Cystic fibrosis in blacks in Washington, DC: fifteen years' experience

Controversies exist regarding the clinical presentation and characteristics of cystic fibrosis (CF) in American blacks. Between 1971 and 1986, 188 patients with CF (165 whites, 20 blacks, and 3 others) seen at Children's Hospital National Medical Center, Washington, DC, were evaluated for age at diagnosis, duration of symptoms prior to diagnosis, clinical presentations, initial sputum culture results, and weight and height at diagnosis. Comparisons between black and white patients revealed no statistically significant differences in average age at diagnosis, average duration of symptoms prior to diagnosis, average sweat electrolyte concentrations, or sputum culture results. A breakdown of presenting symptoms by race showed some points of disparity. About twice as many black patients as white patients (40% v 22%) presented with only pulmonary symptoms, whereas slightly more whites presented with only gastrointestinal symptoms (46% v 35%). Those patients presenting with a combination of symptomatology were equally distributed by race (25% black, 21% white). At diagnosis, age-adjusted weight percentiles were significantly lower for black patients than for white patients (chi 2 = 9.60, P less than or equal to 0.05). Although the authors agree that CF is relatively rare among blacks, a high index of suspicion is essential for early diagnosis.     

Restrictive lung disease and serum TGF-beta1 in thalassemia major children

A cross sectional study was performed in 21 thalassemia major (TM) children at King Chulalongkorn Memorial Hospital during March to August, 2003 to determine whether restrictive lung disease (RLD) was related to serum transforming growth factor-beta 1 (TGF-beta1). All studied patients (57% female, age 11.2 +/- 2.6 yrs, duration of transfusion 7.7 +/- 4.1 yrs) never had desferoxamine treatment and their pulmonary function, serum ferritin and serum TGF-beta1 were evaluated. Five (24%) had RLD. RLD patients had significantly longer durations of transfusion and higher serum ferritin levels than non-RLD patients (9.1 +/- 1.9 vs 5.5 +/- 3.2 yrs; p = 0.03 and 3,816.6 +/- 1,715.9 vs 2,084.5 +/- 1,504.8 ng/ml; p = 0.04, respectively). TM children had lower serum TGF-beta1 levels than normal children (7.9 vs 78.8 pg/ml; p < 0.001). The serum TGF-beta1 level was not different between RLD and non-RLD patients (13.3 vs 4.2 pg/ml; ns), concluding that RLD was related to longer duration of transfusion and higher serum ferritin but not related to serum TGF-beta1 levels.     

Prevalence of Mycoplasma and Chlamydia pneumonia in severe community-acquired pneumonia among hospitalized children in Thailand

Pneumonia is the leading cause of pediatric morbidity and mortality worldwide, and Mycoplasma pneumoniae and Chlamydia pneumoniae are the two most common atypical pathogens. This study was designed to determine the prevalence and clinical impact of mycoplasma and chlamydia pneumonia in children hospitalized with severe pneumonia. Children 1 month-15 years old with a diagnosis of severe pneumonia (WHO criteria) were recruited between March 2005 and March 2006. Serologic studies were performed for anti-M. pneumoniae and anti-C. pneumoniae IgG/M on admission and 2-4 weeks afterward using ELISA. Of 52 patients, 13 (25%) were positive for Mycoplasma, 8 (15%) were positive for Chlamydia, 4 (7.6%) were positive for a mixed infection and 27 (52%) were negative. The subjects' mean age was 23.8+/-4.1 months. The mean of initial oxygen saturation on admission was 87.5+/-1.2%. Fever and prolonged cough were the leading symptoms. The mean of hospitalization was 18.8+/-2.6 days, chlamydia pneumonia had the longest duration, 30+/-10.2 days and 13/52 (25%) study subjects developed respiratory failure. Only 10% were treated with adequate antibiotic prior to serologic results. There was one mortality (1/52, 2%). Our study suggests that mycoplasma and chlamydia infections are commonly found among children hospitalized with severe pneumonia. Coverage with an appropriate antibiotic should be considered to hasten recovery.     

