Testing for anabolic steroids in hair: a review

It is generally accepted that chemical testing of biological fluids is the most objective means of diagnosis of drug use. The presence of a drug analyte in a biological specimen can be used to document exposure. The standard in drug testing is the immunoassay screen, followed by the gas chromatographic-mass spectrometric confirmation conducted on a urine sample. In recent years, remarkable advances in sensitive analytical techniques have enabled the analysis of drugs in unconventional biological specimens such as hair. The advantages of this sample over traditional media like urine and blood are obvious: collection is almost noninvasive, relatively easy to perform, and in forensic situations it may be achieved under close supervision of law enforcement officers to prevent adulteration or substitution. Moreover, the window of drug detection is dramatically extended to weeks, months or even years. The aim of this review is to document the current detection of anabolic steroids in hair.     

Severity of acute pulmonary embolism: evaluation of a new spiral CT angiographic score in correlation with echocardiographic data

The purpose of this study was to investigate whether the severity of acute pulmonary embolism (PE) could be quantitatively assessed with spiral CT angiography (SCTA). Thirty-six consecutive patients without underlying cardiopulmonary disease and high clinical suspicion of PE underwent prospectively thin-collimation SCTA and echocardiography at the time of the initial diagnosis (T0) and after initial therapy (T1; mean interval of time T1–T2: 32 days). The CT severity score was based on the percentage of obstructed surface of each central and peripheral pulmonary arterial section using a 5-point scale (1: <25%; 2: 25–49%; 3: 50–74%; 4: 75–99%; 5: 100%). The sum of the detailed scores attributed to 5 mediastinal, 6 lobar and 20 segmental arteries per patient led to the determination of central, peripheral and global CT severity scores and subsequent determination of percentages of obstruction of the pulmonary circulation. Echocardiographic severity criteria included the presence of signs of acute cor pulmonale and/or systolic pulmonary hypertension (>40 mm Hg). The SCTA depicted acute PE in all patients at T0 with complete resolution of endovascular clots in 10 patients at T1. At T0, the mean percentage of obstruction of the pulmonary arterial bed was significantly higher in the 22 patients with echocardiographic signs of severity (56±13 vs 28±32%; p<0.001). A significant reduction in the mean percentage of pulmonary artery obstruction was observed in the 19 patients with resolution of echocardiographic criteria of severity between T0 and T1 T0: 57±14%; T1: 7±11%; p<0.001).The threshold value for severe PE on CT angiograms was 49% (sensitivity: 0.773; specificity: 0.214). The mean (±SD) pulmonary artery pressure was significantly higher in the 26 patients with more than 50% obstruction of the pulmonary artery bed (45±15 mm Hg) than in the 10 patients with less than 50% obstruction of pulmonary artery bed at T0 (31±11 mm Hg; p<0.01). The CT severity score evaluated in the present study enables quantitative assessment of acute PE severity on spiral CT angiograms, readily applicable in routine clinical practice. Electronic Publication     

Late toxicity results of the GORTEC 94-01 randomized trial comparing radiotherapy with concomitant radiochemotherapy for advanced-stage oropharynx carcinoma: comparison of LENT/SOMA,RTOG/EORTC,and NCI-CTC scoring systems

