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)

Total lymphocyte counts, B-, T-, C'3 receptor-bearing lymphocytes, and K-cell activity were studied in peripheral blood in patients with Crohn's disease and inflammatory liver disease. Patients with active untreated Crohn's disease and acute virus B hepatitis exhibited a markedly increased K-cell activity measured in a plaque assay when compared with normal controls (P less than 0.01). Patients with immunosuppressive treated Crohn's disease, HBsAg-positive chronic active hepatitis, and cirrhosis of the liver showed only a slight increase of K-cell activity (P less than 0.01). In the postacute phase of hepatitis (four to 12 weeks from onset) K-cell activity fell to normal levels. The number of B-lymphocytes showed a relative and absolute decrease in all groups of patients. With the exception of patients with acute HBsAg-positive hepatitis and the post-acute phase of hepatitis all the other groups showed statistically decreased absolute numbers for C'3 receptor-bearing lymphocytes. The significant decrease in K-cell activity and the number of T-lymphocytes in Crohn's disease treated with immunosuppressive drugs was interpreted as an effect of azathioprine and prednisone on these lymphocyte subpopulations.
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PMID:K-lymphocytes (killer-cells) in Crohn's disease and acute virus B-hepatitis. 30 25

To clarify the physiologic response of splenic lymphocytes to liver damage and the role of this response in regeneration versus malignant transformation, we cultured rat spleen lymphocytes with portal sera from rats subjected either to partial (70%) hepatectomy or to long-term oral administration of the hepatic carcinogen 3'-methyl-4-dimethylaminoazobenzene. Sera taken within 24h after partial hepatectomy contained a previously described signal protein which serves as a marker of liver damage. The MW 5,000-10,000 serum fraction also contained a factor that promoted cell growth, DNA synthesis, glucose utilization, and the production of anti-sheep erythrocyte plaque-forming cells in cultures of rat splenic lymphocytes. In contrast, the sera of rats subjected to liver damage by the carcinogen had no more effect on the cultured lymphocytes than sera from sham-operated or untreated controls. The signal protein was present initially in portal sera from carcinogen-treated rats, but decreased as hepatitis gave way to cirrhosis. Subsequent malignant transformation was marked by the appearance of serum alpha-fetoprotein. Our results suggest that activation of splenic lymphocytes by serum factor(s) is involved in hepatic regeneration and that this process is deranged in carcinogenesis.
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PMID:In-vitro immune response of splenic lymphocytes to portal serum agents from rats undergoing hepatic regeneration or hepatic carcinogenesis. 139 18

Methotrexate is an effective and convenient treatment for severe psoriasis whose use is limited by the development of hepatic fibrosis and cirrhosis in a small number of patients. The mechanism of hepatotoxicity is unknown, but it is believed to be the result of intracellular polyglutamation and prolonged retention of methotrexate within the cell. Piritrexim isethionate is a lipid-soluble antifolate that has a mechanism of action similar to that of methotrexate. Since it is not polyglutamated, piritrexim could be effective in the treatment of psoriasis without the associated long-term hepatotoxicity. A 12-week phase I/II clinical trial of severe chronic plaque psoriasis assessed the safety and efficacy of oral piritrexim therapy. Based on experience gained from oncologic trials, each patient received a twice-daily dosage for 5 consecutive days every 2 weeks. Dosages ranged from 25 to 100 mg twice a day. Improvement in both lesion scores and percentage of body involvement was significant at a dose of 50 mg or more twice daily. Fifteen of 19 patients who completed 12 weeks of therapy demonstrated greater than 50% improvement in lesion scores. Improvement was limited by recrudescence of lesions over the 9-day rest period. Adverse experiences were minimal and dose related. Piritrexim is efficacious in the treatment of psoriasis.
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PMID:Treatment of psoriasis with piritrexim, a lipid-soluble folate antagonist. 200 83

Peripheral blood killer cell (K-cell) population of patients with chronic hepatitis was investigated by means of a plaque-assay method using sheep red blood cells. The mean K-cell population of 14 control subjects was 5.1 +/- 2.0% (mean +/- SD), and that of 28 patients with chronic hepatitis was 4.4 +/- 3.1%. These 28 patients were divided into three groups: CPH, CAH 2A and CAH 2B. The mean K-cell population of each group was decreased in order of the severity of the disease. Especially, that of patients with CAH 2B was a statistically significant decrease (p less than 0.01) from control subjects. In the course most patients with CAH, K-cell population did not change for three months after admission. K-cell population was observed to decrease in the patients with active stage of liver cirrhosis, but not in patients with the terminal stage of liver cirrhosis, even in hepatoma patients. It is suggested that the K-cell population may play an important role of pathogenesis of chronic hepatitis.
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PMID:Killer cell (K-cell) population in chronic liver disease. 626 41

