Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Parathormone (PTH) excess limits renal bicarbonate reabsorption. This may aggravate the acidosis in patients with renal insufficiency and secondary hyperparathyroidism. Why parathormone, the primary action of which is thought to be stabilization of the inonized fraction of calcium, affects acid-base balance remains uncertain. Parathormone not only promotes the release of calcium from bone but also mobilizes salts, including bicarbonate and phosphate. Accumulation of these anions in the extracellular fluid would limit the ionization of calcium. Teleologically it is not unexpected to find that, coincident with evolution of a mechanism which permits rapid mobilization of calcium from bone, a system had to develop which removed the byproducts of bone dissolution. If this concept is valid, parathormone-induced depression of renal bicarbonate reabsorption in uremia represents an undesired side effect of an adaptive mechanism. This would extend Bricker's "trade-off" hypothesis which ascribes metabolic bone disease due to PTH-induced phosphate loss to include metabolic acidosis resulting from diminished renal bicarbonate regeneration. Parathyroidectomy or phosphate restriction have been proposed for correction of the side effects of secondary hyperparathyroidism. These therapeutic manipulations cannot be recommended for general use. A more rational apprach for prevention of secondary hyperparathyroidism is the combined use of phosphate restriction with a short-acting vitamin D derivative.
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PMID:Parathyroid hormone and the regulation of acid-base balance. 110 50

Over the last 25 years, the perceived clinical spectrum of primary hyperparathyroidism (HPT) has changed dramatically from a disorder characterized by severe bone and renal disease to one typically manifested by few or mild symptoms and little evidence of organ damage. Reasons for this change in spectrum include changing demographics (primary HPT is primarily a disease of the middle-aged and elderly), diffusion of medical knowledge leading to a higher index of suspicion, and improved clinical laboratory technology (especially inexpensive and accurate determination of serum calcium and parathyroid hormone). In the first 343 cases of primary HPT seen at the Massachusetts General Hospital, 57% had renal stones, 23% had hyperparathyroid bone disease, and less than 1% had no symptoms. By contrast, studies dating from the availability of automated serum calcium measurement found renal stones and hyperparathyroid bone disease in less than 5% of cases, and about half of cases had few or no symptoms. Most patients with primary HPT today have mild, nonspecific symptoms, such as weakness, fatigue, and mental depression, and such signs as arterial hypertension and osteopenia, and detection of their hypercalcemia is generally serendipitous. The mildness and slow progression seen in many cases of primary HPT has resulted in much controversy about appropriate management.
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PMID:Clinical spectrum of primary hyperparathyroidism: evolution with changes in medical practice and technology. 176 71

Osteoporosis, a metabolic bone disease most prevalent in older adults, is a major public health problem. Although management of osteoporosis through diet, exercise, and medication has improved, little is known about the psychosocial consequences of this disabling disease. In an attempt to identify patient characteristics that would provide physicians with insight into appropriate management styles for older osteoporotics, we assessed 103 patients with osteoporosis for their health locus of control (HLOC) orientation. We examined the relationship between HLOC and patient outcomes after participation in the Duke University Preventive and Therapeutic Program for Osteoporosis (DUPATPO) to determine whether HLOC was associated with functioning after program participation. More specifically, we asked whether internal or external HLOC was associated with decreases in depression, psychiatric symptoms, and stress symptoms, or with increases in self-esteem, exercise, and disease knowledge. We have shown in our earlier work (Gold et al, J Am Geriatr Soc 1989; 37:417) that program participation is associated with improved functioning in older adults. We now asked whether knowledge of a patient's HLOC would help predict these improvements. A comparison group (ie, older osteoporotics who did not participate in DUPATPO) was also assessed for HLOC to examine the possible association between HLOC and health behaviors regardless of the DUPATPO intervention. Our findings indicate that HLOC provided little useful information regarding patient outcomes. Although improvements were seen in the mental health of program participants, no association between these improvements and HLOC could be found.
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PMID:Osteoporosis in late life: does health locus of control affect psychosocial adaptation? 206 32

