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Biomedical subjects

R Carter

Publications and source records attributed to R Carter.

At least 145 records · Page 8Linked to original sources
PubMed1994

Breathlessness in microvascular angina.

In patients with microvascular angina (MA), there is some evidence from studies of plethysmography, that there are widespread microvascular abnormalities. In addition to exertional chest pain, all these patients complain of breathlessness, with no evidence of airways obstruction or resting left ventricular dysfunction. Progressive exercise testing was performed in 12 age and sex matched controls and 12 patients (three males), in whom the diagnosis of MA was established on the basis of exertional chest pain, abnormal thallium scans, and an attenuated myocardial flow response to a vasodilator challenge, with angiographically entirely normal epicardial vessels. Symptom limited exercise was performed with on line ventilation and expired gas analysis, measuring minute ventilation, oxygen consumption and carbon dioxide production and arterial blood gas values using a transcutaneous system. Anaerobic threshold was calculated by curve fitting a plot of oxygen consumption against carbon dioxide production. Compared to controls (49.7 +/- 7.3 SD% predicted maximum VO2) in patients with MA, the anaerobic threshold was reduced (41.6 +/- 5.82; P < 0.02) although still within accepted normal limits. Maximal (symptom limited) oxygen consumption, as a percentage of predicted, was reduced 60.73 +/- 16.51 compared to 87.21 +/- 5.2 (P < 0.003). The ventilatory response (VE/VCO2 l l-1 CO2 output) was significantly increased in the MA patients compared to controls (35.9 +/- 8.01 and 27.5 +/- 3.08, respectively; P < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Splanchnic blood flow changes in the presence of hepatic tumour: evidence of a humoral mediator.

Intrahepatic tumour is associated with alterations in splanchnic haemodynamics. To investigate the hypothesis that these are the result of a circulating vasoactive agent, rat small bowel segments were cross-perfused with arterial blood from groups (n = 12) of paired tumour-bearing (intrahepatic HSN sarcoma) and control rats. The vascular resistance of the segment was significantly greater during perfusion by tumour-bearing animals (91.6 mmHg ml-1 min, s.e. 21.5, vs 51.7 mmHg ml-1 min, s.e. 7.4, P < 0.05), suggesting that intrahepatic tumour may be associated with a circulating vasoactive agent. A similar mechanism may underlie changes in the hepatic perfusion index in patients with liver metastases.

Animals↗
PubMed1994

Protracted venous infusion 5-fluorouracil and interferon-alpha in advanced and refractory colorectal cancer.

BACKGROUND: The management of patients with advanced colorectal cancer remains dependent on the optimal use of 5-Fluorouracil (5-FU). Enhanced 5-FU activity can be achieved by either adding a modulator or by altering the administration schedule, in particular using a protracted venous infusion. Based on encouraging phase II data using bolus 5-FU and interferon-alpha, we designed a study to investigate the activity of this modulator in patients with colorectal cancer refractory to protracted venous infusion 5-FU. PATIENTS AND METHODS: Patients with advanced colorectal cancer were treated with 5-FU (300 mg/m2/day) given as a protracted venous infusion via an indwelling central venous catheter and portable battery driven pump. At the time the tumour became refractory to 5-FU, interferon-alpha was added and further outcome evaluated. RESULTS: One hundred twenty-four patients were entered on the study, 118 of whom had measurable disease. Fifty-two patients had previously received chemotherapy. The overall tumour response rate with infusional 5-FU was 33% (38/118), however in previously untreated patients was 42% (29/69) and 18% in those given prior chemotherapy (9/49). At the point of refractory disease 64 patients had interferon-alpha added to the 5-FU. Five patients (8%) showed an objective partial response following interferon-alpha addition. Patient toxicities on infusional 5-FU included hand-foot erythroderma, stomatitis and diarrhoea. There were only 15 episodes of grade 3 or 4 toxicity. The addition of interferon-alpha gave fever, lethargy, myelosuppression and depression, but did not increase the incidence or severity of 5-FU related toxicities. Of 67 patients with tumour related pain, 53 (79%) had an improvement in their symptoms. Median survival of the whole group was 7.5 months. CONCLUSIONS: Protracted venous infusion 5-FU is an active and well tolerated palliative treatment for advanced colorectal cancer. The addition of interferon-alpha at the point of 5-FU refractory disease resulted in further significant response in a small number of patients. Further randomised studies, including quality-of-life end-points, are needed before the use of interferon-alpha can be recommended as a modulator of 5-FU in the clinical setting.

