Transition to parenthood and mental health at 30 years: a prospective comparison of mothers and fathers in a large Brazilian birth cohort.

Parenthood represents a major biological, social and environmental life change. Mental health disorders are common in parents and impact both the parent and their offspring. However, the relationship between parenthood and mental health and the direction of these effects are poorly understood. Longitudinal data from the Pelotas 1982 birth cohort, Southern Brazil, on 3701 individuals was used to investigate the association between number of children by age 30 years and mental health disorders using DSM-IV diagnoses at age 30 years, suicidal risk and the change in symptoms using repeated measures (using the SRQ-20) from age 19 to 30 years. Mothers, but not fathers, with higher number of children by age 30 years, were at a substantially increased risk of a wide range of mental health disorders compared to women with no children. There was evidence that motherhood was associated with an increase in symptoms over time rather than higher symptoms at baseline. Younger age at first child was also a risk factor for mental health disorders. Mothers, particularly those with multiple children, are at risk of a wide range of mental health disorders. The mechanisms to explain these risks are yet to be elucidated; however, the risk of mental health disorders was not replicated in fathers, which would be expected if residual confounding explained observed associations. Thus, multiparous mothers represent a high-risk group and should be prioritised for supportive interventions.

Exploring DSM-5 ADHD criteria beyond young adulthood: phenomenology, psychometric properties and prevalence in a large three-decade birth cohort.

BACKGROUND: There are still uncertainties on the psychometric validity of the DSM-5 attention deficit hyperactivity disorder (ADHD) criteria for its use in the adult population. We aim to describe the adult ADHD phenotype, to test the psychometric properties of the DSM-5 ADHD criteria, and to calculate the resulting prevalence in a population-based sample in their thirties. METHOD: A cross-sectional evaluation using the DSM-5 ADHD criteria was carried out in 3574 individuals from the 1982 Pelotas Birth Cohort. Through receiver operator curve, latent and regression analyses, we obtained parameters on construct and discriminant validity. Still, prevalence rates were calculated for different sets of criteria. RESULTS: The latent analysis suggested that the adult ADHD phenotype is constituted mainly by inattentive symptoms. Also, inattention symptoms were the symptoms most associated with impairment. The best cut-off for diagnosis was four symptoms, but sensitivity and specificity for this cut-off was low. ADHD prevalence rates were 2.1% for DSM-5 ADHD criteria and 5.8% for ADHD disregarding age-of-onset criterion. CONCLUSIONS: The bi-dimensional ADHD structure proposed by the DSM demonstrated both construct and discriminant validity problems when used in the adult population, since inattention is a much more relevant feature in the adult phenotype. The use of the DSM-5 criteria results in a higher prevalence of ADHD when compared to those obtained by DSM-IV, and prevalence would increase almost threefold when considering current ADHD syndrome. These findings suggest a need for further refinement of the criteria for its use in the adult population.

Complete meiosis from human induced pluripotent stem cells.

Gamete failure-derived infertility affects millions of people worldwide; for many patients, gamete donation by unrelated donors is the only available treatment. Embryonic stem cells (ESCs) can differentiate in vitro into germ-like cells, but they are genetically unrelated to the patient. Using an in vitro protocol that aims at recapitulating development, we have achieved, for the first time, complete differentiation of human induced pluripotent stem cells (hiPSCs) to postmeiotic cells. Unlike previous reports using human ESCs, postmeiotic cells arose without the over-expression of germline related transcription factors. Moreover, we consistently obtained haploid cells from hiPSCs of different origin (keratinocytes and cord blood), produced with a different number of transcription factors, and of both genetic sexes, suggesting the independence of our approach from the epigenetic memory of the reprogrammed somatic cells. Our work brings us closer to the production of personalized human gametes in vitro.

The impact of maternal post-partum depression on the language development of children at 12 months.

