Nebulized budesonide versus oral steroid in severe exacerbations of childhood asthma.

The aim of this study was to assess whether nebulized budesonide may substitute for oral prednisolone in the management of children whose asthma is severe enough to warrant hospital admission, but who have no life threatening features. In a prospective, double-blind, randomized study nebulized budesonide (2 mg 8 hourly) was compared with oral prednisolone (2 mg/kg at entry and again at 24 h) in 46 children admitted to hospital with severe asthma exacerbations. Efficacy variables (including lung function measurements such as the primary outcome variable, Forced Expiratory Volume in 1 second (FEV1) and symptoms) were measured 24 h after treatment initiation. FEV1 improved significantly compared to baseline in patients who received nebulized budesonide compared to the prednislone group. The data show nebulized budesonide to be at least as effective as oral steroid in improving lung function and symptom severity in severe exacerbations of childhood asthma.

A comparison of the efficacy of long-acting beta 2-agonists: eformoterol via Turbohaler and salmeterol via pressurized metered dose inhaler or Accuhaler, in mild to moderate asthmatics. Force Research Group.

Four hundred and sixty nine patients were randomized to receive either 12 micrograms bd of eformoterol (Oxis, Astra Pharmaceuticals Ltd., Kings Langley, U.K.) delivered via Turbohaler or 50 micrograms bd salmeterol (Serevent, Glaxo-Wellcome Ltd., Uxbridge, U.K.) via either the Accuhaler (Glaxo-Wellcome Ltd.) or pressurized metered dose inhaler (pMDI, Glaxo-Wellcome Ltd.) for 8 weeks. This was followed by a 4-week cross-over period when patients who had received salmeterol in the previous 8 weeks were given eformoterol and patients who had received eformoterol were given either salmeterol via the Accuhaler or pMDI to assess patient device and treatment preference. For the primary efficacy variable, the increase in peak expiratory flow (PEF) rate from run-in to 8 weeks, similar significant improvements were seen in all three treatment groups. Eformoterol Turbohaler (FT) achieved a greater increase in morning PEF than salmeterol Accuhaler (SA) from randomisation to 4 weeks; the increase shown in the eformoterol Turbohaler group was 28.9 1 min-1 compared to 19.91 min-1 for the salmeterol Accuhaler group. The addition of eformoterol Turbohaler 12 micrograms bd, to patients' existing asthma therapy was found to have a significantly more beneficial effect on the severity of patients' daytime asthma symptoms than had salmeterol Accuhaler 50 micrograms bd (P = 0.014). Eformoterol Turbohaler reduced the severity of daytime asthma symptoms by 42% after only 4 weeks of treatment. The patients in the eformoterol Turbohaler treated group experienced a higher percentage of days when they were symptom-free and did not use their short-acting bronchodilator to relieve symptoms (32.8, 24.1 and 28.0% in the FT, SA and SM groups, respectively). At 8 weeks there were no significant differences in any of these variables between the three groups. Patients in all the treatment groups gained an additional 1-1.5 nights undisturbed by asthma per week. The changes in sleep disturbance were not significantly different between the three treatment groups. In addition to the therapeutic benefits provided by eformoterol Turbohaler the device (Turbohaler) was the significant preference of patients given both Turbohaler and pMDI (P = 0.0168) and was also considered to be significantly more convenient to carry around than the Accuhaler (P < 0.0001). No other differences were found between the three devices. The results of this study demonstrate that the addition of a long-acting beta 2-agonist is an effective tool for achieving the goals of asthma treatment. Eformoterol via the Turbohaler is at least as effective as salmeterol via either the Accuhaler or the pMDI in achieving these goals.

A comparison of the efficacy of long-acting beta 2-agonists: eformoterol via Turbohaler and salmeterol via pressurized metered dose inhaler or Accuhaler, in mild to moderate asthmatics. Force Research Group.

