Determinants of change in the intention to use benzodiazepines.

OBJECTIVE: To examine attitudes and beliefs associated with changes in the intention to use benzodiazepines during the six-month period after first benzodiazepine use. DESIGN: Population-based 6-month follow-up with 3 measurement points (baseline, 2 weeks after inclusion, 6 months after inclusion). SETTING: Starting or initial benzodiazepine users were included during a period of 4 months from November 1994 in the only pharmacy of a Dutch community of 13,500 people. MEASURES: Variables proposed by the Model of Planned Behaviour and the Health Belief Model. Drug exposure data from automated pharmacy records. RESULTS: At baseline, the intention to use benzodiazepines was primarily predicted by the perceived norm of the general practitioner regarding benzodiazepine use, and by the participants' own attitudes. After fourteen days, the determinants of change in the intention to use benzodiazepines were the initially perceived norm of the general practitioner and the change in the severity of participants' illnesses. After six months, the change in the severity of the illness and the perceived health benefits of benzodiazepines at the time of inclusion were the main determinants of the change in the intention to use benzodiazepines between the second and third measurement point. The intention to use benzodiazepines showed a decrease during follow-up. The three intention measures were significant predictors of actual benzodiazepine use during the year following baseline assessment. CONCLUSION: The study sheds light on interesting determinants of decrease or increase in the intention to use during the six-month period after first benzodiazepine use.

Evaluation of hepatitis C antibody testing in saliva specimens collected by two different systems in comparison with HCV antibody and HCV RNA in serum.

Two different ELISA assays, the Ortho HCV 3.0 ELISA (Ortho Diagnostics Systems) and the Mono-Lisa anti-HCV Plus (Sanofi Diagnostics Pasteur) were evaluated for the detection of hepatitis C virus (HCV) antibody in saliva samples. Specimens were collected from 152 individuals who participated in a longitudinal cohort study on HIV infection, and who used illicit drugs. Saliva specimens were collected using two different systems: Salivette (Sarstedt) and Omni-Sal (Saliva Diagnostic Systems). Saliva specimens were tested following modified protocols by both ELISAs, and the results were compared with serum specimens that were tested according to the instructions of the manufacturer. Serum samples of 102 (67%) participants were positive by both assays, and 50 persons were negative for HCV antibody. A total of 99 of the 102 serum specimens were confirmed as positive using Ortho Riba HCV 3.0 (Ortho Diagnostics System) and Deciscan HCV (Sanofi Diagnostics Pasteur), and 3 yielded discrepant results. As no cut-off level is known for testing saliva samples by ELISA, 3 different levels were chosen: mean (M) + 1 standard deviation (SD), M + 2 SD, and M + 3 SD of the optical densities of saliva tests of the 50 HCV serum antibody negative persons. At a level of M + 1 SD and M + 2 SD the Salivette/Mono-Lisa combination gave the greatest proportion of HCV antibody positive saliva specimens obtained from the 102 HCV serum antibody positive participants, 88% and 79%, respectively. Differences between the various collection systems and assay combinations were not significant statistically. In 76 of the 102 persons with HCV antibodies in serum, HCV RNA was detected in serum. Salivary presence of HCV RNA, however, could not be demonstrated. The results show that the assays compared are unsuitable for diagnostic use, but the sensitivities of the assays are acceptable for use in epidemiological studies.

Characterization of the Wsc1 protein, a putative receptor in the stress response of Saccharomyces cerevisiae.

Wsc1p, Wsc2p, Wsc3p, and Wsc4p, members of a novel protein family in the yeast Saccharomyces cerevisiae, are putative sensors or receptors in the stress response. Genetic characterization suggests that the WSC family are upstream regulators of the stress-activated PKC1-MAP kinase cascade and are required for the heat shock response and for maintenance of cell wall integrity. The Wsc proteins share sequence characteristics: at their N terminus they have a cysteine motif and a serine/threonine-rich domain predicted to be extracellular, a hydrophobic domain suggested to be transmembranous, and a variable, highly charged C terminus that may be involved in intracellular signaling. Although a role for the WSC genes in maintenance of cell wall integrity has been firmly established, little is known about the properties of the proteins. As reported here, to study its properties in vivo, we epitope tagged the Wsc1 protein. Wsc1p was found to fractionate with the membrane pellet after high-speed centrifugation. Extraction experiments show that Wsc1p is an integral membrane protein present in two forms: one solubilized by detergent, the other Triton X-100 insoluble. Our results also show that Wsc1p is glycosylated and phosphorylated. To characterize the contribution of different domains to the function of Wsc1p, we generated various deletion constructs. Analysis of the properties and function of the mutant proteins shows that the predicted extracellular serine/threonine-rich domain is required for Wsc1p functionality, as well as its glycosylation. A mutant Wsc1 protein lacking the putative transmembrane domain is not functional and partitions to the soluble fraction. Overexpression of full-length Wsc1p inhibits cell growth, with the N terminus alone being sufficient for this inhibition. This suggests that Wsc1p may function in a complex with at least one other protein important for normal cell growth.

