Crésio de Aragão Dantas Alves

Infections in patients with diabetes mellitus: A review of pathogenesis

In general, infectious diseases are more frequent and/or serious in patients with diabetes mellitus, which potentially increases their morbimortality. The greater frequency of infections in diabetic patients is caused by the hyperglycemic environment that favors immune dysfunction (e.g., damage to the neutrophil function, depression of the antioxidant system, and humoral immunity), micro- and macro-angiopathies, neuropathy, decrease in the antibacterial activity of urine, gastrointestinal and urinary dysmotility, and greater number of medical interventions in these patients. The infections affect all organs and systems. Some of these problems are seen mostly in diabetic people, such as foot infections, malignant external otitis, rhinocerebral mucormycosis, and gangrenous cholecystitis. In addition to the increased morbidity, infectious processes may be the first manifestation of diabetes mellitus or the precipitating factors for complications inherent to the disease, such as diabetic ketoacidosis and hypoglycemia. Immunization with anti-pneumococcal and influenza vaccines is recommended to reduce hospitalizations, deaths, and medical expenses.

Withdrawal from glucocorticosteroid therapy: clinical practice recommendations

OBJECTIVE To present an up-to-date and practical review of how to safely withdraw glucocorticosteroid therapy. SOURCES A review of the published literature identified by searching the MEDLINE and LILACS databases (1997-2007), selecting the most representative articles on the subject. SUMMARY OF THE FINDINGS Three clinical situations may occur during glucocorticoid withdrawal: adrenal insufficiency secondary to negative feedback on the hypothalamic-pituitary adrenal (HPA) axis, steroid withdrawal syndrome and relapse of the disease for which the glucocorticoids were prescribed. Although there is no consensus on how to best discontinue prolonged glucocorticosteroid therapy, there is agreement that this withdrawal should be gradual. This article updates pediatricians on how to recognize these problems and provides recommendations on how to safely suspend glucocorticosteroid therapy. A brief review of the pharmacology of glucocorticoids is also presented. CONCLUSIONS There is no good predictive test for predicting the risk of adrenal insufficiency in patients who have been on corticosteroid therapy chronically. There is a need for prospective studies to assess the true incidence of this problem and to propose rational strategies for preventing it. The current recommendation is that patients who have been on chronic and/or high dose glucocorticoids should be administered glucocorticoids during stress situations unless the integrity of the HPA axis has been established by dynamic tests.OBJECTIVE: To compare the prevalence rates of breastfeeding and the principal causes of consultations at the infant and neonatal clinic of a basic healthcare center in the city of Rio de Janeiro, before and after its being accredited by the Breastfeeding Friendly Primary Care Initiative. METHODS: Information was analyzed from 121 and 200 children followed-up at the healthcare center before and after certification, respectively. Type of feeding was classified as exclusive breastfeeding, predominant breastfeeding or breastfeeding, and the 10th International Classification of Diseases was used to classify the complaints causing consultations. RESULTS: A statistically significant increase was observed in the prevalence of exclusive breastfeeding, both among those less than 4 months old (68 vs. 88%; p < 0.0001) and among children aged from 4 to 6 months (41 vs. 82%; p < 0.0001). Furthermore, an impressive increase was observed in the prevalence of breastfeeding in children more than 6 months old, especially those aged 9 to 12 months (24 vs. 82%; p < 0.0001). After certification, there was also a reduction in the number of consultations motivated by some type of disease among infants more than 4 months old. CONCLUSION: Implementation of the Breastfeeding Friendly Primary Care Initiative proved to be an important strategy for increasing the rate of breastfeeding and reducing consultations due to disease among infants less than one year old cared for at this health center.OBJETIVO: Apresentar uma revisao atualizada e pratica sobre como efetuar de forma segura a retirada da corticoterapia. FONTES DOS DADOS: Revisao da literatura utilizando os bancos de dados MEDLINE e LILACS (1997-2007), selecionando os artigos mais atuais e representativos do tema. SINTESE DOS DADOS: Tres situacoes clinicas podem ocorrer durante a retirada da corticoterapia prolongada: insuficiencia adrenal secundaria a supressao do eixo hipotalamo-hipofise-adrenal, sindrome de retirada ou deprivacao dos corticoides e reativacao da doenca de base. Embora nao exista consenso sobre o melhor esquema para descontinuar a terapia prolongada com corticoides, existe concordância quanto ao fato desta retirada ser gradual. Este artigo atualiza o pediatra quanto ao reconhecimento desses problemas e fornece orientacoes para a suspensao do tratamento prolongado com corticoide. Uma breve revisao da farmacologia dos corticoides tambem e descrita. CONCLUSAO: Nao existe teste com bom valor preditivo para antecipar o risco de insuficiencia adrenal nos pacientes que receberam terapia cronica com corticoide. Sao necessarios estudos prospectivos para avaliar a real incidencia desse problema e assim propor estrategias racionais para sua prevencao. No momento, a menos que a integridade do eixo hipotalamo-hipofise-adrenal esteja estabelecida por testes dinâmicos, recomenda-se a administracao de corticoide em situacoes de estresse nos pacientes que fizeram uso de corticoterapia cronica e/ou em doses elevadas.