BACKGROUND: Language is one of the most important acquisitions made during childhood. Before verbal language, a child develops a range of skills and behaviours that allow the child to acquire all communication skills. Factors such as environmental factors, socio-economic status and interaction with parents can affect the acquisition of vocabulary in children. Post-partum depression can negatively affect the first interactions with the child and, consequently, the emotional, social and cognitive development of the child. OBJECTIVE: To analyse the effect of the duration of the mother's depression on the language development of children at 12 months old. METHODS: This was a longitudinal study. The participants of this study were mothers who had received prenatal care from the Brazilian National System of Public Health in Pelotas city, State of Rio Grande do Sul, Brazil. The mothers were interviewed at two different time points: from 30 to 90 days after delivery and at 12 months after delivery; the children were also evaluated at this later time point. To diagnose maternal depression, we used the Mini International Neuropsychiatric Interview, and to assess child development, we used the language scale of the Bayley Scales of Infant Development III. RESULTS: We followed 296 dyads. Maternal depression at both time points (post partum and at 12 months) was significantly associated with the language development of infants at 12 months of age. This impact was accentuated when related to the duration of the disorder. Older women and women with more than two children were more likely to have children with poorer language development, while women who were the primary caregiver had children with higher scores on the language test. CONCLUSION: The findings indicate that maternal age, parity, primary caregiver status and duration of post-partum depression are associated with the language development of the child.

The second Mexican consensus on hepatocellular carcinoma. Part I: Epidemiology and diagnosis.

Hepatocellular carcinoma (HCC) is more frequently manifesting as one of the main complications of cirrhosis of the liver, its principal risk factor. There have been modifications in its incidence over the past decade, related to an epidemiologic transition in the etiology of cirrhosis, with a decrease in the prevalence of hepatitis C and an increase in nonalcoholic fatty liver disease (NAFLD) as a cause, as well as the development of HCC in the non-cirrhotic liver due to NAFLD. Genetic markers associated with the disease have been identified, and surveillance and diagnosis have improved. Regarding treatment, surgical techniques, in both resection and transplantation, have advanced and radiologic techniques, at the curative stage of the disease, have enhanced survival in those patients. And finally, there have been radical changes in the systemic approach, with much more optimistic expectations, when compared with the options available a decade ago. Therefore, the Asociación Mexicana de Hepatología decided to carry out the Second Mexican Consensus on Hepatocellular Carcinoma, which is an updated review of the available national and international evidence on the epidemiology, risk factors, surveillance, diagnosis, and treatment of the disease, to offer the Mexican physician current information on the different topics regarding hepatocellular carcinoma. In this first part of the document, the topics related to epidemiology and diagnosis are presented.

The second Mexican consensus on hepatocellular carcinoma. Part II: Treatment.

Hepatocellular carcinoma (HCC) is more frequently manifesting as one of the main complications of cirrhosis of the liver, its principal risk factor. There have been modifications in its incidence over the past decade, related to an epidemiologic transition in the etiology of cirrhosis, with a decrease in the prevalence of hepatitis C and an increase in nonalcoholic fatty liver disease (NAFLD) as a cause, as well as the development of HCC in the non-cirrhotic liver due to NAFLD. Genetic markers associated with the disease have been identified, and surveillance and diagnosis have improved. Regarding treatment, surgical techniques, in both resection and transplantation, have advanced and radiologic techniques, at the curative stage of the disease, have enhanced survival in those patients. And finally, there have been radical changes in the systemic approach, with much more optimistic expectations, when compared with the options available a decade ago. Therefore, the Asociación Mexicana de Hepatología decided to carry out the Second Mexican Consensus on Hepatocellular Carcinoma, which is an updated review of the available national and international evidence on the epidemiology, risk factors, surveillance, diagnosis, and treatment of the disease, to offer the Mexican physician current information on the different topics regarding hepatocellular carcinoma. In this second part of the document, the topics related to the treatment of HCC are presented.

Hidden mosaicism in patients with Klinefelter's syndrome: implications for genetic reproductive counselling.

