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Coronary artery disease kills more women than all cancers combined, yet the clinical picture in women is different enough from men that the diagnosis can be missed or delayed. A cardiologist highlights these gender-based differences and explains why certain diagnostic tests are better than others at identifying CAD in women. Coronary artery disease (CAD) is the leading killer of women in the US. After menopause, mortality rates from CAD in women nearly equal those of men. Yet the clinical picture in women is different enough from that in men that it can obscure the correct diagnosis. Women are 10 years older than men, on average, when presenting with CAD, possibly due to delayed diagnosis or presentation. Differences in symptomatology between men and women are important to note. For example, other diseases, such as arthritis or osteoporosis, can obscure CAD symptoms. Further, compared with men, women's chest pain is more often associated with abdominal pain, dyspnea, nausea, and fatigue. More women than men with CAD have diabetes, hypertension, hypercholesterolemia, and a family history of CAD. Clinicians need to know how to assess the gender-specific pretest likelihood of CAD in women, starting with a careful review of the patient's chest pain history. Other risk factors, including smoking, abdominal obesity, and certain comorbidities, should be taken into consideration. The diagnostic accuracy of exercise testing is slightly lower for women than men. Certain diagnostic tests, particularly exercise echocardiography and exercise thallium/sestamibi testing, offer more prognostic information than traditional exercise electrocardiographic studies without imaging. Mortality associated with interventional procedures--such as angioplasty and coronary artery bypass grafting (CABG)--is slightly higher in women, although long-term survival rates are similar for both sexes. Detection of CAD at an earlier stage in women may result in earlier referrals for CABG, with the benefit of lower associated mortality rates.
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PMID:Coronary artery disease in women: understanding the diagnostic and management pitfalls. 980 15

The cardinal clinical manifestations of major depression with melancholic features include sustained anxiety and dread for the future as well as evidence of physiological hyperarousal (e.g., sustained hyperactivity of the two principal effectors of the stress response, the corticotropin-releasing-hormone, or CRH, system, and the locus ceruleus-norepinephrine, or LC-NE, system). Sustained stress system activation in melancholic depression is thought to confer both behavioral arousal as well as the hypercortisolism, sympathetic nervous system activation, and inhibition of programs for growth and reproduction that consistently occur in this disorder. Data also suggest that activation of the CRH and LC systems in melancholia are involved in the long-term medical consequences of depression such as premature coronary artery disease and osteoporosis, the two-three-fold preponderance of females in the incidence of major depression, and the mechanism of action of antidepressant drugs. In addition, recent data reveal important bidirectional interactions between stress-system hormonal factors in depression and neural substrates implicated in many discrete behavioral alterations in depression (e.g., the medial prefrontal cortex, important in shifting affect based on internal and external cues, the mesolimbic dopaminergic reward system, and the amygdala fear system). We have also advanced data indicating that the hypersomnia, hyperphagia, lethargy, fatigue, and relative apathy of the syndrome of atypical depression are associated with concomitant hypofunctioning of the CRH and LC-NE systems. These data indicate the need for an entirely different therapeutic strategy than that used in melancholia for the treatment of atypical depression, and they suggest that this subtype of major depression will be associated with its own unique repertoire of long-term medical consequences.
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PMID:The endocrinology of melancholic and atypical depression: relation to neurocircuitry and somatic consequences. 989 54

The interdisciplinary approach to the management of MS patients includes the services of both physical and occupational therapy. These professions complement one another in their concerted effort to mobilize the patient, thereby minimizing the symptoms of progressive weakness, fatigue, and spasticity. The ambulant patient is far less likely to develop complications of inactivity such as contractures, decubitus ulcers, venous thrombosis, or osteoporosis (with its associated fatigue fractures), as well as bowel or bladder complications.
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PMID:Physical and occupational therapy in the treatment of patients with multiple sclerosis. 989 12

