Adopting an information management approach to the design and implementation of information systems.

As the NHS adopts an information management approach to coordinated handling of total information resources, methods of systems analysis and design require assessment to ensure that they are appropriate. Mandatory use of Structured Systems Analysis and Design Methodology (SSADM) may be encouraging a damagingly narrow view of information systems. Research is described in which an holistic view of information systems is applied, allowing the needs of information users to play a stronger role in determining how information will be supplied to them. The techniques may also assist the training activities associated with implementing new systems.     

Demonstration of low frequency of human papillomavirus DNA in cervical adenocarcinoma and adenocarcinoma in situ by the polymerase chain reaction and in situ hybridization.

There is evidence that cervical adenocarcinoma is increasing in incidence, particularly in young women. In order to assess the possible role of human papillomaviruses in cervical glandular oncogenesis, 16 cases of invasive adenocarcinoma and eight cases of adenocarcinoma in situ have been examined by in situ DNA hybridization using biotinylated probes to human papillomavirus types 6, 11, 16, 18, and 31, and assessed by polymerase chain reaction analysis for human papillomavirus types 11, 16, and 18 sequences. Of the invasive adenocarcinomas, four of 16 contained human papillomavirus type 16 sequences and one of 16 contained type 18 sequences as assessed by polymerase chain reaction analysis. Five of eight cases of adenocarcinoma in situ contained human papillomavirus type 16 sequences by polymerase chain reaction analysis. Only one invasive adenocarcinoma and one case of adenocarcinoma in situ showed a positive in situ hybridization signal. The low rate of carriage of the human papillomavirus sequences examined suggests that these viral types may not play a major role in cervical glandular neoplasia.     

The frequency of type I heterozygous protein S and protein C deficiency in 141 unrelated young patients with venous thrombosis

The frequency of heterozygous protein C and protein S deficiency, detected by measuring total plasma antigen, in a group (n = 141) of young unrelated patients (less than 45 years old) with venous thrombotic disease was studied and compared to that of antithrombin III, fibrinogen, and plasminogen deficiencies. Among 91 patients not receiving oral anticoagulants, six had low protein S antigen levels and one had a low protein C antigen level. Among 50 patients receiving oral anticoagulant therapy, abnormally low ratios of protein S or C to other vitamin K-dependent factors were presented by one patient for protein S and five for protein C. Thus, heterozygous Type I protein S deficiency appeared in seven of 141 patients (5%) and heterozygous Type I protein C deficiency in six of 141 patients (4%). Eleven of thirteen deficient patients had recurrent venous thrombosis. In this group of 141 patients, 1% had an identifiable fibrinogen abnormality, 2% a plasminogen abnormality, and 3% an antithrombin III deficiency. Thus, among the known plasma protein deficiencies associated with venous thrombosis, protein S and protein C deficiencies (9%) emerge as the leading identifiable associated abnormalities.     

Immunoadsorbent purification of carcinoembryonic antigen using a monoclonal antibody: a direct comparison with a conventional method

Carcinoembryonic antigen (CEA) has been extracted and purified by two different methods from a single aqueous homogenate of liver metastases from a primary adenocarcinoma of the colon, thus enabling direct comparison to be made between a conventional technique using gel filtration and a monoclonal antibody immunoadsorbent method. Yield, immunoreactivity and purity have been determined in both cases by direct weighing, enzyme-linked immunoadsorbent assay, radioimmunoassay and SDS-polyacrylamide gel electrophoresis. Reactivity of the antigen with monoclonal and polyclonal anti-CEA antibodies recognising different epitopes was analysed by Western blotting. There appears to be no significant difference in immunoreactivity or purity by these criteria, but the immunoadsorbent method gave a higher yield of CEA for far less expenditure of time and effort. A variant of CEA with a lower molecular weight was also identified in both preparations.     

The pharmacokinetics of 125I-atrial natriuretic factor in anaesthetized rats. Effects of neutral endopeptidase inhibition with candoxatrilat and of ANF-C receptor blockade.

