Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024523 (malabsorption)
 7,319 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To investigate the pathogenesis of hepatic osteodystrophy (HOD) in parenchymal liver disease, we developed a laboratory model in animals using carbon tetrachloride (CCl4) and thioacetamide. Biochemical and histological parameters in the model were measured. In rats with both chronic non-cirrhotic liver injury and CCl4-induced cirrhosis, tibial bone volume was significantly lower than in controls. In CCl4-treated cirrhotic rats, the osteoid volume decreased while the urinary calcium/creatinine ratio increased. In all CCl4-treated rats, bone volume was significantly correlated with both the serum albumin concentration and the number of goblet cells reflecting intestinal villous atrophy. The serum concentration of vitamin D metabolites was not correlated with bone volume. Whole body retention of 47Ca was significantly lower in CCl4-treated cirrhotic rats than in controls. Furthermore, the bone volume in thioacetamide-treated cirrhotic rats was significantly lower than in controls. These data demonstrate that chronic parenchymal liver injury itself causes osteoporosis (i.e. HOD) due to a combination of low bone formation rates and high resorption rates, that HOD begins at the stage of chronic non-cirrhotic liver injury, that bone volume in HOD parallels liver damage and that the principal pathogenesis of HOD seems to be intestinal Ca malabsorption due to lower serum albumin and villous atrophy, while serum levels of vitamin D metabolites have little influence on the pathogenesis of HOD.
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PMID:Bone changes and mineral metabolism disorders in rats with experimental liver cirrhosis. 903 34

The interposition of a bowel segment as a bladder substitute into the urinary tract may result in impaired calcium metabolism. We studied 25 male patients (aged 45 to 77 yr) who had undergone a Vescica Ileale Padovana (VIP) reconstruction following cystectomy 29 to 75 mo before. Bone mineral density of the spine and femur was measured by dual x-ray absorptiometry. Blood and 24-h urine samples were analyzed for the main parameters of bone metabolism. Sixteen healthy men were enrolled as a control group. Although blood pH did not differ between patients and control subjects, VIP subjects showed lower levels of plasma HCO3- (P < 0.005) and higher serum chloride (P < 0.001). Bone alkaline phosphatase was higher (P < 0.001), and urine calcium, phosphate, and creatinine levels were lower in VIP patients (P < 0.01, P < 0.01, and P < 0.05, respectively). Bone mineral density at the femoral neck (P < 0.03) and Ward's triangle (P < 0.05) was decreased in VIP patients. When subdivided according to time since operation, patients who had the ileal neobladder implanted for a shorter period of time showed lower blood pH (P < 0.03) and urine calcium (P < 0.05) levels and higher urinary hydroxyproline (P < 0.02). Duration of the ileal neobladder was positively correlated with PTH (r = 0.46, P < 0.03) and blood pH (r = 0.47, P < 0.02). Furthermore, pH values were positively correlated with urine calcium (r = 0.48, P < 0.02). In conclusion, in patients with ileal neobladder, a mild metabolic acidosis is responsible for an increased bone turnover and lower bone mass. Moreover, a decrease over time in the absorption capacity of the ileal pouch might result in calcium malabsorption, which represents an additional risk factor for reduced bone mass in these patients.
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PMID:Bone density and skeletal metabolism in patients with orthotopic ileal neobladder. 933 83

