Physical activity engendering loads from diverse directions augments the growing skeleton.

OBJECTIVE: An experiment was conducted to determine if modifying habitual activities to involve mechanical loading from more diverse directions can enhance the growing skeleton. METHODS: Growing female C57BL/6J mice were housed individually for 3 months in enclosures designed to accentuate either non-linear locomotion (diverse-orientation loading) or linear locomotion (stereotypic-orientation loading) (n=10/cage type). Behavioral assessments were performed daily to quantify cage activity level. Following the experiment, trabecular and cortical bone structure in the humeral head and distal femoral metaphysis were analyzed with µCT. RESULTS: Throughout the experiment, groups did not differ in cage activity level. Yet, following the experiment, the proximal humeri of mice that experienced increased diverse-orientation loading had significantly greater trabecular bone volume fraction (p=0.004), greater cortical bone area (p=0.005), greater cortical area fraction (p=0.0007), and thicker cortices (p=0.002). No significant group differences were detected in the distal femoral metaphysis. CONCLUSIONS: Diverting habitual activities to entail loading from more diverse orientations can augment the growing mouse skeleton. This study suggests that low-intensity activities that produce loads from diverse directions may represent a viable alternative to vigorous, high-impact exercise as a means of benefiting skeletal health during growth.

Role of Nonbehavioral Factors in Adjusting Long Bone Diaphyseal Structure in Free-ranging Pan troglodytes.

Limb bones deform during locomotion and can resist the deformations by adjusting their shapes. For example, a tubular-shaped diaphysis best resists variably-oriented deformations. As behavioral profiles change during adulthood, patterns of bone deformation may exhibit age trends. Habitat characteristics, e.g., annual rainfall, tree density, and elevation changes, may influence bone deformations by eliciting individual components of behavioral repertoires and suppressing others, or by influencing movements during particular components. Habituated chimpanzee communities provide a unique opportunity to examine these factors because of the availability of morphological data and behavioral observations from known-age individuals inhabiting natural habitats. We evaluated adult femora and humeri of 18 female and 10 male free-ranging chimpanzees (Pan troglodytes) from communities in Gombe (Tanzania), Mahale Mountains (Tanzania), and Taï Forest (Côte d'Ivoire) National Parks. We compare cross sections at several locations (35%, 50%, 65% diaphyseal lengths). Community comparisons highlight different diaphyseal shapes of Taï females relative to Mahale and Gombe females, particularly in humeral diaphyses. Age trends in diaphyseal shapes are consistent with reduced activity levels in general, not only reduced arboreal activity. Age-related bone loss is apparent among community females, but is less striking among males. Community trends in diaphyseal shape are qualitatively consistent with ranked annual rainfall at localities, tree density, and elevation change or ruggedness of terrain. Habitat characteristics may contribute to variation in diaphyseal shape among chimpanzee communities, much like among modern human groups, but verification awaits further rigorous experimental and comparative analyses.

Multidisciplinary women's health care and quality of care.

Multidisciplinary women's health centers have appeared in academic and community settings throughout the United States as a response to the historical fragmentation of women's health care. This paper addresses the influence of this model for comprehensive primary care on quality of care for women. Attributes of care that may differ between multidisciplinary centers and traditional sites for women's health care and quality measurements sensitive to these differences are considered. The paper reviews the literature on characteristics of patients who attend women's health centers and studies evaluating quality of care in these centers as compared to traditional settings.

Comparison of fatty acid tracers FTHA and BMIPP during myocardial ischemia and hypoxia.

