Cortisol and 17-a-hydroxy-progesterone levels in infants with refractory hypotension born at 30 weeks of gestation or less

Refractory hypotension is frequent in very low-birth weight infants, whose hypothalamic-pituitary-adrenal axis has been suggested to be immature. The objective of the present study was to evaluate basal cortisol and 17-a-OH-progesterone in the first 36 h of life in preterm infants with and without refractory hypotension (mean arterial blood pressure below the lower limit for gestational age throughout the study despite aggressive volume expansion and use of vasopressors). Thirty-five infants with £30 weeks of gestation and a birth weight £1250 g, with no postnatal use of corticosteroid or death in the first 48 h were studied. Mean arterial pressure was measured every 4 h during the first 48 h. Cortisol and 17-a-OH-progesterone were determined at 12 and 36 h and patients were divided into refractory hypotensive (N = 15) and control (N = 20) groups. The groups were not different regarding type of delivery, use of prenatal corticosteroid, requirement of mechanical ventilation, use of vasopressor drugs, morphine, fentanyl, prophylactic indomethacin, and mean sample timing. Although refractory hypotensive newborns were more immature, were smaller, suffered more deaths after 48 h of life and had a higher SNAPPE-2 score, their cortisol and 17-a-OH-progesterone levels were not different from controls at 12 h and at 36 h. The increase of cortisol in newborns with refractory hypotension 36 h after birth was significantly higher than in controls. Despite the fact that refractory hypotensive very low-birth weight neonates were submitted to a very stressful condition, their cortisol and 17-a-OH-progesterone levels were similar to controls.

Breathing disorders in congestive heart failure: gender, etiology and mortality

We investigated the relationship between sleep-disordered breathing (SDB) and Cheyne-Stokes respiration (CSR) while awake as well as mortality. Eighty-nine consecutive outpatients (29 females) with congestive heart failure (CHF; left ventricular ejection fraction, LVEF <45%) were prospectively evaluated. The presence of SDB and of CSR while awake before sleep onset was investigated by polysomnography. SDB prevalence was 81 and 56%, using apnea-hypopnea index cutoffs >5 and >15, respectively. CHF etiologies were similar according to the prevalence of SDB and sleep pattern. Males and females were similar in age, body mass index, and LVEF. Males presented more SDB (P = 0.01), higher apnea-hypopnea index (P = 0.04), more light sleep (stages 1 and 2; P < 0.05), and less deep sleep (P < 0.001) than females. During follow-up (25 ± 10 months), 27% of the population died. Non-survivors had lower LVEF (P = 0.01), worse New York Heart Association (NYHA) functional classification (P = 0.03), and higher CSR while awake (P < 0.001) than survivors. As determined by Cox proportional model, NYHA class IV (RR = 3.95, 95%CI = 1.37-11.38, P = 0.011) and CSR while awake with a marginal significance (RR = 2.96, 95%CI = 0.94-9.33, P = 0.064) were associated with mortality. In conclusion, the prevalence of SDB and sleep pattern of patients with Chagas' disease were similar to that of patients with CHF due to other etiologies. Males presented more frequent and more severe SDB and worse sleep quality than females. The presence of CSR while awake, but not during sleep, may be associated with a poor prognosis in patients with CHF.

Pattern of functional antibody activity against Haemophilus influenzae type b (Hib) in infants immunized with diphtheria-tetanus-pertussis/Hib Brazilian combination vaccine

We evaluated the functional activity of Haemophilus influenzae B (Hib) antibodies elicited in a group of infants immunized with the diphtheria-tetanus-pertussis vaccine combined with an Hib vaccine produced totally in Brazil after technological transfer of Hib vaccine production from Glaxo SmithKline, Belgium. Blood samples from immunized infants (N = 985) were collected for the determination of Hib antibodies. Total Ig and IgM and IgG subclasses of antibodies against polyribosyl ribitol phosphate (PRP) were analyzed by ELISA. Almost all vaccinees (97.56%, 961/985) developed a strong anti-PRP IgG antibody response (≥1.0 μg/mL), while an anti-PRP IgM response was observed in 64.24% (634/985) of them (≥0.15 μg/mL). Only 18.88% (186/985) of the infants in the group with high PRP antibody IgG concentrations (≥1.0 μg/mL) developed a high IgM antibody response. Anti-PRP IgG antibody levels were significantly higher than anti-PRP IgM. These results demonstrate the predominance of IgG antibodies over IgM antibodies in response to PRP, with a ratio of 17:1. IgG antibodies were predominantly of the IgG1 subclass. An increase in IgG avidity was also observed during the course of immunization.

