Preparing educators for problem-based and community-based curricula: a student''s experiences

Doing a liver test before the use of OCs is advisable for women who face risks, those with previous history of liver disease and familial benign hyperbilirubinemia. For those women who have a negative anamnesis with regard to each of these risk factors, it is not necessary to carry out a liver test before prescribing OCs. The risk of worsening latent chronic hepatitis is very small, and the occurrence of subsequent liver lesions is extremely rare. It is sufficient to carry out the test in women at risk after 3 months and after 1 year of OC use. This applies to patients with intensified cholestatic reactions, which have been asymptomatic, as well as to patients with latent chronic liver disease. The liver test needs to be repeated at regular intervals only when the following clinical symptoms are present: dyspepsia, pruritus, and icterus. Benign and malignant liver tumors cannot be confirmed by liver tests; therefore, there is no justification for this. On the other hand, it is believed that the very low incidence of liver tumors in a small group of women who continue to use OCs for more than 8 years would meet the indication for liver examination. Absolute contraindications for the use of OCs with regard to liver function are considered only for liver disease with prolonged higher liver test values, cholestatic jaundice in pregnancy, and liver tumor.     

Differential localization of mRNAs for mammalian trps, presumptive capacitative calcium entry channels, in the adult mouse brain

The value of routine chronic graft-versus-host disease (GVHD) screening studies performed between 70 and 120 days after allogeneic marrow transplantation was retrospectively evaluated among 241 patients. All patients received methotrexate and cyclosporine for GVHD prophylaxis and survived without relapse more than 4 months after transplant. Ninety-one patients (38%) developed clinical extensive chronic GVHD requiring systemic therapy. Data on patients who developed clinical extensive chronic GVHD were compared with those on patients without chronic GVHD to determine which of the following screening tests predicted the subsequent development of clinical extensive chronic GVHD: skin biopsy, oral exam, lip biopsy, Schirmer's test, serum alkaline phosphatase, aspartate transaminase, immunoglobulin level and platelet count. In a univariable analysis, a positive oral examination and a low platelet count were predictive of chronic extensive GVHD development. In a multivariable analysis which adjusted for the contribution of other chronic GVHD risk factors, such as age and a history of acute GVHD none of the screening tests were predictive of chronic GVHD development. The risk factors in this multivariable analysis which had the strongest association with the development of chronic GVHD was a history of acute GVHD and use of corticosteroids at day 100 (RR = 3.9, P = 0.001). The use of corticosteroids for acute GVHD at day 100 had a predictive effect on chronic GVHD development independent of the grade of acute GVHD (RR = 2.1, P = 0.004). Based on these study results, the use of chronic GVHD screening tests may not be of value in predicting who will develop this complication. Patients on corticosteroids at day 100 should be considered for clinical trials to determine the efficacy of new immunosuppressive agents in preventing chronic GVHD.     

Clinical spectrum of chronic liver disease in north Indian children

Recent advances in serodiagnosis of hepatotropic viruses have revolutionized the approach to diagnosis and understanding of chronic liver disease (CLD). There are few studies on CLD in children from India. The present study was planned to define the clinical spectrum of CLD in children, its histopathology and seroepidemiology. Forty children with clinical features satisfying the criteria for diagnosing chronic liver disease were studied. All underwent routine laboratory investigations, liver function tests and ultrasound scan of the abdomen. Liver biopsy, upper GI endoscopy and other special investigations were done wherever indicated. The most common presenting features were jaundice (70%), fever (67%), and abdominal distention (60%). On examination hepatomegaly and icterus (80% each) and splenomegaly (67%) were the commonest findings. Serum transaminases were raised in 62.5% of children while prothrombin time was prolonged in 75% patients. Oesophageal and/or gastric varices were seen in 13 out of 29 patients subjected to upper GI endoscopy. Hepatitis B surface antigen (HbsAg) was positive in 5 children (12.5%) while 3 (7.5%) tested positive for anti HCV antibody. The commonest histopathological diagnosis was infantile cholangiopathy (20%) followed by cryptogenic cirrhosis and idiopathic chronic active hepatitis (17.5% each). The study suggests that the incidence of chronic hepatitis B and C is rather low in childhood. However larger and longer studies are required to delineate the exact incidence of these conditions in childhood and their progression in adolescence and early adulthood.     