Repeated restraint stress and corticosterone injections during late pregnancy alter GAP-43 expression in the hippocampus and prefrontal cortex of rat pups

In the offspring of prenatal stress animals, overactivity and impaired negative feedback regulation of the hypothalamic–pituitary–adrenal axis are consistent finding. However, little was known about how prenatal stress can permanently alter developmental trajectories of pup's brain. Growth-associated protein-43 (GAP-43) is a presynaptic membrane phosphoprotein whose expression increases during developmental events such as axonal outgrowth or remodeling and synaptogenesis. Phosphorylation of GAP-43 by protein kinase C was correlated with enhanced axonal growth and transmitter release. In adult animals, increase of GAP-43 correlated with monoaminergic deficit in neuropsychiatric disorders. The present study examines the effects of repeated maternal restraint stress on the level of GAP-43 in the brain of rat pups. The results showed that prenatal stress significantly increased GAP-43 level in the PFC of rat pup during PND 7–14 as compared to control but not significant difference when observed at PND 21. Increased GAP-43 expression was also observed in the pup's hippocampus during the same postnatal periods. However, when observed at PND 60, pups born from stressed mother showed a significant lower (p < 0.001) GAP-43 expression as compare with control group. These changes indicate the direct effect of corticosteroid hormone, since repeated maternal injection with corticosterone (CORT, 40 mg/kg) during GD 14–21 also gave the same results. PND 7–14 is the peak period of synaptogenesis in these brain areas and abnormal axon sprouting and reorganization may lead to a defect in synaptic pruning at later stage of life. The results suggested that maternal stress is harmful to the developing brain and upregulation of GAP-43 indicated a protective mechanism against the toxicity of maternal stress hormone. Prenatal stress alter the normal developmental trajectories in the pup's brain may underlies the mechanism link between early life stress and neuropsychopathology in later life.     

Prenatal stress alters presynaptic marker proteins in the hippocampus of rat pups

Exposure to stress during critical periods of an organism's maturation can result in permanent behavioral changes and induced hyper-responsive to aversive stimuli as adult. Hippocampus is a plastic and vulnerable brain structure that is susceptible to damage during aging and repeated stress. The present study examines the effect of maternal restraint stress on the level of GAP-43, pGAP-43 and synaptophysin in the hippocampus of rat pups. Prenatal stress (PS) causes a significant increase of GAP-43 and pGAP-43 (p ≤ 0.001) in the pup's hippocampus during postnatal days 7 and 14, but not at later ages. Up-regulation of GAP-43 and pGAP-43 may alter the pattern of axonal growth and synapses’ formation in the pup's brain since the first two postnatal weeks are correlated with peak period of synaptogenesis in the rat brain. We also examined the level of synaptophysin, a synaptic vesicle membrane protein, in the pup's brain. Our finding revealed that, PS causes a significant decrease of synaptophysin in the pup's hippocampus as compared to control (p ≤ 0.001). These changes are due to the direct effects of maternal stress hormone since repeated injection with corticosterone (CORT, 40 mg/kg) to pregnant rat during gestation days (GDs) 14–21 also gave the same results. Abnormal axonal sprouting and reorganization together with the alterations in synaptic vesicle membrane protein during the critical period of synaptogenesis may lead to a defect in synapse formation and axonal pruning in the hippocampus. These changes may be associated with stress-induced impairment of hippocampal function that occurs in later life of the offspring.     