Sixty-one consecutive patients were examined to determine the current mode of presentation of primary hyperparathyroidism (pHPT). Of these patients, 37.7% were asymptomatic, and the initial indication of pHPT was hypercalcemia, which was found unexpectedly on biochemical screening of the serum in elderly patients. Hypertension was twice as common among patients with pHPT as in the general population (36.1%). The next most common presentations were urinary calculi (18%) and mental depression (18%). The most useful discriminant laboratory tests were serum calcium, phosphorus, chloride, and parathormone (PTH). The calculated coefficient of correlation of PTH to land weight was high (r = 0.571, p less than 0.001). There was very significant correlation between PTH and seriousness of bone disease (r = 0.620, p less than 0.001). After parathyroidectomy, 3.3% of patients remained hypercalcemic, 93% were normocalcemic, and 1.6% were hypocalcemic.
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PMID:Clinical and biochemical features in primary hyperparathyroidism. 291 78

X-linked hypophosphatemia is a genetic bone disease in humans and mice. Two closely linked mutations in mice, Hyp and Gy, cause low plasma phosphate and a rachitic and osteomalacic bone disease. Because of the controversy as to whether Gy is a good model for X-linked hypophosphatemia, the phenotypic severity of these two mutations was compared in both sexes and on two genetic backgrounds. The depression in plasma levels of phosphate was similar in all 10-week-old mutant mice. Male Hyp mice and heterozygous female Hyp mice were affected with similar severity in terms of reduced tail growth, shortened femora, reduced femoral mineral content, and abnormal mineral composition of the femoral matrix. In contrast, male Gy mice did not survive on the C57BL/6J background and were more severely affected than female Gy mice on the B6C3H background. The hybrid B6C3H background ameliorated the bone disease compared with the inbred C57BL/6J background for both mutant strains. There was no evidence of change in the plasma levels of 1,25-dihydroxyvitamin D, duodenal level of vitamin D-dependent calcium-binding protein, or urinary level of calcium in these adult mutant mice. In summary, Gy mice have a sexual dimorphism not present in Hyp mice. These two genes may indicate the presence of multiple gene loci in the human disease, with multiple proteins involved in the pathophysiology of the bone disease.
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PMID:Femoral abnormalities and vitamin D metabolism in X-linked hypophosphatemic (Hyp and Gy) mice. 785 1

The biochemistry and function of vanadate and its possible role in health as well as in disease remains one of the most fascinating stories in biology. This review has surveyed the pertinent literature regarding its effect in the normal kidney and other tissues. While inhibition of the Na(+)-K+ ATPase enzyme was the first described and perhaps the most widely studied, the element clearly has other actions. Speculation as to whether vanadate is a part of the pathogenesis of the 'uremic syndrome', acquired cystic kidney disease, depression, and bone disease should provoke the clinical investigator and the basic researcher alike to a myriad of new and intriguing experiments.
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PMID:Biochemistry and pathophysiology of vanadium. 807

Osteoporosis has obvious physical and functional consequences such as kyphosis, restricted range of motion, and pain. What are not so obvious are the psychosocial sequelae that result from this metabolic bone disease. Many patients in the initial phases of the disease express substantial anxiety, especially about the possibility of future fractures and physical deformity. As the disease progresses, depression can become profound for those who experience hip or multiple vertebral fractures. The effects of the chronicity of osteoporosis, its disabling and disfiguring aspects, and the chronic postural pain that develops as time passes challenge even the most stable individuals. In addition, osteoporosis has substantial impact on interpersonal relationships and social roles. The dependency created by this disease affects close relationships, because the patient with osteoporosis cannot reciprocate in social support. Today's older women find the restrictions of the disease socially devastating. These women, unlikely to work in the labor force, took pride in their roles of housekeeper and cook. Unfortunately, severe osteoporosis can force women to relinquish even these social roles, leaving them with no source of self-esteem or accomplishment. In all, osteoporosis is devastating both psychologically and socially.
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PMID:The clinical impact of vertebral fractures: quality of life in women with osteoporosis. 877 86

