Long term disease burden post-transplantation: three decades of observations in 25 Hurler patients successfully treated with hematopoietic stem cell transplantation (HSCT).

BACKGROUND: Mucopolysaccharidosis type I-Hurler syndrome (MPSI-H) is a lysosomal storage disease characterized by severe physical symptoms and cognitive decline. Early treatment with hematopoietic cell transplant (HSCT) is critical to the survival of these patients. While survival rates and short-term outcomes are known to be improved by HSCT, the long-term cognitive, adaptive and psychosocial functional outcomes of children with (MPSI-H) post-HSCT are not well documented. This manuscript focuses on retrospective long-term follow-up (7-33 years) of 25 MPSI-H patients, transplanted between 1986 and 2011. RESULTS: The median age at transplantation was 21 months (range 12-57 months). Except for one death, all successfully transplanted MPSI-H patients surviving at least 1 year after HSCT are alive to-date, with a median age of 21 years (range 8-36 years) at the last follow-up evaluation. A majority of HSCT grafts were bone marrow transplants (BMT), resulting in durable full chimerism in 18 (72%). Pre-HSCT, the onset of first symptoms occurred very early, at a median age of 3 months (range birth-16 months). The most prevalent symptoms before MPSI-H diagnosis involved progressive dysostosis multiplex; almost all patients suffered from hip dysplasia and thoracolumbar spine Kyphosis. Despite HSCT, considerable residual disease burden and ensuing corrective surgical interventions were observed in all, and at every decade of follow-up post HSCT. Late-onset psychiatric manifestations were significant (n = 17 patients; 68%), including depression in 13 patients at a median onset age of 18 years (range 13-31 years), hyperactivity and attention deficit disorder (n = 4), and multiple acute psychotic episodes (APE), independent of depression observed (n = 3) at a median onset age of 18 years (range 17-31 years). The adult Welscher Intelligence Scale results (n = 16) were heterogenous across the four scale dimensions; overall lower scores were observed on both working memory index (median WMI = 69.5) and processing speed index (median PSI = 65), whereas verbal comprehension index (median VCI = 79) and perceptual reasoning index (median PRI = 74) were higher. CONCLUSION: With advanced treatment options, MPSI-H are living into 3rd and 4th decades of life, however not disease free and with poor adaptation. Residual disease (loss of mobility, limited gross and fine motor skills; low cognitive ability; suboptimal cardiopulmonary function, vision and hearing) negatively impacts the quality of life and psychosocial functioning of affected individuals.

Impact of spiramycin treatment and gestational age on maturation of Toxoplasma gondii immunoglobulin G avidity in pregnant women.

The objective of the present study was to investigate the maturation of immunoglobulin G (IgG) avidity after Toxoplasma gondii seroconversion during pregnancy and the factors that affect IgG avidity over time. The study used 309 serum samples from 117 women and a multiple linear mixed regression analysis to show the patterns of variation of IgG avidity throughout gestation. The IgG avidity ratios and the patterns of their evolution with time were quite diverse among the women and were statistically heterogeneous (P = 0.011); however, the trend was toward a statistically significant increase (P < 0.0001). On average, a 1.0167-fold increase was observed for each additional gestational week after the putative date of infection. At 12 weeks after putative infection (the expected IgG avidity maturation time), the mean avidity ratio was 16.6% (95% confidence interval, 15.4 to 17.9%). At all times, the avidity ratio remained significantly heterogeneous among the women (P < 0.05); for 95% of them, that ratio ranged from 7.8 to 35.3% at 12 weeks after putative infection. Maternal age at the putative time of infection did not influence the maturation of IgG avidity. However, on average, a 1.009-fold decrease (P = 0.03) in that avidity was observed for each additional week of gestational age before infection and a 1.03-fold increase (P = 0.0003) was observed for each additional week of delay to the onset of spiramycin treatment. The rate of increase in the avidity ratio was lower if infection occurred late in pregnancy and higher if the delay to treatment was long. This information cannot allow accurate determination of the delay since the time of infection. The present results provide support for interpretation of the assay and caution against overinterpretation.

[The presence of asbestos bodies in induced sputum as an indicator of asbestos exposure]. / La presenza di corpuscoli dell'asbesto nell'espettorato indotto come indicatore di esposizione ad amianto.

BACKGROUND: Very few references on the usability of presence of asbestos bodies (AB) in induced sputum as an indicator of asbestos exposure are to be found in the scientific literature. OBJECTIVES: The purpose of this study was to prove whether the presence of AB in induced sputum is a valid assessor of asbestos exposure. METHOD: This was achieved by comparing the above-mentioned method with the search for AB in bronchoalveolar lavage (BAL) fluid and repeating the trials over time in order to study the reproducibility of the results. RESULTS: There was good agreement of results for the presence/absence of AB in induced sputum and in BAL among subjects who were environmentally exposed and those with 'a medium-high risk occupational exposure (100%), and poor agreement (66%) among subjects with a low risk occupational exposure. Agreement of results regarding the amount of particles per test was low. The method showed a sufficient reproducibility level (Cohen K=0.5). CONCLUSION: Although the presence of asbestos bodies in induced sputum cannot replace bronchoalveolar lavage, it can however be used as a screening test for selecting subjects who should undergo BAL.

