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A progressive decrease in androgen production is common in aging men. The physiological causes for this phenomenon seem to be multifactorial. The magnitude of the decline in testosterone with age and the prevalence of older men with low testosterone levels have not been well established. The extent to which an age-dependent decline in androgen levels leads to health problems that might affect or alter the quality of life remains under debate. In men older than middle age, total testosterone levels may be misleading because of an increase in sex hormone-binding globulin levels. The mechanism of the age-associated decrease of the endocrine testicular function is also essentially due to primary testicular failure, but important changes occur at the hypothalamopituitary level. The most prominent endocrinological alterations with aging are related to the sex steroids, but others, such as growth hormone, melatonin cortisol, and thyroxine, are also affected. The clinical picture of andropause syndrome is characterized by diminished sexual desire and erectile capacity, decrease in intellectual activity, fatigue, depression, decrease in lean body mass, skin alterations, decrease in body hair, decrease in bone mineral density that results in osteoporosis, and increase in visceral fat and obesity. Current medical treatments for androgen supplementation include oral tablets, intramuscular injections, and scrotal and nonscrotal patches. Unfortunately, none of these preparations mimic the circadian rhythm, even if some of them may approximate the circadian rhythm by dose adjustments. Moreover, the androgen supplementation could have adverse effects on different organs, namely, the liver, lipid profile, cardiovascular disease, prostate, sleep disorders, and emotional behavior. Clinical response is a better guide to dose requirements, regardless of serum testosterone levels. This important field must be actively investigated by the medical, behavioral, and social sciences.
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PMID:Male andropause: myth, reality, and treatment. 1215 25

Diabetes mellitus, caused by the malfunction of insulin-dependent glucose and lipid metabolism, presents with the classical triad of symptoms: polydypsia, polyuria, and polyphagia which are often accompanied by chronic fatigue and loss of weight. Complications of diabetes mellitus include retinopathy, nephropathy, neuropathy, and cardiovascular disease. Periodontal diseases are infections affecting the periodontium and resulting in the loss of tooth support. The association between diabetes mellitus and periodontitis has long been discussed with conflicting conclusions. Both of these diseases have a relatively high incidence in the general population (diabetes 1% to 6% and periodontitis 14%) as well as a number of common pathways in their pathogenesis (both diseases are polygenic disorders with some degree of immunoregulatory dysfunction). On the one hand, numerous reports indicate a higher incidence of periodontitis in diabetics compared to healthy controls, while other reports fail to show such a relationship. Clarification of this dilemma is occurring as the diagnostic criteria for periodontitis and diabetes mellitus improve, controlled studies with increased sample sizes are carried out, and the studies take into account major confounding variables that impact on the pathogenesis of both diseases. Current studies tend to support a higher incidence and severity of periodontitis in patients with diabetes mellitus. The overview looks at the bidirectional relationship between periodontitis and diabetes. An analysis of the National Health and Nutrition Examination Survey (NHANES) III data set confirms the previously reported significantly higher prevalence of periodontitis in diabetics than in non-diabetics (17.3% versus 9%). The analysis of the data also shows that the prevalence of diabetes in patients with periodontitis is double that seen in the non-periodontitis patients (12.5% versus 6.3%) and that this difference is also statistically significant. The pathogenesis of the 2 diseases is reviewed with an emphasis on common genetic and immune mechanisms. On the basis of the overview, 2 hypotheses for testing the relationship between periodontitis and diabetes are discussed. The first proposes a direct causal or modifying relationship in which the hyperglycemia and hyperlipidemia of diabetes result in metabolic alterations that may then exacerbate bacteria-induced inflammatory periodontitis. The second hypothesis proposes that a fortuitous combination of genes (gene sets) could result in a host who, under the influence of a variety of environmental stressors, could develop either periodontitis or diabetes or both.
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PMID:The relationship between periodontal diseases and diabetes: an overview. 1188 77

Building on the work of the late John Myers, MD, the author has used an intravenous vitamin-and-mineral formula for the treatment of a wide range of clinical conditions. The modified "Myers' cocktail," which consists of magnesium, calcium, B vitamins, and vitamin C, has been found to be effective against acute asthma attacks, migraines, fatigue (including chronic fatigue syndrome), fibromyalgia, acute muscle spasm, upper respiratory tract infections, chronic sinusitis, seasonal allergic rhinitis, cardiovascular disease, and other disorders. This paper presents a rationale for the therapeutic use of intravenous nutrients, reviews the relevant published clinical research, describes the author's clinical experiences, and discusses potential side effects and precautions.
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PMID:Intravenous nutrient therapy: the "Myers' cocktail". 1241 Jun 23

