Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Twelve of fourteen female patients with primary biliary cirrhosis, receiving vitamin D supplementation, exhibited unequivocal signs of osteoporosis but not of osteomalacia. Vitamin D treatment reproduced normal 25-hydroxyvitamin D levels in all but two patients and the 1,25 and 24,25-dihydroxyvitamin D metabolic pathways appeared to be unimpaired. A possible mechanism for the vitamin D resistant osteoporosis has been identified following the observation that, in those patients with severe cirrhosis, the circulating concentration of intact PTH was elevated. The increase in intact hormone appears to be at the expense of the carboxyl-regional PTH produced by hepatic Kupffer cell mediated cleavage of intact PTH. As a defect in Kupffer cell function is documented in primary biliary cirrhosis we postulate that the increased intact PTH/decreased carboxyl-regional PTH concentrations arise as a result of diminished Kupffer cell mediated cleavage. The reduced generation of cleaved PTH, due to this loss of Kupffer cell activity, would thus contribute to the development of osteoporosis in primary biliary cirrhosis.
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PMID:Hepatic osteodystrophy in primary biliary cirrhosis: a possible defect in Kupffer cell mediated cleavage of parathyroid hormone. 631 59

In a study of 56 alcoholics with liver cirrhosis, 18 (32%) had decreased bone density and low levels of serum 25-hydroxyvitamin D (25-OH-D) (less than 20 ng per ml). To compare the efficacy of vitamin D2 and 25-OH-D treatment in correcting the metabolic bone disease in alcoholic cirrhosis, the 18 patients were randomized in the following manner, in groups of six patients each: Group 1, control (received no supplemental vitamin D treatment); Group 2, given vitamin D2 (50,000 IU p.o.) two to three times weekly, and Group 3, treated with 25-OH-D (20 to 50 mg p.o.) daily as required to attain normal serum 25-OH-D levels. The study period lasted 6 to 12 months (mean, 10.7 months). Initial histomorphometric study of transiliac bone biopsy with double tetracycline labeling in nine patients in whom biopsy was feasible showed only osteoporosis without evidence of osteomalacia. By the end of the study, serum 25-OH-D levels in the control group (Group 1) raised slightly while showing marked improvement in Groups 2 and 3. Bone density results remained unchanged in control patients but demonstrated a significant increase in both treatment groups. Vitamin D2 and 25-OH-D were equally effective in increasing bone density measurements. Posttreatment biopsies were performed in three patients of Group 2 and two patients of Group 3. While the histomorphometric results in Group 3 were not conclusive, in Group 2 improvement in static measures of bone remodeling was noted. Osteoporosis is the usual form of bone disease in alcoholic cirrhosis and a response to either vitamin D2 or 25-OH-D treatment is suggested.
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PMID:Metabolic bone disease in alcoholic cirrhosis: a comparison of the effect of vitamin D2, 25-hydroxyvitamin D, or supportive treatment. 660 83

We describe the association between transient osteoporosis of the hip (TOH) and liver cirrhosis in a female patient. The clinical course, radiographic and scintigraphic features were similar to cases of TOH described previously. The pathogenesis of this syndrome is unknown and we suggest there may be a relationship between the hemodynamic changes common in cirrhotic patients and in pregnant women and the development of TOH.
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PMID:Transient osteoporosis of hip joint with liver cirrhosis. 672 22

Fifteen female patients with primary biliary cirrhosis were evaluated for vitamin D status and evidence of metabolic bone disease. Full-thickness iliac crest bone biopsy specimens with histomorphometric analysis after double tetracycline labeling were performed before and after 1 yr of treatment with oral 25-hydroxyvitamin D (100 micrograms/day). Initially, serum 25-hydroxyvitamin D levels were low (less than 15 ng/ml) in 11 of the 15 patients and were increased to normal (greater than 25 ng/ml) in all patients within 3 mo. Serum parathyroid hormone levels were low normal or not detectable in all patients and did not change with therapy. No patient had a fracture during the treatment. No evidence of osteomalacia was found initially or in follow-up study in any patient. Follow-up histomorphometric analysis at the end of the 1-yr treatment showed that bone volume decreased during the study interval despite therapy (p less than 0.001). Photon beam densitometry confirmed the loss in trabecular density of the radius over the study interval (p less than 0.03). The mean fractional osteoid surface was not increased initially and did not change with therapy. The mean linear bone appositional rate as measured by double tetracycline labeling was not decreased initially and did not change with therapy. It was concluded that in moderate to severe primary ciliary cirrhosis, initial 25-hydroxyvitamin D levels are low and are rapidly corrected by oral 25-hydroxyvitamin D. These patients have significant osteoporosis which progresses despite 25-hydroxyvitamin D.
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PMID:Bone disease in primary biliary cirrhosis: histologic features and response to 25-hydroxyvitamin D. 697 27