BACKGROUND: Most individuals with Klinefelter's syndrome (KS) are azoospermic but residual foci of spermatogenesis have been observed in some patients. However, no consistent predictive factors for testicular sperm extraction success have been established and mosaicism could be a factor to investigate. In this study, we have assessed the degree of mosaicism in somatic and germinal tissues in KS, the meiotic competence of 47,XXY germ cells and the aneuploidy rate of post-reductional cells. METHODS: Five patients with KS previously diagnosed as pure 47,XXY have been studied. Samples from four donors were processed as controls. The chromosome constitution of lymphocytes, buccal mucosa and testicular tissue was assessed by interphase fluorescence in situ hybridization for chromosomes X, Y and 18. In meiotic figures, sex chromosome number and pairing was confirmed. RESULTS: 46,XY cell lines were observed in all patients and tissues analysed. The degree of mosaicism (mean ± SD) differed among tissues (lowest in lymphocytes: 4.8 ± 2.5%; highest in Sertoli cells: 42.3 ± 11.1%). Meiotic figures were found in three cases (KS1, KS2 and KS5), all of them showed an XY complement. Hyperhaploid post-reductional cells were found in all patients (range: 3.3-36.4%) and increased rates versus controls (P< 0.05) were observed. CONCLUSIONS: Diagnosis of homogeneous KS based on lymphocyte karyotyping should be contrasted in other tissues. Mucosa cells could help to better approximate the degree of germ cell mosaicism. Our results indicate that 47,XXY germ cells are not meiotically competent. Increased post-reductional aneuploidy rate is related to meiotic errors in 46,XY cells. Appropriate genetic counselling is recommended in KS.

[Genotyping and antibacterial resistance of Campylobacter spp strains isolated in children and in free range poultry]. / Genotipificación y resistencia antibacteriana de cepas de Campylobacter spp aisladas en niños y en aves de corral.

Poultry is a main reservoir and source of human infection in campylobacteriosis. Three hundred and forty one stool samples (291 human, 50 avian) were analyzed. In the human group, 220 samples were collected from children with acute diarrheal disease (183 inpatients, 37 outpatients) and 71 from healthy children. Erythromycin and ciprofloxacin agar dilution MIC tests, Penner serotyping and RAPD-PCR genotyping were performed on 23 strains isolated. C. jejuni was reported only in patients with acute diarrhea (5.4% inpatients, 2.2% outpatients). Campylobacter prevalence in poultry was 34%. Cross-resistance to nalidixic acid and ciprofloxacin was found in 33.3% of human samples and 11.8% of animal samples. Human samples could not be typed using the Penner method. F serotype was the most expressed in poultry. We obtained a total of 14 genotypes (4 / 5 human and 10/15 avian). In conclusion, the predominant species in poultry and humans was C. jejuni, a significant amount of quinolone-resistant human and avian samples were obtained, and avian genotypes and serotypes were not found in human samples. The latter would mean that another source of infection could exist; therefore other reservoirs must be studied.

Influence of extracardiac activity and perfusion abnormalities on myocardial perfusion gated SPECT parameters: interobserver analysis.

OBJECTIVE: Extracardiac activity (ECA) may affect interpretation of gated SPECT myocardial perfusion studies (MPSs). To solve this problem, available softwares include myocardial edge delimitation. PURPOSE: To evaluate the influence of ECA in automatic myocardial edge detection under normal conditions and with abnormal perfusion and also evaluate the reproducibility of semi-automatic processing. METHODS: A total of 100 MPSs, 50 with ECA, were analyzed. Each subgroup included 25 cases with perfusion abnormalities. The cases were processed automatically and by 4 independent operators with different levels of experience. Commercial QGS and QPS softwares were used with tools to mask and relocate the left ventricle area. Functional parameters (final diastolic and systolic volumes and ejection fraction) and perfusion parameters such as the reversibility perfusion score and rest perfusion defect extension were analyzed. The data were compared with Pearson's correlation and Student's test. RESULTS: Interobserver correlation significantly worsened with the presence of ECA and was moderately affected by perfusion abnormalities. More experienced observers presented better correlation. Reproducibility was greater for the functional perfusion parameters, independently of the observer's experience. CONCLUSIONS: ECA significantly affects automatic edging delimitation, affecting the MPS values. Interobserver reproducibility with manual processing was more altered regarding functional parameters than in the perfusion scores. Perfusion abnormalities did not interfere with software reproducibility, and when present, better correlation was found. If ECA is not present, manual intervention should be avoided.

[Agreement between observers with different experience in the interpretation of the stress myocardial perfusion electrocardiogram in SPECT]. / Concordancia entre observadores con distinta experiencia en interpretación de electrocardiograma de esfuerzo en SPECT de perfusión miocárdica.

