Interpretation of blood films in diagnosis of malaria.
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Biomedical subjects
Publications and source records attributed to M G Brook.
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OBJECTIVE: To confirm the findings of pilot studies that interferon alfa is an effective treatment of Europid men with chronic hepatitis B virus infection. DESIGN: Randomised controlled trial of three months treatment with interferon alfa followed by 12 months of observation. SETTING: Outpatient clinic of a tertiary referral centre. PATIENTS: 37 Treated men (six anti-HIV positive) and 34 untreated men (nine anti-HIV positive) who met the criteria for the trial. Four controls failed to complete follow up. INTERVENTIONS: The treated group received subcutaneous injections of 5-10 MU interferon alfa/m2 daily for five days, then 10 MU/m2 thrice weekly for 11 weeks. Follow up continued at monthly intervals for 12 months. Untreated controls were monitored over the same period. MAIN OUTCOME MEASURE: Hepatitis B e antigen and hepatitis B virus DNA state after 15 months of observation. RESULTS: 12 Of the 37 treated patients cleared hepatitis B e antigen and hepatitis B virus DNA, whereas only one of 30 untreated controls seroconverted over the same period--an increased response rate of 29% (95% confidence interval 13% to 45%). The life table estimate of response at 15 months was 35% in treated patients, an increase of 32% above controls (95% confidence interval 16% to 48%). The response rates in groups by predictive pretreatment variables were 12 of 31 anti-HIV negative patients (excess response 34%; 95% confidence interval 14% to 54%), 12 of 26 with chronic active hepatitis before treatment (excess response 46%; 27% to 65%), and 12 of 21 with a pretreatment serum aspartate aminotransferase activity greater than 70 IU/l (excess response 46%; 16% to 76%). The combination of these factors predicted response with a sensitivity of 100% and a specificity of 80%. Four of the 12 responders, who had all been infected for less than two years, also lost hepatitis B surface antigen. Treatment was well tolerated. CONCLUSIONS: Interferon alfa is effective in the treatment of a proportion of Europid men with chronic hepatitis B virus infection, who might be identified before treatment. Additional strategies are required to improve the rate of response.
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Twenty-one pretreatment variables were assessed for their significance in response prediction using data from 114 patients given alpha-interferon for chronic hepatitis B virus infection. In those patients who had received a minimum of 90 million units per m2 total dose over 12 weeks, a negative anti-human immunodeficiency virus antibody status (p less than 0.001), chronic active hepatitis on liver biopsy (p less than 0.005), high AST level (p less than 0.001), low hepatitis B virus DNA level (p less than 0.001) and a history of acute hepatitis (p less than 0.005) were all associated with an increased likelihood of response on univariate analysis. On stepwise logistic regression analysis, hepatitis B virus DNA, AST and a history of acute hepatitis predicted response independently (p less than 0.05). The most reliable combination of predictive factors was a negative anti-human immunodeficiency virus antibody status, with either a positive history of acute icteric hepatitis and AST greater than 45 IU per liter or no history of acute icteric hepatitis and AST greater than 85 IU per liter, which predicted response in 77% with a specificity of 79% (p less than 0.001). The loss of HBsAg in addition to HBeAg and hepatitis B virus DNA was more likely to occur in patients with chronic infection of less than 2 years duration (p less than 0.001).
Sequential liver biopsies were taken from 66 patients with chronic hepatitis B virus (HBV) infection being followed in randomised controlled trials of therapy with alpha interferons or adenine arabinoside 5'-monophosphate. In the group of 23 patients responding to treatment with the permanent loss of HBe antigen and HBV-DNA from their serum, there was a significant reduction in hepatic inflammatory activity and none developed cirrhosis. In contrast, inflammatory activity continued in the group of 24 patients that did not respond to therapy, and in the group of 19 patients who received no therapy. Two untreated controls progressed to cirrhosis. Further studies confirmed that in those clearing HBeAg and HBV-DNA from the serum, HBcAg and HBeAg were also lost from the liver. This study demonstrates that, as in natural seroconversion, successful treatment of chronic HBV infection is associated with loss of hepatic as well as serum markers of HBV replication, and is followed by a reduction in hepatic inflammation. Antiviral therapy may prevent progression to cirrhosis in some cases.