A quantitative assessment of bone tissue stresses and strains is essential for the understanding of failure mechanisms associated with osteoporosis, osteoarthritis, loosening of implants and cell-mediated adaptive bone-remodeling processes. According to Wolff's trajectorial hypothesis, the trabecular architecture is such that minimal tissue stresses are paired with minimal weight. This paradigm at least suggests that, normally, stresses and strains should be distributed rather evenly over the trabecular architecture. Although bone stresses at the apparent level were determined with finite element analysis (FEA), by assuming it to be continuous, there is no data available on trabecular tissue stresses or strains of bones in situ under physiological loading conditions. The objectives of this project were to supply reasonable estimates of these quantities for the canine femur, to compare trabecular-tissue to apparent stresses, and to test Wolff's hypothesis in a quantitative sense. For that purpose, the newly developed method of large-scale micro-FEA was applied in conjunction with micro-CT structural measurements. A three-dimensional high-resolution computer reconstruction of a proximal canine femur was made using a micro-CT scanner. This was converted to a large-scale FE-model with 7.6 million elements, adequately refined to represent individual trabeculae. Using a special-purpose FE-solver, analyses were conducted for three different orthogonal hip-joint loading cases, one of which represented the stance-phase of walking. By superimposing the results, the tissue stress and strain distributions could also be calculated for other force directions. Further analyses of results were concentrated on a trabecular volume of interest (VOI) located in the center of the head. For the stance phase of walking an average tissue principal strain in the VOI of 279 strain was found, with a standard deviation of 212 microstrain. The standard deviation depended not only on the hip-force magnitude, but also on its direction. In more than 95% of the tissue volume the principal stresses and strains were in a range from zero to three times the averages, for all hip-force directions. This indicates that no single load creates even stress or strain distributions in the trabecular architecture. Nevertheless, excessive values occurred at few locations only, and the maximum tissue stress was approximately half the value reported for the tissue fatigue strength. These results thus indicate that trabecular bone tissue has a safety factor of approximately two for hip-joint loads that occur during normal activities.
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PMID:Tissue stresses and strain in trabeculae of a canine proximal femur can be quantified from computer reconstructions. 1021 36

Chronic heart failure (CHF) is a complex syndrome affecting many body systems. Body wasting (ie, cardiac cachexia) is a serious complication of CHF long known but little investigated. Although no specific diagnostic criteria have been established, we have suggested that cardiac cachexia be defined on the basis of the presence of documented nonintentional and nonedematous weight loss > 7.5% of the premorbid normal weight, occurring over a time period of > 6 months. Using this definition, 16% of an unselected CHF outpatient population was found to be cachectic. The cachectic state is predictive of impaired prognosis independently of age, functional disease classification, left ventricular ejection fraction, and peak oxygen consumption. The mortality in the cachectic cohort is 50% at 18 months. Analyzing body composition in detail, it has been found that patients with cardiac cachexia suffer from a general loss of fat tissue (ie, energy reserves), lean tissue (ie, skeletal muscle), and bone tissue (ie, osteoporosis). Cachectic CHF patients are weaker and fatigue earlier, which is due to both reduced skeletal muscle mass and impaired muscle quality. The pathophysiologic alterations leading to cardiac cachexia remain unclear, but initial cross-sectional studies have suggested that humoral neuroendocrine and immunologic abnormalities are linked, independently of established heart failure severity markers, to the presence of body wasting. Comparing the features of cachectic and noncachectic CHF patients with those of healthy control subjects, it is mainly the cachectic CHF patients who show raised plasma levels of epinephrine, norepinephrine, and cortisol; the highest plasma renin activity and aldosterone plasma concentrations; and the lowest plasma sodium level. Several studies have shown that cardiac cachexia is linked to raised plasma levels of tumor necrosis factor-ac. The degree of body wasting is strongly correlated with neurohormonal and immune abnormalities. The available evidence suggests that cardiac cachexia is a multifactorial neuroendocrine and metabolic disorder with a poor prognosis. A complex imbalance of different body systems may cause the development of body wasting.
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PMID:Cardiac cachexia: a syndrome with impaired survival and immune and neuroendocrine activation. 1008

