A comprehensive clinical and genetic study of a large Mexican population with spinocerebellar ataxia type 7.

Spinocerebellar ataxia type 7 (SCA7) is an inherited neurodegenerative disorder characterized by progressive cerebellar ataxia associated with macular degeneration. We recently described one of the largest series of patients with SCA7 that originated from a founder effect in a Mexican population, which allowed us to perform herein the first comprehensive clinical, neurophysiological, and genetic characterization of Mexican patients with SCA7. In this study, 50 patients, categorized into adult or early phenotype, were clinically assessed using standard neurological exams and genotyped using fluorescent PCR and capillary electrophoresis. Patients with SCA7 exhibited the classical phenotype of the disease characterized by cerebellar ataxia and visual loss; however, we reported, for the first time, frontal-executive disorders and altered sensory-motor peripheral neuropathy in these patients. Semiquantitative analysis of ataxia-associated symptoms was performed using Scale for the Assessment and Rating of Ataxia (SARA) and the Brief Ataxia Rating Scale (BARS) scores, while extracerebellar features were measured employing the Inventory of Non-ataxia Symptoms (INAS) scale. Ataxia rating scales confirmed the critical role size of cytosine-adenine-guanine (CAG) repeat size on age at onset and disease severity, while analysis of CAG repeat instability showed that paternal rather than maternal transmission led to greater instability.

Analysis of CAG repeats in five SCA loci in Mexican population: epidemiological evidence of a SCA7 founder effect.

Spinocerebellar ataxias (SCA) are a heterogeneous group of neurodegenerative disorders. CAG (cytosine-adenine-guanine) trinucleotide repeat expansions in the causative genes have been identified as the cause of different SCA. In this study, we simultaneously genotyped SCA1, SCA2, SCA3, SCA6, and SCA7 applying a fluorescent multiplex polymerase chain reaction assay. We analyzed 10 families with SCA (64 patients) from five different communities of Veracruz, a Mexican southeastern state, and identified 55 patients for SCA7 and 9 for SCA2, but none for SCA1, SCA3, or SCA6. To our knowledge, this sample represents one of the largest series of SCA7 cases reported worldwide. Genotyping of 300 healthy individuals from Mexican population and compiled data from different ethnicities showed discordant results concerning the hypothesis that SCA disease alleles arise by expansion of large normal alleles.

The selective inhibition of the D1 dopamine receptor results in an increase of metabolized dopamine in the rat striatum.

Our aim was to study the specific role of the postsynaptic D(1) receptors on dopaminergic response and analyze the metabolized dopamine (DA) in the rat striatum. We used male Wistar rats to evaluate the effects of different doses of a D(1) agonist (SKF-38393) and a D(1) antagonist (SCH-23390), and their co-administration. The levels of DA and L-3, 4-dihydroxyphenylacetic acid (DOPAC) were measured using high performance liquid chromatography. The systemic injection of SKF-38393 alone at 1, 5 and 10 mg/kg did not alter the DA and DOPAC levels or the DOPAC/DA ratio. In contrast, injection of SCH-23390 alone at 0.25, 0.5 and 1 mg/kg significantly increased the DA and DOPAC levels, as well as the DOPAC/DA ratio, compared with the respective control groups. The co-administration of SCH-23390+SKF-38393 did not alter the DA or DOPAC levels, but it did significantly inhibit the SCH-23390-induced increase of the DA and DOPAC levels. The SCH-23390+SKF-38393 and the SCH-23390-only groups showed an increase in the DOPAC/DA ratio. The co-administration of SCH-23390+PARGYLINE significantly decreased the DOPAC levels and the DOPAC/DA ratio compared with the control and SCH-23390 groups. Taken together, our results showed that selective inhibition with SCH-23390 produced an increase in metabolized DA via striatal monoamine oxidase. These findings also contribute to the understanding of the role of postsynaptic D(1) receptors in the long-loop negative feedback system in the rat striatum.

Piracetam-induced changes on the brainstem auditory response in anesthetized juvenile rhesus monkeys (Macaca mulatta). Report of two clinical cases.

