Insulin and oral agents for managing cystic fibrosis-related diabetes.

BACKGROUND: Insulin therapy is recommended by the Cystic Fibrosis Foundation when cystic fibrosis-related diabetes has been diagnosed. Diagnosis is based on an elevated fasting blood glucose level greater than 6.94 mmol/liter (125 mg/deciliter) or symptomatic diabetes for random glucose levels greater than 11.11 mmol/liter (200 mg/deciliter). OBJECTIVES: To examine the evidence that, when treated with agents for managing diabetes, people with cystic fibrosis improve their sugar metabolic control resulting in beneficial impact on lung function and the ability to maintain optimal weight. SEARCH STRATEGY: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. We also handsearched abstracts from pulmonary and North American Cystic Fibrosis Conference symposia. Date of the most recent search of the Group's Trials Register: December 2004. SELECTION CRITERIA: Randomized controlled trials comparing all methods of diabetes therapy for one month or longer in people with cystic fibrosis. DATA COLLECTION AND ANALYSIS: No studies were found which were eligible for inclusion in this review. MAIN RESULTS: Six references to four studies were identified by the searches, but none were eligible for inclusion in the review as they were not randomized controlled trials. AUTHORS' CONCLUSIONS: While some cystic fibrosis centers use oral medications to help control diabetes, a condition which complicates the course of cystic fibrosis, insulin therapy is the recommended and most widely used treatment method. Lung function has been reported to improve with the use of insulin, but this has not been correlated to the degree in which sugar metabolism has been affected. While the Cystic Fibrosis Foundation recommends insulin therapy be used in managing diabetes, this systematic review identifies the need for a multicentre randomized controlled trial assessing both the efficacy of insulin or other insulin-releasing or insulin-sensitizing medications and their possible adverse effects in managing cystic fibrosis-related diabetes.

A community collaborative practice experience between Med/Peds and family practice.

PURPOSE: The medical literature has followed educational outcomes of Medicine-Pediatric (Med/Peds) physicians, but limited studies exist as to clinical outcomes for these combined specialty physicians. Although a variety of practice environments are available for a growing number of Med/Peds physicians, a collaborative practice setting with family physicians may optimize the Med/Peds practice potential. This study investigates clinical practice outcomes and utilization efficiencies of collaborative Med/Peds family practice physicians within a community, which should provide an effective model in a growing managed care environment. PATIENTS AND METHODS: Two collaborative practice settings in a moderate size Midwest community were analyzed with respect to patient demographics and utilization scores provided by a practice management group and a nationally based health care network. Current Procedural Terminology (CPT) coding was used to follow demographic trends for over 45,000 patient visits for 1 year. Efficiency ratings (Z-scores) were used over the same year for over 6,000 health care network patient visits to 10 collaborative practice-based physicians, which were then compared to 141,101 community family practice patient encounters, 26,617 general internist patient encounters, and 29,995 patient encounters to pediatricians for utilization trends. RESULTS: Med/Peds and Family Practice patient care data reflected nearly identical patient demographics between specialties with only a few exceptions. Med/Peds physicians cared for three times the total number of children less than 2 years old. Med/Peds physicians experienced a higher complexity of illness, in part due to a 40% increase in internal referrals from family practice colleagues in the ambulatory care setting, while maintaining a third of the proportion of outpatient referrals. Cost-effective interoffice utilization was still maintained, supported by a more optimal efficiency rating for Med/Peds physicians compared to collaborative family practice colleagues. Inpatient efficiency was demonstrated for Med/Peds specialists even though a threefold increase in hospitalizations was observed, in part resulting from physicians within these collaborative practices arranging all newborn nursery and pediatric admissions be covered by Med/Peds physicians. Both collaborative primary care specialists demonstrated more cost-effective overall practice utilization scores when compared to community-based primary care specialists. CONCLUSIONS: Med/Peds physicians in this study have been trained to provide cost-effective patient care in both outpatient and inpatient settings. Decreased outside referrals by collaborative family practice physicians through utilization of Med/Peds colleagues serves to optimize practice economy by eliminating the threat of competition that exists among community-based generalists. Such a model helps to control an overused referral system to subspecialists.

Collaboration in the preparation of the generalist physician.

