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Biomedical subjects

R H Jones

Publications and source records attributed to R H Jones.

At least 73 records · Page 4Linked to original sources

Lansoprazole 30 mg daily versus ranitidine 150 mg b.d. in the treatment of acid-related dyspepsia in general practice.

AIM: To compare lansoprazole 30 mg daily with ranitidine 150 mg b.d. in the treatment of acid-related dyspepsia in general practice. METHODS: In a double-blind, parallel group, randomized, mutlicentre study conducted in 32 general practices in the UK, 213 patients were randomized to receive lansoprazole 30 mg daily, and 219 to receive ranitidine 150 mg b.d., for 4 weeks. All patients had experienced symptoms of reflux-like or ulcer-like dyspepsia on at least 4 of the 7 days prior to the study; 75% had experienced dyspepsia in the past, and 74 of the lansoprazole patients and 77 of the ranitidine patients had documented histories of acid-related disorders, investigating by either radiology or endoscopy. RESULTS: After 2 weeks 55% of the lansoprazole patients and 33% of the ranitidine group were symptom-free (P = 0.001, chi 2 = 7.12) with corresponding 4-week figures of 69% and 44%, respectively (P = 0.001, chi 2 = 18.03). Similar figures were found at both 2 and 4 weeks for daytime and night-time heartburn and epigastric pain scores; in the lansoprazole group, at 4 weeks, 80% of patients were free of daytime heartburn and 81% of night-time epigastric pain, compared with 55% (P = 0.001, chi 2 = 15.44) and 65% (P = 0.01, chi 2 = 6.10) in the ranitidine group. CONCLUSION: Superior symptom relief for patients presenting with ulcer-like and reflux-like symptoms in general practice is provided by lansoprazole 30 mg daily compared with ranitidine 150 mg twice daily.

2-Pyridinylmethylsulfinylbenzimidazoles↗

The effect of an intravenous infusion of IGF-I and insulin on IGFBP-1, IGFBP-3, acid labile subunit, free and bound IGF-I, catecholamines and potassium in normal volunteers during an amino acid and glucose clamp.

OBJECTIVES: To investigate the effects of IGF-I and insulin at doses equipotent with respect to hypoglycaemic effect on IGF-I concentrations (free and bound), IGF binding proteins, catecholamines and potassium levels. DESIGN: A glucose and amino acid clamp technique was used to investigate the effects of a 3 h intravenous infusion of either IGF-I 43.7 pmol/kg/min (20 micrograms/kg/h) or insulin 3.4 pmol/kg/min (0.5 mU/kg/min). MEASUREMENTS: Circulating levels of total IGF-I, free and bound IGF-I, Insulin, IGFBP-1, IGFBP-3, ALS, catecholamines and potassium were measured. PATIENTS: 6 normal human volunteers aged 21-49. RESULTS: During the IGF-I infusion, IGF-I levels increased (P < 0.01) (26.6 +/- 2.8-88.9 +/- 14.2 nmol/l) and insulin levels fell (P < 0.05) (16.7 +/- 2.9-7.2 +/- 1.6 mu/l). During the insulin infusion, insulin levels increased (P < 0.01) (11.7 +/- 1.6-56.7 +/- 16 mu/l) and there was no change in IGF-I. There was no significant change in IGFBP-3 or ALS during the IGF-I or insulin infusions. There was a significant (P < 0.05) fall in IGFBP-1 levels from 27.1 +/- 4.1-8.06 +/- 1.6 micrograms/l during the insulin infusion and a significant (P < 0.05) rise during the first 120 min of IGF-I infusion from 28.6 +/- 6.3-67.9 +/- 10.6 micrograms/l. There was a significant (P < 0.05) increase in free IGF-I and IGF-I bound to the 150 and 50 kD plasma fractions during the IGF-I infusion. At basal and the end of the IGF-I infusion adrenaline levels (pmol/l) were: 173 +/- 22 and 174 +/- 28; dopamine levels (pmol/l) were: 415 +/- 87 and 470 +/- 87; plasma potassium (mmol/l) was 4.2 +/- 0.06 and 3.56 +/- 0.13. At basal and the end of the insulin infusion adrenaline levels (pmol/l) were: 160 +/- 38 and 163 +/- 21; dopamine levels (pmol/l) were: 238 +/- 26 and 316 +/- 31; plasma potassium (mmol/l) was 4.2 +/- 0.07 and 3.92 +/- 0.17. There were no significant changes in plasma catecholamine concentrations with either infusion but potassium concentrations were significantly (P < 0.05) reduced during the IGF-I infusion. CONCLUSIONS: We conclude that an infusion of IGF-I resulted in increased levels of both free and bound IGF-I. IGF-I and insulin under conditions of adequate substrate supply have acute effects on IGFBP-1 and potassium physiology, but have little effect on IGFBP-3, ALS or catecholamines.

