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Biomedical subjects

J Newton

Publications and source records attributed to J Newton.

At least 55 records · Page 3Linked to original sources

Determination of SR 49059 in human plasma and urine by LC-APCI/MS/MS.

SR 49059 ((2S 1-[(2R 3S)-5-chloro-3-(2-chlorophenyl)-1-(3, 4-dimethoxybenzene-sulfonyl)-3-hydroxy-2,3-dihydro-1 H-indole-2-carbonyl]-pyrrolidine-2-carboxamide) is an orally active non-peptide vasopressin V1a antagonist. A sensitive, selective, and robust LC-MS/MS method was developed to determine the plasma and urine concentrations of SR 49059 in support of clinical studies. Plasma samples were prepared based on a rapid extraction procedure using Chem Elut cartridges. The extracted samples were analyzed on a C18 HPLC column interfaced with a Finnigan TSQ 700 mass spectrometer. Positive atmospheric chemical ionization (APCI) was employed as the ionization source. The analyte and its internal standard (2H6-SR 49059) were detected by use of multiple reaction monitoring (MRM) mode. The plasma matrix had a calibration range 0.2-20 ng ml-1, with within and between run accuracy and precision both less than 10%. The chromatographic run time was approximately 3 min. Urine samples were prepared based on a simple dilution with water, followed by analysis under the same conditions as plasma. The calibration range for urine matrix was 20-5000 ng ml-1, with within and between run accuracy and precision less than 11%. The method has been successfully applied to the clinical sample analysis. The plasma assay was also evaluated on a Finnigan TSQ 7000 mass spectrometer. The performance based on precision and accuracy was virtually identical to that on the TSQ 700, with the exception of linearity in calibration curve (the TSQ 700 was linear, the TSQ 7000 was quadratic).

Antidiuretic Hormone Receptor Antagonists↗

Perfectionism and suicide ideation in adolescent psychiatric patients.

This study was conducted to examine the relations between dimensions of perfectionism and suicide ideation in an adolescent psychiatric sample. A sample of 66 adolescents from an inpatient psychiatric facility completed the Child and Adolescent Perfectionism Scale, the Child's Hopelessness Scale, and the Suicide Ideation Questionnaire. Overall, the results indicated that socially prescribed perfectionism was associated with greater suicide ideation and that it, along with hopelessness, accounted for unique variance in suicide ideation scores. The findings are discussed in terms of their practical and theoretical significance as well as their consistency with similar research with adults.

Adolescent↗

Mucus and H. pylori.

A continuous, adherent mucus gel layer with mucosal bicarbonate secretion is the initial protective barrier in the stomach and duodenum against erosion by the gastric juice. H. pylori resides within the adherent mucus gel layer close to the epithelial surface. The barrier function of the mucus layer in vivo depends on (i) its thickness, and (ii) its gel structure, a property which is linearly dependent on the polymeric mucin content. We have shown in vivo that H. pylori colonisation alone did not decrease the thickness of the adherent gastric mucus barrier, although there was a mean 20% decrease in mucus thickness in those H. pylori positive subjects with underlying gastric atrophy. There was, however, a significant mean 18% reduction in the gel-forming polymeric mucin content of mucus from H. pylori subjects, independent of underlying atrophy. Studies in vitro suggest this loss of gel structure might arise from a H. pylori mediated, high local pH generated by urease activity rather than by proteolysis. This study shows that H. pylori infection alone does not compromise the overall integrity of the mucus barrier in vivo. However, in the immediate environment of the organism there appears to be a localised loss of mucus gel structure. The mucus barrier is compromised if H. pylori associated gastric atrophy or peptic ulceration follows.

Animals↗

Early response gene signalling in bryostatin-stimulated primary B chronic lymphocytic leukaemia cells in vitro.

The protein kinase C activator bryostatin induces differentiation and antagonizes the effects of tumour-promoting phorbol esters in a number of different cell types. We show here that bryostatin preferentially inhibits phorbol 12-myristate 13-acetate (PMA)-induced proliferation compared with differentiation in a number of different B chronic lymphocytic leukaemia (BCLL) cell populations examined. By using a panel of 11 early-response gene probes in Northern hybridization analysis, we found that the profile of genes induced in response to bryostatin and PMA was qualitatively similar and displayed comparable sensitivities to inhibition with the serine-threonine kinase inhibitor 1-(5-isoquinolinylsulphonyl)-2-methylpiperazine hydrochloride (H7), consistent with common signalling through protein kinase C. However, the nuclear oncogene. c-myc, which was induced strongly in response to PMA treatment, was only marginally up-regulated by bryostatin. In addition, bryostatin selectively inhibited the magnitude of PMA-responsive induction of c-myc, to a degree commensurate with its antagonistic effects seen at the biological level. Finally, an anti-sense oligonucleotide blockade of c-myc inhibited PMA-induced proliferation but not the differentiation of BCLL cells, implicating this nuclear oncogene as an important determinant distinguishing PMA from bryostatin-coupled biological responses and also as a candidate third-messenger effector target for the anti-tumour effects of bryostatin.

