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Effect of a single oral dose of prednisolone in acute childhood asthma.

140 children of 184 with acute asthma entered a randomised double-blind trial of oral prednisolone (n = 67) compared with placebo (n = 73) administered soon after admission. The dose of prednisolone was 30 mg in children under 5, otherwise 60 mg. All children also received salbutamol. All had moderate or severe dyspnoea. Initial evaluation was similar for both groups. On reassessment after a few hours 20 children in the prednisolone group were fit for discharge compared with only 2 in the placebo group. There were no early reattendances. Children remaining in hospital had a shorter median duration of stay and were less likely to require further steroid therapy if they had initially received prednisolone. In acute asthma the prompt use of a single dose of oral prednisolone can reduce morbidity and the need for hospital care.

Acute Disease↗

The modification of human tumour blood flow using pentoxifylline, nicotinamide and carbogen.

AIM: To assess the effect of combining oral nicotinamide, oral pentoxifylline and carbogen gas (2% CO2, 98% O2) breathing on human tumour red cell flux. METHODS AND MATERIALS: Microregional red blood cell flux was measured in accessible tumour nodules using laser Doppler microprobes in 11 patients with histologically proven malignancy. Patients received single oral doses of nicotinamide 40 mgkg-1 and pentoxifylline 1200 mg 2h before a 10-min period of carbogen gas breathing, corresponding to peak plasma concentrations of these drugs. Red cell flux in up to six microregions in each tumour was measured for 30 min, recording pre-, during and post-carbogen breathing for 10 min each. RESULTS: Data from ten of the 11 patients could be assessed. The red cell flux in 48 microregions was analysed and the mean red cell flux was calculated. A mean relative increase in red cell flux of 1.18 (+/-0.09, 95% confidence interval (CI)) was observed after 6 min of carbogen breathing, 2h after the administration of nicotinamide and pentoxifylline. This compares to relative increases of 1.4 (+/-0.39, 95%CI) after nicotinamide with carbogen and 1.15 (+/-0.10, 95%CI) after pentoxifylline with carbogen. These differences are not statistically significant (P>0.05). The increased red cell flux persisted after the cessation of carbogen gas breathing. CONCLUSIONS: A combination of pentoxifylline, nicotinamide and carbogen produces an increase in human tumour red cell flux, similar to that observed when each of the drugs are used alone with carbogen breathing.

Administration, Inhalation↗

Accelerated radiotherapy with carbogen and nicotinamide (ARCON) for laryngeal cancer.

BACKGROUND AND PURPOSE: Tumor hypoxia and tumor cell repopulation are known factors determining radiation response. Accelerated radiotherapy as a method to counteract cellular repopulation was combined with carbogen (95% O2 + 5% CO2) breathing and oral administration of nicotinamide as a means to improve tumor perfusion and oxygenation. The feasibility, toxicity and clinical effectiveness of this approach as a voice-preserving treatment for carcinoma of the larynx was assessed in a prospective study. PATIENTS AND METHODS: Sixty-two patients with stage III-IV laryngeal carcinoma were treated with a schedule of accelerated radiotherapy. The total radiation dose to the primary tumor was 64 Gy and that to the metastatic nodes was 68 Gy delivered in fractions of 2 Gy over 35-37 days. Radiotherapy was combined with carbogen breathing in the initial 11 patients and with both carbogen and nicotinamide administration in the subsequent 51 patients. RESULTS: After a median follow-up of 24 months, the actuarial local control rate at 2 years was 92%. This is higher than any previous report in the literature for this category of patients. Five patients had a local tumor recurrence and underwent laryngectomy. There was one regional recurrence. Including salvage surgery the loco-regional control rate was 100%. Four patients developed distant metastases and died. The actuarial overall survival rate at 2 years was 85%. Toxicity was increased relative to conventional radiotherapy but was considered as acceptable. One patient underwent laryngectomy for radiation-induced cartilage necrosis. CONCLUSION: These preliminary results indicate that advanced laryngeal cancer can be controlled in a high proportion of patients when treated with accelerated radiotherapy combined with carbogen and nicotinamide. This approach offers excellent possibilities for larynx preservation.

Actuarial Analysis↗

Evaluation of SaO2 as a predictor of outcome in 280 children presenting with acute asthma.

