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Biomedical subjects

R D Baker

Publications and source records attributed to R D Baker.

At least 37 records · Page 2Linked to original sources

A random-effects model for analysis of infectious disease final-state data.

Ball (1986, Advances in Applied Probability 18, 289-310) presented an extension to the "General Epidemic Model" in which an individual's (random) infectious period could have any distribution whose Laplace transform could be specified. This paper describes the fitting of Ball's model to data on the final state of infection within households, and gives an intuitive mathematical derivation of the corresponding likelihood function. We extend the model in several ways, including an extension to allow for random-effects heterogeneity in disease transmission rate between individuals. We give an algorithm for the efficient numerical computation of maximum likelihood estimators of the transmission rates, and describe the assessment of goodness of model fit. The methodology is illustrated with recent survey data on outbreaks of Shigella sonnei in 102 households in Manchester, UK. The results are consistent with previous anecdotal evidence of the infectiousness and susceptibility of individuals within households as a function of age and sex.

Adult↗

Functional encopresis: symptom reduction and behavioral improvement.

This study assessed the relationship between functional encopresis and accompanying problems: emotional, behavioral, and social. Symptom resolution and changes in these concomitant problems were studied. Seventy-six children, 6 to 12 years of age, enrolled in this "self-selected," nonequivalent, control (contrast) group research design with 38 children in each group. Using the Child Behavior Checklist, children were tested before treatment and 6 months later. The results showed that children with encopresis had significantly more emotional/behavioral problems and poorer social competence before treatment than children in the contrast group; combined medical and psychotherapeutic intervention led to a significant reduction in soiling frequency, and children with encopresis experienced significantly fewer behavioral problems and significantly improved social competence after treatment. There was a small group of children for whom treatment was difficult. The data suggest that highly elevated behavior problem scores, especially in association with parental negativeness, may be related to poor treatment outcome.

Behavior Therapy↗

Selenium regulation of glutathione peroxidase in human hepatoma cell line Hep3B.

Glutathione peroxidase is an important enzyme in cellular antioxidant defense systems, detoxifying peroxides and hydroperoxides. As a component of the glutathione cycle, it protects the liver from reactive oxygen metabolites. Selenocysteine is present at the catalytic site of glutathione peroxidase, and selenium availability regulates glutathione peroxidase enzyme activity. Hep3B cells, a well-differentiated human hepatoma-derived cell line, exhibited time-dependent decrease in glutathione peroxidase activity (nmol NADPH oxidized/min/mg protein, mean +/- SE) when incubated in selenium-free medium for 10 days (Day 0, 21.8 +/- 7.3; Day 2, 10.9 +/- 1.2; Day 4, 7.9 +/- 0.8; Day 6, 4.0 +/- 0.7; Day 8, 4.5 +/- 0.6; Day 10, 1.6 +/- 0.4). With the reintroduction of selenium, glutathione peroxidase activity returned. A second human hepatoma cell line, HepG2, demonstrated a similar pattern when depleted of and then repleted with selenium. To assess protein synthesis, glutathione peroxidase activity was measured in deficient and replete Hep3B cells incubated with and without selenium and with and without cycloheximide. Deficient cells (mean +/- SE) (4.9 +/- 0.2) showed an increase in glutathione peroxidase activity after 24 h in selenium-containing medium (11.6 +/- 0.2), but not when cycloheximide was included in the medium (6.9 +/- 0.5) or when cycloheximide and no selenium was included (5.3 +/- 0.8). Replete Hep3B cells (40.1 +/- 1.1) demonstrated decreased glutathione peroxidase after 24 h in medium without selenium (34.0 +/- 1.4), medium with both cycloheximide and selenium (34.0 +/- 2.6), and medium without selenium and containing cycloheximide (37.6 +/- 1.3). These data suggest that protein synthesis is needed for selenium repletion to exert control on glutathione peroxidase activity. Using a cDNA for human glutathione peroxidase (GPx1), selenium-deficient and replete Hep3B cell RNA was analyzed by Northern blot. mRNA for GPx was quantified by densitometry. The steady-state mRNA level for glutathione peroxidase in deficient cells was 40% of that in replete cells. Nuclear run-on studies to determine the rate of GPx-specific mRNA synthesis showed no difference between nuclei from selenium-replete and selenium-deficient cells. This finding eliminated the possibility of differential transcription rates as an explanation for the observed reduction in mRNA brought about by selenium deficiency and suggested instead a stabilization of mRNA in selenium-replete cells. While selenium deficiency decreased mRNA levels by 60%, glutathione peroxidase enzyme activity decreased by 93%, suggesting a co- and/or post-translational control mechanism in addition to the effect on mRNA stability.

