Analysis of deaths in patients awaiting heart transplantation: impact on patient selection criteria.

OBJECTIVE: To analyse the clinical characteristics of patients who died on the Stanford heart transplant waiting list and to develop a method for risk stratifying status 2 patients (outpatients). METHODS: Data were reviewed from all patients over 18 years, excluding retransplants, who were accepted for heart transplantation over an eight year period from 1986 to 1994. RESULTS: 548 patients were accepted for heart transplantation; 53 died on the waiting list, and 52 survived on the waiting list for over one year. On multivariate analysis only peak oxygen consumption (peak VO2: 11.7 (SD 2.7) v 15.1 (5.2) ml/kg/min, P = 0.02) and cardiac output (3.97 (1.03) v 4.79 (1.06) litres/min, P = 0.04) were found to be independent prognostic risk factors. Peak VO2 and cardiac index (CI) were then analysed in the last 141 consecutive patients accepted for cardiac transplantation. All deaths and 88% of the deteriorations to status 1 on the waiting list occurred in patients with either a CI < 2.0 or a VO2 < 12. In those with a CI < 2.0 and a VO2 < 12, 38% died or deteriorated to status 1 in the first year on the waiting list. Patients with CI > or = 2.0 and a VO2 > or = 12 all survived throughout follow up. Using a Cox's proportional hazards model with CI and peak VO2 as covariates, tables were constructed predicting the chance of surviving for (a) 60 days and (b) 1 year on the waiting list. CONCLUSIONS: These data provide a basis for risk stratification of status 2 patients on the heart transplant waiting list.     

The effect of major railway accidents on the psychological health of train drivers—I. Acute psychological responses to accident

The acute psychological reactions of 101 train drivers to on-the-track accidents were studied by means of clinical interviews and questionnaires (Impact of Event Scale, GHQ-20 and a questionnaire addressing stress symptoms, pre-accident expectancies and worries). More than half of the train drivers reported moderate to high intrusive distress (mean 11.3) within hours to days after the accident but only 1/3 reported symptoms of acute psychophysiological arousal. Intrusive symptoms related to visual impressions were most frequently reported. Avoidance was less prevalent (mean 8.8).

Clinical interviews, relationship between pre-accident worries and severity of the acute responses and positive correlation between GHQ-scores relating to the fortnight preceding the accident and IES-intrusion scores, suggest that premorbid variables may influence the stress response. Involvement in more than two previous accidents invoked a feeling of vulnerability and produced stronger acute responses. Post-accident experiences involving various personal contacts did not correlate with the stress responses in this study and only a few drivers experienced such events in a negative way. Denial of the possibility of being involved in accidents was not associated with increased risk of strong acute responses, indicating that denial does not predict poor outcome in healthy persons exposed to situations where possibility of avoiding the event is outside the control of the person.     

Recombinant human stem cell factor stimulates growth of a human glioblastoma cell line expressing c-kit protooncogene.

The growth of a panel of eight different human glioblastoma cell lines was examined in a human tumor cloning assay in agar, a tritiated thymidine uptake assay, and by counting cell numbers, in cultures performed in the absence or presence of increasing concentrations (1 to 100 ng/ml) of recombinant human stem cell factor (SCF). Growth of 7 of 8 cell lines was not significantly and reproducibly affected by recombinant human SCF. However, growth of the CRL 1620 cell line could be stimulated up to 5-fold by the cytokine. In contrast to the other cell lines investigated, CRL 1620 expressed the c-kit protooncogene assessed on the mRNA and protein level. Furthermore, SCF-induced proliferation of CRL 1620 cells was sensitive to the tyrosine kinase inhibitor erbstatin. Our data suggest that SCF can be operative in growth modulation of malignant cells outside the hematopoietic system, and this finding should be further studied for its possible clinical implications.     

Why is coronary heart disease of uraemic patients so frequent and so devastating?

On September 6, 2001, Professor Fernando Valderrabano (Hospital Gregorio Mara?on, Madrid) died at the age of 59 years. He was a leading figure in Spanish nephrology, a full professor of Medicine/Nephrology at the University Complutense of Madrid, and an outstanding scientist who published more than 300 articles in medical journals. He was a very intelligent and cultured person, and a man of great style who enjoyed a wide range of hobbies and interests in addition to his medical work. All his colleagues and friends mourn his passing.     