Anti-C1q receptor/calreticulin autoantibodies in patients with systemic lupus erythematosus (SLE)

We report a case of acute glomerulonephritis associated with acute Q fever. An abattoir worker with a nonspecific febrile illness and pneumonia and abnormal liver function test results developed hematuria, proteinuria, and acute renal failure that resolved with appropriate antimicrobial therapy. Renal biopsy demonstrated diffuse proliferative and exudative glomerulonephritis. Serological tests confirmed recent infection with Coxiella burnetii, with a fourfold rise in the titer of phase II antibody, positive phase II IgM antibody, and negative phase I antibody. Other known causes of glomerulonephritis were excluded. Most reports of renal complications of C. burnetii infection describe glomerulonephritis associated with endocarditis due to chronic Q fever. Renal involvement in patients with acute C. burnetii infection has been rarely described. Glomerulonephritis should be recognized as a complication of acute C. burnetii infection and endocarditis due to chronic Q fever.     

The prevalence of chronic Chlamydia pneumoniae infection as detected by polymerase chain reaction in pharyngeal samples from patients with ischaemic heart disease

AIMS: Cross-sectional serological studies have suggested an association between ischaemic heart disease and infections from Chlamydia pneumoniae and Helicobacter pylori. We therefore sought to find out if patients with ischaemic heart disease had an increased prevalence of C. pneumoniae in the pharynx. As the course of the C. pneumoniae infection remains unclear, both acute and follow-up samples were taken and compared with antibody levels. METHODS AND RESULTS: We studied 282 patients with ischaemic heart disease. One hundred and two subjects without history or symptoms of ischaemic heart disease served as controls. Pharyngeal specimens for polymerase chain reaction detection of C. pneumoniae, and blood samples for C. pneumoniae and H. pylori antibody detection, were collected. In patients with positive polymerase chain reaction or C. pneumoniae IgA titres > or = 32, indicating current infection, convalescent samples were taken at least 6 weeks later. An immunofluorescent antigen detection test was used to confirm the presence of C. pneumoniae elementary bodies in specimens found to be polymerase chain reaction positive. The prevalence of positive polymerase chain reaction tests was 36% among patients and 22% among controls (P<0.05). Forty-seven percent of patients with positive polymerase chain reaction remained positive in the convalescent test. Elevated C. pneumoniae IgG titres > or = 512 were found in 39% of patients and 26% of the controls (P<0.05). IgA titres > or = 32 were found in 46% of the patients and 44% of the controls (ns). Antibody titres remained largely unchanged at convalescent testing. Two patients and none of the controls had IgM titres > 16. There was no link between positive H. pylori serology and positive C. pneumoniae polymerase chain reaction tests. CONCLUSIONS: The high prevalence and persistence of positive pharyngeal C. pneumoniae polymerase chain reaction and elevated antibody titres in patients with ischaemic heart disease indicate a chronic infection. The pharyngeal presence of C. pneumoniae might contribute to a low grade inflammatory activation or be a source for further spread of the bacteria to atherosclerotic vessels.     

Acquired tracheomalacia--a case report

Divalproex sodium is an effective drug for the treatment of migraine. Most adverse drug events are transient and not of great clinical concern. Although rare, well-documented examples of liver toxicity have been reported in children under 2 years of age on polypharmacy. Additional cases occur in children under 10 who are receiving polypharmacy, particularly those who have intractable seizures and degenerative central nervous system disease. Clinicians who treat migraineurs with divalproex sodium do not need to be overly preoccupied with monitoring of drug levels and liver function tests. The most valuable test is clinical observation of the patient.     

