Clinical safety assessment of oral higenamine supplementation in healthy, young men.

OBJECTIVE: Higenamine, an herbal agent also known as norcoclaurine, is thought to stimulate ß-androgenic receptors and possess lipolytic activity. It is currently making its way into the dietary supplement market. To our knowledge, no studies have been conducted to determine the safety profile of oral higenamine when used alone and in conjunction with other commonly used lipolytic agents. METHODS: Forty-eight men were assigned to ingest either a placebo, higenamine, caffeine, or higenamine + caffeine + yohimbe bark extract daily for a period of 8 weeks. Before and after 4 and 8 weeks of supplementation, the following variables were measured: resting respiratory rate, heart rate, blood pressure, urinalysis, complete blood count, metabolic panel, liver enzyme activity, and lipid panel. RESULTS: No interaction effects were noted for any variable (p > 0.05), with no changes of statistical significance occurring across time for any of the four conditions (p > 0.05). CONCLUSION: This is the first study to determine the safety profile of oral higenamine intake in human subjects. Our data indicate that 8 weeks of daily higenamine supplementation, either alone or in conjunction with caffeine and yohimbe bark extract, does not result in a statistically significant change in any of the measured outcome variables. Additional studies, inclusive of a larger sample size, are needed to extend these initial findings.

Congenic mice reveal sex-specific genetic regulation of femoral structure and strength.

Genetic linkage studies in C3H/HeJ (C3H) and C57BL/6J (B6) mice identified several chromosomal locations or quantitative trait loci (QTL) linked to femoral volumetric bone mineral density (vBMD). From QTL identified on chromosomes (chr) 1, 4, 6, 13, and 18, five congenic mouse strains were developed. In each of these mice, genomic DNA from the QTL region of the donor C3H strain was transferred into the recipient B6 strain. Here we report the effects of donated C3H QTL on femoral structure, cortical vBMD and bending strength. Femoral structure was quantified by the polar moment of inertia (Ip) at the mid-diaphysis, which reflects the bending or torsional rigidity of the femur. Although the C3H progenitor mice have a smaller Ip than B6 progenitor mice, the congenic mice carrying the C3H segment at Chr 4 had significantly increased Ip in both males and females, giving these mice stronger femora. In female mice from the congenic Chr 1 strain, Ip was increased whereas male mice from the Chr 1 strain had smaller femoral cross-sections and significantly reduced Ip. This sex-specific effect on femoral structure was seen to a lesser extent in Chr 18 congenic mice. In addition, cortical vBMD was measured using peripheral quantitative computed tomography. Cortical vBMD was similar among most congenic strains except in Chr 6 congenic mice, where cortical vBMD was significantly less in females, but not in males. We conclude that (1) chromosomal QTL from C3H mice, which are genetically linked to total femoral vBMD, also regulate femoral structure; (2) the QTL on Chr 4 improves femoral structure and strength; (3) QTL on Chr 1 and 18 impart sex-specific effects on femoral structure; and (4) the QTL on Chr 6 imparts a sex-specific effect on cortical vBMD and femoral strength.

Inhibitors of bradykinin-inactivating enzymes decrease myocardial ischemia/reperfusion injury following 3 and 7 days of reperfusion.

Inhibitors of bradykinin (BK)-inactivating enzymes protect from myocardial ischemia/reperfusion injury after short periods of reperfusion. However, protection after 2 to 3 h of reperfusion does not mean that myocardium remains viable for an extended time. Therefore, we examined the effects of inhibitors of angiotensin-converting enzyme (ramiprilat), EP24.11 (cFP-F-pAB), and EP24.15 (cFP-AAF-pAB) in a chronic model of myocardial ischemia/reperfusion injury. A left descending coronary artery was occluded for 30 min in anesthetized rabbits. Saline, ramiprilat, or endopeptidase inhibitors were given after 27 min of occlusion. The BK(2) receptor antagonist HOE140 was administered in certain experiments. After ischemia, the occlusion was released, and the animal allowed to recover for 3 or 7 days. Surgery was then repeated, and the heart removed for determination of infarct size. In separate experiments, the heart was removed after 2 h of reperfusion for determination of BK tissue levels. Ramiprilat and endopeptidase inhibitors reduced infarct size at 3 and 7 days. Combining inhibitors further reduced infarct size after 3 days. The protective effect of the endopeptidase inhibitors was blocked by HOE140. Infarct sizes at 7 days were larger than at 3 days. The additive effect of multiple inhibitors was absent at 7 days. Ramiprilat and cFP-F-pAB significantly increased tissue BK levels. We conclude that inhibition of BK-inactivating enzymes protects endogenous BK from degradation and provides long-lasting protection from myocardial ischemia/reperfusion injury. A single treatment at the time of reperfusion does not prevent extension of the infarction between 3 and 7 days.