UNLABELLED: To study the sensitivity of two fatty acid tracers to changes in beta-oxidation, the myocardial retention kinetics of 125I-iodine-15-(p-iodophenyl)-3(R,S)-methylpentadecanoic acid (BMIPP) and 14-18F-fluoro-6-thia-heptadecanoic acid (FTHA) were compared in states of oxygen deprivation due to ischemia and hypoxia. METHODS: Nineteen swine were studied by extracorporeal perfusion of the three coronary arteries. Fatty acid beta-oxidation rates were determined by infusion of tritiated palmitate into the left anterior descending artery (LAD) and by measurement of labeled water production in the LAD perfusion bed. After a baseline period of 30 min, animals were divided into three groups and subjected to a 50-min intervention period. For the control group, there was no change in perfusion; for the ischemia group, there was a 60% decrease in LAD perfusion; and for the hypoxia group, the perfusion rate was unchanged, but venous blood was used as the LAD perfusate. Continuous infusion of FTHA and BMIPP into the LAD started 10 min into the intervention period and continued until the end of the intervention period. Retention rates of the two tracers were compared between the LAD and circumflex perfusion beds. RESULTS: No difference in beta-oxidation rate occurred from the baseline to the intervention period in the control group. A 50% reduction in beta-oxidation occurred in the ischemia group, and an 80% reduction occurred in the hypoxia group. No difference in retention of BMIPP or FTHA occurred in the control group. In the ischemia group, reduction in retention of both tracers occurred. However, in the hypoxia group, FTHA uptake was unchanged, whereas BMIPP retention increased compared to the circumflex arterial bed. CONCLUSION: Decreased retention of both BMIPP and FTHA occurred with ischemia, despite the known differences in metabolism of the two tracers. This difference in metabolism was further highlighted in the setting of hypoxia with increased BMIPP uptake. Thus, these results suggest that uptake of both FTHA and BMIPP tracks reduction of fatty acid utilization in myocardial ischemia but fails in tracking reduction of fatty acid oxidation during hypoxia.

Outcomes of hysterectomy.

Recent randomized trials and prospective cohort studies have provided new information on the health outcomes of hysterectomy for nonmalignant conditions. These studies consistently have demonstrated a marked improvement in symptoms and quality of life during the early years after surgery. The long-term effects of premenopausal hysterectomy on ovarian function have not been established, but existing evidence suggests there is no adverse effect on risk for cardiovascular disease from hysterectomy alone. Epidemiologic studies have indicated that premenopausal hysterectomy with ovarian preservation is associated with a modest decrease in future risk for ovarian cancer and possibly breast cancer. There is no consistent evidence for adverse effects on bowel or bladder function. Hysterectomy does not cause long-term psychiatric morbidity, and psychological status generally improves. Studies of sexual function have shown varying results, with most suggesting improvement or no change in sexual function for the majority of women.

Comparing prospective and retrospective measures of treatment outcomes.

This study examines the correspondence between retrospective and prospective assessments of treatment outcomes among female patients treated for gynecologic symptoms (n = 800) and male patients having surgery for benign prostatic hyperplasia (n = 434). The overall health and symptom status of patients in both samples was assessed at enrollment and again 3 months after treatment; at the 3-month follow-up, patients also were asked to compare retrospectively their current health and how they were feeling with their condition before treatment. Findings indicate that prospective and retrospective measures of change do not yield the same results. Retrospective assessments consistently produce higher estimates of the benefits of treatment, although that pattern was clearer for overall health status than for measures of symptoms. Patients' posttreatment health and symptom status contributes as much to retrospective assessments of change as does prospectively measured change, although the retrospective assessments of female patients whose gynecologic symptoms were medically managed were more strongly related to prospective change than those of hysterectomy patients or prostate surgery patients. Overall, we conclude that these alternative measurement strategies yield divergent assessments of change, depending on the type of treatment a patient receives and, to some extent, what is being measured.

Screening for ovarian cancer.

PURPOSE: To critically review the available evidence for screening asymptomatic women for ovarian cancer with ultrasonography or the CA 125 radioimmunoassay (CA 125) or both. DATA SOURCES: A MEDLINE search of the English-language literature and bibliographies of published studies providing estimates of ovarian cancer risk and test operating characteristics (based on observational studies and meta-analyses) and effectiveness of treatment according to stage of disease (based on randomized trials). Published mathematical models simulating screening for ovarian cancer in specific populations were also included. Death from ovarian cancer and morbidity from surgical procedures were the principal outcomes considered. RESULTS: Age and family history are the most important risk factors for ovarian cancer. Annual screening with CA 125 or ultrasound in women older than 50 years without a family history of ovarian cancer would result in more than 30 false-positive results for every ovarian cancer detected. False-positive tests are likely to require invasive testing, often including laparotomy. There is currently no direct evidence that mortality from ovarian cancer would be decreased by screening. CONCLUSIONS: Available evidence does not support either screening of pre- or postmenopausal women without a family history of ovarian cancer or routine screening in women with a family history of ovarian cancer in one or more relatives (without evidence of a hereditary cancer syndrome). Women from a family with the rare hereditary ovarian cancer syndrome are at high risk for the disease and should be referred to a gynecologic oncologist.

The Maine Women's Health Study: I. Outcomes of hysterectomy.

