Treatment of Ph1-positive chronic myelogenous leukemia in children: comparison between allogeneic bone marrow transplantation and conventional chemotherapy. Spanish Working Party for BMT in Children (GETMON)

BACKGROUND AND OBJECTIVE: To compare the estimated survival and disease-free survival between children with Ph1-positive chronic myeloid leukemia treated with allogeneic bone marrow transplantation or conventional chemotherapy. DESIGN AND METHODS: In this retrospective study we compared the results obtained in a group of 14 children who received allogeneic bone marrow transplantation (BMT) between 1983 and 1993, and another group of 27 children treated with busulfan, hydroxyurea or alpha-interferon during the same time period. Patients were transplanted at a median of 7 months from diagnosis and all except one were in their first chronic phase. Conditioning consisted in total body irradiation and cyclophosphamide in 12 cases, and busulfan was added in two. RESULTS: Of the 14 patients treated with BMT, two died of transplant-related complications and two relapsed 18 and 48 months after the BMT. Ten children remain alive and disease free at a median follow up of 60 months. The probability of DFS at 5 years is 70%. Of the 27 patients treated with chemotherapy, 22 have died at a median of 36 months from diagnosis. The probability of survival at 5 years is 5% versus 83% for the BMT group (p = 0.001). INTERPRETATION AND CONCLUSIONS: Allogeneic BMT is a safe and very effective treatment for Ph-positive CML in children. Patients who have an HLA-identical sibling donor must receive a transplant as soon as possible after being diagnosed.     

Advisory statements of the International Liaison Committee on Resuscitation (ILCOR) CPR in pregnancy

OBJECTIVE: To investigate the associations of individual and area-based socioeconomic indicators with cardiovascular disease risk factors and mortality. DESIGN: Prospective study. SETTING: The towns of Renfrew and Paisley in the west of Scotland. PARTICIPANTS: 6961 men and 7991 women included in a population-based cardiovascular disease screening study between 1972 and 1976. MAIN OUTCOME MEASURES: Cardiovascular disease risk factors and cardiorespiratory morbidity at the time of screening: 15 year mortality from all causes and cardiovascular disease. RESULTS: Both the area-based deprivation indicator and individual social class were associated with generally less favourable profiles of cardiovascular disease risk factors at the time of the baseline screening examinations. The exception was plasma cholesterol concentration, which was lower for men and women in manual social class groups. Independent contributions of area-based deprivation and individual social class were generally seen with respect to risk factors and morbidity. All cause and cardiovascular disease mortality rates were both inversely associated with socioeconomic position whether indexed by area-based deprivation or social class. The area-based and individual socioeconomic indicators made independent contributions to mortality risk. CONCLUSIONS: Individually assigned and area-based socioeconomic indicators make independent contributions to several important health outcomes. The degree of inequalities in health that exist will not be demonstrated in studies using only one category of indicator. Similarly, adjustment for confounding by socioeconomic position in aetiological epidemiological studies will be inadequate if only one level of indicator is used. Policies aimed at reducing socioeconomic differentials in health should pay attention to the characteristics of the areas in which people live as well as the characteristics of the people who live in these areas.     

Serum and urinary zinc levels in urolithiasis

Zinc has an important place amongst inhibitors of crystallisation and crystal growth. These views are supported by in vivo and in vitro studies which suggest that the urinary zinc level is a significant factor in urolithiasis. Some recent studies have given contradictory results. Blood serum and urinary zinc levels were measured in 30 normal healthy controls and 42 stone forming patients (renal, ureteric and vesical). Statistically significant levels were found in all groups, varying according to the number of calculi. Increased urinary zinc levels and decreased serum zinc levels appear to be secondary to the process of stone formation. The role of zinc as an inhibitor of urolithiasis is questionable.     

Growth-associated synthesis of recombinant human glucagon and human growth hormone in high-cell-density cultures of Escherichia coli

Synthesis of two recombinant proteins (human glucagon and human growth hormone) was investigated in fed-batch cultures at high cell concentrations of recombinant Escherichia coli. The glucose-limited growth was achieved without accumulation of metabolic by-products and hence the cellular environment is presumed invariable during growth and recombinant protein synthesis. Via exponential feeding in the two-phase fed-batch operation, the specific cell growth rate was successfully controlled at the desired rates and the fed-batch mode employed is considered appropriate for examining the correlation between the specific growth rate and the efficiency of recombinant product formation in the recombinant E. coli strains. The two recombinant proteins were expressed as fusion proteins and the concentration in the culture broth was increased to 15 g fusion growth hormone 1(-1) and 7 g fusion glucagon 1(-1). The fusion growth hormone was initially expressed as soluble protein but seemed to be gradually aggregated into inclusion bodies as the expression level increased, whereas the synthesized fusion glucagon existed as a cytoplasmic soluble protein during the whole induction period. The stressful conditions of cultivation employed (i.e., high-cell-density cultivation at low growth rate) may induce the increased production of various host-derived chaperones and thereby enhance the folding efficiency of synthesized heterologous proteins. The synthesis of the recombinant fusion proteins was strongly growth-dependent and more efficient at a higher specific growth rate. The mechanism linking specific growth rate with recombinant protein productivity is likely to be related to the change in cellular ribosomal content.     

Angiotensin II signal transduction pathways

It has been 100 years since the discovery of renin by Tigerstedt and Bergman. Since that time, numerous discoveries have advanced our understanding of the renin-angiotensin system, including the observation that angiotensin II is the effector molecule of this system. A remarkable aspect of angiotensin II is the many different physiological responses this simple peptide induces in different cell types. Here, we focus on the signal transduction pathways that are activated as a consequence of angiotensin II binding to the AT1 receptor. Classical signaling pathways such as the activation of heterotrimeric G proteins by the AT1 receptor are discussed. In addition, recent work examining the role of tyrosine phosphorylation in angiotensin II-mediated signal transduction is also examined. Understanding how these distinct signaling pathways transduce signals from the cell surface will advance our understanding of how such a simple molecule elicits such a wide variety of specific cellular responses.