A recently developed gel-filtration technique allows protein-bound calcium fractions to be separated and quantitated; the protein is separated under physiological conditions of pH, temperature, and concentrations of Na, Mg, and Ca to assure that the calcium-proteinate equilibrium is not disturbed. We used this gel-filtration technique to study the protein-bound calcium fractions in 18 patients with hyperparathyroidism, multiple myeloma, diabetes, osteoporosis, or liver cirrhosis. We calculated the amount of calcium bound per gram of protein for each of the three protein peaks and the intrinsic association constant (Ka) for calcium/albumin. Results with the multiple myeloma patients (three IgG, one IgA) indicated that IgG did not bind calcium appreciably, that IgA had about the same affinity as albumin for Ca, and that Ka was slightly low for one patient of the IgG type (79 L/mol) and normal for the other three myeloma patients (106, 90, and 91 L/mol). Results for patients with the other diseases were also essentially normal, except for the osteoporesis patients (two men, one woman), whose Ka values (69, 75, and 73 L/mol) were lower than normal.
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PMID:Clinical studies of protein-bound calcium in various diseases. 707 38

A prospective survey of radiological bone and joint changes was undertaken in 42 patients with primary biliary cirrhosis (PBC) and 23 patients with alcoholic or cyptogenic cirrhosis who formed a control population. PBC patients were commonly found to have hypertrophic osteoarthropathy (38%), joint erosions (31%) and osteoporosis, these results being significantly different from the control group. Hypertrophic osteoarthropathy most frequently affected the first metacarpal and was rarely associated with finger clubbing or clinical symptoms. Joint erosions were most evident in the hands, often associated with a positive rheumatoid factor but only accompanied by symptomatic arthritis in four cases. Patients with PBC show a high prevalence of symptomless bone and joint changes which may become manifest clinically only as the disease progresses; radiography of the hands is recommended as a screening test for these changes.
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PMID:A prospective survey of radiological bone and joint changes in primary biliary cirrhosis. 723 12

In the last decade our knowledge on vitamin D has grown considerably due to the identification of numerous steps of the vitamin D metabolism and to the isolation and synthesis of active metabolites. Therefore a lot of progress had been made in the understanding of the physiological mechanism of regulating blood calcium homeostasis and of the pathogenesis of many related diseases. The diseases connected to the calcium-phosphate metabolism requiring treatment with vitamin D and its metabolites are numerous. The basis for a rational therapeutic approach is provided by the new concepts on the pathogensis of the various diseases and on the pharmacology of vitamin D metabolites. Pure vitamin D depletion may be controlled with physiological doses of vitamin D. Administration of 25-OHD3 is advisable in chronic hepatitis or cirrhosis accompanied by a defect of 25-hydroxylation and/or intestinal loss of the metabolite. A defect in the synthesis of 1,25-(OH)2D3, the metabolite of renal origin, is present in an interesting and wide group of diseases. These are: chronic renal insufficiency, hypoparathyroidism, hypocalcemic D-resistant rickets and senile or post-menopausal osteoporosis. In the treatment of this group of diseases, which sometimes is of a preventive nature, it is preferable to administer the dihydroxylated metabolites of vitamin D. The results of treatments and prevention in a few selected conditions are reported.
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PMID:[Physiopathological and therapeutic aspects of vitamin D (author's transl)]. 724 90

