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Biomedical subjects

M Jones

Publications and source records attributed to M Jones.

At least 253 records · Page 14Linked to original sources

Quantitative assessment of chronic aortic regurgitation with 3-dimensional echocardiographic reconstruction: comparison with electromagnetic flowmeter measurements.

Two-dimensional echocardiography and color Doppler are useful in the qualitative assessment of aortic regurgitation. However, color Doppler planar methods are not accurate in quantifying regurgitant flow, in part because of the complex geometry of aortic regurgitant flow events. Three-dimensional echocardiographic reconstruction is a new technique that provides dynamic 3-dimensional images of intracardiac color flow jets. We sought to determine whether the measurement of aortic regurgitant jet volume by 3-dimensional echocardiography correlated with the true regurgitant volume, measured by electromagnetic flowmeter in vivo, to accurately reflect the severity of aortic regurgitation. We performed volume-rendered 3-dimensional echocardiography in 6 sheep with surgically induced chronic eccentric aortic regurgitation. We obtained a total of 22 aortic regurgitation states by altering loading conditions. Instantaneous regurgitant flow rates were obtained by aortic and pulmonary electromagnetic flowmeters. The maximum aortic regurgitant jet volume by 3-dimensional echocardiography and the maximum jet area by 2-dimensional echocardiography were measured and compared with electromagnetic flowmeter data. By electromagnetic flowmeter, aortic regurgitant flow rate varied from 0.14 to 3.1 L/min (mean 1. 25 +/- 0.78); aortic regurgitant stroke volume varied from 1 to 34 mL/beat (mean 12 +/- 8), and regurgitant fraction varied from 3% to 42% (mean 25% +/- 12%). The maximum jet volume by 3-dimensional echocardiography correlated very well with the aortic regurgitant stroke volume (r = 0.92; P <.0001), with the mean regurgitant flow rate (r = 0.87; P <.0001), and with the regurgitant fraction (r = 0. 87; P <.0001) derived from electromagnetic flowmeter. Both intraobserver and interobserver variability on the measurement of the jet volume by 3-dimensional echocardiography were excellent (r = 0.98; P <.0001 and r = 0.90; P <.001, respectively). The maximum jet area by 2-dimensional echocardiography did not correlate with the aortic regurgitant stroke volume (r = 0.41; P = not significant) and related poorly with the regurgitant fraction (r = 0.52; P <.05) by electromagnetic flowmeter. Dynamic 3-dimensional echocardiography can allow better determination of the geometry of the aortic regurgitant jet and may assist of quantifying the severity of aortic regurgitation.

Animals↗

Polymeric micelles - a new generation of colloidal drug carriers.

Polymeric micelles have recently emerged as a novel promising colloidal carrier for the targeting of poorly water soluble and amphiphilic drugs. Polymeric micelles are considerably more stable than surfactant micelles and can solubilize substantial amounts of hydrophobic compounds in their inner core. Due to their hydrophilic shell and small size they sometimes exhibit prolonged circulation times in vivo and can accumulate in tumoral tissues. This review examines the chemical nature of polymeric micelles as well as the methods used to characterize them with regard to drug delivery. Special emphasis is put on the determination of critical micelle concentration and on drug loading procedures. Potential medical applications, especially in cancer chemotherapy, are described and discussed.

Animals↗

Granular cell tumor of the parotid.

A case of granular cell tumor of the major salivary glands is presented. This tumor appeared as an expansive multinodular mass that arose from facial nerve trunks. The presenting symptoms of facial pain and paresis and the intraoperative findings of tumor adhesion to nerves led to the clinical impression of malignancy. At intraoperative consultation, the tumor resembled an acinic cell carcinoma. Pathologists should be aware that granular cell tumors may involve the major salivary glands and that it should be considered in the diagnostic differential diagnosis.

Female↗

Possible improved survival of patients with stage IV AJCC melanoma receiving SRL 172 immunotherapy: correlation with induction of increased levels of intracellular interleukin-2 in peripheral blood lymphocytes.

