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The liver is the main organ for the elimination of bacterial endotoxin involving Kupffer and parenchymal cells. This process is accompanied by the release of free radicals. Parenchymal cells possess especially high levels of glutathione, which make them a key point in the response to free radicals. Sinusoidal cells regulate hepatic function in a very important fashion through the release of cytokines and/or adhesion molecules. These facts suggest the importance of finding new in vitro experimental models representing an intermediate step towards in vivo models. The treatment with LPS of sinusoidal and parenchymal cell co-cultures on porous membranes provokes an intense reduction of parenchymal cell intracellular glutathione, which does not correspond to in vivo results. However, the addition of supernatants of LPS-treated sinusoidal cells to parenchymal cells renders increases in glutathione which agree better with in vivo results. We conclude that the regulation of liver hepatocyte glutathione content and NO release in the presence of LPS is strongly modulated by liver non parenchymal cells. The study of this phenomenon requires new in vitro models taking into account liver histophysiology and histopathology and anatomical restrictions in cell communication.

Background: The inherent seriousness of IgE mediated hypersensitivity to hymenopteran venoms makes it necessary to reach, in the shortest period of time, the maintenance dose in immunotherapy with poisons. The aim of this article is to evaluate the safety of a cluster schedule of subcutaneous hymenopteran venom immunotherapy, which reduces the time needed to reach the maintenance dose from 12 to 3 weeks., Material and Methods: Thirty patients, 24 men and 6 women with an average age of 46.06 years, who had been diagnosed with hypersensitivity to the poison of hymenopterans and for whom immunotherapy had been prescribed participated in the study. The patients received Pharmalgen (ALK Abelló) immunotherapy against hymenopteran venoms, 13 Apis mellífera, 12 Véspula spp, and 5 Polistes spp, with a cluster schedule that consisted of: day 1 (4 microg + 6 microg), day 8 (10 microg + 30 microg) and day 15 (40 microg + 60 microg). The reactions occurring during the starting phase between April 2005 and February 2008 were evaluated., Results: Of the 30 vaccinated patients 2 presented an exaggerated local reaction, there were other non-specific symptoms on two occasions, and another 2 presented systemic reaction. One following administration of the dose of 40 microg presented a grade III systemic reaction, and the other after receiving the dose of 60 microg presented a grade II systemic reaction. Both passed to a conventional model of immunotherapy administration and had new grade III reactions, and were therefore kept on immunotherapy with premedication with oral antihistamines., Discussion: The study confirms that the model employed is safe with a low incidence of adverse reactions, 1.67% presented an exaggerated local reaction, 1.11% had an non-specific reaction and 1.11% a systemic reaction.

Amiodarone causes changes in thyroid function tests in about 15-20% of patients, inducing either hypothyroidism or thyrotoxicosis. The iodine load and the destructive thyroiditis caused by amiodarone produce thyrotoxicosis. We report a case of amiodarone-induced thyrotoxicosis diagnosed when investigating the reason for worsening of cardiac function. Prognosis and treatment of cardiac disorder were determined by thyrotoxicosis. The management needed a closed monitoring of thyroid function. Treatment was based on high doses of propylthiouracil and dexamethasone, but they couldn t control cardiac condition and surgery was warranted. When amiodarone-induced thyrotoxicosis is refractory to medical treatment, we believe surgery should be considered earlier.

An inadequate balance between oxidant species and antioxidant mechanisms may constitute the primary mechanisms of a number of pathologies. The liver plays a central role in this balance: parenchymal hepatic cells contain and export especially high levels of the antioxidant glutathione and activated Kupffer cells release inflammation mediators and reactive oxygen species. There is growing evidence of a paracrine regulation of hepatic function by means of a fluent intercellular communication which must still be fully elucidated, especially in basal conditions. In vivo models provide often too complex results but, in vitro, tissue interactions are left aside; therefore it is important to find new experimental models to address cell communication studies. Here we propose the complementary use of three models to study liver glutathione system regulation in basal conditions: pure parenchymal cells primary cultures, addition of sinusoidal cell conditioned media to parenchymal cells and co-culture of sinusoidal cells using porous membranes. We have also developed a high specifity immunofluorescent method for the complete characterization of sinusoidal cell populations by flow cytometry and confocal microscopy. Our results show that Kupffer cells possess higher levels of reactive oxygen species than sinusoidal endothelial cells even in basal conditions. We also report that the glutathione content of hepatic parenchymal cells in basal conditions is regulated by a sinusoidal-parenchymal cells cross-talk and suggest the existence of a paracrine circuit in the management of liver oxidative stress.

