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.     

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.     

Digital movement analysis,a new objective method of measuring tardive dyskinesia and drug-induced parkinsonian tremor: acceptability,reliability and validity

Digital movment analysis (DMA) is a new instrumental approach to assessing oral tardive dyskinesia (TD) by means of digital image processing of a video signal, tracking five paper dots placed around the patient's mouth. A total of 40 schizophrenic patients, 30 with and 10 without TD, were examined twice (with a 3-month interval) with this new device. The patients were further examined with two TD rating scales: the St. Hans Rating Scale for extrapyramidal syndromes (SHRS) and the Abnormal Involuntary Movement Scale (AIMS).The schizophrenic patients accepted the instrumental assessment without any anxiety or resistance. The internal relibility of the apparatus was high, with correlation coefficients of 0.80–0.99. The DMA TD values correlated with the SHRS and AIMS scores with correlation coefficients of 0.48–0.73 indicating an acceptable, although not strong, concurrent validity. Fluctuations occurred from the first to the second examination independent of medication. For these fluctuations no correlation was found between DMA values and rating scores. Finally, the DMA device was able to detect perioral tremor as a sign of parkinsonism.It has been concluded that DMA is a useful supplement to classical TD rating, although further validity evaluation is warranted.     

Intravenous Lidocaine Relieves Spinal Cord Injury Pain: A Randomized Controlled Trial

Background: Neuropathic pain in spinal cord injury is a common challenging therapeutic condition. The current study examines the analgesic effect of the sodium channel blocker lidocaine on neuropathic pain in patients with spinal cord injury and the predictive role of concomitant evoked pain on pain relief with lidocaine.

Methods: Twenty-four spinal cord injury patients with neuropathic pain at or below the level of injury were randomized and completed a double-blind crossover trial of 5 mg/kg lidocaine and placebo infused over 30 min. Twelve patients reported evoked pain, and 12 patients had no evoked pain. Spontaneous and evoked pains were assessed using a visual analog scale and quantitative sensory testing.

Results: Lidocaine significantly reduced spontaneous pain in all patients (P < 0.01) and in each of the two groups with (P < 0.01) and without (P = 0.048) evoked pain, with no difference in number of responders (pain reduction >= 33%) between the patients with (n = 6) and without (n = 5) evoked pain. Lidocaine significantly relieved both at-level and below-level neuropathic pain and decreased brush-evoked dysesthesia but not cold allodynia, pinprick hyperalgesia, or pain evoked by repetitive pinprick.     

Diagnosis of somatisation: effect of an educational intervention in a cluster randomised controlled trial.

BACKGROUND: Somatisation is highly prevalent in primary care (present in 25% of visiting patients) but often goes unrecognised. Non-recognition may lead to ineffective treatment, risk of iatrogenic harm, and excessive use of healthcare services. AIM: To examine the effect of training on diagnosis of somatisation in routine clinical practice by general practitioners (GPs). DESIGN OF STUDY: Cluster randomised controlled trial, with practices as the randomisation unit. SETTING: Twenty-seven general practices (with a total of 43 GPs) in Vejle County, Denmark. METHOD: Intervention consisted of a multifaceted training programme (the TERM [The Extended Reattribution and Management] model). Patients were enrolled consecutively over a period of 13 working days. Psychiatric morbidity was assessed by means of a screening questionnaire. GPs categorised their diagnoses in another questionnaire. The primary outcome was GP diagnosis of somatisation and agreement with the screening questionnaire. RESULTS: GPs diagnosed somatisation less frequently than had previously been observed, but there was substantial variation between GPs. The difference between groups in the number of diagnoses of somatisation failed to reach the 5% significance (P = 0.094). However, the rate of diagnoses of medically unexplained physical symptoms was twice as high in the intervention group as in the control group (7.7% and 3.9%, respectively, P = 0.007). Examination of the agreement between GPs' diagnoses and the screening questionnaire revealed no significant difference between groups. CONCLUSION: Brief training increased GPs' awareness of medically unexplained physical symptoms. Diagnostic accuracy according to a screening questionnaire remained unaffected but was difficult to evaluate, as there is no agreement on a gold standard for somatisation in general practice.     

Intraincisional antibiotic in addition to systemic antibiotic treatment fails to reduce wound infection rates in contaminated abdominal surgery

One hundred ninety patients with peritonitis at the time of abdominal surgery were allocated at random to systemic antibiotic treatment alone or systemic antibiotic treatment combined with topical application of antibiotics in the wound at the time of wound closure. The overall wound infection rate was 17 percent without significant difference between the two treatment groups (P>0.80).     

Comparison of the potential therapeutic effects of interleukin 2 or interleukin 4 secretion by a single tumour.

Engineering of a variety of rodent tumour cells to secrete either interleukin 2 (IL-2), or interleukin 4 (IL-4), has been demonstrated to reduce their tumorigenicity. However the mechanisms of action of secreted IL-2 and IL-4 have not been compared in a single rodent tumour. Here we demonstrate that the weakly immunogenic murine fibrosarcoma FS29 had reduced growth rate and in some cases was rejected by syngeneic animals, when modified to secrete either IL-2 or IL-4, but not IL-5. Immunohistochemical analysis of tumour nodules undergoing regression showed stimulation of a largely lymphocytic infiltrate by IL-2 and a macrophage and granulocyte infiltrate, with a small number of lymphocytes by IL-4. Indeed, secretion of low levels of IL-2 and IL-4 in combination resulted in optimal rejection, suggesting that the two cytokines might mobilise different and complementary effector cell mechanisms. Both IL-2 and IL-4-secreting cells failed to induce the rejection of admixed, unmodified FS29 cells. The loss of cytokine secreting cells from such admixtures occurred more rapidly for IL-2-secreting cells. Injection of IL-4-secreting, but not IL-2-secreting FS29 cells could protect mice from a delayed challenge with unmodified FS29 cells. These data suggest that IL-4 secretion stimulates the better long-term host anti-tumour response.     

Frequency and causes of shunt revisions in different cerebrospinal fluid shunt types

Summary Shunt complications and revisions are common in hydrocephalic patients treated with a ventriculo-atrial or a ventriculo-peritoneal shunt. The reported revision rate differs very much but the rate of revision is close to 50% in many papers. Data from 884 hydrocephalic patients treated with various shunt types in the period 1958–1989 were recorded retrospectively in order to evaluate the frequency of revision for various shunt types and secondly to analyse the specific reasons for the shunt revisions.The rate of shunt revision was 45%. The Pudenz shunt was revised more often (62%) than the remaining shunt types. The Hakim and the Orbis-Sigma shunts had fewer revisions (35% and 27%, respectively) than the other observed shunt types. A defect of or an obstruction in the ventricular catheters was a frequent cause of revision followed by a defect or an obstruction of the distal catheter, a displacement of the distal catheter and an acute infection. Because of the higher rate of revision for the Pudenz shunt the rate of the above mentioned specific complications is also higher in most of the subgroups for that specific shunt type. Driven by these experiences it is reasonable to seek to develop and introduce new shunt types in an attempt to reduce the complication rate.