High doses of riboflavin and the elimination of dietary red meat promote the recovery of some motor functions in Parkinson's disease patients

Abnormal riboflavin status in the absence of a dietary deficiency was detected in 31 consecutive outpatients with Parkinson's disease (PD), while the classical determinants of homocysteine levels (B6, folic acid, and B12) were usually within normal limits. In contrast, only 3 of 10 consecutive outpatients with dementia without previous stroke had abnormal riboflavin status. The data for 12 patients who did not complete 6 months of therapy or did not comply with the proposed treatment paradigm were excluded from analysis. Nineteen PD patients (8 males and 11 females, mean age ± SD = 66.2 ± 8.6 years; 3, 3, 2, 5, and 6 patients in Hoehn and Yahr stages I to V) received riboflavin orally (30 mg every 8 h) plus their usual symptomatic medications and all red meat was eliminated from their diet. After 1 month the riboflavin status of the patients was normalized from 106.4 ± 34.9 to 179.2 ± 23 ng/ml (N = 9). Motor capacity was measured by a modification of the scoring system of Hoehn and Yahr, which reports motor capacity as percent. All 19 patients who completed 6 months of treatment showed improved motor capacity during the first three months and most reached a plateau while 5/19 continued to improve in the 3- to 6-month interval. Their average motor capacity increased from 44 to 71% after 6 months, increasing significantly every month compared with their own pretreatment status (P < 0.001, Wilcoxon signed rank test). Discontinuation of riboflavin for several days did not impair motor capacity and yellowish urine was the only side effect observed. The data show that the proposed treatment improves the clinical condition of PD patients. Riboflavin-sensitive mechanisms involved in PD may include glutathione depletion, cumulative mitochondrial DNA mutations, disturbed mitochondrial protein complexes, and abnormal iron metabolism. More studies are required to identify the mechanisms involved.

Clinical signs of pneumonia in children: association with and prediction of diagnosis by fuzzy sets theory

The present study compares the performance of stochastic and fuzzy models for the analysis of the relationship between clinical signs and diagnosis. Data obtained for 153 children concerning diagnosis (pneumonia, other non-pneumonia diseases, absence of disease) and seven clinical signs were divided into two samples, one for analysis and other for validation. The former was used to derive relations by multi-discriminant analysis (MDA) and by fuzzy max-min compositions (fuzzy), and the latter was used to assess the predictions drawn from each type of relation. MDA and fuzzy were closely similar in terms of prediction, with correct allocation of 75.7 to 78.3% of patients in the validation sample, and displaying only a single instance of disagreement: a patient with low level of toxemia was mistaken as not diseased by MDA and correctly taken as somehow ill by fuzzy. Concerning relations, each method provided different information, each revealing different aspects of the relations between clinical signs and diagnoses. Both methods agreed on pointing X-ray, dyspnea, and auscultation as better related with pneumonia, but only fuzzy was able to detect relations of heart rate, body temperature, toxemia and respiratory rate with pneumonia. Moreover, only fuzzy was able to detect a relationship between heart rate and absence of disease, which allowed the detection of six malnourished children whose diagnoses as healthy are, indeed, disputable. The conclusion is that even though fuzzy sets theory might not improve prediction, it certainly does enhance clinical knowledge since it detects relationships not visible to stochastic models.

Twenty-four-hour esophageal pH monitoring in children and adolescents with chronic and/or recurrent rhinosinusitis

Gastroesophageal reflux (GER) disorder was studied in children and adolescents with chronic and/or recurrent rhinosinusitis not associated with bronchial asthma. Ten children with a clinical and radiological diagnosis of chronic and/or recurrent rhinosinusitis, consecutively attended at the Pediatric Otolaryngology Outpatient Clinic, Federal University of São Paulo, were evaluated. Prolonged esophageal pH monitoring was used to investigate GER disorder. The mean age of the ten patients evaluated (eight males) was 7.4 ± 2.4 years. Two patients presented vomiting as a clinical manifestation and one patient presented retrosternal pain with a burning sensation. Twenty-four-hour esophageal pH monitoring was performed using the Sandhill apparatus. An antimony probe electrode was placed in the lower third of the esophagus, confirmed by fluoroscopy and later by a chest X-ray. The parameters analyzed by esophageal pH monitoring included: total percent time of the presence of acid esophageal pH, i.e., pH below 4 (<4.2%); total number of acid episodes (<50 episodes); number of reflux episodes longer than 5 min (3 or less), and duration of the longest reflux episode (<9.2 min). One patient (1/10, 10%) presented a 24-h esophageal pH profile compatible with GER disorder. This data suggest that an association between chronic rhinosinusitis not associated with bronchial asthma and GER disorder may exist in children and adolescents, especially in those with compatible GER disorder symptoms. In these cases, 24-h esophageal pH monitoring should be performed before indicating surgery, since the present data suggest that 10% of chronic rhinosinusitis surgeries can be eliminated.

