Development and validation of an improved HPLC method for the control of potentially counterfeit isometamidium products.

Isometamidium, a mixture of related substances of which 8-(3-m-amidinophenyl-2-triazeno)-3-amino-5-ethyl-6-phenylphenanthridinium chloride hydrochloride (M&B4180A) is the principal active component, is the only chemical agent available for prophylaxis of veterinary trypanosomiasis. A method for the simultaneous quantitation of the major constituents M&B4180A, 3-(3-m-amidinophenyl-2-triazeno)-8-amino-5-ethyl-6-phenylphenanthridinium chloride hydrochloride (M&B38897), 7-(m-amidinophenyldiazo)-3,8-diamino-5-ethyl-6-phenylphenanthridinium chloride hydrochloride (M&B4250) and 3,8-di(3-m-amidinophenyltriazeno)-5-ethyl-6-phenylphenanthridinium chloride dihydrochloride (M&B4596) is described. The related substances are resolved on a Gemini C18 column (150 mm x 4.6 mm, 5 microm) using a mobile phase composed of a mixture of acetonitrile and 50 mM ammonium formate buffer pH 2.8 (25:75 v/v) at a flow rate of 1 ml/min with UV detection at 320 nm. The method is compatible with electrospray ionisation mass spectrometry and provides a tool for the control of substandard and counterfeit commercial preparations of isometamidium.

Determination of rifampicin in human plasma and blood spots by high performance liquid chromatography with UV detection: a potential method for therapeutic drug monitoring.

A high performance liquid chromatography method has been developed that allows quantification of concentrations of rifampicin in human plasma and blood spots. Rifampicin and papaverine hydrochloride (internal standard) were extracted from plasma using a Strata-X-CW extraction cartridge. These analytes were also extracted into acetonitrile from blood spots dried onto a specimen collection card. The recovery of rifampicin from plasma and blood spots was 84.5% and 65.0%, respectively. Separation was achieved by HPLC on a Kromasil C(18) column with a mobile phase composed of ammonium acetate (20 mM, pH 4.0) and acetonitrile, delivered on a gradient programme. Optimum detection was at 334 nm. The assay was linear over the concentration range of 0.5-20 microg/ml. The limit of quantification was 0.5 microg/ml in plasma; 1.5 microg/ml in blood spots. Both intraday and interday precision data showed reproducibility (R.S.D.< or =8.0, n=9). Stability studies showed rifampicin was stable in plasma for up to 9h after thawing; the samples were also stable for up to 9h after preparation. Five patient samples were analysed using the methods described. A correlation was found between the concentrations of RIF in plasma and blood spots (r(2)=0.92). This method is proposed as a means of therapeutic drug monitoring of rifampicin in patients with tuberculosis.

Certainty and uncertainty in genetic counselling: a qualitative case study.

This study examines the communication that occurs during routine genetic counselling sessions. It involves the qualitative analysis of nine consultations with one member of a clinical genetics team. The consultations were characterised by a contrast between the sense of certainty apparent in how the clinicians talked about the power and promise of the new genetics and the uncertainty communicated regarding the actual information produced by genetic tests and their limitations in solving people's problems. There was also a contrast between how the clinician seemed to control the format and agenda of the consultation and the apparently uncontrollable personal and social implications of the topics discussed. We speculate that this may be explained in terms of the clinician giving some order and certainty in an area of inherent uncertainty, and where great promises are as yet unrealised.

Incorrect recall of residual risk three years after carrier screening for cystic fibrosis: a comparison of two-step and couple screening.