The cellular proteome shows a dynamic profile and is subjected to changes in response to various stimuli and disease progression. Lung cancer remains the leading cause of cancer death in industrialized countries. In an attempt to find new disease markers, patients suffering from lung carcinoma have been selected to achieve differential protein expression patterns between normal and neoplasic tissue. After two-dimensional electrophoresis, the spots of interest were digested and identified by matrix-assisted laser desorption/ionization (MALDI) peptide mass fingerprinting. This information will provide a more comprehensive understanding of the disease progression and might constitute a method to complement histopathological diagnosis.

Background and Objective: Our purpose was to evaluate in a cross-section, populational study the association between daily physical activity and various metabolic and cardiovascular disease risk factors., Patients and Method: A total of 1226 randomly selected persons (aged 18-65 years) from a town in southeast Spain were evaluated for studying the association between the level of daily physical activity, both in and out of working hours, and the following variables: body mass index, plasma lipids, hypertension, obesity, altered baseline glycemia, and abnormal glucose tolerance., Results: The intensity of the physical activity at work was related negatively with insulin resistance and levels of LDL cholesterol, and positively with HDL cholesterol. The probability of hypertension, altered baseline glycemia, and abnormal glucose tolerance was greater in those undertaking less daily physical activity., Conclusions: Daily physical activity, considered as part of the lifestyle, is related with the presence of components of the metabolic syndrome. An increase in daily physical activity should contribute to improve preventible cardiovascular risk factors.

A phase I clinical trial was conducted in patients with stage III/IV breast cancer who were treated with the anti-idiotype mAb 1E10 specific to an Ab1 mAb able to react specifically with N-glycolyl-containing gangliosides and with antigens expressed on human melanoma and breast carcinoma cells. Patients were treated with 1 or 2 mg of aluminum hydroxide-precipitated 1E10 mAb every other week for six injections. Two patients at each dose were reimmunized 7-9 months after completing the induction phase. In hyperimmune sera from eight of the nine patients who received at least four doses of anti-Id vaccine preparations, strong specific responses were observed both against 1E10 mAb and NeuGc-GM3 ganglioside (Ab3 Id+Ag+). Nonclassical Ab1' antibodies (Id-Ag+) were also elicited by 1E10 mAb vaccine treatment. There were no differences between the two levels of dose tested in relation to toxicity and immunogenicity. No evidence of serious or unexpected effects was observed.

Objective: The objective of this open study of 104 patients was to determine whether the somatostatin analogue lanreotide shrinks GH-secreting adenomas and to identify the predictive factors of a significant tumour volume reduction (> 20%)., Patients: A total of 104 previously untreated and newly diagnosed acromegalic patients received the prolonged release (PR) formulation of lanreotide (lanreotide 30 mg, one intramuscular injection every 10 days) for either 1 (n = 84), 2 (n = 13), or 3 or more (n = 7) months before transsphenoidal surgery., Measurements: Pituitary tumour volumes, tumour extension grade and possible cavernous sinus invasion were assessed in blinded conditions by a centralized team of radiologists. Factors such as demographics, tumour characteristics, GH and IGF-I levels were evaluated as possible predictive factors of a significant tumour volume reduction. The clinical activity and random GH, IGF-I, IGFBP-3, PRL, TSH, free T4 and lanreotide levels serum concentrations were measured under basal conditions and in the 10 days before surgery. All analyses were done in a centralized laboratory. The tolerability of preoperative PR lanreotide and the surgical outcome at the 6th month after surgery were assessed., Results: The presurgical treatment improved the symptoms of acromegaly and induced a statistically significant reduction of GH, IGF-I and IGFBP-3. Despite the short duration of the preoperative lanreotide 30 mg treatment, IGF-I levels were normalized in 25% of patients. A statistically significant reduction in tumour volume (P < 0.001) was observed. The median value of the differences was -152 mm3. A reduction in tumour volume was observed in 66% of patients and was > 20% in 29% of all patients included. Both the univariate analyses and the logistic regression model demonstrated that a positive hormone response to preoperative lanreotide 30 mg was the sole predictive factor of a significant tumour shrinkage (odds ratio of 7.8, 95% confidence interval 1.6-37.1). Preoperative PR lanreotide did not modify the expected soft consistence of the tumour. The main adverse events consisted of minor gastrointestinal problems. Univariate analyses revealed that younger age, higher GH and IGF-I levels at diagnosis, higher preoperative tumour volume, more than one tumour extrasellar extension and the presence of cavernous sinus invasion were statistically significant determinants of persistent disease at the 6th month after surgery. The multivariate analysis revealed that higher IGF-I levels at diagnosis and the preoperative cavernous sinus invasion were each statistically significant prognostic factors of persistent disease., Conclusions: A short administration of preoperative lanreotide 30 mg induced a statistically significant shrinkage of GH-secreting pituitary adenomas where this reduction was > 20% of the pretreatment value in 29% of the whole population. Among the factors considered was the fact that positive hormone response to preoperative lanreotide 30 mg was the sole predictive factor of this significant tumour volume reduction.

