The Effect of an Individualized Practice-Based CME Program on Physician Performance and Patient Outcomes

The Professional Competence Assurance Program (PROCAP) is an individualized educational program that examines physicians'' performance in ambulatory practice. It uses medical record review to identify deficiencies in the care process that guides development of the educational intervention. Medical care is reassessed one year later. This program was used with 51 private practitioners to assess the care of 1,229 hypertensive patients. The educational program included a computer printout comparing one physician''s performance with that of peers, readings targeted to management problems, and a conference call or group seminar with an expert stressing issues relevant to each physician''s performance. Postintervention assessment showed that physicians prescribed beta-blockers (P<.01) and vasodilators (P<.01) more often. Improvement (P<.05) occurred in the control of diastolic blood pressure (≤90 mm of mercury) and in several other criteria. These results show that well-designed, individualized continuing medical education addressing specific deficiencies can change physicians'' performance and patients'' intermediate outcome.     

Diabetogenic action of GH and cortisol in insulin-dependent diabetes mellitus. Aspects of the mechanisms behind the Somogyi phenomenon

The effect on glucose homeostasis of a transient elevation of plasma growth hormone (GH) and cortisol was studied over 6 h in 14 male patients with insulin-dependent diabetes mellitus (IDDM) by using an i.v. somatostatin (100 micrograms/h) - insulin (0.4 mU/kg/min) glucose (3 mg/kg/min) - infusion test (SIGIT). GH (20 mU/kg) was given as a 60 min i.v. infusion during the initial SIGIT period raising the plasma GH level to about 40 micrograms/l, and returning to low basal within 3 h. ACTH (0.1 mg) was given as an i.v. bolus injection at the start of the SIGIT, resulting in plasma cortisol peak values of about 900 nmol/l within 2-3 h. GH raised blood glucose after a lag of 4 h while ACTH alone had no effect. However, ACTH added to GH enhanced the diabetogenic effect of GH. It is concluded that an episodic increase in circulating GH-cortisol, resembling the responses of these hormones to an insulin-induced hypoglycemia, exerts a diabetogenic effect in IDDM-patients not deprived of insulin. While GH is essential in this respect the diabetogenic effect of cortisol is evident only in conjunction with GH.     

Retrovirus-induced feline pure red cell aplasia: the kinetics of erythroid marrow failure

Cats viremic with feline leukemia virus subgroup C (FeLV-C) develop pure red cell aplasia (PRCA) characterized by the loss of detectable late erythroid progenitors (CFU-E) in marrow culture. Normal numbers of early erythroid progenitors (BFU-E) and granulocyte-macrophage progenitors (CFU-GM) remain, suggesting that the maturation of BFU-E to CFU-E is impaired in vivo. We have examined the cell cycle kinetics of BFU-E and their response to hematopoietic growth factor(s) to better characterize erythropoiesis as anemia develops. Within 3 weeks of FeLV-C infection, yet 6-42 weeks before anemia, the traction of BFU-E in DNA synthesis as determined by tritiated thymidine suicide increased to 43 +/- 4% (normal 23 +/- 2%) while there was no change in the cell cycle kinetics of CFU-GM. In additional studies, we evaluated the response of marrow to the hematopoietic growth factor(s) present in medium conditioned by FeLV-infected feline embryonic fibroblasts (FEA/FeLV CM). With cells from normal cats or cats viremic with FeLV-C but not anemic, a 4-fold increase in erythroid bursts was seen in cultures with 5% FEA/FeLV CM when compared to cultures without CM. However, just prior to the onset of anemia, when the numbers of detectable CFU-E decreased, BFU-E no longer responded to FEA/FeLV CM in vitro. BFU-E from anemic cats also required 10% cat or human serum for optimal in vitro growth. These altered kinetics and in vitro growth characteristics may relate to the in vivo block of BFU-E differentiation and PRCA. Finally, when marrow from cats with PRCA was placed in suspension culture for 2 to 4 days in the presence of cat serum and CM, the numbers of BFU-E increased 2- to 4-fold although no CFU-E were generated. By 4 to 7 days, CFU-E were detected, suggesting that conditions contributing to the block of erythroid maturation did not persist. The suspension culture technique provides an approach to study further the defect in erythroid differentiation characteristic of feline PRCA.     

