The Unna's boot as a treatment for venous ulcers.

The optimal clinical management of venous ulcers is not clear, but compression therapy is the mainstay of medical management. The Unna's boot is a popular and effective compression dressing for venous ulcers despite incomplete clinical endorsement and minimal research evidence supporting its advantages over other compression dressing modalities. This article reviews the most recent professional and research-based literature concerning the use of the Unna's boot for venous ulcer healing. It discusses issues of venous ulcer prevalence, risk factors, recurrence, financial impact, physiological and psychological complications, and treatment choices. An overview of venous ulcer etiology is provided, culminating in this disorder's clinical presentation. Relevant wound-healing theory is related and functional explanations are given of lower-limb arterial circulation assessment measures, compression therapy, and the Unna's boot. Clinical protocol guidelines and patient education are highlighted.

First-pass metabolism of midazolam by the human intestine.

The in vivo intestinal metabolism of the CYP3A probe midazolam to its principal metabolite, 1'-hydroxymidazolam, was investigated during surgery in 10 liver transplant recipients. After removal of the diseased liver, five subjects received 2 mg midazolam intraduodenally, and the other five received 1 mg midazolam intravenously. Simultaneous arterial and hepatic portal venous blood samples were collected during the anhepatic phase; collection of arterial samples continued after reperfusion of the donor liver. Midazolam, 1'-hydroxymidazolam, and 1'-hydroxymidazolam glucuronide were measured in plasma. A mass balance approach that considered the net change in midazolam (intravenously) or midazolam and 1'-hydroxymidazolam (intraduodenally) concentrations across the splanchnic vascular bed during the anhepatic phase was used to quantitate the intestinal extraction of midazolam after each route of administration. For the intraduodenal group, the mean fraction of the absorbed midazolam dose that was metabolized on transit through the intestinal mucosa was 0.43 +/- 0.18. For the intravenous group, the mean fraction of midazolam extracted from arterial blood and metabolized during each passage through the splanchnic vascular bed was 0.08 +/- 0.11. Although there was significant intersubject variability, the mean intravenous and intraduodenal extraction fractions were statistically different (p = 0.009). Collectively, these results show that the small intestine contributes significantly to the first-pass oxidative metabolism of midazolam catalyzed by mucosal CYP3A4 and suggest that significant first-pass metabolism may be a general phenomenon for all high-turnover CYP3A4 substrates.

Use of midazolam as a human cytochrome P450 3A probe: I. In vitro-in vivo correlations in liver transplant patients.

The clearance of midazolam (MDZ) in humans is principally due to metabolic biotransformation catalyzed by CYP3A isoforms. A study was conducted in patients who had undergone liver transplants that provides evidence that MDZ can be used as an in vivo probe of interindividual hepatic CYP3A variability. The clearance of MDZ and cyclosporine after i.v. administration were determined in 10 patients approximately 10 days after transplant surgery. Liver biopsy specimens were obtained within 24 hr of the pharmacokinetic study and CYP3A content and MDZ 1'-hydroxylation activity were measured in 13,000 x g tissue supernatants (S-13). The in vitro rate of 1'-hydroxy-MDZ formation was found to correlate significantly with the total CYP3A content in hepatic S-13 fractions (r = .84, P < .01). The total MDZ clearance measured in vivo was highly correlated with the hepatic CYP3A content measured in vitro (r = .93, P < .001) and with in vivo cyclosporine clearance (r = .81, P < .001). For five of the patients, the intrinsic clearance of midazolam to 1'-hydroxy-MDZ (Vmax/Km) in vitro measured in S-13 preparations was scaled for total liver mass and applied to the well stirred model of hepatic clearance to yield a prediction of MDZ clearance in vivo. The mean MDZ clearance predicted from in vitro 1'-hydroxylation data was identical to the mean clearance observed in vivo (0.60 +/- 0.24 versus 0.59 +/- 0.25 liter/min). Together, the results suggest that variability in hepatic CYP3A expression in liver transplant recipients, and possibly in other populations, can be determined by the measurement of MDZ metabolic clearance.

Use of midazolam as a human cytochrome P450 3A probe: II. Characterization of inter- and intraindividual hepatic CYP3A variability after liver transplantation.

