Marrow fibrosis associated with a Philadelphia chromosome.

Three patients had marked marrow fibrosis and an apparent Philadelphia (Ph) chromosome. Hematologic, cytogenetic, and molecular studies demonstrated the heterogeneity of such cases, including the first example of clinically typical myelofibrosis (MF) associated with a bcr gene rearrangement characteristic of chronic myelogenous leukemia (CML).     

Cerebellar toxicity with high-dose cytosine arabinoside

CNS dysfunction, especially impaired cerebellar function, is the dose-limiting toxicity associated with high-dose cytosine arabinoside, which precludes doses of greater than 48 g/m2. Four hundred eighteen patients between the ages of 2 and 74 years with leukemia or lymphoma received 36 to 48 g/m2 cytosine arabinoside either alone or with anthracycline antibiotics, 4'-(9-acridinylamino) methane sulfon-m-anisidine (m-AMSA), or total body irradiation. In only 35 of 418 patients (8%) did severe cerebellar toxicity develop; it was irreversible or fatal in four (1%) patients. The age of the patient was a critical factor in the incidence of severe cerebellar toxicity. Patients greater than 50 years old had a statistically significant greater incidence of cerebellar toxicity compared with younger patients (26/137, 19%, v 9/281, 3%; P less than .0005, chi 2). Neither the diagnosis, disease status, sex, nor the regimen altered the incidence of severe cerebellar toxicity (when corrected for age). A second course of high-dose cytosine arabinoside, administered to 62 patients, did not increase the incidence of severe cerebellar toxicity, which occurred in five (8%) of these patients. Two of the five patients had severe toxicity with the initial course. Of the 60 patients with no antecedent cerebellar dysfunction, three (5%) had severe toxicity with the second course: one of 41 patients were less than 50 years old; two of 19 patients were greater than or equal to 50 years. Since the occurrence of severe cerebellar dysfunction is greatly affected by age, reduced doses of high-dose cytosine arabinoside should be given to patients greater than 50 years old, and methods for reducing the cerebellar toxicity should be investigated in these patients.     

Kynurenine aminotransferase activity in human liver: identity with human hepatic C-S lyase activity and a physiological role for this enzyme

The C-S lyase enzymes are responsible for the generation of mutagenic and cytotoxic metabolites via aberrant drug-metabolising pathways in mammalian tissues. We have examined human hepatic cytosolic, mitochondrial and microsomal fractions for evidence of C-S lyase activity. The cytosolic enzyme was purified using fast protein liquid chromatography over FFQ Sepharose, Mono P and Superose 12. An homogeneous protein (monitored by SDS-PAGE) was obtained following purification, and an 11-fold increase in C-S lyase specific activity was observed. The molecular weight of the enzyme was found to be 37 kDa in denaturing conditions, 82.3 kDa in non-denaturing conditions, and the C-S lyase activity was shown to co-purify with kynurenine aminotransferase activity when the transaminase activity of the enzyme was examined with kynurenine as the substrate.     

Quality of Life in Progressive Ovarian Cancer

When ovarian cancer progresses, goals change from cure to prolongation of life with the best possible quality for the patient. Criteria for futility must be established to guide the transition from active to palliative management. Pain control can be achieved by following established WHO guidelines. Continued education of the medical community, legislators, and the public is needed to assure pain control for the cancer patient. Limited surgery or radiation can be used to control symptoms from locally progressive disease. Other symptoms to be actively controlled include nausea and vomiting, nutrition, hydration, and fatigue. Support services, including home services, psychological counseling, and nutritional support need funding for both home and hospital settings. Quality of life assessment must be as specific as possible and address the patient's concerns by self-assessment techniques. Funding must be provided to develop specific quality of life tools and to then apply them clinically, both as part of research protocols and to assess success of palliative care.     

Use of the objective structured clinical examination for assessment of vocational trainees for general practice

General practice training schemes currently have no structured methods of assessment and most rely on a variety of subjective ratings of performance. In West Cumbria the `objective structured clinical examination' has been used to assess training performance in areas covered by small group teaching during the preceding terms. Consultation skills, interpretation of clinical data and a number of aspects of practice management were tested. The examination was conducted in the local postgraduate centre and assessed 20 trainees. Each trainee received feedback of his performance on each problem set and also an overall comparison with his peers.

This method of assessment appeared to be well received by trainees and was practicable within the limited resources available. In addition, the variety of problems set allowed for a broad range of trainees' performances to be assessed.

     

The stability and chemical stress relaxation of peroxide cured polyurethane elastomers

The chemical stress relaxation of two polyurethane elastomers Genthane S and Adiprene CM has been studied in air and in nitrogen in the temperature range 60 to 150°C. Both continuous and intermittent stress relaxation measurements were made on well characterized samples covering a range of crosslink densities. Scission and crosslinking reactions were observed for both the polyester based Genthane S and the polyether based Adiprene CM. The degradation of Genthane S is largely non oxidative and the scission reaction involves the main chain. The behaviour of Adiprene CM under nitrogen broadly resembles that of Genthane S; it differs from Genthane S in that it also undergoes an oxidative reaction. Activation energies for the scission and crosslinking processes were evaluated from kinetic analysis. Pretreatment of the elastomers with isocyanates inhibits both of these reactions. A mechanism involving the urethane group is proposed to account for the degradation behaviour and the role of water in this respect is discussed briefly.