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Biomedical subjects

J Main

Publications and source records attributed to J Main.

At least 73 records · Page 4Linked to original sources

Dual-centre, double-blind, randomised trial of lymphoblastoid interferon alpha with or without steroid pretreatment in children with chronic hepatitis B.

Thirty-five children with chronic HBV infection, HBV-DNA and eAg serum positivity, and HBcAg in liver tissue were treated with lymphoblastoid human interferon alpha with (16 cases) or without (19 cases) prednisolone pretreatment. The patients were double-blind randomized to receive steroid or placebo for 4 weeks, followed after 2 weeks by 5 or 10 MU/m2 interferon for 12 weeks. The e anti-e seroconversion rate reached 48%, which is much higher than the spontaneous seroconversion rate. The influence of "prednisolone priming" was not statistically significant. HBeAg clearance was similar in both groups (44% after prednisolone/interferon and 53% after interferon alone). The response to either treatment did not correlate with the pretreatment serum transaminase. HBV-DNA or degree of histological activity. Interferon was well tolerated, the side effects being less severe than in adults, and never led to suspension of the treatment.

Adolescent↗

An unusual gastrointestinal presentation of leishmaniasis.

While visceral leishmaniasis (VL) generally occurs in immunocompetent subjects in endemic areas, it has been increasingly recognised as an important opportunistic infection in the immunocompromised including those infected with the human immunodeficiency virus. We report an unusual presentation of visceral leishmaniasis in a patient with the acquired immunodeficiency syndrome (AIDS) with disease which appeared to be limited to the gastrointestinal tract.

AIDS-Related Opportunistic Infections↗

Diagnosis of cytomegalovirus (CMV) disease in renal allograft recipients: the role of semiquantitative polymerase chain reaction (PCR).

BACKGROUND: Cytomegalovirus disease remains a significant cause of morbidity and mortality in the renal allograft recipient. There is a need for rapid and sensitive techniques predictive of CMV disease to allow initiation of early antiviral therapy. METHODS: Seventy-seven renal allograft recipients were enrolled in a prospective study where CMV viruria (shell vial culture/DEAFF test), viraemia (shell vial culture), serology and detection of virus DNA in peripheral blood leukocytes by PCR (CMV DNAemia) were correlated with clinical evidence of CMV disease. RESULTS: Serology and shell vial culture had poor sensitivity for the early diagnosis of CMV disease. CMV DNAemia appeared to correlate with active virus replication. CMV DNAemia had a sensitivity and negative predictive value of 100% and a positive predictive value of 27% for CMV disease. Patients with symptomatic CMV disease were shown to have higher levels of CMV DNAemia than those with asymptomatic infection. CONCLUSIONS: A negative CMV DNAemia result excluded CMV disease with confidence, but a positive result (given the low positive predictive value) did not by itself provide a reliable guide for the initiation of pre-emptive antiviral therapy. However, the semiquantitative CMV DNAemia result taken together with the clinical findings provided useful information for patient management.

Adolescent↗

Future studies of combination therapy for chronic hepatitis C: optimizing response rates for each hepatitis C population.

Interferon alfa, the only treatment currently approved for chronic hepatitis C virus infection, has a limited response rate (20-25%) in most patients. Ribavirin has also been used to treat hepatitis C virus infection, but treatment results in only a modest reduction in HCV-RNA levels; most patients relapse after the drug is discontinued. Combination therapy with ribavirin and interferon seems to be a logical approach to the treatment of hepatitis C virus infection. Small studies suggest that combination therapy results in improved sustained response rates compared with either interferon or ribavirin alone. In one study, 6 months of combination therapy was compared with 6 months of ribavirin monotherapy and 6 months of interferon alfa monotherapy. The sustained virologic response rates were 47% for combination therapy, 13% for interferon monotherapy, and 0% for ribavirin monotherapy. This study suggests that combination therapy can potentially double the sustained response rate, but larger studies are needed to evaluate this further. In trial design for clinical studies, many factors must be considered. Determining the response to interferon monotherapy might include establishing liver histology (especially in patients with cirrhosis) and hepatitis C virus genotype--types 1b and 4 are associated with a poor response, which is likely to affect the response to combination therapy. Patients in treatment trials should be followed long term at regular intervals; it is only with prolonged, detailed follow-up that the full effects of antiviral therapy on health and prevention of cirrhosis and hepatocellular carcinoma can be determined. Large multicenter studies are also needed to determine the effect of combination therapy in liver transplant patients. These studies must also address toxicity issues, as interferon may increase the risk of graft rejection post-transplant, and the low-grade hemolysis associated with ribavirin may stimulate hepatic iron deposition.

Antiviral Agents↗

Rapid catastrophic onset of Wegener's granulomatosis in a renal transplant.

A 62-year-old man with chronic renal failure secondary to Wegener's granulomatosis received a cadaveric renal graft in December 1990 after 2 years' treatment with continuous ambulatory peritoneal dialysis. Early graft function was good and serum creatinine fell steadily. On day 5 he became anuric and the graft became swollen and tender. Isotope renography showed no perfusion and the kidney was removed. Pathological examination showed widespread acute arteritis consistent with recurrent Wegener's granulomatosis. Recurrence of Wegener's granulomatosis in renal grafts is rare. The 4 previously reported cases are reviewed.

Granulomatosis with Polyangiitis↗

Adverse effects of drugs used in the management of opportunistic infections associated with HIV infection.