Adult↗
PubMed1994

Agreement between death certificate and autopsy diagnoses among atomic bomb survivors.

Based on the Atomic Bomb Casualty Commission/Radiation Effects Research Foundation series of over 5,000 autopsies, we examined death certificate accuracy for 12 disease categories and assessed the effect of potential modifying factors on agreement and accuracy. The overall percentage agreement between death certificate and autopsy diagnoses was only 52.5%. Although neoplasms had the highest detection rate, almost 25% of cancers diagnosed at autopsy were nevertheless missed on death certificates. Confirmation and detection rates were above 70% for neoplasms and external causes of death only. Confirmation rates were between 50 and 70% for infectious diseases and heart and other vascular diseases. Detection rates reached a similar level for infectious, cerebrovascular, and digestive diseases. Specificity rates were above 90% for all except the cerebrovascular disease category. Overall agreement decreased with increasing age at death and was worse for deaths occurring outside of hospital. There was some suggestion that agreement improved over time, but no indication that radiation dose, sex, city of residence, or inclusion in a biennial clinical examination program influenced agreement. Since the inaccuracy of death certificate diagnoses can have major implications for health research and planning, it is important to be aware that their accuracy is low and that it can vary widely depending on cause, age and place of death.

Aged↗
PubMed1994

Plasmodium falciparum malaria transmission-blocking immunity under conditions of low endemicity as in Sri Lanka.

Sera from acute primary Plasmodium falciparum patients in Sri Lanka were tested for the presence of antibodies against gamete antigens and for their functional effects of transmission blocking activity. Comparisons were made with corresponding data from a previous study from sera of patients from Papua New Guinea where malaria is more highly endemic. Although the prevalence of anti-gamete antibodies in the two groups were broadly similar, the prevalence of infectivity suppressive effects in the Sri Lankan sera (56%) was less than in Papua New Guinea sera (75%), suggesting that the generation of functionally effective transmission blocking antibodies requires prolonged exposure to multiple inoculations of malaria. In Papua New Guinea sera there was a good correlation between transmission blocking effects and antibody responses to Pfs 230, a known target of transmission blocking antibodies. Among the Sri Lankan sera no strong correlation was found between transmission blocking effects and the presence of antibodies to gamete surface antigens Pfs 230 nor Pfs 48/45 as detected by immunoprecipitation of radio-iodinated gamete proteins; a strong correlation was however, found between the intensity of response to gamete surface antigens by IFA and transmission blocking effects of these sera. It is possible therefore, that the antigens identified by IFA include non-protein moieties and that these may be the targets of transmission blocking antibodies in sera from acute primary infections of P. falciparum.

Animals↗
PubMed1994

Transmission-blocking antibodies against multiple, non-variant target epitopes of the Plasmodium falciparum gamete surface antigen Pfs230 are all complement-fixing.

We have studied the properties of 16 newly derived monoclonal antibodies (MoAbs) against Pfs230, a gamete surface protein of Plasmodium falciparum and a target of transmission-blocking antibodies. All 16 MoAbs recognized Pfs230 by immunoprecipitation from non-ionic detergent extracts of the protein radio-labelled with 125Iodine. The MoAbs also recognized this protein on Western blots under non-reducing conditions but none of them recognized the protein under reducing conditions. Using an immunoradiometric assay the MoAbs appear to define nine different epitope regions. The MoAbs were tested for their ability to lyse extra-cellular female gametes of P. falciparum isolate 3D7. Eight of the MoAbs, all of isotype IgG2a, mediated complement-dependent lysis of the gametes; seven of the MoAbs, all isotype IgG1, failed to lyse the gametes in the presence of active complement. The eight complement-fixing MoAbs mediated almost total suppression of infectivity of gametocytes of P. falciparum 3D7 to mosquitoes; where tested this suppression was mainly complement-dependent. The seven non-complement-fixing MoAbs had no significant effect on the infectivity of gametocytes of P. falciparum 3D7 to mosquitoes. When tested by immunofluorescence the target epitopes of all the MoAbs were conserved in each of the five different isolates of P. falciparum which were tested.

Animals↗
PubMed1994

Human antibody responses to Pfs 230, a sexual stage-specific surface antigen of Plasmodium falciparum: non-responsiveness is a stable phenotype but does not appear to be genetically regulated.

