A comparison of insulin lispro Mix25 and human insulin 30/70 in the treatment of type 2 diabetes during Ramadan.

OBJECTIVE: To compare insulin lispro Mix25 and human insulin 30/70 with regard to their effect on morning and evening postprandial glucose (PPG) control, and on average daily blood-glucose (BG), in patients with Type 2 diabetes who wish to fast during Ramadan. METHOD: Insulin lispro Mix25 and human insulin 30/70 were compared in an open-label, multicenter, randomised, crossover study involving 151 patients. Each treatment period had a duration of 14 days during which the patients self-monitored their BG before and 2 h after the main meals on any 3 days within the last 5 days of each treatment period. RESULTS: The 2 h PPG excursion following the main evening meal after sunset was significantly lower with insulin lispro Mix25 (3.4+/-2.9 mmol/l) compared with human insulin 30/70 (4.0+/-3.2 mmol/l, P=0.007). The evening pre-meal fasting BG values were also lower with insulin lispro Mix25 (7.1+/-2.2 mmol/l) versus human insulin 30/70 (7.5+/-2.6 mmol/l, P=0.034). The average daily BG concentration was 9.5+/-2.4 mmol/l during treatment with insulin lispro Mix25 versus 10.1+/-2.5 mmol/l with human insulin 30/70 given in identical doses (P=0.004). CONCLUSION: When compared with human insulin 30/70, treatment of insulin-requiring Type 2 patients with insulin lispro Mix25 during Ramadan resulted in better average daily glycaemia, and better BG control before and after the evening meal. Insulin lispro Mix25 should be considered as a therapeutic option during Ramadan.

Rural origin and rural medical exposure: their impact on the rural and remote medical workforce in Australia.

Australia, like many countries, finds it difficult to recruit enough medical practitioners to live and work in rural and remote communities. Over the last decade the Australian Commonwealth Government has invested in a national strategy to train its medical workforce to encourage recruits to rural and remote general practice. This strategy is based on overseas experience that rural origin students, and those experiencing early and repeated rural exposure during training, are more likely to practise in a rural location. The importance of rural origin as a predictor of rural practice is well documented in the literature. More recent studies have tended to focus on rural exposure during both undergraduate and early postgraduate years, and on developing rural curricula in a multifaceted approach to medical training. All 11 medical schools in Australia have modified their selection criteria to encourage students from rural and remote locations, and have, to a varying degree, encouraged rural exposure in parallel with developing uniquely rural content in their curricula. Many of these initiatives are quite recent and have not yet been thoroughly evaluated against their success in addressing shortages in the rural and remote medical workforce. The aim of the review is to explore how the relationship between rural origin and rural exposure during undergraduate and postgraduate training and choice of practice location has underpinned initiatives in medical education in Australia in the years 1990-2003.

Job-based health insurance in 2001: inflation hits double digits, managed care retreats.

Drawing on the results of a national survey of 1,907 firms with three or more workers, this paper reports on several facets of job-based health insurance, including the cost to employers and workers; plan offerings and enrollments; patient cost sharing and benefits; eligibility, coverage, and take-up rates; and results from questions about employers' knowledge of market trends and health policy initiatives. Premiums increased 11 percent from spring 2000 to spring 2001, and the percentage of Americans in health maintenance organizations (HMOs) fell six percentage points to its lowest level since 1993, while preferred provider organization (PPO) enrollment rose to 48 percent. Despite premium increases, the percentage of firms offering coverage remained statistically unchanged, and a relatively strong labor market has continued to shield workers from the higher cost of coverage.

Use it or lose it: is de-skilling evidence-based?

'De-skilling' is a buzzword applied to the alleged attrition of skills through their infrequent practice. However, the belief that continuing competence in procedural medicine requires the consistent practice of a minimum number of procedures is based on anecdotal evidence. This not withstanding, accreditation or continuing practice requirements are imposed, often specifying a number of procedures that must be performed each year in order to retain the right to perform them. The following is a review of the literature into the evaluation of procedural skill competence as is related to use.

Tax subsidies for health insurance: costs and benefits.

