Abstract in English:ßS-Globin haplotypes were studied in 80 (160 ßS chromosomes) sickle cell disease patients from Salvador, Brazil, a city with a large population of African origin resulting from the slave trade from Western Africa, mainly from the Bay of Benin. Hematological and hemoglobin analyses were carried out by standard methods. The ßS-haplotypes were determined by PCR and dot-blot techniques. A total of 77 (48.1%) chromosomes were characterized as Central African Republic (CAR) haplotype, 73 (45.6%) as Benin (BEN), 1 (0.63%) as Senegal (SEN), and 9 (5.63%) as atypical (Atp). Genotype was CAR/CAR in 17 (21.3%) patients, BEN/BEN in 17 (21.3%), CAR/BEN in 37 (46.3%), BEN/SEN in 1 (1.25%), BEN/Atp in 1 (1.25%), CAR/Atp in 6 (7.5%), and Atp/Atp in 1 (1.25%). Hemoglobin concentrations and hematocrit values did not differ among genotype groups but were significantly higher in 25 patients presenting percent fetal hemoglobin (%HbF) > or = 10% (P = 0.002 and 0.003, respectively). The median HbF concentration was 7.54 ± 4.342% for the CAR/CAR genotype, 9.88 ± 3.558% for the BEN/BEN genotype, 8.146 ± 4.631% for the CAR/BEN genotype, and 4.180 ± 2.250% for the CAR/Atp genotype (P = 0.02), although 1 CAR/CAR individual presented an HbF concentration as high as 15%. In view of the ethnic and geographical origin of this population, we did not expect a Hardy-Weinberg equilibrium for CAR/CAR and BEN/BEN homozygous haplotypes and a high proportion of heterozygous CAR/BEN haplotypes since the State of Bahia historically received more slaves from Western Africa than from Central Africa.
Abstract in English:Hydroxyurea is used for sickle-cell disease patients in order to increase fetal hemoglobin synthesis and consequently decrease the severity of pain episodes. Fetal hemoglobin, which is formed by gamma-globin chains A and G, is present in a constant composition throughout fetal development: about 75% of Ggamma and 25% of Agamma. In contrast, adult red cells contain about 40% of Ggamma and 60% of Agamma. In the present study, we analyzed the effect of hydroxyurea induction on the gamma chain composition of fetal hemoglobin in 31 sickle-cell disease patients treated with hydroxyurea. The control group was composed of 30 sickle-cell disease patients not treated with hydroxyurea in clinical steady state. The patients were older than 13 years and were not matched for age. All patients were seen at Hemocentro/UNICAMP and Boldrini Infantile Center, Campinas, SP, Brazil. The levels of total hemoglobin were significantly higher in patients treated with hydroxyurea (mean ± SD, 9.6 ± 2.16 g/dl) than in untreated patients (8.07 ± 0.91 g/dl). Fetal hemoglobin levels were also higher in treated patients (14.16 ± 8.31%) than in untreated patients (8.8 ± 4.09%), as was the Ggamma/Agamma ratio (1.45 ± 0.78 vs 0.98 ± 0.4, P < 0.005). The increase in the Ggamma/Agamma ratio in patients treated with hydroxyurea suggests the prevalence of a pattern of fetal hemoglobin synthesis, whereas patients not treated with hydroxyurea maintain the adult pattern of fetal hemoglobin synthesis. Because no correlation was observed between the Ggamma/Agamma ratio and total hemoglobin or fetal hemoglobin levels, the increase in Ggamma chain synthesis may not imply a higher production of hemoglobin.