Epidermal growth factor receptor (EGFR) overexpression has been detected in many tumors of epithelial origin, and it is often associated with tumor growth advantages and poor prognosis. h-R3 is a genetically engineered humanized antibody (mAb) that recognizes an epitope located in the extracellular domain of human EGFR. The antibody exhibited potent in vitro and in vivo antitumor effect on EGFR overexpressing cell lines. To study safety, pharmacokinetics, and biodistribution, 12 patients with advanced epithelial-derived tumors received single intravenous infusion of h-R3 at four dose levels. Safety evaluation was made according to World Health Organization toxicity criteria. For biodistribution, 3 mg of the total dose were labeled with Technetium and then pooled with the rest of the dose. Anterior and posterior whole-body images were acquired using a gamma camera. Blood samples were taken for pharmacokinetics, antiidiotypic response, and for soluble EGFR detection. After hR3 administration, no evidence of severe toxicity was observed. Secondary reactions were mild and moderate and mainly consisted of tremors, fever, and vomiting. No anaphylactic or skin reactions were detected. Qualitative analysis of whole-body images showed that the liver had the highest mAb uptake. Pharmacokinetic analysis revealed that elimination half-lives and the AUC increased linearly with dose, while total body clearance decreased when increasing doses of h-R3. No relation between shed EGFR and mAb clearance was found. No antiidiotypic response against h-R3 was detected. Several phase II trials are now underway to evaluate the efficacy of h-R3 in the treatment of advanced cancer patients.

Objective: To study the prevalence of diabetes mellitus and islet autoantibodies in an adult population from Southern Spain., Research and Methods: A cross-sectional study in Southern Spain of 1226 people, age 18-65 years. Clinical data were obtained and a blood sample taken to measure autoantibodies (glutamic acid decarboxylase antibodies (GADAb), tyrosine phosphatase antibodies (IA2Ab), and insulin antibodies (IAA)). An oral glucose tolerance test (OGTT) was also given to 982 of the subjects., Results: The overall prevalence of diabetes mellitus according to the WHO 1979 criteria was 10.9% and according to the ADA 1997 criteria it was 14.7% (8.8% were unaware of their diabetes). The prevalence of impaired fasting glucose (IFG) was 12.4% and of impaired glucose tolerance (IGT) 11.5%. The prevalence of GADAb+ in the general population was 0.9% and in the diabetic population 3.7%. There were no significant differences between groups in the prevalence of IA2Ab or IAA (both were 0.8% in the general population). Of the three autoantibodies studied, only GADAb were significantly different in the diabetic population (P=0.0006)., Conclusions: The prevalence of Type 2 diabetes and LADA are high in the south of Spain.

We have previously reported that endotoxin induces in vivo oxidative stress in liver and a significant increase in hepatic and plasma glutathione concentrations during the acute phase of reversible endotoxic shock in rats. In the present study we examined the in vitro effects of E. coli 0111:B4 endotoxin (lipopolysaccharide, LPS), IL-1beta and TNF-alpha on antioxidant status of cultured hepatocytes in order to differentiate between the direct and mediated endotoxin action. LPS increased total glutathione (tGSH) levels after 2 h treatment but decreased oxidized glutathione (GSSG) content which lead to a marked decrease in GSSG/tGSH index. At shorter treatment times a biphasic and dose-dependent behaviour was observed. Cytokines (IL-1beta and TNF-alpha) produced significant decreases in tGSH and GSSG after 30 min treatment. Despite its prooxidant effect, TNF-alpha significantly reduced GSSG/tGSH index. Although no significant effects were observed on glutathione reductase activity, both LPS and cytokines induced an important inhibition of glutathione peroxidase which can justify the lipid peroxidation previously observed both in liver during reversible endotoxic shock and in cultured hepatocytes after treatment with endotoxin. The inhibition of hepatic glutathione peroxidase, besides the stimulation of GSH synthesis by LPS and GSH efflux by cytokines, guarantees the export of hepatic glutathione in its reduced form for other organs, contributing to the interorgan homeostasis. On the other hand, the results presented here support a new role for GSSG/tGSH index different from a mere indicator of oxidative stress.