In a randomised controlled trial recombinant interferon alpha 2A (Roferon-A, rIFN alfa A) given at a dosage of 10 million units (MU)/m2 thrice weekly for six months was significantly better (p less than 0.02) than no treatment in producing a sustained loss of hepatitis Be antigen (HBeAg) in hepatitis B virus (HBV) chronic carriers. Although lower doses (5 MU/m2 and 2.5 MU/m2) also produced some responses, the seroconversion rate was not significantly greater than that observed in the control group. Sixteen of the 45 patients receiving interferon were human immunodeficiency virus (HIV) antibody positive: none of these responded. Forty one per cent of the anti-HIV negative patients receiving interferon (12/29, p less than 0.005) lost HBeAg and 17% (5/29) lost hepatitis B surface antigen (HBsAg). The response rate among these anti-HIV negative patients receiving at least three months therapy was 46% and 19% respectively. Low pretreatment HBV-DNA and absence of anti-HIV were the only significant independent variables predicting response to therapy (p less than 0.03 and p less than 0.05 respectively). In six patients, neutralising antibodies to alpha interferon were detected during therapy, the majority being non-responders.
We describe our experience over a three-year period in the detection of antenatal patients with hepatitis B virus (HBV) carriage, and the successful prevention of vertical transmission in the infants of HBsAg-positive women. Nine of the 26 infants born to HBsAg-positive mothers were considered to be at high risk of infection. Eight of these nine remained HBsAg-negative after passive or passive/active immunization. The majority of infants tested had anti-HBs antibody titres above 10 i.u./l from the first month. In comparison with the cost of caring for patients with chronic hepatitis B infection and decompensated cirrhosis, non-selective testing of pregnant women for HBsAg is found to be cost effective.
Ten patients with evidence of continuing HDV replication were treated with lymphoblastoid alpha-interferon and eight more were followed as a non-randomized control group. Four out of eight patients who completed one year of follow-up had cleared HDV-RNA from the serum whilst none of the control group did so. In these four responding cases there was a transient increase in transaminase levels during treatment and in two, this was followed by improvement. One patient also cleared HBV and seroconverted to anti-HBs (antibody to hepatitis B surface antigen--HBsAg). In one patient with sustained loss of HDV, recurrence of HDV infection was detected 18 months after completion of treatment. These data suggest that alpha-interferon can inhibit HDV replication in the short term but relapse after one to two years may occur. Inhibition of HDV-RNA is associated with improvement in the inflammatory liver disease and now larger studies are required to determine whether it influences survival.
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We describe a patient who presented with a widespread erythematous rash, diarrhoea, confusion, pre-renal uraemia and hyponatraemia. The diagnosis of staphylococcal toxic shock syndrome seemed likely as she was menstruating and there was no evidence of pharyngitis. A rising ASO titre confirmed a streptococcal aetiology and thus 'toxic' scarlet fever. Toxic shock syndrome and toxic scarlet fever are compared.
We report 2 cases of Streptococcus milleri infection of the lung. One patient, a 58-year-old woman, presented with a large abscess in a previously normal lung, the other, a 53-year-old man, had a secondary infection of lung previously scarred by tuberculosis and surgery. Both patients had severe dental caries. Four weeks of therapy with high dose antibiotics and physiotherapy were required. Invasive techniques were needed to isolate the organism.
Five HIV p24 antigen (p24Ag)-positive patients received alpha interferon during trials of therapy for hepatitis B. Four of these showed marked falls in p24Ag during treatment. One of the two patients who became p24Ag-negative [corrected] developed anti-p24 antibodies (anti-p24). Five out of nine p24Ag-negative HIV-antibody-positive patients showed a rise in anti-p24 titres during interferon therapy, whereas only two out of six untreated controls showed a similar rise. This study provides evidence that alpha interferon has anti-HIV activity in vivo.
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Human lymphoblastoid interferon, in an initial dose of 2.5 MU m-2 weekly i.m., was given with mitozantrone 12 mg m-2 i.v. every 3 weeks to 15 patients with hepatocellular carcinoma. The survival curve for these patients was worse than that of 15 patients previously treated with mitozantrone alone; there were more long-term survivors in those not given interferon; more side-effects were seen in the group given interferon. The addition of interferon to mitozantrone in the management of hepatocellular carcinoma is not recommended.
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Current knowledge of Escherichia coli strains responsible for bowel infections, including the more recently defined entero- hemorrhagic and entero-adherent types, is reviewed.