Adult↗

Comparison of different methods of temporomandibular joint disc reconstruction--an animal model.

The optimum method of temporomandibular joint (TMJ) reconstruction has not been defined despite numerous surgical treatments and several well controlled clinical trials. Animal models offer an experimental method allowing direct comparison of standardized surgical techniques. Advanced osteoarthrosis was induced bilaterally in 12 mature merino sheep. Three months alter unilateral surgical reconstruction was performed. Four sheep had discectomy alone, four discectomy with fresh TMJ disc grafts, and four discectomy with fresh auricular grafts. All three surgical methods resulted in some reversal and repair of the osteoarthritic process, with the best result being from the auricular graft, next discectomy alone, next the disc graft, with the untreated osteoarthritic joint showing the most advanced pathosis. This study supports the role of surgical reconstruction in advanced degenerative disease of the temporomandibular joint, in particular, auricular graft reconstruction.

Animals↗

Simulation of IGF-I pharmacokinetics after infusion of recombinant IGF-I in human subjects.

The pharmacokinetics of recombinant human insulin-like growth factor I (IGF-I) were studied in four healthy volunteers by a 3-h infusion at a rate of 20 micrograms.kg-1.h-1. A compartmental model was used to simulate the plasma "free" IGF-I and IGF-I associated with the 50- and 150-kDa plasma protein fractions. The model is based on the concept that free IGF-I and IGF binding proteins (IGFBPs) are the substrates for their own degradation and that they act as reservoirs for retention of IGF-I in the vascular compartment or inhibiting IGF-I action. The metabolic clearance rate (MCR) of free IGF-I is estimated as 2.62 +/- 0.94 ml.min-1.min-1 with a production rate of 4.75 +/- 1.74 mg/day (621.0 +/- 227.34 nmol/day). The simulation shows that higher concentrations of IGFBP-3 would increase the estimate of MCR for free IGF-I by reducing free IGF-I concentration. The model will be of value for simulation of dynamic profiles of free IGF-I and receptor-bound IGF-I in a variety of pathophysiological conditions.

Computer Simulation↗

An improved statistical methodology to estimate and analyze impedances and transfer functions.

Estimating the mathematical relationship between pulsatile time series (e.g., pressure and flow) is an effective technique for studying dynamic systems. The frequency-domain relationship between time series, often calculated as an impedance (pressure/flow), is known more generally as a frequency-response or transfer function (output/input). Current statistical methods for transfer function analysis 1) assume erroneously that repeated observations on a subject are independent, 2) have limited statistical value and power, or 3) are restricted to use in single subjects rather than in an entire sample. This paper develops a regression model for transfer function analysis that corrects each of these deficiencies. Spectral densities of the input and output time series and the cross-spectral density between them are first estimated from discrete Fourier transforms and then used to obtain regression estimates of the transfer function. Statistical comparisons of the transfer function estimates use a test statistic that is distributed as chi2. Confidence intervals for amplitude and phase can also be calculated. By correctly modeling repeated observations on each subject, this improved statistical approach to transfer function estimation and analysis permits the simultaneous analysis of data from all subjects in a sample, improves the power of the transfer function model, and has broad relevance to the study of dynamic physiological systems.