Abstract in English:Data obtained during the past five years have indicated that there are important age- and gender-based differences in the regulation and action of leptin in humans. To study the physiological changes of leptin during puberty in both sexes, and its relationship with body composition and sexual maturation, we measured leptin concentrations in 175 healthy adolescents (80 girls, 95 boys, 10-18 years of age), representing all pubertal stages. We excluded individuals with a body mass index (BMI) below the 5thor above the 95th percentile relative to age. Serum concentrations of leptin were determined by a monoclonal antibody-based immunofluorimetric assay, developed in our laboratory. Body composition was determined by dual-energy X-ray absorptiometry. Pubertal stage was assigned by physical examination, according to Tanner criteria for breast development in females and genital development in males. Leptin concentration in girls (N = 80) presented a positive linear correlation with age (r = 0.35, P = 0.0012), BMI (r = 0.65, P < 0.0001) and %fat mass (r = 0.76, P < 0.0001). In boys (N = 95) there was a positive correlation with BMI (r = 0.49, P < 0.0001) and %fat mass (r = 0.85, P < 0.0001), but a significant negative linear correlation with Tanner stage (r = -0.45, P < 0.0001) and age (r = -0.40, P < 0.0001). The regression equation revealed that %fat mass and BMI are the best parameters to be used to estimate leptin levels in both sexes. Thus, the normal reference ranges for circulating leptin during adolescence should be constructed according to BMI or %fat mass to assure a correct evaluation.
Abstract in English:Fetuses of mothers with gestational diabetes mellitus are at increased risk to develop perinatal complications mainly due to macrosomia. However, in view of the marked heterogeneity of this disease, it seems difficult to set guidelines for diagnosis and treatment. This complicates the choice of assigning patients either to diet or to insulin therapy. Also of concern is how much benefit could be expected from insulin therapy in preventing fetal complications in these patients. In a systematic review of the literature assessing the efficacy of insulin in preventing macrosomia in fetuses of mothers with gestational diabetes, we found six randomized controlled trials comparing diet alone to diet plus insulin. The studies included a total of 1281 patients (644 in the diet plus insulin group and 637 in the diet group), with marked differences among trials concerning diagnostic criteria, randomization process and treatment goals. Meta-analysis of the data resulted in a risk difference of -0.098 (95%CI: -0.168 to -0.028), and a number-necessary-to-treat of 11 (95%CI: 6 to 36), which means that it is necessary to treat 11 patients with insulin to prevent one case of macrosomia. This indicates a potential benefit of insulin, but not significantly enough to set treatment guidelines. Because of the heterogeneous evidence available in the literature about this matter, we conclude that larger trials addressing the efficacy of these two therapeutic modalities in preventing macrosomia are warranted.
Abstract in English:Pancreatic ß cell function and insulin sensitivity, analyzed by the homeostasis model assessment, before and after 24 weeks of insulin therapy were studied and correlated with the presence of autoantibodies against ß cells (islet cell and anti-glutamic acid decarboxylase antibodies), in a group of 18 Brazilian lean adult non-insulin-dependent diabetes mellitus (NIDDM) patients with oral hypoglycemic agent failure (OHAF). Median fasting plasma glucose before and after insulin treatment was 19.1 and 8.5 mmol/l, respectively (P < 0.001); median HbA1c was 11.7% before vs 7.2% after insulin treatment (P < 0.001). Forty-four percent of the patients were positive (Ab+) to at least one autoantibody. Fasting C-peptide levels were lower in Ab+ than Ab- patients, both before (Ab+: 0.16 ± 0.09 vs Ab-: 0.41 ± 0.35 nmol/l, P < 0.003) and after insulin treatment (Ab+: 0.22 ± 0.13 vs Ab-: 0.44 ± 0.24 nmol/l, P < 0.03). Improvement of Hß was seen in Ab- (median before: 7.3 vs after insulin therapy: 33.4%, P = 0.003) but not in Ab+ patients (median before: 6.6 vs after insulin therapy: 20.9%). These results show that the OHAF observed in the 18 NIDDM patients studied was due mainly to two major causes: autoantibodies and ß cell desensitization. Autoantibodies against ß cells could account for 44% of OHAF, but Ab- patients may still present ß cell function recovery, mainly after a period of ß cell rest with insulin therapy. However, the effects of ß cell function recovery on the restoration of the response to oral hypoglycemic agents need to be determined.