OBJECTIVE: This study was undertaken to compare long-term recall of the meaning of test results after a negative result of 2-step or couple antenatal screening. STUDY DESIGN: In a randomized controlled trial a subject-completed questionnaire was sent to 275 women who had undergone couple testing 3 years earlier and 83 women who had undergone 2-step testing 3 years earlier (n = 263/358 for a response rate of 73%). The main outcome measure was understanding of test results. RESULTS: Three years after testing women who had undergone couple testing were 4.5 times (95% confidence interval 2.4-8.4 times) more likely than those who had undergone 2-step testing to accurately recall that the test result meant that they were unlikely to be carriers for cystic fibrosis (80%, 95% confidence interval 74%-86%, versus 49%, 95% confidence interval 36%-61%). Anxiety level, plans to have more children, and age were unrelated to recall. CONCLUSION: The results of this study, together with those from other evaluations, suggest that not only does couple testing avoid the high levels of anxiety associated with 2-step testing but it also results in greater awareness of the residual risk inherent in a negative screening test result.

Objectives of genetic counselling: differing views of purchasers, providers and users.

BACKGROUND: This study aimed to compare the views of purchasers, providers and users about the objectives of genetic counselling. METHODS: A modified Delphi technique was used, incorporating two postal questionnaires that were sent to six study groups with a three-month interval: purchasers (public health doctors (n = 37) and regional advisers in general practice (n = 35)); providers (clinical geneticists (n = 33) and genetic counsellors (n = 25)); and users (out-patients (n = 36) and members of genetic support groups (n = 32)). The response rate for the first questionnaire was 115/198 (58 per cent) and for the second, 102/198 (52 per cent). The first questionnaire asked an open-ended question about what the objectives of genetic counselling should be and asked respondents to rank order them. The second questionnaire summarized the views expressed in the first questionnaire and asked respondents to rank order the most frequently cited and most highly ranked five objectives. RESULTS: The five most frequently cited and highly ranked objectives from Questionnaire One were, in descending order: provide information, give support, facilitate decision-making, assess risk and achieve understanding. In response to Questionnaire Two, purchasers differed from providers and users in rating 'facilitate decision-making' more highly than did providers and users. By contrast, providers and users rated 'give information' more highly than did purchasers. CONCLUSIONS: Purchasers hold different views from providers and users about what the objectives of genetic counselling should be. This raises two questions: (1) Which views are or should be most influential in the future development of genetic counselling? (2) By what processes can more than one view on genetic counselling be integrated?

Information recall in genetic counselling: a pilot study of its assessment.

One of the main aims of genetic counselling is to provide information to patients that they can understand and recall. Measuring information recall is problematic and most studies do not make the comparison between recalled information and the information that is given in consultations. The aim of this study was to determine the validity of using genetic counsellors' reports of information given in genetic consultations as the basis for a measure of patient recall. Counsellors in 35 routine genetic counselling consultations were asked to indicate important information given during consultations by highlighting items in their summary letters sent to patients. This was checked by a researcher against tape-recordings of the consultations. One month later, patients were telephoned by the researcher and asked to recall as much information as they could from the consultation and to rate its importance. Over 95% of the information that counsellors identified as important had been given during the consultation. Patients rated this information as important. Although there was an association between the overall number of items that counsellors and patients judged to be important, patients more frequently judged information about family implications to be important than did counsellors. On the other hand, counsellors more frequently judged information about test, diagnosis and prognosis to be important than did patients. These results suggest that counsellors' summary letters are a valid baseline against which to measure patient recall. This measure will not, however, capture all the information that patients consider important.

Presentation of screen negative results on serum screening for Down's syndrome: variations across Britain.

OBJECTIVES: To document current practice of communicating screen negative results to pregnant women undergoing a test for Down's syndrome. SETTING: 169 British NHS hospital antenatal clinics currently offering multiple marker serum screening for Down's syndrome and giving results directly to women. METHODS: All 169 clinics were sent a letter asking about the method and form of communicating screen negative results. RESULTS: In only 29% of programmes were specific arrangements made to inform women of screen negative results, and in 5% these results were not given at all. Screen negative results were given as a verbal phrase in 44% of programmes, as a risk figure in 16% of programmes and as both in 40% of programmes. CONCLUSIONS: These results highlight a gap between screening policy guidelines and practice in the case of Down's syndrome serum screening.