Linking drugs to obscure illnesses: lessons from pure red cell aplasia, nephrogenic systemic fibrosis, and Reye's syndrome. a report from the Southern Network on Adverse Reactions (SONAR).

Identification of serious adverse drug reactions (sADRS) associated with commonly used drugs can elude detection for years. Reye's syndrome (RS), nephrogenic systemic fibrosis (NSF), and pure red cell aplasia (PRCA) among chronic kidney disease (CKD) patients were recognized in 1951, 2000, and 1998, respectively. Reports associating these syndromes with aspirin, gadodiamide, and epoetin, were published 29, 6, and 4 years later, respectively.

Salicylates and pandemic influenza mortality, 1918-1919 pharmacology, pathology, and historic evidence.

The high case-fatality rate--especially among young adults--during the 1918-1919 influenza pandemic is incompletely understood. Although late deaths showed bacterial pneumonia, early deaths exhibited extremely "wet," sometimes hemorrhagic lungs. The hypothesis presented herein is that aspirin contributed to the incidence and severity of viral pathology, bacterial infection, and death, because physicians of the day were unaware that the regimens (8.

The clinical course of patients with idiopathic pulmonary fibrosis.

Background: Prospective data defining the clinical course in idiopathic pulmonary fibrosis (IPF) are sparse.

Objective: To analyze the clinical course of patients with mild to moderate IPF.

Design: Analysis of data from the placebo group of a randomized, controlled trial evaluating interferon-gamma1b.

High-resolution computed tomography in idiopathic pulmonary fibrosis: diagnosis and prognosis.

Rationale: High-resolution computed tomography (HRCT) is an integral aspect of the evaluation of patients with suspected idiopathic pulmonary fibrosis (IPF). However, few studies have evaluated its use in a large cohort.

Objectives: To describe HRCT features in patients with mild to moderate IPF, compare diagnostic evaluations by a radiology core (three thoracic radiologists) with those by study-site radiologists, correlate baseline clinical and physiologic variables with HRCT findings, and evaluate their association with mortality.

Physiologic and chemical simulation of cyanide and sarin toxicity and therapy.

The possibility of mass terrorism has become increasingly apparent. Accurate and relevant teaching tools are needed for healthcare givers and emergency personnel of all experience. We describe one of these tools, BODY Simulation, and its use in training caregivers to respond to chemical terrorism.

The physiology and pharmacology of growing old, as shown in body simulation.

Geriatric medicine is becoming increasingly important, due to the aging of our population. Healthcare givers need methods that can teach efficiently and painlessly the complexities involved with aging. One important tool in this area comprises modeling and simulation.

Analyses of efficacy end points in a controlled trial of interferon-gamma1b for idiopathic pulmonary fibrosis.

Background: Idiopathic pulmonary fibrosis (IPF) is a devastating disease, yet validated, reliable criteria for evaluating patient response to therapies in clinical trials are lacking.

Methods: To optimize selection of end point criteria for the study of interferon (IFN)-gamma1b in patients with IPF, we retrospectively analyzed the components of the primary efficacy end point used in a large, controlled study of 330 patients for reliability, validity, and sensitivity to treatment effect. The primary end point components were death, disease progression defined as a > or = 5 mm Hg increase in resting alveolar-arterial oxygen pressure gradient (P[A-a]O2), and disease progression defined as a > or = 10% decrease in percentage of predicted FVC.

Randomized, double-blind, placebo-controlled, dose-escalating study of aerosolized interferon gamma-1b in patients with mild to moderate cystic fibrosis lung disease.

Interferon gamma-1b (IFN-gamma1b) is a pleiotropic cytokine with immunomodulatory activities that could decrease bacterial burden, inflammation, and obstruction in patients with CF. Patients with CF (> or =12 years old, FEV1 > or =40% predicted) were randomly assigned to sequential dose cohorts inhaling 500 microg IFN-gamma1b, 1,000 microg IFN-gamma1b, or placebo by Respirgard II nebulizer thrice weekly for 12 weeks. Sputum bacterial density and spirometry were measured.

Effects of interferon-gamma 1b on biomarker expression in patients with idiopathic pulmonary fibrosis.

In a recent study of IFN-gamma 1b in 330 patients with idiopathic pulmonary fibrosis (IPF), progression-free survival was unchanged; however, a trend toward lower mortality was seen in IFN-gamma 1b-treated patients compared with placebo-treated patients (9.9 vs. 16.

A placebo-controlled trial of interferon gamma-1b in patients with idiopathic pulmonary fibrosis.

Background: Idiopathic pulmonary fibrosis is a progressive, fatal disease with no known efficacious therapy.

Methods: In a double-blind, multinational trial, we randomly assigned 330 patients with idiopathic pulmonary fibrosis that was unresponsive to corticosteroid therapy to receive subcutaneous interferon gamma-1b or placebo.

Results: Over a median of 58 weeks, interferon gamma-1b therapy did not significantly affect the primary end point of progression-free survival, defined as the time to disease progression or death, and no significant treatment effect was observed on measures of lung function, gas exchange, or the quality of life.

Virtual medical trainer. Patient assessment and trauma care simulator.

