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Although worker injury and fatalities have decreased since adoption of the Occupational Safety and Health Act in 1970, it remains an important safety issue. This article describes a 27-year-old white male who died from occupational exposure to airborne chemicals. Several trends in the last several decades, both in the types of injuries and the occupations associated with fatalities, are noted. Additionally, individual risk factors such as age, gender, chronic disease, smoking, and alcohol and drug use are implicated in worker health and safety. The role of the forensic pathologist in the investigation of workplace deaths is highlighted, in addition to the future of occupational safety and current improvements brought about by such incidents., (© 2014 American Academy of Forensic Sciences.)

Background & Aims: The efficacy and safety of long-term acid suppression remains a subject for debate. We report data from patients with refractory reflux esophagitis who were undergoing maintenance therapy with >/=20 mg omeprazole daily for a mean period of 6.5 years (range, 1.4-11.2 years)., Methods: Patients with severe reflux esophagitis resistant to long-term therapy with H(2)-receptor antagonists and who were not eligible for surgery were evaluated at least annually for endoscopic relapse and histological changes in the gastric corpus., Results: In 230 patients (mean age, 63 years at entry; 36% were >/=70 years), there were 158 relapses of esophagitis during 1490 treatment years (1 per 9.4 years), with no significant difference in relapse rates between Helicobacter pylori-positive and -negative patients. All patients rehealed during continued therapy with omeprazole at the same or higher dose. The annual incidence of gastric corpus mucosal atrophy was 4.7% and 0.7% in H. pylori-positive and -negative patients, respectively, which was mainly observed in elderly patients who had moderate/severe gastritis at entry. In patients with baseline moderate/severe gastritis, the incidences were similar: 7.9% and 8.4%, respectively. Corpus intestinal metaplasia was rare, and no dysplasia or neoplasms were observed. The adverse event profile was as might be expected from this elderly group of patients., Conclusions: Long-term omeprazole therapy (up to 11 years) is highly effective and safe for control of reflux esophagitis.

A meta-analysis was performed on pooled data from five large double-blind studies (a total of 1057 patients), which were conducted in Asia to compare the effects of omeprazole with H2-receptor antagonists (H2-RA) in duodenal ulcer. As each study followed the same protocol and data evaluation procedures, a detailed analysis of ulcer healing, symptom relief and influence of prognostic factors across the data was possible. Patients received omeprazole 20 mg om or standard doses of H2-RA for a minimum of 2 and a maximum of 4 weeks, depending on healing (as verified by endoscopy). All efficacy analyses were based on per protocol data. The mean healing rates at 2 weeks were 72% for omeprazole and 42% for H2-RA (difference 30%; 95% CI: 24-36%; P < 0.0001) and at 4 weeks were 96% for omeprazole and 83% for H2-RA (difference 13%; 95% CI: 10-17%; P < 0.0001). In addition to treatment, ulcer size had a significant influence on healing, with large ulcers (diameter > 10 mm) taking longer to heal than small ulcers. There was no significant influence of smoking and alcohol drinking on ulcer healing. Patients on omeprazole experienced significantly less epigastric pain after 2 weeks than those on H2-RA, 79% of them being completely symptom-free on omeprazole compared with 65% on H2-RA. The incidence of adverse events was approximately 5% on each treatment and profiles were similar for each drug. It is concluded that omeprazole, even in the presence of adverse prognostic influences, results in significantly better healing of duodenal ulcer and relief from symptoms than H2-RA.

1 The effects of the prostaglandin precursor, arachidonic acid, and the non-steroidal anti-inflammatory drug, indomethacin, on gastric acid secretion were studied in the rat, in vivo and in vitro. Gastric mucosal blood flow was also measured in vivo. 2 Arachidonate produced significant inhibition of acid secretion stimulated by pentagastrin or histamine. It did not significantly affect dibutyryl cyclic adenosine 3',5'-monophosphate (db cyclic AMP)-induced acid secretion. 3 Inhibition of acid secretion by arachidonate was accompanied by a rise in the ratio of mucosal blood flow to acid secretion. 4 Indomethacin did not significantly alter histamine- or pentagastrin-induced acid secretion. 5 In the presence of indomethacin, the inhibitory effect of arachidonate was significantly reduced. 6 These results provide evidence that the rat gastric mucosa is capable of synthesizing, from exogenous precursor, products of cyclo-oxygenase which inhibit gastric acid secretion.