Gender, race and socioeconomic influence on diagnosis and treatment of thyroid disorders in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil)

Thyroid diseases are common, and use of levothyroxine is increasing worldwide. We investigated the influence of gender, race and socioeconomic status on the diagnosis and treatment of thyroid disorders using data from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil), a multicenter cohort study of civil servants (35-74 years of age) from six Brazilian cities. Diagnosis of thyroid dysfunction was by thyrotropin (TSH), and free thyroxine (FT4) if TSH was altered, and the use of specific medications. Multivariate logistic regression models were constructed using overt hyperthyroidism/hypothyroidism and levothyroxine use as dependent variables and sociodemographic characteristics as independent variables. The frequencies of overt hyper- and hypothyroidism were 0.7 and 7.4%, respectively. Using whites as the reference ethnicity, brown, and black race were protective for overt hypothyroidism (OR=0.76, 95%CI=0.64-0.89, and OR=0.53, 95%CI=0.43-0.67, respectively, and black race was associated with overt hyperthyroidism (OR=1.82, 95%CI=1.06-3.11). Frequency of hypothyroidism treatment was higher in women, browns, highly educated participants and those with high net family incomes. After multivariate adjustment, levothyroxine use was associated with female gender (OR=6.06, 95%CI=3.19-11.49) and high net family income (OR=3.23, 95%CI=1.02-10.23). Frequency of hyperthyroidism treatment was higher in older than in younger individuals. Sociodemographic factors strongly influenced the diagnosis and treatment of thyroid disorders, including the use of levothyroxine.

Metodological issues in measuring the detection of emotional disorders by primary care physicians: a review of the literature

A series of studies in the field of Epidemiological Psychiatry have been performed over the last two decades, and these have focused on the ability of primary care physicians to detect emotional disorders in the patients that attend their practices. The scientific methodology utilized in these studies is the subject of this review, which contains a discussion concerning: a) interviewer awareness bias; b) accuracy of the instruments and c) medical and psychological concepts involved in defining minor emotional disorders. Suggestions for change in the methodology are made in each of the sections of the review.

Prevalence of and risk factors for late diagnosis of HIV infection in Brazilian infants and children

INTRODUCTION: Late human immunodeficiency virus (HIV) diagnosis is an important cause of HIV-related morbidity and mortality in infants and children. METHODS: This retrospective cohort study of HIV-infected children diagnosed in Sergipe, in northeastern Brazil, between 2002 and 2011 aimed to determine the prevalence of and risk factors for late HIV diagnosis. RESULTS: Of 55 infants and children with confirmed infection, 42 (76.5%) were diagnosed at ≥ 12 months old. No antiretroviral prophylaxis during delivery (OR 5.48, 95% CI 1.11-32.34) was associated with late diagnosis. CONCLUSIONS: More than 75% of cases were diagnosed late. Efforts are needed to improve early HIV diagnosis in infants.