The effects of candoxatrilat (cis-4-([2-carboxy-3-(2-methoxyethoxy)propyl]-1-cyclopentanecarbonyla mino)- 1-cyclohexane carboxylic acid) and the ring-deleted atrial natriuretic factor (ANF) analogue C-ANF4-23 (des[Gln18, Ser19, Gly20, Leu21, Gly22]ANF4-23-NH2) on the clearance of (3-[125I]iodotyrosyl28)ANF (125I-ANF) were studied in both intact and nephrectomized anaesthetized rats. HPLC analysis was used to verify that the 125I-labelled material isolated by solid phase extraction of rat plasma was intact ANF. In intact animals, clearance of 125I-ANF was biphasic with a T1/2 alpha of 17 sec and T1/2 beta of 95 sec. Volume of distribution (Vd) was 564 mL/kg and plasma clearance (Clp) 248 mL/min/kg. Candoxatrilat, over the dose range 0.01-10 mg/kg i.v., increased T1/2 beta (by a maximum of 56%) and decreased Clp (by up to 52%) with no effect on T1/2 alpha or Vd. C-ANF4-23 (10 micrograms/kg+1 microgram/kg/min i.v.) reduced Vd (by 57%) and Clp (by 54%) with no effect on T1/2 beta, whilst abolishing the T1/2 alpha phase in over 50% of animals. Increasing the dose of C-ANF4-23 did not increase the effect on any of these parameters, apart from a small increase in T1/2 beta. Combining the two agents resulted in a substantial decrease in Clp (76%) whilst the reduction in Vd and increase in T1/2 beta were comparable to those seen with C-ANF4-23 and candoxatrilat alone, respectively. In nephrectomized rats, the pharmacokinetics of 125I-ANF and the changes induced by candoxatrilat were similar to those observed in intact animals, whilst the effects of C-ANF4-23 alone were greater than in intact animals. The combination of C-ANF4-23 and candoxatrilat again produced a substantial increase in T1/2 beta (153%) and decreases in Vd (55%) and Clp (78%) in nephrectomized animals, although these changes could not be distinguished from those seen in intact animals treated with the same combination. Our studies indicate that neutral endopeptidase and ANF-C receptors are both major, and approximately equal, clearance mechanisms for 125I-ANF, together accounting for at least 75% of the total clearance of this peptide in the rat.     

Routinely collected general practice data aids identification of people with hyperglycaemia and metabolic syndrome.

AIMS: To assess the performance of a risk score comprising data routinely available in general practice records (age, gender, body mass index, family history of diabetes, smoking habits and prescribed anti-hypertensive drugs or steroids) in detecting diabetes, impaired glucose tolerance and metabolic syndrome. METHODS: In a population-based, cross-sectional study in a semi-rural general practice in Jutland, Denmark, Cambridge Risk Scores were calculated for 1355 patients without known diabetes (69% response rate) who completed questionnaires and underwent anthropometric measurement and an oral glucose tolerance test. RESULTS: Prevalences of diabetes, impaired glucose tolerance and metabolic syndrome were 2.29% (95% CI: 1.56-3.23), 6.64% (95% CI: 5.38-8.10) and 13.4% (95% CI: 11.5-15.2), respectively. Area under the ROC curve for the risk score and diabetes was 83.8% (75.9-91.7) and for metabolic syndrome [European Group for the Study of Insulin Resistance (EGIR)] was 78.1% (74.6-81.6). Twenty per cent of the population had a risk score above 0.246; at this threshold the sensitivity to detect diabetes was 71.0% (53.4-83.9), the specificity 81.2% (79.0-83.2), positive predictive value 8.1% (6.6-10.0) and likelihood ratio 3.77 (2.94-4.85). For metabolic syndrome (EGIR) corresponding values for sensitivity were 50.3% (43.1-57.5), specificity 84.7% (82.5-85.6), positive predictive value 33.6% (28.2-39.4), and likelihood ratio 3.28 (2.69-4.00). CONCLUSIONS: Undiagnosed hyperglycaemia and metabolic syndrome are common. The Cambridge Risk Score is a practical first step in a screening procedure to identify individuals with these disorders who might benefit from diagnostic testing or to direct preventive interventions.     

