Prevention of erosive oesophagitis relapse with pantoprazole

AIM: To compare the safety and efficacy of pantoprazole and ranitidine in maintaining erosive oesophagitis healing. METHODS: Gastro-oesophageal reflux disease patients (349) with endoscopically documented healed erosive oesophagitis (grade 0 or 1) were randomly assigned to receive pantoprazole (10, 20 or 40 mg/q.d.s.) or ranitidine (150 mg/b.d.). Erosive oesophagitis status was assessed endoscopically at months 1, 3, 6 and 12 or when relapse symptoms appeared (relapse = reappearance of erosive oesophagitis grade 2 within 12 months). Symptom-free days were also assessed. RESULTS: Pantoprazole 20- and 40-mg were significantly more effective than ranitidine in maintaining healing regardless of initial erosive oesophagitis grade. Response was dose-related. After 12 months 78, 55, 46 and 21% of patients remained healed (40-, 20-, 10-mg pantoprazole and ranitidine). Pantoprazole 40-mg produced significantly more symptom-free days (83%) than ranitidine (58%). Heartburn-free days/nights were significantly higher with pantoprazole 40-mg (92 and 93%) than ranitidine (73 and 77%). The most frequent reason for discontinuation, unsatisfactory efficacy, occurred most often with ranitidine (P < 0.001). CONCLUSION: Once-daily pantoprazole therapy prevented relapse of healed erosive oesophagitis more effectively than ranitidine and with fewer heartburn days. Response to pantoprazole was dose-related. Pantoprazole 40-mg was the most effective regimen and consistent in maintaining erosive oesophagitis healing with a good safety and tolerability profile.     

Toxicology and carcinogenesis study of chloral hydrate (ad libitum and dietary controlled) (CAS no. 302-17-0) in male B6C3F1 mice (gavage study)

[structure: see text] Chloral hydrate is used medically as a sedative or hypnotic and as a rubefacient in topical preparations, and it is often given to children as a sedative during dental and other medical procedures. Chloral hydrate is used as a central nervous system depressant and sedative in veterinary medicine and as a general anesthetic in cattle and horses. It is a byproduct of the chlorination of water and has been detected in plant effluent after the bleaching of softwood pulp. Chloral, the anhydrous form of chloral hydrate, is used as a synthetic intermediate in the production of insecticides and herbicides. Chloral hydrate was nominated for study by the Food and Drug Administration based upon widespread human exposure and its potential hepatotoxicity and the toxicity of related chemicals. A dietary control component was incorporated in response to concerns within the regulatory community relating to increased background neoplasm incidences in rodent strains used for toxicity testing and to the proposed use of dietary restriction to control background neoplasm incidence in rodent cancer studies. Male B6C3F1 mice (ad libitum-fed or dietary-controlled) received chloral hydrate (99% pure) by gavage for 2 years. 2-YEAR STUDY IN MALE MICE: Groups of 120 male mice received chloral hydrate in distilled water by gavage at doses of 0, 25, 50, or 100 mg/kg 5 days per week for 104 to 105 weeks. Each dose group was divided into two dietary groups of 60 mice. The ad libitum-fed mice had free access to feed, and the dietary-controlled mice received feed in measured daily amounts calculated to maintain body weight on a previously computed idealized body weight curve. Twelve mice from each diet and dose group were evaluated at 15 months. SURVIVAL, FEED CONSUMPTION, AND BODY WEIGHTS: Survival of dosed groups of ad libitum-fed and dietary-controlled mice was similar to that of the corresponding vehicle controls. When compared to the ad libitum-fed groups, dietary control significantly increased survival in the vehicle controls and 25 and 50 mg/kg groups. Mean body weights of all dosed groups were similar to those of the vehicle control groups throughout the study. The dietary-controlled mice were successfully maintained at or near their target idealized body weights. There was less individual variation in body weights in the dietary-controlled groups than in the corresponding ad libitum-fed groups. Feed consumption by 25 and 50 mg/kg ad libitum-fed mice was generally similar to that by the vehicle controls throughout the study. Feed consumption by 100 mg/kg ad libitum-fed mice was slightly less than that by the vehicle controls throughout the study. HEPATIC ENZYME ANALYSIS: Chloral hydrate did not significantly induce either lauric acid 4-hydroxylase activity or CYP4A immunoreactive protein in any of the dosed groups of ad libitum-fed mice. However, 100 mg/kg did significantly induce both lauric acid 4-hydroxylase activity and CYP4A immunoreactive protein in the dietary-controlled mice. Moreover, the induction response profile of CYP4A was similar to the increase in the incidence of liver neoplasms at 2 years in the dietary-controlled mice with the major effect occurring in the 100 mg/kg group. The serum enzymes alanine aminotransferase, amylase, aspartate aminotransferase, and lactate dehydrogenase were also assayed at 2 years. In the ad libitum-fed groups there was a significant increase in aspartate aminotransferase activity in the 50 mg/kg group. There were no other significant effects in any dosed group, but in general the dietary-controlled groups exhibited lower values than the corresponding ad libitum-fed groups. ORGAN WEIGHTS AND PATHOLOGY FINDINGS: The heart weight of ad libitum-fed male mice administered 100 mg/kg and the kidney weights of 50 and 100 mg/kg ad libitum-fed mice were significantly less than those of the vehicle controls at 2 years. The liver weights of all dosed groups of ad libitum-fed and dietary-controlled mice were greater than those of the vehicle control groups at 2 years, but the increases were not statistically significant. The incidence of hepatocellular adenoma or carcinoma (combined) in ad libitum-fed mice administered 25 mg/kg was significantly greater than that in the vehicle controls at 2 years. The incidences of hepatocellular carcinoma and of hepatocellular adenoma or carcinoma (combined) occurred with positive trends in dietary-controlled male mice at 2 years, and the incidence of hepatocellular carcinoma in 100 mg/kg dietary-controlled mice was significantly increased. CONCLUSIONS: Under the conditions used in this 2-year gavage study, there was some evidence of carcinogenic activity of chloral hydrate in male B6C3F1 mice based on increased incidences of hepatocellular adenoma or carcinoma (combined) in ad libitum-fed mice and on increased incidences of hepatocellular carcinoma in dietary-controlled mice. In the dietary-controlled mice, induction of enzymes associated with peroxisome proliferation was observed at higher doses.     