The effect of interleukin-1alpha on outflow facility in rat eyes

BACKGROUND: There are few reports in Mexico on the prevalence of infection by virus D. OBJECTIVE: The aim of the present study was to study the hepatitis D virus infection prevalence in patients entering to the University Hospital. METHODS: Seventy three HBsAg positive patients sera were studied. There were 38 patients with acute hepatitis, 28 patients with chronic liver disease and 7 were asymptomatic HBsAg carriers. Serological markers for hepatitis viruses B, D and C were detected by means of ELISA test (Abbott). RESULTS: Anti-HDV was detected in 3 cases (4%). The first two cases were men with acute hepatitis B. Both had a coinfection by viruses B and D, however IgM anticore could not be demonstrated in the first case, this patient developed hepatic cirrhosis within 13 months, in addition he had a concurrent infection by hepatitis C virus with a positive second generation ELISA antibody. The second case recovered from the acute hepatitis. The third case was a female nurse with acute hepatitis and a coinfection by viruses B and D who recovered from the acute attack. Antibody to hepatitis C was present in 3 out of 22 patients with chronic liver disease (13.6%), one of them having an hepatocellular carcinoma. CONCLUSIONS: Our results coincide with the previously reported low incidence of hepatitis D and represent the first report in Mexico of concurrent infections by viruses B-C and B-D-C.     

Hepatitis G virus infection before and after liver transplantation. Liver Transplantation Database

The hepatitis G virus is a newly discovered flavivirus that has been linked to acute and chronic hepatitis of unknown cause. We determined the prevalence of hepatitis G virus infection in 179 selected patients undergoing liver transplantation at three centers participating in the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Liver Transplantation Database. Pretransplantation and posttransplantation specimens were tested for hepatitis G virus RNA by polymerase chain reaction. Before transplantation, 9 of 38 (24%) patients with fulminant hepatic failure, 9 of 62 (15%) with cryptogenic cirrhosis, 3 of 35 (9%) with cholestatic liver disease, and 5 of 44 (11%) with chronic hepatitis C were positive for hepatitis G virus RNA (P = .27). Patients with and without viral RNA were similar in clinical features, liver test abnormalities, and survival after transplantation. Posttransplantation serum specimens were tested from 73 patients; 9 of 11 (82%) who were positive for viral RNA before transplantation remained positive, but 35 of 62 (56%) patients who were initially negative became positive after transplantation, a rate consistent with that predicted from the number of blood products administered. Only 5% of de novo HGV infections could be attributed to preexisting hepatitis G virus RNA in the donor. Comparison of patients with and without hepatitis G virus infection showed no difference in incidence of hepatitis after transplantation. Thus, hepatitis G virus infection was present in 15% of patients before and appeared de novo in half of patients after liver transplantation. Although hepatitis G virus infection was not associated with poor outcome, the frequency of this infection after transplantation calls for further long-term evaluation.     

Current results and evolving indications for liver transplantation in children

Liver transplantation continues to be successful and effective treatment for acute and chronic liver failure, and many important lessons have been learned. The development of innovative operative techniques has much reduced the waiting list mortality rate and has extended transplantation to younger and sicker children and to those with functionally normal livers who may benefit from auxiliary liver transplantation. The incidence and range of postoperative complications have improved with increased medical and surgical expertise. As information on long-term outcome for liver transplantation is gained, it is clear that many children will benefit from early elective liver transplantation before the development of significant growth or psychosocial retardation. Early transplantation is also indicated in children with cirrhosis and intrapulmonary shunting or cystic fibrosis with moderate lung disease. During the same period, evolving medical therapy has altered the natural history, patient selection, and timing of transplantation in children with tyrosinaemia type I, primary bile acid disorders, neonatal haemochromatosis, and potentially, cystic fibrosis. It is now clear that children with significant multisystem disease, such as mitochondrial disorders or severe systemic oxalosis, are no longer suitable candidates for liver transplantation. The successful development of liver transplantation has brought good quality life to many children and their families. There are still many lessons to learn and there are future challenges such as the ever-increasing problems of donor scarcity and the search for potent but less toxic immunosuppressive agents.     