UNLABELLED: Coronary artery disease (CAD) is the leading cause of death in many countries. Stress electrocardiogram (ECG) is able to detect myocardial ischemia and also has prognostic value, which may be impaired in presence of electrical baseline abnormalities. Stress myocardial single photon emission tomography (SPECT) has recognized utility yield in assessment of CAD, requiring independent interpretation of ECG and myocardial images. PURPOSE: To analyze stress ECG interpretation reproducibility among observers with different training level, including pre- and post-graduate medical students, compared to an experienced cardiologist and also with SPECT. METHOD: We studied 95 patients under CAD evaluation, mean age 61+/-9.3 years (range: 42-85), 56% male. Interobserver correlation kappa (k) between perfusion gated (99m)Tc-Sestamibi SPECT and exercise ECG were calculated as normal/abnormal, presence of necrosis, ischemia or mixed pattern. Interobserver kappa (k) analysis was made. RESULTS: 49.5% stress ECG and 45% SPECT studies were abnormal at the initial report with 62.1% concordance (k: 0.24) for normal/abnormal and 58.9% for ischemia (k: 0.14). Agreement between stress ECG initial report and independent cardiologist was 89.5% (k: 0.78). The correlation between independent observers and the initial report ranged between 62.1% and 48.4%, for baseline ECG between 41.1% and 90.5% considering normal/abnormal, and between 80% and 93.7% (k: 0.59-0.87) for the presence of ischemia. CONCLUSION: Stress ECG interpretation presented adequate interobserver reproducibility with greater agreement in the most experienced observers, confirming the importance of training.

Helicobacter pylori eradication in Mexico with a levofloxacin-based scheme versus standard triple therapy: Results from an open-label, randomized, noninferiority phase iiib trial. / Erradicación de Helicobacter pylori en México con un esquema basado en levofloxacina versus la triple terapia estándar: resultados de un estudio clínico de fase iiib, abierto, aleatorizado, de no inferioridad.

INTRODUCTION AND AIMS: Helicobacter pylori (H. pylori) infection remains the leading cause of several gastroduodenal diseases. Despite the fact that multiple antibiotic regimens have been used to change its associated morbidity and mortality, the prevalence of this bacterial infection continues to be disproportionately high worldwide, mainly due to antibiotic resistance. To assess the noninferiority efficacy and safety of 210-day triple regimens on H. pylori eradication, we evaluated clarithromycin 500mg, lansoprazole 30mg, and amoxicillin 1g, all bid (standard triple therapy or CLA, Group 1) vs. pantoprazole 80mg, levofloxacin 500mg and azithromycin 500mg, all od (PLA, Group 2). Both regimens were compared in treatment-naïve patients. MATERIALS AND METHODS: An open label phase IIIb randomized and noninferiority trial comparing CLA vs. PLA was carried out for a 10-day period, within the time frame of June 2012 and March 2014. Eradication was verified with 13C-urea breath testing. Gastric biopsies were tested for fluorescence in situ hybridization (FISH)-clarithromycin resistance prior to any antibiotic administration. Efficacy and safety results were analyzed according to the noninferiority methodological approach. RESULTS: From the 227 H. pylori positive subjects that were randomized, 194 were finally analyzed as per-protocol. The group 2 eradication rate was 63% and was noninferior to the group 1 eradication rate of 58.5% (upper limit 95% CI: 0.11608; below the noninferiority margin: 0.1200). FISH clarithromycin-resistance was found in 28.2% of the cases. Adverse events, all minor and self-limited, were significantly higher in group 1 than in group 2 (86 vs. 65.4%; p=0.001). CONCLUSIONS: First-line H. pylori eradication with pantoprazole/levofloxacin/azithromycin combination therapy is as effective as the standard triple therapy, with better tolerability and easier dosing. Clarithromycin resistance should be considered when selecting antibiotics in Helicobacter pylori eradication treatments. ClinicalTrials.gov identifier NCT02726269.

[Interobserver correlation in the interpretation of 99mTc-sestamibi SPECT in reperfused acute myocardial infarction]. / Correlación interobservadores en interpretación de SPECT de perfusión con 99mTc-sestamibi en infarto agudo de miocardio reperfundido.