Seroprevalence of human herpesvirus 8 infection in children born to HIV-1- infected women in São Paulo, Brazil

Human herpesvirus-8 (HHV-8) appears to be transmitted mainly by sexual contact. However, several studies suggest that in developing countries the infection may be acquired early in life by routes other than sexual transmission. The present study estimated the seroprevalence of HHV-8 in Brazilian children born to HIV-1-infected mothers. The serum samples were collected in a cross-sectional cohort study from 99 children born to HIV-infected mothers (median age 3.27 years; range 1.5-13.8 years) attending the outpatient clinic of the Federal University of São Paulo. IgG antibodies to HHV-8 latency-associated nuclear antigen and lytic phase antigens were detected by immunofluorescence assays. The samples tested were collected from children aged 12 months or older to exclude the possibility of cross-placental antibody transport. The total prevalence of anti-lytic antibodies in this population (5/99; 5%) reveals that HHV-8 infection can occur during childhood. Children aged 1.5 to 2 years had a seroprevalence of 2% (1/50) and children aged 3.25 to 13.8 years had a seroprevalence of 8% (4/49). This difference was not statistically significant, probably because of the small size of the sample, but it suggests that HHV-8 infection occurs more commonly late in infancy. Further prospective studies are necessary to evaluate the timing and risk factors for primary HHV-8 infection in the pediatric population.

Etiology of diarrheal infections in children of Porto Velho (Rondonia, Western Amazon region, Brazil)

In the present study, 470 children less than 72 months of age and presenting acute diarrhea were examined to identify associated enteropathogenic agents. Viruses were the pathogens most frequently found in stools of infants with diarrhea, including 111 cases of rotavirus (23.6% of the total diarrhea cases) and 30 cases of adenovirus (6.3%). The second group was diarrheogenic Escherichia coli (86 cases, 18.2%), followed by Salmonella sp (44 cases, 9.3%) and Shigella sp (24 cases, 5.1%). Using the PCR technique to differentiate the pathogenic categories of E. coli, it was possible to identify 29 cases (6.1%) of enteropathogenic E. coli (EPEC). Of these, 10 (2.1%) were typical EPEC and 19 (4.0%) atypical EPEC. In addition, there were 26 cases (5.5%) of enteroaggregative E. coli, 21 cases (4.4%) of enterotoxigenic E. coli, 7 cases (1.4%) of enteroinvasive E. coli (EIEC), and 3 cases (0.6%) of enterohemorrhagic E. coli. When comparing the frequencies of diarrheogenic E. coli, EPEC was the only category for which significant differences were found between diarrhea and control groups. A low frequency of EIEC was found, thus EIEC cannot be considered to be a potential etiology agent of diarrhea. Simultaneous infections with two pathogens were found in 39 diarrhea cases but not in controls, suggesting associations among potential enteropathogens in the etiology of diarrhea. The frequent association of diarrheogenic E. coli strains was significantly higher than the probability of their random association, suggesting the presence of facilitating factor(s).