Abstract in English:Deficiency of 21-hydroxylase is the most common form of congenital adrenal hyperplasia (CAH-21OH). We determined by allele-specific PCR the frequency of microconversion in the CYP21A2 gene in 50 Brazilian patients with the classical (salt wasting: SW and simple virilizing: SV) forms and nonclassical (NC) form of CAH-21OH and correlated genotype with phenotype. Genotypes were classified into three mutation groups (A, B, and C) based on the amount of enzymatic activity in in vitro studies using adrenal cells. In 94 unrelated alleles, we diagnosed 76% of the affected alleles after screening for 7 microconversions. The most frequent point mutations observed in this series were I172N (19%), V281L (18%), and IVS2,A/C>G,-12 (15%). In the SW form, the most frequent mutation was IVS2,A/C>G,-12 (38%), in the SV form it was I172N (53%), and in the NC form it was V281L (57.7%). We observed a good correlation between genotype and phenotype. Discordance between genotype and phenotype was found in one SV patient with a mild mutation in one of the alleles (R356W/V281L). However, we cannot rule out the presence of an additional mutation in these alleles. We also observed a good correlation of genotype with 17alpha-hydroxyprogesterone, testosterone, and androstenedione levels. The severity of external genitalia virilization correlated with the severity of mutation. In conclusion, the frequencies described in the present study did not differ from worldwide studies, including the Brazilian population. The few differences observed may reflect individual sample variations. This new Brazilian cohort study suggests the presence of new mutations in Brazilian patients with different forms of CAH-21OH.
Abstract in English:Short stature, a marker for undernutrition early in life, has been associated with obesity in Brazilian women, but not in men. We tested the hypothesis that weight gain during the reproductive years could explain this gender difference. A national two-stage household survey of mothers with one or more children under five years of age was conducted in Brazil in 1996. The subjects were women aged 20 to 45 years (N = 2297), with last delivery seven months or more prior to the interview. The regions of the country were divided into rural, North/Northeast (urban underdeveloped) and South/Southeast/Midwest (urban developed). The dependent variables were current body mass index (BMI) measured, BMI prior to childbearing (reported), and BMI change. Socioeconomic variables included mother's years of education and family purchasing power score. A secondary analysis was restricted to primiparous women. The prevalence of current overweight and overweight prior to childbearing (BMI > or = 25 kg/m²) was higher among shorter women (<1.50 m) compared to normal stature women only in the urban developed region (P < 0.05). After adjustment for socioeconomic variables, age, parity, BMI prior to childbearing, and age at first birth, current BMI was 2.39 units higher (P = 0.008) for short stature women living in the urban developed area compared with short stature women living in the urban underdeveloped area. For both multiparous and primiparous women, BMI gain compared to the value prior to childbearing was significantly higher among short stature women living in the urban developed region (P <= 0.04). These results provide clear evidence that short stature was associated with a higher BMI and with an increased risk of weight gain/retention with pregnancy in the developed areas of Brazil, but not in the underdeveloped ones.
Abstract in English:Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive disorder due to an inborn error of cholesterol metabolism, characterized by congenital malformations, dysmorphism of multiple organs, mental retardation and delayed neuropsychomotor development resulting from cholesterol biosynthesis deficiency. A defect in 3ß-hydroxysteroid-delta7-reductase (delta7-sterol-reductase), responsible for the conversion of 7-dehydrocholesterol (7-DHC) to cholesterol, causes an increase in 7-DHC and frequently reduces plasma cholesterol levels. The clinical diagnosis of SLOS cannot always be conclusive because of the remarkable variability of clinical expression of the disorder. Thus, confirmation by the measurement of plasma 7-DHC levels is needed. In the present study, we used a simple, fast, and selective method based on ultraviolet spectrophotometry to measure 7-DHC in order to diagnose SLOS. 7-DHC was extracted serially from 200 µl plasma with ethanol and n-hexane and the absorbance at 234 and 282 nm was determined. The method was applied to negative control plasma samples from 23 normal individuals and from 6 cases of suspected SLOS. The method was adequate and reliable and 2 SLOS cases were diagnosed.