Ior egf/r3, a neutralizing monoclonal antibody (mAb) against Epidermal Growth Factor Receptor (EGFR) was generated at the Cuban Institute of Oncology. Immunoscintigraphic studies in 148 patients with this 99-m Technetium (99Tc) labeled mAb, showed a high sensitivity and specificity for in vivo detection of epithelial tumors. To study safety, pharmacokinetic and immunogenicity of ior egf/r3 at high doses, a phase I clinical trial was conducted. Nineteen patients with advanced epithelial tumors received 4 mAb intravenous infusions at 6 dose levels: from 50 to 500 mg. Previously, immunoscintigraphic images using the same mAb labeled with 99Tc were acquired. Blood samples were collected for pharmacokinetic analysis and HAMA response. After mAb therapy, objective response was classified according to WHO criteria. Ior egf/r3 was well tolerated in spite of the high-administered doses. Only a severe adverse reaction consisting of hypotension and lethargy was observed. In 13 patients, selective accumulation of 99Tc-labeled mAb was observed at the site of the primary tumor or the metastasis. Pharmacokinetic analysis revealed that elimination half-life and the area under the time-concentration curve increased linearly with dose. HAMA response was detected in 17 patients. After 6 months of mAb therapy, 4 patients had stable disease. One patient had a tumor partial remission after 3 cycles of ior egf/r3.

Introduction: Transcranial magnetic stimulation (TMS) permits stimulation of the cerebral cortex in humans without requiring open access to the brain and is one of the newest tools available in neuroscience. There are two main types of application: single-pulse TMS and repetitive TMS., Development: The magnetic stimulator is composed of a series of capacitors that store the voltage necessary to generate a stimulus of the sufficient intensity of generate an electric field in the stimulation coil. The safety of TMS is supported by the considerable experience derived from studies involving electrical stimulation of the cortex in animals and humans, and also specific studies on the safety of TMS in humans., Conclusions: In this article we review historical and technical aspects of TMS, describe its adverse effects and how to avoid them, summarize the applications of TMS in the investigation of different cerebral functions, and discuss the possibility of using TMS for the treatment of neuropsychiatric disorders.

Background: The triggering of cellular responses during endotoxic shock is initiated for the binding of endotoxin (lipopolysaccharide; LPS) to the cell surface. Kupffer and endothelial liver cells, involved in the removal of endotoxin from blood circulation, show in vitro a rapid response to LPS in the absence of serum., Methods: A double-labeling fluorescent assay was designed to evaluate the binding properties of Escherichia coli O111:B4 LPS to individual endothelial and Kupffer cells in suspension, where both populations occurred in the same relative proportion as in liver. After immunolabeling of the Kupffer cell population with the monoclonal antibody ED1 conjugated to R. phycoerythrin, the binding characteristics of LPS labeled with fluorescein to both endothelial and Kupffer cells were simultaneously studied by flow cytometry in serum-free conditions., Results: Specific and saturable binding of endotoxin was observed with both populations, showing properties of a receptor-mediated process. The Kupffer cell population showed a faster capacity and a higher affinity for LPS binding. The Hill coefficients indicated positive cooperativity in the LPS interaction with both populations., Conclusions: Specific endotoxin binding to liver sinusoidal cells occurs in a serum-independent manner, particularly at high LPS concentrations. Flow cytometry is a fast, precise, and efficient technique to evaluate the simultaneous interaction of a ligand with two different cell types.