The 230 kD gamete surface protein of the malaria parasite Plasmodium falciparum (Pfs 230) is a target of transmission blocking antibodies. Anti-Pfs 230 antibodies are induced following natural infection with malaria but are not found in all P. falciparum-exposed individuals. In this study we have shown that approximately 40% of malaria-exposed Gambians do not make antibodies to the native Pfs 230 molecule. This phenotype is remarkably stable over time and does not appear to be related to age, malaria exposure or major histocompatibility complex genotype. Comparison of antibody responses in twins indicates that the anti-Pfs 230 response is not strictly genetically controlled, but a high degree of concordance within both dizygous and monozygous twin pairs suggests that factors associated with exposure to malaria in childhood may be important in determining the subsequent immune response.

Adolescent↗
PubMed1994

Resting energy expenditure and nutritional state of patients with increased oxygen cost of breathing due to emphysema, scoliosis and thoracoplasty.

BACKGROUND: Weight loss is a well recognised feature of patients with emphysematous chronic obstructive pulmonary disease (COPD). It has been suggested that this weight loss could be due to a hypermetabolic state resulting from the increased oxygen cost of breathing (OCB). To clarify the relation between resting energy expenditure (REE), nutritional state, and OCB these indices were measured in patients with respiratory impairment and an increased OCB due to COPD, scoliosis, and thoracoplasty. METHODS: Eighteen patients (six COPD, six scoliosis, six thoracoplasty) of mean (SD) age 59.9 (8.6) years (8M, 10F) and six controls (45.5 (9.9) years; 2M, 4F) were studied. OCB was estimated by the addition of dead space to the breathing circuit and REE was measured by indirect calorimetry using a ventilated canopy system. Height, arm span, weight, triceps skin fold thickness (TSF), mid-arm muscle circumference (MAMC), forced expiratory volume in one second (FEV1), and vital capacity (VC) were measured in all study subjects. RESULTS: OCB was elevated in all patient groups (mean 7.0 ml/l) compared with controls (1.9 ml/l). All patients with COPD, four with scoliosis, three with thoracoplasty, and none of the controls were < 90% ideal body weight. Mean (SD) measured REE as % predicted (Harris-Benedict equation) was 103.8 (7.6) in patients with COPD, 105.5 (10.9) in those with scoliosis, 106.3 (6.9) in the thoracoplasty patients, and 103.3 (3.4) in controls. One patient with COPD, two with scoliosis, two with thoracoplasty, but no controls were hypermetabolic (REE > 110% predicted). In all groups there was a negative relation between OCB and lung function (OCB v FEV1 r = -0.83 in COPD, -0.62 in scoliosis, -0.67 in thoracoplasty, and -0.76 in controls). There was no correlation between REE and OCB or MAMC. CONCLUSIONS: In patients with respiratory disease OCB (augmented ventilation) is related to lung function but not to REE. This is evidence against the hypothesis that hypermetabolism due to increased oxygen cost of breathing at rest is the sole or major cause of malnutrition in patients with lung disease.

Aged↗
PubMed1994

Differing effects of airway obstruction on physical work capacity and ventilation in men and women with COPD.

BACKGROUND: Although the natural history of COPD is thought to be well known, studies assessing differences in the onset and course of the disease by gender are surprisingly lacking. This study is a cross-sectional analysis using progressive cycle ergometry exercise testing to assess male and female patients at specific levels of airway obstruction to see if they differ in their exercise capacity and decline in functional capacity. METHODS: The study group included 417 patients with COPD, 55 to 85 years of age, who were compared with 29 controls of similar age; all patients had COPD (FEV1/FVC < 75% predicted) without restrictive disease. Exercise testing in groups based on the level of pulmonary dysfunction defined by FEV1/FVC ratios (mild, 60.5 to 69.5%; moderate, 50.5 to 60.5%; severe < 50.5%) was analyzed. Data were evaluated using the Statistical Analysis System, analyzing gender and degree of airway obstruction and adjusting for any difference in age and peak exercise heart rate (covariate analysis of variance). RESULTS: Men demonstrated progressive reductions of body weight, exercise ability (assessed by the VO2), oxygen pulse (O2P, an indicator of stroke volume), and maximum exercise ventilation (VEmax) even with mild pulmonary dysfunction. Women did not lose weight, and maintained usual exercise ability (VO2, VEmax) and O2P until moderate or severe disease was present. Additional confirmation of a decrease in cardiac function for men with mild airway obstruction (p < 0.0001, controls), but not for women with mild airway disease, was obtained by estimation of cardiac output. Further, women presented with COPD at lower levels of tobacco smoke exposure than men for the entire group (43.8 vs 63.0 pack-years, p < 0.0001) and for each subgroup of disease severity. There were proportionally more life-time female nonsmokers than male nonsmokers with COPD (16 vs 5, p < 0.001). CONCLUSIONS: Male and female patients with COPD differed in their decline of functional aerobic capacity even at equivalent levels of pulmonary dysfunction. One reason for this appeared to be a decrease in the O2P occurring early in the natural history of the disease in the men and not in the women. Although general body de-conditioning may be the cause, heart disease may also be a contributing aspect. The relative delay in the loss of exercise capacity and body mass by the women may relate to predisease differences in physical activity. Women manifested significant lung disease with less cigarette smoking than men. This may be attributable to a different susceptibility to cigarette smoke between the sexes. These results suggest that there appear to be differences in the natural history of COPD in men and women.

