MDA in plasma as a biomarker of exposure to pyrolysed MDI-based polyurethane: correlations with estimated cumulative dose and genotype for N-acetylation

The object of this study was to investigate whether exposure of pipe-layers to thermal degradation products of diphenylmethane diisocyanate (MDI) could be assessed by analysing 4,4-methylenedianiline (MDA) in hydrolysed plasma and urine, and whether the genotype for N-acetylation affected these biomarker levels. Blood and urine samples were drawn from 30-pipe-layers who had been welding polyurethane (PUR) insulated pipes during the preceding 3 months. MDA in hydrolysed plasma and urine was determined with a gas chromatography-mass spectrometry technique, and genotype for N-acetylation was analysed with a polymerase chain reaction technique. MDA in plasma was detected in 18 of the 30 pipe-layers. Their plasma concentrations of MDA varied from 0.05 to 8.48 g/1. There was a significant negative correlation between time since last welding of PUR-insulated pipes and P-MDA (r _s = 0.50, P = 0.005). There was also a significant positive correlation between the estimated number of welded PUR-insulated pipes during the preceding 3 months and P-MDA (r _s = 0.68, P = < 0.001). No significant association between genotype of N-acetylation and P-MDA was observed in a multiple regression analysis when adjustment was made for the estimated cumulative exposure to thermal degradation products of MDI. MDA in urine was detected in only four of the 30 pipe-layers. These four subjects had been welding PUR pipes on the same day as the sampling, or on the day before. The present results indicate the spot plasma samples analysed for MDA may give a rather good estimate of exposure to MDI during the preceding months. P-MDA, but not U-MDA, therefore seems to be a useful biomarker of long-term exposure to MDI. The individual N-acetylation capacity did not affect the plasma levels of MDA.     

Assessment of left ventricular function: comparison between radionuclide angiography and semiquantitative two-dimensional echocardiographic analysis

Measurement of global left ventricular function is important in the follow-up of cardiac patients and is a good prognostic indicator in acute cardiac situations. We compared quantitative measurements of global left ventricular function made with radionuclide angiography (RNA) and contrast cardiac ventriculography (CVG) to visual semiquantitative estimates from two-dimensional echocardiographic images (2D-echo). Three hundred and thirty-nine consecutive patients who underwent RNA were assessed with 2D-echo within 3 months. In addition, 92 of these patients also underwent CVG (correlation of ejection fraction between CVG and RNA:r=0.82;P<0.0001). The RNA mean ejection fractions in the four 2D-echo groups (0=normal, 1=slightly, 2=moderate, or 3=severe reduced left ventricular function) differed markedly (P<0.0001); however, there was overlapping among the groups (2D-echo score/RNA ejection fraction: 0=57.3%±12.8%; 1=46.0%±12.9%; 2=29.6%±12.2%; and 3=24.6%±11.5%) and the difference between 2D-echo scores 2 and 3 was not significant. 2D-echo showed a good concordance in RNA classes (0=505; 1=35%–49%; 2=21%–34%; and 3=520% ejection fraction) 0 (133/166; 80%) and 3 (18/30; 60%) but low concordance in classes 1 (27/82; 33%) and 2 (21/61; 34%). For accurate assessment of global left ventricular ejection fraction, visual semiquantitative judgement of a 2D echocardiographic image is limited in comparison to CVG or RNA, especially in patients with a slight or moderate reduction in left ventricular ejection fraction.     