Although about 25% of all hip fractures occur in men, little is known about the pattern of their age-related bone loss and its main determinants. The aim of this cross-sectional study was to evaluate the age-related changes of intestinal calcium absorption, bone mass, and bone turnover in normal men. In 70 normal males (age 17-91 years), we measured spinal and forearm bone density (FBD) (by DXA), fractional intestinal calcium absorption (by oral test), serum immunoreactive parathyroid hormone (PTH), dietary calcium intake (diet records), biochemical markers of bone turnover (serum alkaline phosphatase (ALP), osteocalcin, urine calcium, creatinine, and hydroxyproline), and 1,25(OH)2D3 serum levels. Vertebral bone density (VBD) showed a modest decline before age 50 and a greater decline after age 50, whereas FBD presented a significant decrease with advancing age starting at age 40, suggesting a predominant age-related cortical bone loss. Intestinal calcium absorption (47CaFA) and serum 1,25(OH)2D3 also presented an age-related decline similar to FBD. Simple correlation analysis revealed that age was significantly related to 47CaFA (r = 0.60), calcium intake (r = 0.32), VBD and FBD (r = 0.79 and 0.63, respectively), serum 1,25(OH)2D3 (r = 0.69), and serum iPTH (r = 0.72). No significant correlation was found between age and biochemical markers of bone remodeling. Partial correlation and stepwise variable selection analyses, using 47CaFA and bone mass as dependent variables, showed that in normal males, serum 1,25(OH)2D3 and dietary calcium intake were the main contributors (64%) to 47CaFA variability, whereas only age accounted for 63% of VBD and age and dietary calcium accounted for 45% of FBD variability. These results indicate that bone loss in men accelerates after age 50 years and that among other factors, intestinal calcium malabsorption and 1,25(OH)2D3 serum levels play a role.
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PMID:Age-related decline of bone mass and intestinal calcium absorption in normal males. 970 22

Bone mineral density (BMD) in cystic fibrosis (CF) patients falls progressively below normal with advancing age, in part due to steroid administration, low levels of sex hormones, chronic inflammatory disease, physical inactivity, and chronic malabsorption of calcium and/or vitamin D. The purpose of this study was to compare the fractional absorption of (45)Ca and urinary excretion of calcium in CF subjects and normal controls following a high-calcium breakfast containing (45)Ca. Seven young men and 5 young women with CF with pancreatic insufficiency were studied on two separate occasions, with and without administration of pancreatic enzymes. Eleven healthy young adults with normal BMD measurements served as controls. Mean T-scores at the lumbar spine and femur were significantly lower in the CF subjects (p<0.002). Following baseline, fasting collections, timed serum and urine samples were obtained for 5 h after the meal. Fractional absorption (FA) of (45)Ca was estimated by the method of Marshall and Nordin. At baseline, CF subjects had lower mean serum 25-hydroxyvitamin D, calcium and albumin values (p<0.03 for each), slightly, but not significantly (p = 0.12), lower albumin-corrected calcium values, equivalent serum 1, 25-dihydroxyvitamin D values and a trend toward a higher mean serum parathyroid hormone (PTH) value (p = 0.10). Without pancreatic enzymes, CF subjects showed significantly impaired calcium absorption (5 h FA: 11.8 +/- 0.5 for controls vs 8.9 +/- 0.2 for CF subjects, p = 0.02) and excretion (4 h excretion: 0.20 +/- 0.08 mg Ca/mg creatinine for controls vs 0.16 +/- 0.09 mg Ca/mg for CF subjects, p = 0.025). Addition of pancreatic enzymes did not fully compensate for this deficiency. In addition, CF patients had higher serum PTH values after a high-calcium meal (p = 0.03), suggesting mild secondary hyperparathyroidism. Altered calcium homeostasis is likely to be a factor in the development of bone disease in CF patients.
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PMID:Altered calcium homeostasis in adults with cystic fibrosis. 1050 88

Urolithiasis is uncommon in adolescence and rare in early childhood. In pediatric populations, congenital urinary tract anomalies associated with stasis and infection, idiopathic urolithiasis (adolescents), and nephrocalcinosis (premature infants) account for the majority of urolithiasis patients. Inborn errors of metabolism, such as the primary hyperoxalurias, are rare causes of urolithiasis in childhood. We report six children (mean age at symptom onset 1.3 years; range 0.32-4.1 years) with moderate hyperoxaluria (mean 1.10 +/- 0.58 mmoL/1.73m2 per day; range 0.69-2.19 mmoL/1.73m2 per day). Urolithiasis was present in four. Stones from two children were comprised of calcium oxalate dihydrate. Calcium oxalate crystalluria was seen in two of the patients. Findings included a mean urine calcium concentration of 6.61 +/- 2.28 mg/kg per day, urine citrate of 925.5 +/- 291.29 mg/g of creatinine per day, and mean renal clearance of 99.83 +/- 23.27 mL/min. All children were born full term, none was receiving diuretics, and none had recurrent urinary tract infections. Secondary causes of hyperoxaluria, including dietary oxalate excess, pyridoxine deficiency, and malabsorption, were excluded. Urine glycolate and glycerate were normal in all patients. In one hyperoxaluric member of each sibship, hepatic alanine-glyoxylate aminotransferase and D-glycerate dehydrogenase/glyoxylate reductase activity were normal. The clinical and biochemical features of these children are unlike those in previously recognized hyperoxaluric states. Thus, our description of a separate hyperoxaluric entity, referred to as unclassified hyperoxaluria.
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PMID:Hyperoxaluria and urolithiasis in young children: an atypical presentation. 1060 14

