Intracranial venous thrombosis in the first trimester of pregnancy.

We describe a fatal case of intracranial venous thrombosis occurring in early pregnancy. Such thrombosis usually occurs in late pregnancy or the puerperium but rarely during the first trimester of pregnancy. Computerized axial tomography suggested massive cerebral venous infarction. Necropsy findings showed not only cerebral venous thrombosis but also extensive pelvic and iliac vein thromboses. The relationship of cerebral venous thrombosis and pregnancy is discussed and the literature reviewed.     

Haemodialysis patients' beliefs about renal failure and its treatment

Patients' beliefs about illness are important because they influence adherence and adjustment, but they are often surprising and idiosyncratic. Qualitative research can identify them in ways that are not shaped by psychological theory, but quantification is necessary if clinicians are to be informed about the beliefs that are likely to be prevalent in their patients. Qualitative analysis of interviews with 16 haemodialysis (HD) patients identified beliefs about end-stage renal failure (ESRF) and its treatment that were formed into a questionnaire, completed by 156 similar patients. Patients attributed ESRF to diverse factors including lack of self-care and inadequate medical care. Patients lacked a clear belief in the mechanism of action of dietary control, and its necessity was not readily acknowledged. The common view of haemodialysis as 'cleansing' extended to the reassuring belief that it would purge the body of disallowed food or drink. Many patients regarded haemodialysis and dietary control as externally imposed challenges that dominated life. The findings identify potential targets for educational intervention to improve adherence and adjustment and predictions about effects of patients' beliefs that can be tested in future prospective studies.     

Carboplatin-based chemotherapy for refractory and recurrent Ewing's tumours

BACKGROUND: Failure of first line therapy for the Ewing's family of tumours (EFT) is associated with a very poor outlook. Studies of second line chemotherapy are therefore necessary to identify active agents and drug combinations. Cisplatin-based therapy is frequently used in these circumstances but there are few studies to clearly define activity and toxicity. This report details outcome in a cohort of patients with poor risk EFT treated with a carboplatin-based combination. PROCEDURE: Between 1990 and 1998, 23 males and 16 females aged between 6 and 48 years (median 23) with relapsed or refractory EFT were treated with carboplatin-based chemotherapy. Previous chemotherapy had included ifosfamide and doxorubicin in all but two patients. Twenty patients were treated at the time of recurrence, and 19 after a poor response to initial chemotherapy. Treatment comprised of carboplatin to give an area under the plasma carboplatin concentration versus time curve of (AUC) 6 mg/ml, etoposide 120 mg/m2 for 3 days, and cyclophosphamide 500-750 mg/m2 for 2 days, repeated every 21 days. RESULTS: A total of 105 cycles were given, median 2 per patient (range 1-5). Overall response was 26%, with one complete response and nine partial responses. Median time to progression was 10 weeks (range 2-54). Haematological toxicity was severe requiring dose reductions in 53% of patients. Six patients proceeded to high dose consolidation treatment with bone marrow or peripheral stem cell rescue. CONCLUSIONS: This combination results in a substantial response rate in previously treated patients but with significant toxicity. Responses are, however, relatively short.     

Intravenous bisphosphonate therapy for osteoporosis: Where do we stand?

The use of oral bisphosphonates, particularly members of the aminobisphosphonate subclass, is well established for the treatment of osteoporosis. In a number of clinical settings, intravenous administration appears to be advantageous. However, current dosing and efficacy data are limited while definitive, long-term trials with some of these agents are ongoing. In this article, we review the available information and discuss the use of these drugs on that basis.     

Changing concepts in the pathological basis of soft tissue and bone sarcoma treatment

Though soft tissue sarcomas are rare considerable progress has been made in the clinical and biological understanding of these neoplasms. This has led to the launch of a new WHO classification of soft tissue tumours in 2002, which integrate morphological data with tumour specific (cyto-) genetics. Moreover worldwide consensus has grown how to predict clinical behaviour based on a specific grading system and which specific types of tumours seem not to obey these rules. As a consequence entry criteria for multi-institute prospective trials have changed over the last few years. The recent identification of tumour specific drug targets by immunohistochemistry has had impact on specimen requirements and handling as well as laboratory standards. These changes in concepts, classification, and processing of soft tissue sarcomas have had impact on patient selection and treatment and formats of multi-institute trials.     

Use of c-KIT/PDGFRA mutational analysis to predict the clinical response to imatinib in patients with advanced gastrointestinal stromal tumours entered on phase I and II studies of the EORTC Soft Tissue and Bone Sarcoma Group

Previous studies have shown that activating mutations of c-KIT/PDGFRA, potential therapeutic targets for imatinib mesylate, are implicated in the pathophysiology of gastrointestinal stromal tumours (GISTs). In this study, GISTs from 37 patients enrolled in an European Organisation for Research and Treatment of Cancer (EORTC) phase I/II clinical study of imatinib were examined for mutations of c-KIT/PDGFRA in order to explore whether the mutational status of the tumour predicts the clinical response to therapy. Mutations were screened by denaturing high-pressure liquid chromatography (DHPLC) and characterised by bi-directional DNA sequencing. Activating mutations of c-KIT or PDGFRA were found in 29 (78%) and 2 (6%) GISTs, respectively. Most c-KIT mutations involved exon 11 (n=24; 83%), all but one being an in-frame deletion; no isolated point mutations were found. The other c-KIT mutations included exon 9 AY 502-503 duplication (n=4; 14%) and exon 13 Lys-->Glu(642) missense mutation (n=1; 3%). Two tumours with no detectable c-KIT mutations demonstrated PDGFRA Asp-->Glu(842) amino acid substitutions. Patients with GISTs harbouring exon 11 mutations were more likely to achieve a partial response (PR) on imatinib therapy (83%) than all of the others (23%). The overall survival and progression-free survival rates for the entire group at 106 weeks were 78.3% and 46.9%, respectively. Based on a Kaplan-Meier analysis, patients with GISTs harbouring c-KIT mutations had longer median survival times and were less likely to progress than the other patients. These findings indicate that the mutational status of the c-KIT/PDGFRA oncoproteins could be useful to predict the clinical response of patients imatinib therapy.