Dyspnoea is a frequent and devastating symptom of advanced cancer. The purpose of this prospective, double-blind, crossover trial was to assess the effects of supplemental oxygen on the intensity of dyspnoea. 14 patients with hypoxaemic dyspnoea due to advanced cancer were randomised to receive either oxygen or air; the gases were delivered at 5 L/min by mask. After 5 min of stable oxygen saturation (pulse oximetry), patients were crossed over to receive the other treatment. The crossover was repeated twice. Dyspnoea was assessed with a visual analogue scale (O = no dyspnoea, 100 = worst dyspnoea). Mean difference in dyspnoea visual analogue scale between air and oxygen treatment was 20.5 (95% confidence interval 13.5 to 27.6). 12 patients consistently preferred oxygen to air; similarly, the investigator consistently chose oxygen for the same 12 patients. In a global rating questionnaire, patients reported little or no benefit during the air phase compared with moderate to much benefit during the oxygen phase. We conclude that oxygen is beneficial to patients with hypoxia and dyspnoea at rest.

Treatment of atopic dermatitis with essential fatty acids remains controversial. A double-blind, placebo-controlled, parallel-group study was done to investigate the response of patients with atopic dermatitis to essential fatty acid supplements. Patients with atopic dermatitis were randomised to receive evening primrose oil, evening primrose oil and fish oil, or placebo for 16 weeks. Disease activity was monitored by clinical severity scores recorded by the investigator, topical steroid requirement, and symptom scores recorded by subjects. Of 123 subjects recruited, 102 completed the treatment period. No improvement with active treatment was demonstrated. Our study, which avoided the methodological and analytical problems of previous studies, found no effect of essential fatty acid supplementation in atopic dermatitis.

Acute exacerbations of chronic obstructive airways disease (COAD) are a common cause of admission to hospital, and have a high mortality. Nasal intermittent positive pressure ventilation (NIPPV) has been used successfully in patients with respiratory failure due to neuromuscular and skeletal disorders, but the outcome of treatment in patients with COAD is less well known. We carried out a prospective randomised controlled trial of conventional treatment versus conventional treatment plus NIPPV, in 60 patients with acute ventilatory failure due to exacerbations of COAD. For the NIPPV group there was a rise in pH, compared with a fall in the controls (mean difference of change between the groups 0.046 [95% CI 0.06-0.02, p < 0.001]), and a larger fall in PaCO2 (mean difference in change between the groups 1.2 kPa [95% CI 0.45 to 2.03, p < 0.01]). Median visual analogue scores over the first 3 days of admission showed less breathlessness in the NIPPV group (2.3 cm [range 0.1-5.5]) than in the control group (4.5 cm [range 0.9-8.8]) (p < 0.025). Survival rates at 30 days were compared for intention-to-treat and efficacy populations. In the efficacy mortality comparison, mortality in the NIPPV group was reduced: 1/26 vs 9/30 (relative risk = 0.13, CI = 0.02-0.95, p = 0.014). This effect was less in the intention-to-treat analysis: 3/30 vs 9/30 (relative risk = 0.33, CI = 0.10-1.11, p = 0.106). In patients with acute ventilatory failure due to COAD who received NIPPV there was a significant rise in pH, a reduction in PaCO2 and breathlessness, and reduced mortality.

In many developing countries, the immunogenicity of three doses of live, attenuated, oral poliovirus vaccine (OPV) is lower than that in industrialised countries. We evaluated serum neutralising antibody responses in 368 children aged 6 months and 346 children aged 9 months in Côte d'Ivoire who had previously received three doses of OPV at 2, 3, and 4 months of age, and who were then randomised to receive a supplemental dose of OPV or enhanced-potency inactivated poliovirus vaccine (IPV) at the time of measles vaccination. Although both vaccines increased seroconversion to all three poliovirus types, antibody responses were greater in the IPV group. Among children with no detectable antibody at baseline, IPV was 2 to 14 times more likely than OPV to induce seroconversion (type 1, 80% vs 40% at 6 months [p < 0.001] and 81% vs 14% at 9 months [p < 0.001]; type 3, 76% vs 22% at 6 months [p < 0.001], and 67% vs 5% at 9 months [p < 0.001]. Among children with detectable antibody at baseline, IPV was 1.4 to 7 times more likely than OPV to elicit 4-fold or more rises in antibody titre (p < 0.01). Geometric mean titres (GMTs) to all three poliovirus types were also consistently higher among IPV recipients than in OPV recipients when measured 4-6 weeks and 13-17 months after vaccination. Administration of a supplemental dose of IPV or OPV, which requires no additional visits or changes in the existing immunisation schedule, might improve protection against paralytic poliomyelitis in communities with suboptimum seroconversion rates after three doses of OPV.