Background: The importance of cultural and adverse family-environment variables as risk factors for Disruptive Behaviour Disorder has been repeatedly shown, and hence a variation in rates and risk factors between cultures could be expected. Lower rates should be found in countries with strong and stable family ties, such as Spain., Objective: Prevalence rate, severity and comorbidity of Disruptive Behaviour Disorder, as well as risk factors and help-seeking behaviour relating to this disorder, were studied in a general population random sample of 387 10 year-old children living in Valencia (Spain)., Methods: DSM-III-R diagnosis was established by means of the KIDDY-SADS (Kiddy Schedule for affective diseases and Schizophrenia (epidemiological version)) interview and severity of the disorder was evaluated with the General Assessment Functioning (GAF) Scale. Other variables measured were: sex, number of siblings, parental occupation, single-parent home, school failure, socioeconomic level, chronic somatic ailments and use of mental health services., Results: Prevalence and severity parameters were low (for GAF70, prevalence = 11.1; for GAF60, prevalence = 4.9), albeit falling within the range reported in other countries. Morbidity profile and use of services did not substantially depart from the findings reported in other cultures. Different risk factors were associated with Attention Deficit Hyperactivity Disorder, Conduct Disorder and Oppositional Defiant Disorder, thus confirming the validity of considering them as separate dimensions., Conclusions: The findings did not support the hypothesis of lower rates and different risk factors and morbidity patterns in the Spanish sample studied.

Objective: To find the control degree of a population of hypertension patients. To evaluate the cost effectiveness of health services., Setting: EAP Salvador Pau. Valencia (Spain)., Patients: 200 patients diagnosed of hypertension included in the health center file., Measurements and Results: Items studied were age, sex, diagnosis and program inclusion year, number of visits, other explorations and its cost, TAS and TAD, drugs and its cost, personnel cost. We established different well control levels and we obtained the cost of each of them. Twenty six point five per cent of patients had TA values below 140/90 mmHg; Sixty four point five per cent had values below 160/90 mmHg. And sixty six point nine had values below 90 mmHg. Monthly medium cost per patient was 3242 pts. Monthly medium cost per patient well controlled was 12234 pts., Conclusions: Only a third of our patients are well controlled according the current standards. Efficiency decreases noteworthy when control levels are lower.

The prevalence of dental injuries in Spanish children living in an urban area was studied in 4000 schoolchildren ages six to twelve years. A total of 227 children experienced dental injuries. Simple enamel fracture was the predominant injury (46.2 percent). Boys showed a higher prevalence than girls In the majority of cases (74.9 percent), the trauma affected one tooth only. The maxillary central incisor was the most frequently affected tooth (87.9 percent). The most common fracture site was the mesioincisal angle (40.6 percent) followed by distoincisal angle (27.3 percent). Twenty-four percent of the children with dental injuries had an overjet of more than 3 mm.

Functional imaging studies of people who were blind from an early age have revealed that their primary visual cortex can be activated by Braille reading and other tactile discrimination tasks. Other studies have also shown that visual cortical areas can be activated by somatosensory input in blind subjects but not those with sight. The significance of this cross-modal plasticity is unclear, however, as it is not known whether the visual cortex can process somatosensory information in a functionally relevant way. To address this issue, we used transcranial magnetic stimulation to disrupt the function of different cortical areas in people who were blind from an early age as they identified Braille or embossed Roman letters. Transient stimulation of the occipital (visual) cortex induced errors in both tasks and distorted the tactile perceptions of blind subjects. In contrast, occipital stimulation had no effect on tactile performance in normal-sighted subjects, whereas similar stimulation is known to disrupt their visual performance. We conclude that blindness from an early age can cause the visual cortex to be recruited to a role in somatosensory processing. We propose that this cross-modal plasticity may account in part for the superior tactile perceptual abilities of blind subjects.

The objective of our work was to measure plasma melatonin levels in patients with Parkinson's Disease (PD) following electrical stimulation of the internal globus pallidus (GPi), and to compare these levels with groups of PD patients under drug therapy and healthy controls. The levels of melatonin were measured twice daily at 1000 and 1200. The GPi stimulation at 130 Hz lowered melatonin levels, while no changes were observed in the absence of stimulation. The melatonin levels from healthy subjects were lower than those observed in PD patients. The melatonin levels from PD patients under drug therapy were also measured during the night (2000-2400-0400) and at 0800 in order to observe their circadian changes. The Internal Globus Pallidus (GPi) stimulation was effective in lowering the melatonin levels during the day and, therefore returned these levels to those observed in normal subjects.