PURPOSE: This phase I-II study was designed to assess safety and clinical efficacy of SRL 172 vaccine in patients with advanced stage IV (AJCC) malignant melanoma. Induction of intracellular cytokines (IL-2 and INF-gamma) in peripheral blood lymphocytes (PBLCs) from these patients was assayed and correlated to clinical outcome. PATIENTS AND METHODS: SRL 172 was administered intradermally to 24 patients with stage IV malignant melanoma, initially at 15-day intervals for three vaccinations and then at monthly intervals. Lymphocyte activation for cytokines in PBLCs was assayed prior to each vaccine administration using a FACS-based intracellular cytokine assay. Survival was compared to historical controls. RESULTS: The vaccination schedule resulted in sustained intracellular IL-2 induction in PBLCs in 9 of 23 patients (39%) who received at least three doses. Cytokine induction became apparent within the first three administrations of vaccine and was maximal at 8-12 weeks. Induction of intracellular IL-2 production (group 1) was associated with improved survival (P < 0.036). The median survival of the nine patients demonstrating IL-2 induction was 59 (95% confidence interval (95% CI): 47-71) weeks compared to 31 (95% CI: 18-44) weeks for the non-inducers. Induction of INF-gamma (group 2) was found in 10 patients and 6 patients had IL-2 and INF-gamma induction (group 3). There was no survival advantage for these patient groups. Although no objective responses were documented the group as a whole had a median survival of 44 (95% CI: 31-59) weeks which is better than that of historical controls. SRL 172 was safe and well tolerated. CONCLUSION: SRL 172 is effective in inducing intracellular IL-2 responses in PBLCs of a significant number of patients with stage IV (AJCC) melanoma. This is correlated with improved survival. The survival analysis is sufficiently encouraging to suggest that further prospective trials are justified. The methodology we present in this study may help in developing surrogate markers that will allow rational immunotherapeutic strategies to be designed for cancer patients.

Cancer Vaccines↗

Development of a new dyspepsia impact scale: the Nepean Dyspepsia Index.

BACKGROUND: There is not at present a suitable disease-specific health-related quality of life instrument for uninvestigated dyspepsia and functional (non-ulcer) dyspepsia. AIM: To develop a new multi-dimensional disease-specific instrument. METHODS: The Nepean Dyspepsia Index (NDI) was designed to measure impairment of a subject's ability to engage in relevant aspects of their life and also their enjoyment of these aspects; in addition, the individual importance of each aspect is assessed. A 42-item quality of life measure was developed and tested, both in out-patients presenting to general practice with upper gastrointestinal complaints (n = 113) and in a randomly chosen population-based sample (n = 347). RESULTS: Adequate face and content validity was documented by an expert panel. Factor analysis identified four clinically relevant subscales: interference with activities of daily living, work, enjoyment of life and emotional well-being; lack of knowledge and control over the illness; disturbance to eating or drinking; and disturbance to sleep because of dyspepsia. These scales had high internal consistency. Both symptoms and the quality of life scores discriminated dyspepsia from health. CONCLUSION: The Nepean Dyspepsia Index is a reliable and valid disease-specific index for dyspepsia, measuring symptoms and health-related quality of life.

Adult↗

Lymphocyte-specific protein 1: a specific marker of human leucocytes.

While both murine and human homologues of the LSP1 gene (lymphocyte-specific gene 1) and its protein products have been identified, studies on human LSP1 have been limited. The present report describes a detailed immunocytochemical study of the distribution and localization of human LSP1 in both normal and neoplastic cells and tissues. The specificity of the monoclonal anti-LSP1 reagent was confirmed by expression cloning and transfection studies. The intracellular 60 000 MW LSP1 protein was found to be present in peripheral blood B cells, monocytes and granulocytes but absent in a subpopulation of circulating T cells (10-15% of CD3-positive T cells). The presence of LSP1 protein in medullary thymocytes, but only in scattered cortical thymocytes, provided additional evidence for heterogeneity of expression in T cells. Novel observations also included the presence of LSP1 in plasma cells, dendritic cells and Langerhans' cells. The leucocyte-restricted distribution of LSP1 protein means that it may play an important role in haematopathology. LSP1 protein was detected in a wide range of leukaemias and lymphomas, particularly of B-cell origin, and in tumour cells in classical Hodgkin's disease. Of interest was the indication of a reciprocal relationship in the expression of LSP1 and ALK (anaplastic lymphoma kinase) proteins in patients with anaplastic large cell lymphoma. As the anti-LSP1 reagent used in the present study recognizes a formalin-resistant epitope it should be of considerable value in the diagnosis of routinely fixed material.