INTRODUCTION AND OBJECTIVES: The correct interpretation of myocardial perfusion single photon emission computed tomography (SPECT) requires knowledge of the technique reproducibility. The objective was analyze the interobserver correlation of different experience in the interpretation of myocardial perfusion SPECT in patients following acute myocardial infarction (AMI) in order to improve the quality of our site. METHODS: Sixty cases (56 +/- 11 years, 87 % men) with transmural AMI who had recently undergone successful thrombolysis were included. Resting perfusion with (99m)Tc-sestamibi was performed at one week post-AMI. ANALYSIS: Semiquantitative interpretation using 17 segment-model by 2 independent specialists and 5 observers, was performed blindly. Left ventricular ejection fraction (LVEF) was measured with isotopic ventriculography one month after AMI, with a mean of 38 %. RESULTS: Using independent and then agreed on perfusion analysis, average involved segments/patient was 9.3 +/- 4 and the sum of severity 25 +/- 13. Readings of other observers ranged from 7 +/- 3.7 to 9.4 +/- 3.9 and 16.7 +/- 9.7 to 24.6 +/- 13, respectively, consistent with the reading of the specialists of between 0.779-0.871 (kappa: 0.565-0.741). There was no significant difference when the number of segments were analyzed in 40 % of the cases and for intensity in 60 % of them in more experienced observers. Correlation with consensus reading for the number of segments ranged from 0.84 to 0.94 and for severity from 0.79 to 0.89. Identification of culprit arteries was acceptable, with r values between 0.612 and 0.683 and kappas between 0.629 and 0.656. Correlation of the number of involved segments and severity with LVEF performed one month after AMI was 0.73 and 0.74, respectively. CONCLUSIONS: There was good correlation in the interpretation of myocardial perfusion SPECT, with a significantly better fit in more experienced observers. This academic exercise was also helpful in improving our residents' skills in cardiology.

Consequences of quality of reduction on osteosynthesis complications and quality of life in elderly patients with subtrochanteric fracture. / Consecuencias de la calidad de reducción sobre complicaciones en la osteosíntesis y calidad de vida en pacientes adultos de edad avanzada con fractura subtrocantérea.

OBJECTIVE: To compare results in terms of orthopaedic complications and quality of life in elderly patients with subtrochanteric fracture treated with intramedullary nailing according to fracture reduction status. PATIENTS AND METHODS: A prospective cohort study including 90 elderly patients with subtrochanteric fractures of the femur treated with a cephalomedullary nail, with a minimum 1-year follow up. The inclusion criteria were: aged 60 years or older, without severe cognitive dysfunction and independent ambulatory capability before the fracture. We defined 3different groups in relation to fracture reduction status: good, acceptable and poor, according to modified criteria from Baumgartner et al. We compared clinical and surgical characteristics and healthy quality of life, social function and mobility according to the EQ-5D, Jensen Index and Mobility Score of Parker and Palmer questionnaires. RESULTS: We found differences in time to union, better in the good reduction group (P=.002); need for open reduction, more frequent in the good reduction group (P<.001), and in postoperative complications, more frequent in the poor reduction group (P=.001). We found no significant differences between the 3groups regarding scores in quality of life, social function and mobility. CONCLUSIONS: Reduction in subtrochanteric fractures in older people is key to obtaining better clinic and surgical results, improving time to union and decreasing surgical complications. Exposure of the focus fracture seems to be a safe manoeuvre. Quality of life had substantially deteriorated n these patients, but a there was a tendency, although not statistically significant, for it to improve in patients after good surgical reduction.

Osteoporosis grave secundaria a enfermedad de Gaucher: reporte de caso / Severe osteoporosis secondary to Gaucher disease: case report

La enfermedad de Gaucher (EG) es un trastorno genético lisosomal autosómico recesivo infrecuente, que conduce a la acumulación de lípidos y disfunción en múltiples órganos. La afectación del esqueleto es uno de los hallazgos más frecuentes de la EG y una de las principales causas de dolor y reducción de calidad de vida. El compromiso esquelético incluye anomalías en el remodelado óseo con pérdida mineral ósea, adelgazamiento cortical, lesiones líticas, fracturas por fragilidad y deformidades articulares. A continuación presentamos el caso de una paciente 61 años con osteoporosis grave secundaria a EG diagnosticada en la vida adulta, con antecedente de dos hermanas con EG. La paciente refería dolores óseos y lumbago crónico desde los 53 años. El 2012 fue evaluada en policlínico de hematología por trombocitopenia y debido a sus antecedentes familiares se le solicitaron exámenes que fueron compatibles con EG. El año 2016 la densitometría ósea (DXA) de columna lumbar y cuello femoral izquierdo, que mostró una osteoporosis. Se inició tratamiento con Alendronato, Calcio y Vitamina D, pero la paciente tuvo escasa adherencia. El 2018 se inició tratamiento de su EG con Taliglucerasa α. Al año siguiente se le realizó nueva DXA que evidenció persistencia de la osteoporosis y por mantención del lumbago se le solicitó una TAC de columna lumbar que mostró fracturas por aplastamiento de cuerpos vertebrales dorsales bajos. Se derivó a endocrinología para manejo de su osteoporosis grave. A su ingreso a endocrinología la paciente persitía con dolor lumbar alto y destacaba una marcada cifosis. Se decidió retomar tratamiento con Alendronato, calcio y vitamina D, además, se le solicitó una nueva evaluación densitométrica junto a una radiografía de columna total y evaluación dental. Durante el seguimiento la paciente mantuvo niveles de vitamina D adecuados con funciones renal, hepática y tiroidea normales.

