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R H Jones

Publications and source records attributed to R H Jones.

At least 91 records · Page 5Linked to original sources
PubMed1995

Smoothing splines for longitudinal data.

In a longitudinal data model with fixed and random effects, polynomials are used to model the fixed effects and smoothing polynomial splines are used to model the within-subject random effect curves. The splines are generated by modelling the data for each subject as observations of an integrated random walk with observational error. The initial conditions for each subject's deviation from the fixed effect curve are assumed to have zero mean and arbitrary covariance matrix which is estimated by maximum likelihood, producing an empirical Bayes estimate. This is in contrast to modelling a single curve using a diffuse prior. An example is presented using unbalanced longitudinal data from a pilot study in breast cancer patients.

Bayes Theorem↗
PubMed1995

Determining one or more change points.

A statistical method is presented for determining whether a line has one or more change points at unknown locations. A change point is a point where a line suddenly changes its slope but is continuous, i.e. it does not jump. Change points are also referred to as break points or join points. A step-wise procedure is suggested which starts by fitting a straight line without points. Next a line with a single change point is fit to the data, and a statistical test is used to determine if the line with a single change point provides a significantly better fit to the data than the line with no change points. This can then be followed by fitting a line with two change points, etc. The problem of determining the number of change points that best fits the data is discussed. A modified version of Akaike's information criterion (AIC) is used to select the best number of change points to avoid over fitting. An example of fluorescence anisotropy measurements of the total phospholipid from the liver of a marine fish as a function of temperature is presented.

Animals↗
PubMed1995

Guidelines on appropriate indications for upper gastrointestinal endoscopy. Working Party of the Joint Committee of the Royal College of Physicians of London, Royal College of Surgeons of England, Royal College of Anaesthetists, Association of Surgeons, the British Society of Gastroenterology, and the Thoracic Society of Great Britain.

Upper gastrointestinal endoscopy is a valuable diagnostic tool, but for an endoscopy service to be effective it is essential that it is not overloaded with inappropriately referred patients. A joint working party in Britain has considered the available literature on indications for endoscopy, assessed standard practice through a questionnaire, and audited randomly selected cases using an independent panel of experts and an American database system. They used these data to produce guidelines on the appropriate and inappropriate indications for referral for endoscopy, although they emphasise that under certain circumstances there may be reasons to deviate from the advice given. The need for endoscopy is most difficult to judge in patients with dyspepsia, and this aspect is discussed in detail. Early endoscopy will often prove more cost effective than delaying until the indications are clearer.

Adult↗
PubMed1995

Effect of diabetes and dietary ubiquinone supplementation on the post-translational modification of rat lens beta L crystallin.

The effect of streptozocin diabetes of 14 days duration on the integrity of lenticular crystallins has been determined by the measurement of characteristic markers of protein modification in the lens crystallins of rats. Further, the susceptibility of the crystallins to modification has also been determined by measurement of the same markers after the application of a metal-catalyzed oxidative insult in vitro. The results show that the previously reported increased post-translational modification of lens crystallins in vivo and increased susceptibility to modification in vitro of diabetic crystallins after 21 days of uncontrolled diabetes are also evident after just 14 days of diabetes. Treatment of the diabetic animals with the antioxidant ubiquinone by dietary supplementation was unable to prevent the post-translational modifications sustained by the crystallin when subjected to diabetes in vivo or the increase in susceptibility to an in vitro oxidative stress. While the present results support the proposal that cataract formation is initiated by protein post-translational modification factors such as glycation, ubiquinone supplementation does not appear to be beneficial in the inhibition of post-translational crystallin modification in diabetic cataractogenesis.

Animals↗
PubMed1995

Demonstration of a relatively hepatoselective effect of covalent insulin dimers on glucose metabolism in dogs.