1 Prostaglandin E(2) dose-dependently and reversibly inhibited the noradrenaline overflow resulting from nerve stimulation of the rabbit kidney.2 The magnitude of this inhibition varied inversely with the frequency of stimulation employed.3 The prostaglandin synthesis inhibitors, indomethacin and meclofenamic acid, both increased the transmitter overflow resulting from renal nerve stimulation, suggesting that endogenous prostaglandin has a role in the regulation of transmitter release.4 In the presence of indomethacin, the inhibitory effect of exogenous prostaglandin E(2) was enhanced.5 The prostaglandin precursor, arachidonic acid, also caused a significant, dose-dependent and reversible inhibition of transmitter overflow. This inhibition became insignificant when arachidonic acid was applied in the presence of indomethacin, suggesting that the inhibition was mediated by newly formed prostaglandin rather than by arachidonic acid itself.6 It is proposed that newly formed prostaglandin controls noradrenaline release primarily from inner cortical nerve endings, thereby maintaining juxtamedullary blood flow under periods of increased sympathetic nerve activity.

Plasma terbutaline levels and peak expiratory flow rates were measured in 5 asthmatic children using doses of 0.25 and 0.075 mg/kg. The higher dose resulted in safe, non-toxic plasma levels and returned the peak expiratory flow rate to normal. This dose (maximum 5 mg) is safe in children.

Increasing doses of fenoterol and terbutaline were administered by inhaler to 12 stable asthmatics in a double-blind crossover trial. 100 microgram doses of fenoterol were shown to be equal in potency to 250 microgram doses of terbutaline, as measured by increases in forced expiratory volume in the first second (FEV1) and specific airways conductance (sGaw). FEV1 and sGaw remained significantly greater than pretreatment levels up to five hours after both drugs and terbutaline showed a significantly greater effect on FEV1 than fenoterol after four hours suggesting a small but significantly longer duration of activity. Fenoterol used at the dosage of 100 micrograms per puff (half the standard commercially available dose of 200 micrograms per puff) caused significantly more cardiac effects than terbutaline, as measured by the magnitude and duration of increases in heart rate, and the incidence of reported palpitations.

The relative prednisolone-sparing effects of inhaled budesonide 400 micrograms daily and beclomethasone dipropionate (BDP) 400 micrograms daily were compared in a double-blind crossover study of 26 patients with chronic asthma requiring treatment with BDP and oral prednisolone in a daily dose of 5 mg or greater. During each period of the trial budesonide and BDP were inhaled via conventional pressurized inhalers in a dose of 100 micrograms four times daily. Prednisolone was reduced by 1 mg per month from the patient's normal maintenance dose to zero or to the point at which asthmatic symptoms became unacceptable. The mean reduction in prednisolone dose during BDP treatment was 2.65 mg compared with 1.8 mg at the end of the budesonide period. The difference between the prednisolone-sparing properties of BDP and budesonide assessed in this way in this group of patients was statistically significant in favour of BDP. The mean minimum prednisolone doses at the end of the treatment periods were 3.46 mg for BDP and 4.3 mg for budesonide. Since inhaled steroids were not withdrawn the absolute prednisolone-sparing properties of the two drugs were not assessed, and thus a pharmacological potency ratio cannot be derived from the results. It is concluded that BDP is marginally more potent than budesonide in its prednisolone-sparing properties.

The efficacy and side-effects of a new corticosteroid, budesonide, was assessed by comparison with beclomethasone dipropionate in double-blind, cross-over study of 30 patients with chronic asthma. The treatment regimens were budesonide 200 micrograms twice daily by conventional pressurized aerosol with a tube spacer attached and beclomethasone 100 micrograms four times daily via a conventional inhaler. Each treatment was given for four weeks. Results were analyzed using Student's t-test for paired comparisons. No significant differences were found for morning and evening peak flow rates, symptom scores, bronchodilator inhaler usage or forced vital capacity. Forced expiratory volume in one second after 4 weeks on each treatment was significantly higher following budesonide therapy (p less than 0.05), but the absolute changes were small and unlikely to be of clinical relevance. There were no major side-effects during either treatment period, but compared with pre-treatment levels serum creatinine and lactic dehydrogenase levels rose significantly during treatment with budesonide (p less than 0.01 and p less than 0.05 respectively). None of these results reflected clinically important biochemical or haematological changes. There was a significant reduction in neutrophil counts following treatment with beclomethasone (p less than 0.05). In the short term treatment of chronic asthma, budesonide administered twice daily is as effective as four times daily beclomethasone. A twice daily dosage regimen should improve patient compliance with therapy.