Anaplastic Lymphoma Kinase↗

A survey of the advertising of nine new drugs in the general practice literature.

OBJECTIVE: To undertake a survey of the advertising of new drugs in the general practice literature as part of a larger study investigating the factors which influence the introduction of new drugs into clinical practice. METHOD: The advertisements for nine new drugs from a range of therapeutic groups were monitored for 30 months in 12 journals, which are received by most GPs. The amount of prescribing, in defined daily doses, of each new drug by 50 GPs, selected as regular users of a teaching hospital, was also recorded during this period. RESULTS: Of the journals, 798 issues were surveyed (93% of the total published). The total number of advertisements was almost 33 000, of which 2163 (6.6%) were for the study drugs. The pattern of advertising of each study drug was very complex and varied from month to month and between journals. There was no consistent pattern in the way the drugs were advertised, with large variations in the amount and timing of advertisements. The prescribing data showed wide variations in the number of GPs prescribing each drug and in the amount prescribed. CONCLUSION: There was no clear relationship between the extent of the advertising of a drug and the amount of prescribing by the GPs. This suggests that advertising in journals is only one of many factors which are important in influencing GPs to prescribe new drugs. However, the study may have been insufficiently comprehensive to capture complex relationships between advertising and prescribing.

Advertising↗

Maternal and child constitutional factors and the frequency of melanocytic naevi in children.

This study examined the association between numbers of benign melanocytic naevi in 7-year-old children in Oxfordshire born in 1988-9 with their mother's arm naevus count, and maternal and child pigmentation factors. We believe this is the first time that the relationship between child and maternal naevus counts has been reported. A high naevus count in the child was associated with male sex (P = 0.009), freckling (P = 0.001) and propensity of the child to burn in the sun (P = 0.05). A low naevus count was observed in red-haired children (P = 0.02). The strongest association of child's naevus count was with a high maternal arm naevus count, independent of the child's pigmentation factors (trend P < 0.0001). Maternal pigmentation factors were not associated with child's naevus count independent of the child's own pigmentation factors. Maternal arm naevus counts may be a better predictor of child naevus count than the child's own pigmentation factors and children. There has not been examination, however, of the relationship between naevus counts in children and those in their parents. We therefore conducted a study of the occurrence of naevi in children aged 7-8 years in Oxfordshire, examining, in addition to sex and pigmentation factors in the child, the relationship of maternal pigmentation factors and maternal naevus counts with naevi in their offspring.

Age Factors↗

A model for clinical and educational psychiatric service delivery in remote communities.

OBJECTIVE: A model of intermittent psychiatric service provision to rural and remote New South Wales communities by metropolitan psychiatrists and mental health professionals has been evaluated. The services provided included peer support to lone mental health and generic health workers, direct psychiatric care to clients in their own environment and skills development education sessions to general health staff and other professionals affiliated with health care (e.g. police and ambulance officers). METHOD: There were 10 visits of teams made up of a psychiatrist and another mental health professional to six rural and remote locations. Outcomes of the services delivered were examined including clinical services and teaching skills training sessions. Indirect outcome measures included changes to Pharmaceutical Benefits Scheme prescription patterns in areas serviced and data regarding transfer of clients for psychiatric care in regional centres. Difficulties in evaluation are discussed. RESULTS: The feasibility of intermittent service provision was demonstrated. Education packages were well received and a positive change in workers' attitudes toward mental health practice was found. CONCLUSION: Intermittent psychiatric services in remote settings add value to health care delivery particularly when dovetailed with skills-based education sessions.

Adolescent↗

A p90(rsk) mutant constitutively interacting with MAP kinase uncouples MAP kinase from p34(cdc2)/cyclin B activation in Xenopus oocytes.