The Shiga toxin 2 B subunit inhibits net fluid absorption in human colon and elicits fluid accumulation in rat colon loops

Shiga toxin (Stx)-producing Escherichia coli (STEC) colonizes the large intestine causing a spectrum of disorders, including watery diarrhea, bloody diarrhea (hemorrhagic colitis), and hemolytic-uremic syndrome. It is estimated that hemolytic-uremic syndrome is the most common cause of acute renal failure in infants in Argentina. Stx is a multimeric toxin composed of one A subunit and five B subunits. In this study we demonstrate that the Stx2 B subunit inhibits the water absorption (Jw) across the human and rat colonic mucosa without altering the electrical parameters measured as transepithelial potential difference and short circuit current. The time-course Jw inhibition by 400 ng/ml purified Stx2 B subunit was similar to that obtained using 12 ng/ml Stx2 holotoxin suggesting that both, A and B subunits of Stx2 contributed to inhibit the Jw. Moreover, non-hemorrhagic fluid accumulation was observed in rat colon loops after 16 h of treatment with 3 and 30 ng/ml Stx2 B subunit. These changes indicate that Stx2 B subunit induces fluid accumulation independently of A subunit activity by altering the usual balance of intestinal absorption and secretion toward net secretion. In conclusion, our results suggest that the Stx2 B subunit, which is non-toxic for Vero cells, may contribute to the watery diarrhea observed in STEC infection. Further studies will be necessary to determine whether the toxicity of Stx2 B subunit may have pathogenic consequences when it is used as a component in an acellular STEC vaccine or as a vector in cancer vaccines.

Analysis of acylcarnitine profiles in umbilical cord blood and during the early neonatal period by electrospray ionization tandem mass spectrometry

Acylcarnitine profiling by electrospray ionization tandem mass spectrometry (ESI-MS/MS) is a potent tool for the diagnosis and screening of fatty acid oxidation and organic acid disorders. Few studies have analyzed free carnitine and acylcarnitines in dried blood spots (DBS) of umbilical cord blood (CB) and the postnatal changes in the concentrations of these analytes. We have investigated these metabolites in healthy exclusively breastfed neonates and examined possible effects of birth weight and gestational age. DBS of CB were collected from 162 adequate for gestational age neonates. Paired DBS of heel-prick blood were collected 4-8 days after birth from 106 of these neonates, the majority exclusively breastfed. Methanol extracts of DBS with deuterium-labeled internal standards were derivatized before analysis by ESI-MS/MS. Most of the analytes were measured using a full-scan method. The levels of the major long-chain acylcarnitines, palmitoylcarnitine, stearoylcarnitine, and oleoylcarnitine, increased by 27, 12, and 109%, respectively, in the first week of life. Free carnitine and acetylcarnitine had a modest increase: 8 and 11%, respectively. Propionylcarnitine presented a different behavior, decreasing 9% during the period. The correlations between birth weight or gestational age and the concentrations of the analytes in DBS were weak (r £ 0.20) or nonsignificant. Adaptation to breast milk as the sole source of nutrients can explain the increase of these metabolites along the early neonatal period. Acylcarnitine profiling in CB should have a role in the early detection of metabolic disorders in high-risk neonates.

Correlations of circulating peptide YY and ghrelin with body weight, rate of weight gain, and time required to achieve the recommended daily intake in preterm infants

The objective was to elucidate the relationships between serum concentrations of the gut hormone peptide YY (PYY) and ghrelin and growth development in infants for potential application to the clinical observation index. Serum concentrations of PYY and ghrelin were measured using radioimmunoassay from samples collected at the clinic. For each patient, gestational age, birth weight, time required to return to birth weight, rate of weight gain, time required to achieve recommended daily intake (RDI) standards, time required for full-gastric feeding, duration of hospitalization, and time of administration of total parenteral nutrition were recorded. Serum PYY and ghrelin concentrations were significantly higher in the preterm group (N = 20) than in the full-term group (N = 20; P < 0.01). Within the preterm infant group, the serum concentrations of PYY and ghrelin on postnatal day (PND) 7 (ghrelin = 1485.38 ± 409.24; PYY = 812.37 ± 153.77 ng/L) were significantly higher than on PND 1 (ghrelin = 956.85 ± 223.09; PYY = 545.27 ± 204.51 ng/L) or PND 3 (ghrelin = 1108.44 ± 351.36; PYY = 628.96 ± 235.63 ng/L; P < 0.01). Both serum PYY and ghrelin concentrations were negatively correlated with body weight, and the degree of correlation varied with age. Serum ghrelin concentration correlated negatively with birth weight and positively with the time required to achieve RDI (P < 0.05). In conclusion, serum PYY and ghrelin concentrations reflect a negative energy balance, predict postnatal growth, and enable compensation. Further studies are required to elucidate the precise concentration and roles of PYY and ghrelin in newborns and to determine the usefulness of measuring these hormones in clinical practice.