PURPOSE: To prospectively assess 5-year late toxicity in patients treated by concomitant radiochemotherapy for locally advanced oropharynx carcinoma using three different toxicity scales. METHODS AND MATERIALS: A total of 226 patients were entered in a Phase III multicenter, randomized trial comparing radiotherapy alone (70 Gy in 35 fractions: Arm A) with concomitant radiochemotherapy (70 Gy in 35 fractions with three cycles of a 4-day regimen containing carboplatin and 5-fluorouracil: Arm B). Five living patients, free of local or distant recurrences, could not be evaluated for late toxicity. Forty-four patients were eligible for late toxicity with a median follow-up of 5 years. Late toxicity was evaluated by the radiation oncologist using a large questionnaire containing 120 mixed items of three scales (NCI-CTC, LENT/SOMA, and RTOG). The data were then transposed on separate scales using corresponding grades. RESULTS: The 5-year overall survival rate was 22% in Arm B and 16% in Arm A (p = 0.05). The 5-year locoregional control rate was 48% in Arm B and 25% in Arm A (p = 0.002). The spinal cord was not affected by the concomitant adjunct of chemotherapy, and no deaths were caused by late toxicity. Using the three late toxicity scales, 100% of the patients treated with the combined modality (Arm B) developed one or more late complications vs. 94% in the radiotherapy-alone arm (Arm A). The difference was not statistically significant. The most commonly damaged organs (all Grade 1-4) were the salivary glands (100% in Arm B vs. 82% in Arm A, p <0.05), skin (78% vs. 47%, p <0.05), teeth (67% vs. 18%, p <0.05), mucosa (59% vs. 63% p = not significant), and mandible (44% vs. 12%, p <0.05). One or more Grade 3-4 complications occurred in 82% of the patients in Arm B vs. 47% in Arm A (p = 0.02) but concerned only the teeth. The correlation between the RTOG and LENT/SOMA scale and between the NCI-CTC and LENT/SOMA scale were low for Grade 1-4 toxicity (near 30%). The transposability of a patient's symptoms was significantly greater using the LENT/SOMA or RTOG/EORTC scaling systems than using the NCI-CTC system. CONCLUSION: Concomitant radiochemotherapy increased overall survival and locoregional control rates. The difference between the two treatment groups for Grade 3-4 complications was only significant for the teeth. The late toxicity assessment of a treatment may depend on the toxicity scale used. The LENT/SOMA scale seems to be the most accurate scale, but most of the score results were not concordant with those obtained with other scales. The results of this study confirm the necessity of using a common late toxicity scale in clinical trials.     

Chronic myeloproliferative disorders with rearrangement of the platelet-derived growth factor alpha receptor: a new clinical target for STI571/Glivec

Two cases of atypical chronic myeloid leukaemia (CML) carrying the t(4;22)(q12;q11) translocation involving the breakpoint cluster region (BCR) and platelet-derived growth factor alpha receptor (PDGFRA) genes have been recently characterized. We report a third case of atypical CML with the same translocation but with a distinct breakpoint fusing BCR exon 1 with PDGFRA exon 13. The patient had a clinical presentation of CML with progressive transformation in B-cell acute lymphoblastic leukaemia. The involvement of PDGFRA led us to treat the patient with the small organic compound imatinib mesylate/STI571 (Glivec) that blocks the ATP binding site of tyrosine kinases such as Abelson, KIT and platelet-derived growth factor receptors. The patient subsequently achieved a rapid clinical and molecular response clearly demonstrating, for the first time, that Glivec is active against PDGFRA in vivo. Therefore, our study expands the list of Glivec targets and has direct biological and also clinical implications.     

Breast cancer revisited using DNA array-based gene expression profiling

Breast cancer is a complex genetic disease characterized by the accumulation of multiple molecular alterations. The resulting clinical heterogeneity makes current diagnostic and therapeutic strategies less than perfectly adapted to each patient. Pathological and clinical factors are insufficient to capture the complex cascade of events that drive the clinical behavior of tumors. High-throughput molecular technologies provide novel tools to tackle this complexity. In particular, DNA arrays allow the simultaneous and quantitative analysis of the mRNA expression levels of thousands of genes in a single assay. Potential applications are multiple in the cancer field and the first research results are promising; comprehensive gene expression profiles of breast tumors are providing insights into mammary oncogenesis and are revealing new tumor subgroups previously indistinguishable. Significant advances will be the identification of new diagnostic, prognostic and predictive biomarkers as well as the discovery of new potential therapeutic targets. This review presents recent applications of DNA arrays in breast cancer research and discusses some issues to address in the near future to allow the technology to reach its full potential.     

