Longitudinal left ventricular strain impairment in type 1 diabetes children and adolescents: a 2D speckle strain imaging study.

AIM: Type 1 diabetes (T1D) involves complex metabolic disturbances in cardiomyocytes leading to morphological and functional abnormalities of the myocardium. The relationship between T1D and cardiac structure and function in children is not well established. Our study investigated whether T1D is associated with early subclinical myocardial disturbances in children and adolescents, and whether the state of metabolic control and diabetes duration are influential factors. METHODS: Standard echocardiography, tissue Doppler imaging (TDI) and two-dimensional (2D) strain imaging were prospectively performed in 100 T1D children (age: 11.3 ± 3.6 years, 52 boys) and compared with 79 controls. RESULTS: The diabetic and control children were comparable with respect to age, gender, heart rate and blood pressure. There were no significant differences between the two groups in left ventricular (LV) ejection fraction, LV remodelling and TDI parameters. Conventional mitral Doppler demonstrated significantly fewer diastolic filling abnormalities with an early filling wave in the diabetes group. Global longitudinal strain (GLS) was also significantly lower in the T1D children, while circumferential strain and radial strain did not differ. GLS correlated with HbA1c (r=0.52; P<0.01), but there was no correlation with diabetes duration. CONCLUSION: Our results suggest that LV longitudinal myocardial deformation is decreased in young patients with T1D, and glycaemic control may be the main risk factor for these changes. Further follow-up is now necessary to precisely determine the clinical significance of these myocardial changes detected by 2D strain imaging in T1D children.

Phosphodiesterase (PDE) 7 in inflammatory cells from patients with asthma and COPD.

In inflammatory cells, the low K(m) cyclic adenosine monophosphate (cAMP)-specific phosphodiesterase (PDE) 4 subtype is predominant in terms of expression and function, although more recently it has been suggested that PDE 7 may also play a role in regulating inflammatory cell activity. In the present study, PDE 4 and PDE 7 subtype messenger ribonucleic acid (mRNA) transcripts in CD4 and CD8 lymphocytes from healthy (n=10) and asthmatic (n=10) subjects and polymorphonuclear neutrophils (PMNs) and CD8 lymphocytes obtained from healthy (n=10) and chronic obstructive pulmonary disease (COPD) (n=7) subjects were identified and quantified. PDE 4A, PDE 4B, PDE 4D and PDE 7A mRNA were present in similar quantities in both CD4 and CD8 lymphocytes obtained from healthy and asthmatic subjects and in CD8 lymphocytes obtained from healthy and COPD subjects. Expression of PDE 4C and PDE 7B mRNA was also observed, although transcript levels were low and variable between individuals. In addition, the effects of selective PDE 7 inhibition on both phytohaemagluttinin (PHA)-induced human peripheral blood mixed mononuclear cell (HPBMNC) proliferation and fMLP-induced neutrophil elastase (NE) release were studied. HPBMNC and human neutrophils, isolated from the venous blood of healthy volunteers (n=6) were treated with either a novel selective PDE 7 inhibitor PF 0332040 alone or in combination with rolipram. Proliferation of HPBMNC was stimulated by PHA (2microgml(-1)) and assessed by [(3)H]-thymidine incorporation, while fMLP-induced (100nM) NE release was determined using a chromogenic substrate. Both rolipram (0.003-10microM) and PF 0332040 (0.003-10microM) significantly inhibited PHA-stimulated proliferation of HPBMNC ((**)P<0.01). Co-administration of rolipram (0.3-10microM) and PF 0332040 (0.003-10microM) significantly increased the degree of inhibition observed, compared to when either drug was administered alone ((**)P<0.01). PF 0332040 (0.003-10microM) had no inhibitory effect on NE release from human peripheral blood neutrophils stimulated with fMLP (100nM), while rolipram (0.003-10microM) significantly inhibited neutrophil degranulation ((**)P<0.01). These findings suggest no evidence of altered PDE 4 or PDE 7 mRNA transcript levels in inflammatory cells isolated from the peripheral venous blood of mild asymptomatic asthmatic subjects or stable COPD subjects, however, inhibition of PDE 7 may influence mononuclear cell function.

DMSO-treated HL60 cells: a model of neutrophil-like cells mainly expressing PDE4B subtype.

The human promyelocytic HL60 cells acquired a neutrophilic phenotype after a 7- to 10-day DMSO treatment. Fc gammaRII was up-regulated. Fc gammaRI was also up-regulated by an additional IFN-gamma treatment. These cells are able to produce O2*- by NADPH oxidase activation in the presence of immune complexes or phorbol-12-myristate-13-acetate (PMA). A change of their PDE4 subtype profile was also observed: PDE4B was the predominant isoenzyme, PDE4D was down-regulated and PDE4A was no longer detectable. Additionally, the more NADPH oxidase was activated by PMA, the less PDE4A was expressed, suggesting that NADPH oxidase activity could be used as a surrogate marker of PDE4A down-regulation. Rolipram and Ariflo (cilomilast), two selective PDE4 inhibitors, dose-dependently inhibited receptor-coupled activation of superoxide. These results suggest that PDE4B is the main subtype involved in regulating superoxide induced by Fc gammaRs activation. Furthermore, these cells, expressing almost exclusively PDE4B subtype, could be useful to identify selective PDE4B inhibitors.

Toxicity of ethylene oxide on the lens and on leukocytes: an epidemiological study in hospital sterilisation installations.