Background: Lesion and neuroimaging studies suggest that left prefrontal lobe dysfunction is pathophysiologically linked to depression. Rapid-rate transcranial magnetic stimulation (rTMS) to prefrontal structures has a lateralised effect on mood in normal volunteers, and several preliminary studies suggest a beneficial effect of rTMS on depression. However, adequately controlled studies have not been conducted., Methods: We have studied the effects of focal rTMS on the depressive symptoms in 17 patients with medication-resistant depression of psychotic subtype. The study was designed as a multiple cross-over, randomised placebo-controlled trial. Sham rTMS and stimulation of different cortical areas were used as controls., Findings: Left dorsolateral prefrontal cortex rTMS resulted in a significant decrease in scores on the Hamilton depression rating scale HDRS (from 25.2 to 13.8) and the self-rated Beck questionnaire BQ (from 47.9 to 25.7). 11 of the 17 patients showed pronounced improvement that lasted for about 2 weeks after 5 days of daily rTMS sessions. No patient experienced any significant undesirable side-effects., Interpretation: Our findings emphasise the role of the left dorsolateral prefrontal cortex in depression, and suggest that rTMS of the left dorsolateral prefrontal cortex might become a safe, non-convulsive alternative to electroconvulsive treatment in depression.

Reactive oxygen species are important mediators of cellular damage during endotoxic shock. In order to investigate the hepatic response to the oxidative stress induced by endotoxin, hepatic and plasma glutathione (total, GSH and GSSG), GSSG/GSH ratio as well as Mn-superoxide dismutase and catalase activities were determined during the acute and recovery phases of reversible endotoxic shock in the rat. A significant increase in liver and plasma total glutathione content was observed 5 h after endotoxin treatment (acute phase), followed by a diminution of these parameters below control values at 48 h (recovery phase). The significant increases of GSSG levels and GSSG/GSH ratio are indicative of oxidative stress occurring during the acute phase. Liver Mn-SOD activity showed a similar time dependency as the GSSG/GSH ratio; however, a marked decrease in the liver catalase activity was observed during the process. These results indicate the participation of liver glutathione in the response to endotoxin and the possible use of plasma glutathione levels and GSSG/GSH ratio as indicators of the acute phase during the endotoxic process.

We studied the effects of rapid-rate transcranial magnetic stimulation (rTMS) of different scalp positions on mood. Ten normal volunteers rated themselves before and after rTMS on five analog scales labeled "Tristeza" (Sadness), "Ansiedad" (Anxiety), "Alegria" (Happiness), "Cansancio" (Tiredness), and "Dolor/Malestar" (Pain/Discomfort). rTMS was applied to the right lateral prefrontal, left prefrontal, or midline frontal cortex in trains of 5 seconds' duration at 10 Hz and 110% of the subject's motor threshold intensity. Each stimulation position received 10 trains separated by a 25-second pause. No clinically apparent mood changes were evoked by rTMS to any of the scalp positions in any subject. However, left prefrontal rTMS resulted in a significant increase in the Sadness ratings (Tristeza) and a significant decrease in the Happiness ratings ("Alegria") as compared with right prefrontal and midfrontal cortex stimulation. These results show differential effects of rTMS of left and right prefrontal cortex stimulation on mood and illustrate the lateralized control of mood in normal volunteers.

The point prevalence of Attentional Deficit Disorder with Hyperactivity is estimated in a random sample of 387 10-year-old children selected from the municipal census of the city of Valencia (Spain). A number of associated factors are described, along with the utilization of public health services. Diagnosis was established according to DSM-III-R criteria. The instruments used were: K-SADS-E; GAF Scale; Raven Progressive Matrices Test and Sociodemographic, Health and Services Use Information Questionnaire. Prevalence was estimated at 8.01 +/- 2.7% (mild 3.9%; moderate 3.9%; severe 0.3%). The male/female ratio was 2:1. Attentional Deficit Disorder with Hyperactivity was significantly associated with low academic performance and the condition of living with only one parent. These children made use of the psychological support services with significantly greater frequency than non hyperactive children, regardless of the degree of severity or academic performance.

We describe a 45 year-old man, with scleromyxedema associated to systemic manifestations, including myopathy. After 6 years of dermatologic manifestations, muscular weakness, with proximal predominance resulting in incapacity, was established. Corticosteroids plus cyclophosphamide treatment suppressed muscular symptomatology, and a second biopsy was normal. The common association between scleromyxedema and myopathy and other systemic alterations suggest that this entity should probably be considered as a systemic disease instead as a skin disease.

