A preliminary taxonomy of medical errors in family practice.

OBJECTIVE: To develop a preliminary taxonomy of primary care medical errors. DESIGN: Qualitative analysis to identify categories of error reported during a randomized controlled trial of computer and paper reporting methods. SETTING: The National Network for Family Practice and Primary Care Research. PARTICIPANTS: Family physicians. MAIN OUTCOME MEASURES: Medical error category, context, and consequence. RESULTS: Forty two physicians made 344 reports: 284 (82.6%) arose from healthcare systems dysfunction; 46 (13.4%) were errors due to gaps in knowledge or skills; and 14 (4.1%) were reports of adverse events, not errors. The main subcategories were: administrative failure (102; 30.9% of errors), investigation failures (82; 24.8%), treatment delivery lapses (76; 23.0%), miscommunication (19; 5.8%), payment systems problems (4; 1.2%), error in the execution of a clinical task (19; 5.8%), wrong treatment decision (14; 4.2%), and wrong diagnosis (13; 3.9%). Most reports were of errors that were recognized and occurred in reporters' practices. Affected patients ranged in age from 8 months to 100 years, were of both sexes, and represented all major US ethnic groups. Almost half the reports were of events which had adverse consequences. Ten errors resulted in patients being admitted to hospital and one patient died. CONCLUSIONS: This medical error taxonomy, developed from self-reports of errors observed by family physicians during their routine clinical practice, emphasizes problems in healthcare processes and acknowledges medical errors arising from shortfalls in clinical knowledge and skills. Patient safety strategies with most effect in primary care settings need to be broader than the current focus on medication errors.

Altered insulin secretion associated with reduced lipolytic efficiency in aP2-/- mice.

Recent studies have shown that genetic deficiency of the adipocyte fatty acid-binding protein (aP2) results in minor alterations of plasma lipids and adipocyte development but provides significant protection from dietary obesity-induced hyperinsulinemia and insulin resistance. To identify potential mechanisms responsible for this phenotype, we examined lipolysis and insulin secretion in aP2-/- mice. Beta-adrenergic stimulation resulted in a blunted rise of blood glycerol levels in aP2-/- compared with aP2+/+ mice, suggesting diminished lipolysis in aP2-/- adipocytes. Confirming this, primary adipocytes isolated from aP2-/- mice showed attenuated glycerol and free fatty acid (FFA) release in response to dibutyryl cAMP. The decreased lipolytic response seen in the aP2-/- mice was not associated with altered expression levels of hormone-sensitive lipase or perilipin. The acute insulin secretory response to beta-adrenergic stimulation was also profoundly suppressed in aP2-/- mice despite comparable total concentrations and only minor changes in the composition of systemic FFAs. To address whether levels of specific fatty acids are different in aP2-/- mice, the plasma FFA profile after beta-adrenergic stimulation was determined. Significant reduction in both stearic and cis-11-eicoseneic acids and an increase in palmitoleic acid were observed. The response of aP2-/- mice to other insulin secretagogues such as arginine and glyburide was similar to that of aP2+/+ mice, arguing against generally impaired function of pancreatic beta-cells. Finally, no aP2 expression was detected in isolated pancreatic islet cells. These results provide support for the existence of an adipo-pancreatic axis, the proper action of which relies on the presence of aP2. Consequently, aP2's role in the pathogenesis of type 2 diabetes might involve regulation of both hyperinsulinemia and insulin resistance through its impact on both lipolysis and insulin secretion.

The effect of carbon source, temperature and aeration on the production of ascosteroside, a novel antifungal agent, by Ascotricha amphitricha.

This paper describes the optimization of production of ascosteroside, a novel antifungal agent with an alpha-linked glycoside of a lanosterone-type triterpenoid structure. Glucose, sorbose and inositol were determined to be the best carbon sources for the production of ascosteroside. Temperature affected levels of ascosteroside, with production being highest at 16 degrees C with 1% glucose, and lowest at 32 degrees C. Dissolved oxygen levels were found to be critical in the production of ascosteroside in fermenter cultures. In order for production of ascosteroside to occur in fermenter cultures, the threshold level of dissolved oxygen was found to be above 26%.

Beta 3-adrenergic receptor-mediated lipolysis and oxygen consumption in brown adipocytes from cynomolgus monkeys.

Primary adipocytes were isolated from axillary brown adipose tissue from adult cynomolgus monkeys. That this tissue contained brown adipocytes was verified by morphological examination and by demonstrating the presence of uncoupling protein messenger ribonucleic acid in the isolated adipocytes. The contributions of beta 1-, beta 2-, and beta 3-adrenergic receptors (AR) to lipolysis and oxygen consumption of isolated brown adipocytes were determined after agonist stimulation. Dose responses were determined using isoproterenol (a nonselective beta-AR agonist), denopamine (beta 1-AR agonist), procaterol (beta 2-AR agonist), and CGP12177A (beta 1- and beta 2-AR antagonist, beta 3-AR agonist). Isoproterenol, denopamine, and procaterol stimulated lipolysis with EC50 values of 4,500, and 83 nmol/L, respectively. Intrinsic activities (relative to isoproterenol maxima) were 100%, 74%, and 59%, respectively. The presence of beta 3-ARs coupled to lipolysis was demonstrated by the activity of CGP12177A (EC50 = 1.6 mumol/L; intrinsic activity = 62%). Isoproterenol stimulated oxygen consumption of brown adipocytes by 75-100% above the basal rate, with an EC50 of 1 mumol/L. Denopamine, procaterol, and CGP12177A stimulated oxygen consumption at a concentration of 100 mumol/L. These results demonstrate that all three beta-adrenergic receptor subtypes are coupled to lipolysis and oxygen consumption in brown adipocytes from cynomolgus monkeys.