Cytosine arabinoside-metabolizing enzyme genes are underexpressed in children with MLL gene-rearranged acute lymphoblastic leukemia

Infant acute lymphoblastic leukemia (IALL) is characterized by mixed lineage leukemia (MLL) gene rearrangements, unique gene expression profiles, poor prognosis, and drug resistance. One exception is cytosine arabinoside (Ara-C) to which IALL cells seem to be more sensitive. We quantified mRNA expression of Ara-C key enzymes in leukemic lymphoblasts from 64 Brazilian ALL children, 15 of them presenting MLL gene rearrangement, and correlated it with clinical and biological features. The diagnosis was based on morphological criteria and immunophenotyping using monoclonal antibodies. MLL gene rearrangements were detected by conventional cytogenetic analysis, RT-PCR and/or fluorescence in situ hybridization. The DCK and HENT1 expression levels were determined by real-time quantitative PCR using SYBR Green I. Relative quantification was made by the standard curve method. The results were analyzed by Mann-Whitney and Fisher exact tests. A P value of £0.05 was considered to be statistically significant. DCK and HENT1 expression levels were significantly lower in children with MLL gene-rearranged ALL compared to children with MLL germ line ALL (P = 0.0003 and 0.03, respectively). Our results differ from previous ones concerning HENT1 mRNA expression that observed a higher expression level in MLL gene-rearranged leukemias. In conclusion, the expression of the genes related to Ara-C metabolism was lower in MLL-positive children in the sample studied, suggesting the presence of population differences in the expression profile of these genes especially for HENT1.

Novel word learning ability in chronic post-stroke aphasia : variability and modality effects

Novel word learning has been rarely studied in people with aphasia (PWA), although it can provide a relatively pure measure of their learning potential, and thereby contribute to the development of effective aphasia treatment methods. The main aim of the present thesis was to explore the capacity of PWA for associative learning of word–referent pairings and cognitive-linguistic factors related to it. More specifically, the thesis examined learning and long-term maintenance of the learned pairings, the role of lexical-semantic abilities in learning as well as acquisition of phonological versus semantic information in associative novel word learning. Furthermore, the effect of modality on associative novel word learning and the neural underpinnings of successful learning were explored. The learning experiments utilized the Ancient Farming Equipment (AFE) paradigm that employs drawings of unfamiliar referents and their unfamiliar names. Case studies of Finnishand English-speaking people with chronic aphasia (n = 6) were conducted in the investigation. The learning results of PWA were compared to those of healthy control participants, and active production of the novel words and their semantic definitions was used as learning outcome measures. PWA learned novel word–novel referent pairings, but the variation between individuals was very wide, from more modest outcomes (Studies I–II) up to levels on a par with healthy individuals (Studies III–IV). In incidental learning of semantic definitions, none of the PWA reached the performance level of the healthy control participants. Some PWA maintained part of the learning outcomes up to months post-training, and one individual showed full maintenance of the novel words at six months post-training (Study IV). Intact lexical-semantic processing skills promoted learning in PWA (Studies I–II) but poor phonological short-term memory capacities did not rule out novel word learning. In two PWA with successful learning and long-term maintenance of novel word–novel referent pairings, learning relied on orthographic input while auditory input led to significantly inferior learning outcomes (Studies III–IV). In one of these individuals, this previously undetected modalityspecific learning ability was successfully translated into training with familiar but inaccessible everyday words (Study IV). Functional magnetic resonance imaging revealed that this individual had a disconnected dorsal speech processing pathway in the left hemisphere, but a right-hemispheric neural network mediated successful novel word learning via reading. Finally, the results of Study III suggested that the cognitive-linguistic profile may not always predict the optimal learning channel for an individual with aphasia. Small-scale learning probes seem therefore useful in revealing functional learning channels in post-stroke aphasia.

Sodium taste threshold in children and its relationship to blood pressure

Popular science has emphasized the risks of high sodium intake and many studies have confirmed that salt intake is closely related to hypertension. The present mini-review summarizes experiments about salt taste sensitivity and its relationship with blood pressure (BP) and other variables of clinical and familial relevance. Children and adolescents from control parents (N = 72) or with at least one essential hypertensive (EHT) parent (N = 51) were investigated. Maternal questionnaires on eating habits and vomiting episodes were collected. Offspring, anthropometric, BP, and salt taste sensitivity values were recorded and blood samples analyzed. Most mothers declared that they added "little salt" when cooking. Salt taste sensitivity was inversely correlated with systolic BP (SBP) in control youngsters (r = -0.33; P = 0.015). In the EHT group, SBP values were similar to control and a lower salt taste sensitivity threshold. Obese offspring of EHT parents showed higher SBP and C-reactive protein values but no differences in renin-angiotensin-aldosterone system activity. Salt taste sensitivity was correlated with SBP only in the non-obese EHT group (N = 41; r = 0.37; P = 0.02). Salt taste sensitivity was correlated with SBP in healthy, normotensive children and adolescents whose mothers reported significant vomiting during the first trimester (N = 18; r = -0.66; P < 0.005), but not in "non-vomiter offspring" (N = 54; r = -0.18; nonsignificant). There is evidence for a linkage between high blood pressure, salt intake and sensitivity, perinatal environment and obesity, with potential physiopathological implications in humans. This relationship has not been studied comprehensively using homogeneous methods and therefore more research is needed in this field.