Abstract in English:Two radioaerosol preparations, TechneScan®-DTPA (99mTc-DTPA, 40 mCi/3 ml; IPEN-CNEN, São Paulo, SP, Brazil) and TechneScan®-DTPA/AEROSOL (99mTc-DTPA/A, 15 mCi/1.5 ml with 0.5 ml ethanol; Mallinckrodt Medical, St. Louis, MO, USA), were compared in pulmonary ventilation studies in terms of total radiocounts and clearance after inhalation. An aerosol with ethanol is supposed to better distribute the radioparticles in the lungs. Twenty normal nonsmoking volunteers (10 men and 10 women), mean age of 23.2 years (range: 20 to 35 years), were studied. Images were obtained immediately and 30, 60 and 90 min after inhalation. Total and regional counts were obtained and the clearance half-lives of both lungs were determined. There was no difference in total counts between the two types of radioaerosol at any time (mean of ~188,000 cpm for male and female subjects at time zero in both aerosols). The highest count was obtained in the middle region of both lungs (P<0.001) with both preparations. The clearance half-life did not differ between aerosols (mean of ~80-88 min for male and female subjects for both aerosols). Small nonsignificant regional differences were observed. No differences between genders or between right and left lung were observed. 99mTc-DTPA/A generated the highest output of radioaerosol. 99mTc-DTPA with alcohol costs approximately five times more than the aerosol without alcohol. The present results show that either kind of aerosol may be adopted routinely for use in pulmonary examinations without affecting diagnosis. We suggest that the amount of 740 mBq (20 mCi) of 99mTc-DTPA in 1.5 ml saline can be used for routine examinations resulting in reduction of costs in pulmonary ventilation studies without diagnostic impairment.
Abstract in English:Rounded atelectasis (RA) is a benign and unusual form of subpleural lung collapse that has been described mostly in asbestos-exposed workers. This form of atelectasis manifests as a lung nodule and can be confused with bronchogenic carcinoma upon conventional radiologic examination. The objective of the present study was to evaluate the variation in contrast uptake in computed tomography for the identification of asbestos-related RA in Brazil. Between January 1998 and December 2000, high-resolution computed tomography (HRCT) was performed in 1658 asbestos-exposed workers. The diagnosis was made in nine patients based on a history of prior asbestos exposure, the presence of characteristic (HRCT) findings and lesions unchanged in size over 2 years or more. In three of them the diagnosis was confirmed during surgery. The dynamic contrast enhancement study was modified to evaluate nodules and pulmonary masses. All nine patients with RA received iodide contrast according to weight. The average enhancement after iodide contrast was infused, reported as Hounsfield units (HU), increased from 62.5 ± 9.7 to 125.4 ± 20.7 (P < 0.05), with a mean enhancement of 62.5 ± 19.7 (range 40 to 89) and with a uniform dense opacification. In conclusion, in this study all patients with RA showed contrast enhancement with uniform dense opacification. The main clinical implication of this finding is that this procedure does not permit differentiation between RA and malignant pulmonary neoplasm.
Abstract in English:Tumor necrosis factor-alpha (TNF-alpha) is one of the most important proinflammatory cytokines which plays a central role in host defense and in the acute inflammatory response related to tissue injury. The major source of TNF-alpha are immune cells such as neutrophils and macrophages. We tested the hypothesis that pentoxifylline, a methylxanthine derivative, down-regulates proinflammatory cytokine expression during acute lung injury in rats. Male Wistar rats weighing 250 to 450 g were anesthetized ip with 50 mg/kg sodium thiopental and randomly divided into three groups: group 1 (N = 7): tidal volume (V T) = 7 ml/kg, respiratory rate (RR) = 50 breaths/min and normal saline infusion; group 2 (N = 7): V T = 42 ml/kg, RR = 9 breaths/min and normal saline infusion; group 3 (N = 7): V T = 42 ml/kg, RR = 9 breaths/min and pentoxifylline infusion. The animals were ventilated with an inspired oxygen fraction of 1.0, a positive end-expiratory pressure of 3 cmH2O, and normal saline or pentoxifylline injected into the left femoral vein. The mRNA of TNF-alpha rapidly increased in the lung tissue within 180 min of ventilation with a higher V T with normal saline infusion. The concentrations of inflammatory mediators were decreased in plasma and bronchoalveolar lavage (BAL) in the presence of higher V T with pentoxifylline infusion (TNF-alpha: plasma, 102.2 ± 90.9 and BAL, 118.2 ± 82.1; IL-1ß: plasma, 45.2 ± 42.7 and BAL, 50.2 ± 34.9, P < 0.05). We conclude that TNF-alpha produced by neutrophil influx may function as an alert signal in host defense to induce production of other inflammatory mediators.