Gaucher disease (GD) is a rare autosomal recessive lysosomal genetic disorder, leading to the accumulation and dysfunction of lipids in multiple organs. Skeletal involvement is one of the most prevalent aspects of GD and one of the main causes of pain and reduced quality of life. Abnormalities of bones, which cause changes in the development and loss of bone mineral, cortical thinning, lytic lesions,fragility fractures and deformities. We present a case of a patient diagnosed with severe osteoporosis, secondary to GD diagnosed in adult life. The patient presents a disease pattern composed of bone pain and chronic low back pain since the age of 53. In 2012, she was evaluated at the hematology for thrombocytopenia and due to her family history, tests were performed to diagnose GD, which were compatible with it. In 2016 Bone Densitometry (DXA) of the lumbar spine and left femoral neck was requested, being consistent with osteoporosis. Treatment with Alendronate, Calcium and Vitamin D was started, however, there is little adherence. In 2018, treatment for Gaucher's disease was started with Taliglucerase α. The following year, DXA was performed with few changes and a CT scan of the lumbar spine was performed diagnosing crush fractures of the low dorsal vertebral bodies. She was referred to endocrinology. Upon admission to Endocrinology, it was decided to resume initial osteoporosis treatment and to perform skeletal evaluation with DXA of the lumbar spine and hips, total spine X-ray and dental evaluation. During follow-up, it maintains vitamin D at adequate levels and normal kidney, liver and thyroid functions.

Blockade of electrophysiological properties of muscle fibres by lycorine.

This study concerns the action of the alkaloid lycorine on electrophysiological properties of single sartorius muscle fibres. Lycorine caused a decrease of the resting membrane potential, a lengthening in the rise and decay times of the action potential and a fall of the muscle accommodation. The depolarizing effect was not affected when Na+ is replaced by choline in the Ringer solution. Lycorine did not inhibit the (Na+ + K+) ATPase activity. The results suggest that action of lycorine on the electrophysiological properties can be attributed to an interference with potassium channels.

Carcinoid tumors of the duodenum and ampulla of vater: a clinicomorphologic, immunohistochemical, and cell kinetic comparison.

Carcinoid tumors of the ampulla of Vater (ACs) differ from duodenal carcinoid tumors (DCs). A search for AC and DC was made between 1980 and 2000. The clinicopathologic features and follow-up were assessed. Immunohistochemistry for panneuroendocrine markers, hormone products, proliferating cell nuclear antigen (PCNA), Ki- 67, p21(cip1), and p27(kip1) were performed. A blind proliferative index counting 500 cells was made. Differences were contrasted using the Fisher exact and 2-sided Student t test. Five ACs and 8 DCs were identified in 9 women and 4 men with median ages of 59 and 64 years and mean tumor diameters of 1.6 and 1.85 cm, respectively. All patients with AC presented jaundice, and most patients with DC were asymptomatic (P = .047). Metastases were present in 4 ACs and 1 DC (P =.03). Tumor cells expressed synaptophysin and chromogranin in 60% of ACs and in 100% and 87% of DCs. Gastrin was expressed in 75% of DCs and 20% of ACs (P < .05). The mean value for PCNA index was 4.0% in ACs and 3.2% in DCs, and mean values for Ki-67 were 12.2% and 10.2%, respectively (P = NS). Expression of p21(cip1) and p27(kip1) was observed in 40% of ACs and 37.5% and 12.5% of DCs. Three of 5 patients with AC died of the disease within an average of 11 months, and none of the patients with DC had died at 103 months of follow-up. The more aggressive behavior of ACs is not associated with higher proliferative indices or with different expression of cell cycle inhibitors.