The v-erbA oncogene requires cooperation with tyrosine kinases to arrest erythroid differentiation induced by ligand-activated endogenous c-erbA and retinoic acid receptor.

The v-erbA oncogene, a mutated version of the thyroid hormone receptor alpha (c-erbA/TR-alpha), cooperates with tyrosine kinase oncogenes in erythroblast transformation. Here we show that the ligand-activated, endogenous retinoic acid receptor (RAR-alpha), in cooperation with c-erbA/TR-alpha, efficiently reverses the transforming effect of kinase oncogenes, overcoming oncogene-induced self-renewal by triggering terminal differentiation of the transformed cells into healthy erythrocytes. This differentiation induction was accompanied by up-regulation of erythrocyte gene expression. Similarly, RAR-alpha and over-expressed exogenous c-erbA/TR-alpha efficiently abolished the differentiation arrest caused by v-erbA, while the low levels of endogenous TR-alpha had no effect. In contrast, transformation by v-erbA plus a kinase oncogene was not affected at all by ligand-activated endogenous or over-expressed exogenous TR-alpha and RAR-alpha. These results suggest that oncogene cooperation is required to protect leukemic erythroblasts from differentiation induction via endogenous, nuclear hormone receptors. Endogenous c-erbA/TR-alpha and RAR-alpha apparently cooperated in abolishing erythroblast self-renewal and inducing differentiation, since the respective ligands acted in a synergistic fashion, and overexpressed, non-ligand-bound c-erbA/TR-alpha suppressed endogenous RAR-alpha function in differentiation induction. Genetic evidence is presented that this functional cooperation requires the receptor dimerization domain, suggesting that TR-alpha/RAR-alpha heterodimers play a role in regulation of erythroid differentiation.     

High dose melphalan and total body irradiation with autologous marrow rescue in childhood acute lymphoblastic leukaemia after relapse

High dose melphalan (HDM 110-140 mg/m2) and total body irradiation (TBI, 10.5 Gy, single fraction) followed by infusion of autologous bone marrow (ABMT) was evaluated for toxicity and efficacy in 24 children with acute lymphoblastic leukaemia (ALL) in second (CR2) or third remission (CR3). Marrow was purged with Campath 1 in six children (four were children in CR3). All children had engraftment with a median of 30 days (range 18-70 days) to neutrophil count greater than 0.5 x 10(9)/l. Four children (16%) died from toxicity 1-4 months after autograft, two from pneumonitis, one from an intracerebral haemorrhage and one from sepsis. Apart from fever and mucositis the procedure was well tolerated. Nine of 17 children treated in CR2 remain in complete remission 6-72 months after ABMT (median 25 months). Seven of these have a follow-up of greater than 12 months. Three of the seven children treated in CR3 are alive 17, 22 and 29 months post ABMT. Seven children relapsed within 10 months (median 4 months) of the autograft. Only one relapse has occurred beyond 10 months. HDM and TBI followed by ABMT is a relatively well tolerated regimen and may contribute to survival in children with relapsed ALL.     

The meaning of work after acquired brain injury.

PURPOSE: Research in the field of brain injury rehabilitation has tended to regard return to work as a measure of outcome. Researchers have not paid particular attention to the experiences of people living with a brain injury. The aim of the phenomenological study reported here was to identify and describe what characterizes the meaning of work to those with acquired brain injury. METHODS: Ten participants of working age were interviewed about the meaning of work 1-5 years after being inflicted with a brain injury. Data were analyzed and interpreted using the Empirical Phenomenological Psychological method. RESULTS: The findings revealed a meaning structure consisting of four main characteristics. Work was no longer experienced as the primary event in life and the social dimension had become more important. The perceived competence and work identity were threatened after the injury. A common theme across all interviews was the struggle to return to a state of normality, and working was considered to be evidence of success. CONCLUSION: The findings described the altered meaning of work 1-5 years after brain injury. This knowledge should lead to an increased understanding among occupational therapists engaged in work rehabilitation after brain injury and can serve as a basis for individualized intervention strategies.