Prekallikrein-Kallikrein conversion rate as a predictor of contrast material catastrophies

An in vitro is described that attempts to detect patients with a potential for adverse systemic reactions to contrast material. This test involves measuring the rate of conversion of prekallikrein to kallikrein under certain standard conditions. In a preliminary retrospective study, the test could be used to identify such patients with a sensitivity of 88%, a specificity of 82%, and a predictive value of 79%.     

The status of hematopoietic stem cell transplantation in lysosomal storage disease

Lysosomal storage diseases are a group of disorders which have in common an inherited defect in lysosomal function—in most cases, a missing intralysosomal enzyme. Research into potential treatment options for this group of disorders has focused on enzyme replacement. Over the past two decades, hematopoietic stem cell transplantation has been used with increasing frequency to treat patients with lysosomal storage disease by providing a population of cells with the capacity to produce the missing enzyme. The success of marrow transplantation depends on the specific enzyme deficiency and the stage of the disease. Generally, visceral symptoms can be improved, whereas skeletal lesions remain relatively unaffected. The effect on neurologic symptoms varies. Hematopoietic stem cell transplantation remains a viable treatment option in those lysosomal storage diseases where data supportive of disease stabilization or amelioration are known. Early transplantation is the goal so that enzyme replacement may occur before extensive central nervous system injury becomes evident. When inadequate clinical data are available, the decision to perform transplantation requires experimental data demonstrating that the enzyme in question is both excreted from normal cells and taken up by affected cells as evidenced by elimination of storage material in vitro.     

Evaluation of thrombopoiesis kinetics by measurement of reticulated platelets and CD34(+) cell subsets in patients with solid tumors following high dose chemotherapy and autologous peripheral blood progenitor cell support

BACKGROUND AND OBJECTIVES: The transplantation of mobilised peripheral progenitor cells has resulted in shortening of neutrophil and platelet engrafment times following high-dose chemotherapy. Since reticulated platelet percentage (PR%) has been established as a measure of bone marrow platelet production, we performed this type of analysis on the thrombopoietic compartment during transplant-related chemotherapy. DESIGN AND METHODS: Kinetics of thrombopoiesis of 19 patients with solid tumors undergoing a single or double autologous peripheral blood progenitor cell transplant was characterized by evaluating the level of RP. The correlation between CD34(+) cell subsets and the time of highest percentage of RP was also evaluated. RESULTS: The percentage of RP increases since day +8 after single transplant reaching the peak (3.4%) at day +10. In the group of patients receiving double transplant, the RP value of peak observed after second transplant is not significantly different from that one observed after the first transplant (3 vs 3.7%). In a subgroup of patients both the number of CD34(+) cells/Kg infused and the percentage of CD34(+) CD61(+) cell subsets correlate with the day of RP peak. INTERPRETATION AND CONCLUSIONS: These results suggest that RP measurement is an early indicator of engraftment. Additionally, the observation that RP percentage is high at the time of platelet transfusion in 13 out of 20 cases of transfusions (the 7 cases with low RP value being transfused during the period of obligate thrombocytopenia) suggests that the evaluation of this parameter, together with the platelet count, can be used to monitor the need for platelet transfusion.     

Dietary fat, body weight, and cancer: contributions of studies in rodents to understanding these cancer risk factors in humans

Understanding diet and energy balance as risk factors for breast, colon, and other cancers requires information on the contribution of each factor and of interactions among factors to cancer risk. Rodent models for breast cancer provide extensive data on effects of dietary fat and calories, energy balance, body weight gain, and physical activity on tumor development. Analyses of the combined data from many studies have shown clearly that quality and quantity of dietary fat and energy balance contribute independently to increased mammary gland tumorigenesis. These findings were seen in female rats fed diets high in fat (35-40% of calories) compared to rats fed control diets, with approximately 10% of calories as fat (Fay and Freedman, 1997, Breast Cancer Res. Treat. 46, 215-223). The methods used permit comparison of experimental and epidemiological data, and they may be useful in extrapolating between species and developing public health recommendations. In addition to the contributions of lifetime-diet composition, intake, energy balance, and physical activity to cancer risk, there are questions about the timing and duration of alterations in these factors and about the "dose-response" characteristics of cancer risk to the factors. Endocrine mechanisms may be significant in mammary gland tumor risk, but experimental and epidemiological data indicate that cancers at other sites, such as colon and liver, also are influenced by the factors listed. Other diet and lifestyle factors that influence energy, or specifically fat, metabolism may also affect risk for cancers that are promoted by increased intake of fat and calories. Studies of separate and interactive effects of dietary fat, black tea, weight gain, and mammary gland tumorigenesis (Rogers, et al, 1998, Carcinogenesis 19, 1269-1273) have been analyzed. Using adjustment of carcinogenesis endpoints for body weight, tumor burden, and latency, they were found to be related to weight gain within treatment groups in 2 of 3 experiments.      

Successful pregnancy in transfusion-dependent thalassaemia

Successful pregnancy in a transfusion-dependent thalassaemic patient receiving subcutaneous desferrixaomine is reported. This is the first such case to be described.     

Hypoaldosteronism in three sibs due to 18-dehydrogenase deficiency

Three sibs all presented in the early neonatal period with a salt-losing syndrome. The salt-losing form of congenital adrenal hyperplasia was diagnosed and appropriate treatment with glucocorticosteroids, mineralocorticosteroids, and additional dietary salt started. Although early life was maintained with difficulty, with age all 3 children required decreasing amounts of replacement steroids to maintain normal plasma electrolyte balance. They were reinvestigated at the ages of 15 years and 8 years (twins), when cortisol synthesis and metabolism proved normal, but aldosterone synthesis was blocked by deficiency of 18-dehydrogenase. Rational treatment of these cases of a salt-losing syndrome in which aldosterone synthesis alone is blocked due to lack of the enzyme 18-dehydrogenase requires the administration of a mineralocorticosteroid drug only. Since deoxycorticosterone (acetate or pivalate) requires intramuscular administration, as life-long therapy oral fludrocortisone is preferable. Although fludrocortisone has glucocorticoid activity, the "hydrocortisone equivalent" effect of the small dosage used was unlikely to inhibit either pituitary corticotrophin or growth hormone production.