Four hundred and sixty nine patients were randomized to receive either 12 micrograms bd of eformoterol (Oxis, Astra Pharmaceuticals Ltd., Kings Langley, U.K.) delivered via Turbohaler or 50 micrograms bd salmeterol (Serevent, Glaxo-Wellcome Ltd., Uxbridge, U.K.) via either the Accuhaler (Glaxo-Wellcome Ltd.) or pressurized metered dose inhaler (pMDI, Glaxo-Wellcome Ltd.) for 8 weeks. This was followed by a 4-week cross-over period when patients who had received salmeterol in the previous 8 weeks were given eformoterol and patients who had received eformoterol were given either salmeterol via the Accuhaler or pMDI to assess patient device and treatment preference. For the primary efficacy variable, the increase in peak expiratory flow (PEF) rate from run-in to 8 weeks, similar significant improvements were seen in all three treatment groups. Eformoterol Turbohaler (FT) achieved a greater increase in morning PEF than salmeterol Accuhaler (SA) from randomisation to 4 weeks; the increase shown in the eformoterol Turbohaler group was 28.9 l min-1 compared to 19.9 l min-1 for the salmeterol Accuhaler group. The addition of eformoterol Turbohaler 12 micrograms bd, to patients' existing asthma therapy was found to have a significantly more beneficial effect on the severity of patients' daytime asthma symptoms than had salmeterol Accuhaler 50 micrograms bd (P = 0.014). Eformoterol Turbohaler reduced the severity of daytime asthma symptoms by 42% after only 4 weeks of treatment. The patients in the eformoterol Turbohaler treated group experienced a higher percentage of days when they were symptom-free and did not use their short-acting bronchodilator to relieve symptoms (32.8, 24.1 and 28.0% in the FT, SA and SM groups, respectively). At 8 weeks there were no significant differences in any of these variables between the three groups. Patients in all the treatment groups gained an additional 1-1.5 nights undisturbed by asthma per week. The changes in sleep disturbance were not significantly different between the three treatment groups. In addition to the therapeutic benefits provided by eformoterol Turbohaler the device (Turbohaler) was the significant preference of patients given both Turbohaler and pMDI (P = 0.0168) and was also considered to be significantly more convenient to carry around than the Accuhaler (P < 0.0001). No other differences were found between the three devices. The results of this study demonstrate that the addition of a long-acting B2-agonist is an effective tool for achieving the goals of asthma treatment. Eformoterol via the Turbohaler is at least as effective as salmeterol via either the Accuhaler or the pMDI in achieving these goals.

The management of acid-related dyspepsia in general practice: a comparison of an omeprazole versus an antacid-alginate/ranitidine management strategy. Compete Research Group [corrected].

BACKGROUND: There is need for an evidence-based comparison of clinical management strategies to provide the rationale for selection of a particular therapeutic approach to treatment. Ideal dyspepsia treatment should quickly and conveniently alleviate patient symptoms whilst also minimizing the use of healthcare resources. AIM: To examine dyspepsia symptom relief over 16 weeks and compare an omeprazole clinical management strategy with a commonly used combination of antacid-alginate followed by H2-antagonist. METHODS: Seven hundred and twenty-five patients participated in this randomized, open, parallel group comparison over 16 weeks. Patients were randomized to receive either an omeprazole treatment strategy (363) consisting of omeprazole 10 mg stepping up to 20 mg and 40 mg as required, or an antacid-alginate/ranitidine treatment strategy (362) consisting of antacid-alginate 10 mL q.d.s. stepping up to ranitidine 150 mg b.d. and 150 mg q.d.s. as required. RESULTS: A greater proportion of patients receiving the omeprazole clinical management strategy had achieved the stringent health target of complete symptom relief (61 vs. 40%, P < 0.0001) at 16 weeks. Forty-six per cent of omeprazole-treated patients were symptom free after the first 10 mg step compared to only 17% in the antacid-alginate treated group (P = 0.0001). Total relief of heartburn, the most common symptom at entry, was achieved by more patients in the omeprazole treatment group than the antacid-alginate/ranitidine treatment group, 62 vs. 36%, respectively, at 4 weeks, and 81 vs. 60% at 16 weeks (P = 0.0001). CONCLUSION: Treatment with the omeprazole clinical management strategy was superior to the antacid-alginate/ranitidine management strategy in providing relief of acid-related dyspepsia symptoms after 16 weeks. In addition, the omeprazole treatment strategy involved fewer GP consultations and thus minimized the use of other healthcare resources.