STUDY OBJECTIVES: To evaluate the initial measurement of arterial oxygen saturation (SaO2) as a predictor of outcome in acute childhood asthma compared with other factors of past and present asthma history. DESIGN: Prospective observational double-blind study. SETTING: The emergency department of an urban pediatric hospital with a 1988 annual census of 50,000 children. TYPE OF PARTICIPANTS: Two hundred eighty children with recurrent wheezing that was diagnosed by a physician as asthma, who presented to the ED with wheezing. INTERVENTION: SaO2 was measured on arrival in the ED, and a detailed history of the present attack and past asthma was recorded. Children were treated according to then-current practice guidelines. Parents were contacted by telephone to determine the outcome of the attack; a "poor outcome" was defined as admission to hospital or re-presenting with ongoing symptoms to receive medical care if sent home from the ED. A "worst outcome" was defined as receiving IV aminophylline and steroids after failing to respond to repeated bronchodilation and oral steroids. MEASUREMENTS AND MAIN RESULTS: The proportion of children at each percent SaO2 who had a poor outcome increased with decreasing SaO2 (r = .97). Likelihood ratios for a poor outcome were 35 (confidence interval [CI], 11 to 150) for an SaO2 of 91% or less compared with 96% or more and 4.2 (CI, 2.2 to 8.8) for an SaO2 of 92% to 95% compared with 96% or more. An SaO2 of 91% or less predicted with a sensitivity of 100% and a specificity of 84% those children with a worst outcome who required IV therapy. Other factors of current or past asthma history failed to predict outcome. CONCLUSION: We have shown that in acute childhood asthma, the initial level of SaO2 reflects severity as it predicts the likelihood of poor outcome. This predictive quality of SaO2 is independent of current or past clinical factors.

Acute Disease↗

Safety and efficacy of nebulized racemic epinephrine in conjunction with oral dexamethasone and mist in the outpatient treatment of croup.

STUDY OBJECTIVE: To identify patients with croup who after treatment with nebulized racemic epinephrine, oral dexamethasone, and mist may be safely discharged home after a period of observation. DESIGN: Prospective interventional. SETTING: Urban children's hospital emergency department. PARTICIPANTS: Children with croup who received racemic epinephrine for the treatment of stridor at rest. INTERVENTIONS: After treatment with .5 mL racemic epinephrine, .6 mg/kg dexamethasone PO, and mist, patients who were assessed as being safe for discharge after 3 hours of observation were discharged home and contacted for 48-hour follow-up. RESULTS: Fifty-five patients with croup were treated with racemic epinephrine. Thirty patients (55%) had sustained responses and were discharged home after 3 hours of observation. No recurrence of respiratory distress and no return visits for medical care were reported (95% confidence interval, 0% to 8.0%). CONCLUSION: Patients with croup who are treated with racemic epinephrine, oral dexamethasone, and mist may be safely discharged home if the patient is assessed as ready for discharge after 3 hours of observation.

Administration, Inhalation↗

Nasal immunization with group B streptococci can induce high levels of specific IgA antibodies in cervicovaginal secretions of mice.

We have studied the cervicovaginal antibody responses in mice, by ELISA, following mucosal immunizations with group B streptococci (GBS) serotype III/R4. Immunizations were carried out either: (1) rectally with GBS alone; (2) rectally with GBS plus cholera toxin (CT); (3) nasally with GBS alone; (4) nasally with GBS+CT; or (5) nasally under general anesthesia with GBS+CT. Nasal immunizations with GBS alone led to at least tenfold higher levels of specific IgA-antibodies to GBS in cervicovaginal secretions than with any other immunization. These mucosal antibody levels were higher than after rectal immunizations, and 2-17 times higher than the corresponding IgA antibody levels in sera. Markedly lower cervicovaginal antibody levels were found in mice which had received GBS together with CT as a mucosal adjuvant than in mice immunized by the same routes with GBS alone. Our observations indicate that a nasal vaccine consisting of GBS might induce sufficient antibody levels to protect against genital colonization of these bacteria.

Adjuvants, Immunologic↗

Intranasal murine model of Bordetella pertussis infection. I. Prediction of protection in human infants by acellular vaccines.

Bicomponent, tricomponent and pertactin DTPa vaccines were tested in sublethal aerosol, and lethal and sublethal intranasal murine Bordetella pertussis respiratory challenge models. Pertactin and bicomponent vaccines induced protective immunity against lethality but with little or no bacterial clearance. Intranasal challenge discriminated in a reproducible, statistically significant manner between the efficacies of bicomponent and tricomponent DTPa, in agreement with clinical trial data. This discrimination was not observed in the aerosol challenge. Pertactin had a synergistic effect with bicomponent DTPa. Intranasal challenge may be useful as part of the preclinical evaluation of new acellular pertussis formulations or DTPa-based combinations.

Administration, Inhalation↗

Acute toxicity of ethylene glycol mono-n-butyl ether in the guinea pig.

