Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019209 (hepatomegaly)
 5,798 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Various metabolic studies were performed in a patient with the idiopathic Fanconi syndrome in whom constant ketonuria suggested that organic acidemia might contribute to the metabolic acidosis. Glucose intolerance with a diminished insulin release was found after PO or IV glucose loads and after glucagon administratio. An insulinopenic "diabetes-like" state has not previously been described in such patients. The patient had impaired galactose-glucose interconversion, elevated blood lactate levels, reduced pyruvate levels, and an increased lactate:pyruvate ratio. Hepatomegaly and hypoglycemia were not present, and liver and muscle biopsies revealed no enzymatic evidence of glycogenosis. The erythrocyte UDP galactose transferase activity was normal. The patient failed to convert fructose to glucose and had a rise in blood lactate after ethanol administration. Further studies revealed no production of glucose after alanine or glycerol administraion, each test being associated with elevated blood lactate levels and, after alanine, an increased lactate:pyruvate ratio. The lactate:pyruvate ratio was elevated after glucagon administration with increased lactate and reduced pyruvate concentrations.
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PMID:Abnormalities of carbohydrate metabolism in idiopathic Fanconi syndrome. 738 41

A baby with congenital lactic acidosis is described. The blood levels of lactic acid and alanine as well as the excretion of these compounds in the urine were largely elevated. Clinically the illness presented with vomiting, poor feeding, areflexia, muscular hypotonia and hepatomegaly. The baby died at the age of three months. The pyruvate dehydrogenase complex in cultured fibroblasts showed an activity of 14% of normal values.
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PMID:[Chronic infantile lactate acidosis]. 741 Jan 11

Classical galactosaemia, deficiency of galactose-1-phosphate uridyltransferase (GALT), is characterized by acute symptoms of hepatomegaly, jaundice, sepsis, cataracts and growth retardation. Treatment with dietary galactose restriction corrects these complications immediately; however, most of these children develop long-term complications of verbal dyspraxia, mental retardation and ovarian failure. Our previous molecular study showed that the most common mutation of the GALT gene is a missense mutation of Q188R (replacement of glutamine-188 by arginine) in approximately 60-65% of the German galactosaemic population. The coding region of GALT was amplified by the polymerase chain reaction from genomic DNA of classical galactosaemic individuals, who are negative or heterozygous for Q188R, and was further characterized by direct sequencing. Three new disease-causing mutations, two missense and a stop codon mutation, were identified in three patients from two families with mild galactosaemic variants: firstly R67C, replacement of arginine-67 by cysteine and W316X, the stop codon at tryptophan-316 in one male; secondly A330V, replacement of alanine-330 by valine in two female siblings. In the first family the patient was also heterozygous for the polymorphism N314D and in the second family both girls were compound heterozygotes for Q188R and A330V. All three galactosaemic individuals have a considerable amount of the residual GALT activity in RBC and the galactose-1-phosphate (GALP) level decreased much faster on treatment than that of other galactosaemic patients with missense mutations such as Q188R. The clinical and biochemical data of these patients were much more favourable in comparison with those of two female galactosaemic individuals, one homozygous for L195P and the other compound heterozygous for Q188R and L195P. These three missense mutations (R67C, L195P and A330V) also occur in highly conserved regions. These observations suggest that the phenotypic variation in galactosaemic individuals may be due to different molecular aetiologies.
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PMID:Mutations in the galactose-1-phosphate uridyltransferase gene of two families with mild galactosaemia variants. 859 37

Since 1983 large number of people are being encountered with arsenic toxicity due to drinking of arsenic contaminated water (0.05-3.2 mg/l) in 6 districts of West Bengal. Clinical and various laboratory investigations were carried out on 156 patients to ascertain the nature and degree of morbidity and mortality that occurred due to chronic arsenic toxicity. All the patients studied had typical rain drop like skin pigmentation (being inclusion criteria) while thickening of palm and sole were found in 65.5% patients. Other features included weakness (70%), gastro-intestinal symptoms (58.6%), involvement of respiratory system (57.08%) and nervous system (50.6%). Lung function tests showed restrictive lung disease in 53% (9/17) and combined obstructive and restrictive lung disease in 41% (7/17) of patients. Abnormal electromyography was found in 34.8% (10/29) and altered nerve conduction velocity in 34.8% (10/29) of cases. Enlargement of liver was found in 120 cases (76.9%) while splenomegaly in 31.4% cases. Liver function test showed elevated globulin level in 15.8% and alkaline phosphatase in 51.3%, alanine amino transferase (ALT) in 11.8% and aspartate amino transferase (AST) in 27.6% of cases. Evidence of portal hypertension was found in 33.3% patients. Liver biopsy reports of 45 patients showed non-cirrhotic portal fibrosis in 41, cirrhosis in 2 and normal histology in 2 cases. There was no correlation between the quantity of arsenic taken through water and the level of arsenic in hair, nail, liver tissues and the degree of fibrosis. There were 5 deaths of which one had skin cancer. The various non-cancer manifestations which were observed in these patients were much severe than those reported in similar cases in other parts of the world.
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PMID:Chronic arsenic toxicity in west Bengal--the worst calamity in the world. 960 Nov 81