BACKGROUND: We describe two clinical cases and examine the effects of piracetam on the brainstem auditory response in infantile female rhesus monkeys (Macaca mulatta). RESULTS: We found that the interwave intervals show a greater reduction in a 3-year-old rhesus monkey compared to a 1-year-old rhesus monkey. DISCUSSION: In this report, we discuss the significance of these observations.

Burden of disease related to hepatitis C and hepatitis B in Spain: a methodological challenge of an unfolding health problem.

Most previous studies of burden of disease (BoD) in the area of transmissible diseases have assessed the burden of hepatitis C and B without including the end stages of the disease and using an incident approach. We aimed to assess the disability-adjusted life years (DALYs) related to hepatitis C and B in Spain in 2006 taking into account related cirrhosis and liver cancer. A prevalence approach was used to estimate current years lived with disability (YLD) because of viral hepatitis contracted years/decades before. We added years of life lost (YLL) to obtain DALYs. Around 76,000 DALYs were attributed to hepatitis C virus (HCV) and 15,323 to hepatitis B virus (HBV) when calculated without applying social values. Applying the discount rate and age-weighting used in the Global Burden Disease study, the BoD nearly halved. In any case, the burden related to hepatitis C including long-term outputs becomes the leading cause of DALYs among transmissible diseases in Spain. The mortality component (YLL) represents more than 90% of the BoD in both HCV and HBV. The findings emphasize the need to provide good surveillance systems not only concerning acute viral hepatitis, but also chronic and end-stage consequences to allow a reliable assessment of the prevention and public health control policies.

A dot-ELISA using a partially purified cathepsin-L-like protein fraction from Taenia solium cysticerci, for the diagnosis of human neurocysticercosis.

Human neurocysticercosis (NCC), caused by the cestode Taenia solium, is responsible for a significant amount of neurological morbidity and epilepsy in developing countries. The disease remains highly endemic in many areas, despite several efforts and interventions to control it. A simple, cheap and fast diagnostic assay that is suitable for use in field conditions is highly desired. In immunodiagnostics based on western immunoblots or standard ELISA, a cathepsin-L-like protein purified from the cysticercus fluid has previously performed well as an antigen. In a recent study in Peru, the same 53/25-kDa antigen was therefore used in the development of a dot-ELISA that could be employed for mass screenings under field conditions. The assay was standardized and tested not only against sera from a large group of NCC cases but also against sera from patients with other common parasitic infections, so that sensitivity and specificity could be assessed. For NCC, the assay gave better sensitivity in the detection of individuals with extraparenchymal cysts (94·4%-100%) or multiple parenchymal cysts (74·6%-80·0%) than in the detection of individuals with single parenchymal cysts (29·4%-45·1%). The assay also showed a high specificity for NCC (99·0%-100%), with a very low level of cross-reactivity with other parasitic infections. The dot-ELISA developed in this study is a highly specific, simple, cheap and rapid test for NCC that could be used under field conditions, even in the low-resource settings that are common in developing countries.

Sensitivity analysis of surface runoff generation in urban flood forecasting.

Reliable flood forecasting requires hydraulic models capable to estimate pluvial flooding fast enough in order to enable successful operational responses. Increased computational speed can be achieved by using a 1D/1D model, since 2D models are too computationally demanding. Further changes can be made by simplifying 1D network models, removing and by changing some secondary elements. The Urban Water Research Group (UWRG) of Imperial College London developed a tool that automatically analyses, quantifies and generates 1D overland flow network. The overland flow network features (ponds and flow pathways) generated by this methodology are dependent on the number of sewer network manholes and sewer inlets, as some of the overland flow pathways start at manholes (or sewer inlets) locations. Thus, if a simplified version of the sewer network has less manholes (or sewer inlets) than the original one, the overland flow network will be consequently different. This paper compares different overland flow networks generated with different levels of sewer network skeletonisation. Sensitivity analysis is carried out in one catchment area in Coimbra, Portugal, in order to evaluate overland flow network characteristics.

Indications for and results of liver retransplantation.