Recently, cases of porphyria cutanea tarda (PCT) have been reported associated with infection due to human immunodeficiency virus (HIV). We presented the cases of three males, former ethanol users, and which have had previously a contact with the Hepatitis B virus. In one of the patients symptomatology appeared after treatment with zidovudine was begun. We suggest that HIV infection associated with other toxic or viral factors could contribute to the early development of a PCT latent until that moment.

Lower gastrointestinal tract bleeding as a manner of presentation of the Crohn's disease is uncommon. In most cases there is an other concomitant pathology responsible for that bleeding. We report a case of lower gastrointestinal tract bleeding to an inflammatory fibroid bowel polyp in a patient with ileal Crohn's disease. A commentary is made about the etiopathogenic factors of the both diseases.

We evaluated 40 diabetic patients (with a duration of the disease longer than 10 years) with diabetic neuropathy, to assess the effect of a good metabolic control maintained for six months on the nervous conduction velocity. The motor nervous conduction velocity (NCV) and the sensory latency and potentials were evaluated in the median and external popliteal nerves. In the groups of patients with a good metabolic control (mean basal glucose blood levels 109 +/- 12 mg/dl, or 6.04 +/- 0.66 mmol/l) there was a significant clinical improvement with improved test results; the NCV if the external popliteal nerve changed from 40.5 +/- 5.9 m/sec to 43.5 +/- 5.8 m/sec (p less than 0.05). An improvement of motor involvement and sensory potentials were found in 35 and 20%, respectively, of group I patients. The differences with those patients without a good metabolic control, in whom no study parameter improved, were significant. These studies apparently show a good metabolic control may reverse or at least improve diabetic neuropathy. However, wider studies are required to elucidate whether diabetic neuropathy is reversible or not.

We report the results of an intervention trial comparing the counseling (group A) of the general practitioner to encourage to quit smoking in dissonant smokers and an intervention based on counseling and offer of follow up at 2 and 3 weeks and at 3 and 6 months (group B). Both interventions were globally evaluated to assess the influence of the smoking habits of health professionals on the results. In the 93 group B patients there was a higher quitting rate than in group A. The rates of success after one year follow up were 26.9% and 11.9% (p less than 0.05). Forty-seven of the 152 patients were counseled by smoking physicians and 105 by non-smoking physicians; at one-year follow-up, the verified quitting rates were 10.6% and 25.7%, although the difference was not significant. It was concluded that the reinforcement of counseling by follow-up may increase the rate of quitting smoking in dissonant smokers in a primary care setting, and that the influence of the habit of the health professional can be limited through more systematic interventions.

Male adult albino rats were divided into six groups: two pinealectomized (Px); two sham-operated (Sh) and two serving as controls (C). Half of these groups were studied in daylight and the other half at night. The animals were open-field tested and then conditioned by the avoidance behavior test in the appropriate light period. No differences were observed among the groups when they were conditioned in the dark; however, the Px were conditioned significantly more rapidly than Sh or C in daylight. Intragroup comparisons between night/day conditioning showed them to be similar in Px but more rapid at night in both Sh and C. The Sh group is unique and not comparable to controls.

Pineals from male Long-Evans rats (60-65 days old; adapted to a 0700-1900 photoperiod) were cultured for 6 h either in light (1200-1800) or in dark (1800-2400). The objective was to ascertain the effects of tryptophan (trp) and phenylalanine (phe) levels and ratios in the culture medium on melatonin levels in the pineals and their respective media. Total culture (pineal + medium) melatonin levels, determined by RIA, were similar under all conditions. However, in cultures during the early dark phase (1800-2400) lower trp:phe ratios in the medium led to lower pineal:medium ratios of melatonin content. In cultures during the late light phase (1200-1800) the trp:phe ratio had little impact on the pineal:medium distribution of melatonin. Trp:phe ratio rather than absolute level of either amino acid appeared responsible for this effect. Functionally this means that during early dark phase, but not late light phase, movement of melatonin from cultured pineal to medium is progressively facilitated by lower trp:phe ratios. It remains to be determined to what extent darkness per se and/or endogenous pineal rhythmic mechanisms have a permissive role in the action of trp:phe ratio on pineal melatonin release. A melatonin compartmentalization/release effect of these or other amino acids, or their ratios, has not been reported previously and may possibly contribute to mechanisms for melatonin's transport or release at night.