Long-term use of depot-norethisterone enanthate: effect on blood lipid fractions.

This is the third report of a metabolic study on 56 long-term users (24 for 2-5 yr; 32 for over 5 yr) of the injectable contraceptive norethisterone enanthate (Net-En) and deals with the effects on the blood levels of lipoprotein fractions. There was no significant difference between this group and a group of 30 non-users in serum concentrations of triglycerides, total cholesterol, low density and very low density lipoproteins. There was a significant reduction in mean high density lipoprotein levels between the controls and the user groups (16% for the intermediate duration and 12% for the longer duration). Age, ethnic group, body-mass index and a close family history of cardiovascular disease were taken into account, as were various lifestyle factors: diet, exercise, alcohol consumption and smoking. In a smaller group, levels of apoproteins A and B were also assayed. There was a significant reduction in apoprotein A between controls and all users, but the significance was lost on adjusting for confounding variables. Consideration was given to the ratio of total cholesterol to high density lipoprotein cholesterol as an index of coronary risk. There were no significant differences in the total cholesterol:HDL-C ratio between controls and user groups. There was a significant interaction with ethnic group (Caucasian or Afro-Caribbean) in the response to duration of use.     

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.