The periodontal condition of a well-described group of cirrhotic patients was compared with that of a control group, matched for age, sex ratio and socio-economic background, expressed as years of education. The test group comprised 30 cirrhotic patients, 35-64 years of age. The diagnosis cirrhosis of the liver was confirmed histologically, and no other systemic diseases were present. The material was grouped according to age, 35-44, 45-54 and 55-64 years of age. The examination included determination of tooth loss, a plaque index, a gingival index, retentive calculus, retentive decay and fillings, and loss of attachment. The amount of plaque was equal in test and control groups, whereas the cirrhotics had a higher degree of severity of gingival inflammation as well as a greater amount of subgingival calculus than the controls. Test and control groups exhibited no significant difference as regards loss of attachment and tooth loss, and similar correlations between loss of attachment and age were demonstrated in the two groups. Patients suffering from cirrhosis for more than 3 years showed significantly greater loss of attachment, as well as more plaque and calculus compared with those with a disease duration of less than 3 years. It is suggested that this aggravation of the periodontal condition is related to increasing neglect of the teeth, as the cirrhotic condition aggravates.
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PMID:Relationship between periodontal disease and cirrhosis of the liver in humans. 694 18

Five Tupaia herpesviruses have been isolated until now: four in our laboratory which were termed THV-2, 3, 4, and 5, whereas THV-1 has been isolated by Melnick and his colleagues. THV-2 was isolated from tumour cell culture of a high-grade malignant lymphoma of a Tupaia, THV-3 was released from a cell culture of another Tupaia lymphoma, THV-4 from a spleen tissue culture of a moribund animal with finely granulated liver cirrhosis, and THV-5 from cultured spleen cells of an apparently healthy tree shrew. THV-1 to 5 were efficiently propagated, plaque-purified and cloned on Tupaia embryonic fibroblasts. The five isolates of Tupaia herpesviruses are easily distinguished from each other by restriction enzyme analysis of their genomes. THV-1 to 4 are highly pathogenic (lethality 100%) for juvenile Tupaias by intravenous inoculation. In contrast, only 25% lethality was found by intraperitoneal administration. THV-1 to 4 can persist as a latent infection in spleens of Tupaias and rabbits, which allows the recovery of infectious virus from cultured spleens of both animals. THV-2 and 3 induced hyperplasia of the thymus of rabbits which developed malignant thymoma in a few cases. The biological properties and genomic size and structure indicate that THV cannot be considered to belong to one of the three existing subfamilies of herpesviruses.
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PMID:Tree shrew (Tupaia) herpesviruses. 716 1

Fluvastatin, the first fully synthetic HMG-CoA reductase inhibitor, has been shown to reduce cholesterol in patients with hyperlipidaemia, to prevent subsequent coronary events in patients with established coronary heart disease, and to alter endothelial function and plaque stability in animal models. Fluvastatin is relatively hydrophilic, compared with the semisynthetic HMG-CoA reductase inhibitors, and, therefore, it is extensively absorbed from the gastrointestinal tract. After absorption, it is nearly completely extracted and metabolised in the liver to 2 hydroxylated metabolites and an N-desisopropyl metabolite, which are excreted in the bile. Approximately 95% of a dose is recovered in the faeces, with 60% of a dose recovered as the 3 metabolites. The 6-hydroxy and N-desisopropyl fluvastatin metabolites are exclusively generated by cytochrome P450 (CYP) 2C9 and do not accumulate in the blood. CYP2C9, CYP3A4, CYP2C8 and CYP2D6 form the 5-hydroxy fluvastatin metabolite. Because of its hydrophilic nature and extensive plasma protein binding, fluvastatin has a small volume of distribution with minimal concentrations in extrahepatic tissues. The pharmacokinetics of fluvastatin are not influenced by renal function, due to its extensive metabolism and biliary excretion; limited data in patients with cirrhosis suggest a 30% reduction in oral clearance. Age and gender do not appear to affect the disposition of fluvastatin. CYP3A4 inhibitors (erythromycin, ketoconazole and itraconazole) have no effect on fluvastatin pharmacokinetics, in contrast to other HMG-CoA reductase inhibitors which are primarily metabolised by CYP3A and are subject to potential drug interactions with CYP3A inhibitors. Coadministration of fluvastatin with gastrointestinal agents such as cholestyramine, and gastric acid regulating agents (H2 receptor antagonists and proton pump inhibitors), significantly alters fluvastatin disposition by decreasing and increasing bioavailability, respectively. The nonspecific CYP inducer rifampicin (rifampin) significantly increases fluvastatin oral clearance. In addition to being a CYP2C9 substrate, fluvastatin demonstrates inhibitory effects on this isoenzyme in vitro and in vivo. In human liver microsomes, fluvastatin significantly inhibits the hydroxylation of 2 CYP2C9 substrates, tolbutamide and diclofenac. The oral clearances of the CYP2C9 substrates diclofenac, tolbutamide, glibenclamide (glyburide) and losartan are reduced by 15 to 25% when coadministered with fluvastatin. These alterations have not been shown to be clinically significant. There are inadequate data evaluating the potential interaction of fluvastatin with warfarin and phenytoin, 2 CYP2C9 substrates with a narrow therapeutic index, and caution is recommended when using fluvastatin with these agents. Fluvastatin does not appear to have a significant effect on other CYP isoenzymes or P-glycoprotein-mediated transport in vivo.
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PMID:Clinical pharmacokinetics of fluvastatin. 1136 92