Risk factors of bronchial hyperresponsiveness in children with wheezing-associated respiratory infection

The objectives of this study were to identify possible risk factors of bronchial hyperesponsiveness (BHR) in children up to 5 years of age with wheezing-associated respiratory infection (WARI), and to study the prevalence of BHR. Children up to 5 years of age with WARI were enrolled in the study. The parents or caregivers of children were asked about their demographic data and clinical histories. Physical examination and clinical score assessment were performed. Pulmonary function tests, i.e., tidal breathing flow volume (TBFV), were performed to measure tidal breathing parameters before and after salbutamol nebulization. If volume at peak tidal expiratory flow/expiratory tidal volume and time to peak expiratory flow/total expiratory time increased > or = 20%, or tidal expiratory flow at 25% of tidal volume/peak tidal expiratory flow increased > or = 20% after nebulization therapy, BHR was diagnosed. The number in the positive BHR group was used to calculate the prevalence of BHR, and clinical features were compared with those of the negative BHR group. Categorical data were analyzed for statistical significance (P < 0.05) by chi-square test or Fisher's exact test, or Student's t-test, as appropriate. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for those with statistical significance. One hundred and six wheezing children underwent pulmonary function tests before and after salbutamol nebulization. With the aforementioned criteria, 41 cases (38.7%) were diagnosed with BHR. History of reactive airway disease, (OR, 6.31; 95% CI, 1.68-25), maternal history of asthma (OR, 3.45; 95% CI, 1.34-9), breastfeeding less than 3 months (OR, 3.18; 95% CI, 1.26-8.12), and passive smoking (OR, 3; 95% CI, 1.15-7.62) were significant risk factors of BHR. The eosinophil count was significantly higher in the BHR (+) group particularly, in children 1-5 years of age (P < or = 0.01). Patchy infiltrates were more commonly found in patients with negative BHR but not statistically significant. In conclusion, a history of reactive airway disease, maternal history, breastfeeding less than 3 months, and passive smoking were significant risk factors for BHR.     

Afebrile pneumonia associated with chlamydial infection in infants less than 6 months of age: initial results of a three year prospective study

During the year 1986-1988, 112 infants younger than 6 months of age with the diagnosis of afebrile pneumonia were studied at Chulalongkorn Hospital, Bangkok, Thailand. Thirty cases (26.78%) were caused by Chlamydia trachomatis. The clinical and laboratory findings which differed significantly from pneumonia caused by other organisms included longer duration of symptoms (greater than 1 week), younger age of onset (less than 12 weeks), history of conjunctivitis after birth, no wheezing detected, white blood cell count greater than or equal to 10,000 cells/microliters with eosinophilic count greater than or equal to 300 cells/microliters and reticulonodular infiltration on the chest x-ray.     

Clinical outcomes after utilizing surviving sepsis campaign in children with septic shock and prognostic value of initial plasma NT-proBNP

Background and Objective:

The surviving sepsis campaign treatment guideline (SSC) implementation is associated with improved outcome in adults with severe sepsis. The effect on outcome of pediatric sepsis is less clear.

Purpose:

To determine the clinical outcomes of SSC implementation and to investigate the prognostic value of initial plasma NT-proBNP and procalcitonin in children.

Materials and Methods:

Infants and children (aged 1month/0-15 years with severe sepsis or septic shock) were prospectively enrolled and treated according to the guidelines. Initial blood drawn was saved for NT-pro-BNP, procalcitonin measurements and clinical data were also recorded.

Results:

A total of 47 subjects were recruited. Since the application of the SSC, our mortality rate had significantly decreased from 42-19% (P = 0.003) as compared to the data in the previous 3 years. Clinical factors that significantly increased the mortality rate were: Initial central venous oxygen saturation < 7 0% after fluid resuscitation [odds ratio (OR) = 23.3; 95% confidence interval (CI) 3.7-143; P = 0.001], and initial albumin level (≤ 3 g/dl, OR = 6.7; 95% CI 1.2-37.5, P = 0.03). There was asignificant difference between the initial NT-proBNP levels between survivors and non survivors, (6280.3 ± 9597 ng/L, P < 0.001), but not for procalcitonin (12.7 ± 24.8, 29.3 ± 46 μg/L, P = 0.1), respectively. An initial NT-proBNP level of more than 11,200 pg/ml predicted Pediatric Intensive Care Unit (PICU) mortality with a sensitivity of 85.7% and a specificity of 90%.

Conclusions:

A modified SSC for severe sepsis and septic shock significantly reduced the mortality rate in our PICU. High initial NT-ProBNP level was associated with mortality.