Moderate-term reproducibility of heart rate variability during rest and light to moderate exercise in children

Previous studies have demonstrated the high reproducibility of heart rate variability (HRV) measures in adults while little information exists concerning HRV reproducibility in children. Subsequently, the aim of the current study was to examine the moderate-term reproducibility of heart rate and frequency domain measures of HRV during rest and light to moderate exercise in children. Ten healthy children (6 males, 4 females) aged between 7 and 12 years of age volunteered for this study with HRV recordings obtained during supine rest and three treadmill walking exercise work rates (≤60% maximum heart rate), initially and then 8 weeks later. Differences (P < 0.05) between variables were examined using paired t-tests or Wilcoxon signed rank tests while reliability and reproducibility were examined by intraclass correlation coefficients (ICC), coefficients of variation (CV), and mean bias ratio and ratio limits of agreement (LOA). Heart rate and all measures of HRV at rest and exercise were unchanged after 8 weeks. Significant ICC were documented primarily during rest (0.72-0.85) while weaker relationships (-0.02-0.87) were evident during exercise. A large range of CV was identified during rest (6-33%) and exercise (3-128%) while the ratio LOA were variable and substantial (1.04-2.73). Despite similar HRV over an 8-week period, variable ICC and sizable CV and ratio LOA indicate moderate to poor reproducibility of HRV in children, particularly during light to moderate exercise. Studies examining HRV in children should include age- or maturation stage-matched control participants to address the age-related change in HRV and inadequate HRV reliability.

Delta sleep instability in children with chronic arthritis

The objective of the present study was to evaluate the expression of a cyclic alternating pattern (CAP) in slow wave sleep (SWS) in children with the well-defined chronic syndrome juvenile idiopathic arthritis (JIA). Twelve patients (9-17 years of age), 7 girls, with JIA were compared to matched controls by age, pubertal stage and gender. After one night of habituation in the sleep laboratory, sleep measurements were obtained by standard polysomnography with conventional sleep scoring and additional CAP analyses. The sleep parameters of the JIA and control groups were similar for sleep efficiency (91.1 ± 6.7 vs 95.8 ± 4.0), sleep stage in minutes: stage 1 (16.8 ± 8.5 vs 17.8 ± 4.0), stage 2 (251.9 ± 41 vs 262.8 ± 38.1), stage 3 (17.0 ± 6.0 vs 15.1 ± 5.7), stage 4 (61.0 ± 21.7 vs 77.1 ± 20.4), and rapid eye movement sleep (82.0 ± 27.6 vs 99.0 ± 23.9), respectively. JIA patients presented nocturnal disrupted sleep, with an increase in short awakenings, but CAP analyses showed that sleep disruption was present even during SWS, showing an increase in the overall CAP rate (P < 0.01). Overall CAP rate during non-rapid eye movement sleep was significantly higher in pediatric patients who were in chronic pain. This is the first study of CAP in pediatric patients with chronic arthritis showing that CAP analyses can be a powerful tool for the investigation of disturbance of SWS in children, based on sleep EEG visual analysis.

Effect of auditory training on the middle latency response in children with (central) auditory processing disorder