Omeprazole 10 milligrams once daily, omeprazole 20 milligrams once daily, or ranitidine 150 milligrams twice daily, evaluated as initial therapy for the relief of symptoms of gastro-oesophageal reflux disease in general practice.

BACKGROUND: The efficacy of omeprazole, 20 mg once daily, in the treatment of reflux oesophagitis and the therapeutic advantages over the histamine H2 receptor antagonists are well documented. This study assessed 20 mg omeprazole daily (OM20), 10 mg omeprazole daily (OM10), and 150 mg ranitidine (RAN) twice daily for symptom relief in gastro-oesophageal reflux disease (GORD). METHODS: Patients (n = 994) presenting with heartburn to their general practitioner underwent endoscopy to exclude peptic ulcer disease and were randomized into a UK, multicentre, parallel-group, double-blind comparison of the three treatments for 4 weeks. Symptoms were assessed at clinic visits after 2 and 4 weeks. RESULTS: Symptom relief after 4 weeks was achieved by 61% (OM20), 49% (OM10), and 40% (RAN) patients (OM20 versus OM10, P < 0.0167; OM20 versus RAN, P < 0.0001; OM10 versus RAN, P < 0.01). Among the patients (32%) with erosive reflux oesophagitis, symptom relief was achieved in 79% (OM20), 48% (OM10), and 33% (RAN) (OM20 versus OM10, P < 0.0001; OM20 versus RAN, P < 0.0001; OM1O versus RAN, NS). CONCLUSION: Omeprazole, 20 mg, is the most effective initial therapy for relief of GORD symptoms.

Two omeprazole-based Helicobacter pylori eradication regimens for the treatment of duodenal ulcer disease in general practice.

BACKGROUND: Helicobacter pylori is the main acquired factor in the pathogenesis of duodenal ulcer disease. METHODS: This multicentre study conducted in 32 general practice centres in the UK and Ireland was a double-blind, placebo-controlled, randomized, parallel-group comparison of triple therapy (n = 98: omeprazole 40 mg once daily and amoxycillin 1 g b.d. for 2 weeks, and metronidazole 400 mg t.d.s. for the first week) and dual therapy (n = 85: omeprazole 40 mg once daily and amoxycillin 1 g b.d. for 2 weeks, with placebo during the first week) for the eradication of H. pylori in patients with symptomatic duodenal ulcer disease. Patients who were successfully treated entered a follow-up phase for 12 months to assess symptomatic relapse and use of health-care resources. RESULTS: Eradication of H. pylori based on a second 13C-urea breath test was successful in 95% (95% confidence interval (CI) = 90-100%) of patients receiving omeprazole triple therapy and 53% (95% CI = 41-65%) of those receiving omeprazole dual therapy (P < 0.0001 between groups, all data available analysis). The all-patients-treated analysis gave eradication rates of 80 and 44% for omeprazole triple therapy and omeprazole dual therapy, respectively. Symptomatic relapse occurred in 16% (18/116) of the H. pylori-negative patients who entered the 12-month follow-up period, and there were significant reductions in the number of consultations, investigations and prescriptions relating to upper gastrointestinal symptoms compared with the 12 months prior to the eradication therapies (all P < 0.0001). The two treatment strategies were comparable in terms of the number of adverse events reported. CONCLUSIONS: Omeprazole triple therapy provides a highly effective treatment for the eradication of H. pylori infection in patients in general practice, with an adverse event profile similar to that seen with omeprazole dual therapy. The successful eradication of H. pylori with these omeprazole regimens results in a significant decrease in the use of health-care resources in the 12 months following treatment.

Maintenance treatment for gastro-oesophageal reflux disease. A placebo-controlled evaluation of 10 milligrams omeprazole once daily in general practice.