Lipodystrophic syndrome in children and adolescents infected with the human immunodeficiency virus

The introduction of highly active antiretroviral therapy (HAART) for the treatment of acquired immunodeficiency syndrome (AIDS) has resulted in greater survival of patients infected with the human immunodeficiency virus (HIV). However, the use of these drugs has been associated with lipodystrophic syndrome (LS), which is characterized by metabolic alterations (dyslipidemia, insulin resistance, diabetes, and lactic acidosis) and abnormal corporal fat distribution. Clinically, LS may manifest as three different forms: lipohipertrophy (accumulation of fat in the central part of the body), lipoatrophy (loss of fat in the extremities, face and buttocks) and mixed (lipohipertrophy + lipoatrophy). Although its physiopathology has not been elucidated, some mechanisms have been described, including leptin and adiponectin deficiency, mitochondrial dysfunction and use of antiretroviral drugs. The type, dose and duration of the antiretroviral treatment, as well as age and puberty are the main risk factors. LS is also associated with increased incidence of cardiovascular illnesses, atherosclerosis and diabetes mellitus. Treatment includes physical activity, cautious restriction of caloric intake, changes in antiretroviral therapy, and use of insulin-sensitizing and lipid-lowering agents. Follow up must be periodic, consisting of measurement of body fat distribution, evaluation of the lipid profile and insulin resistance.

Impacto da atividade física e esportes sobre o crescimento e puberdade de crianças e adolescentes

Objective: To present an up-to-date critical review about the impact of sports and physical activity on growth, pubertal development and bone mineralization of children and adolescents. Data source: Bibliographic search of Medline and Lilacs databases (1987-2007) with selection of studies written in English, Portuguese or Spanish, with the descriptors “sports” and “exercise” in combination with “growth”, “puberty” and “bone mineralization”. A total of 252 articles were retrieved and 48 of them were selected. Data synthesis: Light to moderate physical activity has a beneficial effect on growth and bone development, while intense physical training, specially if associated to dietary restrictions, may attenuate linear growth, pubertal development, reproductive function and bone mineralization. Different sports do not have specific effects on final height. There is a selection bias in which constitutional factors contribute to select favored biotypes to specific sports. Weight-training by pre-pubertal children may be harmful, if not supervised, due to the potential risk of injure to the growth plates; however, if performed under strict supervision, may provide muscle strength and resistance. Conclusions: Deleterious effects of sports in growth and development of children and adolescents were only observed in elite athletes submitted to intensive training and dietetic restriction. Longitudinal studies are neded to

Immunogenetics and infectious diseases: special reference to the mayor histocompatibility complex.

Many studies have tried to identify genetic markers for infectious diseases, some of them have focused on human leukocyte antigens (HLA). The products of HLA genes interact with surface-specific receptors of T lymphocytes, resulting in activation of the hosts immune response. Association of bacterial, viral, parasitic and fungal infections with the hosts HLA has been widely investigated. The type and strength of this association differs among distinct populations, as well as among racial and/or ethnic groups. The new molecular methods for the identification of the HLA alleles, and the resulting new nomenclature, have contributed to a better understanding of this system. Unfortunately, this information has not been adequately transmitted to clinicians, which hampers the understanding of the association between the HLA system and diseases. We revised relevant studies on the association of HLA genes with infectious diseases, demonstrating their importance in the pathogenic mechanisms, through increased susceptibility or protection against infections and their complications.

Exposição ambiental a interferentes endócrinos com atividade estrogênica e sua associação com distúrbios puberais em crianças

Endocrine disruptors are exogenous substances with adverse health effects in intact organisms or their progeny, secondary to changes in endocrine function. Recent years have witnessed constant reports of environmental factors with hormone-like effects causing pubertal or reproductive abnormalities in animals. The few cases proven to be associated with pubertal disorders in humans have been related to accidental exposure. Nevertheless, pediatricians and parents recommend suspending all possible estrogen-contaminated food, especially meat (poultry, beef) and soy products, when the child presents with a pubertal disorder. These recommendations, if not scientifically sound, may have deleterious consequences by eliminating sources of dietary protein and possibly delaying the investigation of other potential and treatable causes. On the other hand, not investigating potential side effects of these products could have similar harmful effects. The current article describes the main endocrine disruptors associated with pubertal disorders in humans and concludes that except for accidental exposure to high doses, more research is needed on the effects of chronic and low-dose exposures in altering human pubertal development.

