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

The submitted paper is a contribution to the problem of cholestasis from the aspect of contemporary knowledge recorded in the literature as well as the author's experience assembled in a hepatological department. The author expands on individual steps of the diagnostic procedure--is it a case of cholestasis? What type of cholestasis? The most frequent causes of intrahepatic cholestasis are discussed. The main point is a summary of therapeutic possibilities, in particular in chronic forms of cholestasis. The author emphasizes that dietary provisions are always essential, a as well as treatment of itching, malabsorption and prevention of the development of osseous changes. Drugs which are considered specific therapy are mentioned and their effect and side-effects are briefly evaluated. It appears that ursodeoxycholic acid is most promising. In the terminal stage under local conditions treatment is symptomatic in future we may be able to ensure liver transplantations which are indicated in chronic cholestasis.
 ...
PMID:[Diagnosis and therapy of cholestasis]. 830 80

Primary biliary cirrhosis (PBC) is a presumed autoimmune disease of the liver, which predominantly affects women once over the age of 20 years. Most cases are diagnosed when asymptomatic (60%). The antimitochondrial antibody is present in serum in most, but not in all, patients with PBC. The disease generally progresses slowly but survival is less than an age- and gender-matched general population. The symptomatic patient may have fatigue, generalized pruritus, portal hypertension, osteoporosis, skin xanthomata, fat soluble vitamin deficiencies, and/or recurrent asymptomatic urinary tract infections. Many nonhepatic autoimmune diseases are found in association with PBC and may prompt initial presentation. To date, immunosuppressive therapy has not been shown to prolong survival in PBC. The hydrophilic bile acid, ursodeoxycholic acid (UDCA), has been shown when given in a dose of 13 to 15 mg/kg daily for up to 4 years to delay the time to liver transplantation or death. This therapy also causes a significant improvement of all the biochemical markers of cholestasis but has no beneficial effects on any of the symptoms or associated disorders. Treatment with UDCA does not obviate the need for liver transplantation. Therapies to prevent complications arising from malabsorption, portal hypertension, and/or osteoporosis are required as well. Good control of pruritus can be achieved in most patients. PBC is diagnosed with increasing frequency, but the agent(s) responsible for this slowly progressive destruction of the interlobular bile ducts remains elusive and hence a specific therapy remains unavailable.
 ...
PMID:Management of primary biliary cirrhosis. The American Association for the Study of Liver Diseases practice guidelines. 1073 59

Cholestasis is decrease or absence of bile flow into the duodenum. It can be either or in combination pathology of hepatocytes, intrahepatic bile ducts or extrahepatic bile ducts. Hepatocyte with their bile secretory apparatus and tight junction between hepatocytes are of specific importance in this. Bile is formed by several different energy-dependent transport processes. Secretion of bile is a complex metabolic process, which depends upon multiple structural and functional components in the hepatocytes and bile duct cells. The regulation of bile flow is regulated by many hormones. Bile is secreted in bile ducts having pressure of 15-25 cm of water. Rise in pressure in these bile ducts of more than 35 cm of water result suppression of bile flow and jaundice. A rise of conjugated serum bilirubin above the value of 400-500 mumol/L finds an alternate excretory pathway like urine. Various conditions are responsible for infantile cholestasis and can have different outcome of chronic cholestasis. These can be extrahepatic or intrahepatic and acute or chronic. Pathological consequences of infantile cholestasis are mainly because of malabsorption of fat and fat-soluble vitamins and hepatocellular dysfunctions. A battery of tests are required to diagnose the early infantile cholestasis. In the management of cholestasis diet rich in MCT is needed. Further, a high caloric intake up to 200 kcal/day to get adequate weight gain is desirable. Phototherapy, phenobarbitone and rifampicin is helpful in the pruritus of cholestasis by enhancing the excretion of bile. Ursodeoxycholic acid is specifically helpful in the cholestasis. A number of anti-inflammatory and immunosuppressive agents and a new compound, FK 506 has specific role in the management.
 ...
PMID:Infantile cholestasis--advances in its understanding: new concepts. 1091 May 52

