Bronchiolitis obliterans after bone marrow transplantation: evaluation with lung scintigraphy

Hypophosphatasia is a rare disorder characterised by low levels of serum alkaline phosphatase activity resulting in abnormal phosphorylated metabolites and varying skeletal abnormality. We have followed a patient with adult type hypophosphatasia for over ten years who has also shown a persistently elevated tartrate resistant acid phosphatase activity (TRAP) without any obvious cause. Characterisation of this TRAP by polyacrylamide gel electrophoresis (pH 4.0) showed migration to band 5 position. Molecular weight determination by FPLC and an estimate of the molecular weight by gradient gel electrophoresis gave a molecular weight of 29,000-43,600. This molecular weight makes it unlikely for this to be a IgG/TRAP complex persisting in the circulation. Paranitrophenylphosphate was the preferred substrate. This characterises the enzyme as type 5 acid phosphatase which is of the mononuclear/phagocyte type, possibility of osteoclastic origin, though the tissue source remains unknown.     

Bronchiolitis obliterans syndrome in heart-lung transplantation: surveillance biopsies

Transbronchial biopsies (TBBs) are useful to diagnose acute rejection and infection in patients with lung transplants. The value of routine surveillance biopsies (S-TBBs) is not known, and such biopsies with a clinical indication are not without risk and are expensive. One hundred twenty-six 6-mo survivors of heart-lung transplantation (HLT) were studied to determine the effect of stopping S-TBBs on the development of bronchiolitis obliterans syndrome (BOS) and subsequent survival. Fifty-one received transplants while S-TBB was part of routine care (group A), and 75 received transplants after this practice was stopped (group B). There was no difference in patient characteristics. Group A had shorter graft ischemia (p < 0.01) and longer postoperative ventilation (p < 0.01). Maintenance immunosuppression was similar, but group A had more steroid pulses in the second 6 mo after HLT (p < 0.01). The number of patients free from any functional deterioration at 49 to 60 mo after HLT declined to 39% in group A and 64% in group B. The risk of developing BOS grade 1 in group A relative to group B was 1.63 (95% confidence intervals: 0.96-2.79, p = 0.07). Patient survival was similar in the two groups. A total of 86 TBBs were taken in the absence of any signs or symptoms and had low diagnostic yield. In summary, there was no increased incidence of BOS after stopping S-TBBs.     

Bronchiolitis obliterans organizing pneumonia and chronic graft-versus-host disease in a child after allogeneic bone marrow transplantation

BACKGROUND: Human immunodeficiency virus type 1 (HIV-1) subtype O infections are not reliably detected by commonly used anti-HIV-1/2 screening assays. Therefore, anti-HIV-1/2 assays have been modified to increase their sensitivity in detecting antibodies to HIV-1 subtype O. STUDY DESIGN AND METHODS: Two new anti-HIV-1/2 enzyme-linked immunosorbent assays (ELISAs) (Abbott Plus and Ortho Enhanced) were compared with a currently used anti-HIV-1/2 ELISA (Abbott Recombinant) in various serum panels: 91 Western blot-confirmed anti-HIV-1-positive samples, 20 samples from Western blot-confirmed HIV-1-infected patients in log3 serial dilutions, and 1463 samples from consecutive, volunteer, nonremunerated blood donors. RESULTS: Among 91 anti-HIV-1 Western blot-positive samples, 2 (2.2%) were missed by the Abbott Recombinant ELISA, but all 91 were detected by the Abbott Plus and Ortho Enhanced ELISAs. In contrast, two discrepant samples were found to react in viral lysate-based assays. In serial dilutions, Ortho Enhanced ELISA was significantly less sensitive than the Abbott Recombinant and Abbott Plus ELISAs, with the latter two being of comparable sensitivity. The specificities of Abbott Recombinant, Abbott Plus, and Ortho Enhanced ELISAs in 1463 blood donors were 100, 99.93, and 99.86 percent, respectively. Routine testing of 29,102 donations with the enhanced Abbott Plus ELISA revealed a specificity of 99.93 percent. CONCLUSION: Two Western blot-confirmed anti-HIV-1-positive samples were missed by the Abbott Recombinant ELISA but detected by the Abbott Plus and Ortho Enhanced ELISAs. The analytic sensitivity of the Ortho Enhanced ELISA was inferior to that of both Abbott ELISAs. The specificities of the Abbott Recombinant, Abbott Plus, and Ortho Enhanced ELISAs were comparable.     

Primary care of infants and young children with Down syndrome

Down syndrome is caused by triplicate material of chromosome 21. The syndrome has a variable physical expression, but congenital cardiac defects, transient myelodysplasia of the newborn and duodenal atresia are highly specific for this chromosomal disorder. Routine health maintenance is important because infants and children with Down syndrome are more likely to have otitis media, thyroid disease, congenital cataracts, leukemoid reactions, dental problems and feeding difficulties. Since infants with this syndrome are prone to respiratory infections, immunization recommendations should be followed closely. Motor, language, social and adaptive skills should be assessed at each office visit. The psychosocial aspects of care should be discussed with the parents of an infant with Down syndrome. If necessary, the parents should be referred to family support and specialty resources. Institutionalization of infants with Down syndrome is now unlikely. With newer surgical techniques, early therapy to minimize developmental delay and proper health supervision, the functional prognosis for infants with Down syndrome is considerably improved.     