Acute toxicity values, such as oral and percutaneous LD50s, are often used as the basis for classifying chemicals into toxicity categories, and their subsequent regulation. Such values obtained for ethylene glycol mono-n-butyl ether (EGBE; 2-butoxyethanol) in rats and rabbits indicate that it is moderately toxic. However, the cause of death in these acute studies appeared to be secondary to acute intravascular haemolysis, an effect for which guinea pigs and humans are much less sensitive than rats, mice and rabbits. Recently-conducted acute toxicity studies in the guinea pig resulted in an acute oral LD50 of 1400 mg/kg, an acute percutaneous LD50 of greater than 2000 mg/kg, and a 1-hr LC50 greater than 633 ppm. These data are compared with published acute toxicity values, and indicate that the predicted acute toxicity of EGBE in humans, based on data from the guinea pig, would be less than that observed in other animal species. Based in part on the guinea pig data, EBGE is no longer classified as a poisonous substance by either the United Nations or US Department of Transportation.

Administration, Inhalation↗

A murine model for low molecular weight chemicals: differentiation of respiratory sensitizers (TMA) from contact sensitizers (DNFB).

Exposure to low molecular weight (LMW) chemicals contributes to both dermal and respiratory sensitization and is an important occupational health problem. Our goal was to establish an in vivo murine model for hazard identification of LMW chemicals that have the potential to induce respiratory hypersensitivity (RH). We used a dermal sensitization protocol followed by a respiratory challenge with the evaluation of endpoints typically associated with RH in human disease. Trimellitic anhydride (TMA) was used as a prototype respiratory sensitizer and was compared to the dermal sensitizer; 2,4-dinitrofluorobenzene (DNFB), along with vehicle controls. BALB/c mice were dermally sensitized using two exposure protocols. Mice in both protocols were dermally exposed on experimental days; D-18 and D-17 (abdomen), and D-13 (ear). On D 0 mice received an intratracheal (IT) challenge. The mice in Protocol 2 were abdominally exposed twice with the addition of exposures on D-25 and D-24. Results indicate that mice required the additional dermal sensitization and the IT challenge (Protocol 2) to significantly elevate total IgE in serum and bronchoalveolar lavage fluid (BALF). Additional responses suggestive of RH were seen following Protocol 2, including increases in BALF cell numbers and neutrophils post IT with TMA (but not DNFB). These data suggest that the dermal sensitization and IT challenge followed by evaluation of serum antibodies and lung parameters are a reasonable and logistically feasible approach towards the development of a model for RH responses to LMW chemicals.

Administration, Inhalation↗

How constant is an individual's route of heroin administration? Data from treatment and non-treatment samples.

Three routes of heroin use were identified--injecting, 'chasing the dragon' and snorting. Whilst injecting and 'chasing the dragon' accounted for virtually all current heroin use, snorting had been the first route of use for nearly a fifth of heroin users in both the treatment and community samples. Overlap of lifetime experience of the different routes was widespread, with the majority of heroin users in both the treatment and community samples having used heroin by more than one route. Although less than half of the treatment sample had used heroin by injection on the first occasion, more than 90% had injected at least once, and over 80% had at some time used by 'chasing the dragon'. Only a quarter of the community sample had first used heroin by injecting, and yet, by the time of interview, two-thirds of the sample had injected. The majority of durable changes in route of heroin use were towards injecting and 'chasing the dragon', with transitions to snorting being extremely rare. For both the samples, transitions to injecting were twice as frequent as transitions to 'chasing'. Snorting appeared to be an unstable route of use, with almost all who initially snorted their heroin now using by injecting or 'chasing the dragon'.

Administration, Inhalation↗

Isolated airway exposure to toluene diisocyanate results in skin sensitization.

Toluene diisocyanate (TDI), a highly reactive industrial chemical is a leading cause of occupational asthma in westernized countries. It has also been reported to be a skin sensitizer in mice and guinea pigs although instances of skin sensitivity in humans are rare. It is uncertain if skin-contact is necessary to initiate the dermal sensitization. This study sought to determine if exclusive airway exposure to TDI could result in skin sensitivity. A group of guinea pigs was administered 50 microl of 0.6% TDI intratracheally (it.), another group received intranasal (in.) application of 0.6, 1.2, or 1.8% TDI. Eighty percent (4/5) of the it.-dosed animals, and 92% (11/12) of in.-dosed animals exhibited skin sensitivity. None of 14 control animals gave a positive reaction to patch challenge with TDI. These findings indicate that exclusive exposure of the airways to TDI can result in skin sensitivity and suggest that such events may be possible in TDI workers and should be considered in all workers exposed via the airways to chemical sensitizers.

Administration, Inhalation↗