Liver retransplantation (LReTx) is the therapeutic option for the irreversible failure of a hepatic graft. Our aim was to evaluate the rate of and indications for LReTx and actuarial patient survivals. Among 1260 LTx were 79 LReTx (6.3%). During the first LTx, there were no apparent differences between patients who did or did not required LReTx. The most frequent reasons were hepatic artery thrombosis (31.6%), recurrence of the VHC cirrhosis (30.4%), and primary graft failure (21.5%). The actuarial survivals at 1 and 5 years were 83% and 69% among those without LReTx versus 71% and 61% among early LReTx, and 64% and 34% among late LReTx (P < .001). Although there exists high morbidity and mortality with LReTx, it seems that this therapeutic alternative continues to be valid for patients with early hepatic loss, but not when the graft loss was late. It becomes necessary to define the minimal acceptable results that patient can benefit from LReTx.

Effect of pentobarbital on pH and electrolyte levels after induced seizure in rats.

We studied the effects of high doses of pentobarbital (PB) and carbamazepine (CBZ) on electrolyte levels and pH in an epileptic animal model. Pentobarbital decreased Ca2+ and Na+ levels without pentylenetetrazole (PTZ). After this, Ca2+ and Na+ levels continued to decrease except when CBZ was used, which preserved the Ca2+ levels PTZ may have opposed effects on PB. Our results suggest that PB causes changes in electrolyte levels and pH, but these changes are diminished by CBZ.

Serotonin and 5-hydroxy-indole-acetic acid contents in dorsal raphe and suprachiasmatic nuclei in normal, malnourished and rehabilitated rats under 24 h of sleep deprivation.

It has been discussed that serotonin (5-HT) could be involved in the effects of sleep deprivation (SD) and/or malnutrition (M) on the sleep-wake cycle. The aim of this work was to study the effects of the M, SD and its interaction on 5-HT and 5-hydroxy-indole-acetic acid (5-HIAA) contents in the dorsal raphe (DR) and the suprachiasmatic nuclei (SCN), two sleep-wake cycle regulators. Forty-eight puppets rats were obtained from mothers fed with low or normal casein diet. They were allocated in 3 groups (n=16 each): prenatal/postnatal casein malnutrition (6/6%), prenatal casein malnutrition/nutritional casein rehabilitation (6/25%) and prenatal/postnatal casein well-nourished state (25/25%). When rats were 60 days old, 24 animals were exposed to sleep deprivation by means of forced locomotion during 24 h. The remaining 24 were kept under normal conditions of sleep-wake cycle. Then, all animals were sacrificed by decapitation. DR and SCN were dissected and processed to determine the 5-HT and 5-HIAA contents by means of HPLC. It was observed that 6/6% rats showed a 5-HT increase (DR p<0.011; SCN p<0.019) as well as in SD (DR p<0.0008; SCN p<0.0009) with respect to 25/25% rats. No differences were found in 6/25% rats. Therefore, 5-HIAA decreased significantly in both nuclei in all the groups, notably in M+SD animals (DR p<0.001; SCN p<0.001). We conclude that the sleep-wake cycle disruptions produced by chronic M and SD are mediated in part by a synergistic effect on 5-HT in the DR-SCN pathway, perhaps due to a delay in the development of such brain structures.

Pyrazinamide susceptibility testing in Mycobacterium tuberculosis using the fast resazurin microtiter assay plate.

SETTING: Department of Clinical Analysis and Biomedicine, State University of Maringa, Maringa, PR, Brazil. OBJECTIVE: To evaluate the performance of the resazurin microtiter assay (REMA) plate at pH 5.5 in detecting Mycobacterium tuberculosis susceptibility to pyrazinamide (PZA). DESIGN: The minimal inhibitory concentration (MIC) of PZA in M. tuberculosis H37Rv and M. bovis AN5 reference strains and in 34 clinical M. tuberculosis isolates (26 PZA-susceptible and eight PZA-resistant) was determined using REMA at pH 5.5 and compared to REMA at pH 6.0. RESULTS: REMA at pH 5.5 was helpful in discriminating PZA-susceptible from resistant M. tuberculosis isolates when â©¿50 µg/ml PZA was considered as the cut-off for PZA susceptibility. Furthermore, it provided results in 8 days. However, two PZA-resistant isolates failed to grow at pH 5.5. CONCLUSION: As the REMA method is rapid, inexpensive, easy to perform and read, it would be of great usefulness in low-income countries for detecting PZA-resistant M. tuberculosis. REMA at pH 5.6-5.9 should be evaluated on an extended panel of clinical M. tuberculosis isolates with a greater range of MIC values in different laboratories for a better understanding of its utility in differentiating PZA-resistant from PZA-susceptible isolates.