A double-blind crossover study has been performed in 14 patients with moderately severe chronic asthma to compare the bronchodilator efficacy of two dosage regimens of intravenous enprofylline (high dose = 2 mg/kg bolus and 1 mg/kg/hour infusion; low dose = 1 mg/kg bolus and 500 micrograms/kg/hour infusion) with aminophylline (5 mg/kg/bolus and 500 micrograms/kg/hour infusion) and placebo. The bolus injections were given over 20 minutes and infusion over 160 minutes. Twelve subjects completed the study. High dose enprofylline was more effective than aminophylline in increasing PEF (P = 0.008) and FEV1 (P = 0.004). Low dose enprofylline and aminophylline were of similar efficacy. Side-effects, notably headaches and nausea, were more common with enprofylline; three out of 14 subjects receiving the high dose regimen developed severe nausea. The plasma enprofylline levels achieved with the high dose regimen were greater than anticipated. Further studies are required in acute severe asthma to clarify the therapeutic role of intravenous enprofylline and the most appropriate dosage regimen.

Topical steroid therapy is now widely used in the treatment of chronic asthma, but few controlled studies have been conducted to evaluate the most efficient dosage regimen. The present study was designed to assess, in a double-blind fashion, the relative efficacy of a new topical steroid, budesonide (Pulmicort) in controlling pulmonary function and asthma symptoms during twice-and 4-times daily dosing. Both active and placebo drug were administered via the tube spacer inhaler. Objective lung function measurements indicate that twice-daily dosing is at least as effective as 4-times daily dosing, and it is suggested that the twice-daily dosage regimen may lead to better patient compliance.

An open, cross-over trial was conducted on 25 asthmatic children, aged 6-13 years, who required inhaled steroids. They inhaled Budesonide 200 micrograms twice daily, either directly from the metered dose inhaler or via the pear spacer (PS), for 2 months on each, in randomized order. The effects of the treatment were monitored with diary cards recording peak expiratory flow rates twice daily, symptoms and treatment taken, and with monthly clinical assessments including more sensitive lung function studies (flow-volume loops and single breath nitrogen wash-out tests). There was no specifically PS-related improvement in symptoms or in the majority of tests, but the results showed improvement with time when using either method. The improvement was more distinct in some tests reflecting proximal airway calibre (i.e., PEFR) than in tests thought to reflect predominantly peripheral airway calibre (i.e., F50, RV). The bronchodilator responsiveness, as shown by the increase in lung function tests after a beta-agonist was given, was significantly greater for FVC during the periods when the PS was used, although there was no significant improvement in FEV2 or PEFR. The improvement in tests reflecting proximal airways may have been due to optimization of the inhalation technique, greater understanding of asthma, or better compliance with medication associated with regular attendance for the study. The greater bronchodilator response whilst children were inhaling budesonide by the PS may have been due to increased deposition or better distribution of the steroid but was probably related to a difference between the two groups in initial baseline function tests.

Increasing dose of budesonide, each dose given for a minimum of 1 month, were administered via a Nebuhaler to 14 patients. Two consecutive abnormally low fasting morning plasma cortisol values, taken 2 weeks apart, were accepted as evidence of hypothalamo-pituitary-adrenal (HPA) hypofunction. Data from nine of the 14 patients entering the study were available for analysis. One patient developed HPA hypofunction while inhaling 2.4 mg budesonide per day and another retained normal HPA function on a dose of 12 mg. In the remaining patients, intermediate doses resulted in suppression, or the patients were withdrawn unsuppressed for other reasons (n = 3). The results in this small patient sample suggest that budesonide administered via the Nebuhaler in doses up to 1.6 mg daily does not significantly affect plasma cortisol.