Use of Hsf1(-/-) mice reveals an essential role for HSF1 to protect lung against cadmium-induced injury

Cadmium (Cd) is known to activate heat shock (HS) response, which is characterized by overexpression of heat shock proteins (Hsps) under the control of heat shock factor 1 (HSF1). The potential protection provided by the HS response, induced by increasing the body temperature of animals before Cd exposure or by Cd itself, against pathophysiological changes occurring after Cd intranasal instillation (1 to 100 microg/mouse) was examined. HSF1-deficient mice were used to evaluate the role of this factor in lung protection. Cd instillation caused dose- and time-dependent changes in the respiratory pattern measured by plethysmography (Penh), and significant increases in lactate dehydrogenase (LDH) activity as well as macrophage and neutrophil counts in bronchoalveolar lavage fluids. HS preconditioning induced Hsp overexpression and reduced the Penh (-30%), LDH (-25%), and neutrophil (-55%) responses to subsequent administration of the highest Cd doses (50 and 100 microg) in wild-type mice. HSF1 deficiency abolished the HS response and its protective effect. In the absence of preconditioning, Hsf1(-/-) mice exhibited higher values of Penh (+70%) and LDH activity (+42%) compared with wild-type animals when exposed to the lowest Cd doses. Higher macrophage (+80%) and neutrophil counts (+115%) were recorded whatever the dose. Western blot analyses indicated that lung protection might be related to the kinetics of HSF1-dependent Hsp70 expression. Altogether, our data demonstrate that HS response elicited both by prior HS and by Cd itself moderates pulmonary injuries due to Cd instillation, and that HSF1 is a major mediator in this protection.     

Fatal outcome in a female monozygotic twin with X-linked hypohydrotic ectodermal dysplasia (XLHED) due to a de novo t(X;9) translocation with probable disruption of the EDA gene

Ectodermal dysplasias are a group of congenital disorders with defective development of the epidermis and its appendages. X-linked hypohydrotic ectodermal dysplasia (XLHED; OMIM 305100) is the most common form of ectodermal dysplasia. We report on two monozygotic twin girls with XLHED due to a t(X;9) translocation causing a disruption of the EDA gene and non random inactivation of the normal X chromosome. One of the girls died unexpectedly at 2.5 years of age. Autopsy revealed that lack of normal tracheobronchial secretions leading to complete tracheal obstruction by mucous debris was the probable cause of death. Conclusion Morbidity and mortality of ectodermal dysplasias in infancy and early childhood can be significant. Early diagnosis by paediatricians is important and complications should be anticipated. Received: 2 January 2001 and revised form: 17 January 2001 / Accepted: 18 January 2001     

Occupational blood and body fluids exposures in health care workers: four-year surveillance from the Northern France network

The risk of accidental blood and body fluid (BBF) exposure is a daily concern for health care workers throughout the world, and various strategies have been introduced during the past decade to help reduce that risk. To assess the impact of multifocal reduction strategies introduced in hospitals affiliated with the Northern France network, we recently examined data from 4 years of BBF-exposure reports filed by network employees. A total of 7,649 BBF exposures were reported by health care workers to occupational medicine departments in 61 hospitals. Nurses and nursing students accounted for 4,587 (60%) of exposures, followed by nurses' aides and clinicians. Most (77.6%) of the reports were related to needlestick injury (NSI). In addition, we examined BBF exposure trends over time by analyzing data from 18 hospitals (29.5%) with data available for the time period of 1995 to 1998. These were assessed in nurses, who have the highest and most consistent reporting rate. We noted that the BBF-exposure incidence rate for all BBF exposures in nurses decreased from 10.8 to 7.7 per 100 nurses per year between 1995 and 1998 (P <.001), whereas the NSI rate decreased 8.9 per 100 nurses per year in 1995 to 6.3 in 1998 (P <.001). The percentage of NSIs that resulted from noncompliance with universal precautions also decreased significantly (P =.04). Widespread improvements in procedures and engineering controls were implemented in the Northern France network before and during the study period. Significant reductions were observed in reports of BBF exposures and NSIs, particularly in nurses. These findings are similar to those in other countries and reflect the overall improvement in the management of occupational risk of BBF in health care workers.