Diminution of large pituitary tumor after replacement therapy for primary hypothyroidism.

Thyroid-stimulating, hormone-producing tumors of the pituitary may be associated with primary hypothyroidism. The case presented here illustrates the rapid resolution of a large pituitary tumor after thyroid hormone replacement in a patient with primary hypothyroidism.

Aggressive natural-killer cell lymphoma presenting with skin lesions, breast nodule, suprarenal masses and life-threatening pericardial and pleural effusions.

We report the clinical and laboratory findings of a patient with an aggressive Epstein-Barr virus positive CD2+/CD56+ natural killer-cell lymphoma with a high mitotic activity and complex chromosomal abnormalities presenting with life-threatening pericardial and pleural effusions, disseminated skin lesions, breast nodule and large suprarenal masses. The clinical course was characterized by resistance to chemotherapy and relapsing pericardial and pleural effusions with respiratory and haemodynamic failure. Death occurred 4 months after the first manifestations of the disease as a consequence of cardiac tamponade.

Sleep alterations and brain regional changes of serotonin and its metabolite in rats exposed to ozone.

Sleep alterations and brain regional changes of serotonin were studied in rats exposed to 1.5 ppm of ozone (O3). Results showed a significant decrease in the time spent in wakefulness (W) and paradoxical sleep (PS) and a significant increase in the time spent in slow wave sleep (SWS). Neurochemical analysis showed a significant increase in the metabolism of serotonin in medulla oblongata, pons and midbrain, while both serotonin and its metabolite were reduced in hypothalamus. Although other neurotransmitters could be affected by O3 exposure, the sleep disorders observed in the present work may be related to alterations in the metabolism of serotonin produced by the exposure to O3.

Effects of lactation on hormonal levels in rural women.

Luteinizing hormone, follicle-stimulating hormone and prolactin levels were compared in ten rural and ten urban women, all of whom were experiencing lactational amenorrhea. The values of luteinizing hormone and follicle-stimulating hormone were similar in both groups. The prolactin levels were significantly elevated in the rural group.

PIP: Luteininzing hormone (LH), follicle-stimulating hormone (FSH) and prolactin levels were compared in 10 rural and 10 urban women in Mexico who were experiencing lactational amenorrhea in an effort to define any differences for these 2 groups. All the women had breast fed their babies without supplementation, and none of the women had menstruated or had taken oral contraceptives. Another 20 women who attended the Clinic for Family Planning and who did not take OCs served as controls. All the women had an extended postpartum period that varied from 9-12 months. The levels of LH in the urban group fluctuated between 1.0 and 12.0 Imu-ml, with an average of 5.1 Imu-ml. The FSH levels among the urban group ranged from 3.0 to 15.0 with an average of 7.3 Imu-ml, while the average prolactin level was 20.4 ng-ml. Duration of lactation varied from 7 to 16 months for the rural women. Their LH and FSH levels were similar to those of the urban group, but their prolactin levels were more elevated than those found in the urban group. The average prolactin level was 38.1 mg.ml, and this elevation was statistically significant. The LH values among the 20 controls fluctuated between 3.0 and 20.0 Imu-ml, with an average of 9.2 ImU-ml. The FSH levels for the control group ranged from 3.4 to 17.0 ImU-ml, with an average of 8.1 ImU-ml. Prolactin levels varied between 10.1 and 17.0 ng-ml, with an average of 14.5 ng-ml.

[Sigmoid stenosis as a complication of severe acute pancreatitis]. / Estenosis de sigma como complicación de una pancreatitis aguda severa.