Some particularities of sodium nitroprusside stimulatory effects on food intake.

It was previously shown that sodium nitroprusside (NP) stimulates food (FI) and water (WI) intakes when injected intraperitoneally (i.p.) in male rats deprived for 1-h of both food and water during day time. The present work shows that: 1) intramuscular NP increased only water intake; 2) when NP was i.p. injected simultaneously without 1-h deprivation it slightly reduced both intakes in the first 30 min but stimulated significantly FI between 30 and 60 min, and 3) it increased significantly FI even in absence of available water, while WI in absence of food was practically not affected. In conclusion NP effect on FI does originate mainly in the splanchnic area, it requires a latency of about 30 min, and stimulation of FI by NP triggers an increase in WI and not the other way around.

Norepinephrine inhibition of water and food intake: comparison with vasopressin effects.

UNLABELLED: In a previous publication we showed that intraperitoneally (IP) injected norepinephrine (NE) induces hypodipsia (hD) in rats by an alpha 1-adrenergic effect which might be due to splanchnic vasoconstriction. In the present work we administered two vasoconstrictive hormones: NE 250 ug/kg and arginine vasopressin (VP) 550 mU/kg either by IP or intramuscular (IM) route to fasted rats in two different thirst-inducing conditions: (a) water-deprivation; or (b) induced hyperosmolarity. IP NE inhibited significantly food and water intake under both conditions. IM NE did not affect food intake and elicited significantly less hD and this only in (a). VP did not affect food intake but induced hD regardless of the route of administration in (a) but not in (b). NE administrated to anesthetized rats after food and water deprivation increased arterial pressure by both routes while VP effect was weaker and more variable. IN CONCLUSION: blood pressure elevation may be implicated in the hD effect but IP NE elicits a specific splanchnic action; splanchnic-induced hypophagia is not necessarily related to water intake inhibition.

Potentiation of the immobility response elicited by bandaging and clamping in mesencephalic rats.

In earlier work, we showed that adult rats exhibit immobility response (IR) if a clamp is fastened to the skin of the nape of the neck, but not at other areas of the body, and not by bandaging. The present study characterizes IR in adult rats with complete mesencephalic transections. In the mesencephalic rats, the duration of the IR not only increased, but the stimuli capable of eliciting it were more diverse. All head and body areas clamped or bandaged were capable of inducing a profound IR. In contrast, the IR in intact rats was of shorter duration, and was only induced by clamping the neck, or by bandaging the upper or the lower torso. Furthermore, unlike the mesencephalic rats the ability of the bandaging to induce IR is reduced after the first trial and finally disappears. Only clamping the neck was able to persistently induce IR in intact rats. These data support the hypothesis that the IR control system is in the midbrain, hindbrain or spinal cord, and that systems above the mesencephalon modulate the IR. Such modulation appears to involve the ability to discriminate amongst tactile stimuli, and to integrate previous experience.

Effect of intraperitoneal nitroprusside and adrenergic agonists on food and water intake.

In previous works it was shown that catecholamine-induced hypodipsia is mediated by alpha1-adrenergic receptors while food intake (FI) inhibition supposes also beta-adrenergic participation. We used sodium nitroprusside (N) as a vasodilator, alone or mixed with various adrenergic agonists and measured FI and water intake (WI) in rats either deprived food and water overnight or in postprandial conditions after only 1 hour of deprivation in day time. N injected alone had no effect after overnight deprivation but diminished significantly norepinephrine (NE)-induced inhibition of both intakes, while epinephrine (E) inhibited only FI. In day time, N stimulated 30 min FI by 60% and WI by 84% in male but not in female rats. Isoproterenol (I) stimulated only WI (by 155%), while phenylephrine (P) and E inhibited it by 55%. In the presence of N, I increased WI even more (by 220%) but reduced FI. P + N and E + N increased FI by 41% and 128% as compared with P and E, respectively. Only P-induced inhibition of WI was canceled in presence of N. The results show that N, probably due to nitric oxide production, may induce hyperphagia and hyperdipsia in 1 hour-deprived male rats and also that catecholamine effects on FI and WI are differently modulated by N.