Health outcomes skills for care management.

There are several skills nurses can develop or expand to improve their ability to manage outcomes. This is an exciting area for nurses and one that is valued during times of cost reduction in healthcare. In addition to increasing skills in the health outcomes management arena, nurses will benefit from a continual increase in knowledge of case management, clinical pathways, and guidelines. The healthcare market-place is likely to reward nurses with these skills.

Merging clinical pathway programs as part of overall health system mergers: a ten-step guide. Spectrum Health.

BACKGROUND: Mergers, acquisitions, and reorganizations can be stressful and accompanied by ambivalence, confusion, and uncertainty. Providing clear and simple steps for merging clinical pathways may help organizations move through the transition process more smoothly. The ten steps according to which Spectrum Health merged its pathway program-conduct an inventory of previous efforts, plan for the ideal program, bring staff together early in the merger process, decide on a common format, standardize the development and revision process, standardize a reporting tool, create a clinical pathway manual, implement an educational plan, present the program to key customers, and appoint an advisory group-need not be done sequentially. The ten-step pathway merger program uses pathways as a means to improve the quality of the care provided, with a focus on multidisciplinary clinical pathway teamwork. Before the merger, the two hospital systems' pathway programs used different approaches to operations and pathway format. When the announcement to merge came in September 1997, steps to merge the clinical pathway programs began. DISCUSSION: More than two years into the merger, Spectrum Health continues to struggle with the evolution of the health system. Clinical pathways represent just one of the significant and extensive issues related to organizational mergers; organizational values, finances, vision, mission, customer relations, strategic priorities, and people issues are a few of the others. Focusing on merging programs such as clinical pathway programs can help put one large piece of the merger puzzle in place and reduce some of the ambiguity associated with all mergers. Executive support is critical to the success of the clinical pathway program.

Combining case management, pathways, and report cards for secondary cardiac prevention.

BACKGROUND: Many disease treatment tools can be shifted into prevention. Many cardiac rehabilitation programs have focused on a 12-week exercise plan with minimal long-term follow-up. In 1995 Butterworth Hospital established a cardiac prevention and rehabilitation program focusing on long-term modification of cardiovascular risk factors. CLINICAL PATHWAY: The pathway was created as the outpatient extension of three inpatient cardiovascular pathways. Unlike inpatient pathways, the outpatient pathway was integrated into the medical record as a major care planning and documentation tool. ENROLLMENT: Since the entry of the first group of patients in January 1995, average quarterly enrollment has increased from less than 15% to 32% of eligible patients. THE REPORT CARD: Butterworth adopted Dartmouth Medical Center's (Hanover, NH) value compass and instrument panel approach under the rubric of report card. As an internal, clinical quality improvement tool, the report card is not used for public reporting, although prevention and rehabilitation report cards are provided to payers. Information on cost and utilization, patient satisfaction, functional health status, and clinical outcomes, as well as the current improvement activities, are covered. Report cards have been issued in June 1996, September 1996, and January 1997, each highlighting activities that drive program improvements. CONCLUSION: The combination of case management, pathways, an outcomes database, and report cards creates a marketable program for secondary prevention of cardiac disease.

Report cards: tools for managing pathways and outcomes.

An overriding concern of many health care providers is how to maintain quality in such a turbulent, cost-driven environment. It is essential for health care providers to determine the effectiveness of their care and to institute changes in practice to affect patient outcomes in a positive fashion. Determining the appropriate outcomes to measure and formatting the report in an easy-to-read manner with meaningful information is important for presentation to a variety of audiences. We describe a report card methodology for disseminating outcome information that can easily be adapted in other settings.

The Quality Cup winner: Fletcher Allen Health Care's early extubation team.

Many organizations are looking for ways to reduce the cost and improve the quality of open-heart surgery. Fletcher Allen Health Care in Burlington, Vermont used a total quality management approach to do just that. The result was a dramatic improvement in outcomes. Fletcher Allen won the 1994 USA Today Quality Cup for its efforts.

Endopeptidase inhibitors decrease myocardial ischemia/reperfusion injury in an in vivo rabbit model.