Abstract in English:Congenital heart defects are the most common of all human birth defects. Numerous studies have shown that a deletion within chromosome 22q11 is associated with DiGeorge syndrome and certain forms of sporadic congenital cardiovascular disease. We have determined the value of a PCR assay using markers D22S941, D22S944 and D22S264 designed for the screening of 22q11.2 deletion through consecutive homozygosity in an ethnically admixed urban population. The study population comprised 149 unrelated men and women from three different ethnic groups (white, mulatto and black). Test specificity for the overall population was estimated at 98.3%. We found no significant difference when comparing heterozygosity indices and ethnicity (P value = 0.43 (D22S944), 0.22 (D22S264), and 0.58 (D22S941)). There was no significant difference regarding assay specificity between the three different ethnic groups studied. This assay could constitute a cost-effective way to screen a large number of patients at increased risk, since PCR techniques are easily available, are fast, can be automatized, and are significantly less expensive than fluorescence in situ hybridization.
Abstract in English:The predominant type of liver alteration in asymptomatic or oligosymptomatic chronic male alcoholics (N = 169) admitted to a psychiatric hospital for detoxification was classified by two independent methods: liver palpation and multiple quadratic discriminant analysis (QDA), the latter applied to two parameters reported by the patient (duration of alcoholism and daily amount ingested) and to the data obtained from eight biochemical blood determinations (total bilirubin, alkaline phosphatase, glycemia, potassium, aspartate aminotransferase, albumin, globulin, and sodium). All 11 soft and sensitive, and 13 firm and sensitive livers formed fully concordant groups as determined by QDA. Among the 22 soft and not sensitive livers, 95% were concordant by QDA grouping. Concordance rates were low (55%) in the 73 firm and not sensitive livers, and intermediate (76%) in the 50 not palpable livers. Prediction of the liver palpation characteristics by QDA was 95% correct for the firm and not sensitive livers and moderate for the other groups. On a preliminary basis, the variables considered to be most informative by QDA were the two anamnestic data and bilirubin levels, followed by alkaline phosphatase, glycemia and potassium, and then by aspartate aminotransferase and albumin. We conclude that, when biopsies would be too costly or potentially injurious to the patients to varying extents, clinical data could be considered valid to guide patient care, at least in the three groups (soft, not sensitive; soft, sensitive; firm, sensitive livers) in which the two noninvasive procedures were highly concordant in the present study.
Abstract in English:Dipyrone administered intravenously (iv) delays gastric emptying (GE) in rats. The objectives of the present study were to assess: 1) the effect of the dose of dipyrone and time after its iv administration on GE in rats, 2) the effect of subdiaphragmatic vagotomy (VgX) and bilateral electrolytic lesion of the paraventricular nucleus (PVNX) on the delayed GE induced by the drug, and 3) the intracerebroventricular (icv) action of dipyrone and of one of its metabolites, 4-aminoantipyrine on GE. Male Wistar rats received saline labeled with phenol red intragastrically as a test meal. GE was indirectly assessed by the determination of percent gastric retention (GR) of the test meal 10 min after administration by gavage. Dipyrone delays GE in a dose- and time-dependent manner. Thirty minutes after the iv administration of 80 mg/kg dipyrone, the animals showed significantly higher GR (mean = 62.6%) compared to those receiving vehicle (31.5%). VgX and PVNX significantly reduced the iv effect of 80 mg/kg dipyrone (mean %GR: VgX = 28.3 vs Sham = 55.5 and PVNX = 34.5 vs Sham = 52.2). Icv administration of 4 µmol dipyrone caused a significant increase in GR (54.1%) of the test meal 10 min later, whereas administration of 4 µmol 4-aminoantipyrine had no effect (34.4%). Although the dipyrone dose administered icv was 16 times lower than that applied iv, for the same time of action (10 min), the GR of animals that received the drug icv (54.1%) or iv (54.5%) did not differ significantly. In conclusion, the present results suggest that the effect of dipyrone in delaying GE is due to the action of the drug on the central nervous system, with the participation of the PVN and of the vagus nerve.