Detection of psychiatric morbidity in the primary medical care setting in Brazil

The aims of this study were a) to assess the ability of primary care doctors to make accurate ratings of psychiatric disturbance and b) to evaluate the use of a case-finding questionnaire in the detection of psychiatric morbidity. The estudy took place in three primary care clinics in the city of São Paulo, Brazil, during a six-month survey. A time sample of consecutive adult attenders were asked to complete a case-finding questionnaire for psychiatric disorders (the Self Report Questionnaire - SRQ) and a subsample were selected for a semi-structured psychiatric interview (the Clinical Interview Schedule - CIS). At the end of the consultation the primary care doctors were asked to assess, in a standardized way, the presence or absence of psychiatric disorder; these assessments were then compared with that ratings obtained in the psychiatric interview. A considerable proportion of minor psychiatric morbidity remained undetected by the three primary care doctors: the hidden morbidity ranged from 22% to 79%. When these were compared to those of the case-finding questionnaire, they were consistently lower, indicating that the use of these instruments can enhance the recognition of psychiatric disorders in primary care settings. Four strategies for adopting the questionnaire are described, and some of the clinical consequences of its use are discussed.

The social adjustment of patients with schizophrenia: implications to the mental health policy in Brazil

A sample (n=124) of schizophrenic patients from a defined catchment area of the city os S.Paulo, Brazil, who had been consecutively admitted to hospital, was assessed for psychopathological status and social adjustment levels. Sociodemographic, socio-economic and occupational characteristics were recorded: almost 30% of the subjects had no occupation and received no social benefit, more than two-thirds had a monthly per capita income of US$ 100.00 or less. Sixty-five percent presented with Schneiderian firstrank symptoms. Nearly half the sample showed poor or very poor social adjustment in the month prior to admission. The most affected areas of social functioning were participation in the household activities, work and social withdrawal. The current mental health policy of promoting extra-mural care as an alternative to the previous hospital-based model will then mean the investment in a network of new community-based services, that give effective treatment and support to patients and their families. The need of further research into the current picture of mental disorders in the country is stressed.

Cost of schizophrenia: direct costs and use of resources in the State of São Paulo

OBJECTIVE: To estimate the direct costs of schizophrenia for the public sector. METHODS: A study was carried out in the state of São Paulo, Brazil, during 1998. Data from the medical literature and governmental research bodies were gathered for estimating the total number of schizophrenia patients covered by the Brazilian Unified Health System. A decision tree was built based on an estimated distribution of patients under different types of psychiatric care. Medical charts from public hospitals and outpatient services were used to estimate the resources used over a one-year period. Direct costs were calculated by attributing monetary values for each resource used. RESULTS: Of all patients, 81.5% were covered by the public sector and distributed as follows: 6.0% in psychiatric hospital admissions, 23.0% in outpatient care, and 71.0% without regular treatment. The total direct cost of schizophrenia was US$191,781,327 (2.2% of the total health care expenditure in the state). Of this total, 11.0% was spent on outpatient care and 79.2% went for inpatient care. CONCLUSIONS: Most schizophrenia patients in the state of São Paulo receive no regular treatment. The study findings point out to the importance of investing in research aimed at improving the resource allocation for the treatment of mental disorders in Brazil.