OBJECTIVE: To assess the effect of hysterectomy for nonmalignant conditions on symptoms and quality of life and to identify adverse effects 1 year after surgery. METHODS: The Maine Women's Health Study was a prospective cohort study of 418 women ages 25-50 years undergoing hysterectomy for any nonmalignant condition. Patients recruited from the practices of 63 physicians performing hysterectomy throughout Maine were interviewed at the time of surgery and 3, 6, and 12 months later. Clinical and hospitalization data were obtained from physician reports and from a statewide hospital discharge data base. The primary outcomes of interest were symptom relief, changes in quality of life, and the development of new symptoms or problems during the year following surgery. RESULTS: The most frequent indications for hysterectomy were leiomyomas (35%), abnormal bleeding (22%), and chronic pelvic pain (18%). For these indications, hysterectomy resulted in marked improvements in a range of symptoms, including pelvic pain, urinary symptoms, fatigue, psychological symptoms, and sexual dysfunction. Significant improvements in scores for indices of mental health, general health, and activity were evident at 6 months and sustained at 1 year. New problems after hysterectomy (measured in those free of the symptom preoperatively) included hot flashes (13%), weight gain (12%), depression (8%), and lack of interest in sex (7%). CONCLUSIONS: Hysterectomy is highly effective for relief of symptoms associated with common nonmalignant gynecologic conditions. Symptom relief following hysterectomy is associated with a marked improvement in quality of life. New problems are reported after hysterectomy by a limited number of women.

The Maine Women's Health Study: II. Outcomes of nonsurgical management of leiomyomas, abnormal bleeding, and chronic pelvic pain.

OBJECTIVE: To assess the effect of nonsurgical management of leiomyomas, abnormal uterine bleeding, and chronic pelvic pain on symptoms and quality of life. METHODS: We performed a prospective cohort study of women receiving nonsurgical management (n = 380) or hysterectomy (n = 311) for leiomyomas, abnormal uterine bleeding, or chronic pelvic pain. Patients recruited from the practices of 63 physicians throughout Maine were interviewed at the outset of treatment and 3, 6, and 12 months later. The principal outcome measures were frequency and severity of physical and psychological symptoms, and quality of life as measured by validated indices of mental and general health and physical activity. RESULTS: Medical therapy for abnormal bleeding and chronic pelvic pain produced significant improvements in symptoms and quality of life. However, almost one-quarter of patients initially treated nonsurgically subsequently underwent hysterectomy; of patients continuing nonsurgical therapy, 25% with abnormal bleeding and 50% with chronic pelvic pain reported substantial levels of symptoms after 1 year. There were no significant changes in symptoms and quality of life in patients treated nonsurgically for leiomyomas. New problems including tiredness, hot flashes, weight gain, and depression developed in 10% or less of women who did not report these symptoms preoperatively. A logistic regression analysis controlling for age, reproductive history, and severity of symptoms showed that hysterectomy was the factor most highly correlated with a positive outcome at 1 year for all three conditions. CONCLUSIONS: Many women with leiomyomas, abnormal bleeding, and chronic pelvic pain report improved symptoms over time with nonsurgical management. Hysterectomy remains an important alternative when conservative treatment fails.

Extracorporeal shock wave lithotripsy and percutaneous nephrostolithotomy for urinary calculi: comparison of immediate and long-term effects.

Extracorporeal shock wave lithotripsy and percutaneous nephrostolithotomy have become widely used technologies for removal of urinary calculi, despite a lack of adequate evaluative studies. The possibility of long-term adverse effects of these treatments has been raised, particularly an increase in stone recurrence and development of hypertension following extracorporeal shock wave lithotripsy. We conducted a retrospective study of 1,000 patients treated with extracorporeal shock wave lithotripsy or percutaneous nephrostolithotomy for upper tract stone disease to assess immediate effectiveness and complications, with prospective follow-up to assess stone recurrence and development of hypertension. The effectiveness of each treatment (defined in terms of patients rendered stone-free or having only fragments at discharge) was similar for most stone types. While stone recurrence rates in the first 2 years after treatment were similar in the two groups, cumulative recurrence at 3 years was higher following extracorporeal shock wave lithotripsy compared to percutaneous nephrostolithotomy (39% vs. 23%, p = 0.04). However, logistic regression and Kaplan-Meier analyses showed no significant difference in clinically evident recurrence for patients treated with extracorporeal shock wave lithotripsy. Cumulative incidence of clinically evident stone recurrence did not differ significantly between patients with fragments at discharge (20%) and patients rendered stone-free (15%) (p = 0.24). There was no difference in the development of new hypertension requiring medical treatment. Our findings indicate that extracorporeal shock wave lithotripsy is effective and associated with lower short-term morbidity than percutaneous nephrostolithotomy. Stone fragments left behind by lithotripsy do not appear to confer significant risk of early stone recurrence. Further study is necessary to define long-term risk of recurrence following extracorporeal shock wave lithotripsy.