Periods of ischemia followed by reperfusion of the ischemic tissue are associated with myocardial damage and ventricular arrhythmia. Angiotensin converting enzyme inhibitors limit the occurrence of these arrhythmias. The protective effects of angiotensin converting enzyme inhibitors may be due to inhibition of bradykinin (BK) degradation, rather than inhibition of angiotensin II formation. Other enzymes which catabolize BK include the endopeptidases EP24.11 and EP24.15. The purpose of this study was to determine if inhibitors of EP24.11 and EP24.15 decrease ischemia/reperfusion injury and if this protection is mediated by BK receptors. Rabbits were anesthetized and prepared for recording of cardiovascular parameters. The chest was opened and a left ventricular artery occluded for 30 min, followed by a 2-hr reperfusion period. Infarct size was determined using triphenyl tetrazolium chloride staining immediately after reperfusion. The enzyme inhibitors, ramiprilat, N-[1-(R,S)-carboxy-3-phenylpropyl]-Phe-pAB, and N[1-(R,S)-carboxy-3-phenylpropyl]-Ala-Ala-Phe-pAb, singly and in combinations were administered 3 min before reperfusion. Compared to saline (32.1 +/- 2.1), ramiprilat (18.3 +/- 2.8) and the EP inhibitors (14.4 +/- 1.4 for the combination) significantly decreased infarct size, with the greatest decrease occurring when all three inhibitors were combined (10.6 +/- 1.5). The protective effect of the EP inhibitors was blocked by the BK2 receptor antagonist, HOE 140 (30.1 +/- 2.6). Enzyme assays demonstrated EP24.11 and EP24.15 in the rabbit heart. We conclude that the EP inhibitors decreased ischemia/reperfusion injury by protecting BK from metabolism and that a combination of inhibitors provides superior protection to that given by a single agent.

Strategies for involving physicians in continuous quality improvement.

To realize significant and sustained improvement in quality and in overall performance, hospitals must have the support and participation of the medical staff. Although it sometimes is difficult to recruit busy physicians to join the effort, they will become champions if their experience is productive and results in improved patient care. This article outlines a number of straightforward approaches that will help healthcare quality professionals obtain physician involvement in the improvement effort.

Managing critical pathway variances.

As the use of critical pathways expands at an increasing rate, we are faced with the issue of how to manage variances from the pathway. Variance management is not clearly defined in the literature, and many institutions search for the best approach. We have implemented a number of different techniques for variance management at Fletcher Allen Health Care. Our success benefits both patients and providers.

Improving breastfeeding support: a community health improvement project.

BACKGROUND: Because of the brevity of the postpartum hospital stay, mothers and their newborns are discharged home before breastfeeding is well established. In 1992, feedback from patients who had given birth at Fletcher Allen Health Care (Burlington, VT) suggested a need for more consistent, expert, and timely assistance with breastfeeding in the hospital and better continuity of care during the first few weeks at home. QUALITY IMPROVEMENT TEAM: In 1993 a team developed objectives, analyzed the problem and possible solutions, and made eight recommendations on how the hospital could do more to promote breastfeeding. Implementation by team members and hospital staff included policy development, staff education, acquisition of funding, a visiting professorship, development of a lactation consultant coordinator and team, and patient surveys to evaluate the program. A late 1994 survey of 63 postpartum patients on their day of discharge indicated a high level of satisfaction with breastfeeding support in the hospital. CURRENT STATUS: Activities are being undertaken for lactation consultation coverage, further policy development, implementation of nurse competency validation, improved patient and family education materials, and continued evaluation of the breastfeeding support program through patient surveys. CONCLUSION: In the face of barriers such as the project's large scope, a paucity of internal team members, and a large number and variety of recommendations, some of the recommendations and follow-up plans have yet to be implemented. Yet the project has yielded improvements in care and provides a model of how hospitals can expand their traditional boundaries of care and quality improvement into community health issues.

The synergy of pathways and algorithms: two tools work better than one.

BACKGROUND: Clinical quality improvement efforts at the Medical Center Hospital of Vermont (MCHV) led to the development of critical pathways, which show the ideal plan of care, and algorithms, which help clinicians make one of many complicated decisions within a plan of care. A synergy appears to develop when pathways and algorithms are used together. DEVELOPMENT OF PATHWAYS AND ALGORITHMS: A steering committee supports and oversees pathway and algorithm efforts. A quarterly tracking report updating progress for all pathways and algorithms is circulated to all nurse managers, medical staff, and administrators. When combining pathways and algorithms, the pathway is created first. Algorithms are developed for trouble spots within a pathway. CORONARY ARTERY BYPASS GRAFT (CABG) PATIENTS: Having developed the pathway for CABG patients, the CABG case management team meets monthly to review outcomes and variances. For example, an algorithm for managing atrial arrhythmias--the chief cause of variance for one month's results--was developed. The combination of pathways and algorithms for CABG patients has resulted in a reduction of 2.5 days for total length of stay (including 1 day on the surgical intensive care unit [SICU]), for a mean cost savings of $3,500. Re-admission to the SICU, reintubation, and mortality rates have all decreased. CONCLUSION: The idea of reaping the benefits of both pathways and algorithms is becoming more popular at MCHV, where teams use algorithms to improve on complicated processes underlying the pathways.