Oral ganciclovir has been used as prophylaxis and therapy against cytomegalovirus in patients with HIV infection and following organ transplantation. Oral ganciclovir has clear practical advantages over intravenous ganciclovir but has a relatively low bioavailability and this may be problematic in at-risk patients with malabsorption. The bioavailability and therefore therapeutic potential of oral ganciclovir in cystic fibrosis (CF) patients post-lung transplant (LT) might be expected to be inadequate given the high incidence of malabsorption in these patients. An 8 h pharmacokinetic study was performed in 12 CF patients 160 +/- 122 days post-transplant who had been taking 1 g oral ganciclovir tds for 3 days with food (plus normal enzyme supplements). Mean (range) serum creatinine was 150 Imol/L (70-280). Blood was sampled at 0.5, 1, 2, 3, 4, 6 and 8 h post-final dose. Plasma was stored at -20 degrees C and later analysed by highperformance liquid chromatography. Mean peak concentration (C(max)) was 4.8 mg/L (0. 96-12.8), mean minimum concentration (C(min)) was 3.6 mg/L (0.78-11. 7) and mean area under the curve (AUC) was 35.4 mg.8 h/L (8-99). C(max), C(min) and AUC correlated significantly with one another (P < 0.001) as well as with serum creatinine and creatinine clearance (P < 0.01). When corrected for alterations in renal function, plasma oral ganciclovir levels are as predicted for other transplant populations. Three days of oral ganciclovir results in therapeutically useful plasma drug levels in the CF LT population, despite a background of general malabsorption. C(max), C(min) and AUC are highly correlated, allowing for the possibility of steady-state drug monitoring to confirm that the recommended dosing algorithm produces appropriate plasma levels.
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PMID:Pharmacokinetic assessment of oral ganciclovir in lung transplant recipients with cystic fibrosis. 1074 29

A squirrel monkey (Saimiri sciureus) presented with wasting, vomiting and diarrhoea. Haematology revealed elevation of creatinine phosphokinase, lactic dehydrogenase, alanine aminotransferase, amylase and lipase, together with azotaemia and hypoalbuminaemia. Prominent findings were chronic pancreatitis with acinar and ductal plugs, granulomatous and necrotizing peripancreatic steatitis, degenerative myopathy, testicular atrophy, candidiasis and bacterial necrotizing glossitis. Antioxidant analyses revealed low concentrations of serum vitamin E (and apparently A), hepatic selenium and hair zinc. Pancreatitis may have caused malabsorption and maldigestion, associated with deficiency of multiple antioxidants.
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PMID:Antioxidant status in a squirrel monkey (Saimiri sciureus) with chronic pancreatitis and degenerative myopathy. 1103 77

A component of ATP, phosphate is at the hub of the energy-related mechanisms operative in muscle cells. Together with calcium, phosphate is involved in bone tissue mineralization: thus, a chronic alteration in the metabolism of phosphate can induce bone and joint disorders. Diagnosis of chronic hypophosphatemia. Serum phosphate, calcium, and creatinine should be assayed simultaneously. Serum calcium is increased in hypophosphatemia caused by hyperparathyroidism and decreased in osteomalacia. Urinary phosphate excretion should be measured in patients with a normal serum calcium level and a serum phosphate level lower than 0.80 mmol/L. A decrease in urinary phosphate excretion to less than 10 mmol/24 h strongly suggests a gastrointestinal disorder, such as malabsorption, antacid use, or chronic alcohol abuse. In patients with a urinary phosphate excretion greater than 20 mmol/24 h, the maximal rate of tubular reabsorption of phosphate (TmPO4) and the ratio of TmPO4 over glomerular filtration rate (GFR) should be determined to look for phosphate diabetes. Manifestations and causes of phosphate diabetes in adults. Moderately severe phosphate diabetes in adults manifests as chronic fatigue, depression, spinal pain, and polyarthralgia, with osteoporosis ascribable to increased bone resorption. Although many cases are idiopathic, investigations should be done to look for X-linked vitamin D-resistant rickets missed during childhood, a mesenchymatous tumor, or Fanconi's syndrome with renal wasting of phosphate, glucose, and amino acids. Management of phosphate diabetes. Phosphate supplementation and, in patients with normal urinary calcium excretion, calcitriol produce some improvement in the symptoms and increase the bone mineral density. Whether dipyramidole is clinically effective remains unclear.
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PMID:Phosphate, the renal tubule, and the musculoskeletal system. 1139 20

