Errors during the preparation of drug infusions: a randomized controlled trial.

BACKGROUND: We investigated the extent and frequency of dose errors and treatment delays made as a consequence of preparing drug infusions at the bedside, rather than using pre-filled syringes. METHODS: Forty-eight nurses with critical care experience volunteered to take part in this randomized, blinded, controlled study conducted in the simulation centre of an urban hospital. They assisted in the management of a simulated patient with septic shock. Vasopressor infusions were prepared either by diluting concentrated drugs from ampoules or were provided in syringes pre-filled beforehand by an intensive care unit resident. RESULTS: The time taken for the infusion to be started and the final concentration of the drugs were measured. We also measured the concentration of infusions prepared by a pharmacist and a pharmaceutical company. Nurses took 156 s to start infusions when using pre-filled syringes compared with 276 s when preparing them de novo, a mean delay of 106 s [95% confidence interval (CI) 73-140 s, P<0.0001]. One infusion prepared from ampoules contained one-fifth of the expected concentration of epinephrine; another contained none at all. Medication errors were 17.0 times less likely when pre-filled syringes were used (95% CI 5.2-55.5), and infusions prepared by pharmacy and industry were significantly more likely to contain the expected concentration (P<0.001 for norepinephrine and P=0.001 for epinephrine). CONCLUSIONS: Providing drug infusions in syringes pre-filled by pharmacists or pharmaceutical companies would reduce medication errors and treatment delays, and improve patient safety. However, this approach would have substantial financial implications for healthcare providers, especially in less developed countries.

Heterogeneity of O6-alkylguanine DNA-alkyltransferase expression in human breast tumours.

An important determinant of cellular resistance to chemotherapeutic O6-alkylating agents, which comprise methylating and chloroethylating agents, is the ability of cells to repair alkylation damage at the O6-position of guanine in DNA. This is achieved by a specific DNA repair enzyme O6-alkylguanine DNA-alkyltransferase. In this study O6-alkylguanine DNA-alkyltransferase expression was measured in human breast tumours using both biochemical and immunohistochemical techniques. O6-alkylguanine DNA-alkyltransferase activity was then compared with known clinical prognostic indices to assess the potential role of O6-alkylguanine DNA-alkyltransferase in predicting the behaviour of this common malignancy. The application of both biochemical and immunohistochemical techniques was feasible and practical. Most breast tumours expressed high levels of O6-alkylguanine DNA-alkyltransferase. Immunohistochemical analysis showed marked variation in expression not only between individuals but also within individual tumours, and in the same patient, between metastases and between primary tumour and metastatic site. O6-alkylguanine DNA-alkyltransferase activity in tissue extracts significantly correlated not only with immunohistochemical staining intensity determined by subjective quantitation, but also with measures of protein levels using a computerised image analysis system including mean grey (P<0.001), percentage of cells positive for O6-alkylguanine DNA-alkyltransferase (P<0.001), and integrated optical density (P<0.001). O6-alkylguanine DNA-alkyltransferase expression did not correlate with any of the established clinical prognostic indicators for current treatment regimens. However, immunohistochemical offers a rapid and convenient method for assessing potential utility of O6-alkylating agents or O6-alkylguanine DNA-alkyltransferase inactivating agents in future studies of breast cancer treatment.

WT1 regulates the expression of the major glomerular podocyte membrane protein Podocalyxin.

The WT1 tumor suppressor gene encodes a zinc finger transcription factor expressed in differentiating glomerular podocytes. Complete inactivation of WT1 in the mouse leads to failure of mesenchymal induction and renal agenesis, an early developmental phenotype that prevents analysis of subsequent stages in glomerular differentiation [1]. In humans with Denys-Drash Syndrome, a heterozygous germline mutation in WT1 is associated with specific defects in glomeruli and an increased risk for developing Wilms Tumor [2,3]. WT1 target genes implicated in cell cycle regulation and cellular proliferation have been proposed [4], but the link between WT1 function and glomerular differentiation is unexplained. Here, we show that inducible expression of WT1 in rat embryonic kidney cell precursors leads to the induction of endogenous Podocalyxin, the major structural membrane protein of glomerular podocytes, which is implicated in the maintenance of filtration slits. Binding of WT1 to conserved elements within the Podocalyxin gene promoter results in potent transcriptional activation, and the specific expression pattern of Podocalyxin in the developing kidney mirrors that of WT1 itself. These observations support a role for WT1 in the specific activation of a glomerular differentiation program in renal precursors and provide a molecular basis for the glomerulonephropathy that is characteristic of Denys-Drash Syndrome.

Value of routine, non-targeted biopsies in the diagnosis of gastric neoplasia.

AIM: To explore how often a diagnosis of gastric neoplasia is made on routine, non-targeted biopsies taken for determination of Helicobacter pylori status, compared with directed biopsies from endoscopically abnormal mucosa. METHODS: Records of all patients with a biopsy diagnosis of gastric cancer or dysplasia during a two year period were reviewed to determine whether the biopsy had been targeted at an area of mucosal abnormality, and whether there was any evidence of dysplasia or malignancy before endoscopy. RESULTS: Of the 8907 endoscopic examinations that included biopsy, histology showed malignancy in 115 cases and dysplasia in 20. Of these, in 128 cases the biopsies were targeted from focal abnormal areas of mucosa, and six were from areas of diffuse mucosal thickening. In one case, adenocarcinoma was diagnosed in a patient with a "normal" endoscopic appearance; this patient was undergoing repeat endoscopy for previous dysplasia. CONCLUSIONS: Gastric malignancy or dysplasia was detected histologically in 1.5% of endoscopies that included biopsy. The performance of routine biopsies not targeted at a visible lesion from patients without previous diagnosis of neoplasia did not increase the detection of gastric malignancy. Such biopsies are indicated, however, if histological aspects of a patient's gastritis (such as atrophy or intestinal metaplasia) influence the clinical management, as in the treatment of helicobacter gastritis.