Insulin analogues with relatively greater effect on hepatic glucose production than peripheral glucose disposal could offer a more physiological approach to the treatment of diabetes mellitus. The fact that proinsulin exhibits this property to a minor degree may suggest that analogues with increased molecular size may be less able than insulin to obtain access to peripheral receptor sites. Covalent insulin dimers have previously been shown to possess lower hypoglycaemic potencies than predicted by their in vivo receptor binding affinities. Reduced rates of diffusion to peripheral target tissues might be an explanation for the lower in vivo potency compared to insulin. To test the relative hepatic and peripheral effects of covalent insulin dimers, glucose clamp procedures with D-[3-3H]glucose tracer infusions were used in anaesthetised greyhounds to establish dose-response curves for rates of hepatic glucose production and glucose disposal with insulin, N alpha B1, N alpha B'1,-suberoyl-insulin dimer, and N epsilon B29, N epsilon B'29,-suberoyl-insulin dimer. With N alpha B1, N alpha B'1,-suberoyl-insulin dimer molar potencies relative to insulin were 68%, (34-133) (mean and 95% fiducial limits), for inhibition of hepatic glucose production and 14.7%, (10.3-20.9) for glucose disposal. With N epsilon B29,N epsilon B'29,-suberoyl-insulin dimer potencies were 75%, (31-184) and 2.5%. (1.5-4.3), for inhibition of hepatic glucose production and for glucose disposal, respectively. The demonstration that both dimers exhibit a significantly greater effect on glucose production than on glucose disposal supports the suggestion that analogues with increased molecular size may exhibit reduced ability to gain access to peripheral target cells.

Analysis of Variance↗
PubMed1995

Molecular architecture and biophysical properties of phospholipids during thermal adaptation in fish: an experimental and model study.

Phospholipids from livers of carps (Cyprinus carpio L.) adapted to winter (5 degrees C) and summer (25 degrees C) temperatures were isolated, and the fatty acid composition of total phospholipids, as well as molecular species composition of diacyl phosphatidylcholines and ethanolamines, were determined. Order parameter of 5-doxyl stearic acid and steady-state fluorescence anisotropy of different anthroyloxy fatty acids--[2-, 12(N-9-anthroyloxy)stearic acid and 16(N-9-anthroyloxy)palmitic acid--embedded in native and synthetic (16:0/16:0, 16:0/22:6, 18:0/22:6, 18:1/22:6, 20:4/20:4, 22:6/22:6 phosphatidylcholines and 16:0/18:1, 18:1/22:6 phosphatidylethanolamines) phospholipid vesicles was also determined between -30 and 30 degrees C and 5 and 30 degrees C, respectively. There is an accumulation of 1-monoenoic, 2-polyenoic diacyl phosphatidylcholine and ethanolamine with a concomitant reduction of 1-stearoyl,2-docosahexaenoyl species in the cold-adapted state. Despite a 30% accumulation of long-chain polyunsaturated fatty acids in phospholipids in cold, there is only a 5 degrees C downshift in the solid-gel to liquid-crystalline phase transition temperature (-8 vs. -13 degrees C). Vesicles from total phospholipids of cold-adapted fish proved to be more disordered in all segments than from the warm-adapted ones when assayed using 2,12-(N-9-anthroyloxy)stearic and 16-(N-9-anthroyloxy)palmitic acid. Vesicles made from purified phosphatidylcholines showed the same pattern, but they were more disordered than the corresponding total phospholipids. This could be modelled using mixed phospholipid vesicles made of synthetic 16:0/22:6 phosphatidylcholine (75%) and either 18:1/22:6 phosphatidylethanolamine (25%) vs. 16:0/18:1 phosphatidylethanolamine (25%) and comparison of the anisotropy parameters of 100% 16:0/22:6 and 100% 18:1/22:6 phosphatidylcholine vesicles. Mixing either 16:0/18:1 (25%) or 18:1/22:6 (25%) phosphatidylethanolamines to 18:0/22:6 (75%) phosphatidylcholine shifted down or up, respectively, the transition temperature of vesicles compared to 100% 18:0/22:6 vesicles assayed by electron spin resonance spectroscopy using 5-doxylstearic acid. It is concluded that it is not the gross amount of long-chain polyunsaturated fatty acids in phospholipids, but rather their specific combination with cis delta 9 monounsaturated fatty acids in the position sn-1, especially in phosphatidylethanolamines, that is important in determining the physical properties of biomembranes in relation to adaptational temperature.

Adaptation, Physiological↗
PubMed1995

MARKOV: a computer program for multi-state Markov models with covariables.

