusion. The basal concentrations of AVP were similar in all groups. The administration of MCP induced a striking elevation in plasma AVP levels in the normal controls and in the diabetic subjects of groups I and II. However, the AVP rise was significantly higher in group I and group II than in normal controls. Furthermore, group I diabetics showed higher AVP increments than group II. Insulin induced a similar hypoglycaemic nadir in all subjects at 30 min, even though the diabetic subjects of groups I and II had a delayed recovery in blood glucose levels. The hypoglycaemic pattern was similar in group I and II. Hypoglycaemia induced a striking AVP increase in the normal controls.(ABSTRACT TRUNCATED AT 400 WORDS)

Dopaminergic and cholinergic control of arginine-vasopressin secretion in type I diabetic men.

Enhanced cholinergic and dopaminergic controls of anterior pituitary function have been described in insulin-dependent diabetes mellitus (IDDM). In order to verify whether similar neurotransmitter alterations also affect the regulation of posterior pituitary hormone secretion, the arginine-vasopressin (AVP) responses to the dopaminergic agonist apomorphine and in a different occasion to physostigmine, an acetylcholinesterase inhibitor, were evaluated in normal (n = 10) and type I diabetics (n = 16). In addition, a control test with normal saline was performed in all subjects. None of the diabetic patients were affected by neuropathy or other diabetic complications. They were divided into two groups according to the duration of their disease (less than 10 years: group 1, n = 8; more than 10 years: group 2, n = 8). Physostigmine (12.5 micrograms kg-1) was infused intravenously over 10 min; apomorphine (60 micrograms kg-1) was injected subcutaneously. Basal AVP concentrations were similar in all groups and remained constant during the control test. In contrast, both drugs induced significant increments in plasma AVP levels in the normal controls and diabetic subjects. However, physostigmine- and apomorphine-induced AVP increments were twofold higher in diabetics than in control subjects. No significant differences were observed between diabetics of groups 1 and 2. No significant correlations between duration of diabetes and peak AVP responses to physostigmine or apomorphine were found within each group or when all diabetic subjects were considered together. These data indicate enhancement of both dopaminergic and cholinergic stimulatory regulations of AVP secretion in patients with uncomplicated IDDM, regardless of the duration of diabetes.

Opioid modulation of the gamma-aminobutyric acid-controlled inhibition of exercise-stimulated growth hormone and prolactin secretion in normal men.

The possible involvement of endogenous opioids in the gamma-aminobutyric acid-controlled (GABAergic) inhibition of growth hormone (GH) and prolactin (PRL) during physical exercise was evaluated in normal men. After fasting overnight, seven subjects were tested on four mornings at least 1 week apart. Exercise was performed on a bicycle ergometer. The workload was gradually increased at 3-min intervals until exhaustion and lasted about 15 min in all subjects. Tests were carried out under administration of placebo, the opioid antagonist naloxone (10 mg as an iv bolus injection), the GABAergic agonist sodium valproate (600 mg in three divided doses orally) or naloxone plus sodium valproate. During exercise, plasma GH and PRL levels rose 5.5- and 1.9-fold, respectively. The administration of naloxone did not modify, whereas sodium valproate significantly reduced the plasma GH and PRL rise during exercise. In the presence of sodium valproate, GH and PRL levels rose 3- and 1.5-fold, respectively, in response to exercise. When naloxone was given together with sodium valproate, both GH and PRL responses to exercise were abolished completely. These data suggest the involvement of a GABAergic mechanism in the regulation of GH and PRL responses to physical exercise in men. Furthermore, the data argue against a role of naloxone-sensitive endogenous opioids in the control of these hormonal responses to exercise, whereas they suggest a modulation by opioids of the GABAergic inhibitory action.

Influence of thyroid status on the paradoxical growth hormone response to thyrotropin-releasing hormone in human obesity.

Thyrotropin-releasing hormone (TRH) tests were performed in 38 age- and weight-matched obese but otherwise healthy men. In all subjects, total thyroxine (T4) and triiodothyronine (T3) concentrations were in the normal range. According to basal and TRH-stimulated serum thyrotropin (TSH) levels, subjects were divided into the following three groups: group I (n = 14), euthyroid subjects; group II (n = 11), euthyroid subjects with normal basal but abnormally elevated TSH responses to TRH; group III (n = 13), subjects with elevated basal and TRH-induced TSH levels (subclinical hypothyroidism). Basal TSH levels were 1.8 +/- 0.4 mU/L in group I, 1.7 +/- 0.3 in group II, and 6.0 +/- 0.7 in group III. In both groups II and III, TRH-induced TSH increments were above the normal range (maximal increment > 14 mU/L) and were significantly higher than in group I. The definition of euthyroidism for groups I and II and of subclinical hypothyroidism for group III according to the basal levels of TSH was confirmed by clinical (Billewicz index), hormonal (serum free-T4 levels), and metabolic (serum apoprotein [apo] AI levels) parameters. Basal concentrations of growth hormone (GH) were similar in all groups. When GH levels after TRH stimulation were measured, significant increments (peak minus baseline > 5 micrograms/L) were observed in nine of 13 hypothyroid obese men. The overall mean peak GH increase in group III was 4.5 times higher than baseline and was observed at 45 minutes. None of the euthyroid obese subjects of groups I and II showed any significant change in GH levels in response to TRH.(ABSTRACT TRUNCATED AT 250 WORDS)