Menopause and the accompanying reduction in estrogen production may cause a number of symptoms in women which include hot flushes, sweating, mood and sleep disturbances, fatigue and urogenital dysfunction. The effectiveness of estrogen-based hormone replacement therapy (HRT) in ameliorating these symptoms, and in preventing long term sequelae such as osteoporosis, is well established. Comparative trials indicate that oral conjugated estrogens 0.625mg, oral ethinyl estradiol 0.02mg and transdermal estradiol 0.05mg have equivalent efficacy in relief of mild to moderate menopausal symptoms and prevention of bone mineral loss. Concomitant progestogen therapy is usually prescribed for women with intact uteri to protect against endometrial hyperplasia and carcinoma. The addition of progestogen maintains and may even enhance the bone-conserving effects of estrogen, and continuous regimens appear to reduce the incidence of irregular menses. Adverse reactions are predominantly local skin irritation with transdermal preparations (14% of patients) and systemic effects common to most forms of HRT including breast tenderness, flushing, headache and irregular bleeding, occurring in less than or equal to 2% of patients. Data concerning the effect of HRT on quality of life are limited, but most analyses have assigned utility values of 0.99 for mild and 0.95 for severe menopausal symptoms. However, recent clinical data suggest that these utility values may underestimate the impact of menopausal symptoms on quality of life. The cost benefit and cost effectiveness of HRT in the treatment of menopausal symptoms have not been fully researched, although preliminary results suggest that conjugated estrogens and transdermal estradiol compare well with alternative therapies such as veralipride and Chinese medicines. A Swedish study using a prevalence-based approach estimated that estriol treatment in all women with urinary incontinence aged greater than or equal to 65 years resulted in monetary savings compared with treating 20% of women. Cost-utility data indicated that the change in quality-adjusted life years (QALYs) with HRT was always positive, but the degree of change was determined by the baseline assumptions. Estimated changes in QALYs with HRT ranged from 0.006 for 5 years of treatment with unopposed estrogen in women with intact uteri, to 0.5 for 10 years of the same treatment in women with severe menopausal symptoms following hysterectomy. Compliance with HRT is suboptimal as 5 to 50% of women withdraw from therapy, thereby increasing costs per year of life saved.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Hormone replacement therapy: I. A pharmacoeconomic appraisal of its therapeutic use in menopausal symptoms and urogenital estrogen deficiency. 1014 33

A quantitative assessment of bone tissue stresses and strains is essential for the understanding of failure mechanisms associated with osteoporosis, osteoarthritis, loosening of implants and cell- mediated adaptive bone-remodeling processes. According to Wolff's trajectorial hypothesis, the trabecular architecture is such that minimal tissue stresses are paired with minimal weight. This paradigm at least suggests that, normally, stresses and strains should be distributed rather evenly over the trabecular architecture. Although bone stresses at the apparent level were determined with finite element analysis (FEA), by assuming it to be continuous, there is no data available on trabecular tissue stresses or strains of bones in situ under physiological loading conditions. The objectives of this project were to supply reasonable estimates of these quantities for the canine femur, to compare trabecular-tissue to apparent stresses, and to test Wolff's hypothesis in a quantitative sense. For that purpose, the newly developed method of large-scale micro-FEA was applied in conjunction with micro-CT structural measurements. A three-dimensional high-resolution computer reconstruction of a proximal canine femur was made using a micro-CT scanner. This was converted to a large-scale FE-model with 7.6 million elements, adequately refined to represent individual trabeculae. Using a special-purpose FE-solver, analyses were conducted for three different orthogonal hip-joint loading cases, one of which represented the stance-phase of walking. By superimposing the results, the tissue stress and strain distributions could also be calculated for other force directions. Further analyses of results were concentrated on a trabecular volume of interest (VOI) located in the center of the head. For the stance phase of walking an average tissue principal strain in the VOI of 279 strain was found, with a standard deviation of 212 microstrain. The standard deviation depended not only on the hip-force magnitude, but also on its direction. In more than 95% of the tissue volume the principal stresses and strains were in a range from zero to three times the averages, for all hip-force directions. This indicates that no single load creates even stress or strain distributions in the trabecular architecture. Nevertheless, excessive values occurred at few locations only, and the maximum tissue stress was approximately half the value reported for the tissue fatigue strength. These results thus indicate that trabecular bone tissue has a safety factor of approximately two for hip-joint loads that occur during normal activities.
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PMID:Tissue stresses and strain in trabeculae of a canine proximal femur can be quantified from computer reconstructions. 1005 22