Carcinoma, Hepatocellular↗

Caco-2 cell metabolism of oxygen-derived radicals.

Reactive oxygen metabolites have been associated with gastrointestinal injury and may play a role as mediators of inflammation. The effect of oxygen metabolites on Caco-2 cell viability (trypan blue exclusion and 51Cr release), hexose monophosphate shunt activity, and glutathione was assessed. Caco-2 cells were incubated with amino acid oxidase, xanthine oxidase, menadione, and t-butylhydroperoxide in the presence and absence of superoxide dismutase, catalase, mannitol, and butylated hydroxytoluene. With amino acid oxidase, trypan blue exclusion decreased (P < 0.01) and 51Cr release, oxidized glutathione, and shunt activity increased (P < 0.05). The addition of catalase attenuated these changes. Trypan blue exclusion decreased (P < 0.005) and 51Cr release, oxidized glutathione, and shunt activity increased (P < 0.01) with xanthine oxidase. The addition of superoxide dismutase caused a further increase in 51Cr release, oxidized glutathione, and shunt activity (P < 0.01), which was prevented by the addition of catalase or mannitol. t-Butylhydroperoxide did not effect 51Cr release or trypan blue exclusion, but oxidized glutathione and shunt activity increased (P < 0.01). The increase in shunt activity was prevented by preincubation with butylated hydroxytoluene (P < 0.01). Menadione did not alter trypan blue exclusion or 51Cr release, but caused an increase in oxidized glutathione and shunt activity (P < 0.001). The increase in shunt activity was attenuated by preincubation with butylated hydroxytoluene (P < 0.001). Menadione also caused a depletion of total glutathione.(ABSTRACT TRUNCATED AT 250 WORDS)

Chromium Radioisotopes↗

Modelling trypanosomiasis prevalence and periodic epidemics and epizootics.

Existing mathematical models of trypanosomiasis epidemiology and epizootiology are extended by including some relevant biology of the disease vector, the tsetse fly. Rickettsia-like organisms, or RLO, are a vertically transmitted symbiont of tsetse, which confer an increased susceptibility to trypanosomiasis infection. Tsetse populations are also limited by density-dependent starvation. Modelling leads to the prediction of a stable dimorphism with a fraction of tsetse possessing RLO. The equilibrium prevalence of trypanosomiasis in the vertebrate hosts is no longer in RLO models determined simply by such traditional parameters as vectorial capacity. Only the RLO-positive tsetse carry infection, and their number is itself regulated by trypanosomiasis prevalence. The result of a naive model is that controlling tsetse numbers does not decrease prevalence until all tsetse are RLO-positive. However, under the density-dependent starvation model derived in this paper, the relative mortality of RLO-positive flies is greater at lower tsetse numbers. This tips the balance towards lower equilibrium prevalence of trypanosomiasis as tsetse numbers are decreased. The presence of RLO also gives rise to long-term oscillations in trypanosomiasis prevalence in humans and animals. However, when another mechanism that can also cause periodic epizootics (of shorter periodicity) is included, namely host immunity, the two epizootic processes combine to produce periodic epizootics (and therefore epidemics) at a single frequency. There are two decaying modes, one in which the tsetse population size quickly reaches equilibrium in a few weeks, and a second very slowly decaying mode in which host immunity and RLO effects interact. The equilibrium reached is shown to be asymptotically stable. In view of the seeming importance of RLO in trypanosomiasis epidemiology, it is important that field biologists enable RLO models to be validated by measuring the proportion of tsetse with RLO, in conjunction with vector density and trypanosomiasis prevalence and incidence in tsetse and vertebrate hosts.

Animals↗

A double blind placebo controlled trial of recombinant tissue plasminogen activator in the treatment of digital ischemia in systemic sclerosis.

The treatment of digital ischemia in systemic sclerosis remains inadequate. We report a double blind, placebo controlled trial of recombinant tissue plasminogen activator (rtPA), a potent thrombolytic agent. Ten patients received rtPA. A potent, acute fibrinolytic effect was observed. During the infusion of rtPA, improvements in skin blood flow were seen. These improvements were shortlived.

Adolescent↗

Effects of breed, age of donor and dosage of follicle stimulating hormone on the superovulatory response of beef cows.