Abstract in English:Gastric antral dysmotility has been implicated in the pathogenesis of indomethacin-induced gastric damage, but the relationship between gastric motor abnormalities and mucosal lesions has not been extensively studied. We investigated whether changes in gastric tone and gastric retention correlate with mucosal lesions and neutrophil migration in indomethacin-induced gastric damage in rats. Indomethacin, either 5 or 20 mg/kg (INDO-5 and INDO-20), was instilled into the stomach, and then gastric damage, neutrophil migration, gastric tone and gastric retention were assessed 1 or 3 h later. Gastric damage was calculated as the sum of the lengths of all mucosal lesions, and neutrophil migration was measured by assaying myeloperoxidase activity. Gastric tone was determined by a plethysmometric method, and gastric retention of either saline or Sustacal® was evaluated by a scintigraphic method. Gastric damage was detectable 3 h after either INDO-5 or INDO-20, but not after 1 h. Neutrophil migration was significantly higher 3 h after INDO-20 as compared with INDO-5 or control group, but not after 1 h. Values of gastric tone 1 and 3 h after either INDO-5 (1 h = 1.73 ± 0.07 ml; 3 h = 1.87 ± 0.03 ml) or INDO-20 (1 h = 1.70 ± 0.02 ml; 3 h = 1.79 ± 0.03 ml) were significantly lower than in controls (1 h = 1.48 ± 0.05 ml; 3 h = 1.60 ± 0.06 ml). Gastric retention of saline was higher 1 h after INDO-5 (58.9 ± 3.3%) or INDO-20 (56.1 ± 3.1%) compared to control (45.5 ± 1.7%), but not after 3 h. There were no differences concerning gastric retention of Sustacal® between the various groups. Indomethacin induced decreased gastric tone and delayed gastric emptying, which precede mucosal lesion and neutrophil infiltration. These results indicate that there is no relationship between these gastric motor abnormalities and mucosal lesion in indomethacin-induced gastropathy.
Abstract in English:The efficacy of erythromycin was assessed in the treatment of 14 children aged 4 to 13 years with refractory chronic constipation, and presenting megarectum and fecal impaction. A double-blind, placebo- controlled, crossover study was conducted at the Pediatric Gastroenterology Outpatient Clinic of the University Hospital. The patients were randomized to receive placebo for 4 weeks followed by erythromycin estolate, 20 mg kg-1 day-1, divided into four oral doses for another 4 weeks, or vice versa. Patient outcome was assessed according to a clinical score from 12 (most severe clinical condition) to 0 (complete recovery). At enrollment in the study and on the occasion of follow-up medical visits at two-week intervals, patient score and laxative requirements were recorded. During the first 30 days, the mean ± SD clinical score for the erythromycin group (N = 6) decreased from 8.2 ± 2.3 to 2.2 ± 1.0 while the score for the placebo group (N = 8) decreased from 7.8 ± 2.1 to 2.9 ± 2.8. During the second crossover phase, the score for patients on erythromycin ranged from 2.9 ± 2.8 to 2.4 ± 2.1 and the score for the patients on placebo worsened from 2.2 ± 1.0 to 4.3 ± 2.3. There was a significant improvement in score when patients were on erythromycin (P < 0.01). Mean laxative requirement was lower when patients ingested erythromycin (P < 0.05). No erythromycin-related side effects occurred. Erythromycin was useful in this group of severely constipated children. A larger trial is needed to fully ascertain the prokinetic efficacy of this drug as an adjunct in the treatment of severe constipation in children.
Abstract in English:Mycobacterium avium is an important pathogen among immunodeficient patients, especially patients with AIDS. The natural history of this disease is unclear. Several environmental sources have been implicated as the origin of this infection. Polyclonal infection with this species is observed, challenging the understanding of its pathogenesis and treatment. In the present study 45 M. avium strains were recovered from 39 patients admitted to a reference hospital between 1996 and 1998. Species identification was performed using a species-specific nucleic acid hybridization test (AccuProbe®) from Gen-Probe®. Strains were genotyped using IS1245 restriction fragment length polymorphism typing. Blood was the main source of the organism. In one patient with disseminated disease, M. avium could be recovered more than once from potentially sterile sites. Strains isolated from this patient had different genotypes, indicating that the infection was polyclonal. Four patient clones were characterized in this population, the largest clone being detected in eight patients. This finding points to a common-source transmission of the organism.