We report a case of severe acute pancreatitis, of biliary etiology, complicated with a pancreatic pseudocyst and colonic stenosis localized in the sigmoid, that we interpret as secondary to the lesion produced by pancreatic enzymes spread. The treatment was surgical. Possible colonic complications in the context of an acute pancreatitis and their possible etiopathogenic mechanisms are commented. The incidence of these complications is rare and much more so the stenosis localized in the sigmoid colon.

Response to treatment with interferon-alfa in patients with chronic hepatitis C and high titers of -M2, -M4 and -M8 antimitochondrial antibodies.

UNLABELLED: The prevalence of antimitochondrial antibodies (AMA) in chronic hepatitis C is 2%; titers of AMA are usually low (< 1:40). The prevalence decreases to 0.5% when the results are verified by determination of the M2 subtype (anti-M2, ELISA). In patients in whom both hepatitis C virus (HCV) and AMA are present, the therapeutic decision to give interferon-alfa is complicated, because AMA may be 'real', and if it reflects primary biliary cirrhosis, cholestasis can be triggered or exacerbated. This does not occur when AMA positivity results from induction by hepatotropic C virus; however, this is rarely the case when AMA titers are high (> 1:160). OBJECTIVE: to undertake a preliminary analysis of the submitochondrial profile of AMA in three patients with chronic hepatitis C and positive AMA titers (> 1:160). METHODS: we determined antibodies to submitochondrial particles (subtypes) -M2, -M4 and -M8 by ELISA, complement binding (CB) and western immunoblotting with Immunoblot-M2 or WIB-M2 (immunoreactive bands). RESULTS: two patients were positive for mitochondrial subtypes by ELISA (IgG/IgM subclass) and CB (ELISA M2 470/365 in patient 1 and 600/1370 in patient 2; M4 490/1200 in patient 2. CB M2 1:128, M4 1:64, M8 1:64 in patient 1, M2 1:128 in patient 2). Immunoreactive epitopes (bands) were detected with WIB-M2 for 70, 56, 51, 45 and 36-kDa molecules. Interferon-alfa treatment was unsuccessful, with biochemical exacerbation of cholestasis. In contrast, the patient with no submitochondrial particles according to ELISA, CB and WIB-M2 results responded favorable to this drug. CONCLUSION: these preliminary results suggest that analyses to detect antibodies to submitochondrial particles (-M2, -M4 and -M8 subtypes) and -M2-immunoreactive epitopes in patients with chronic hepatitis C and AMA titers > 1:160 facilitates the diagnosis of primary biliary cirrhosis, and establishes a contraindication for treatment with interferon-alfa despite the presence of HCV infection.

[Refractory heart failure in a 26-year-old woman with idiopathic hemochromatosis]. / Insuficiência cardíaca refractária numa mulher de 26 anos com hemocromatose idiopática.

Idiopathic hemochromatosis, the most frequent inherited disease in Caucasians, is frequently undiagnosed. In this disorder, characterized by a continued inappropriated absorption of dietary iron, the clinical manifestations result from damage to those organ systems in which iron has been pathologically deposited, namely, the heart and the liver. Typically, hemochromatosis becomes clinically manifest in later life and in men more frequently than in women. This has been attributed to the extra loss of iron in women through menstruation and pregnancies. Removal of the excess iron by phlebotomy will prevent all of the complications of hemochromatosis of when begun early. In this paper, we report a case of a young woman with a eight years evolution of amenorrhea, cardiac failure, diabetes mellitus and increased pigmentation of the skin, associated with biochemical markers of iron overload. It is emphasized that hemochromatosis most be excluded in all patients with a unexplained cardiac failure.

[Asymptomatic renal carcinoma diagnosed based on synchronous metastasis in the thyroid gland]. / Carcinoma renal asintomático diagnosticado a partir de una metástasis sincrónica en tiroides.

Secondary tumors of the thyroid are very rare, being the kidney the most frequent place of the primary tumor. The majority of these metastases appear months or years after the primary renal tumor. We report the case of an asymptomatic renal carcinoma discovered after the histological analysis of a thyroidectomy piece. The treatment of the primary renal tumor was radical nephrectomy. Three years after diagnosis and treatment the patient is free of relapse.