BACKGROUND: Gastro-oesophageal reflux disease (GORD) is a frequent cause for consultation in general practice and is a chronically relapsing disease. METHODS: This general practice study was a 6-month randomized, double-blind parallel-group placebo-controlled assessment of the efficacy and safety of continuous treatment with 10 mg omeprazole every morning after initial symptom control in 495 patients with GORD but without erosive oesophagitis. RESULTS: On the basis of life-table estimates for cumulative relapse rates, patients in the placebo group (52%) were almost twice as likely as those in the omeprazole group (27%) to discontinue therapy before 24 weeks because of inadequate relief of heartburn or for other reasons including adverse events (all-patients-treated analysis, log rank test, P = 0.0001). CONCLUSIONS: This study has shown that 10 mg omeprazole once daily is an effective and well-tolerated treatment strategy in general practice for the long-term management of symptoms of GORD in patients without erosive oesophagitis.

Bambuterol: effective in nocturnal asthma.

Bambuterol was compared with placebo in 28 patients with nocturnal asthma in a randomized, double-blind cross-over study. All patients were symptomatic despite taking inhaled beta 2-agonists, inhaled corticosteroids (in 26 patients the median daily dose was 1500 micrograms) and oral corticosteroids (in eight patients the median daily dose was 10 mg). Patients demonstrated > or = 20% overnight fall in peak expiratory flow (PEF) for at least half of the 14-day run-in period. They then entered two treatment periods lasting 14 days when bambuterol 20 mg nocte and placebo were given in random order. Compared to placebo, bambuterol produced a 16% improvement in mean PEF on waking (271 l min-1 vs. 239 l min-1 P = 0.0002) and a 10% improvement in evening PEF measured 24 h after drug intake (318 l min-1 vs. 296 l min-1 P = 0.01). Bambuterol significantly reduced frequency of nocturnal awakening from 1.1 to 0.7 per night (P = 0.01) and nocturnal beta 2-agonist use from 2.7 to 2.1 puffs (P = 0.0004). Other nocturnal symptoms: cough, wheeze and dyspnoea were also significantly reduced during bambuterol treatment and patients quality of sleep was improved. The results indicate bambuterol (20 mg nocte) provides effective nocturnal bronchodilation with sustained effect for 24 h and may have a useful therapeutic role in the control of symptomatic nocturnal asthma.

Localization of elevated transforming growth factor-alpha in psoriatic epidermis.

Biopsies of involved and uninvolved skin from five patients with plaque psoriasis and normal skin from four healthy volunteers were investigated for steady-state quantities of TGF-alpha RNA and protein by in situ hybridization and immunohistochemistry. Increased levels of TGF-alpha RNA were found only in the high-level keratinocytes of involved psoriatic skin (p less than 0.001). Elevated levels of TGF-alpha protein were seen in both the high-level and basal layers of involved psoriatic skin compared to uninvolved psoriatic and normal control skin. Elevated TGF-alpha gene expression is thus implicated in the hyperproliferation of keratinocytes and possibly the altered maturation pattern seen in psoriasis.

A comparison of the dermal lymphoid infiltrates in discoid lupus erythematosus and Jessner's lymphocytic infiltrate of the skin using the monoclonal antibody Leu 8.

Jessners lymphocytic infiltration of the skin (14 cases) and discoid lupus erythematosus (13 cases) were studied and the lymphoid infiltrates in the dermis were compared in the two conditions, using a standard immunoperoxidase technique. Mouse monoclonal antibodies were used to identify T helper lymphocytes, T suppressor lymphocytes and, using the antibody Leu 8, "immunoregulatory lymphocytes". It was shown that the proportions of Leu 8 positive cells was significantly different in the two conditions. The average percentage of Leu 8 positive lymphocytes in the dermal infiltrate found in the cases of Jessner's was 65% (range 40-80%) whereas the average percentage in the cases of discoid LE was 15% (range 2-30%). This observation is further evidence that Jessner's lymphocytic infiltration and chronic discoid lupus erythematosus should be regarded as separate entities.

Immunophenotyping of the cutaneous infiltrate and of the mononuclear cells in the peripheral blood in patients with atopic dermatitis.