Immunosuppression therapy with cyclosporine is often hampered by significant interindividual variability in the metabolic clearance of the drug. It has been suggested that much of the variability in cyclosporine clearance is due to differences in the cytochrome P450 3A4 (CYP3A4) content in the liver and intestinal mucosa. A study was conducted in liver transplant recipients to characterize hepatic CYP3A variability during the first 10 days after surgery. The formation of 1'-hydroxymidazolam (1'-OH MDZ) was followed in the plasma after i.v. midazolam (MDZ) administration to 21 multiple-organ donors and to recipients of 10 of the 21 donor livers. Liver biopsy tissue was obtained from donors and recipients after the in vivo pharmacokinetic test. For liver donors, the plasma 1'-OH MDZ/MDZ concentration ratio 30 min after the i.v. MDZ dose was well correlated with the hepatic CYP3A4 content (r = .87, P < .001). Much of the variability in the two parameters was attributed to the administration of enzyme-inducing drugs before organ procurement. The mean hepatic CYP3A4 content and plasma 1'-OH MDZ/MDZ concentration ratio in six inducer-treated donors was 4.7-fold and 2.3-fold higher than the respective mean value for all other donors. The hepatic CYP3A4 content and plasma 1'-OH MDZ/MDZ ratio for liver recipients, studied on postoperative day 10, was negatively correlated with the respective parameter measured in donors on day 0 (r = -0.60 for CYP3A4 and r = -0.79 for 1'-OH MDZ/MDZ; P < .05 and P < .01).(ABSTRACT TRUNCATED AT 250 WORDS)

Meeting the challenge of research in family medicine: report of The Study Group on Family Medicine Research.

The challenge of research in family medicine is addressed in this paper by describing the rationale for research, appropriate content areas, resources available, and needs for the future. Family medicine has the opportunity to study health and disease in humans within their natural habitat over long periods of time, and to examine the multiple aspects of personal and family health care delivery. Resources for research include large primary care study populations, practitioner and faculty researchers, and technical support systems. The basic needs for the future are to increase the quantity and quality of researchers and to attract more funds designed for research. It is recommended that family medicine practitioners and teachers support research and participate more actively; that family medicine academic units provide their learners more research curricular time and their faculties more research activity time, and that they develop Family Medicine Research Centers; that family medicine professional organizations raise funds to support research, promote research opportunities for their members, and communicate to others the research activities, resources, and needs of family medicine; and that the requirements for residency training be modified to include elective research opportunities.

Primary and consultant care. Can they be distinguished?

Four of five national data sets were adequate to distinguish primary and consultant care by specialty. The one data set that could not be used in this way includes most acute hospital care provided in the United States. Using a functional classification that was independent of specialty, one of five national data sets is purported by its sponsors to distinguish primary from consultant care, and that effort is not ongoing. Greater effort is needed to collect ongoing data distinguishing primary and consultant care specialties by function.

Primary and specialized care: implications for learning situations.

Existing data suggest that there are differences between primary and specialized (consultant) care in clinical practice and in clinical decision-making. In addition, there are distinctions attributable to the nature of the two functions, the clinical settings, and the use of knowledge and technique. The most important difference, however, centers around the varying prevalence of disease between primary and specialized care and the practitioner's relative use of disease frequency in decision-making. Because of these differences, medical schools should develop primary care situations which are equally as valued as specialty care situations. Although the impact of substantial and attractive primary care curricula is unknown, their potential value in guiding appropriate students to enter primary or specialized care careers could be considerable.

Quality assurance in primary care: a strategy based on outcome assessment.

We describe an outcome-based approach to quality assurance in primary care and present data from an initial study made to explore its usefulness. A questionnaire, which asked patients to report on the status of their problem in terms of the amount of symptoms, activity limitation, and anxiety it caused, was mailed to adults who had been seen a month previously for upper respiratory tract infection, sore throat, or urinary tract infection. Outcome standards developed for these conditions indicated that patients should report no symptoms, activity limitation, or anxiety. Of the 127 patients who responded, 17% failed to meet these standards. A review of their medical records was conducted to test the value of using substandard problem-status outcome as an indicator of important deficiencies in care. Definite deficiencies in care were found for 57% of those with substandard outcomes and for 2% of those with acceptable outcomes. Corrective action was judged likely to benefit 95% of the cases with substandard outcome and 7% of those with acceptable outcomes. Data from the medical records were insufficient to explain the reasons for substandard outcome in all cases, thus emphasizing the need to examine also patient- and system-related variables not evident in the medical record. An approach to quality assurance that is based on measuring outcome and then determining the reasons for poor outcome in useful for uncovering correctable errors in the delivery of primary care. In order for the approach to be effective in improving care, the outcome measures used must be sensitive to the role of primary care in assisting partients to resolve health problems.

Undergraduate education in primary care: the Rockford experience.

Four years of experience with an undergraduate program in primary care in a new community-based medical school are described. Students are intimately involved over a two-and-a-half-year period in the delivery of primary care in rural and semi-rural community health centers. Despite problems of financing and, especially, faculty recruitment and development, the program has been enthusiastically endorsed by students and patients and appears to represent a viable new model for medical education.

The Rockford School of Medicine undergraduate quality assurance program.

An undergraduate program of ambulatory care quality assurance has been operational at the Rockford School of Medicine for three years. The original intent of the program was to increase the acceptance of quality assurance activities among student physicians, inculcating in them the importance of peer review at an early stage in professional development. The program experience is described, results of preliminary evaluation reported, and generalizations offered. Activities in the first year of a hospital care quality assurance program are described.