This paper discusses a computer program, called MARKOV, designed to fit a multi-state Markov model with covariables, with a particular emphasis on the analysis of survival data. The Markov model consists of k-1 transient disease states and one absorbing state. The exact transition times are not observed, except in situations such as death. Baseline transition intensities and regression coefficients are estimated via the method of maximum likelihood using a quasi-Newton optimization algorithm. The program's output includes the parameter estimates, the standard error of the estimates, the matrix of the correlation of the estimates and minus two times the log-likelihood function, evaluated at the initial values and at the maximum likelihood estimates. Optionally, survival curves can be generated from each transient state, for one or more combination of covariable values and simple tests about the parameters. The program is illustrated by using a four-state model to determine factors influencing diabetic retinopathy in young subjects with insulin-dependent diabetes mellitus.

Algorithms↗
PubMed1995

A comparison of the effects of IGF-I and insulin on glucose metabolism, fat metabolism and the cardiovascular system in normal human volunteers.

The metabolic and cardiovascular effects of recombinant human IGF-I were compared to insulin in six normal subjects. Subjects were studied twice and intravenously received an infusion of [6,6-2H2]glucose (0-480 min) and in random order either IGF-I 20 micrograms kg-1 h-1 (43.7 pmol kg-1 min-1 or insulin 0.5 mU kg-1 min-1 (3.4 pmol kg-1 min-1) with an euglycaemic clamp. One subject was withdrawn following a serious adverse event. During the IGF-I infusion glucose appearance rate (Ra) decreased from 1.79 +/- 0.13 at baseline (150-180 min) to 0.35 +/- 0.26 mg kg-1 min-1 (P < 0.01) at 360 min, and glucose utilization rate (Rd) increased from 1.79 +/- 0.28 to 4.17 +/- 0.84 mg kg-1 min-1 (P < 0.01). There was no change in free fatty acids (FFA) and an increase (percentage change from pre-infusion mean) in cardiac output +l37.3% +/- 9% (P < 0.01), heart rate +13% +/- 2% (P < 0.01) and stroke volume +21% +/- 7% (P < 0.05). During the insulin infusion glucose Ra decreased from 1.89 +/- 0.13 to 0.34 +/- 0.33 mg kg-1 min-1 (P < 0.01) and FFA from 0.546 mmol l-1 to 0.198 mmol l-1 (P < 0.01), glucose Rd increased from 1.89 +/- 0.18 to 5.41 +/- 1.47 mg kg-1 min-1 (P < 0.01) and there were no significant changes in the cardiovascular variables.

Adult↗
PubMed1995

A comparison of the effects of insulin-like growth factor-I, insulin and combined infusions of insulin and insulin-like growth factor-I on glucose metabolism in dogs.

The effect of infusions of recombinant insulin-like growth factor-I (IGF-I) (34, 103 or 688 pmol kg-1 min-1), insulin (3.4, 10.3 or 68.8 pmol kg-1 min-1) or combined infusions (34 pmol IGF-I + 3.4 pmol kg-1 min-1 insulin or 103 pmol IGF-I + 3.4 pmol kg-1 min-1 insulin) on glucose metabolism was investigated in dogs using a [3-3H]-glucose infusion and euglycaemic clamp. All insulin doses decreased glucose production rate (Ra) in a dose-dependent manner (P < 0.05). All IGF-I doses decreased glucose Ra (P < 0.05) but this decrease was not dose dependent. The decrease in glucose Ra with the combined infusion of 34 pmol kg-1 min-1 IGF-I + 3.4 pmol kg-1 min-1 insulin was greater than 34 pmol kg-1 min-1 IGF-I (P < 0.05) but not different from 3-4 pmol kg-1 min-1 insulin. All insulin and IGF-I doses increased glucose utilization rate (Rd) in a dose-dependent manner (P < 0.01). The increase in glucose utilization was greater following both combined infusions than with either component infused alone (P < 0.05). Although at the doses selected, insulin and IGF-I had similar effects on glucose utilization with additive effects when the two peptides were combined, IGF-I was less effective than insulin in suppressing glucose production.

Animals↗
PubMed1995

A simulation model for glucose kinetics and estimates of glucose utilization rate in type 1 diabetic patients.