Estrogen and progestin therapy to prevent osteoporosis: attitudes and practices of general internists and gynecologists.

STUDY OBJECTIVE: To assess combined hormone therapy (CHT) prescribing patterns, possible impediments to CHT prescribing, and use of endometrial biopsy to monitor therapy. DESIGN: Mailed questionnaire survey. SUBJECTS: Gynecologists and general internists at two Boston teaching hospitals. MEASUREMENTS AND MAIN RESULTS: Based on a 71% response rate, 72% of internists and 100% of gynecologists reported ever having prescribed CHT. Almost 60% of internists, compared with 8% of gynecologists, reported that over half of their female patients were older than 50 years of age. By logistic regression analysis of the internists' data, female gender of physician (odds ratio 11.0), belief that CHT decreases myocardial infarction risk (odds ratio 3.4), and knowledge of CHT's benefits and risks (odds ratio 2.8) were associated with prescribing. Endometrial biopsy was performed by a majority of physicians only when unexpected vaginal bleeding occurred and in cases of unclear menopausal transition. Physicians who were concerned about litigation were seven times more likely to perform baseline endometrial biopsy. CONCLUSIONS: In the authors' sample, as well as nationally, internists are more likely to provide care for menopausal women. Among internists, gender and knowledge are strongly associated with CHT prescribing. These findings have important educational implications if internists are to routinely provide information and counseling to women about osteoporosis and CHT.

Cost-effectiveness analysis of single-dose therapy of urinary tract infection compared to conventional treatment.

A cost effectiveness analysis comparing single-dose with conventional antibiotic treatment for uncomplicated urinary tract infection is described. The analysis is based on aggregated effectiveness and side effect rates reported in the medical literature. A comparison of single-dose and conventional regimens of trimethoprim-sulfamethoxazole and amoxicillin indicates that single-dose regimens are preferable to conventional regimens of either drug, and that trimethoprim-sulfamethoxazole is preferable to amoxicillin, on the grounds both of days of morbidity averted and of medical care costs. Thus single-dose therapy is cost-effective compared to conventional treatment.

Management of acute dysuria. A decision-analysis model of alternative strategies.

A decision-analysis model was developed to estimate the effects and costs of alternative initial management strategies for women presenting with dysuria and pyuria. We compared days of morbidity and direct medical costs associated with single-dose and multiple-dose regimens of amoxicillin and trimethoprim-sulfamethoxazole and examined the cost-effectiveness of doing an initial urine culture. We used varying assumptions for prevalence of etiologic agents, treatment efficacy, frequency of side effects, and duration of symptoms. Single-dose regimens were preferable to multiple-dose regimens of either drug, and trimethoprim-sulfamethoxazole was preferable to amoxicillin. Single-dose trimethoprim-sulfamethoxazole therapy resulted in the fewest expected symptom-days (2.7) and the lowest expected cost (+54). The advantage of single-dose strategies in minimizing expected symptom-days resulted largely from the threefold to fourfold increase in the incidence of side effects reported with multiple-dose therapy. Obtaining an initial urine culture in all patients reduced expected symptom-days by about 10% but increased expected cost by about 40%.

An analysis of physicians' reasons for prescribing long-term digitalis therapy in outpatients.

We examined by medical-record review why long-term digitalis therapy was prescribed in 150 outpatients, the reasons were: supraventricular tachyarrhythmias (35): supraventricular tachyarrhythmias and heart failure (33); and heart failure with sinus rhythm (82). In the patients without supraventricular tachyarrhythmias we scrutinized the diagnosis of heart failure using a clinicoradiographic scoring system and found the diagnosis unlikely in 32 patients. When these 32 patients are combined with the 31 patients who had only one occurrence of supraventricular tachyarrhythmias or heart failure, 42% of the patients were on long-term digitalis therapy for a questionable reason. We conclude that a substantial fraction of general medical outpatients might benefit from digitalis withdrawal, if evidence for heart failure is lacking or if the reason prompting digitalis therapy is isolated to the distant past.