Fourteen adult patients with chronic atopic dermatitis and active skin lesions had a skin biopsy and venous blood sample taken on the same day. Absolute numbers of circulating lymphocytes were normal in all patients. Fluorescence-activated cell sorter (FACS) analysis revealed normal numbers of total T lymphocytes and T-helper and T-suppressor subsets (helper:suppressor ratio, 2:1) in the atopic patients' peripheral blood, but an increase in circulating B lymphocytes and in HLA-D-related antigen-bearing cells. The skin biopsy showed a dermal infiltrate of predominantly T-helper lymphocytes (helper:suppressor ratio, 7:1). These cells showed strong HLA-DR plasma membrane staining. There was no HLA-DR staining in the membranes of epidermal keratinocytes. Using a monoclonal antihuman IgE, positive staining was observed in the dermis, though none was identified in the epidermis. The dermal anti-IgE staining was concentrated around clusters of T lymphocytes.

An assessment of the diagnostic value of the monoclonal antibodies Leu 8, OKT9, OKT10 and Ki67 in cutaneous lymphocytic infiltrates.

Biopsies from 63 patients, 40 with mycosis fungoides (MF) and 23 with other lymphocytic infiltrates, were stained with a panel of monoclonal antibodies to differentiation antigens (OKT10, Leu 8), to activation antigens (OKT9), and to an antigen expressed by all dividing cells (Ki67) to establish whether this panel was of value in the diagnosis of mycosis fungoides. None of these antibodies used in isolation was found to give a staining pattern specific for mycosis fungoides, but the phenotype Leu 3a+, OKT9+, Leu 8- of the majority of lymphocytes in the cutaneous infiltrate was strongly suggestive. The presence of Leu 3a+ Leu 8- lymphocytes is of particular interest in that in the peripheral blood both of normal subjects and of MF patients Leu 3a+ lymphocytes also are predominantly Leu 8+, were the lymphocytes in the cutaneous infiltrates of the non-MF infiltrates included in this study.

A prospective study of the histological changes in the skin in patients receiving bone marrow transplants.

Fourteen patients who received a bone marrow transplant (BMT) as treatment for leukaemia were included in a prospective study of the histological changes in the skin. The aim of this study was to improve the early diagnosis of graft-versus-host disease (GVHD). It was found that the clinically 'normal' pre-transplant skin was in some cases histologically abnormal on H & E examination in patients who were on regular maintenance cytotoxic chemotherapy. These changes were similar to some of the features of GVHD. Immunocytochemistry, although not specific, was found to be helpful in the diagnosis of some cases of GVHD. Suggestive features included a reduction in the numbers of Langerhans cells, an increase in the number of suppressor (OKT8+) cells in the dermal infiltrate and the presence of Ia positivity of the keratinocytes in the epidermis.

Use of NK1 C3 monoclonal antibody in the assessment of benign and malignant melanocytic lesions.

The monoclonal antibody NK1 C3, synthesised by the Netherlands Cancer Institute, has been used to assess its value in the diagnosis of melanocytic lesions. The antigen recognised by this antibody is not denatured by formalin fixation, with the result that the antibody can be used for retrospective studies on conventionally processed material. Positive results were obtained in primary melanoma (18/18), secondary melanoma (21/21), junctional and compound naevi (32/32), intradermal naevi (9/12), congenital naevi (3/3), so called dysplastic naevi (13/13), blue naevi (5/5), and Spitz tumours (3/14). Non-melanocytic tumours were tested for comparison. The results showed relative but not complete specificity of the antibody for melanocytic tumours, with positive results only in breast and prostate tumours (2/6 and 2/5 respectively). Negative results were obtained with basal and squamous cell carcinoma, appendage tumours, neural tumours, and apudomas. The staining pattern of NK1 C3 was compared with that of antibodies to S100 protein and to neurone specific enolase. Compared with S100 protein NK1 C3 gave stronger staining of a higher percentage of cells in the 12 specimens in which a direct comparison was made. Antibody raised against neurone specific enolase in sheep gave very poor results with heavy background staining. We suggest that NK1 C3 is a useful addition to the battery of monoclonal antibodies of value to the diagnostic histopathologist.

A case of pagetoid reticulosis bearing the T cytotoxic suppressor surface marker on the lymphoid infiltrate: further evidence that pagetoid reticulosis is not a variant of mycosis fungoides.

We describe a patient with pagetoid reticulosis in whom the lymphocytic infiltrate bore the surface membrane marker of the cytotoxic/suppressor subset. This is further evidence that Pagetoid reticulosis is not a variant of mycosis fungoides.