Disparate effects of tumor necrosis factor-alpha/cachectin and tumor necrosis factor-beta/lymphotoxin on hematopoietic growth factor production and neutrophil adhesion molecule expression by cultured human endothelial cells

Tumor necrosis factor-alpha/cachectin (TNF-alpha) and tumor necrosis factor-beta/lymphotoxin (TNF-beta) are inflammatory mediators with similar spectrums of cytotoxic activity against tumors in vitro and in vivo. We compared the effect of purified recombinant human TNF-alpha and TNF-beta on neutrophil adhesion molecule expression and hematopoietic growth factor production by cultured human umbilical vein endothelial cells. Endothelial cells acquired adhesive properties for neutrophils after a 4-hr incubation with as little as 5 U/ml TNF-alpha. TNF-alpha stimulated a dose-dependent increase in endothelial cell adhesiveness for neutrophils, with a maximal effect at 250 U/ml. In contrast, TNF-beta did not enhance endothelial-dependent neutrophil adherence until a concentration of 600 to 1200 U/ml was reached. Endothelial cells cultured for 24 hr with TNF-alpha, 10 to 1,000 U/ml, released hematopoietic colony-stimulating activity. TNF-beta failed to augment growth factor production by endothelial cells at any concentration tested. Inhibitor assays showed that the absence of detectable colony-stimulating activity was not due to direct inhibition of colony growth by TNF-beta or to release of hematopoietic inhibitors by the TNF-beta-stimulated endothelial cells. Purified natural TNF-beta was similar to recombinant TNF-beta in its effect on neutrophil adhesion molecule expression and growth factor production by endothelial cells. These results indicate that the two immunomodulatory proteins TNF-alpha and TNF-beta differ in their effects on a common target tissue. TNF-beta, which retains tumoricidal properties, shows fewer proinflammatory activities on cultured endothelial cells than TNF-alpha in vitro.     

Erythrocyte membrane ATPases in diabetes: effect of dikanut (Irvingia gabonensis)

The levels of the three ATPases found in the erythrocyte membrane of diabetic patients were significantly lower than normal subjects. The distribution of the enzymes was also different. Na+,K+-ATPase and Mg2+-ATPase reflected the status of blood glucose more than Ca2+-ATPase. The ratio between two of the ATPases was sensitive to glycemic response. When dikanut, a viscous preparation, was fed to diabetics for 4 weeks, blood glucose became normal and the activities of the three ATPases increased significantly. The ratio among the enzymes also approached that of normal subjects. A relationship was found between the blood glucose level and erythrocyte membrane ATPases which, if linked to insulin binding or level, may provide a rapid inexpensive assay in diabetes research.     

The differentiation of teratocarcinoma stem cells is marked by the types of collagen which are synthesized.

A cloned line of undifferentiated teratocarcinoma cells (OC15S1) was either maintained as a homogeneous embryonal carcinoma (EC) cell population or was cultured under conditions where the cells differentiated into endoderm-like (END) cells. In this study we examine the synthesis of collagen in both EC and END cells. Cell cultures were incubated with tritiated proline and lysine, and the radioactive collagen secreted into the medium was extracted and purified or immunoprecipitated by antibodies to type IV collagen (Adamson and Ayers, 1979). Radioactive collagens were identified by electrophoretic mobility, by sensitivity to collagenase and to reduction, by insensitivity to pepsin, by cyanogen bromide peptides, and by aminoacid analyses of 3-hydroxyproline, 4-hydroxyproline and proline. OC15S1 EC cells were found to synthesize several collagenous polypeptides, of which 60–70% of the radioactivity was like that of basement membrane (type IV) collagen. Type I-like collagen was the main collagenous product of END cells, but a minor product of EC cells. We concluded that type IV collagen synthesis was suppressed during the differentiation of EC cells to END, while type I-like synthesis was increased. Similarly, other EC cell lines produced mainly type IV-like collagen polypeptides (PC13, F9, PSA1), and following the formation of END cells, two lines produced mainly type I-like collagen polypeptides (PC13, C145b). The type of endoderm formed on embryoid bodies, however, presents an alternate route of differentiation, since immunoperoxidase tests showed that it was synthesizing significant amounts of type IV collagen. We discuss the significance of these findings in relation to a similar change which occurs during normal development.     

Adrenocortical suppression in workers manufacturing synthetic glucocorticoids.

A man who had worked for 16 years in the manufacture of a potent corticosteroid was found to be suffering from chronic adrenocortical insufficiency attributed to chronic absorption of the glucocorticoid. Eleven other symptom-free workers were therefore screened. Two of these workers, like the first patient, gave grossly abnormal responses to the Synacthen (tetracosactrin) test; one had been employed for only seven months. All 12 men had facial plethora, suggesting absorption of the drug in spite of their having adhered to the safety precautions. All workers manufacturing potent steroids should therfore be screened regularly by measurement of their plasma cortisol concentrations and should be moved regularly to processing other drugs.