Metabolic alterations associated with the antidiabetic effect of beta 3-adrenergic receptor agonists in obese mice.

Treatment of obese (ob/ob) mice with the beta 3-adrenergic receptor (beta 3-AR) agonist BRL-35135 (1 mg.kg body wt-1.day-1 for 20 days) normalized plasma glucose levels and significantly decreased plasma insulin and nonesterified fatty acid levels. The time frame for the hypoglycemic effect, which reached a maximum after 10 days of treatment, paralleled an increase in brown adipose tissue DNA and protein content. The basal level of mRNA for the beta 3-AR and mitochondrial uncoupling protein was found to be markedly decreased in the ob/ob animals relative to the lean group. Chronic treatment of ob/ob mice for 20 days resulted in a twofold increase in beta 3-AR mRNA and a fivefold increase in uncoupling protein mRNA in brown adipose tissue relative to the placebo group. These findings indicate that chronic treatment of ob/ob animals with a beta 3-AR agonist results in proliferation of brown adipose tissue, with an upregulation of the beta 3-AR, which is associated with a decrease in plasma glucose, insulin, and nonesterified fatty acid levels.

Inhibition of fatty acid synthesis decreases very low density lipoprotein secretion in the hamster.

The hamster was developed as a model to study very low density lipoprotein (VLDL) metabolism, since, as is the case in humans, the hamster liver was found to synthesize apoB-100 and not apoB-48. The effect of inhibiting fatty acid synthesis on the hepatic secretion of VLDL triglyceride (TG) and apolipoprotein (apo) B-100 in this model was then investigated. In an in vivo study, hamsters were fed a chow diet containing 0.15% TOFA (5-tetradecyloxy-2-furancarboxylic acid), an inhibitor of acetyl-CoA carboxylase. After 6 days of treatment, plasma triglyceride and cholesterol levels were decreased by 30.2% and 11.6%, respectively. When the secretion of VLDL-TG by the liver was measured in vivo after injection of Triton WR 1339, TOFA treatment was found to decrease VLDL-TG secretion by 40%. In subsequent in vitro studies utilizing cultured primary hamster hepatocytes, incubation with 20 microM TOFA for 4 h resulted in 98% and 76% inhibition in fatty acid and triglyceride synthesis, respectively; VLDL-TG secretion was decreased by 90%. When hepatocytes were pulsed with [3H]leucine, incubation with TOFA resulted in a 50% decrease in the incorporation of radiolabel into secreted VLDL apoB-100. The results of this study indicate that inhibition of intracellular triglyceride synthesis decreases the secretion of VLDL-TG and apoB-100, and does not result in the secretion of a dense, triglyceride-depleted lipoprotein.

The use of fluorescent and special staining techniques in the aspiration of nocardiosis and actinomycosis.

This report outlines the techniques and illustrates the utility of special stains and fluorescent microscopy when applied to aspiration cytology material. This procedure allowed quick and accurate diagnosis of opportunistic infectious organisms, specifically nocardiosis and actinomycosis.

Cervicofacial actinomycosis. Rapid diagnosis by thin-needle aspiration.

Thin-needle aspiration cytology is a well-known minimally invasive technique that is used in the diagnosis of neoplastic disease. The same biopsy technique provides a means for immediate identification of actinomycosis. Aspiration specimens may be used for morphologic studies, as well as for microbiologic isolation. The diagnostic histologic feature of sulfur granules remains intact with this cytologic aspiration technique. This technique is a safe, simple, and rapid means of diagnosing actinomycosis and appears to have value in the diagnosis of other infectious diseases as well.

Aspiration cytology for diagnosis of head and neck masses.

Most American clinicans have been relectant to utilize aspiration biopsy due to poor interpretive skills by the pathologists in the past and a fear of tumor spread by the needle. Voluminous European series and recent American series have proved aspiration to be safe and reliable. In our series of 78 cases, both thin-needle aspiration and conventional tissue biopsies were made. The diagnoses were compared and the overall agreement rate was 90%.

Rapid diagnosis of actinomycosis by thin-needle aspiration biopsy.

Actinomycosis was diagnosed in three cases by the use of thin-needle aspiration biopsy technic. Aspiration was utilized for morphologic studies and collection of material for microbiologic isolation. The critical histologic features of sulfur granules remain intact with aspiration technic. Thin-needle aspiration biopsy is a safe, simple, and rapid technic employed in the diagnosis of neoplastic disease. The use of this technic in the diagnosis of actinomycosis is demonstrated in this report.