Blood Pressure↗

Identification of preoperative variables needed for risk adjustment of short-term mortality after coronary artery bypass graft surgery. The Working Group Panel on the Cooperative CABG Database Project.

OBJECTIVES: The purpose of this consensus effort was to define and prioritize the importance of a set of clinical variables useful for monitoring and improving the short-term mortality of patients undergoing coronary artery bypass graft surgery (CABG). BACKGROUND: Despite widespread use of data bases to monitor the outcome of patients undergoing CABG, no consistent set of clinical variables has been defined for risk adjustment of observed outcomes for baseline differences in disease severity among patients. METHODS: Experts with a background in epidemiology, biostatistics and clinical care with an interest in assessing outcomes of CABG derived from previous work with professional societies, government or academic institutions volunteered to participate in this unsponsored consensus process. Two meetings of this ad hoc working group were required to define and prioritize clinical variables into core, level 1 or level 2 groupings to reflect their importance for relating to short-term mortality after CABG. Definitions of these 44 variables were simple and specific to enhance objectivity of the 7 core, 13 level 1 and 24 level 2 variables. Core and level 1 variables were evaluated using data from five existing data bases, and core variables only were examined in an additional two data bases to confirm the consensus opinion of the relative prognostic power of each variable. RESULTS: Multivariable logistic regression models of the seven core variables showed all to be predictive of bypass surgery mortality in some of the seven existing data sets. Variables relating to acuteness, age and previous operation proved to be the most important in all data sets tested. Variables describing coronary anatomy appeared to be least significant. Models including both the 7 core and 13 level 1 variables in five of the seven data sets showed the core variables to reflect 45% to 83% of the predictive information. However, some level 1 variables were stronger than some core variables in some data sets. CONCLUSIONS: A relatively small number of clinical variables provide a large amount of prognostic information in patients undergoing CABG.

Coronary Artery Bypass↗

Effect of perfusion pressure on cerebral blood flow during normothermic cardiopulmonary bypass.

BACKGROUND: We have recently shown that during hypothermic cardiopulmonary bypass (CPB), cerebral autoregulation has a positive slope such that for every 10 mm Hg change in pressure, a 0.86 mL.100 g-1.min-1 change in cerebral blood flow (CBF) is predicted. The purpose of this study was to define the influence of mean arterial blood pressure (MAP) on CBF during normothermic CPB. METHODS AND RESULTS: CBF was measured by use of 133Xe washout and alpha-stat blood gas management during nonpulsatile CPB. CBF measurements were made at a pump flow of 2.4 L.min-1.m-2 at stable normothermia and approximately 15 minutes later after the MAP was increased or decreased > or = 20%. A third data set was recorded after the pressure was returned to the initial value. Forty-five patients were entered into the study. Temperature was held constant. We found a significant effect (P = .016) of change in MAP on change in CBF during normothermic CPB. For a 10 mm Hg increase in MAP, an increase in CBF of 1.78 mL.100 g-1.min-1 is predicted. Along with change in CBF, significant increases in both cerebral metabolic rate and cerebral oxygen delivery were observed. CONCLUSIONS: This information, along with our previous data shows that autoregulation during CPB has a positive slope that is greater with normothermia than hypothermia. Although it is unlikely that these small changes in flow are an important primary effect in the development of hypoperfusion, increased metabolic rate with increased CBF may indicate pressure-dependent collateral flow potentially in regions embolized during CPB.

Adult↗

Bias in murine IgG isotype immobilisation. Implications for IgG glycoform analysis ELISA procedures.