Aged↗
PubMed1994

The cost of obesity: the Australian perspective.

Obesity is a known risk factor for a number of diseases with serious mortality and morbidity implications. Thus, obesity is an economic burden to communities, since it reduces quality of life and leads to premature mortality; in addition, healthcare resources are used to manage obesity-related disease. It was estimated that in 1989, management of disease due to obesity (defined as body mass index greater than 30) cost A$395 million. This estimate covers the healthcare costs for the management of obesity, non-insulin-dependent diabetes mellitus (NIDDM), gallstones, hypertension, coronary heart disease (CHD), breast cancer (among postmenopausal women), and colon cancer. As this estimate excludes the costs of some disease attributable to obesity, it is an underestimate of the true costs. Nonetheless, the estimated cost of the management of obesity-related conditions represents 86% of the healthcare costs used for the management of alcohol-related diseases in Australia. Healthcare costs attributable to obesity have not yet been estimated for countries elsewhere in Asia and the Pacific. However, it is acknowledged that obesity is a major problem in the Pacific, with exceptionally high prevalence rates and concomitant high rates of diseases for which obesity is a major risk factor, particularly NIDDM and CHD. It would, therefore, be useful to explore the cost of disease attributable to obesity in healthcare systems in these communities, and the potential for preventive programmes to reduce these costs.

Asia↗
PubMed1994

Transcriptional regulation of c-Jun expression during late G1/S in normal human cells is lost in human tumor cells.

Previous results from our laboratory have identified a second peak in steady state levels of c-jun mRNA (in addition to the immediate early induction) which occurs at the G1/S border in WI-38 normal human diploid fibroblasts. The present studies were undertaken in an attempt to determine (1) the molecular mechanism responsible for the expression of c-jun in late G1/S, (2) the relationship between this second peak of c-jun mRNA expression and the induction of DNA synthesis and (3) whether this cell cycle specific c-jun expression is deregulated in transformed cells. Our results show that the second peak in steady state levels of c-jun mRNA is the result of new transcription during late G1 and not altered stability of the c-jun mRNA transcribed during G1. We also show that this second peak of expression still occurs even when DNA synthesis is inhibited by either hydroxyurea or aphidicolin. Thus, the second peak precedes and is independent of DNA synthesis. Finally, we find that while two other normal human fibroblast cell lines exhibit a second peak of c-jun mRNA during late G1/S, c-jun expression is not cell cycle-regulated but rather is constitutively expressed in a number of distinct transformed cell lines. Since events occurring throughout G1 are known to regulate cell growth, our results suggest that the extent of regulation of c-jun expression during G1 may affect molecular events which ultimately lead to altered growth control as a result of cellular transformation.

Cell Transformation, Neoplastic↗
PubMed1994

Impact of the 1990 contract for general practitioners on night visiting.