Detection of replicative form of HCV RNA in peripheral blood leukocytes and its clinical significance

Nested RT-PCR, done by using degenerated primer pair, was used to detect hepatitis C virus RNA (HCV RNA) in serum, plasma, liver and peripheral blood leukocytes (PBLC) of 30 patients with acute and chronic posttransfusion hepatitis C and 7 asymptomatic anti-HCV positive subjects. The results showed that the percentage of positive HCV RNA in PBLC, including both the plus and minus strands, in patients with chronic hepatitis C was significantly higher than that in acute hepatitis C and asymptomatic anti-HCV positive subjects (P < 0.05-0.001). All the 7 asymptomatic anti-HCV positive subjects did not have detectable minus strand of HCV RNA in their PBLC, serum or plasma. In 17 patients who had liver histologic examination, the positive rate of both strands of HCV RNA in PBLC of acute hepatitis (AH) was lower than that of chronic active hepatitis (CAH) (P < 0.05). Both strands of HCV RNA were detected in the liver of one AH and 6 CAH patients. The present data confirmed that PBLC of patients with hepatitis C were indeed infected by HCV. The longer the infection time, the more the chance of PBLC being infected by HCV. Patients with active liver disease (CAH) had usually higher positive rate of minus strands of HCV RNA in PBLC. In the serum and plasma of all the 37 cases, minus strand of HCV RNA was not detected and the positive rate of the plus strand of HCV RNA in their serum and plasma was similar. Futhermore, the positive rate of both plus and minus strands of HCV RNA in PBLC of 30 patients with chronic hepatitis C was also similar. It is suggested that HCV not only may infect PBLC, but also replicate in PBLC and that the occurrence of minus strand of HCV RNA is associated with activity of liver disease.     

Detection of IgA antibodies as important markers of acute primary infection with Toxoplasma gondii

The diagnosis of Toxoplasma gondii infection is currently based on immunological tests, but tests for IgM and IgG antibodies alone are often insufficient to estimate the risk of active disease, especially during pregnancy and in immunodeficient patients. Classically the study of anti-toxoplasma immunity involves titration of IgG antibodies, which reflect immunity to the parasite, and IgM antibodies which of present, reveal acute infection. However, technical advances have shown the limitations of these tests as tests for IgM can be positive because of residual specific IgM or even in subjects free of acute infection due to the existence of natural interfering IgM. In addition, IgM can be absent in children with congenital toxoplasmosis or subjects with secondary reactivation. The purpose of our study was to evaluated of IgA antibodies to T. gondii in serum samples which were positive in screening test. Our results confirm the diagnostic value of testing for anti-toxoplasma IgA antibodies. These antibodies are absent in uninfected subjects and are detected rapidly after primary infection. The determination of IgA complements IgM determination for the diagnosis of toxoplasmosis.     

Abnormal liver function tests in the primary care setting

Results of laboratory tests ordered during a primary care encounter may reveal findings of abnormal liver function tests, including elevated liver enzymes, hyperbilirubinemia, hypoalbuminemia or abnormal coagulation tests. The object of this study was to describe the spectrum of these liver function test (LFT) abnormalities in primary care. Results of all laboratory tests ordered during 10 months in an urban primary care clinic were retrospectively reviewed and the medical charts of patients with abnormal LFTs were studied. In 217/1088 (20%) of the tests at least 1 LFT abnormality was found in 156 patients. New diagnoses were made in 104 patients. The main diagnostic groups were: non-alcoholic fatty liver changes, Gilbert's disease, acute infectious hepatitis, alcoholic liver disease and cirrhosis and hepatotoxic drug injury. In 60 patients the physician classified the abnormality as negligible and not associated with significant disease. However, an abnormal test that had been ordered for evaluation of a specific complaint, was indeed likely to represent significant disease (X2 = 29.5, p < 0.001). We conclude that finding abnormalities in liver function tests is common in the primary care clinic but does not often indicate significant liver disease.     