This study investigates immobilisation of murine IgG in various ELISA procedures. Monoclonal murine IgG isotypes and polyclonal IgG from sera were studied. Similar binding curves to plastic were found for all four individual murine IgG isotypes. Single isotypes displayed different affinities for both protein A and protein G, in particular IgG1 was poorly and IgG3 strongly bound to both of these proteins. When mixtures of the isotypes were bound to either plastic, protein A or protein G, competition was observed in which IgG3 was dominant. Paradoxically, studies on the binding rates of single isotypes direct to plastic revealed that IgG3 had the slowest binding rate. Heating of bound IgGs resulted in significant but isotypically non-selective losses from the plates. The data demonstrate that despite obtaining equivalent individual IgG isotype binding curves, mixtures of IgG isotypes behave very differently, with competition for binding occurring even on plastic. The IgG isotype levels of murine sera were measured for individual mice, and the capture efficiency of each IgG isotype by protein A determined at different serum dilutions. Comparisons were made between the observed capture levels of IgG isotypes and their known serum levels. At all dilutions tested, greater than expected binding of IgG3, IgG2b and IgG2a was observed. At a serum dilution of 1/100 the binding of these three isotypes was increased 16-, 2.9- and 0.4-fold, respectively. These increases were balanced by a decrease in IgG1 binding which was the most prevalent serum IgG isotype. The results described above suggest that capture techniques are biased and unlikely to provide a coating of IgG isotypes that accurately reflects that of the serum. This bias is derived from the specificity of the individual isotypes for either protein A or protein G, and the errors further compounded by direct competition between isotypes whatever the capture surface. Induced coalescence of IgG3 may explain the latter observations.

Animals↗

Polynomials with asymptotes for longitudinal data.

I use Laguerre polynomials to model growth curves or time--response curves known to approach an asymptote as time approaches infinity. An example is with measurements on a variable or variables from subjects recovering from surgery. These variables can often vary in a non-monotonic fashion for which a functional form of the curve is unknown. Using a longitudinal data mixed model, one can include in the model random subject effects, within-subject serial correlation and fixed or time varying covariates. I present two examples that involve groups of subjects recovering from surgery.

Anterior Cruciate Ligament↗

Quantitative measurement of 3-O-methyl-D-glucose by gas chromatography-mass spectrometry as a measure of glucose transport in vivo.

Existing methods of measuring glucose kinetics are subject to errors. There is considerable interest in improved methods of measuring glucose kinetics to allow the development of new regimes for the treatment of diabetes mellitus. 3-O-Methyl-D-glucose is transported but not metabolized and therefore allows independent estimation of transport parameters. We describe a method by which 3-O-methyl-D-glucose in plasma samples can be measured in protocols during which glucose flux is assessed with simultaneous use of two isotopically labeled glucoses to quantitate and validate measurements of the rate of glucose appearance and disappearance. Quantitative gas chromatographic/mass spectrometric (GC/MS) analysis of 3-O-methyl-D-glucose, D-glucose, D-[U-13C] glucose and D-[6,6-2H2] glucose in human plasma using methoxime-trimethylsilyl ether derivatives is described. Measurements of all four derivatives were performed together in a small sample volume (50 microliters) with high precision. The intra-assay (inter-assay) coefficients of variation at an isotope content of 0.25 atom% excess for D-[6,6-2H2] glucose, D-[U-13C] glucose and 3-O-methyl-D-glucose were 0.8% (1.0%), 0.5% (4.0%) and 0.1% (3.7%), respectively. This method provides the basis for quantitative estimation of parameters of glucose kinetics in man and the rates of glucose flux across the cell membrane.

3-O-Methylglucose↗

Effects of valve replacement on ventricular mechanics in mitral regurgitation and aortic stenosis.