Collaborative efforts among health care professionals and institutions at all levels will be essential to the increased production of generalist physicians. There have been many successful collaborations in education and patient care among certifying boards, faculty, physicians in practice, specialists, generalists, and non-physician health professionals, as well as among the three generalist specialties. Recommended strategies to encourage collaboration in the preparation of generalist physicians include: creation of an institutional collaborative curriculum committee; design of a longitudinal curriculum on collaboration for physicians-in-training and other health professionals; implementation of collaborative patient care in ambulatory care teaching clinics; development of integrated systems of care that link inpatient, outpatient, and community-based health services; and education of physicians-in-training in these and other collaborative and co-practice models of patient care.

Monooxygenase activity of human hemoglobin: role of quaternary structure in the preponderant activity of the beta subunits within the tetramer.

Catalysis of para hydroxylation of aniline was measured for human ferrihemoglobin and various derivatives in a reconstituted system consisting of the appropriate hemoprotein (at 4 microM heme), reduced nicotinamide adenine dinucleotide phosphate (NADPH), cytochrome P-450 reductase, and aniline under atmospheric O2. The isolated subunits of hemoglobin (alpha 3+ and beta 3+4) were prepared by treatment with p-(hydroxymercuri)benzoate. Semihemoglobin (alpha heme2 beta 02) was prepared from ferrihemoglobin and apohemoglobin. Converse valency hybrids alpha 3+2(beta 2+-CO)2 and (alpha 2+-CO)2 beta 3+2 were prepared from appropriately ligated alpha and beta subunits. After chromatography, the hemoglobin derivatives were characterized by visible and 1H NMR spectroscopy and electrophoresis. At the same concentration of aniline, the alpha and beta subunits were much less active than the normal tetramer. alpha-Semihemoglobin and the alpha 3+2(beta 2+-CO)2 hybrid also displayed lower hydroxylase activity. The (alpha 2+-CO)2 beta 3+2 hybrid was about as active as normal alpha 3+2 beta 3+2. This result suggests that the activity of tetrameric hemoglobin primarily involves the beta subunits. Also transfer of the beta subunits from the beta 4 molecular environment to the alpha 2 beta 2 state enhances their monooxygenase activity approximately 15-fold. The hemoglobin derivatives were differently susceptible to substrate inhibition, the beta 4 species being most sensitive. Estimates of Vmax from the linear portions of the corresponding Lineweaver-Burk plots showed agreement within a factor of 2.5 for all of the hemoglobin derivatives, suggesting that the intrinsic O2-activating capacities of the derivatives are similar.(ABSTRACT TRUNCATED AT 250 WORDS)

Monooxygenase activity of human hemoglobin: NMR demonstration of different modes of substrate binding corresponding to different activities of hemoglobin derivatives.

In the accompanying paper [Ferraiolo, B. L., Onady, G. M., & Mieyal, J. J. (1984) Biochemistry (preceding paper in this issue)] we reported different aniline hydroxylase activities for ferrihemoglobin, its isolated subunits, and the converse pair of valency hybrids alpha 3+2(beta 2+-CO)2 and (alpha 2+-CO)2 beta 3+2 in a reconstituted system containing reduced nicotinamide adenine dinucleotide phosphate (NADPH) and cytochrome P-450 reductase. To investigate the molecular basis for the different activities, 1H NMR T1 relaxation studies of aniline were performed in the absence and presence of each of the hemoglobin (Hb) species. The paramagnetic contribution of the ferric heme iron atoms of each Hb derivative to the enhanced relaxation of the proton nuclei of aniline was determined relative to control experiments in which the hemoproteins had been converted fully to the corresponding (carbonmonoxy)ferrous forms, which are diamagnetic. According to the known distance dependence of the paramagnetic effect and the relative changes in T1 for the upfield and downfield signals in the spectrum of aniline, it was ascertained that aniline binds in the same manner to the beta-ferric hybrid and to ferrihemoglobin. These two forms displayed equivalent hydroxylase activities that were the highest among the Hb derivatives for the same aniline concentration. The T1 changes observed with the alpha-ferric hybrid suggest a different orientation for aniline in that complex. The T1 data for the isolated subunits alpha 3+ and beta 3+4 would indicate that overall binding of aniline includes a component of direct aniline-heme ligation in each case.(ABSTRACT TRUNCATED AT 250 WORDS)