Acute Q fever hepatitis in Taiwan

We report a case of a chronic hepatitis B carrier with an episode of acute hepatitis. The patient presented with a headache, arthralgias, jaundice and fever. While the laboratory tests mimicked chronic hepatitis B with an acute exacerbation, lipogranulomatous changes seen in the liver biopsy strongly suggested the presence of Q fever. Serology testing for Coxiella burneti proved positive and the patient responded to tetracycline therapy. While previously unreported in Taiwan, Q fever is important to consider in an atypical hepatitis presentation because it is a treatable condition.     

Human fascioliasis: comparison of a fasciolicidal effect of bithionol and praziquantel

BACKGROUND: The frequency of gliadin antibody (GA) positivity has been found to be increased among patients with chronic liver disease, as has that of coeliac disease (CD). CD has also been found to be increased among patients with primary biliary cirrhosis (PBC) or primary sclerosing cholangitis (PSC). METHODS: To investigate these relationships further, a micro-enzyme-linked immunosorbent assay and immunofluorescence tests for GAs and endomysial antibodies (EMAs) were performed in large subgroups of patients representing various chronic liver diseases and in healthy blood donors. RESULTS: As compared with blood donors (among whom it was 5%) the frequency of IgA GA positivity was higher in all patient subgroups: alcoholic liver disease, 20% (22 of 110, P < 0.001); PBC, 16% (16 of 101, P < 0.001); PSC, 24% (19 of 80, P < 0.001); chronic hepatitis, 19% (13 of 70, P < 0.001); and hepatitis C virus infection, 11% (11 of 104, P < 0.01). Two patients with autoimmune chronic hepatitis were EMA-positive, and in both cases the presence of CD was verified by small-bowel biopsy. CONCLUSIONS: IgA GA positivity generally occurs at increased frequency among patients with chronic liver disease and may represent non-specific immune activation. In liver disease GA testing is not useful in screening for CD, whereas the EMA test seems to be highly specific. CD is more prevalent than expected among patients with autoimmune chronic hepatitis but not among those with PBC or PSC.     

Chronic hepatitis C infection. A disease ideally suited to management in the primary care setting

BACKGROUND: The currently sub-optional efficacy of therapy for chronic hepatitis C infection makes other management modalities a priority. OBJECTIVE: To address issues in overall management of hepatitis C infection through case studies. DISCUSSION: Management of hepatitis C infection should cover discussion of hepatitis C transmission, natural history (prognosis) and therapy. A polymerase chain reaction (PCR) for detection of hepatitis C RNA should be ordered in those patients with persistently normal liver function tests to determine the presence or absence of chronic infection. Other measures include assessment and counselling in relation to alcohol intake, and vaccination against both hepatitis A and hepatitis B. In patients with abnormal liver function tests a liver biopsy should be considered in order to determine the stage of disease, thus enabling targeting of therapy to those at highest risk of progression to advanced liver disease.     

Plasma levels of fibronectin in patients with chronic viral and alcoholic liver disease

BACKGROUND/AIMS: Plasma fibronectin levels are reportedly decreased in patients with cirrhosis, while increases are associated with acute and chronic hepatitis. We studied 101 patients with chronic liver disease to determine the relationship between disease etiology and plasma fibronectin levels. METHODOLOGY: Plasma fibronectin levels and standard liver function parameters were measured in all patients and 11 healthy controls. Antipyrine metabolism was also evaluated in 39 patients. Results were analyzed according to etiology (HBV, HCV, alcohol abuse) and histological findings (chronic active hepatitis (CAH) with/without fibrosis, steatosis, cirrhosis). RESULTS: The fibronectin levels were similar in patients with HBV, HCV and alcohol-related disease. Analysis of the groups based on histological features showed that fibronectin levels in cirrhotics (mean 270.69 microg/ml) were significantly lower than those of the control (mean 372.00 microg/ml) and other patient groups (steatosis: 470.37 microg/ml; CAH: 417.93 microg/ml; CAH and fibrosis: 426.72 microg/ml). Plasma fibronectin displayed a positive correlation with antipyrine metabolism and parameters of hepatic synthesis. CONCLUSIONS: Plasma fibronectin appears to be an index of hepatic parenchymal function but shows no relation to the etiology of the liver disease.     

