Life-expectancy projection by modelling and computer simulation (UKPDS 46)

A method is described for estimating the life-expectancy of cohorts of type 2 diabetic patients, based on computer simulation from a parametric model. The method can be used where non-parametric methods, such as the Kaplan-Meier estimate, fail due to lack of the data. The simulation algorithm combines observed and modelled information to estimate the life-expectancy implications of event rates observed within a study. The use of bootstrap methods to estimate confidence intervals is discussed. The methods are illustrated with results that have been previously published, without derivation, in a health economic analysis of tight blood pressure (BP) control in the UK Prospective Diabetes Study (UKPDS), and the application to other health economic analyses of UKPDS data is discussed.     

Cadaveric and Angiographic Anatomical Considerations in the Genicular Arterial System: Implications for Genicular Artery Embolisation in Patients with Knee Osteoarthritis

CardioVascular and Interventional Radiology - Genicular artery embolisation (GAE) is a novel treatment for patients with knee osteoarthritis (OA). Cadaveric dissection was undertaken to provide a...     

Lymphocyte blastogenesis in patients receiving hemodialysis.

Lymphocyte blastogenic transformation in response to plant lectins and allogenic cells was studied in patients with nonuremic, far-advanced, chronic renal failure and in healthy controls. Cell cultures were studied in the presence of normal sera, patient's sera, and with media of different buffering capacities. Minimal blastogenic depression was observed when patient's lymphocytes were cultured in indifferent plasma with effective bicarbonate buffering compared with the use of pooled patient's plasma or HEPES buffer. Fresh plasma in culture depressed concanavalin A (Con A) blastogenesis. The data suggest that, under optimal conditions, lymphocytes from patients with chronic severe renal insufficiency are more responsive to stimuli than previously reported and as a group are near normal control values. Further, the defect observed may be a result of intracellular acidosis.     

Failure of recombinant human interleukin-3 therapy to induce erythropoiesis in patients with refractory Diamond-Blackfan anemia [see comments]

In two previous studies, we observed that recombinant human interleukin- 3 (IL-3) induced an increase in marrow burst-forming unit-erythroid- derived colonies in vitro in some patients with Diamond-Blackfan anemia (DBA). To determine whether a similar erythropoietic response could be induced in vivo, we treated 13 patients with DBA (aged 4 to 19 years) with two preparations of IL-3. All patients had absent absolute reticulocyte counts and markedly reduced to absent recognizable bone marrow erythroid elements; patients with circulating reticulocytes in the previous 12 months were excluded from study. All patients except 1 had failed steroid therapy and had been transfusion-dependent since infancy; 1 patient was maintained on high-dose prednisone at the time of enrollment. On the first arm of the study, IL-3 (Immunex Corp, Seattle, WA) was administered subcutaneously using a dose escalation regimen of 125 to 500 micrograms/m2/day in divided dosage at 12-hour intervals, coadministered with 1.5 mg/kg/d of oral ferrous sulphate. Of the 13 patients that entered the trial, 4 stopped prematurely because of adverse side effects. In the other 9 evaluable cases, reticulocytes increased transiently in 1 patient from 0 to 65 x 10(9)/L after 35 days of IL-3 therapy at 250 micrograms/m2, but transfusion dependency persisted. One transient peak in absolute reticulocyte count was noted in 6 other patients, but no erythroid response was observed after completion of a full course of IL-3. Oral prednisone at 0.5 mg/kg/d was then coadministered with IL-3 at 500 micrograms/m2 to 5 of the patients without effect, and treatment was stopped. In 2 patients, a second preparation of IL-3 (Sandoz Canada Inc, Dorval, Quebec, Canada) was initiated in a dose escalation regimen of 2.5 to 10 micrograms/kg and was coadministered with ferrous sulphate. No erythroid response was observed in either patient, and in one of the two, alternate-day subcutaneous recombinant erythropoietin at 300 U/kg was administered for 3 weeks in combination with daily IL-3 at 10 micrograms/kg, but no increased erythropoiesis was seen. Significant increases in white blood cell and eosinophil counts during administration of both preparations of IL-3 were observed in all patients. These data show that the response of DBA patients to IL-3 in vivo is heterogeneous and cannot be predicted from in vitro studies. The absence of a corrective effect of IL-3 in these patients with DBA indicates that a deficiency of the cytokine is not central in the pathogenesis of the disorder.