The purpose of this study was to determine the middle latency response (MLR) characteristics (latency and amplitude) in children with (central) auditory processing disorder [(C)APD], categorized as such by their performance on the central auditory test battery, and the effects of these characteristics after auditory training. Thirty children with (C)APD, 8 to 14 years of age, were tested using the MLR-evoked potential. This group was then enrolled in an 8-week auditory training program and then retested at the completion of the program. A control group of 22 children without (C)APD, composed of relatives and acquaintances of those involved in the research, underwent the same testing at equal time intervals, but were not enrolled in the auditory training program. Before auditory training, MLR results for the (C)APD group exhibited lower C3-A1 and C3-A2 wave amplitudes in comparison to the control group [C3-A1, 0.84 µV (mean), 0.39 (SD - standard deviation) for the (C)APD group and 1.18 µV (mean), 0.65 (SD) for the control group; C3-A2, 0.69 µV (mean), 0.31 (SD) for the (C)APD group and 1.00 µV (mean), 0.46 (SD) for the control group]. After training, the MLR C3-A1 [1.59 µV (mean), 0.82 (SD)] and C3-A2 [1.24 µV (mean), 0.73 (SD)] wave amplitudes of the (C)APD group significantly increased, so that there was no longer a significant difference in MLR amplitude between (C)APD and control groups. These findings suggest progress in the use of electrophysiological measurements for the diagnosis and treatment of (C)APD.

Longitudinal evaluation of hepatic osteodystrophy in children and adolescents with chronic cholestatic liver disease

Bone mass loss is a major complication of chronic cholestatic liver disease (CCD). However, the long-term impact of CCD on bone mass acquisition is unknown. We longitudinally assessed bone mineral density (BMD) and factors involved in bone remodeling in 9 children and adolescents with CCD Child-Pugh A (5 boys/4 girls) and in 13 controls (6 boys/7 girls). The groups were evaluated twice, at baseline (T0) and after 3 years (T1), when osteocalcin, deoxypyridinoline, 25-hydroxyvitamin-D, parathyroid hormone, insulin-like growth factor-I (IGF-I), and BMD (L1-L4, proximal femur and total body) were determined. Serum levels of receptor activator for nuclear factor kB ligand (RANKL) and osteoprotegerin were measured only at T1. Lumbar spine BMD was reanalyzed twice: after adjustment for bone age and to compensate for the height factor. Volumetric density was also estimated mathematically in L2-L4. The BMD of L1-L4 was lower in the CCD group (Z-score at T0: control = -1.2 ± 0.8 vs CCD = -2.2 ± 1.4, P < 0.05; T1: control = -0.7 ± 0.8 vs CCD = -2.1 ± 1.1, P < 0.05). Osteocalcin and deoxypyridinoline were similar for the two groups. The CCD group presented lower IGF-I (Z-score at T1: control = 1.4 ± 2.8 vs CCD = -1.5 ± 1.0, P < 0.05) and RANKL (control = 0.465 ± 0.275 vs CCD = 0.195 ± 0.250 pM, P < 0.05) than control. Children with compensated CCD Child-Pugh A showed early impairment of bone acquisition, with the impact being more severe in an initial phase and then tapering in a slowly progressive way. Reduction in endocrine IGF-I has a crucial role in this process.

Percutaneous sciatic nerve block with tramadol induces analgesia and motor blockade in two animal pain models

Local anesthetic efficacy of tramadol has been reported following intradermal application. Our aim was to investigate the effect of perineural tramadol as the sole analgesic in two pain models. Male Wistar rats (280-380 g; N = 5/group) were used in these experiments. A neurostimulation-guided sciatic nerve block was performed and 2% lidocaine or tramadol (1.25 and 5 mg) was perineurally injected in two different animal pain models. In the flinching behavior test, the number of flinches was evaluated and in the plantar incision model, mechanical and heat thresholds were measured. Motor effects of lidocaine and tramadol were quantified and a motor block score elaborated. Tramadol, 1.25 mg, completely blocked the first and reduced the second phase of the flinching behavior test. In the plantar incision model, tramadol (1.25 mg) increased both paw withdrawal latency in response to radiant heat (8.3 ± 1.1, 12.7 ± 1.8, 8.4 ± 0.8, and 11.1 ± 3.3 s) and mechanical threshold in response to von Frey filaments (459 ± 82.8, 447.5 ± 91.7, 320.1 ± 120, 126.43 ± 92.8 mN) at 5, 15, 30, and 60 min, respectively. Sham block or contralateral sciatic nerve block did not differ from perineural saline injection throughout the study in either model. The effect of tramadol was not antagonized by intraperitoneal naloxone. High dose tramadol (5 mg) blocked motor function as well as 2% lidocaine. In conclusion, tramadol blocks nociception and motor function in vivo similar to local anesthetics.