The efficient activation of p90(rsk) by MAP kinase requires their interaction through a docking site located at the C-terminal end of p90(rsk). The MAP kinase p42(mpk1) can associate with p90(rsk) in G(2)-arrested but not in mature Xenopus oocytes. In contrast, an N-terminally truncated p90(rsk) mutant named D2 constitutively interacts with p42(mpk1). In this report we show that expression of D2 inhibits Xenopus oocyte maturation. The inhibition requires the p42(mpk1) docking site. D2 expression uncouples the activation of p42(mpk1) and p34(cdc2)/cyclin B in response to progesterone but does not prevent signaling through p90(rsk). Instead, D2 interferes with a p42(mpk1)-triggered pathway, which regulates the phosphorylation and activation of Plx1, a potential activator of the Cdc25 phosphatase. This new pathway that links the activation of p42(mpk1) and Plx1 during oocyte maturation is independent of p34(cdc2)/cyclin B activity but requires protein synthesis. Using D2, we also provide evidence that the sustained activation of p42(mpk1) can trigger nuclear migration in oocytes. Our results indicate that D2 is a useful tool to study MAP kinase function(s) during oocyte maturation. Truncated substrates such as D2, which constitutively interact with MAP kinases, may also be helpful to study signal transduction by MAP kinases in other cellular processes.

Animals↗

Evaluation of pressure changes in a new design tracheal tube cuff, the Portex Soft Seal, during nitrous oxide anaesthesia.

We have measured pressure changes in a newly designed tracheal tube cuff, the Portex Soft Seal, during nitrous oxide anaesthesia compared with a Mallinckrodt Lo-Contour tube and a Portex Profile tube. The pressure increases in both control groups were significantly greater than those with the new design (P < 0.0001 in each case). The mean increase in pressure in the Mallinckrodt Lo-Contour tube cuff was 9.9 (SD 3.4) mm Hg compared with 10.3 (1.8) mm Hg in the Portex Profile tube cuff and 2.1 (1.5) mm Hg in the Portex Soft Seal tube cuff. We conclude that the Portex Soft Seal cuff prevented a significant increase in intracuff pressure during nitrous oxide anaesthesia.

Adolescent↗

GPs' perceptions of patient influence on prescribing.

BACKGROUND: Controlling prescribing costs is an issue of concern to many GPs. OBJECTIVE AND METHODS: This paper is based on interviews with 21 GPs in which they were asked about influences on prescribing budgets. RESULTS: The results presented relate specifically to GPs' perceptions of the influence of patients on prescribing. Perceptions of patient demand were described both in terms of a general demand and demand by patients with specific health beliefs or particular social characteristics. Generally, GPs reported that decisions to prescribe were informed by a concern to maintain a good relationship with their patients, and not to risk the relationship by not prescribing when they believed a prescription was expected. CONCLUSIONS: Although information was available about whether practices had a 'high' or 'low' budget, and whether they were under- or overspent, there did not appear to be any relationship between GPs' beliefs that patient expectations affected their prescribing and whether they were under or over budget. This paper suggests that patient demand for prescriptions may not only be overestimated but also perpetuated by GPs' belief in its existence and a wish to maintain a good doctor-patient relationship.

Attitude of Health Personnel↗

Sperm transport and storage in the agile antechinus (Antechinus agilis).

This study was an examination of the timing of ejaculation and the dynamics of sperm transport in the female reproductive tract of the agile Antechinus (Antechinus agilis) and the relationship of these parameters to single and multiple matings. Mating in this species is characteristically long compared with that of other mammals, lasting for up to 8-12 h during which time the pair remain locked together. After the first hour of mating, only approximately 40% of males had ejaculated, but by the third hour all males had ejaculated. The total number of spermatozoa extracted from the female tract remained at approximately 30 x 10(3) spermatozoa per side over the next 9 h of copulation. After completion of male/female access (12 h), approximately 56% of spermatozoa extracted were located in the lower isthmic region of the oviduct where specialized sperm storage crypts are located. The number of spermatozoa extracted from the female reproductive tract did not decline over the next 3 days, but there was a change in the distribution of spermatozoa with an increase in the proportion of extracted spermatozoa stored in the lower isthmus (approximately 76%). However, 7 to 14 days after mating, only approximately 30% of the stored spermatozoa ( approximately 9.4 x 10(3) spermatozoa per side) were still present in the isthmus. When females were mated with a second male on a consecutive day, the sperm numbers extracted from the tract were about twice that deposited during single mating, with sperm transport to the lower isthmus occurring over a similar time frame. Although the occurrence of extended copulations in the wild has not yet been confirmed, these laboratory results suggest that similar periods of copulation are likely, since completion of the ejaculation process requires at least 3 h. The extended copulation in A. agilis reduces the possibility of an early second mating, which might interfere with the normal transport and crypt colonization of spermatozoa through competition.