Nonsurgical and surgical management of infants and children with obstructive sleep apnea syndrome

Obstructive sleep apnea (OSA) syndrome in infants and children is one of the more common problems treated by the otorhinolaryngologist-head and neck surgeon. The authors discuss diagnostic studies, nonsurgical and surgical therapies, and perioperative care, including indications for inpatient stay following surgery. Most children are successfully treated for obstructive breathing by adenotonsillectomy. An awareness of the wide range of treatment modalities, with attention to careful postoperative care, should allow for successful management of nearly all children with OSA.     

Psychomotor development in infants and young children

The functional relationship between brain catecholamines and serotoninergic function was studied in stress-naive and chronically immobilized rats after blockade of catecholamine synthesis with alpha-methyl-p-tyrosine (alpha MpT). The levels of noradrenaline (NA), serotonin, and 5-hydroxyindole acetic acid (5-HIAA) in pons plus medulla, brainstem, hypothalamus, hippocampus, and frontal cortex, and those of 3-methoxy, 4-hydroxyphenile-tileneglicol sulphate (MHPG-SO4) in the hypothalamus were measured by HPLC. Chronic immobilization (IMO) resulted in higher NA levels in pons plus medulla and hypothalamus, the latter area (the only one in which the NA metabolite was determined) also showing slightly elevated MHPG-SO4 levels as compared to stress-naive rats. Chronic IMO did not alter either serotonin or 5-HIAA levels, but acute stress consistently increased 5-HIAA levels in all areas, independently of previous chronic stress. Administration of alpha-MpT drastically reduced NA and increased 5-HIAA levels in all brain regions excepting the frontal cortex. The effect of the drug on serotoninergic function was not altered by previous chronic exposure to IMO. These data suggest that the noradrenergic system appears to exert a tonic inhibitory effect on serotoninergic activity in the brain, with the intensity of the effect depending on the brain area studied. In addition, chronic stress does not appear to alter the functional relationship between noradrenergic and serotoninergic activities, although interactions might exist in more restricted brain areas; this deserves further study.     

Phimosis of infants and young children in Japan

Bacterial and viral infections may be associated with the onset of a number of autoimmune diseases and relapses of these conditions. We describe a patient in whom there was a close temporal relationship between a suppurative wound infection and the onset of microscopic polyarteritis. The clinical features of this disease responded to treatment with high dose prednisolone and cyclophosphamide. The patient had several further infective episodes while being treated, but there were no disease exacerbations or relapses related to these. Anti-neutrophil cytoplasmic antibodies (ANCA) were never demonstrated in this patient. Thus while it is likely that the infection precipitated the onset of the systemic vasculitic illness, this occurred independently of ANCA.     

Tietze's syndrome in children and infants

Tietze's syndrome, characterized by isolated swelling and tenderness of a costochondral junction, usually occurs in adults. We describe eight cases of Tietze's syndrome in children, four of them aged 1 year or less. The clinical aspects and laboratory and imaging findings should enable the clinician to recognize this benign entity, thereby avoiding invasive diagnostic procedures to rule out other conditions.     

Pulmonary complications and respiratory function changes after bone marrow transplantation in children

We prospectively assessed the frequency of pulmonary complications and the natural course of lung function after bone marrow transplantation (BMT), as well as the effect of several risk factors in a homogeneous group of 39 children who underwent allogeneic or autologous BMT for haematological malignancies between 1992 and 1995. Four patients developed pneumonia within the first 3 months and three 3-6 months after BMT. A considerable percentage of acute bronchitis was recorded throughout the follow-up. Three patients died after the 6 month visit because of pneumonia (two patients) and pulmonary aspergillosis (one patient). No patients had obstructive lung disease syndrome. At 3 months after BMT, forced vital capacity (FVC), forced expiratory volume in one second (FEV1) and transfer factor of the lung for carbon monoxide (TL,CO) significantly decreased, but FEV1/FVC ratio and maximal expiratory flow at 25% of FVC remained unchanged, suggesting a restrictive defect with diffusion impairment. At 18 months, there was a progressive recovery in lung function, although only 11 patients had normalized. Seropositivity for cytomegalovirus had a significant effect on lung function whereas graft-versus-host disease also had an effect, although it was not statistically significant. Baseline respiratory function, type of transplant, type of conditioning regimen and respiratory infections did not significantly affect the outcome of BMT. The high frequency of severe lung function abnormalities found in this study, suggests a careful functional monitoring in all subjects undergoing bone marrow transplantation, even in the absence of respiratory symptoms.     