A glucose kinetic model is described that contains insulin-independent and insulin-dependent pathways of glucose uptake and includes a saturating flux term for glucose transport into the cells by the glucose transporters. The rate of glucose utilization was estimated in control subjects and diabetic patients by use of a bolus of [3-3H]glucose. Diabetic patients were studied after three regimens of insulin therapy: 1) after 24 h of insulin withdrawal, 2) after conventional insulin therapy, and 3) after an overnight insulin infusion such that plasma glucose was maintained between 4 and 6 mmol/l. In addition, the model was used to simulate published results from glucose clamp experiments with a range of glycemic levels and insulin concentrations. Estimates of glucose utilization flux in diabetic patients and model simulation suggest that high plasma glucose concentrations in uncontrolled diabetic patients can be attributed to a high glucose production rate by the liver associated with a reduction in glucose metabolic clearance rate due to relative saturation of the available pool of glucose transporters.

Adolescent↗
PubMed1995

Hypoxia, hypercapnia, and hypertension: their effects on pulsatile cerebral blood flow.

Pulsatile cerebral blood flow reflects characteristics of arterial blood pressure as well as the structure and mechanical properties of the cerebrovascular network. Although the effects of changes in systemic blood gases and blood pressure on mean cerebral flow are established, their effects on pulsatile cerebral blood flow are unknown. These studies assessed the effects of hypoxia-hypercapnia (combined; both arterial PO2 and PCO2 approximately 55 Torr) and acute hypertension (+30-35 mmHg by aortic occlusion) on pulsatile cerebral blood flow in ketamine-anesthetized rabbits. We characterized the relationship between pulsatile systemic blood pressure (Millar catheter) and cerebral cortical capillary blood-flow (laser-Doppler) by calculating the transfer function, a frequency-domain expression that relates amplitudes and phase angles of flow output to those of the pressure input. During hypoxia-hypercapnia, mean flow increased 17% (P < 0.001), but the amplitude and contour of pulsatile cortical blood flow were unchanged (P > 0.10). Although aortic occlusion, during hypoxia-hypercapnia as well as during normoxia-normocapnia, increased systemic pulse pressure by 40%, the amplitude of cortical flow pulsations was unaffected. Changes in dynamic properties of the cerebral vasculature (P < 0.0001 by analysis of the transfer function) minimized alterations in pulsatile cortical blood flow and thus intrabeat vessel wall stress during acute hypertension; on the basis of analysis of an electrical analogue, we propose that these changes reflect alterations in both resistance and compliance.

Animals↗
PubMed1995

High fasting insulin levels associated with lower rates of weight gain in persons with normal glucose tolerance: the San Luis Valley Diabetes Study.

OBJECTIVE: to investigate whether increased insulin resistance is associated with a reduced risk of weight gain among Hispanic and non-Hispanic white persons in Colorado. DESIGN: measurements were taken at baseline and after an average of 4.3 years. SUBJECTS: 789 normal glucose tolerant subjects 20 to 74 years of age were studied. MEASUREMENTS: fasting insulin levels were used as an indirect marker of insulin resistance. RESULTS: the average baseline body mass index (BMI) was 26.1 (+/- 3.6 s.d.) in men and 25.2 (+/- 4.4 s.d.) in women. The average weight change at follow-up was 0.8 kg (+/- 4.3 s.d.) in men and 1.3 kg (+/- 5.0) in women. A doubling in initial fasting insulin was associated with a reduced risk of gaining 5 kg (n = 134) and 10 kg (n = 24) of weight in logistic regression models (OR5kg = 0.76, 95% CI: 0.59, 0.99 and OR10kg = 0.61, 95% CI: 0.36, 1.02). Similarly, a doubling of initial fasting insulin was associated (P = 0.006) on average with a 6.3 kg less weight gain in linear regression models, independently of initial body weight, age, sex, ethnicity and BMI. The relation was consistently observed in men and women and in both ethnic groups. CONCLUSION: higher initial fasting insulin decreases the risk of subsequent weight gain in both Hispanic and non-Hispanic white normal glucose tolerant individuals similar to Pima Indians. This appears to be a common biologic characteristic in moderate to low as well as high risk populations for NIDDM.

Adult↗
PubMed1994

General practitioners' views about the statutory annual practice report.