From July 1999 to December 2002, a total of 27 baboons underwent transplantation with human decay accelerating factor (hDAF) transgenic porcine kidneys. The immunosuppressive protocol included combinations of 1 or more of the following immunosuppressive agents: cyclosporine, TPC, cyclosphophamide, methylprednisolone, GAS914 (a polymeric alpha-Gal), rabbit antithymocyte serum (RATS), and rapamycin derivative (RAD). The animals were followed up clinically with monitoring of renal function based on daily creatinine and urinary output. Histopathological examination of the tissue samples was performed after paraffin embedding. Electron microscopy was performed on occasion. All pathology was read blindly with a semiquantitative scoring method to assess the presence or absence of histological features of xenotransplant rejection. Mean survival time was 20.7 days (range, 4-75 days) with 15 animals dying of classic humoral rejection and 12 dying of complications unrelated to rejection. The most frequent complications were as follows: chronic diarrhea with malabsorption, bleeding diathesis, infections, and drug toxicity. Irrespective of the immunosuppressive regimen, a significant number of baboons (10) developed untreatable diarrhea and gastrointestinal bleeding. Samples of their gastrointestinal tracts showed evidence of varying degrees of necrotizing vasculitis with immunoglobulin (Ig)G,IgM, and fibrin deposition. The survival in pig-to-baboon kidney xenotransplantation continues to be limited by acute xenograft rejection and complications of immunosuppression. Although significantly increased survivals have been obtained, an ideal protocol has not yet been achieved. Efforts will continue in an attempt to develop a protocol with minimal complications and long-term survival beyond 90 days.
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PMID:Xenotransplantation of human decay accelerating factor transgenic porcine kidney to non-human primates: 4 years experience at a Canadian center. 1535 Apr 60

The somatostatin analogue lanreotide is effective in reducing growth hormone levels in patients with acromegaly. Acromegaly is characterized by calcium homeostasis alterations. The aim of our study was to evaluate the effects of lanreotide on bone turnover markers in a group of acromegalic patients and to verify a possible increase of intact parathormone (iPTH) levels in a transient or persistent way. Serum GH, IGF-I and serum and urinary markers of bone metabolism were measured before treatment and on months 3 and 24. In short-term treatment (3 months), lanreotide significantly decreased GH, IGF-I, serum calcium, osteocalcin and alkaline phosphatase levels, but increased iPTH level (49 +/- 16.7 vs pre-treatment 28.3 +/- 7.6 ng/L, p<0.001). During long-term study (24 months) GH and IGF-I were significantly still low; serum calcium and alkaline phosphatase levels returned to pre-treatment levels. iPTH level was significantly still higher compared with pre-treatment (46.4 +/- 9.2 vs 28.3 +/- 7.6 ng/L, p<0.05). No changes were seen in serum albumin, creatinine and vitamin D during short and long term treatment. The changes of most bone markers during lanreotide treatment can be explained by the decrease of GH and IGF-I. The increase of iPTH concentration suggests that lanreotide has ulterior and long-standing actions on calcium homeostasis: intestinal malabsorption of calcium due to the lanreotide could contribute to this "secondary" hyperparathyroidism. The clinical relevance of these long-standing effects needs to be further investigated.
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PMID:Long-term treatment of acromegaly with lanreotide: evidence of increased serum parathormone concentration. 1564 68


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