Data were obtained on 1039 recoveries of embryos from beef cows of four breeds at two locations, in clinic and on farm. General linear models procedures were utilized to determine the effects of breed, location, age of donor, dosage of follicle stimulating hormone (FSH) and the interaction of age and FSH on the following dependent variables: 1) the mean number of ova (unfertilized oocytes and embryos) recovered; 2) the mean number and percentage of embryos (fertilized; live and dead) recovered; and 3) the mean number and percentage of transferable embryos recovered. The interaction of age of donor and dosage of FSH with breed and location prevented the pooling of data over breed and location. The mean number of ova recovered was affected by age of the donor (Charolais-in clinic), or the interaction between age of donor and dosage of FSH (Polled Hereford-in clinic and -on farm and Simmental -on farm). The mean number of embryos was affected by age of donor (Polled Hereford-in clinic), dosage of FSH (Simmental-in clinic) or their interaction (Angus-on farm). The mean number of transferable embryos was affected by age of donor (Polled Hereford-in clinic and -on farm, Simmental-in clinic and Angus-on farm). General linear models procedures were utilized to determine the effects of the embryo (stage of development and quality) and the recipient (synchrony with the donor) on the rate of pregnancy. Rate of pregnancy varied with embryo quality score and synchrony of the recipient and the embryo. In conclusion, the superovulatory response was found to be highly breed-specific, and most of the variability in embryos produced was attributed to the number of ova recovered. However, the number of ova, embryos and transferable embryos recovered was further influenced by age of the donor, dosage of FSH or their interaction.

Journal Article↗

A randomized cross-over study of the effects of proinsulin on lipid metabolism in type 2 diabetes.

The effects of human proinsulin and insulin on lipid metabolism in Type 2 diabetes were examined in a randomized cross-over study in 15 patients. Blood glucose control was indistinguishable at the end of the two treatment periods, but fasting levels of triglycerides appeared somewhat lower after proinsulin (1.17(SE 0.16) vs 1.39(0.21) mmol I-1; p less than 0.07), and the maximal postprandial triglyceride response (2.19 (0.25) vs 2.87(0.28) mmol I-1, p less than 0.001) and triglyceride area under the curve (p less than 0.01) were significantly reduced. In five hyperlipidaemic patients postprandial triglyceridaemia was reduced with proinsulin (2.89(0.60) vs 3.68(0.56); p less than 0.001), but in addition fasting serum triglycerides (1.20(0.30) vs 1.96(0.30) mmol I-1, p less than 0.04) and possibly VLDL-cholesterol (0.49(0.15) vs 0.60(0.20) mmol I-1; p less than 0.10) were lower and fasting LDL-cholesterol levels higher (4.82(0.42) vs 3.92(0.57) mmol I-1, p less than 0.03) after proinsulin therapy. Proinsulin appears to preferentially suppress the production of triglyceride-rich lipoproteins in Type 2 diabetes, particularly postprandially, and may enhance their clearance and conversion to LDL, especially in hyperlipidaemic Type 2 diabetes.

Adult↗

The possible role of Rickettsia-like organisms in trypanosomiasis epidemiology.

A simple model of human and animal trypanosomiasis is proposed in which the Ross equation for disease transmission is supplemented by a differential equation describing the inheritance of susceptibility in the vector. The model predicts an equilibrium state of balanced polymorphism for the fraction, theta, of susceptible tsetse and the occurrence of periodic epidemics at roughly the observed intervals. A loss of infectivity to tsetse of mechanically transmitted strains of trypanosome would seem to be a good evolutionary strategy for the trypanosome. The main implication for disease control is that measures initially reducing trypanosomiasis incidence could trigger off subsequent epidemics. Since theta leads incidence, monitoring theta could give several years advance warning of major epidemics. The model leads to oscillations in prevalence which are only lightly damped. Other mechanisms producing periodic epidemics would interact with this mechanism, and result in only one sequence of recurrent epidemics. With typical random variation of tsetse numbers about the seasonal norm the model shows the behaviour of a narrow-band system excited by broad-band noise, i.e. predicted trypanosomiasis incidence exhibits an undamped series of oscillations of variable amplitude and phase, similar to what is actually observed.

Animals↗

Acute phase proteins in neonatal rabbits: diminished C-reactive protein response.

Acute phase protein response accompanies tissue injury, inflammation, or infection. During the acute phase, serum levels of C-reactive protein (CRP) can increase as much as 1,000-fold. We found that in response to an intramuscular injection of turpentine, neonatal rabbit CRP-specific RNA and serum CRP rose minimally. In contrast, adult serum levels of CRP increased 20-fold and mRNA for CRP in adults increased commensurately. However, during neonatal acute phase reactions, changes in the synthesis of the third component of complement (C3) and albumin were induced, implying a dysynchronous development of the response of various acute phase proteins.