An epidemiological study was conducted in 55 subjects (mean age: 41) in hospitals to determine the prevalence of lens opacities and cataracts in workers exposed to ethylene oxide in six sterilisation units. The 21 exposed subjects over 45 were then compared with 16 non-exposed subjects, matched for age and sex. The relation between occupational exposure to ethylene oxide and white blood cell concentrations was also investigated. Lens opacities (independently of visual acuity) were observed in 19 of the 55 exposed. Among both exposed and non-exposed aged over 45, there were no significant differences with regard to the characteristics of lens opacities--prevalence (19 in the 21 exposed; 10 in the 16 non-exposed), distribution of the location, and importance and type (opalescence or discontinuous opacities). No link was found between the characteristics of the lens opacities and the characteristics of exposure: habitual exposure, measured between 0.06 and 39 ppm (cumulated in ppm-number of weekly hours-years) and accidental over-exposures (regular and irregular). For cataracts, defined by the association of lens opacities and a visual acuity less than 20/25 (this loss not being attributable to another cause), their prevalence differed significantly (p less than 0.05) between the exposed (six of 21) and the non-exposed (0 of 16); there was no relation between their existence and overexposures (the analysis for habitual exposure was not possible because of the small size of the sample). The risk of lens opacifications by ethylene oxide in cases of massive exposures as previously described could also exist during chronic exposure to low concentrations. It could be explained by saturation of protective mechanisms against alkylating action of this product. Linear relations were found between the logarithms of blood concentrations of polymorphoneutrophils (R=-0.54; p<0.005) and of lymphocytes (R=-0.45;p<0.05).

[Toxicity of ethylene oxide on the crystalline lense in an occupational milieu. Difficulty of epidemiologic surveys of cataract]. / Etude en milieu professionnel de la toxicité de l'oxyde d'éthylène sur le cristallin. Difficulté des enquêtes épidémiologiques sur la cataracte.

Ethylene oxide is a sterilizing gas for heat-sensitive materials. Eight cases of subcapsular cataract were attributed to this compound from 1982 to 1985. This epidemiological study was conducted in 55 persons to determine the prevalence of lens opacities and cataracts in workers exposed to this gas. The 21 persons of more than 45 years of age were then compared to 16 non-exposed persons matched for age and gender. Lens opacities (independently of visual acuity) were observed in 19 of the 55 exposed. Among exposed and non-exposed persons of more than 45 years of age, there were no significantly differences with regard to the following characteristics of lens opacities: prevalence (13 in the 21 exposed; 10 in the 16 non-exposed), distribution of the localisations, morphology and importance of the cortical opacities. No link was found between the characteristics of the lens opacities and the characteristics of the exposure: habitual exposure and accidental overexposures. For cataracts, defined by the association of lens opacities and a visual acuity less than 20/25 (this loss not being attributable to another cause), their prevalence differed significantly (p less than 0.05) between the exposed (6 of 21) and the non-exposed (0 of 16). There was no relation between their existence and accidental overexposures. The risk of lens opacification by ethylene oxide, established in cases of massive exposures as previously described, could also exist during chronic exposure to low concentrations, but is to be confirmed by other studies. It could be explained by saturation of the protective mechanisms against alkylating action of this product. This study prompted us to discuss the epidemiological difficulties in studies of cataracts.

[Rapid imaging in orbito-ocular pathology. Contribution of gadolinium]. / Imagerie rapide en pathologie orbito-orbitaire. Apport du gadolinium.

To evaluate Gradient-Echo Imaging (GEI) in orbito-ocular pathology, 15 volunteers and 34 patients (40 lesions) were examined with GEA T1 and GEA T2 (0.5 T). Results were compared with SE T1 in all cases, with SE T2 in 20 cases and with other imaging modalities (CT). 30 patients were examined before and after injection of gadolinium. Final diagnosis was obtained by surgery or biopsy in 24 cases or by combined results of imaging and clinical findings in 16 cases. Compared with SE, GEA demonstrated a better visualisation of optic nerve, orbital muscles, choroidal-retinal layer, lens capsule and episclera and a better detection of small lesions. It is very helpful for characterisation of lesions containing hemorrhages or paramagnetic components (melanine, gadolinium) or of vascular nature (angioma). Gadolinium was useful for detection of small lesions or characterisation of a few lesions. Thus GEA seems to be an efficient method for the evaluation of orbito-ocular pathology.

[Histiocytofibroma of the sclerocorneal limbus]. / Histiocytofibrome du limbe scléro-cornéen.

A case of epibulbar benign fibrous histiocytoma is presented, with an optical microscopic study. A greyish vascularised nodule developed at the corneoscleral limbus in a 65 year-old male. The clinical diagnosis was confirmed by histopathologic evaluation. Complete surgical excision had a curative effect.

[Corneal dysplasia]. / Dysplasie cornéenne.

Corneal dysplasia has been recently reported. Clinically, it is characterized by a progressive epithelial corneal opacity with pearly or greyish white coloration. Its topography may be either next to either far from the limbus. The recurrences are frequent after surgical treatment. Histologically, many aspects are described. Morphological changes affecting the cells and/or the architecture of the modified epithelium, may vary from light dysplasia to true carcinoma in situ. Some peculiar clinical conditions may coexist with corneal dysplasia, which may also be isolated. Three clinical cases are reported, with detailed pathological data. The signification of the use of the term "dysplasia" and the histogenesis are discussed, and the conclusions for treatment are drawn.