Longitudinal anthropometric assessment of infants born to HIV-1-infected mothers, Belo Horizonte, Southeastern Brazil

OBJECTIVE: To evaluate the growth parameters in infants who were born to HIV-1-infected mothers. METHODS: The study was a longitudinal evaluation of the z-scores for the weight-for-age (WAZ), weight-for-length (WLZ) and length-for-age (LAZ) data collected from a cohort. A total of 97 non-infected and 33 HIV-infected infants born to HIV-1-infected mothers in Belo Horizonte, Southeastern Brazil, between 1995 and 2003 was studied. The average follow-up period for the infected and non-infected children was 15.8 months (variation: 6.8 to 18.0 months) and 14.3 months (variation: 6.3 to 18.6 months), respectively. A mixed-effects linear regression model was used and was fitted using a restricted maximum likelihood. RESULTS: There was an observed decrease over time in the WAZ, LAZ and WLZ among the infected infants. At six months of age, the mean differences in the WAZ, LAZ and WLZ between the HIV-infected and non-infected infants were 1.02, 0.59, and 0.63 standard deviations, respectively. At 12 months, the mean differences in the WAZ, LAZ and WLZ between the HIV-infected and non-infected infants were 1.15, 1.01, and 0.87 standard deviations, respectively. CONCLUSIONS: The precocious and increasing deterioration of the HIV-infected infants' anthropometric indicators demonstrates the importance of the early identification of HIV-infected infants who are at nutritional risk and the importance of the continuous assessment of nutritional interventions for these infants.

Pertussis booster vaccine for adolescents and young adults in São Paulo, Brazil

OBJECTIVE: To develop a model to assess different strategies of pertussis booster vaccination in the city of São Paulo. METHODS: A dynamic stationary age-dependent compartmental model with waning immunity was developed. The "Who Acquires Infection from Whom" matrix was used to modeling age-dependent transmission rates. There were tested different strategies including vaccine boosters to the current vaccination schedule and three of them were reported: (i) 35% coverage at age 12, or (ii) 70% coverage at age 12, and (iii) 35% coverage at age 12 and 70% coverage at age 20 at the same time. RESULTS: The strategy (i) achieved a 59% reduction of pertussis occurrence and a 53% reduction in infants while strategy (ii) produced 76% and 63% reduction and strategy (iii) 62% and 54%, respectively. CONCLUSION: Pertussis booster vaccination at age 12 proved to be the best strategy among those tested in this study as it achieves the highest overall reduction and the greatest impact among infants who are more susceptible to pertussis complications.

Respiratory complications in Brazilian patients infected with human immunodeficiency virus

PURPOSE: To determine how often and by what means an indentifiable pulmonary pathogen can be recognized in human immunodeficiency virus (HIV) infected patients with respiratory disorders in Brazil, which are the most frequently observed microorganisms and what impact specific therapy has on these agents. PATIENTS AND METHODS: Thirty-five HIV seroposiüve subjects with respiratory complaints were studied. All patients had a complete history, physical examination and blood counts. The pulmonary assessment included chest radiograms; sputum examination for bacterial and fungal pathogens; bronchoscopy with bronchoalveolar lavage and transbronchial biopsy. Patients with treatable complications received standard antimicrobial therapy. RESULTS: One or more microorganisms were found in 24 subjects and another 3 individuals showed nonspecific interstitial pneumonitis. The sputum examination identified the pulmonary pathogens in 7 cases. The bronchoalveolar lavage and the histopathologic examination were diagnostic in 14% and 83%, respectively, of the 28 individuals that were submitted to bronchoscopy. The most frequently identified microorganism was P. carinii (55%), followed by M. tuberculosis (41%) and cytomegalovirus (8%). The clinical, laboratory and radiographic findings failed to distinguish the specific pulmonary pathogens. Twenty-three individuals with P. carinii pneumonitis and/or tuberculosis received specific therapy; among the evaluable patients the therapeutic response rates were 79% for PCP and 100% for TB. CONCLUSIONS: We have determined that tuberculosis, P. carinii and cytomegalovirus pneumonitis are the most common respiratory opportunistic diseases in Brazilian patients infected with HIV. The histologic evaluation was crucial in order to identify the pulmonary pathogens. Tuberculosis in AIDS individuals displayed clinical and radiographic findings atypical for reactivation disease. However, most of the features observed in HIV infected patients had been previously described in infection of the normal host. Furthermore, the AIDS subjects showed a good therapeutic response to anti-tuberculous drugs.