Bifid direct aortic arch origin of left vertebral artery: a unique vascular variant

The present report describes an unusual case of a duplicated origin of the left vertebral artery from the aorta discovered incidentally in a young patient. Computed tomographic angiography followed by conventional angiography demonstrated this anomaly. Angiographic findings and vertebral artery embryogenesis and anomalies are discussed.     

Consensus guidelines on evaluation and management of the febrile child presenting to the emergency department in India

Justification

India, home to almost 1.5 billion people, is in need of a country-specific, evidence-based, consensus approach for the emergency department (ED) evaluation and management of the febrile child.

Process

We held two consensus meetings, performed an exhaustive literature review, and held ongoing web-based discussions to arrive at a formal consensus on the proposed evaluation and management algorithm. The first meeting was held in Delhi in October 2015, under the auspices of Pediatric Emergency Medicine (PEM) Section of Academic College of Emergency Experts in India (ACEE-INDIA); and the second meeting was conducted at Pune during Emergency Medical Pediatrics and Recent Trends (EMPART 2016) in March 2016. The second meeting was followed with futher e-mail-based discussions to arrive at a formal consensus on the proposed algorithm.

Objective

To develop an algorithmic approach for the evaluation and management of the febrile child that can be easily applied in the context of emergency care and modified based on local epidemiology and practice standards.

Recommendations

We created an algorithm that can assist the clinician in the evaluation and management of the febrile child presenting to the ED, contextualized to health care in India. This guideline includes the following key components: triage and the timely assessment; evaluation; and patient disposition from the ED. We urge the development and creation of a robust data repository of minimal standard data elements. This would provide a systematic measurement of the care processes and patient outcomes, and a better understanding of various etiologies of febrile illnesses in India; both of which can be used to further modify the proposed approach and algorithm.

     

Expedited computed tomography perfusion and angiography in acute ischemic stroke: a feasibility study

Background

Acute ischemic stroke diagnosis and treatment are among the most challenging in Emergency Medicine. Perfusion computed tomography (CTP) can increase the sensitivity for detecting ischemic stroke and, especially with the addition of CT angiography (CTA), improve decision-making regarding thrombolytic therapy compared to non-contrast computed tomography (NCCT) alone. However, because acute stroke protocols do not generally include procedures for multimodal imaging, they are not commonly performed. In addition, there is concern that additional studies could delay or preclude therapy in patients otherwise eligible for thrombolytic therapy.

Objectives

To demonstrate the feasibility of perfusion CTP and CTA in addition to NCCT of the brain in the emergency assessment of patients with acute ischemic stroke. Methods: Starting January 2008, multimodal (CTP and CTA) imaging was added to NCCT in the Emergency Department (ED) initial assessment of patients with stroke of ≤ 5 h duration. Over the subsequent 9 months, we measured the time from ED arrival to imaging and to recombinant tissue plasminogen activator (rt-PA) treatment and compared these times to patients evaluated with CT alone.

Results

From January to October 2008, 95 patients had CTP and CTA studies in addition to NCCT for acute ischemic stroke. There were no differences between the average time to CT study or to rt-PA treatment between patients evaluated with multimodal CT imaging and patients assessed with NCCT alone.

Conclusions

Combining CTP and CTA with NCCT is feasible and does not adversely increase the time to CT imaging or rt-PA treatment in patients with acute ischemic stroke.