Many studies document bone loss at diagnosis in patients with PHPT (including mild PHPT) that is greater than would be expected in comparable persons without this condition. However, there is no general agreement regarding the severity of bone mass loss in these patients and the rate at which it progresses. A few studies suggest that such accelerated osteoporosis may be self-limited, with patients showing no further decline in BMD after diagnosis. There is insufficient evidence to conclude that PTH-related bone loss is associated with an increased risk of fracture. The few studies that have evaluated the risk of fracture in these patients are conflicting. Some evidence also suggest that, like bone loss in these patients, fracture risk may change during the course of the disease. One study found that patients with PHPT (including those with mild hypercalcemia) were more likely than matched controls to have a history of fractures prior to diagnosis, but that both groups had similar rates of fractures during followup. Moreover, the studies of fractures suffer from several limitations, such as nonrandomization of patients, different definitions of vertebral fractures, small study populations, and short followup times. There is also insufficient evidence to determine the effect of parathyroidectomy on the incidence of fractures in patients with mild PHPT, partly because the natural history of this condition is incompletely understood. Although studies demonstrate that patients with PHPT gain bone mass following parathyroidectomy, the bone reparation is incomplete and bone mass density remains below normal, even though the hyperparathyroidism is cured. Currently, decisions to perform parathyroidectomy are based on signs and symptoms of bone disease, metabolically active renal stones, decreased renal function, fatigue and/or depression, and high levels of serum calcium. Although the use of bone mass measurements has been advocated to aid clinical decisions regarding the risks and benefits of surgery, specific bone changes that indicate the need for parathyroidectomy have not been clearly established. There are virtually no prospective data that evaluate decisions to operate based upon bone mass measurements nor randomized clinical trials comparing the outcome of surgically treated patients with those who have not had surgery. Based on the literature, bone mass measurements cannot predict who among asymptomatic patients will require parathyroidectomy. There is some evidence that nonsurgically treated patients and those who remained hypercalcemic after unsuccessful surgery lost bone at the same percentage rate as normal control subjects.
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PMID:Bone densitometry: patients with asymptomatic primary hyperparathyroidism part I. Technical report. 893 32

From June 1994 to June 1996, 18 fledgling American crows (Corvus brachyrhynchos brachyrhynchos) from multiple locations on Long Island, New York, were presented with signs of metabolic bone disease characterized by folding fractures of the proximal tibiotarsus. Plasma alkaline phosphatase levels were elevated, and the calcium/phosphorus ratio and 25-hydroxycholecalciferol (25-(OH)D3) levels were decreased. The histopathologic diagnosis was parathyroid hyperplasia and generalized osteodystrophia fibrosa. A diet low in bioavailable calcium and/or vitamin D3 was the probable cause. Also, exposure to xenobiotics could have contributed to the depression of 25-(OH)D3 levels.
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PMID:Nutritional secondary hyperparathyroidism in free-living fledgling American crows (Corvus brachyrhynchos brachyrhynchos). 1036 50

Pruritus, fatigue and metabolic bone disease represent three major extrahepatic manifestations of chronic cholestatic liver disease that considerably affect the patient's quality of life. The present article reviews pathogenetic aspects of and current therapeutic approaches to extrahepatic manifestations of cholestatic liver disease. Pathogenesis of pruritus of cholestasis remains poorly understood. The involvement of putative peripherally acting pruritogens, such as bile acids or endogenous opioids, is being discussed. More recently, central mechanisms, including an increased central opioidergic tone and pertubations in the serotonergic system have been proposed. Treatment of the underlying disease is beneficial also for the control of cholestasis-associated pruritus. Current therapeutic recommendations include ursodeoxycholic acid, cholestyramine, rifampicin and opioid antagonists. Liver transplantation may be indicated when severe pruritus is refractory to medical treatment. Fatigue is being recognized as the most frequent and one of the most disabling complaints in chronic cholestasis. Fatigue is presumably of central origin and its association with other neuropsychiatric disorders (e.g. depression, obsessive-compulsive disorders) is consistent with defective central neurotransmission. No specific therapies are currently available and a healthy lifestyle, regular sleep and avoidance of unnecessary stress and other precipiting factors are recommended. Antidepressant therapy may be warranted in selected patients. Osteopenia and osteoporosis are common in chronic cholestatic liver disease, whereas osteomalacia is rare. The pathophysiology of cholestasis-associated metabolic bone disease is regarded as multifactorial. Therapeutic recommendations include regular exercise, calcium and vitamin D supplementation in late stage disease, hormone replacement therapy in postmenopausal women and bisphosphonates.
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PMID:Extrahepatic manifestations of cholestasis. 1216 13


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