Interstitial lung disease in patients with ataxia-telangiectasia

Ataxia-telangiectasia (A-T) is an autosomal-recessive multiorgan disease characterized by progressive neurologic deterioration in which the most common causes of death are diseases of the respiratory system and cancers. The aim of this retrospective study was to delineate the clinical, radiographic, and pathologic manifestations of the chronic progressive interstitial lung disease seen in patients with A-T. The medical records of 97 patients with A-T and chronic lung disease were reviewed. Interstitial lung disease (ILD) was specifically diagnosed in 25 of 97 patients. None of these patients had evidence of an infectious process preceding the onset of their lung disease, and none had lasting clinical improvement after treatment with antibiotics. Although many medications were used to treat their ILD, only treatment with systemic corticosteroids early in the course of their illness was associated with clinical and radiographic improvement. Nineteen of these 25 patients with ILD died within 24 months of the onset of their ILD, and of 7 patients treated with corticosteroids, 5 are still alive. Recognition of interstitial lung disease in patients with A-T and its early treatment could reduce or eliminate pulmonary disease as a leading cause of death for these patients.     

Atrial septal defect in adults > or =40 years old: negative impact of low arterial oxygen saturation

BACKGROUND: Although good prognosis and clinical long-term outcome have been commonly reported in minimally symptomatic adult patients with ASD, this information has been based on studies with a relatively small number of adult patients. We studied unoperated patients aged over 40 years to define the patterns of presentation, anatomical characteristics, outcome and predictive factors for free-event survival of major cardiovascular and pulmonary events. METHODS AND RESULTS: Two-hundred survivors of atrial septal defect aged over 40-yr attended from 1985 to 1998 were reviewed and followed-up from 1.6 to 22 years. Patients were classified in three groups according to age at entry: Group 1, between 40 and 49; Group 2; 50 and 59; and Group 3, > or =60 years old. The mean age at presentation was 48.8+/-9.2 years, and the most common clinical presentations were arrhythmia and dyspnea (51.4%). There were 37 (18.5%) events: 7 heart failure-related, 5 sudden death, 13 severe pulmonary infections, 5 embolisms, and 4 strokes. According to Cox's regression analysis, predictors of primary end point included age group at presentation (hazard ratio 1.71, 95% confidence limits 1.16 to 2.54), and either pulmonary hypertension (mean pulmonary pressure >35 mmHg; hazard ratio=0.65 (4.6, confidence limits 2.2 to 9.5) or, arterial oxygen saturation <80% (hazard ratio 1.71, 95% confidence limits 1.16 to 2.54). CONCLUSIONS: This study supports that long term outcome of patients aged >40 years with unoperated ASD is importantly determined by the mPAP (>35 mmHg), SaO2% (_80) and the age at diagnosis. Nevertheless we identified an inverse association between the mPAP level and SaO2% (interaction). The event-free survival expectancy may be estimated using the age at diagnosis and either SaO2% or mPAP. This prognostic stratification based on pathophysiological principles, may help in making decisions for therapeutic interventions. SaO2% should always be measured as a part of the initial clinical approach of those patients with atrial septal defect aged over 40 years.     

Rapid steroid taper and neoral monotherapy in liver transplantation in Chile: a step in the right direction?

Diabetes, hypercholesterolemia, hypertension, obesity, osteopenia, and increased risk of viral recurrence are among the complications associated with posttransplant steroid use. Steroid withdrawal or rapid taper has been reported to be safe. The aim of this study was to compare the rejection incidence and severity among patients treated with two different steroid taper strategies. METHODS: This retrospective study included all the adult liver transplant recipients since the program's inception from 1993 to January 2002. The minimum follow-up was 1 year. Exclusions included patients receiving an immunosupressive regimen other than mycophenolate mofetil, steroids, and Neoral, or suffering an autoimmune etiology, or displaying patient or graft survival less than 1 year. The incidence and severity of rejection episodes were compared between the two groups of steroid taper protocols: group A received methylprednisolone (1 g) intraoperatively with a slow taper to 10 mg prednisone per day at 1 year. Group B received methylprednisolone (2 g) intraoperatively followed by a rapid reduction with intention to withdraw by month 4, continuing on Neoral monotherapy. Rejection diagnosis was made on histological bases. RESULTS: One-month and 1-year rejection rates were 47% and 53%, respectively, among the rapid taper group with Neoral monotherapy, which was similar to 60% and 64%, respectively, in the slow taper group. Rejection severity was also comparable between the two groups. CONCLUSIONS: Patients treated with a rapid steroid taper protocol followed by Neoral monotherapy or a slow taper protocol showed similar acute rejection incidences and severities. Their survival rates were also comparable. Further study is necessary to evaluate the impact of rapid steroid taper to prevent the complications of steroid use.     