We studied the prevalence of hepatitis C virus (HCV) antibody seropositivity using ELISA (Ortho Diagnostic system, 3rd generation test) polymerase chain reaction testing of HCV-RNA (PCR, Promega) and serum alanine transferase (ALT) level in 100 healthy, HIV-negative, pregnant women who delivered spontaneously at the Alexandria University Hospital, and their newborns. Some risk factors were studied using Fisher's exact test. Nineteen per cent of pregnant women were HCV seropositive and 14 of them (14/19) had circulating HCV-RNA, detected by PCR. Nine of the babies born to the 19 HCV seropositive females had circulating antibodies, whereas HCV-RNA was detected in five of them. This gives a vertical transmission risk of 5/14 (36 per cent) for mothers carrying the HCV-RNA and 5/19 (26 per cent) for those having circulating HCV antibodies. History of previous blood transfusion, elevated serum ALT level, and history of infection with schistosomiasis were significant risk factors for HCV infection in mothers. In addition to the previous factors, maternal history of jaundice, stillbirth and hepatomegaly were significant risk factors for neonatal infection. The occurrence of early jaundice and the presence of congenital anomalies in the newborns were non-significant risk factors. In conclusion, our data indicate a high prevalence of HCV seropositivity in Egyptian HIV-negative pregnant women with a significant high rate of vertical transmission of HCV.
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PMID:Prevalence of hepatitis C virus (HCV) infection and its vertical transmission in Egyptian pregnant women and their newborns. 1099 85

A descriptive study was carried out in 104 patients with Plasmodium vivax malaria, from the region of Turbo (Antioquia, Colombia). Clinical features and levels of hemoglobin, glycemia, serum bilirubin, alanine-aminotransferase (ALT), aspartate-aminotransferase (AST), creatinine and complete blood cell profile were established. 65% of the studied individuals were men and their mean age was 23. Of all individuals 59% had lived in the region for > 1 year and 91% were resident in the rural area. 42% were farmers and 35% had a history of malaria. The mean parasitaemia was 5865 parasites/mm3. The evolution of the disease was short (average of 4.0 days). Fever, headache and chills were observed simultaneously in 91% of the cases while the most frequent signs were palmar pallor (46%), jaundice (15%), hepatomegaly (17%), and spleen enlargement (12%). Anemia was found in 39% of the women and in 51% of the men, 8% of individuals had thrombocytopaenia and 41% had hypoglycemia.
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PMID:Clinical and laboratory findings of Plasmodium vivax malaria in Colombia, 2001. 1275 19

Adefovir is classified as a nucleotide reverse transcriptase inhibitor because it acts by inhibiting hepatitis B virus DNA polymerase (reverse transcriptase) and causing DNA chain termination after its incorporation into the viral DNA. Adefovir dipivoxil is indicated for the treatment of chronic hepatitis B in adults with evidence of active viral replication and either evidence of persistent elevations in serum aminotransferases (alanine [ALT] or aspartate [AST]) or histologically active disease. It is useful in the treatment of patients with either hepatitis B e antigen-positive or -negative chronic hepatitis B. The recommended adefovir dipivoxil dose in the treatment of chronic hepatitis B in patients with adequate renal function is 10 mg once daily. Adefovir dipivoxil therapy can reduce viral load, improve ALT, and produce histologic improvement in patients with chronic hepatitis B. Improvements are generally seen within the first few weeks of therapy and have shown persistence up to at least 3 years with continued therapy. Therapy with adefovir dipivoxil is generally well tolerated. However, nephrotoxicity is a risk with adefovir therapy, especially in patients receiving higher doses (30-120 mg/d). Patients should have their renal function monitored closely throughout therapy and may require an adjustment in dose relative to changes in the creatinine clearance. Lactic acidosis and severe hepatomegaly with steatosis may also occur during therapy.
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PMID:Adefovir dipivoxil: focus on its use in the treatment of chronic hepatitis B. 1597 40