Psoriasis is a chronic, debilitating skin condition that affects millions of people and is attributed to both genetic and environmental factors. Topical therapy is generally considered to be the first-line treatment of psoriasis. However, many patients do not respond to topical therapy or have disease so extensive that topical therapy is not practical. For these patients, systemic therapy is indicated. Presently, there are four available systemic treatments, psoralen with ultraviolet A (PUVA), methotrexate, oral retinoids (acitretin), and cyclosporin. Unfortunately, all of these treatments have significant potential adverse effects. PUVA may acutely cause nausea, pruritus and sunburn. More chronic and concerning is the development of PUVA lentigines, ocular complications and skin cancer. Non-melanoma skin cancer has been directly linked to PUVA; however, the association with melonoma is more elusive. Methotrexate use most notably carries the risk of hepatic fibrosis and cirrhosis, which is not always evident on liver function tests. Other more rare, but potentially life-threatening adverse effects include pancytopenia, lymphoproliferative disorders and acute pneumonitis. The addition of folic acid may help to reduce the risk of increasing liver enzymes and haematological toxicity seen in those taking methotrexate. Both methotrexate and oral retinoids are teratogenic and should never be used in pregnancy. Oral retinoids are probably the least effective available systemic medication for the treatment of plaque psoriasis. The effects are improved with the addition of other systemic therapies. Acitretin has replaced the formerly used etretinate primarily because of the significantly shorter half-life. The adverse effects are generally mild and reversible, making the drug fairly safe for long-term use. The most commonly seen adverse effects include elevated serum lipids, generalised xerosis and alopecia. Bony abnormalities, while somewhat controversial, have also been described and include diffuse idiopathic skeletal hyperostosis, skeletal calcifications and osteoporosis. Cyclosporin is the most recently approved systemic medication for plaque psoriasis. The nephrotoxicity associated with the use of cyclosporin can be minimised when used in lower doses and for a limited duration. Hypertension is usually mild and can be seen in up to about one-third of patients receiving long-term therapy. Cutaneous and internal malignancies have also been reported with cyclosporin and tend to be correlated with duration of treatment. In this review, we will examine the potential adverse effects with these US Food and Drug Administration-approved treatments in adults, with specific emphasis on the controversies that surround long-term therapy with these agents and their cumulative adverse effects.
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PMID:Comparative tolerability of systemic treatments for plaque-type psoriasis. 1238 Dec 13

A liver tumor (2.5x3 cm) with malignant features on computed tomography (CT) and magnetic resonance imaging (MRI) was detected in a 69-year-old man with hepatitis B virus (HBV)-associated cirrhosis. On exploratory laparotomy a mass at the right diaphragmatic dome adherent to the liver segment VIII was found. En-block resection of this segment and the part at diaphragm hosting the tumor was carried out. On histology the tumor was a diaphragmatic hyaline plaque while in the resected liver no tumor was found.
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PMID:Localized hyaline plaque of the diaphragmatic peritoneum: report of a rare entity mimicking a hepatic tumor. 1733 44

Ultrasound (US) elasticity imaging is an extension of the ancient art of palpation and of earlier US methods for viewing tissue stiffness such as echopalpation. Elasticity images consist of either an image of strain in response to force or an image of estimated elastic modulus. There are 3 main types of US elasticity imaging: elastography that tracks tissue movement during compression to obtain an estimate of strain, sonoelastography that uses color Doppler to generate an image of tissue movement in response to external vibrations, and tracking of shear wave propagation through tissue to obtain the elastic modulus. Other modalities may be used for elasticity imaging, the most powerful being magnetic resonance elastography. With 4 commercial US scanners already offering elastography and more to follow, US-based methods may be the most widely used for the near future. Elasticity imaging is possible for nearly every tissue. Breast mass elastography has potential for enhancing the specificity of US and mammography for cancer detection. Lesions in the thyroid, prostate gland, pancreas, and lymph nodes have been successfully imaged using elastography. Evaluation of diffuse disease including cirrhosis and transplant rejection is also possible using both imaging and nonimaging methods. Vascular imaging including myocardium, blood vessel wall, plaque, and venous thrombi has also shown great potential. Elasticity imaging may also be important in assessing the progress of ablation therapy. Recent work in assessing porous materials using elastography suggests that the technique may be useful in monitoring the severity of lymphedema.
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PMID:Imaging and estimation of tissue elasticity by ultrasound. 1809 Aug 36


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