The Virtual Medical Trainer (VMET) combines multimedia sound and graphics with physiological engines, medical-procedures databases, and 3-D patients to produce an interactive environment that can mimic the cognitive pre-hospital assessment and care demands of a real emergency. VMET uses a reconfigurable component software and training framework that allows a uniform user interface, ease of increasing training complexity, and expansion of the software components. VMET provides an opportunity to experience a range of trauma scenarios prior to the challenge of an actual trauma situation.

Safety and effectiveness of long-term interferon gamma therapy in patients with chronic granulomatous disease.

In chronic granulomatous disease (CGD), diminished or absent neutrophil NADPH oxidase function leads to recurrent pyogenic infections and granuloma formation. In a recent randomized, placebo-controlled trail, short-term prophylactic use of recombinant human interferon gamma (rIFN-gamma 1b) reduced the risk of serious infection in CGD patients by 67%, The current study evaluated the safety and effectiveness of long-term rIFN-gamma therapy in CGD patients. Patients were treated three times weekly with rIFN-gamma and evaluated semiannually.

Antibiotic overkill of trauma victims?

Antibiotic usage was assessed in a prospective, randomized trial of recombinant interferon-gamma (rIFN-gamma) versus placebo for 212 severely injured trauma patients in four university hospitals. All patients were observed until death or discharge from the hospital. We found the number of antibiotics used and their associated costs staggering and difficult to justify, although serious antibiotic-related complications were infrequent.

The contribution of open extremity fractures to infection in multiply injured patients.

We sought to determine whether a contaminated open fracture was a reliable component for calculating the Outcome Predictive Score in patients with multiple injuries. We studied 41 patients whose primary source of contamination was open extremity fractures. Only one of the 41 patients developed osteomyelitis.

A randomized prospective clinical trial to determine the efficacy of interferon-gamma in severely injured patients.

Many aspects of the normal immune response are depressed after severe injury. Reduced monocyte human leukocyte antigen-DR (HLA-DR) levels have closely correlated with the development of major infection. After a pilot study with recombinant interferon-gamma (rIFN-gamma) showed restoration of depressed HLA-DR levels after major injury, a multicenter, prospective, randomized, double-blind trial was conducted.

Symptoms associated with vaginal colonization with yeast.

We correlated vulvovaginal symptoms with vaginal cultures for yeast in healthy female college students. Yeasts were isolated from 42 (29.2%) of 144 women.

Hepatitis B virus transmission between heterosexuals.

To determine if heterosexual activity was a risk factor for acquiring hepatitis B virus (HBV) infection, we studied attendees at a sexually transmitted disease (STD) clinic and students at a large university. Responses to self-administered questionnaires were used to exclude persons with factors known to be related to the acquisition of HBV and to determine the number of recent (past four months) and lifetime sexual partners. Serum samples were tested for hepatitis B surface antigen, antibody to hepatitis B surface antigen, and antibody to hepatitis B core antigen.

Campers' diarrhea outbreak traced to water-sewage link.

From June through September 1979, diarrheal illness occurred in an estimated 1,850 persons who had camped at a private campground in Arizona. Illness occurred more frequently among campers at that campground than among those in the adjacent State park (P less than 0.0001).

Diarrheal illness among infants and toddlers in day care centers. II. Comparison with day care homes and households.

During the second year of a prospective study of diarrheal illness among 0- to 36-month-old children in day care centers in Maricopa County, Arizona, we concurrently studied children of the same age in 30 day care homes and 102 households not using day care. The seasonal pattern of diarrhea, frequency of pathogen isolation, and relative frequency of individual pathogens were similar in the three settings. Giardia lamblia and rotavirus were the most common enteropathogens.

Diarrheal illness among infants and toddlers in day care centers. I. Epidemiology and pathogens.

We conducted a 2-year prospective study of diarrheal illness in children ages 0 to 36 months in 22 day care centers in Maricopa County, Arizona. In 7464 child-months of observation, 465 sporadic cases and 170 outbreak-associated cases of diarrhea were identified. Enteric pathogens were identified in 20% of diarrhea episodes.

Hepatic and cerebral pathology findings in children with fatal salicylate intoxication: further evidence for a causal relation between salicylate and Reye's syndrome.

Histology or necropsy records of 13 children with accidental or therapeutically induced salicylate intoxication were examined for the presence of hepatic and cerebral pathology findings characteristic of Reye's syndrome. Liver sections stained with haematoxylin and eosin showed intrahepatocytic microvesiculation (10 of 12 children) and absence of significant inflammation or necrosis (10 of 12 children). All 6 specimens of liver tissue stained with oil red O showed intrahepatocytic microvesicular fat with central hepatocytic nuclei distributed either diffusely throughout the lobule or more prominently in the lobular periphery.

Effect of immunoglobulin on hepatitis A in day-care centers.

Over a 21-month interval, we investigated the effectiveness of immunoglobulin (lg) in preventing hepatitis A spread in day-care centers. Immunoglobulin was given to all center and employees whenever hepatitis occurred in one center child or employee or parents in two families. Immunoglobulin programs were completed in 91 centers during the trial within an average of 17 days of onset of illness in the index case.

Reye's syndrome and salicylate use.

During an outbreak of influenza A, seven patients with Reye's syndrome and 16 ill classmate control subjects were evaluated for characteristics of the patients' prodromal illness and the control subjects illness and for medication usage. Patients during the prodrome and control subjects had similar rates of sore throat, coryza, cough, headache, and gastrointestinal complaints except for documented fever which occurred significantly more often in patients than in control subjects (P = .05).