The continued rise in the uninsured population has lead to considerable interest in tax-based policies to raise the level of insurance coverage. Using a detailed microsimulation model for evaluating these policies, we find that while tax subsidies could significantly increase insurance coverage, even very generous tax policies could not cover more than a sizable minority of the uninsured population. For example, a generous refundable credit that costs $13 billion per year would reduce the ranks of the uninsured by only four million persons. We also find that the efficiency of tax policies, in terms of the cost per newly insured, inevitably would fall as more of the uninsured were covered.

Ternary complex factors Elk-1 and Sap-1a mediate growth hormone-induced transcription of egr-1 (early growth response factor-1) in 3T3-F442A preadipocytes.

In our search for transcription factors induced by GH, we have analyzed immediate early gene activation in a model of GH-dependent differentiation. Here we describe the activation of early growth response factor-1 (egr-1) in GH-stimulated 3T3-F442A preadipocytes and the transcription factors responsible for its transactivation. Binding activity of egr-1 in electrophoretic mobility shift assay (EMSA) increased transiently 1 h after GH stimulation, accompanied by a concomitant increase in egr-1 mRNA. egr-1 induction appeared not to be related to proliferation since it was amplified in quiescent preadipocytes at a time when cells were refractive to GH-stimulated DNA synthesis. Truncations of the proximal 1 kb of the egr-1 promoter revealed that a 374-bp region (-624 to -250) contributes about 80% of GH inducibility in 3T3-F442A cells and approximately 90% inducibility in CHO-K1 cells. This region contains three juxtaposed SRE (serum response element)/Ets site pairs known to be important for egr-1 activity in response to exogenous stimuli. Site-specific mutations of individual SRE and Ets sites within this region each reduced GH inducibility of the promoter. Use of these site-specific mutations in EMSA showed that disruption of either Ets or SRE sites abrogated ternary complex formation at the composite sites. DNA binding of ternary complexes, but not binary complexes, in EMSA was rapidly and transiently increased by GH. EMSA supershifts indicated these ternary complexes contained serum response factor (SRF) and the Ets factors Elk-1 and Sap-1a. Coexpression of Sap-1a and Elk-1 resulted in a marked increase in GH induction of egr-1 promoter activity, although transfection with expression vectors for either Ets factor alone did not significantly enhance the GH response. We conclude that GH stimulates transcription of egr-1 primarily through activation of these Ets factors at multiple sites on the promoter and that stabilization of ternary complexes with SRF at these sites maximizes this response.

Operative treatment of acetabular fractures through the extensile Henry approach.

OBJECTIVE: The purpose of this study was to evaluate the previously unreported application of the extensile Henry approach to the operative treatment of acetabular fractures. METHODS: Thirty-one cases were retrospectively reviewed at an average follow-up of 18.5 months. RESULTS: There were 8 simple and 23 complex associated fracture patterns. The average operative time was 4.5 hours, and the average blood loss was 1,160 mL. Reduction was anatomic in 26 patients (84%), satisfactory in 4 patients (13%), and unsatisfactory in 1 patient (3%). Radiographic results at follow-up were 25 excellent results, 4 good results, and 2 poor results. Twenty-six patients reported no limitation of ordinary activities, whereas five patients had to modify their activities because of pain. No heterotopic ossification occurred in 24 patients (77%). In the seven patients with heterotopic ossification, only one patient had a significant decrease in hip range of motion. Additional complications were two cases of superficial wound infection, one case of hardware failure, and two cases of avascular necrosis of the femoral head. There were no iatrogenic injuries to the sciatic nerve, nor was there any development of flap necrosis. CONCLUSION: The extensile Henry approach is a versatile approach offering an excellent exposure for surgical treatment of acetabular fractures. The rate of complications is comparable with or lower than that of other surgical approaches. By providing a direct exposure of the posterior pelvis, the extensile Henry approach has the advantage of minimizing the risk of iatrogenic injury to the sciatic nerve. In addition, the incidence of clinically significant heterotopic ossification may be reduced through the use of low-dose radiation prophylaxis.