OBJECTIVE: To ascertain the views of primary care professionals about the current purpose, uses, potential, and workload implications of the statutory general practice annual report. DESIGN: Postal questionnaire survey. SETTING: General practices in the Northern region. SUBJECTS: All practices in the region that were singlehanded, fundholding, non-fundholding and with more than five partners, and a one in three random sample of all non-fundholding practices (n = 318). RESULTS: 263 practices responded (83%). The report took a median of 12 hours to produce (95% confidence interval 11 to 15 hours; interquartile range 7-35). The main perceived purpose of the report was to monitor practice activity (165 respondents; 63% (95% confidence interval 57% to 69%)), but 44 respondents (17%; 13% to 22%) produced it only because it was contractually required. Practices included statutory and non-statutory data in these reports and would have liked comparative practice activity information (155 respondents; 59%) and "good ideas" (165 respondents; 63%) fed back to them. Respondents would have liked the annual report used to improve practice development planning (122 respondents; 46% (40% to 52%)), to facilitate audit (115 respondents; 44% (38% to 50%)), and to influence resource allocation (104 respondents; 40% (34% to 46%)). One hundred and eighteen practices (45%; 39% to 51%) would produce an annual report even if not contractually required. Data collected were perceived to be already available elsewhere. CONCLUSIONS: Primary care professionals have concerns about the current annual report. They would prefer to collect relevant, standardised data which could lead to better audit, planning, and resource allocation.

Annual Reports as Topic↗
PubMed1994

Effects of coronary angioplasty, coronary bypass surgery, and medical therapy on employment in patients with coronary artery disease. A prospective comparison study.

OBJECTIVE: To compare return-to-work rates after coronary angioplasty, coronary bypass surgery, and medical therapy in patients with coronary disease. DESIGN: Prospective cohort study. SETTING: Tertiary care referral center. PATIENTS: Between March 1986 and June 1990, we enrolled 1252 patients who were younger than 65 years, who had not had previous coronary revascularization, and who were employed. All patients were followed for 1 year. MAIN OUTCOME MEASURE: One-year employment status. RESULTS: After 1 year, 84% of patients who had coronary angioplasty were still working compared with 79% of patients who had bypass surgery and with 76% of patients who received medicine. After adjusting for the more favorable baseline characteristics of patients who had angioplasty (less severe coronary artery disease, better left ventricular function, and less functional impairment), however, no significant differences were noted in 1-year employment rates among the three groups. These adjusted 1-year return-to-work rates were 84% for angioplasty, 80% for surgery, and 79% for medicine (P > 0.05). In a random subset of 72 patients, 23 patients who had angioplasty returned to work after a median of 18 days (mean, 27 days) compared with 54 days (mean, 67 days) for 24 patients having bypass surgery and with 14 days (mean, 45 days) for 25 patients receiving medicine (P = 0.002). CONCLUSIONS: Patients who had coronary angioplasty were able to return to work earlier than those who had bypass surgery, but by 1 year no significant difference was noted in employment rates. Neither revascularization strategy improved employment rates when compared with initial treatment using medical therapy.

Angioplasty, Balloon, Coronary↗
PubMed1994

Coronary artery bypass grafting in patients with dialysis-dependent renal failure.

Few data exist regarding functional results and long-term survival after coronary bypass in patients on dialysis. Therefore, a retrospective analysis was performed of 21 consecutive patients with dialysis-dependent renal failure who were undergoing coronary artery bypass grafting. Preoperatively, all but 1 patient had associated comorbid illnesses, 15 patients (71%) had class IV angina, and 16 patients (76%) had either left main or three-vessel disease. There were two perioperative deaths (9%), and complications occurred in 10 of the 21 patients (48%). All 19 hospital survivors showed symptomatic improvement with improved overall functional status (mean Karnofsky score increased from 37% +/- 16% preoperatively to 69% +/- 9% at hospital discharge or death; p < 0.001). Actuarial survival rates were 84% +/- 8% and 45% +/- 13% at 1 and 2 years, respectively. Therefore, coronary bypass grafting may be performed in dialysis patients with increased but acceptable morbidity and mortality, with excellent symptomatic relief, and with improved functional status. However, limited long-term survival suggests that the relative costs and benefits of surgical revascularization need further examination in this patient population.

Adult↗