Hepatitis C virus (HCV) is the main cause of parenteral non-A, non-B hepatitis and serum can be tested for the virus itself by reverse-transcription polymerase chain amplification. What of the level of this viraemia? To find out if quantitative study of HCV RNA might be useful clinically we took advantage of participation in trials of interferon-alpha in patients with chronic HCV infection and applied a new assay, branched DNA (bDNA) signal amplification. Paired serum and liver biopsy specimens from 47 patients with confirmed chronic HCV infection and evidence of HCV RNA in their serum were studied. The quantitative bDNA assay (detection limit 350,000 equivalents/mL [eq/mL]) was positive in 34 sera (sensitivity 72%). Patients who acquired HCV infection by blood transfusion had a higher viraemia (median 2,701,000 eq/mL, n = 29) than health workers and intravenous drug users (635,000 eq/mL, n = 13; p < 0.01). Patients with a sustained complete response to interferon-alpha therapy had lower pre-treatment viraemia levels (median at bDNA cut-off, n = 11) than complete responders who relapsed after the drug was stopped (1,613,000 eq/mL, n = 15; p < 0.01) and non-responders (3,066,000 eq/mL, n = 20; p < 0.01). High viraemia levels were not related to the histological diagnosis but were associated with lobular inflammation, lymphoid aggregates, and bile-duct lesions. These findings indicate that mode of acquisition is an important determinant of HCV viraemia and that patients with low HCV viraemia levels are more likely to respond to interferon in a sustained fashion.

Parenteral glutamine dipeptide improves nitrogen balance in postoperative patients on total parenteral nutrition (TPM). Animal studies show that the structure and function of the gut is preserved by glutamine. It is not known if this is the case in human beings. 20 patients admitted to hospital for total parenteral nutrition were randomly allocated to receive parenteral nutrition enriched with glycyl-L-glutamine (Gln TPN), or standard parenteral nutrition (STPN). Mucosal biopsy specimens were taken from the second part of the duodenum before starting parenteral nutrition, and after two weeks. The ratio between the urine concentrations of lactulose and mannitol after enteral administration was used to measure intestinal permeability. After two weeks of parenteral nutrition in the GlnTPN group, intestinal permeability was unchanged, whereas permeability in the STPN group increased. Villus height was unaltered in the GlnTPN group but in the STPN group it decreased. The addition of glutamine to parenteral nutrition prevents deterioration of gut permeability and preserves mucosal structure.

There are no previous reports of trials that have directly compared the effects of adjuvant chemotherapy with oophorectomy in premenopausal women with node-positive breast cancer. During 10 years we recruited 332 such women who were randomised, after mastectomy or conservation therapy, to receive either ovarian ablation or cyclophosphamide/methotrexate/5-fluorouracil (CMF) chemotherapy, each with or without prednisolone 7.5 mg daily for 5 years. After a maximum follow-up of 12 years, we detected no significant overall differences in relapse rates, or in event-free or total survival for ovarian ablation compared with chemotherapy or for prednisolone versus no prednisolone, nor any suggestion of an interaction between these factors. Actuarial total survival at 8 years was 60% overall, irrespective of treatment, with a hazard ratio and 95% Cl of 1.12 (0.76-1.63) for the comparison of CMF with ovarian ablation and 1.26 (0.86-1.84) for prednisolone versus no prednisolone. Oestrogen receptor (ER) assays were done in 270 (81%) primary tumours but these results played no part in the randomisation procedure. When patient outcome was analysed in relation to the concentration of ER in the tumour, there was a statistically significant interaction between ER content and treatment, such that ovarian ablation was associated with improved survival in patients with ER concentrations 20 fmols/mg protein or more and CMF was more beneficial for patients with values less than 20 fmols/mg protein. No such interaction was seen for prednisolone therapy. Oestrogen receptor content has a role in decisions about treatment for primary breast cancer.

Compared with conventional chemotherapy, use of liposomes loaded with therapeutic agents is less toxic and more effective in experimental tumours in vivo. We have assessed efficacy and toxicity of liposomal daunorubicin (40 mg/m2 every 2 weeks) in 25 patients with HIV-associated Kaposi's sarcoma of poor prognosis. In 24 evaluable patients, there were 2 complete remissions (8.3%) and 13 partial remissions (54.2%). 5 of 11 patients with doxorubicin-resistant Kaposi's sarcoma had partial remissions. Median duration of response was 12 weeks. Quality of life improved after treatment with a response rate of 71% for physical performance and 74% for emotion. Myelosuppression was the commonest adverse event. Vomiting, stomatitis, and alopecia were rare and mild. Liposomal daunorubicin is safe and effective in HIV-associated Kaposi's sarcoma and improves quality of life. The treatment is effective even in patients resistant to other chemotherapy.