Does dissatisfaction with health plans stem from having no choices?

Data from a 1997 nationwide telephone survey are used to assess the relationship between choice and public opinion about managed care. We found that only a minority of the working-age population effectively control what health plan they get. Persons without choice were markedly more dissatisfied with their health plan, especially when enrolled in managed care. In multivariate analysis, how respondents rated their health plan depended as much on whether they lacked choice as on whether they were enrolled in managed care. Persons without choice also had more negative opinions about managed care in general. The results suggest that the managed care "backlash" may persist so long as consumers have little control over health insurance decisions.

Transcription occurs in pulses in muscle fibers.

We report a novel mechanism of gene regulation in skeletal muscle fibers. Within an individual myofiber nucleus, not all muscle loci are transcriptionally active at a given time and loci are regulated independently. This phenomenon is particularly remarkable because the nuclei within a myofiber share a common cytoplasm. Both endogenous muscle-specific and housekeeping genes and transgenes are regulated in this manner. Therefore, despite the uniform protein composition of the contractile apparatus along the length of the fiber, the loci that encode this structure are not transcribed continuously. The total number of active loci for a particular gene is dynamic, changing during fetal development, regeneration, and in the adult, and potentially reflects the growth status of the fiber. The data reveal that transcription in particular stages of muscle fiber maturation occurs in pulses and is defined by a stochastic mechanism.

Understanding the managed care backlash.

This paper examines the depth and breadth of the public backlash against managed care and the reasons for it. We conclude that the backlash is real and influenced by at least two principal factors: (1) A significant proportion of Americans report problems with managed care plans; and (2) the public perceives threatening and dramatic events in managed care that have been experienced by just a few. In addition, public concern is driven by fear that regardless of how well their plans perform today, care might not be available or paid for when they are very sick.

Differential production of interleukin-3 in human T lymphocytes following either CD3 or CD2 receptor activation.

Interleukin-3 (IL-3) is expressed in T lymphocytes and stimulates the growth of multipotent hematopoietic progenitors. Little is known, however, about the stimuli that lead to IL-3 protein release. We examined IL-3 and granulocyte-macrophage colony-stimulating factor (GM-CSF) mRNA expression and protein secretion in human T lymphocytes following activation via the TCR/CD3 complex, the CD2 receptor, and the IL-2 receptor. GM-CSF mRNA expression and protein release were found in CD3 and CD2 activated T cells with maximum GM-CSF release following stimulation with IL-2. IL-3 protein release is regulated via the CD2 receptor with virtually no IL-3 release after T cell stimulation via CD3. In contrast, IL-3 mRNA accumulation is more pronounced after CD3 activation than after CD2 activation. This suggests that upregulation of IL-3 protein release following T cell stimulation via CD-2 occurs largely at the translational or posttranslational level. These data also indicate that differential control of cytokine production can occur in response to activation of the alternative T cell receptor. Interaction of the T cell CD2-receptor with its natural ligand LFA-3 expressed on stromal cells might represent a regulatory mechanism for rapid release of IL-3, facilitating proliferation of multipotent hematopoietic cells.

Biology and treatment of adult acute lymphoblastic leukemia.

The molecular analysis of acute lymphoblastic leukemia (ALL) has provided exciting insights into the pathogenesis of this disease. This disease is heterogenous and can be subtyped based on chromosomal, immunophenotypic, and structural criteria. The varying prognostic implications of different ALL subtypes markedly influence the treatment decisions in adults. Many patients with T-cell ALL can be cured with chemotherapy alone. In contrast, patients with early B-lineage ALL with certain chromosomal abnormalities, especially the Philadelphia chromosome, do not have durable responses to chemotherapy and should receive a bone marrow transplantation if an HLA-matched donor is available. Recent reports have shown improved results for adults with B-cell ALL (Burkitt's) after intensive alternating cycles of chemotherapy containing high doses of methotrexate and cyclophosphamide. Future clinical and laboratory investigation should lead to the development of novel and possibly more effective treatments specifically tailored for different subsets of ALL.