Cholestasis results from defective canalicular secretion of bile or obstruction to bile flow distal to the canaliculus. In early primary biliary cirrhosis, bile secretion continues, because of the secretory pressure of bile or because some ductules are not obstructed. With complete cholestasis, a bile acid deficiency occurs in the small intestinal lumen leading to lipid maldigestion and fat-soluble vitamin malabsorption. Bacterial proliferation, bacterial translocation to lymph nodes and endotoxemia may also occur leading to an acute phase reaction. Retention of bile acids in the hepatocyte leads to apoptosis. Accumulation of bile acids in the systemic circulation leads to pruritus, and may contribute to endothelial injury in the lungs and kidney. Early attempts to mimic hepatic excretory function by hemoperfusion over adsorbent columns were unsuccessful for a variety of reasons. Extracorporeal dialysis against albumin offers promise of a realistic albeit partial simulation of hepatic excretory function.
 ...
PMID:Cholestatic liver disease: pathophysiology and therapeutic options. 1222 Feb 97

Primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) are chronic cholestatic liver diseases that affect 0.5 to 40 per 100,000 and 1 to 6 per 100,000 Americans, respectively. Prompt recognition and management of the clinical manifestations of these diseases is essential for the patients' well-being and ultimate outcome. Ursodeoxycholic acid (UDCA), 13 to 15 mg/kg per day, is the standard therapy for PBC and should be offered to every patient. It has been shown to slow progression of the disease and prevent the need for liver transplantation, which is the last recourse for patients with end-stage disease. However, there is no effective therapy for PSC yet. Patients are managed symptomatically, with surgical or endoscopic interventions as needed in cases of significant biliary obstruction. Complications of chronic cholestasis are seen in both PBC and PSC, with pruritus and fatigue being the most common complaints. The first choice for the treatment of pruritus is still cholestyramine, starting at 4 g/d. The pathogenesis of fatigue is poorly understood in this population; unrecognized hypothyroidism should be excluded. The use of antidepressants is currently under evaluation, but there is no specific therapy for fatigue as of yet. For prevention of severe osteoporosis, we recommend supplementation with 800 IU vitamin D and 1500 mg calcium/d. In patients with PBC and established osteoporosis, the use of alendronate and vitamin K appears to cause an increase in bone mineral density. Further studies are necessary before either of these drugs is routinely recommended. Finally, fat-soluble vitamin deficiencies are noted with more advanced disease. We recommend that serum levels be checked in high-risk patients, and that vitamins are replaced as appropriate with water-soluble supplements. However, other causes of malabsorption must be ruled out, including pancreatic insufficiency and celiac sprue.
 ...
PMID:Treatment Options for Primary Biliary Cirrhosis and Primary Sclerosing Cholangitis. 1262 68

Familial hypercholanemia (FHC) is characterized by elevated serum bile acid concentrations, itching, and fat malabsorption. We show here that FHC in Amish individuals is associated with mutations in tight junction protein 2 (encoded by TJP2, also known as ZO-2) and bile acid Coenzyme A: amino acid N-acyltransferase (encoded by BAAT). The mutation of TJP2, which occurs in the first PDZ domain, reduces domain stability and ligand binding in vitro. We noted a morphological change in hepatic tight junctions. The mutation of BAAT, a bile acid-conjugating enzyme, abrogates enzyme activity; serum of individuals homozygous with respect to this mutation contains only unconjugated bile acids. Mutations in both TJP2 and BAAT may disrupt bile acid transport and circulation. Inheritance seems to be oligogenic, with genotype at BAAT modifying penetrance in individuals homozygous with respect to the mutation in TJP2.
 ...
PMID:Complex inheritance of familial hypercholanemia with associated mutations in TJP2 and BAAT. 1270 86

