Lung function abnormalities after bone marrow transplantation in children: has the trend recently changed?

STUDY OBJECTIVES: To evaluate early and late lung function abnormalities and their predictors in a large sample of children who underwent bone marrow transplantation (BMT) for leukemias in the 1990s, highlighting changes with respect to the 1980s. DESIGNS: Prospective cohort. SETTING: A university department of pediatrics. PARTICIPANTS: Seventy-five consecutive children who underwent BMT were enrolled in the study (median age, 11 years; range, 6 to 19 years; 45 male and 30 female children). Twenty-three children received autologous BMT, and 52 children received allogeneic BMT; 50 children completed the study. MEASUREMENTS: Clinical examinations and lung function tests were performed before BMT, and 3 to 6 months, 12 months, and 24 months after BMT. RESULTS: Before BMT, at 3 to 6 months after BMT, and at 24 months after BMT, 44%, 85%, and 62% of children, respectively, had altered lung function in the absence of persistent respiratory symptoms. Between 3 months and 6 months after BMT, a restrictive pattern was the most frequent abnormality. The only predictive factors for late abnormalities were transplantation performed in the advanced disease phase (odds ratio [OR], 6.75; p = 0.005) and bronchopulmonary infections (OR, 3.9; p < 0.05). CONCLUSIONS: These data suggest that a significant proportion of children who undergo BMT, especially if for leukemia in advanced phase, have early and late pulmonary abnormalities. These abnormalities, especially the late ones, seem to be more severe than patients reported in studies analyzing children undergoing BMT in the 1980s. This could be due to the more intensive front-line treatment protocols employed for treatment of children with acute leukemia in the 1990s.     

Pulmonary function in childhood connective tissue diseases.

The term connective tissue diseases (CTD) defines a group of illnesses characterized by the presence of immune abnormalities and by widespread inflammation involving various organs and tissues including the lung. These diseases are not frequent in the paediatric age group. Very few data on pulmonary function are available in paediatric CTD. We investigated possible early lung function abnormalities and any likely relationship with clinical activity of the disease in a group of 81 paediatric CTD patients, without clinical or radiological evidence of pulmonary involvement. Measurement of lung volumes and diffusion lung capacity were performed. A sample of 65 subjects, defined as normal on the basis of history and clinical examination, and matched by age and height with the group of patients, was chosen as control group. CTD patients did not show significant deviations from the control distribution with respect to functional residual capacity (FRC) and maximal expiratory flow at 75% of the forced vital capacity (MEF75) values. On the contrary, both vital capacity (VC) and diffusing capacity of the lungs for carbon monoxide (DLCO) were quite impaired in most CTD during the active phase of the disease. Our results show a functional lung impairment in most children with clinically active CTD, even in absence of abnormalities on chest X-ray pictures.     

Sleep and oxyhemoglobin desaturation patterns in chronic obstructive pulmonary diseases

A polysomnographic study with noninvasive oxyhemoglobin saturation (HbSaO2) monitoring has been conducted in 11 consecutive male nonobese subjects with chronic obstructive pulmonary disease (COPD). The patients with a high arterial CO2 level and markedly reduced functional residual capacity appeared to be more prone to undergo HbSaO2 desaturation during sleep compared to patients with less severe functional and clinical respiratory impairment. The HbSaO2 desaturations were mostly linked to REM sleep and appeared to be concomitant to the inhibition of the tone of the intercostal muscles. Regarding sleep architecture, the patients with less severe COPD and scarce or absent tendency to HbSaO2 desaturation during sleep showed light and fragmented sleep with a marked tendency to arousals and awakenings.     

