Can EGFR mutation status be reliably determined in pre‐operative needle biopsies from adenocarcinomas of the lung?

The identification of EGFR mutations in non‐small‐cell lung cancer is important for selecting patients, who may benefit from treatment with EGFR tyrosine kinase inhibitors. The analysis is usually performed on cytological aspirates and/or histological needle biopsies, representing a small fraction of the tumour volume. The aim of the present investigation was to evaluate the diagnostic performance of this molecular test. We retrospectively included 201 patients with primary adenocarcinoma of the lung. EGFR mutation status (exon 19 deletions and exon 21 L858R point mutation) was evaluated on both pre‐operative biopsies (131 histological and 70 cytological) and on the surgical specimens, using PCR. Samples with low tumour cell fraction were assigned to laser micro‐dissection (LMD). We found nine (4.5%) patients with EGFR mutation in the lung tumour resections, but failed to identify mutation in one of the corresponding pre‐operative, cytological specimens. Several (18.4%) analyses of the pre‐operative biopsies were inconclusive, especially in case of biopsies undergoing LMD and regarding exon 21 analysis. Discrepancy of mutation status in one patient may reflect intra‐tumoural heterogeneity or technical issues. Moreover, several inconclusive results in the diagnostic biopsies reveal that attention must be paid on the suitability of pre‐operative biopsies for EGFR mutation analysis.     

Sex Disparities in Risk of Mortality Among Children With ESRD

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Gatekeeper for coronary angiography: reply

We thank Geluk and Zijlstra for their kind words as well astheir considerations and proposals. The latter hits right intothe heart of the issue: should one stick to the ‘anatomic’paradigm urging us to detect and treat coronary stenoses andcalcifications rather than follow     

Bone turnover in postmenopausal women after withdrawal of estrogen/gestagen replacement therapy

Bone turnover before and after withdrawal of estrogen/gestagen treatment was studied in a randomized trial with 110 healthy female volunteers, who had passed a natural menopause 6 months to 3 years before the start of the study. Urinary excretion of intravenously injected 99m-technetium diphosphonate was measured as an index of bone turnover; plasma bone Gla protein and serum alkaline phosphatase were measured as indices of bone formation; and fasting urinary excretion of hydroxyproline and calcium were measured as estimates of bone resorption. During 2 years of hormone treatment, all variables decreased highly significantly (p less than 0.001) to a constant low level. Three months after withdrawal all variables increased highly significantly (p less than 0.001) towards, but not above, pretreatment and placebo levels. We conclude that withdrawal of estrogen/gestagen replacement therapy in postmenopausal women increases bone turnover, but not in excess of pretreatment values. This indicates that bone loss (after withdrawal) is similar to that seen in the placebo group and that a rebound phenomenon is unlikely.     

The prevalence of chromium allergy in Denmark is currently increasing as a result of leather exposure

Background Chromium allergy has traditionally been caused by occupational skin contact with cement. In 1983, Danish legislation made the addition of ferrous sulphate compulsory in cement to reduce the water‐soluble chromium content to not more than 2 ppm. An effect from this intervention has previously been demonstrated among Danish construction workers. Objectives To investigate the development of chromium allergy among patients with dermatitis tested between 1985 and 2007 in Denmark. Furthermore, to determine causative exposures in patients with chromium allergy. Patients and methods A retrospective analysis of patch test data was performed (n = 16 228) and charts from patients with chromium allergy were reviewed. Comparisons were made using a χ² test. Logistic regression analyses were used to test for associations. Results The prevalence of chromium allergy decreased significantly from 3·6% in 1985 to 1% in 1995 (P_trend < 0·001) but increased to 3·3% in 2007 (P_trend < 0·001). The frequency of clinically relevant cement exposure decreased significantly among patients with chromium allergy from 12·7% in 1989–1994 to 3·0% (P < 0·01) in 1995–2007, whereas the frequency of relevant leather exposure increased significantly from 24·1% during 1989–1994 to 45·5% during 1995–2007 (P < 0·02). Conclusions Chromium allergy is currently increasing in Denmark due to leather exposure.     

Interaction of Propofol and Sevoflurane on Loss of Consciousness and Movement to Skin Incision during General Anesthesia

Background: Loss of consciousness (LOC) and immobility to surgical incision seem to be mediated at different levels of the central nervous system. Pharmacologic studies of hypnotic agents have previously focused on combinations of either volatile or intravenous anesthetics. This study examined the combination of inhaled sevoflurane and intravenous propofol at these two clinically relevant anesthetic end points.

Methods: Thirty-six elective surgical patients were initially enrolled. Conditions approximating steady state were obtained for sevoflurane and target-controlled propofol infusions. Patients were sequentially evaluated for LOC (loud voice plus mild prodding) and immobility to surgical incision. The study was designed using the Dixon up-down method.

Results: The observed propofol effect target with 50% response plus sevoflurane (0.46% end-tidal concentration) was 1.2 [mu]g/ml (95% confidence interval, 1.1-1.3 [mu]g/ml). It was not significantly different from that predicted (1.5 [mu]g/ml; 95% confidence interval, 1.2-1.7 [mu]g/ml) by simple additivity. The effective plasma concentration of propofol that suppressed movement to skin incision in 50% of patients was 5.4 [mu]g/ml (95% confidence interval, 4.8-6.0 [mu]g/ml) plus sevoflurane (0.86%) and was not significantly different from that predicted by additivity (5.4 [mu]g/ml; 95% confidence interval, 4.8-5.9 [mu]g/ml). Both analyses had adequate power (90%) to detect a significant change (+/-19 to 25%) from predicted value. Repeated-measures analysis of variance identified a Bispectral Index value of 70 as the break point between those who responded at LOC or did not.     

Health-related quality of life and its predictive role for analgesic effect in patients with painful polyneuropathy.

Painful polyneuropathy is a common neuropathic pain condition. The present study describes health-related quality of life (HRQL) in a sample of patients with painful polyneuropathy of different origin and the possible predictive role of HRQL for analgesic effect. Ninety-three patients with a diagnosis of painful polyneuropathy were included in the analysis. Data were obtained from three randomised, placebo-controlled cross-over studies testing the effect of different drugs on polyneuropathic pain (St. John's wort, venlafaxine/imipramine and valproic acid). Patients completed a HRQL questionnaire (SF-36) after a drug-free baseline period and at the end of each treatment period. At baseline, all eight SF-36 scores were lower than in the normal population. No significant differences were found between SF-36 scales during placebo and treatment with valproic acid and St. John's wort. Those two drugs had not shown a pain relieving effect in former analysis. The SF-36 scale of bodily pain (BP) was improved by venlafaxine treatment (p=0.023). General health (GH) and vitality (VT) were improved under treatment with imipramine (GH: p=0.006, VT: p=0.015). In a multivariate logistic regression analysis, baseline SF-36 scores predicted subsequent response to pharmacological treatment. Results show an impaired HRQL in painful polyneuropathy and suggest that HRQL may predict response to analgesic treatment.