Post-transplant obstructive lung disease ("bronchiolitis obliterans"): a clinical comparative study of bone marrow and lung transplant patients

Patients at a single pulmonary centre who developed obstructive lung disease after bone marrow transplantation (BMT) and lung transplantation (LT) were studied, in order to compare the clinical expression of post-transplant obstructive lung disease (PTOLD) (bronchiolitis obliterans) in these two conditions, which have so far been studied separately. Nine out of 179 patients surviving more than 100 days after BMT (5%) and 9 out of 44 patients surviving more than 100 days after LT (20%) developed post-transplant obstructive lung disease. This was defined by an irreversible airflow obstruction, as characterized by a forced expiratory volume in one second divided by forced vital capacity (FEV1/FVC) of less than 70%, and a FEV1 of less than 70% of predicted value. The mean interval between transplantation and the diagnosis of post-transplant obstructive lung disease was 262 days and 217 days for BMT and LT patients, respectively. In all cases, pulmonary symptoms consisted of dyspnoea and progressively productive cough. Bronchial dilatation on high-resolution computed tomography scans was the main imaging feature present in both groups of patients at the onset of post-transplant obstructive lung disease. The mean FEV1/FVC ratio was 51 and 54% for BMT and LT patients, respectively. All BMT and LT patients had normal transfer coefficient. Clinical chronic graft-versus-host disease was present in all BMT patients before or concurrent with the onset of post-transplant obstructive lung disease, and all LT patients had presented at least one episode of acute lung rejection.(ABSTRACT TRUNCATED AT 250 WORDS)     

Heart transplantation in children and young adults: early and intermediate-term results

The purpose of this article is to report our short- and intermediate-term follow-up of cardiac transplantation for congenital heart disease and cardiomyopathy in children (age greater than 6 months), adolescents, and young adults. Thirty patients (ages 8 months to 24 years) with end-stage heart failure have undergone cardiac transplantation in our program: 12 (40%) for postoperative end-stage heart failure, 9 (30%) as primary treatment for congenital heart disease, 5 (17%) for dilated cardiomyopathy, and 4 (13%) for restrictive/hypertrophic cardiomyopathy. Nineteen patients (63%) had undergone prior operations; 4 patients received transplants for failed Fontan procedures. Induction therapy with antithymocyte therapy was used routinely, and long-term immunosuppression was by cyclosporine and azathioprine alone. Rejection surveillance/diagnosis was based on echocardiographic criteria. Posttransplantation follow-up ranges from 3 to 78 months. Operative mortality was 3.3% (1/30). No patients have been diagnosed with either accelerated allograft atherosclerosis or posttransplantation lymphoproliferative disease. We conclude that cardiac transplantation may be performed with excellent early and intermediate-term results.     

Heart transplantation in infants and children with situs inversus

Chemokines (chemoattractant cytokines) attract and activate specific leukocyte subsets. With regard to their expression by brain parenchymal cells, they may represent the key molecules that control leukocyte entry into the subarachnoid space. In order to evaluate the contribution of chemokines in vivo, we determined the levels of MCP-1, MIP-1alpha, RANTES, IL-8, as well as of the sIL-2R in three patients with proven herpes simplex encephalitis type 1 (HSE-1). CSF samples were drawn by a subarachnoid catheter system throughout the time course of hospitalisation. Results were compared to chemokine levels in serum drawn in parallel. The clinical status was documented by the Modified Barthel Index and correlated with chemokine levels in the CSF. The results were compared with the chemokine levels in the CSF of 17 control patients with normal CSF routine parameters. High chemokine levels were detectable in the CSF of all HSE-patients. MCP-1 peak levels were found at the time of admission, while maximal IL-8 levels occurred 4 to 8 h later. The levels of MIP-1alpha and RANTES were lower than those of MCP-1 with a maximum at the time of admission. In all patients the levels of the sIL-2R increased later in the time course, at 14 to 20 h after admission. When the levels of MCP-1 were compared with the clinical status by Modified Barthel Index, we found a high reciprocal correlation (r=-0.82). Routine CSF parameters, such as leukocytes, albumin and immunoglobulins did not correlate with the clinical status. Chemokine levels in serum were found to be close to the detection limits of the ELISA systems. Our data suggest that chemokines play an important role in the pathogenesis of HSE. They may be useful parameters to monitor the stage and severity of the disease. The late increase of sIL2-R levels may indicate the beginning of the reconstitution phase.     

Obstructive changes in the lung of young smokers

The results from the spirometric investigations of pulmonary function in comparable grpis pf 28 smokers and 37 non-smokers at the age of 20 are presented. Positive obstructive changes were established to be present in the lungs of the smokers (smoked about 20 cigarettes daily in the course of four years and more); they were varified by the essential decrease of FEO1, MRFR200-1200, MAEFR25-75, EFR25 and EFR10. MMV50 is decreased with a critical statistical significance.