Acute-Phase Reaction↗

Growth of the early bovine fetus.

Testing for bovine hereditary syndactyly used artificial insemination, superovulation, and embryo transfer. Thirty-two suspect bulls and 9 suspect cows were mated with 10 syndactyly cows and two syndactylous bulls, respectively. 209 embryos were recovered and one, two, or three embryos was/were transfered into each recipient cow and 56 to 77 days after transfer, 174 fetuses were recovered. There was a significant relationship between amniotic fluid weights from the left uterine horn, fetal weights from right and left uterine horns, and fetal sex, side of corpus luteum, and number of embryo implants. Fetal membrane weights, amniotic fluid weights, fetal weights, and crown-rump lengths increased significantly with fetal age, but recipient cow weight had no significant effect. Survival data from single, double, and triple embryo implants indicated that it was most profitable under these test conditions to implant two embryos per recipient cow, one in each uterine horn.

Animals↗

Platelet and plasma vasoactive amines in type 1 (insulin-dependent) diabetes mellitus with and without vascular disease.

Platelet and plasma vasoactive amine concentrations were measured in healthy controls and in type 1 (insulin-dependent) diabetic patients with or without vascular disease. Platelet concentrations of serotonin and noradrenaline were similar in all groups and were unrelated to age or gender, or to duration of diabetes, blood pressure, glycaemia or renal function in the diabetic subjects. Plasma concentrations of serotonin in the diabetic groups were comparable (118 +/- 16 (mean +/- SEM) and 127 +/- 21 pmol/mL), and were significantly higher in comparison to the healthy controls (66 +/- 12 pmol/mL, P = 0.002).

Adolescent↗

The management of patients with an intrinsic supratentorial brain tumour.

The management of patients presenting with supratentorial glioma between 1978 and 1986 is reviewed. Complete follow-up in 517 cases was obtained. One hundred and fifty eight patients were not submitted to any form of surgery, 299 patients were biopsied and 60 patients underwent craniotomy and internal decompression. The no surgery group contained a higher proportion of patients with poor prognostic indicators than either the biopsy or craniotomy groups. The craniotomy group consisted of patients with better prognostic indicators than the biopsy group, in particular, younger age and more favourable site, type and grade of tumour. This was reflected in the difference in outcome between the groups. Median survival was 14 months in the craniotomy group, four months in the biopsy group and 2.2 months in the no surgery group. The outcome in patients with histologically proven malignant gliomas was best in those patients who received radiotherapy. The craniotomy group had a median survival of 18.5 months, a two year survival of 48% and a five year survival of 9%. The median survival following radiotherapy of those patients with proven malignant gliomas who had a biopsy was 9.5 months with a two year survival of 16% and a five year survival of 2%. These results compare favourably with studies which have adopted a more aggressive approach, suggesting that outcome is determined as much by patient selection using favourable prognostic indicators as by the treatment itself. The need for prospective trials of the management of unselected consecutive glioma patients randomizing them to conservative and radical treatment groups in order to define the role of both conventional therapy and radical therapy is discussed.

Adolescent↗

Short-term malnutrition in neonatal rabbits: effect on function and synthesis of free radical metabolizing enzymes in the gastrointestinal tract.

Oxygen-derived free radicals are an important component of gastrointestinal injury in necrotizing enterocolitis (NEC). To assess the effect of a 72-h fast on the ability of neonatal small bowel to metabolize free radicals, the activity of superoxide dismutase (SOD), catalase, and the glutathione cycle were quantitated in mucosal scrapings from proximal and distal small bowel of fed and fasted neonatal rabbits. Hexose monophosphate shunt activity, quantitated in enterocytes from fed and fasted neonatal rabbits, was significantly less, p less than 0.01, in fasted animals. SOD activity was lower in distal small bowel from fasted animals than fed. The two mechanisms available to metabolize H2O2, catalase and the glutathione cycle, were significantly lower in both proximal and distal small bowel from fasted animals than in those from fed animals. To determine if fasting caused decreased enzyme activity at the level of gene expression, gastrointestinal tract DNA, RNA and protein, and specific mRNA levels for catalase, glutathione peroxidase (GPx), and SOD were quantitated. DNA, total RNA, and mRNA for SOD were lower in mucosal scrapings from fasted animals. However, mRNA for catalase, and GPx were not lower in fasted animals. Thus, a 72-h fast in neonatal rabbits causes a regional-specific decrease in SOD activity, which may be explained by decreased transcription. Changes in transcription do not completely account for regulation of catalase and glutathione cycle enzymes.

Animals↗