Abstract in English:The Thr(118)Met substitution in the peripheral myelin protein 22 (PMP22) gene has been detected in a number of families with demyelinating Charcot-Marie-Tooth (CMT1) neuropathy or with the hereditary neuropathy with liability to pressure palsy, but in none of them has it consistently segregated with the peripheral neuropathy. We describe here a CMT1 family (a 63-year-old man, his brother and his niece) in which two mutations on different chromosomes were found in the PMP22 gene, the 17p duplication, detected by fluorescent semiquantitative polymerase chain reaction (PCR) of microsatellite markers localized within the duplicated region on chromosome 17p11.2-p12, and the Thr(118)Met substitution, detected by direct sequencing the four coding exons of the PMP22 gene. A genotype/phenotype correlation study showed that the neuropathy segregates with the duplication and that the amino acid substitution does not seem to modify the clinical characteristics or the severity of the peripheral neuropathy. We did not find any evidence to characterize this substitution as a polymorphism in the population studied and we propose that the high frequency reported for this point mutation in the literature suggests that the Thr(118)Met substitution may be a hotspot for mutations in the PMP22 gene.
Abstract in English: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.
Abstract in English:During routine investigations, we are surprised to find that therapy for bone metastases is sometimes delayed for a considerable period of time. To determine the extent of this delay and its causes, we reviewed the medical records of symptomatic patients seen at our hospital who had been recently diagnosed as having bone metastases for the last four years. The treatment delay was defined as the interval between presentation with symptoms and definitive treatment for bone metastases. The diagnostic delay was defined as the interval between presentation with symptoms and diagnosis of bone metastases. The results of diagnostic radiological examinations were also reviewed for errors. The study population included 76 males and 34 females with a median age of 66 years. Most bone metastases were diagnosed radiologically. Over 75% of patients were treated with radiotherapy. The treatment delay ranged from 2 to 307 days, with a mean of 53.3 days. In 490 radiological studies reviewed, we identified 166 (33.9%) errors concerning 62 (56.4%) patients. The diagnostic delay was significantly longer for patients with radiological errors than for patients without radiological errors (P < 0.001), and much of it was due to radiological errors. In conclusion, the treatment delay in patients with symptomatic bone metastases was much longer than expected, and much of it was caused by radiological errors. Considerable efforts should therefore be made to more carefully examine the radiological studies in order to ensure prompt treatment of bone metastases.
Abstract in English:The objective of the present study was to determine the frequency at which people complain of any type of headache, and its relationship with sociodemographic characteristics and psychiatric comorbidity in São Paulo, Brazil. A three-step cluster sampling method was used to select 1,464 subjects aged 18 years or older. They were mainly from families of middle and upper socioeconomic levels living in the catchment area of Instituto de Psiquiatria. However, this area also contains some slums and shantytowns. The subjects were interviewed using the Brazilian version of the Composite International Diagnostic Interview version 1.1. (CIDI 1.1) by a lay trained interviewer. Answers to CIDI 1.1 questions allowed us to classify people according to their psychiatric condition and their headaches based on their own ideas about the nature of their illness. The lifetime prevalence of "a lot of problems with" headache was 37.4% (76.2% of which were attributed to use of medicines, drugs/alcohol, physical illness or trauma, and 23.8% attributed to nervousness, tension or mental illness). The odds ratio (OR) for headache among participants with "nervousness, tension or mental illness" was elevated for depressive episodes (OR, 2.1; 95%CI, 1.4-3.4), dysthymia (OR, 3.4; 95%CI, 1.6-7.4) and generalized anxiety disorder (OR, 4.3; 95%CI, 2.1-8.6), when compared with patients without headache. For "a lot of problems with" headaches attributed to medicines, drugs/alcohol, physical illness or trauma, the risk was also increased for dysthymia but not for generalized anxiety disorder. These data show a high association between headache and chronic psychiatric disorders in this Brazilian population sample.