Bryostatins↗

Can we understand partnerships in general practice? A pilot study.

BACKGROUND: Partnerships have been investigated in different professions, but other than identifying problems, little work has been carried out on general practice. OBJECTIVE: The aim of this present study was to develop methods for studying partnerships in general practice. METHOD: A tripartite methodological approach was used, with questionnaires adapted from other instruments in use in other professions, followed by an individual interview with each partner, and non-participant observation at a partnership meeting. Results for one case-study partnership are given. RESULTS: There were no major differences between the partners on all dimensions measured; the minor differences indicated by the results of the questionnaires were corroborated by the partner interviews and observations. CONCLUSIONS: We conclude that the use of such techniques could provide support to partnerships going through significant periods of change.

Family Practice↗

General practice partnerships: an exploratory review.

Presents the results of a literature review on general practice partnerships. The objective was to find out what has been written and by whom. The results of the review indicate that very little empirical work has been carried out and most of the publications are by doctors addressing the practical problems of working in partnerships. Given this paucity of material, goes on to discuss relevant literature from social science disciplines and presents five perspectives on partnerships. Each perspective yields questions worthy of further investigation particularly at a time when primary care is experiencing rapid change and development.

Conflict, Psychological↗

Human resource management in general practice: survey of current practice.

BACKGROUND: The organization and management of general practice is changing as a result of government policies designed to expand primary health care services. One aspect of practice management which has been underresearched concerns staffing: the recruitment, retention, management and motivation of practice managers. AIM: A study set out to find out who is routinely involved in making decisions about staffing matters in general practice, to establish the extent to which the human resource management function is formalized and specialized, and to describe the characteristics of the practice managers. METHOD: A postal questionnaire was sent to a stratified random sample of 750 general practices in England and Wales in February 1994 enquiring about the practice (for example, the fundholding status and number of general practitioner partners), how the practice dealt with a range of staffing matters and about the practice manager (for example, employment background and training in human resource management). Practices were classed as small (single-handed and two or three general practitioner partners), medium (four or five partners) or large (six or more partners). RESULTS: Replies were received from 477 practices (64%). Practice managers had limited authority to make decisions alone in the majority of practices although there was a greater likelihood of them taking independent action as the size of practice increased. Formality in handling staffing matters (as measured by the existence and use of written policies and procedures) also increased with practice size. Larger practices were more likely than smaller practices to have additional tiers in their management structure through the creation of posts with the titles assistant practice manager, fund manager and senior receptionist. Most practice managers had been recruited from within general practice but larger practices were more likely than smaller practices to recruit from outwith general practice. Three quarters of practice managers reported having received some type of formal training in staff management. CONCLUSION: This study shows that practice size is a major factor associated with differences in the organization and management of staffing. Any initiatives which increase the scale of primary care functions and services would have to address the issues of communication and coordination that might be associated with such a change.

England↗

General practitioners and clinical guidelines: a survey of knowledge, use and beliefs.

BACKGROUND: Clinical practice guidelines are being developed for a variety of reasons. To date, there has been little investigation of the perspectives of those who are recommended to use them. AIM: The survey reported here set out to investigate how familiar general practitioners are with a range of published guidelines, to assess whether they have used them, and to describe their attitudes to the guidelines and the methods of implementing them. METHOD: A postal questionnaire was sent to a random sample of 559 general practitioners in the North and Yorkshire region in March 1995. Questions were organized around the topics of: knowledge; use; practice change; beliefs; pressure felt to use the guidelines; and methods of implementation. Basic classificatory data on gender; year of qualification; partnership and fundholding status were also collected. RESULTS: Replies were received from 300 doctors (54%). Knowledge and use of the three selected guidelines varied, but was generally towards the 'high' end of the scale. Doctors showed a high degree of homogeneity in their attitudes to guidelines, which were generally positive. Only single-handed practitioners varied from this pattern of responses. Most of the pressure to use the guidelines was felt to come from the Department of Health, and the least pressure from patients. Doctors felt that the methods of implementation that involved them in educational events and discussion with colleagues were most likely to have an impact on them. CONCLUSION: General practitioners are receptive to guideline initiatives, and their views are in line with existing or proposed implementation strategies. More investigation of the concept of 'use' is needed.

Attitude of Health Personnel↗

Survey of informed consent for endoscopic retrograde cholangiopancreatography.

Prior to performance of gastrointestinal endoscopic procedures, physicians are generally required to appraise patients of potential risks, benefits, and alternatives. Components of the informed consent process require that: (1) consent be voluntary; (2) the patient be sufficiently mentally capable to engage in rational decision-making; and (3) "adequate information" be conveyed. Controversies reflected in both medical and legal literature concern the definition of "adequate information." To sample current opinion regarding consent for both diagnostic and therapeutic ERCP, members of the Indiana Gut Club and Midwest Gut Club were polled. From this group of academic and private practice physicians, 81 completed evaluations were compiled. Greater than 90% of physicians believed that pancreatitis and pancreatitis/bleeding/perforation must be mentioned for diagnostic and therapeutic ERCP, respectively. There was variation of opinion as to whether patients must be informed of potential need for surgery, prolonged hospital stay, or death. The performing physician was felt to be ultimately responsible for obtaining consent, although other health-care team members, excluding a secretary, could participate.