Spheroplasts of Haemophilus influenzae Induced by Cell Wall-Active Antibiotics and Their Effect upon the Interpretation of Susceptibility Tests

The interpretation of in vitro susceptibility tests of Haemophilus influenzae performed by the agar or broth dilution methods with Levinthal enrichment was found to be markedly influenced by the production of spheroplasts by this species. Using an inoculum of 10(7) organisms/ml, this phenomenon was frequently evident macroscopically as a haziness on agar substrates and in broths containing cell wall-acting agents, such as ampicillin, cephalothin, and penicillin, but was not noted with chloramphenicol. Phase-contrast microscopic examination of the haze from these sources revealed numerous spherical bodies in contrast to the typical cocco-bacillary forms observed in growth controls. With this inoculum size, minimal bactericidal concentrations could not be determined since subculture of 0.1 ml of the hazy broths or the surface haze onto chocolate agar resulted in most instances in the development of a small number of colonies which, upon smear and gram stain, revealed typical Haemophilus morphology. An inoculum of 10(4) organisms/ml abolished the haziness on agar surfaces and in broths and resulted in clear-cut end points. Also, although spherical bodies were still present, they were distinctly less in number as contrasted to tests performed with an inoculum of 10(7) organisms/ml. It is recommended that minimal inhibitory concentration end points in antibiotic susceptibility tests be determined by microscopic, rather than macroscopic, observation of the growth milieu to determine the presence or absence of morphologically typical bacilli which, when observed, is indicative of true in vitro resistance.     

Measles Inclusion‐Body Encephalitis: Neuronal Phosphorylated Tau Protein is Present in the Biopsy but not in the Autoptic Specimens of the Same Patient

Tauopathies are sporadic or familial neurodegenerative diseases characterized by the accumulation of phosphorylated tau in neurons and glial cells and include encephalitis related to measles virus such as subacute sclerosing panencephalitis. We describe a 45‐year‐old woman, with a history of lymphoma treated with immunosuppressant therapy who underwent an open biopsy of the right frontal cortex for a suspect of encephalitis, and died 4 days later. The neuropathological assessment on the bioptic sample revealed edema, severe gliosis and microglial activation, with lymphomonocytic perivascular cuffing and neurons containing both nuclear and cytoplasmic eosinofilic inclusions that ultrastructurally appeared as tubular and curvilinear non‐membrane‐bound 12–18 nm structures, leading to the diagnosis of measles inclusion‐bodies encephalitis. The biopsy specimen showed several cortical neurons with intense perikaryal immunoreactivity for anti‐tau antibodies recognizing phosphorylated epitopes while on autoptic specimens no phosphorylated tau immunoreactivity was detected. Our findings suggest that in specific conditions biopsy‐derived human tau may be phosphorylated at sites that may result not phosphorylated in autopsy‐derived specimens, most likely caused by post‐mortem dephosphorylation.     

Risk of Developmental Coordination Disorder in Italian very preterm children at school age compared to general population controls

Background

Developmental Coordination Disorder (DCD) is a neurodevelopmental disorder that involves difficulties in goal-directed motor coordination, with ineffective control of fine and gross motor movements in the absence of sensory impairment or neurological condition. DCD is frequently reported in children born very preterm (VP) who survive without CP.

Extracorporeal photochemotherapy: a safety and tolerability pilot study with preliminary efficacy results in refractory relapsing-remitting multiple sclerosis

Abstract Extracorporeal photochemotherapy (ECP) is an immunomodulating procedure consisting of autologous reinfusion of peripheral blood mononuclear cells (PBMC) after direct exposure to 8-methoxy-psoralen and UV-A. It has been described as a successful treatment for different T-cell-mediated diseases and preliminary results suggest that ECP might be effective in the treatment of relapsing–remitting multiple sclerosis, but does not significantly alter the course of the progressive form of MS. In this study, we report the safety data and some preliminary efficacy evidence obtained using ECP in the treatment of five patients with refractory relapsing-remitting (RR) MS: in most cases ECP induced a reduction in the relapse rate and an EDSS stabilisation, with an apparent general MRI stabilisation. In conclusion, our results confirm ECP safety and tolerability and suggest that this treatment might be useful as a therapeutic alternative in the subgroup of RRMS patients not responsive to or not eligible for traditional immunomodulating or immunosuppressive treatments.