Patients receiving total intravenous nutrition have inert gallbladders; gallbladder sludge and gallstones often develop, but are preventable if gallbladder emptying can be improved. We measured the effect of giving rapid intravenous infusions of aminoacid solutions in eight normal subjects. Four regimens were tested (250 mL over 30 min, 250 mL over 10 min, 125 mL over 5 min, and 50 mL over 5 min). Gallbladder emptying, as measured by ultrasound and cholecystokinin release, depended on both the amount and the rate of aminoacid infusion. Rapid infusion of 125 mL of an aminoacid mixture (Synthamin 14 without electrolytes) over 5 min (2.1 g per min) produced a 64% reduction in gallbladder volume within 30 min, whereas a 50 mL infusion over 5 min produced only a 22% reduction. Intermittent rapid infusion of small amounts of aminoacids may prevent gallstones in patients receiving intravenous nutrition.

Concern about the risk of transmission of viral infection has led to attempts to reduce transfusion requirements in patients undergoing surgery. To determine whether recombinant human erythropoietin decreases blood transfusion requirements in patients undergoing elective hip arthroplasty, a multicentre double-blind, randomised, placebo-controlled trial was conducted. 208 patients undergoing elective primary or revision hip arthroplasty were randomised to 3 groups. All received daily subcutaneous injections of either erythropoietin or placebo starting 10 days before surgery. Group 1 (78 patients) received 14 days of placebo, group 2 (77 patients) received 14 days of erythropoietin (300 units/kg to a maximum of 30,000 units), and group 3 (53 patients) received placebo for days 10 to 6 before surgery and erythropoietin for the next 9 days. A primary outcome event (any transfusion or a haemoglobin concentration < 80 g/L) occurred in 46% of patients in group 1, 23% in group 2, and 32% in group 3 (p = 0.003). The mean number of transfusions was 1.14 in group 1, 0.52 in group 2, 0.70 in group 3. The mean reticulocyte count the day before surgery was 72 x 10(9)/L in group 1, 327 in group 2, and 170 in group 3. Deep venous thrombi were detected in 5 patients in group 1, 8 patients in group 2, and 8 patients in group 3. Patients who had a haemoglobin concentration before randomisation of < 135 g/L benefited most from erythropoietin. Thus erythropoietin given for 14 days perioperatively decreases the need for transfusion in patients undergoing elective hip arthroplasty.

Because of the high prevalence of hepatitis B virus (HBV) infection in The Gambia, HBV vaccination has been incorporated into the national expanded programme on immunisation. We have assessed the efficacy of the vaccine against HBV infection and chronic carriage by examining 720 3-4-year-old children who had received the vaccine in infancy and 816 who had not received it. The vaccine was 84% (95% CI 78-89%) effective against infection and 94% (84-98%) effective against chronic carriage. Vaccinated infants of mothers positive for hepatitis B surface and e antigens were at greater risk of breakthrough infection and chronic carriage than infants of uninfected mothers. The high vaccine efficacy against the HBV carrier state, the main risk factor for the development of chronic liver disease and liver cancer, offers hope that the prevalence of these diseases may be reduced in the future.

Brain natriuretic peptide (BNP) is a cardiac ventricular hormone that may be a sensitive and specific marker of changes in ventricular function. In a prospective, randomised open trial with 16 patients followed for 6 months after first Q wave anterior myocardial infarction we set out to determine: whether BNP concentrations are raised acutely, the effect on circulating BNP of angiotensin-converting enzyme (ACE) inhibition, how BNP and atrial natriuretic peptide (ANP) concentrations compared as correlates of left-ventricular ejection fraction, and whether plasma BNP concentrations could distinguish patients with low (< 40%) and relatively preserved (> 40%) ejection fractions. Plasma concentrations of BNP measured on days 2, 7, 8, 42, and 180 postinfarction were significantly raised in patients compared with normal controls and to a proportionately greater degree than ANP concentrations. Treatment with placebo (n = 8) or oral captopril (n = 8) from day 8 resulted in significantly lower BNP concentrations at days 42 (p = 0.05) and 180 (p < 0.05) in the captopril-treated group. Compared with ANP, BNP concentrations were much more strongly correlated with radionuclide-measured left-ventricular ejection fraction at days 2, 42, and 180. All 8 patients with baseline (day 2) ejection fractions of 40% or above had plasma BNP concentrations less than 10 pmol/L, whereas the 8 patients with ejection fractions less than 40% had BNP concentrations greater than 10 pmol/L. Our findings suggest that measurements of circulating BNP may identify those patients with significant left-ventricular dysfunction who have been highlighted by the Survival and Ventricular Enlargement study as likely to benefit from long-term ACE inhibition after myocardial infarction.