Environmental exposure and leptospirosis, Peru

Human infection by leptospires has highly variable clinical manifestations, which range from subclinical infection to fulminant disease. We conducted a population-based, cross-sectional seroepidemiologic study in Peru to determine potential relationships of environmental context to human exposure to Leptospira and disease associated with seroconversion. Three areas were studied: a flooded, urban slum in the Peruvian Amazon city of Iquitos; rural, peri-Iquitos villages; and a desert shantytown near Lima. Seroprevalence in Belen was 28% (182/650); in rural areas, 17% (52/316); and in a desert shantytown, 0.7% (1/150). Leptospira-infected peridomestic rats were found in all locales. In Belen, 20 (12.4%) of 161 patients seroconverted between dry and wet seasons (an incidence rate of 288/1,000). Seroconversion was associated with history of febrile illness; severe leptospirosis was not seen. Human exposure to Leptospira in the Iquitos region is high, likely related both to the ubiquity of leptospires in the environment and human behavior conducive to transmission from infected zoonotic sources.     

Breastfeeding patterns in Rio Branco, Acre, Brazil: a survey of reasons for weaning

This paper presents a preliminary profile of infant feeding practices in a peri-urban Amazonian community. A random sample of 180 households with at least one child under the age of five years were interviewed in 1996 as part of a maternal-child health survey conducted in a peri-urban neighborhood in Rio Branco, Acre, Brazil. Since some households had more than one child under the age of five, data were collected for a total of 250 children. The results of the survey indicate that initiation of breastfeeding is nearly universal, with 96.0% of women breastfeeding their infants at birth. However, many mothers terminate breastfeeding before the recommended age. Forty-five percent of infants are weaned before six months and 62.0% are weaned before 12 months. The survey also reveals that mothers give supplemental food and drink at an early age. Finally, while women give a variety of responses for why breastfeeding was terminated, the most common answer (42.0%) was that the infant refused the breast. The meaning and implications of this response merit further investigation.     

Cytomegalovirus pneumonitis in a patient with Hodgkin disease and ataxia-telangiectasia

We describe a child with with Hodgkin disease and ataxia-telangiectasia who also developed an unusual pneumonitis caused by a cytomegalovirus which was fatal.     

Activation of the neuronal c-Abl tyrosine kinase by amyloid-beta-peptide and reactive oxygen species

The deposition and accumulation of amyloid-beta-peptide (Abeta) in the brain are considered a sine qua non for Alzheimer's disease. The experimental delivery of fibrilized Abeta serves as a cellular model for several facets of the disease including the induction of synaptic dysfunction and apoptosis. c-Abl kinase is involved in the regulation of apoptosis and its pro-apoptotic function is in part mediated by its interaction with p73, a p53 homologue. We found that c-Abl activation is involved in cell signals that regulate neuronal death response to Abeta fibrils. Abeta peptide fibrils induced an increase of the c-Abl activity in rat hippocampal neurons as well as an increase in nuclear p73 protein levels and the p73-c-Abl complex. The neuronal cell death induced by Abeta fibrils was prevented by the inhibition of c-Abl with imatinib mesylate (Gleevec or STI571) and by the inhibition c-Abl expression by RNAi. These results directly point to a therapeutic strategy for the treatment of Alzheimer's disease.     

Risk factors for microalbuminuria in children with sickle cell anemia

PURPOSE: To determine the prevalence of microalbuminuria and to establish clinical characteristics associated with microalbuminuria in children with sickle cell anemia. PATIENTS AND METHODS: Urine samples of all children (homozygous SS) followed in the Medical College of Georgia's Children's Medical Center Sickle Cell Clinic were screened for microalbuminuria. Random samples were obtained from continent patients at routine office visits between September 1996 and November 1999. A retrospective chart survey was performed to determine clinical correlates for microalbuminuria. Medical records were reviewed for age, sex, hemoglobin, and episodes of pneumonia, pain, aplasia, acute chest syndrome, priapism, and avascular necrosis. Demographic and clinical variables were compared with microalbuminuria by univariate and multivariate logistic regression. RESULTS: One hundred forty-two patients ages 21 months to 20 years made up the study group. The prevalence of microalbuminuria was 19%. Both increasing age and a lower hemoglobin level were found to correlate with microalbuminuria. By multivariate analysis, boys with microalbuminuria were likely to have a lower hemoglobin level and girls with microalbuminuria were likely to be older. None of the following factors were significantly related to microalbuminuria: pain, pneumonia, acute chest syndrome, priapism, avascular necrosis, or aplastic episodes. CONCLUSIONS: Microalbuminuria is strongly and directly related to age and strongly and inversely related to hemoglobin levels. Identification of risk factors for microalbuminuria may allow earlier intervention to prevent renal complications in patients with sickle cell disease.