Are professional attitudes related to gender and medical specialty?

OBJECTIVES: The importance of professional attitudes in medical care has long been recognized; however, medical training has not stressed attitude development until recently. In previous studies among medical students, we found that gender and specialty preference are important factors in attitudes. In this study, patient-centredness of trainees in general practice and surgery and of final-year clerks preferring one of these specialties was assessed in one medical school in The Netherlands. The effect of gender, specialty and training level on attitude was investigated. DESIGN: In 1995, attitudes of 37 general practice trainees, 31 surgery trainees and 120 clerks were measured anonymously using questionnaires containing the Doctor-Patient Scale. This attitude scale measures patient-centredness vs. doctor-centredness. Response rates were 78%, 58% and 84%, respectively. SETTING: University of Utrecht. SUBJECTS: Medical students. RESULTS: Attitudes were related to specialty. General practice trainees showed more patient-centredness than surgery trainees. In accordance with previous findings among younger students, no differences were found between final-year clerks and vocational trainees. In contrast to previous studies, gender was not related to patient-centredness. CONCLUSIONS: Professional attitudes, in particular patient-centredness, seem to be related to specialty preference in the final year of graduate medical training and specialty as a career choice. It remains unclear whether professional socialization reinforces existing attitudes or whether existing attitudes result in specialty preference.

Assessment of the quality of life of patients with advanced and end-stage cancer or serious infections with a symptom-based or an impact-based instrument.

In 1992 a project was started in which home care technology was made available to patients with cancer or serious infections. Primary care providers were trained and supported to administer parenteral drugs and fluids in the home setting. Between 1992 and 1995 we applied the Rotterdam Symptom Checklist (RSCL) and the Sickness Impact Profile (SIP) as questionnaires for quality of life (QoL) assessment in a group of 112 hospitalized patients who were prepared to receive further treatment at home. Scores on the RSCL revealed a high level of symptomatology in both the physical and the psychological dimension. Factor analysis showed a five-factor rather than a two-factor structure. The SIP showed considerable restrictions in daily living, particularly in the physical dimension. Whereas the RSCL and the SIP correlated well in the psychological and physical dimensions in advanced cancer patients, this correlation disappeared in the group of endstage cancer patients. The data indicate that the health-related QoL of end-stage cancer patients cannot be reliably be assessed with a symptom-based instrument alone; it needs to be supplemented by other instruments, such as the SIP.

Do better quality consultations result in better health? Relationship between quality of consultations and health status of patients with non-acute abdominal complaints in general practice.

BACKGROUND: In theory, a positive relationship is expected between the quality of a consultation and a patient's subsequent health status. However, such a relationship has not yet been firmly established in daily practice. OBJECTIVE: We aimed to study the relationship between the quality of the first consultation in a new episode of non-acute abdominal complaints and subsequent health status of patients in general practice. METHODS: Quality scores for 743 consultations were calculated on the basis of review criteria developed by expert panels. Functional health status was measured by the SIP (Sickness Impact Profile) at baseline, and at 1 and 6 months after the consultation. Multilevel regression analysis was used to examine the relationship between the quality of consultations and health status, and to identify factors of influence on this relationship. RESULTS: In the majority of these patients (97%) health status improved regardless of consultation quality. In patients with malignant disease, and chronic colitis, however, an association between consultation quality and subsequent health status was found: in those with a high consultation quality score (>66-percentile) the health status deteriorated in the first month but improved over the following 5 months; in those with a low consultation quality score (<33-percentile) it deteriorated continuously. CONCLUSION: For the great majority of patients we found no relation between the quality of consultation and health status. However, for a very small subgroup of patients there is proof of benefit from better quality consultations.