Psychological depression is shown to be associated with several aspects of coronary artery disease (CAD), including arrhythmias, myocardial infarction, heart failure and sudden death. The physiological mechanisms accounting for this association are unclear. Hypothalamic-pituitary-adrenal dysregulation, diminished heart rate variability, altered blood platelet function and noncompliance with medial treatments have been proposed as mechanisms underlying depression and cardiovascular disease. Recent evidence also suggests that reduced baroreflex sensitivity, impaired immune function, chronic fatigue and the co-morbidity of depression and anxiety may be involved in the relationship between depression and cardiovascular dysregulation. An experimental strategy using animal models for investigating underlying physiological abnormalities in depression is presented. A key to understanding the bidirectional association between depression and heart disease is to determine whether there are common changes in brain systems that are associated with these conditions. Such approaches may hold promise for advancing our understanding of the interaction between this mood disorder and CAD.
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PMID:Biological mechanisms in the relationship between depression and heart disease. 1266 98

This paper summarizes the associations between long workhours and health, with special attention for the physiological recovery and behavioral life-style mechanisms that may explain the relationship. The evidence for these mechanisms has not been systematically reviewed earlier. A total of 27 recent empirical studies met the selection criteria. They showed that long workhours are associated with adverse health as measured by several indicators (cardiovascular disease, diabetes, disability retirement, subjectively reported physical health, subjective fatigue). Furthermore, some evidence exists for an association between long workhours and physiological changes (cardiovascular and immunologic parameters) and changes in health-related behavior (reduced sleep hours). Support for the physiological recovery mechanism seems stronger than support for the behavioral life-style mechanism. However, the evidence is inconclusive because many studies did not control for potential confounders. Due to the gaps in the current evidence and the methodological shortcomings of the studies in the review, further research is needed.
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PMID:Long workhours and health. 1282 86

Obesity is a progressive disease of unwanted fat accumulation which has multiple, organ-specific pathological consequences. The manifestations of obesity occur within virtually every subspecialty of medicine or surgery and they interact importantly to accelerate the ageing process in many organs. Many of the hazards of obesity have multiple causes (e.g., diabetes, heart disease, stroke, colonic and breast cancer, urinary incontinence, tiredness, back pain, breathlessness). All of these conditions become more prevalent with age and are also more prevalent among overweight persons, particularly those with a central fat distribution marked by a high waist circumference. Hypertension may be caused or aggravated by weight gain. It is mediated by the physical demands of an expanded circulating volume and increased metabolic rate by metabolic mechanisms related to central fat distribution and the "metabolic syndrome", and to increased sodium consumption by overweight people (because they need more food to maintain a higher metabolic rate). Since body mass index (BMI) and waist circumference increase significantly with age there is an escalation of the burden of ill health from obesity with age. The best simple indicator of disease risk with obesity is the waist circumference since this identifies people who have a high body fat content and also those who have an increased intraabdominal accumulation of fat. The quantitative burden of ill health from overweight and obesity varies within different specialties, but up to 80% of type 2 diabetes or polycystic ovarian syndrome can be attributed to obesity. Obesity is the cause of sleep apnea syndrome in around 50% of cases and heart disease in perhaps 10-20% of cases. In Scotland 80% of people with existing cardiovascular disease are overweight compared with 57% of the general population. The financial burden to health services from overweight and obesity has been incompletely assessed, although it is estimated that around 4% of total health care budgets are attributable to people having BMI > 25 kg/m(2). This is similar to the entire cost of diabetes, epilepsy or major cancers. Obesity is therefore an extremely expensive disease based on these conservative estimates from limited evaluations. More general assessments show how obesity increases the amount of time taken off work, the number of drugs prescribed and the expenditure from social services support. Thus, obesity represents a huge burden not only on the individual patient physically, psychologically, socially and financially but also on families and careers and is a huge drain on health care resources. Overweight affects well over half of all adults worldwide, progressing to BMI > 30 kg/m(2) in around 20% outside subsistence rural communities. Its rapidly increasing prevalence now described as an epidemic demands major preventive measures, as well as better medical treatment for individuals affected.
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PMID:Obesity: burdens of illness and strategies for prevention or management. 1284 36

Subclinical hypothyroidism is associated with aspecific complaints such as tiredness, cognitive and depressive complaints, subtle disturbances in lipid values, an increased risk of cardiovascular disease, ovulatory dysfunction and a negative effect on foetal psychomotor development and pregnancy outcome. Subclinical hyperthyroidism is associated with atrial fibrillation, osteoporosis and dementia. Not enough prospective randomised studies with hard outcomes are available to provide evidence-based general recommendations. Therefore, the decision as to whether or not a patient should be treated needs to be made on an individual basis. For subclinical hypothyroidism it is advisable to consider treatment in the case of positive thyroid peroxidase antibody tests, a TSH concentration higher than 10 mU/l, the presence of one or more risk factors for cardiovascular disease, infertility on the basis of ovulatory dysfunction, and pregnancy. In the case of complaints of tiredness and certainly in the case of depression or cognitive dysfunction, a 3-month trial treatment can be considered. This leads to a decrease of the complaints in about 25% of cases. As negative effects are associated with the treatment, we advise an expectant approach in all other cases with a yearly monitoring of the TSH concentration. For subclinical hyperthyroidism it is advisable to consider treatment in the case of a nodular goitre, and especially in the case of atrial fibrillations. If subclinical hyperthyroidism persists in the absence of nodular thyroid disease, an expectant approach appears to be justified.
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PMID:[Subclinical functional disorders of the thyroid gland]. 1284 32