Copper is an essential trace element with a well established mechanism for maintaining balance of the metal in the body, which is controlled by at least two genes. Disruption of one gene on the X chromosome determines a defect in the process of copper absorption, with consequent deficiency of available copper at the cellular level. This results in abnormalities of collagen formation and brain maturation, leading to early death. As yet there is no effective treatment. Disruption of the other copper controlling gene, located on chromosome 13, is associated with accumulation of excess copper in the body, first in the liver leading to cirrhosis, and then in the brain giving rise to destruction of the centre of motor control and, frequently, changes in personality. Copper excess can also cause renal damage, osteoarticular changes and joint pains. If the renal lesion leads to calcium loss in the urine and other tubular defects, there may be osteoporosis or, occasionally, osteomalacia with pathological fractures. In this disease, the abnormal stores of copper can be mobilised with chelating agents or depleted by the administration of zinc salts or thiomolybdate. This usually, but not invariably, leads to improvement or even complete reversal of symptoms. Brain lesions, as demonstrated by computed tomography or magnetic resonance imaging, may also resolve. The mechanism of this phenomenon is obscure but suggests that the long held doctrine that there is no recovery in the central nervous system may have to be reviewed.
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PMID:Copper: not too little, not too much, but just right. Based on the triennial Pewterers Lecture delivered at the National Hospital for Neurology, London, on 23 March 1995. 884

Seventy-two long-surviving liver transplant recipients were evaluated prospectively, including a baseline allograft biopsy for weaning off of immunosuppression. Thirteen were removed from candidacy because of chronic rejection (n = 4), hepatitis (n = 2), patient anxiety (n = 5), or lack of cooperation by the local physician (n = 2). The other 59, aged 12-68 years, had stepwise drug weaning with weekly or biweekly monitoring of liver function tests. Their original diagnoses were PBC (n = 9), HCC (n = 1), Wilson's disease (n = 4), hepatitides (n = 15), Laennec's cirrhosis (n = 1), biliary atresia (n = 16), cystic fibrosis (n = 1), hemochromatosis (n = 1), hepatic trauma (n = 1), alpha-1-antitrypsin deficiency (n = 9), and secondary biliary cirrhosis (n = 1). Most of the patients had complications of long-term immunosuppression, of which the most significant were renal dysfunction (n = 8), squamous cell carcinoma (n = 2) or verruca vulgaris of skin (n = 9), osteoporosis and/or arthritis (n = 12), obesity (n = 3), hypertension (n = 11), and opportunistic infections (n = 2). When azathioprine was a third drug, it was stopped first. Otherwise, weaning began with prednisone, using the results of corticotropin stimulation testing as a guide. If adrenal insufficiency was diagnosed, patients reduced to < 5 mg/day prednisone were considered off of steroids. The baseline agents (azathioprine, cyclosporine, or FK506) were then gradually reduced in monthly decrements. Complete weaning was accomplished in 16 patients (27.1%) with 3-19 months drug-free follow-up, is progressing in 28 (47.4%), and failed in 15 (25.4%) without graft losses or demonstrable loss of graft function from the rejections. This and our previous experience with self-weaned and other patients off of immunosuppression indicate that a significant percentage of appropriately selected long-surviving liver recipients can unknowingly achieve drug-free graft acceptance. Such attempts should not be contemplated until 5-10 years posttransplantation and then only with careful case selection, close monitoring, and prompt reinstitution of immunosuppression when necessary.
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PMID:Weaning of immunosuppression in long-term liver transplant recipients. 783 42

This article reviews osteoporosis (OP) in adults with chronic liver disease. OP in this setting is characterized in general by low bone turnover. The pathogenesis is unclear but is probably not related to vitamin D abnormalities. Patients at high risk of OP include those with evidence of cirrhosis, hypogonadism, overt calcium malabsorption, steroid therapy and choleostatic liver disease (particularly primary biliary cirrhosis). OP is best managed by adequate calcium intake, regular weight bearing exercise, and the avoidance of alcohol and tobacco smoking. There is probably no reason for vitamin D supplementation. Hormonal replacement therapy when necessary is indicated in males and should be considered in females. Finally, liver transplantation has the potential to improve or stabilize OP in the median term, although it is associated with significant short-term deterioration.
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PMID:Osteoporosis in chronic liver disease: pathogenesis, risk factors, and management. 785 Oct 1


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