We describe a 33-year-old woman with a bilateral fracture of the sacrum associated with pregnancy. Dual-energy X-ray absorptiometry of the lumbar spine and femoral neck showed normal bone mineral density, whereas bilateral osteopenic areas in the massae laterales were demonstrated by the initial CT-scan. The question remains whether the correct diagnosis is so-called insufficiency fracture due to transient osteoporosis of the sacrum associated with pregnancy or so-called fatigue fracture due to unaccustomed stress related to rapid and excessive weight gain in the last trimester of pregnancy.
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PMID:Bilateral fracture of the sacrum associated with pregnancy: a case report. 1050 86

Recent realizations have begun to change how 'osteoporoses' are diagnosed, managed and studied. This article explains the nature and basis of some resulting controversies, chiefly for clinicians who manage such patients but do not participate in resolving those controversies. Currently the size of a bone 'mass' deficit serves to diagnose 'osteoporosis', but recently clarified physiology suggests at least three different kinds of osteoporosis could occur in people with identical bone 'mass' deficits. Indeed, they do occur. (a) In one kind, people have less bone than 'normal' but no bone problems unless they sustain injuries. Most of their resulting fractures, usually from falls, affect extremity bones. This condition can affect children, men and women. (b) In a second kind an osteopenia exists in which voluntary physical activities (not injuries) cause spontaneous fractures and/or bone pain, mainly in the spine, more often in women than men and seldom in children (osteogenesis imperfecta excepted). (c) A third kind combines features of the first two. As for the physiology involved in those affections, bone modeling can increase bone strength and 'mass', while BMU (Bone Multicellular Unit)-based bone remodeling can reduce them. Mainly bone strains control those two activities and muscles cause the largest strains, so muscle strength should strongly influence bone modeling, remodeling, strength and 'mass'. If so chronic muscle weakness should usually cause an osteopenia and weakened bones. Excessive amounts of fatigue damage or microdamage can also weaken bones. From that physiology one could argue that chiefly chronic muscle weakness instead of an intrinsic bone disorder would cause (a), while intrinsic but still enigmatic modeling and remodeling disorders would cause (b), and (c) could combine features of both conditions. If so, these ideas could have significant effects on the future criteria used to diagnose osteoporoses and osteopenias, on how they are studied in the clinic and laboratory, and on how they are prevented or, if they occur, are managed.
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PMID:Changing views about 'Osteoporoses' (a 1998 overview). 1059 31

The diagnosis of primary biliary cirrhosis (PBC) is most often made in the asymptomatic phase, sometimes before the development of abnormal liver biochemistry. The antimitochondrial antibody remains the predominant hallmark, although not all patients test positive, even when the most sensitive techniques are used. The etiology of PBC remains elusive; studies suggest that the interlobular bile duct destruction is immune based, and associated autoimmune diseases are common. There are no surrogate markers that predict outcome in asymptomatic patients, whose chance of survival is less than that of age- and sex-matched populations but much better than the median survival of eight years in patients with symptomatic PBC. Symptoms common in this disease are fatigue, pruritus and xanthelasma, as well as complications of portal hypertension and osteoporosis. Treatment includes symptomatic and preventive measures, as well as specific therapeutic measures. Immunosuppressive therapy has yielded disappointing results in the long term management of PBC, and the only therapy shown to improve survival is the hydrophobic dihydroxy bile acid ursodeoxycholic acid. Treatment at a dose of 13 to 15 mg/kg/day is optimal, given in separate doses or as a single dose at least 4 h from giving the oral anion exchange resin cholestyramine, which may be used to control pruritus. However, liver transplantation remains the only cure for this disease, and the best postoperative survival is seen in patients whose serum bilirubin does not exceed 180 micromol/L at the time of liver transplantation. Recurrence takes place but is rarely symptomatic and does not deter from the benefits of transplantation.
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PMID:Update on primary biliary cirrhosis. 1065 26


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