Distribuição e freqüência de alelos e haplotipos HLA em brasileiros com diabetes melito tipo 1

The genetic predisposition to type 1 diabetes (DM1) is associated with genes of the human leukocyte antigen (HLA) system, specially the HLA-DR and -DQ. In Caucasians, the HLA-DR3 and -DR4 antigens are associated with susceptibility and the -DR2, with protection. In Brazil, a country with a large miscegenation of Europeans Caucasians, Native Amerindians and African Blacks, the genetic basis of DM1 has not been adequately studied. The aim of this paper is to present a critical review of articles indexed in the MEDLINE and LILACS-BIREME data basis about the association of HLA with DM1 in Brazilians. Eight papers, all of them from the Southeast region, were found. Immunogenetic susceptibility to DM1 in Brazilians was associated with HLA-DRB1*03, -DRB*04, -DQB1*0201, -DQB1*0302 alleles, and protection against DM1 was associated with HLA-DQB1*0602, -DQB1*0301 alleles and -DR2 and -DR7 antigens. Since the Brazilian population is not racially homogeneous, it is not possible to extrapolate studies from a single region to the remaining of the country. It is necessary to study populations from different regions to identify new associations or to strengthen associations with the ones already identified. This knowledge will contribute to future prophylactic or therapeutic interventions in the group of Brazilians at risk of developing DM1.

Mutations in the Human UBR1 Gene and the Associated Phenotypic Spectrum

Johanson–Blizzard syndrome (JBS) is a rare, autosomal recessive disorder characterized by exocrine pancreatic insufficiency, typical facial features, dental anomalies, hypothyroidism, sensorineural hearing loss, scalp defects, urogenital and anorectal anomalies, short stature, and cognitive impairment of variable degree. This syndrome is caused by a defect of the E3 ubiquitin ligase UBR1, which is part of the proteolytic N‐end rule pathway. Herein, we review previously reported (n = 29) and a total of 31 novel UBR1 mutations in relation to the associated phenotype in patients from 50 unrelated families. Mutation types include nonsense, frameshift, splice site, missense, and small in‐frame deletions consistent with the hypothesis that loss of UBR1 protein function is the molecular basis of JBS. There is an association of missense mutations and small in‐frame deletions with milder physical abnormalities and a normal intellectual capacity, thus suggesting that at least some of these may represent hypomorphic UBR1 alleles. The review of clinical data of a large number of molecularly confirmed JBS cases allows us to define minimal clinical criteria for the diagnosis of JBS. For all previously reported and novel UBR1 mutations together with their clinical data, a mutation database has been established at LOVD.

Salivary flow and dental caries in Brazilian youth with type 1 diabetes mellitus

BACKGROUND Although type 1 diabetes mellitus (T1DM) has a significant impact on oral health, its association with dental caries is yet not clear. AIM The aim of this study was to evaluate the salivary flow rate and caries in Brazilian youth with type 1 diabetes mellitus. SETTING AND DESIGN A Cross-sectional study was performed in a tertiary university hospital. MATERIALS AND METHODS Fifty-one age matched subjects suffering from type 1 diabetes mellitus were selected for the study and evaluated for the following: salivary flow rate, number of decayed, missing and filled tooth in permanent dentition (DMF-T) and decayed, extracted, filled tooth index in the deciduous dentition (def-t); visible plaque index (VPI) and gingival bleeding index (GBI). STATISTICS AND ANALYSIS: The t test was utilized when the variables showed normal distribution. The Mann-Whitney test was utilized for comparing non-normal variables. Kolmorgorov-Smirnov test was used to assess the normality assumption. The differences were considered significant when P < 0.05. RESULTS The age and gender distribution of patients and controls was 11.3 ± 3.4 years (56% males) and 11.9 ± 3.4 years (37% males). The mean glycated hemoglobin value in the diabetics was 9.7 ± 1.9%. Salivary flow rate was lower in the diabetic patients as compared to controls (P = 0.02). No differences were found in the DMF-T/def-t indices of diabetic and non-diabetic patients (P = 0.43/0.14). VPI was similar in both the groups (P = 0.15). GBI was higher in the diabetics (8.1 vs. 5.18; P = 0.11). There were no differences in the dental caries experience and dental plaque in the two groups. CONCLUSION The lower salivary flow rate in diabetics could have been related to their higher GBI. The higher GBI in the diabetics is a matter of concern in the diabetics and is a sign for higher chances of developing periodontal problems.

46,XX Male - Testicular Disorder of Sexual Differentiation (DSD): hormonal, molecular and cytogenetic studies

The XX male syndrome - Testicular Disorder of Sexual Differentiation (DSD) is a rare condition characterized by a spectrum of clinical presentations, ranging from ambiguous to normal male genitalia. We report hormonal, molecular and cytogenetic evaluations of a boy presenting with this syndrome. Examination of the genitalia at age of 16 months, showed: penis of 3.5 cm, proximal hypospadia and scrotal testes. Pelvic ultrasound did not demonstrate Mullerian duct structures. Karyotype was 46,XX. Gonadotrophin stimulation test yielded insufficient testosterone production. Gonadal biopsy showed seminiferous tubules without evidence of Leydig cells. Molecular studies revealed that SRY and TSPY genes and also DYZ3 sequences were absent. In addition, the lack of deletions or duplications of SOX9, NR5A1, WNT4 and NROB1 regions was verified. The infant was heterozygous for all microsatellites at the 9p region, including DMRT1 gene, investigated. Only 10% of the patients are SRY-negative and usually they have ambiguous genitalia, as the aforementioned patient. The incomplete masculinization suggests gain of function mutation in one or more genes downstream to SRY gene.