Modulatory effect of endopeptidase inhibitors on bradykinin-induced contraction of rat uterus.

Bradykinin (BK) affects a variety of smooth muscle types, including uterus. These effects are generally short-lived due to metabolism by a variety of enzymes including angiotensin converting enzyme (ACE), endopeptidase 24.11 (EP-24.11) and endopeptidase 24.15 (EP-24.15). The uterotonic action of BK and the limitation of that action by peptidases were examined using isolated rat uterus. BK contracted the estrus, diestrus and day 22 pregnant rat uterus. N-[1(R,S)-carboxy-3-phenylpropyl]-Phe-p-aminobenzoate (10(-7) M), a specific inhibitor of EP-24.11, and N-[1(R,S)-carboxy-3-phenylpropyl]-Ala-Ala-Phe-p-aminobenzoate (10(-6) M), a specific inhibitor of EP-24.15, enhanced BK-induced contraction in the estrus and pregnant uterus. Enalaprilat (6 x 10(-8) M), an inhibitor of ACE, also enhanced BK-induced contraction. The enzyme inhibitors alone did not contract the uterus. Bradykinin B2 receptor antagonism blocked the effects of the inhibitors. ACE is present in the rat uterus, but there are no reports of EP-24.11 or EP-24.15. Here we report that EP-24.11 and EP-24.15 activities are present in the estrus and pregnant rat uterus. Partially purified uterine homogenates metabolized specific model substrates for EP-24.11 and EP-24.15. The enzyme activities were inhibited by N-[1(R,S)-carboxy-3-phenylpropyl]-Phe-p-aminobenzoate and N-[1(R,S)-carboxy-3-phenylpropyl]-Ala-Ala-Phe-p-aminobenzoate, respectively, and increased 5- to 8-fold at term pregnancy as compared to estrus.(ABSTRACT TRUNCATED AT 250 WORDS)

Diethylstilbesterol- and pregnancy-induced changes in rat neurointermediate lobe oxytocin, arginine vasopressin, methionine enkephalin and dynorphin.

The neurointermediate lobe of the pituitary (NIL) contains the opioid peptides methionine enkephalin (MENK) and dynorphin 1-8 (DYN) in addition to oxytocin (OT) and vasopressin (AVP). If the opioids have a functional role, such as feedback control on OT or AVP release, the content or release of the opioids might be expected to change under conditions in which OT or AVP change. This expectation was examined by studying the synthesis, storage and release of the 4 peptides under conditions in which OT and AVP dynamics are known to be altered. Diestrus, diethylstilbesterol(DES)-treated, and day 22 pregnant rats were decapitated, the hypothalamo-neurohypophysial system (HNS) excised and either superfused in oxygenated Krebs buffer at 37 degrees C or stored at -80 degrees C for measurement of paraventricular and supraoptic nuclei mRNA content by in situ hybridization analysis. Peptide content of superfusates and NIL homogenates were determined by specific RIAs. Compared with diestrus animals, DES treatment increased NIL OT but decreased MENK. In term pregnant rats, NIL OT, AVP, and DYN were increased over diestrus values, while MENK was again decreased. Release of the peptides from the isolated HNS paralleled changes in NIL content. The hypothalamic mRNA for OT was increased in DES-treated and pregnant rats while MENK mRNA was decreased. AVP and DYN mRNA was increased in pregnant animals. Although the NIL was found to contain much more immunoreactive OT and AVP than MENK or DYN, under basal conditions the release of MENK was equal to or greater than the release of OT, while the release of DYN approached that of AVP.(ABSTRACT TRUNCATED AT 250 WORDS)

Decapitation increases plasma sodium and potassium in the rat.

Sodium, potassium, and osmolality were measured in plasma obtained from conscious and decapitated rats. The sodium and potassium content of plasma derived from blood taken from decapitated rats via arterial cannulae or free-flowing trunk blood was significantly greater than that in conscious animals or animals killed by an overdose of pentobarbital. Plasma osmolality was not different. Hemoglobin was present in the plasma of decapitated rats, suggesting hemolysis. Hemolysis and subsequent release of intracellular potassium may be the cause of the elevated plasma potassium. The cause of the elevated sodium is unclear. This study points out the importance of considering the method of obtaining blood in determinations of plasma levels of biologic substances.