Endotoxin shock in newborn dogs: serial hemodynamic studies

Using a newly modified dye dilution method for cardiac output determination, we successfully performed frequent serial hemodynamic measurements in newborn dogs to characterize hemodynamic changes in endotoxin shock in neonates. Sixty-seven mongrel newborn dogs (2 to 20 days old, 300 to 1500 gm) were divided into four groups: group 1 (2 to 20 days old, 300 to 1500 gm) received normal saline solution, group 2 (2 to 10 days old, 300 to 800 gm) received 1.5 mg/kg of Escherichia coli lipopolysaccharide (LPS), group 3 (2 to 10 days old, 300 to 800 gm) received 10 mg/kg of LPS, and group 4 (11 to 20 days old, 801 to 1500 gm) received 10 mg/kg of LPS. Cardiac output, heart rate, mean arterial pressure, systemic vascular resistance, and minute work were measured serially after endotoxin administration for 4 hours. Despite extensive manipulation, these measurements were stable in controls throughout the length of the study. Endotoxin, administered at two different doses of 1.5 mg/kg and 10 mg/kg, had profound effects on hemodynamic responses. These effects included a significant dose-related fall in cardiac output, minimal changes in heart rate, and a marked rise in systemic vascular resistance. The hemodynamic changes reported in this study lend additional support to the hypothesis that maturational factors are involved in the hemodynamic response to LPS.     

Comparison of abdominopelvic computed tomography results and findings at second-look laparotomy in ovarian carcinoma patients

In 35 women with epithelial carcinoma of the ovary, the results of restaging laparotomy were compared with the preoperative abdominopelvic computed tomography (CT) findings to evaluate the accuracy of CT for determining tumor status. In the 36 studies performed, enhanced CT scans at 10-mm to 15-mm intervals had a sensitivity of 84% and a specificity of 88%; in addition, there was 86% agreement between the CT and surgical findings. These results suggest that although CT is not accurate enough to completely replace the restaging laparotomy, its high accuracy in determining residual disease after treatment is helpful for patient management.     

A randomized pilot study in Type 1 diabetes complicated by severe hypoglycaemia, comparing rigorous hypoglycaemia avoidance with insulin analogue therapy, CSII or education alone.

AIM: To determine potential for amelioration of recurrent severe hypoglycaemia without worsening in overall control in individuals with long-standing Type 1 diabetes (T1DM). METHODS: Twenty-one people with T1DM characterized by altered hypoglycaemia awareness and debilitating severe hypoglycaemia were randomized in a pilot 24-week prospective study to optimized analogue therapy (ANALOGUE; lispro/glargine); continuous subcutaneous insulin infusion therapy (CSII; lispro); or re-education with relaxation of blood glucose targets on existing conventional insulin regimen (EDUCATION). Glycaemic profiles and duration of biochemical hypoglycaemia were measured by continuous subcutaneous glucose monitoring and self-monitored blood glucose. RESULTS: Further severe hypoglycaemia was prevented in five participants (71%) in each group (P = 0.06). Incidence of severe hypoglycaemia was: 0.6 (ANALOGUE), 0.9 (CSII), and 3.7 (EDUCATION) episodes per patient year. Restoration of hypoglycaemia awareness was confirmed by validated questionnaire in three (43%) ANALOGUE, four (57%) CSII and five (71%) EDUCATION patients. Glycated haemoglobin (HbA1c) was significantly improved in the ANALOGUE group between weeks 0 and 24 (8.6 +/- 1.1 vs. 7.6 +/- 0.8%; P = 0.04 for change). Non-significant improvement was seen in the CSII group (8.5 +/- 1.9 vs. 7.4 +/- 1.0%; P = 0.06). No change in HbA1c was seen in the EDUCATION group (8.5 +/- 1.1 vs. 8.3 +/- 1.0%; P = 0.54). There were no episodes of diabetic ketoacidosis or any other adverse events in any group. CONCLUSIONS: In this pilot randomized trial comparing optimized ANALOGUE, CSII or EDUCATION alone in unselected individuals with recurrent severe hypoglycaemia, we show potential for restoring hypoglycaemia awareness and preventing further severe hypoglycaemia with concomitant improvement in glycaemic control in ANALOGUE and CSII groups.