BACKGROUND: This study in humans assessed changes in left ventricular function early and late after correction of mitral regurgitation (MR) (n = 9) or aortic stenosis (AS) (n = 10). METHODS: Ventricular function was measured with radionuclide and micromanometer-derived pressure-volume loops during preload manipulation, thermodilution cardiac outputs, and echocardiograms. Late radionuclide and echocardiographic data were acquired at 24 hours and 20 months. RESULTS: Perioperative left ventricular performance (stroke work-end-diastolic volume relationship) did not change for patients with MR or AS. Significant changes in afterload occurred: ejection fraction (MR, 0.49 to 0.37; AS, 0.54 to 0.60; both, p = 0.013), mean left ventricular ejection pressure (MR, 73 to 91 mm Hg; AS, 138 to 93 mm Hg; both, p < 0.01), and end-systolic wall stress (MR, 26 to 42 x 10(3) dynes/cm2; AS, 37 to 22 x 10(3) dynes/cm2; both, p < 0.01). Ejection efficiency improved for MR patients (0.69 +/- 0.26 to 1.0 +/- 0.15; p < 0.05). The 20-month data showed improved New York Heart Association functional class, normal resting ejection fraction, and normal exercise response for both groups. CONCLUSIONS: Early after operation, a significant change in left ventricular load was seen with correction of MR and AS. Data obtained late after operation showed improvement consistent with ventricular remodeling.

Aged↗

Effect of provisional luting agents on polyvinyl siloxane impression material.

Eugenol-containing cements have been traditionally selected for seating provisional restorations, but incomplete polymerization of polyvinyl siloxane impression materials has been attributed to these cements. This study clinically evaluated the inhibitory effect on polymerization of a specific polyvinyl siloxane impression material with five luting agents used for provisional restorations. Three of these luting agents contained eugenol, whereas two interim cements did not contain eugenol. A total of 60 human posterior teeth were prepared for complete crowns, fitted for provisional crowns, and cemented with interim luting agents. After 2.5 weeks the provisional crowns were removed, the cement on tooth preparations was removed with an explorer, and impressions were made. The results revealed that none of the luting agents in this investigation had an inhibitory effect on polymerization of polyvinyl siloxane impression materials.

Calcium Hydroxide↗

Long-term survival benefits of coronary artery bypass grafting and percutaneous transluminal angioplasty in patients with coronary artery disease.

The purpose of this study was to evaluate long-term survival benefits of bypass surgery and angioplasty versus medical therapy in 9263 patients at Duke University Medical Center between 1984 and 1990 with coronary artery disease confirmed by cardiac catheterization to involve one, two, or three vessels. Clinical data were prospectively entered into an established cardiovascular database, and annual follow-up was 97% complete for a mean interval of 5.3 years and a maximal interval of 10 years. Outcomes were analyzed with the Coronary Artery Surgery Study "method A" to define patient groups treated by medicine (n = 2449), angioplasty (n = 2924), or bypass surgery (n = 3890). Differences among treatment groups in baseline characteristics were adjusted by Cox proportional hazard models. The anatomic severity of coronary artery stenosis best defined survival benefit from bypass surgery and angioplasty versus medical treatment. One or both interventional treatments provided better long-term survival than did medical treatment for all levels of disease severity. All patients with single-vessel disease, except those with at least 95% proximal left anterior descending stenosis, benefited from angioplasty versus bypass. All patients with three-vessel disease and those two-vessel patients with > or = 95% proximal left anterior descending stenosis benefited from bypass surgery versus angioplasty. All other patients with two-vessel disease and those with > or = 95% proximal left anterior descending stenosis only had similar survival with either interventional treatment. The absolute survival benefit was greatest for patients with severe three-vessel disease treated with bypass surgery.

Angioplasty, Balloon, Coronary↗

The impact of surgical timing on postoperative motion and stability following anterior cruciate ligament reconstruction.