Heat shock protein 27 overexpression in breast cancer lymph node metastasis

Background: Heat shock protein 27 (hsp-27) is overexpressed in 67% pure ductal carcinoma in situ (DCIS), in 50% DCIS associated with invasive ductal carcinoma (IDC), and in 25% IDC alone. If this decrease in hsp-27 expression has a role in the progression of malignancy in IDC, we postulate a further reduction in expression in nodal metastasis. Methods: To test this hypothesis, we evaluated the distribution of hsp-27 in primary IDC and in synchronous regional lymph node metastasis within the same patient by immunohistochemistry. Results: Nine of 30 primary IDCs (30%) and 22 of 30 lymph node metastases (73%) overexpressed hsp-27. Contrary to our hypothesis, of 21 IDCs with no or low hsp-27 expression, 13 (62%) had overexpression of this protein within nodal metastasis. Conclusions: hsp-27 appears to confer cytoprotection for metastatic cells, which may help explain why hsp-27 overexpression is associated with reduced disease-free survival in breast carcinomas.     

Cognitive functioning in female patients with 21-hydroxylase deficiency

The cognitive functioning of 27 female patients with congenital adrenal hyperplasia (CAH) (aged 11–41 yrs) and 13 of their healthy sisters (13–31 yrs) was compared using short versions of age-appropriate Wechsler scales. In contrast to other studies, neither a higher than average IQ level for CAH patients (mean: 99.0) nor for their sisters (97.7) was found. Unexpectedly, and in contrast to other reports, the subgroup of salt-wasting (SW) patients>16 yrs (N=6; mean score: 111.5) differed from their sisters as well as from simple-virilizing (SV) patients in full IQ (p<0.05) and subtest scorings for Information, Similarities, and Picture Completion (p<0.05–<0.10). SW patients displayed more masculine behaviour (vs. SV patients and sisters) which, in turn, was related to differential prenatal hormonal influences. No clear-cut relationships between IQ/cognitive (subtest) findings and gender-role behaviour were found.

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Zusammenfassung 27 Patientinnen mit dem Adrenogenitalen Syndrom (AGS) (11–41 J.) und 13 ihrer Schwestern (13–31 J.) wurden hinsichtlich intellektueller Funktionen verglichen (Kurzformen von HAWIK, HAWIE). Im Unterschied zu den meisten früheren Untersuchungen wurden weder für Patientinnen (mean: 99.0) noch für Kontrollen (97.7) über dem Durchschnitt liegende IQ-Werte gefunden. Im Gegensatz zur Literatur unterschied sich die Teilgruppe der Salzverlust-Patientinnen (SW)>16 J. (N=6, mean: 111.5) von den Schwestern und den Patientinnen mit einfachem AGS (SV) im Gesamt-IQ (p<0.05) und in den Untertests Allgemeines Wissen, Gemeinsamkeiten und Bilderergänzen (p<0.05–<0.10). SW-Patientinnen hatten signifikant männlichere Verhaltensmuster gezeigt (vs. SV-Patientinnen und Schwestern), die auf differentielle Hormoneffekte pränatal bezogen worden waren. Es fanden sich aber keine klaren Zusammenhänge zwischen IQ-bzw. Untertest-Resultaten und Ergebnissen für Geschlechtsrollenverhalten.

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Résumé Le fonctionnement cognitif de 21 patientes avec une hyperplasie congénitale surrénale (âgée de 11 à 41 ans) et de 13 de leurs soeurs saines (13–31 ans) a été comparé au moyen de versions raccourcies de l'échelle de Wechsler appropriée à l'âge. En contraste avec d'autres études, il n'a été retrouvé un Q.I. plus haut que la moyenne ni pour les patientes (moyenne 99.0) ni pour leurs soeurs (moyenne 97.7). De façon inattendue, et en contraste avec d'autres études, le sous-groupe de patientes déprivées en sel (SW)>16 ans (N=6), moyenne score: 111.5) différait de leurs soeurs aussi bien en tant que patientes présentant des signes de virilsation (SV) pour le Q.I. complet (p<0.05) et les scores aux subtests d'information, de similarité et de complément d'images (p<0.05–0.10). Les patientes déprivées en sel (SW) montraient un comportement plus masculin (vs. SV et leurs soeurs) qui en retour était relié aux influences hormonales prénatales différentes. Il n'y avait pas de relation de différences nettes entre les résultats aux sous-tests cognitifs du Q.I. et le comportement de genre.