How do we compare with our colleagues? Quality of general practitioner performance in consultations for non-acute abdominal complaints.

OBJECTIVE: To investigate what factors influence the quality of general practitioner performance in consultations for non-acute abdominal complaints and to establish the extent to which performance quality differs between general practitioners (GPs). DESIGN: Explorative study in two parts: (i) detection of variables influencing quality scores of consultations; and (ii) comparison of mean quality scores of the consultations, selected by each GP. SETTING: Sixty-two family practices across The Netherlands. SUBJECTS: Eight-hundred and forty consultations concerning non-acute abdominal complaints, first encounters; 62 GPs. METHOD: Multilevel analysis was carried out to detect factors that influence quality. After correction for the effect of significant factors the mean quality scores of individual GPs were calculated and compared. RESULTS: Eighty-eight per cent of the total variance in quality scores was located at the consultation/patient level, and 12% at the GP level. One consultation characteristic had significant influence on quality: quality scores were higher in consultations of longer than average duration (>15 minutes). Several patient characteristics were of significant influence. Consultation quality scores were higher in consultations for patients with upper abdominal or non-specific abdominal complaints. Quality scores were lower in consultations with female patients and with patients aged >40 years. Together these characteristics explained 20% of the variance at the GP level. None of the GP characteristics investigated in this study appeared to have significant influence on the quality of their performance. After correction of the scores for the effect of significant factors the differences in performance quality between GPs remained significant. CONCLUSIONS: Quality of performance is far more influenced by consultation and patient characteristics than by GP characteristics. After correction for influencing factors, the mean quality scores of GPs still differed considerably and significantly. For many GPs the quality scores varied substantially between different consultations; to a large extent this variation remained unexplained. Consultation quality can be improved by booking more time per patient and by giving more medical/technical attention to female and older patients.

Disturbed solid-phase gastric emptying in functional dyspepsia: a meta-analysis.

Functional dyspepsia is a common disorder with a diverse pathophysiological background, but the role of motility disorders in functional dyspepsia remains unclear. We aimed to quantify the relationship between disturbed gastric emptying and functional dyspepsia, using a meta-analytic approach. Through a structured literature search of Medline and Embase from 1983 to 1996, we selected all studies in which scintigraphic solid-phase gastric emptying was measured in both functional dyspeptic patients and controls. Seventeen studies involving 868 dyspeptic patients and 397 controls were pooled. Gastric emptying in patients with functional dyspepsia was 1.46 (1.23-1.69) times slower than controls; the proportion of patients with abnormally slow emptying was either 37% (34-40%, simple numeric pooling) or 39% (29-49%, weighted pooling). We conclude that gastric emptying of solids in patients with functional dyspepsia is 1.5 times slower than in healthy controls and that a significant delay of emptying is present in almost 40% of patients with functional dyspepsia.

How well are patients treated in family practice? Quality of consultations for non-acute abdominal complaints.

OBJECTIVE: To describe the application of weighted review criteria, developed by the Delphi technique, for the assessment of the quality of consultations concerning non-acute, abdominal complaints. DESIGN: Descriptive study in two parts: (i) comparison of actual family doctor (FD)-performance with predefined review criteria; (ii) calculation of quality scores per consultation, utilizing the weighted criteria. SETTINGS: Sixty-two family practices across The Netherlands. SUBJECT: Eight-hundred and forty consultations concerning non-acute abdominal complaints, first encounters. MAIN OUTCOME MEASURES: The percentage of consultations in which each criterion was met; quality scores per consultation and their distribution. RESULTS: (i) Little effort was made to trace risk groups for gastrointestinal malignancies (< 50% of the consultations concerned); medication was often described without dietary advice (17%); inappropriate activities were not carried out on a large scale (6%). (ii) Quality scores were normally distributed. CONCLUSIONS: The Delphi technique yields a useful instrument for assessment of the quality of consultations. The review criteria for quality assessment of FD performance used in this study made it possible to distinguish quite clearly between high- and low-quality consultations. Some important deficiencies in daily practice emerged.

A family of genes required for maintenance of cell wall integrity and for the stress response in Saccharomyces cerevisiae.

