Haematologists' approaches to the management of adolescents and young adults with acute leukaemia

Approaches to the management of adolescents and young adults with acute leukaemia were investigated by sending a questionnaire to hospitals identified as having diagnosed or treated patients aged 15-29 years. The responses demonstrated the types of hospital treating these patients, the haematologists' perceived practice for entry of patients to Medical Research Council (MRC) leukaemia trials and reasons for non-entry. Data were linked to MRC trials data to determine the proportion of patients aged 15-29 years at diagnosis in responding hospitals actually treated in MRC leukaemia trials in the 5 years preceding the questionnaire. Eighty-two per cent of haematologists stated that they entered patients 'always' or 'whenever possible' for acute myeloid leukaemia (AML) and 76% for acute lymphoblastic leukaemia (ALL), but actual entry rates from the study hospitals were 46% of 239 AML patients and 36% of 182 ALL patients. The reasons most commonly reported for not entering eligible patients to national leukaemia trials were clinician preference for one arm of an MRC trial, a regional study or non-trial protocol, and concern about workload and ethical approval.     

Staphylococcus aureus small colony variants, electron transport and persistent infections

Staphylococcus aureus can mutate to form a sub-population of bacteria known as small colony variants (SCVs). These bacteria have a characteristic phenotype defined by slow growth, the lack of pigment, an altered pattern of carbohydrate utilization, and a reduction in toxin production. This complex phenotype can be explained by deficiencies in electron transport. In clinical isolates, the most common mutations that affect electron transport are in the operons encoding menaquinone or heme biosynthesis. These isolates are responsible for persistent antibiotic resistant infections. The clinical presentation of these infections is readily explained by a reduction electron transport. SCVs survive within host cells, increasing the instances of recurrent infections and have a novel mechanism of resistance based upon their altered trans-membrane potential. Additionally, SCVs provide a connection between energy metabolism and toxin production. This link may operate through the bacteria responding to altered levels of NADH and ATP. A more complete understanding of these signaling pathways may provide new targets for the development of drugs to ameliorate staphylococcal virulence and disease.     

High dose ifosfamide in combination with etoposide and epirubicin followed by autologous stem cell transplantation in the treatment of relapsed/refractory Hodgkin's disease: a report on toxicity and efficacy

Patients with Hodgkin's disease (HD) refractory to first line chemotherapy and those who have rapid or multiple relapses have a very poor prognosis. With the increasing use of hybrid chemotherapy these patients will have been exposed to many of the drugs active in HD so it is important to develop salvage regimens that are novel and demonstrate activity in this group of patients. We report the use of a continuous high dose infusion of ?fosfamide at a dose of 9g/m(2) over 3 days in combination with etoposide and epirubicin followed by autologous stem cell transplant with either BEAM or Melphalan/VP16 conditioning in this difficult group. Forty six patients (28M:18F) with a median age of 28 years (range 13-45) were treated. Overall 39 out of 46 (85%) patients responded to treatment, with 17 achieving complete remission and 11 a good partial remission; 28 proceeded to autologous bone marrow/stem cell transplantation. In total, 23 patients are alive and in continuous remission with a follow up of between 12 and 61 months. Median overall survival for the whole group is 36 months. Haematological toxicity, particularly neutropenia (WHO grade IV), was observed in all cases but improved over the 3 courses of treatment in all patients. Non-haematological toxicity was not a major problem; no significant cardiac, hepatic, renal, pulmonary or neuro toxicity was observed and there were no deaths on treatment. This regime shows promise in patients with difficult Hodgkin's disease and warrants further study.     

Staphylocidal action of thrombin-induced platelet microbicidal protein is not solely dependent on transmembrane potential.

Thrombin-induced platelet microbicidal protein (tPMP) is a small, cationic, antimicrobial peptide released from rabbit platelets when stimulated with thrombin. We studied the relationship between staphylococcal transmembrane potential (delta psi) and tPMP staphylocidal activity. A genetically related pair of Staphylococcus aureus strains, 6850 and JB1, which differ in delta psi generation (-143 and -97 mV, respectively) were used. Mutant JB-1 was substantially less susceptible to tPMP than the parental strain, 6850. Menadione supplementation, which normalized the delta psi of strain JB-1, did not restore JB-1 tPMP susceptibility. These findings suggest that the staphylocidal activities of tPMP require factors other than or in addition to an intact delta psi.     

A simple method for short-term (6-hour) transport of the dog heart prior to orthotopic transplantation

A method of transporting the isolated dog heart for periods of up to 6 hours is described. It consists essentially of flush-cooling the heart with a suitable water-based solution at 4-6° C. followed by storage in a specially designed portable container which maintains the temperature of the heart at 4-6° C. The viability of the hearts was tested by orthotopic transplantation. Of nine hearts so stored (six for 6 hours), all supported the recipient circulation immediately after transplantation, with a mean systemic arterial pressure of 70 to 100 mm. Hg and a mean max. dp/dt of the left ventricular pressure of 1,050 mm. Hg/second without catecholamine stimulation. A comparable group of hearts flush-cooled in the same way but stored in ice after the manner of the method used for kidney transport was markedly inferior in performance to those stored at 4-6° C. Some of the limitations of non-perfusion methods of storing the heart are discussed.     

Apomorphine-induced aggression: an evaluation of possible sensitizing factors in the rat.

The effects of prior experience with fighting and prior experience with both apomorphine and fighting were evaluated as possible sensitizing factors in rat intraspecific aggression induced by apomorphine. Results revealed that prior experience with the drug alone, or with fighting alone, had no effect on apomorphine-induced aggression. However, animals that had previously fought under the influence of apomorphine showed even higher levels of aggression suggesting that repeated experience with both the drug and fighting induces a type of sensitization.