Cholangiopancreatography, Endoscopic Retrograde↗

Do clinicians tell each other enough? An analysis of referral communications in two specialties.

Referral letters and replies are an important vehicle for conveying information about patients and for creating and sustaining professional relationships. Studies of communication between hospital specialists and GPs, however, suggest that improvements could be made to the content of letters. In this study, which is part of a larger study of referral expectations, a sample of 39 letters to and from the ENT and Rheumatology departments at Sunderland Royal Infirmary was analysed to find out what objectives were being achieved through the correspondence between consultants and GPs. An analytical framework of letter content was derived from a review of 25 letters to and from each specialty and from a separate study of doctors' opinions of letter content conducted by two of the authors. Doctors recruited to the present study were involved in devising a weighted scoring system for letter content. Analysis showed that the letters accomplish the basic objective of transferring clinical and administrative information. They were less likely to contain items of a socio-psychological type. There was very little difference in the standardized letter scores between the two specialties. While the level of detail recorded in this sample may be adequate for straightforward referrals, there are indications that clinicians' letters are frequently not addressing nonclinical matters that can be a complicating factor in a proportion (perhaps a fifth) of referrals. This may be a possible topic for audit in multidisciplinary groups.

Communication↗

How many patients are admitted in districts other than their own, and why?

Patients may be admitted across administrative boundaries for a number of reasons. We compared cross-boundary flows into a teaching district for individual operations and diagnoses with flows into a group of non-teaching districts. We have attempted to distinguish cross-boundary care that is the result of natural geographic factors from that which reflects specialized supra-district hospital practice. Hospital activity data were analysed for patients treated in six districts in the Oxford Regional Health Authority area in the calendar years 1979-1986 and the financial year 1990-1991. In 1979-1986, 21.1 per cent of patients admitted in the teaching district, and 9.2 per cent in the non-teaching districts, were from other districts. Cross-boundary flows varied greatly between specialties. The non-resident workload in the teaching district increased a little over time from 21.1 per cent (1979-1986) to 24.5 per cent (1990-1991); no appreciable change was seen in the non-teaching districts. For many common conditions, the proportion of non-residents admitted in the teaching district was similar to that in the non-teaching districts, at about 10 per cent or less. For other conditions, it was higher than this but similar in both the teaching and non-teaching districts. Conditions were also identified for which the proportion of non-residents treated was clearly much higher in the teaching district than elsewhere. Geographical convenience accounted for about half the non-resident workload in the teaching district. Specialized supra-district care constituted a small but important part of the total workload.(ABSTRACT TRUNCATED AT 250 WORDS)

Catchment Area, Health↗

A comparative review of gynecological day case surgery between England and Wales, France, and Germany.

A comparison was made of gynecological day case surgery between England and Wales, France, and Germany. Hospital In-Patient Enquiry statistics (1979-1985) as well as Department of Health statistics (after 1985) and the Audit Commission Reports (1990-1992) were used for England and Wales; the Baudelocque Hospital Audit (Paris) between 1985 and 1990 was used for France; the Niedersachsen Regional Audit between 1989 and 1990 was used for Germany. These are the only available statistics for all three countries. A retrospective analysis of these statistics of gynecological day case surgery produced estimates of its rate for common gynecological operations in the three countries. It showed that England and Wales performed significantly more (18 per cent) gynecological procedures as day cases than either France (less than 5 per cent) or Germany (11 per cent). Additional specific comparisons were made for certain procedures between England and Wales and France (TOP) and between England and Wales and Germany (D&C, laparoscopy, TOP, ERPC, and cone biopsy). day case surgery was performed in hospitals in England and Wales and in France whereas it was performed in freestanding units in specialists surgeries in Germany. Furthermore, there seemed to be a wide regional variation in the rate in England and Wales and in Germany. Waiting lists were significant in England and Wales and nonexistent in France and in Germany. However, medical unemployment was almost nonexistent in England and Wales whereas it was alarming in France and in Germany. The methods of financing of the health care systems appear to explain the intercountry variation.

Ambulatory Surgical Procedures↗

Fundholding in Northern Region: practice managers' views.

Describes the views of practice managers in 30 fundholding practices in the Northern Region concerning their role in the scheme. A self-completion questionnaire was mailed to practice managers and general practitioners containing questions designed to elicit their views about changes in relationships inside and outside the practice; their level of involvement in various aspects of fundholding; and the costs and benefits of the scheme. A total of 30 first-, second-, and third-wave fundholding practices in the Northern Region, June 1993 were involved. Replies were received from 22 practice managers (73 per cent) and 83 general practitioners (49 per cent). Concludes that although fundholding has increased the nature and volume of the workload of practice managers, these changes do not appear to be causing any tensions between managers and clinicians. At the moment fundholding extends the support role of practice managers and does not alter existing authority relations in practices.

Attitude of Health Personnel↗