The PKC1-MPK1 pathway in yeast functions in the maintenance of cell wall integrity and in the stress response. We have identified a family of genes that are putative regulators of this pathway. WSC1, WSC2, and WSC3 encode predicted integral membrane proteins with a conserved cysteine motif and a WSC1-green fluorescence protein fusion protein localizes to the plasma membrane. Deletion of WSC results in phenotypes similar to mutants in the PKC1-MPK1 pathway and an increase in the activity of MPK1 upon a mild heat treatment is impaired in a wscDelta mutant. Genetic analysis places the function of WSC upstream of PKC1, suggesting that they play a role in its activation. We also find a genetic interaction between WSC and the RAS-cAMP pathway. The RAS-cAMP pathway is required for cell cycle progression and for the heat shock response. Overexpression of WSC suppresses the heat shock sensitivity of a strain in which RAS is hyperactivated and the heat shock sensitivity of a wscDelta strain is rescued by deletion of RAS2. The functional characteristics and cellular localization of WSC suggest that they may mediate intracellular responses to environmental stress in yeast.

A comparison of three preparations of cytochrome c oxidase. Optical absorbance spectra, EPR spectra and reaction towards ligands.

Three preparations of cytochrome c oxidase, the preparation as traditionally prepared in our laboratory as described by Van Buuren (1992; PhD Thesis, University of Amsterdam), a preparation according to Volpe and Caughey (Biochem. Biophys. Res. Commun. 61 (1974) 502-509) and a preparation of 'fast' cytochrome c oxidase (Brandt, U., Schägger, H. and Von Jagow, G. (1989) Eur. J. Biochem. 182, 705-711), are compared in their reaction with cyanide and carbon monoxide. The reaction with cyanide is nearly as fast for the Van Buuren preparation as for the 'fast' preparation, but much slower for the Volpe-Caughey preparation. Mixed-valence cytochrome c oxidase (cytochrome a3 and CuB reduced with carbon monoxide bound and cytochrome a and CuA oxidized) is prepared by anaerobic incubation with carbon monoxide. With the Van Buuren preparation complete formation of the species takes 4 h, whereas with the Volpe-Caughey preparation it takes 20 h. Longer incubation under CO results in partial reduction of cytochrome a and CuA. With the 'fast' preparation mixed-valence cytochrome c oxidase is formed after more than one day of incubation with CO, but it is stable for at least 3 days. The presence of oxidized cytochrome c did enhance the reactivity towards cyanide and towards carbon monoxide in cytochrome c oxidase of all three preparations. Furthermore, optical and EPR spectra of the preparations of cytochrome c oxidase are compared. The Volpe-Caughey preparation has an intense g' = 12 EPR-signal, the Van Buuren preparation has hardly any g' = 12 signal and the 'fast' preparation has no g' = 12 signal. In the 'fast' preparation the low-spin heme signal is shifted (from g = 3.00 to g = 2.97). The absorbance spectra of the three preparations in the Soret region are similar with a maximum at 424 nm. Only the 'fast' preparation as isolated was completely oxidized, whereas the other preparations were partially reduced. It was concluded that differences in the reaction of cytochrome c oxidase with ligands are determined by the internal or external ligand bound to the cytochrome a3-CuB couple.

Effects of cytochrome c on the oxidation of reduced cytochrome c oxidase by hydrogen peroxide.

The oxidation of the redox centres in reduced cytochrome c oxidase by hydrogen peroxide was studied by stopped-flow spectrophotometry in the absence and presence of reduced cytochrome c. The oxidation rate of cytochrome a decreased in the presence of cytochrome c. This effect was more pronounced at low than at high ionic strength. Cytochrome c did not influence the time-course of the oxidation of CuA or cytochrome a3. The oxidation of cytochrome c itself was faster at low ionic strength. The results suggest that the effect of cytochrome c is caused by re-reduction of cytochrome a by cytochrome c, the rate of which is dependent upon the ionic strength. We conclude that cytochrome a and cytochrome c are in equilibrium and that the equilibrium constant depends on the ionic strength. At low ionic strength, as a complex is formed between cytochrome c and cytochrome c oxidase, cytochrome a is more reduced than at high ionic strength conditions, when no such complex exists. Since CuA is oxidized at the same rate whether cytochrome c is present or not, we conclude that electron transfer from cytochrome a or cytochrome c to CuA is slower than electron transfer from CuA to cytochrome a or/and to the cytochrome a2-CuB couple.