Effect of training on general practitioners'' use of a brief intervention for excessive drinkers

During recent years the outcome of acute hepatitis A in chronic liver disease has been discussed controversially. Data from large hepatitis A epidemics and surveillance data from the United States suggest a significantly higher risk of fatal outcome in patients with chronic hepatitis B. Patients with chronic active hepatitis or liver cirrhosis seem to be at highest risk, while HBsAg carriers may exhibit a benign course of the disease. Patients with chronic hepatitis C also seem to have a significantly higher risk of fulminant hepatic failure when superinfected with hepatitis A. The recently reported unsuspected coincidence of autoimmune markers with a fulminant course of hepatitis A in those patients needs to be confirmed. Vaccination against hepatitis A in patients with chronic liver disease has been shown to be safe and effective.     

Changes in aminophenazone metabolism with acute hepatitis in children (author's transl)

Serum half-life of aminophenazone was measured in 23 children with acute viral hepatitis and children with normal liver biopsy of matched ages. In acute hepatitis the value was 6.71 +/- 3.34, significantly longer than in the normal controls (2.79 +/- 0.53). Two hours after oral intake of the drug the serum concentration was higher in healthy children than in those with hepatitis, but the difference was not significant. Especially in children with intercurrent acute hepatic disease account must be taken of impaired metabolism during long-term drug treatment.     

Renal hypertension in children

Preliminary results of this retrospective-prospective analysis of renal hypertension in 110 children indicate that hypertension may be secondary to a wide variety of acute progresive, and chronic renal diseases which may be either congenital or acquired. Affected children may be detected at any time from infancy through adolescence. Symptoms usually associated with acute glomerulonephritis (i.e., headache, swelling, nausea, vomiting, anorexia, fatigue, dizziness, and fever) occur in both acute and chronic renal diseases associated with hypertension. Headache and swelling are the most common symptoms in this series. Peripheral edema, rales, and increased heart size were found in between 10 and 25% of these children. Differential diagnosis may be approached by a consideration of causes of acute and chronic hypertension. The child with chronic renal disease usually presents with a long history of fatigability, poor growth, and pallor, and laboratory tests reveal elevation of the creatinine and BUN along with anemia, hypocalcemia, and hyperphosphatemia. In contrast, the child with acute renal disease and hypertension presents with a history of prior good health followed by the abrupt onset of signs and symptoms of renal disease; laboratory tests usually reveal modest elevations of creatinine and BUN, anemia is unusual, an abnormal urinalysis is common, and serum calcium and phosphorous levels are usually normal. Renovascular and asymmetric renal parenchymal disease represent uncommon but important conditions because surgery may be curative. Treatment may be surgical, medical, or combined. Surgical conditions include renal trauma, hydronephrosis, asymmetric renal disease, and renal arterial disease. Adequate blood pressure control without medication can be expected following surgery in instances of unilateral involvement with a normal contralateral kidney. Meticulous assessment of the contralateral kidney is needed to determine that it is normal. If surgery is unsuccessful or is not indicated, pharmacologic therapy is initiated with a stepwise regimen starting with the mildest agent (e.g., thiazides) and then adding additional antihypertensive drugs when adequate blood pressure control has not yet been achieved. The goal of therapy is the lowest, safest, tolerated blood pressure levels. Long-term, carefully designed studies of antihypertensive agents for children with renal hypertension are not available. The need for collection and critical analysis of data concerning the clinical course of children with renal hypertension is evident from a review of the literature and from the preliminary data presented in this series. The presentation of such information and a critique of outcome variables will provide a basis for program planning for affected children and improvement in patient care where indicated.