Animals↗

The white coat effect in hypertensive pregnancy: much ado about nothing?

OBJECTIVES: To determine the prevalence of white coat hypertension and white coat effect among hypertensive pregnant women and to assess whether the presence of a significant white coat effect was associated with adverse pregnancy outcome when clinical management was based upon standard sphygmomanometric blood pressure recordings. DESIGN: Prospective blinded studies assessing the presence of a white coat effect. SETTING: Antenatal ward and pregnancy day assessment unit of St George Hospital, a teaching hospital in Sydney, Australia. POPULATION: One hundred and twenty-one hypertensive pregnant women in the second half of their pregnancy admitted to hospital or the day assessment unit for management of their hypertensive disorders. METHODS: Routine sphygmomanometric blood pressures were recorded by midwives in the ward or day assessment unit and awake blood pressure recordings were averaged. These blood pressures were compared with average awake blood pressures recorded by ambulatory blood pressure monitor (ABPM) (Spacelabs 90207, Seattle, Washington, USA). White coat hypertension was defined as an average sphygmomanometer blood pressure > or = 140 mmHg systolic and/or > or = 90 mmHg diastolic with awake ABPM average blood pressure within the normal range for ABPM-derived blood pressures in pregnancy, according to gestation. White coat effect was the difference between average sphygmomanometer blood pressure and average awake ABPM-derived blood pressure. All clinical management was based upon routine sphygmomanometer recordings and clinicians were blinded to ABPM data. MAIN OUTCOME MEASURES: Prevalence of white coat hypertension and white coat effect; maternal and fetal outcomes in those with and without a white coat effect of > or = 20 mmHg systolic and/or > or = 10 mmHg diastolic. RESULTS: Systolic and diastolic white coat hypertension were present in only 3.2% and 4.2% of the group, respectively. A systolic white coat effect > or = 20 mmHg was found in only 4.2% but 20.2% (26% for day assessment unit patients vs 15% for inpatients; P = 0.17) had a diastolic white coat effect > or = 10 mmHg. There was no difference in maternal or fetal outcomes between women with and without a white coat effect. CONCLUSIONS: White coat hypertension is an infrequent occurrence in mildly hypertensive pregnant women. Although a white coat effect is present more often, this is associated with clinical outcomes similar to women who do not exhibit this phenomenon. Using ABPM to identify a white coat effect in women presenting with hypertension in the second half of their pregnancy does not appear to be clinically useful.

Adult↗

Validity of a new quality of life scale for functional dyspepsia: a United States multicenter trial of the Nepean Dyspepsia Index.

OBJECTIVE: The lack of a suitable disease-specific, health-related quality of life instrument for dyspepsia prompted the development of the Nepean Dyspepsia Index (NDI). The utility of the NDI in functional dyspepsia is unknown. We aimed to assess the validity of this new quality of life instrument for the first time in United States patients with documented functional dyspepsia. METHODS: The long form of the NDI contains a symptom index and 42 items designed to measure impairment of subjects' ability to engage in and to enjoy relevant aspects of their life because of dyspepsia, as well as a ranking of the individual importance of each aspect. Patients (n = 101, mean age 51 yr, 62% female) who had a history of functional dyspepsia for > or = 1 month and a negative endoscopy within the prior 1 yr were followed for 14 days. Patients completed the NDI and the validated Speilberger State-Trait Anxiety Inventory, Beck Depression Inventory, Short Form-36, and a global assessment of symptoms and quality of life at baseline and 14 days later; the NDI was also retested at 48 h and 2 wk. RESULTS: Five clinically relevant factors (subscales), namely, tension/sleep, interference, eating/drinking, knowledge/control, and work/study were identified by factor analysis, after incorporating individual importance ratings (25 items total). All subscales had excellent face validity and internal consistency (Chronbach's alpha, all >0.85). Reliability was also excellent (intraclass correlations all >0.84). There were modest typically negative correlations between a number of the NDI subscales and the Short Form-36, anxiety, and depression, indicating that the NDI is disease-specific and supporting its validity. Changes in NDI scales correlated moderately with global assessment of change (total score r = -0.49), indicating initial responsiveness. CONCLUSIONS: The Nepean Dyspepsia Index is a valid, disease-specific index for functional dyspepsia, measuring symptoms and health-related quality of life.

Dyspepsia↗