[Hearing function and solvent exposure: study of a worker population exposed to styrene]. / Udito ed esposizioni a solventi: studio di una popolazione di lavoratori esposti a stirene.

The aim of the study was to investigate the ototoxic effects of occupational styrene exposure, in absence of other risk factors. Pure-tone audiometric thresholds of 32 workers exposed to styrene, but not to noise, in fibreglass reinforced plastic boat manufacturing process were detected and compared to audiometric thresholds of a control unexposed group composed by 60 subjects. Exposure to styrene was measured by urinary mandelic + phenylglyoxylic acid (mean value 149 mg/g crea, SD 80 mg/g crea). For all the frequencies investigated (0,5-1-2-3-4-6-8 KHz) the exposed group showed slight higher mean (median) audiometric thresholds (p < 0.05) compared to controls matched by age and sex, except for 8 KHz in the right ear. The present experience seems to confirm the hypothesis that styrene exposure alone can determine a weak sensorineural high-frequency hearing loss. Such slight impairment, even if statistically significant, does not remarkably limit social hearing and do not involve legal medical aspects. Sample expansion and objective diagnostic tests (auditory brainstem evoked potentials, acoustic otoemissions) are needed.

Delayed maturation of immunoglobulin G avidity: implication for the diagnosis of toxoplasmosis in pregnant women.

The low avidity of immunoglobulin G has been reported to be a useful marker of recent infection with Toxoplasma. Several investigators, however, have published discrepant result on the maturation of avidity over time. The aim of this study was to analyse persistent low avidity of immunoglobulin G in immunocompetent individuals and in pregnant women and how it could interfere in the flowchart of antenatal diagnosis of toxoplasmosis in the latter group. An international literature search was conducted together with a retrospective study of a hospital database. Eleven publications that met the inclusion criteria reported delayed maturation of avidity at a frequency ranging from 0 to 66.6% of the patients. Examination of those publications demonstrated an important heterogeneity in the type of assay used, the calculation of avidity, the cutoff above which avidity was considered to be elevated, and the delay since infection after which indices are expected to be high. In the hospital database, persistent low avidity was found even after a median follow-up period of 6 years. Different factors could interfere with maturation of avidity, such as variations between individuals, the assay system used, and, possibly, the treatment administered. The results of this study clearly demonstrate that, in a pregnant woman, an acute infection cannot be reliably diagnosed solely on the basis of low avidity of immunoglobulin G. Further investigations and standardization of assays are urgently needed. Estimation of the time of infection remains difficult, especially in cases in which the samples are drawn late in pregnancy; the final estimate must be based on several tests repeated at intervals of weeks.

[Cardiac troponin I and C: analytical comparison and clinical-biological interpretation of three troponins assays]. / Troponines I et T cardiaques: comparaison analytique et étude clinicobiologique de trois trousses de troponine.

Many assays 1(st), 2(nd) even 3(rd) generation are at present available to determine the concentration of cardiac troponin I and T. With the redefinition of upper reference value in the acute coronary syndromes, the aim of this study was to evaluate the clinical and analytical performance of 2 troponins assays: Troponin Ic 2(nd) generation (AccuTnI) on Access 2 of Beckman Coulter and Troponin Tc 3(rd)generation (Troponin T STAT) on Elecsys 2010 of Roche Diagnostics. The analytical performance observed with these 2 assays are accurate (analytical and functional sensitivity, repetability and reproductibility). Comparing each method with Dade Behring assay (Flex Troponine-I Cardiaque, TROP) on Dimension RxL, the correlation observed with AccuTnI kit on Access 2 can be put into the equation: AccuTnI = 1.08 (TnIc TROP) - 0.34, r = 0.99. On the contrary, it's more difficult to compare cTnI and cTnT. The study of decisonnal values indicated by Beckman Coulter for cTnI (0.04 microg/L at the 99 degrees percentil, 0.06 microg/L for a CV < or =10%) show a better specificity (76%) and predictive positive value (89%) with a sensitivity at 100% at 0.1 microg/L, fixed and used in the laboratory for its better agreement between sensibility / specificity and its imprecision below 10 %. For the cTnT values published by Roche Diagnostics (0.01 microg/L), at the 99 degrees percentil and 0.03 microg/L for a CV < or = 10%, the specificity is lower, so the decisionnal value 0.1 microg/L seems to be more suitable. During this study, few false positive and negative cTnT values have been observed, in patients with complex pathologies; this eventuality must be taken in consideration if clinical findings are not in good accordance with laboratory results.

[Determination of interleukin-8 in induced sputum of workers exposed to low concentrations of asbestos]. / Determinazione dell'interleuchina-8 nell'espettorato indotto di lavoratori esposti a basse concentrazioni di asbesto.

The concentration of interleukin-8 (IL-8) in the induced sputum of 17 workers exposed to low airborne asbestos levels and of 10 controls was determined. IL-8 levels were statistically significantly increased in the asbestos exposed group compared to controls. This finding underlines the usefulness of the study of proinflammatory mediators as possible predictors of alveolar damage.