Mouse models for urea cycle disorders have been available for the past 30 y; however, until now, no measurements of urea production in vivo have been conducted. Urea entry rate was determined in Otc(spf-ash) and littermate controls employing a primed-continuous infusion of 15N15N urea. A saline infusion control, a complete mixture of amino acids (AA), or a glycine-alanine (GA) mixture was infused at 86 (AA1 and GA1) and 172 mg N.kg(-1).h(-1) (AA2 and GA2) to impose a defined nitrogen load on the urea cycle. Urea entry rate and plasma urea concentration increased (P < 0.001) as a consequence of the increase in the infusion rate of the complete mixture of amino acids, but the 2 genotypes did not differ (P = 0.96 and P = 0.44, respectively). The infusion of the GA mixture, however, decreased (P < 0.001) the plasma urea concentration and urea entry rate in Otc(spf-ash) mice compared with controls. At the highest level (GA2), urea entry rate was further depressed (P < 0.001), Otc(spf-ash) mice became hyperammonemic (1701 +/- 150 micromol/L), and hyperammonemic symptoms were evident. An acute hepatic enlargement (P < 0.001) was also evident in Otc(spf-ash) mice infused with GA2. These results show that despite vestigial OTC activity, Otc(spf-ash) mice were able to maintain ureagenesis at the same rate of control animals when a complete mixture of amino acids was infused. This implies that Otc(spf-ash) mice are able to dispose of ammonia, without apparent adverse effects, when a balance mixture of amino acids is provided, despite reduced enzyme activity.
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PMID:Reduced ornithine transcarbamylase activity does not impair ureagenesis in Otc(spf-ash) mice. 1654 67

Soluble intercellular adhesion molecule-I (sICAM-1) is an important early marker of response to inflammatory mediators and immune activation released from a variety of cells including hepatocytes. At present, the most reliable determination of severity and prognosis in chronic viral hepatitis is the histological staging of the disease which is an invasive procedure and is often not well accepted by patients. The search for alternative non-invasive methods is mandatory especially in follow ups after initial assessment by biopsy. Serum sICAM-1 level was measured in 19 patients with chronic HCV, 19 patients with non-B, non-C chronic liver diseases (NBNC-CLD) and in 19 healthy control subjects using ELISA. Serum sICAM-1 levels were significantly higher in patients with chronic HCV and in NBNC-CLD patients compared to normal subjects (mean +/- SD, [1003 +/- 453 vs. 232 +/- 177, p<0.001], and [881 +/- 328 vs. 232 +/- 177, p<0.001]), respectively. Furthermore, serum levels of sICAM-1 were significantly higher in HCV-RNA positive patients than in HCV-RNA negative patients (p<0.001). Positive correlations were detected between serum levels of sICAM-1 and serum alanine aminotranseferase (ALT) (p<0.001), aspartate aminotranseferase (AST) (p<0.001), prothrompin time (p<0.001), and alkaline phosphatase (p<0.001), while, a negative correlation with albumin was found (p<0.001). Also, there was a significant correlation between clinical, ultrasonic findings and the level of sICAM-1 in chronic HCV patients as regards hepatomegaly, splenomegaly and normal liver echogenecity. High knodell score was significantly associated with high sICAM-1 level (p<0.001) in both patient groups. while no association between sICAM-1 and fibrosis was found. In conclusion, the measurement of sICAM-1 serum levels in chronic hepatitis C and NBNC-CLD patients is a useful non-invasive marker for monitoring liver disease activity that could replace follow up liver biopsies that are mostly not welcomed by the patients.
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PMID:Soluble ICAM-1 in patients with chronic hepatitis C infection: a prognostic marker of disease activity. 1673 23

We showed that Otc(spf-ash) mice, a model of ornithine transcarbamylase deficiency, were able to sustain ureagenesis at the same rate as control mice, despite reduced enzyme activity, when a complete mixture of amino acids was provided. An unbalanced amino acid mixture, however, resulted in reduced ureagenesis and hyperammonemia. To study the effect of ornithine supplementation [316 micromol/(kg.h)] on urea and glutamine kinetics in conscious Otc(spf-ash) mice under a glycine-alanine load [6.06 mmol/(kg.h)], a multiple tracer infusion protocol ([(13)C(18)O]urea, [5-(15)N]glutamine, [2,3,3,4,4 D(5)]glutamine and [ring-D(5)] phenylalanine) was conducted. Ornithine supplementation increased ureagenesis [3.18 +/- 0.88 vs. 4.56 +/- 0.51 mmol/(kg.h), P < 0.001], reduced plasma ammonia concentration (1125 +/- 621 vs. 193 +/- 94 micromol/L, P < 0.001), and prevented acute hepatic enlargement (P < 0.006) in Otc(spf-ash) mice. Ornithine supplementation also increased [96 +/- 20 vs. 120 +/- 16 micromol/(kg.h), P < 0.001] the transfer of (15)N from glutamine to urea, to values observed in the control mice [123 +/- 17 micromol/(kg.h)]. De novo amido-N glutamine flux was higher [1.57 +/- 0.37 vs. 3.04 +/- 0.86 mmol/(kg.h); P < 0.001] in Otc(spf-ash) mice, but ornithine supplementation had no effect (P < 0.56). The flux of glutamine carbon skeleton was affected by both genotype (P < 0.0001) and by ornithine (P 0. 036). In conclusion, ornithine supplementation restored ureagenesis, mitigated hyperammonemia, prevented liver enlargement, and normalized the transfer of (15)N from glutamine to urea. These data strongly suggest that ornithine has the potential for the biochemical correction of OTCD in Otc(spf-ash) mice.
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PMID:Ornithine restores ureagenesis capacity and mitigates hyperammonemia in Otc(spf-ash) mice. 1677 45


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