A prospective study was designed to determine the impact of surgical timing on postoperative motion and stability following anterior cruciate ligament (ACL) reconstructive surgery. The study population was limited to acute ACL ruptures from downhill skiing undergoing arthroscopic ACL surgery without arthrotomy or surgical intervention for other ligamentous structures; 185 patients were entered into four separate groups based on the time interval from injury to surgery. Motion and stability were tested at multiple time points from the index surgery and adverse events were recorded. We found no statistical difference in restoration of extension or flexion in any group at any time point. KT-1000 data at 12 months showed a side-to-side difference of < or = 3 mm in 94%, with 6% showing a side-to-side difference of > 3 and < or = 5 mm. We conclude that, in this population, by using modern arthroscopic surgical techniques and an aggressive postoperative physical therapy protocol, motion and stability can be restored in a high percentage of patients and that surgical success is independent of the timing of surgery.

Adolescent↗

Clinical economics review: gastrointestinal disease in primary care.

Gastrointestinal disorders are common in the general population, with annual prevalence figures ranging from 20% for irritable bowel syndrome to over 40% for dyspepsia. Less than one-third of patients consult general practitioners for these problems, and anxiety about serious disease and cancer are as important in the decision to consult as symptom severity. Gastrointestinal disorders have significant socioeconomic effects in the community, and account for 10% of the work of general practitioners in the UK. The health economics implications of management in primary care relate principally to the costs of investigation and therapy, notably antisecretory drugs, endoscopy, radiology and specialist referral. Although guidelines based on evidence and agreed between primary and secondary care physicians offer an attractive approach to rationalizing the use of resources, there is at present little health service research evidence on which to base important decisions. For example, in dyspepsia, the role of Helicobacter pylori identification and eradication in an overall management strategy in primary care has yet to be defined. An exploration of the clinical economics of gastrointestinal disorders in general practice raises a number of research questions, which will require the attention of both generalists and specialists.

Gastrointestinal Diseases↗

Mediastinitis after coronary artery bypass graft surgery. Risk factors and long-term survival.

BACKGROUND: Mediastinitis is a severe complication of coronary artery bypass graft surgery (CABG). The purpose of the present study was to determine preoperative and intraoperative variables that predict mediastinitis and to determine the impact of this complication on long-term survival. METHODS AND RESULTS: Data on 20 preoperative and intraoperative variables were collected prospectively on 6459 consecutive patients who underwent CABG between January 1987 and January 1994. Eighty-three patients (1.3%) developed mediastinitis postoperatively, and a total of 24 patients (29%) died. Multivariate analysis identified 4 of the 20 variables as highly significant independent predictors for the development of mediastinitis: obesity (P = .0002), New York Heart Association congestive heart failure class (P = .002), previous heart surgery (P = .008), and duration of cardiopulmonary bypass (P = .05). A comprehensive review of the literature identified 13 other studies that evaluated 48 factors as predictors of mediastinitis; these data were critically analyzed and compared with the results from this series. In this series, postoperative interval mortality during the first 90 days after surgery for the patients with mediastinitis was 11.8% compared with 5.5% for the patients without mediastinitis. Interval mortality between 1 and 2 years after surgery remained high for the mediastinitis group (8.1%) relative to the nonmediastinitis group (2.3%). These differences were not eliminated by adjusting for important variables that influenced late survival in this population. CONCLUSIONS: The present study and a review of the literature suggest that obesity and duration of surgery are the most important predictors of mediastinitis. Furthermore, although the early increase in mortality has been well described, the present study documents for the first time that mediastinitis has a significant negative influence on long-term survival independent of the patient's preoperative condition.

Cardiac Surgical Procedures↗

Multi-state models and diabetic retinopathy.

This paper discusses the application of a multi-state model to diabetic retinopathy under the assumption that a continuous time Markov process determines the transition times between disease stages. The multi-state model consists of three transient states that represent the early stages of retinopathy, and one final absorbing state that represent the irreversible stage of retinopathy. By using a model with covariables, we explore the effects of factors that influence the onset, progression, and regression of diabetic retinopathy among subjects with insulin-dependent diabetes mellitus. We can also introduce time-dependent covariables in the model by assuming that the covariables remain constant between two observations. We can also obtain survival-type curves from each stage of the disease and for any combination of patient risk factors.

Adolescent↗