A wide range of cholestatic liver diseases result from various primary defects in bile formation. Clinical features include jaundice, pruritus, failure to thrive, fat malabsorption, cholelithiasis, and variably progressive cirrhosis. Accurate diagnosis of these disorders is essential for determination of prognosis and selection of the most appropriate therapies. Severe genetic defects in canalicular bile acid and phospholipid excretion lead to progressive liver disease that often requires liver transplantation. Defects in bile acid biosynthesis and aminophospholipid transport may be responsive to medical or non-transplant surgical approaches.
 ...
PMID:Disorders of bile formation and biliary transport. 1456 77

Prurigo is a condition of nodular cutaneous lesions that itch (pruire) intensely. Although the acute form can be caused by insect stings, most of the subacute and chronic forms appear to be idiopathic. Toxic agents deposited in the skin by exogenous factors such as parasites, bacteria, or topically or orally administered drugs can induce itch. In susceptible individuals, physical mechanisms such as UV light can induce changes in epidermal innervation that result both in itch generally and in prurigo lesions. Prurigo is sometimes associated with atopy, pregnancy, internal diseases, malabsorption, or malignancy. Some forms of prurigo may be secondary to scratching. Emotional factors can also influence the perception of itch and induce prurigo by provoking scratching. These are the various specialized forms of prurigo, and there are certain others, such as prurigo pigmentosa, that have some ethnic preference. Topical treatments by corticosteroids, coal tar, bath photochemotherapy, UVB, cryotherapy, or capsaicin, as well as systemic regimens involving use of psoralen + UVA (PUVA), erythromycin, arotinoid acid, cyclosporine, chloroquine, dapsone, minocycline, naltrexone, azathioprine or thalidomide are used for the treatment of this condition. Psychotherapeutic agents to treat problems of mood that deteriorate prurigo are also prescribed. Combined sequential treatments for generalized, therapy-resistant cases need to be tailored to the exacerbations that occur and to provide maintenance treatment in order to enable the patient to withstand the intolerable itch.
 ...
PMID:Prurigo: diagnosis and management. 1510 73

Progressive intrahepatic cholestasis (PIHC, also known as progressive familial intrahepatic cholestasis) is a general term encompassing a devastating group of illnesses manifest by severe morbidity and potential mortality. By definition these diseases are characterized by persistent cholestasis that is the result of intra-hepatic rather than extra-hepatic pathology. Recent scientific advances have begun to clarify the molecular basis of many of these disorders. The morbidities of these diseases are primarily the result of profound cholestasis. This cholestasis is often associated with intractable pruritus, which leads to a very poor quality of life. Normal development and sleep are not possible for the affected individual and family dynamics are sometimes irreparably damaged. The cholestasis also leads to complications of fat soluble vitamin malabsorption including osteopenia and pathologic bone fractures, xeropthalmia, and peripheral neuropathy. End-stage liver disease and all of its attendant problems may develop in affected individuals by young adulthood. Optimal therapeutic approaches to PIHC are not well established and disease-specific approaches may be required.
 ...
PMID:Progressive intrahepatic cholestasis: mechanisms, diagnosis and therapy. 1559 35

Any infant who is jaundiced beyond two to three weeks of life should be evaluated for neonatal cholestasis. Neonatal cholestasis is defined as accumulation of bile substances in blood due to impaired excretion. These infants should always have fractionated serum bilirubin levels checked to differentiate the conjugated hyperbilirubinemia of cholestasis from unconjugated hyperbilirubinemia that is usually benign and spontaneously resolves. Conjugated hyperbilirubinemia, pale stools and dark urine are the cardinal features of neonatal cholestasis. The differential diagnosis of cholestasis is extensive and a systematic approach is helpful to quickly establish the diagnosis. Biliary atresia is a common cause of neonatal cholestasis and affected infants need surgery before 60 days of life for better prognosis. Premature infants have multifactorial cholestasis and need a modified approach to the evaluation of cholestasis. Management of cholestasis is mostly supportive, consisting of medical management of complications of chronic cholestasis like pruritus and nutritional support for malabsorption and vitamin deficiency.
 ...
PMID:Neonatal cholestasis. 1568 66


<< Previous 1 2 3 4 Next >>