C-reactive protein (CRP) is an acute-phase reactant whose levels increase in response to a variety of inflammatory stimuli. Elevated levels in serum are observed after trauma, tissue necrosis, infection, surgery, and myocardial infarction and are associated with an increased risk of cardiovascular disease. CRP levels are also elevated in noninflammatory states, such as obesity, sleep disturbances, depression, chronic fatigue, aging, and physical inactivity. In this study, the performance of a highly sensitive CRP enzyme immunoassay was evaluated, along with common laboratory variables (specimen type, processing time, and storage conditions) that may influence measured blood concentrations of CRP. The measurement range of the assay was from 0.4 to 50 microg/liter. Total imprecision (coefficient of variation) ranged from 8.1 to 11.4%. CRP levels obtained with the enzyme immunoassay were highly correlated with those obtained with an automated immunonephelometric assay. Comparable results were obtained for plasma (heparin and EDTA treated) and serum samples, and levels were unaffected by delays in sample processing and storage temperature. CRP levels were also unaffected by up to seven freeze-thaw cycles. The median CRP concentration in healthy adults was determined to be 0.94 mg/liter, with a 95% working reference interval of 0 to 6.9 mg/liter. In view of these data, we recommend that serial serum or plasma samples for CRP should be stored at 4 degrees C for short periods of time or at -70 degrees C for longer periods and tested within the same run to minimize interassay variability.
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PMID:Analytical performance of a highly sensitive C-reactive protein-based immunoassay and the effects of laboratory variables on levels of protein in blood. 1285

Carnitine is a trimethylamine molecule that plays a unique role in cell energy metabolism. Mitochondrial betaoxidation of long-chain fatty acids, the major process by which fatty acids are oxidized, is ubiquitously dependent on carnitine. Control of mitochondrial beta-oxidation through carnitine adapts to differing requirements in different tissues. The physiological role of carnitine and its system in body composition is understood from insights into skeletal muscle metabolism, which converge into the metabolic heterogeneity of muscle fibers, and contractile properties that are correlated with phenotypes of resistance to fatigue. In skeletal muscle, the importance of the function of the carnitine system in the control and regulation of fuel partitioning not only relates to the metabolism of fatty acids and the capacity for fatty acid utilization, but also to systemic fat balance and insulin resistance. The carnitine system is shown to be determinant in insulin regulation of fat and glucose metabolic rate in skeletal muscle, this being critical in determining body composition and relevant raised levels of risk factors for cardiovascular disease, obesity, hypertension, and type 2 diabetes.
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PMID:The carnitine system and body composition. 1461 47

Respiratory failure is still an important complication of chronic obstructive pulmonary disease (COPD) and hospitalisation with an acute episode being a poor prognostic marker. However, other comorbid conditions, especially cardiovascular disease, are equally powerful predictors of mortality. The physiological basis of acute respiratory failure in COPD is now clear. Significant ventilation/perfusion mismatching with a relative increase in the physiological dead space leads to hypercapnia and hence acidosis. This is largely the result of a shift to a rapid shallow breathing pattern and a rise in the dead space/tidal volume ratio of each breath. This breathing pattern results from adaptive physiological responses which lessen the risk of respiratory muscle fatigue and minimise breathlessness. Treatment is directed at reducing the mechanical load applied to each breath, correcting specific precipitating factors, e.g. bacterial infection, and maintaining gas exchange. Both bronchodilators and oral corticosteroids can improve spirometric results in exacerbations of COPD and should be routinely offered to patients with respiratory failure. Controlled oxygen is still not always prescribed appropriately and high inspired oxygen concentrations can lead to severe acidosis by either worsening ventilation/perfusion mismatching and/or inducing a degree of hypoventilation. Ventilatory support using noninvasive ventilation has revolutionised the approach to these patients. Acute respiratory failure due to chronic obstructive pulmonary disease remains a common medical emergency that can be effectively managed. More attention should be focused on the prevention of these episodes and identifying the factors which cause early relapse.
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PMID:Respiratory failure in chronic obstructive pulmonary disease. 1462 Nov 14


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