Abstract in English:The ideal therapy for early stages of hemorrhoids is always debated. Some are more effective but are more painful, others are less painful but their efficacy is also lower. Thus, comfort or efficacy is a major concern. In the present randomized study, a comparison is made between infrared coagulation and rubber band ligation in terms of effectiveness and discomfort. One hundred patients with second degree bleeding piles were randomized prospectively to either rubber band ligation (N = 54) or infrared coagulation (N = 46). Parameters measured included postoperative discomfort and pain, time to return to work, relief in incidence of bleeding, and recurrence rate. The mean age was 38 years (range 19-68 years). The mean duration of disease was 17.5 months (range 12 to 34 months). The number of male patients was double that of females. Postoperative pain during the first week was more intense in the band ligation group (2-5 vs 0-3 on a visual analogue scale). Post-defecation pain was more intense with band ligation and so was rectal tenesmus (P = 0.0059). The patients in the infrared coagulation group resumed their duties earlier (2 vs 4 days, P = 0.03), but also had a higher recurrence or failure rate (P = 0.03). Thus, we conclude that band ligation, although more effective in controlling symptoms and obliterating hemorrhoids, is associated with more pain and discomfort to the patient. As infrared coagulation can be conveniently repeated in case of recurrence, it could be considered to be a suitable alternative office procedure for the treatment of early stage hemorrhoids.
Abstract in English:The prone position can be used for the planning of adjuvant radiotherapy after conservative breast surgery in order to deliver less irradiation to lung and cardiac tissue. In the present study, we compared the results of three-dimensional conformal radiotherapy planning for five patients irradiated in the supine and prone position. Tumor stage was T1N0M0 in four patients and T1N1M0 in one. All patients had been previously submitted to conservative breast surgery. Breast size was large in three patients and moderate in the other two. Irradiation in the prone position was performed using an immobilization foam pad with a hole cut into it to accommodate the breast so that it would hang down away from the chest wall. Dose-volume histograms showed that mean irradiation doses reaching the ipsilateral lung were 8.3 ± 3.6 Gy with the patient in the supine position and 1.4 ± 1.0 Gy with the patient in the prone position (P = 0.043). The values for the contralateral lung were 1.3 ± 0.7 and 0.3 ± 0.1 Gy (P = 0.043) and the values for cardiac tissue were 4.6 ± 1.6 and 3.0 ± 1.7 Gy (P = 0.079), respectively. Thus, the dose-volume histograms demonstrated that lung tissue irradiation was significantly lower with the patient in the prone position than in the supine position. Large-breasted women appeared to benefit most from irradiation in the prone position. Prone position breast irradiation appears to be a simple and effective alternative to the conventional supine position for patients with large breasts, since they are subjected to lower pulmonary doses which may cause less pulmonary side effects in the future.
Abstract in English:The aim of the present study was to determine the expression of the genes for type 1 (SDR5A1) and type 2 (SDR5A2) 5alpha-reductase isoenzymes in scalp hairs plucked from 33 hirsute patients (20 with polycystic ovary syndrome and 13 with idiopathic hirsutism) and compare it with that of 10 men and 15 normal women. SDR5A1 and SDR5A2 expression was estimated by RT-PCR using the gene of the ubiquitously expressed protein ß2-microglobulin as an internal control. The results are expressed as arbitrary units in relation to ß2-microglobulin absorbance (mean ± SEM). SDR5A2 expression was not detected in any hair samples analyzed in this study. No differences were found in SDR5A1 mRNA levels between men and normal women (0.78 ± 0.05 vs 0.74 ± 0.06, respectively). SDR5A1 gene expression in the cells of hair plucked from the scalp of normal women (0.85 ± 0.04) and of women with polycystic ovary syndrome (0.78 ± 0.05) and idiopathic hirsutism (0.80 ± 0.06) was also similar. These results indicate that SDR5A1 gene expression in the follicular keratinocytes from the vertex area of the scalp seems not to be related to the differences in hair growth observed between normal men and women and hirsute patients. Further studies are needed to investigate the expression of the 5alpha-reductase genes in other scalp follicular compartments such as dermal papillae, and also in hair follicles from other body sites, in order to elucidate the mechanism of androgen action on the hair growth process and related diseases.