Pneumocystis carinii pneumonia (PCP) is one of the most common AIDS-defining diagnoses. First-line therapy is cotrimoxazole (trimethoprim-sulfamethoxazole), despite a high incidence of toxic effects, and a greater incidence of hypersensitivity reactions among HIV-positive patients compared with the seronegative population. Alternative agents such as intravenous pentamidine, or clindamycin with primaquine, and trimethoprim with dapsone, also have a wide range of serious adverse effects, but remain treatment options. Atovaquone appears promising for the treatment of both PCP and toxoplasmosis, and has a lower reported incidence of toxicity than the alternative agents. The most toxic antifungal drugs are reserved for serious infections, such as cryptococcal meningitis. Liposomal amphotericin B has less renal toxicity than standard formulations, and exemplifies that new formulations of existing drugs, although often expensive, may have a better adverse effect profile. There are 2 different drugs currently available for cytomegalovirus (CMV) infections, ganciclovir and foscarnet. Both have a high incidence of serious adverse effects; ganciclovir mainly causes bone marrow toxicity and foscarnet leads to renal toxicity. The drugs used for mycobacterial infection (including mycobacteria as well as tuberculosis) have a wide range of adverse effects, particularly skin rashes and drug-induced hepatitis. Some of these compounds are quite new, such as rifabutin and clarithromycin, and it is important to be ever vigilant for previously unreported adverse effects.

AIDS-Related Opportunistic Infections↗

Doppler color flow mapping of epicardial coronary arteries: initial observations.

OBJECTIVES: We addressed the hypothesis that blood flow could be imaged by Doppler color flow mapping of the coronary arteries and characteristic patterns described in normal and diseased vessels. BACKGROUND: Echocardiographic imaging of the epicardial coronary arteries has been suggested as a useful adjunct to their intraoperative evaluation. Addition of Doppler color flow mapping could potentially enhance this evaluation by displaying the flow disturbance produced by anatomic lesions whose physiologic significance may otherwise be uncertain. In experimental models, such displays could also potentially provide insights into the pathophysiology of coronary blood flow and stenosis. METHODS: Epicardial coronary arteries were examined with a high resolution 7-MHz linear phased-array transducer both in vivo and in vitro. 1) The coronary arteries were studied in the beating hearts of 10 open chest dogs in which experimental stenoses were also created; the maximal extent of the arterial tree in which flow could be seen in the most ideal setting was also examined in four additional excised perfused canine hearts. 2) Six excised human coronary arteries were perfused in a pulsatile manner to determine whether abnormal flow patterns could be prospectively identified and subsequently correlated with pathologic evidence of stenosis. RESULTS: All normal coronary artery segments studied showed homogeneous flow without evidence of flow disturbance. In the excised heart, flow could be visualized to the distal extent of the epicardial vessels; in the open chest model, visualization of the proximal 5 to 6 cm was comparable, although surrounding structures limited access to the terminal portions of the vessels. The stenotic lesions created in the canine hearts (n = 9) showed recognizable alterations in the flow pattern: localized aliasing, proximal blood flow acceleration, distal flow disturbance and recirculatory flow. In the excised human arteries, these features identified 12 lesions, all of which corresponded to areas of > or = 50% lumen narrowing by pathologic examination. CONCLUSION: Blood flow in the epicardial coronary arteries can be imaged by Doppler color flow mapping and characteristic flow patterns described in normal and diseased vessels.

Animals↗

Short report: prednisolone withdrawal followed by lymphoblastoid interferon in the therapy of adult patients with presumed childhood-acquired chronic hepatitis B virus infection.

Eighteen patients with presumed childhood acquisition of chronic hepatitis B virus infection were initially entered into this randomized controlled trial. Twelve were treated with prednisolone for 4 weeks followed, after a 2-week gap, by thrice weekly lymphoblastoid alpha-interferon for 12 weeks. Two of these had previously acted as untreated controls. Three of the 12 patients (25%) [who were initially hepatitis B virus (HBV) surface antigen (HBsAg), 'e' antigen (HBeAg) and HBV-DNA positive] became HBeAg and HBV-DNA negative during therapy and remained so after 12 months post-therapy follow-up. One of these also lost HBsAg. A further two patients lost HBeAg and HBV-DNA during therapy but relapsed 6 and 9 months later. Two additional patients were HBV-DNA negative but HBeAg positive at the end of follow-up. None of the eight untreated control patients seroconverted during an identical follow-up period. Two further patients were HBsAg and HBeAg positive but HBV-DNA negative at the start of therapy. These were omitted from the final analysis: both subsequently lost HBeAg. The treatment response was associated with a rise in aspartate aminotransferase, peaking 2-6 weeks after prednisolone withdrawal, loss of HBV-DNA 0-8 weeks later and subsequent normalization of liver function tests. Treatment was well tolerated.

Adolescent↗

Cytomegalovirus mononucleosis: risk for fathers of young children.

A case of pyrexia of unknown origin in a 35-year-old man, who had become a father nine months earlier, is presented. A diagnosis of cytomegalovirus mononucleosis was achieved only after extensive investigations. It is suggested that cytomegalovirus mononucleosis should be added to the differential diagnosis when investigating pyrexia of unknown origin in fathers of young children.

Adult↗

The diagnosis and management of viral hepatitis.

Recent developments make it possible to identify the causative virus in most cases of acute and chronic viral hepatitis. Improvements in supportive care and the availability of hepatic transplantation have considerably reduced mortality for the fulminant forms of acute viral hepatitis, and advances in antiviral therapy have led to the possibility of cure for some patients with chronic viral hepatitis and improvement for many others. Algorithms are presented as a guide to the diagnosis and management of acute and chronic viral hepatitis.

Acute Disease↗