BACKGROUND: The 1990 contract for general practitioners extended the hours of eligibility for night visiting claims by 25% and introduced financial incentives to discourage the use of deputizing services. AIM: This study set out to examine the impact of these contract changes on the rate and pattern of night visiting. METHOD: Family health services authority data were used to compare trends in night visiting before and after the introduction of the new contract. Rates were calculated separately for those authorities which might be expected to have a high rate of visiting because of their demographic structure and those that might be expected to have a high rate because of their socioeconomic composition, thus separating out these two sets of factors combined in the Jarman index. RESULTS: Rates of night visiting increased by 33% between 1989 and 1990 while the proportion of visits made by deputies fell by 19%. These changes could not simply be explained either by the extension of eligible hours or the success of financial incentives in changing behaviour in the appropriate direction. It was found that the effect of the new contract was to increase visiting most in family health services authorities with a high proportion of elderly people living alone, that is, where demand would be expected to be higher. In previous years there had been little variation in visiting rates between authorities with a high proportion of those aged 65 years and over living alone and those with a low proportion. The effect of the contract was also to increase rates of visiting most in affluent authorities, that is, where demand would be predicted to be lower. This again marked a sharp break with trends in previous years in that the gap between the high rates in the deprived family health services authorities and lower rates in the most affluent authorities narrowed. CONCLUSION: The 1990 contract achieved the government's policy aims of promoting night visiting by principals and discouraging the use of deputies in its first year. However, the finding that doctors responded more to demand from elderly people and affluent people than from deprived people presents a challenge both for analysis and for policy. It underlines the importance of disaggregating the Jarman index when examining the impact of policy change on local populations and suggests that general practitioners in the most deprived family health services authorities may lack the capacity or the incentive to respond to the changes introduced in the 1990 contract.

Adolescent↗
PubMed1993

Influence of death certificate errors on cancer mortality trends.

BACKGROUND: Evaluation of mortality data is an important tool in assessing both disease time trends and differences in populations. However, the reasons for changes in cancer mortality rates have been controversial. Questions have been raised concerning whether these increases are real or simply the result of changing diagnoses and death certificate reporting. PURPOSE: Our purpose was to determine on the basis of autopsy data if death certificate reporting varies over age, time, and cancer type and to explore the effect of death certificate error on recent cancer mortality trends. METHODS: Data were analyzed from 5886 autopsies collected by the Radiation Effects Research Foundation in Hiroshima, Japan, between 1961 and 1987. Death certificates were linked to autopsy data for analyses. An adjustment factor was calculated as a ratio of the accuracy of these death certificates in identifying cancer (detection rate) and listing cancer (confirmation rate) as the cause of death. This adjustment factor measures bias in mortality rates due to death certification errors and quantifies underestimation and overestimation of cancer mortality rates. RESULTS: Our analyses focused on lymphoma, breast cancer, neoplasms of the brain, multiple myeloma, and melanoma because of reported mortality increases. For these cancers, the adjustment factor decreased significantly (P = .02) over time, implying that death certificate accuracy has improved. This change appears to account for 60% of the observed increase in these cancers during the time period of study. For total cancer, persons 75 years or older have a high adjustment factor but it decreased over time. This decrease suggests an artifactual increase in total cancer mortality rates of about 1% per year for this older group. CONCLUSIONS: The quality of death certificate reporting has generally remained constant for most groups during the period 1961-1987. In the study population, there was a consistent underestimation of total cancer mortality of about 18%. For the five types of cancer studied, there has been less underestimation of cancer mortality since 1976. For some specific cancers and for persons 75 years or older, improvements in death certificate accuracy have occurred over time. These data imply that the total death certificate error rate varies considerably by cancer type, time period, and age at death. IMPLICATIONS: The changes in death certificate reporting for some sites and the elderly appear to have artifactually created increases in cancer mortality rates. These artifacts need to be considered when using mortality data for prevention research and health care planning.

Aged↗
PubMed1993

Transfection of the malaria parasite and expression of firefly luciferase.

The goal of this work is to develop a method for the functional analysis of malaria genes using the method of DNA transfection. We have developed a transient transfection vector by constructing a chimeric gene in which the firefly luciferase gene was inserted in frame into the coding region of the pgs28 gene of Plasmodium gallinaceum. This plasmid DNA was introduced into P. gallinaceum gametes and fertilized zygotes by electroporation, and luciferase expression was assayed after 24 hr. This report of successful introduction and expression of a foreign gene in a malaria parasite demonstrates the feasibility of this approach to developing methods for the functional analysis of parasite genes.

Animals↗
PubMed1993

Uniparental inheritance of the mitochondrial gene cytochrome b in Plasmodium falciparum.

The inheritance of an extrachromosomal 6-kb element has been examined in the human malaria parasite Plasmodium falciparum. A single base pair difference in the cytochrome b gene from the 6-kb element of two different cloned lines of the parasite was identified, and used as a marker in a cross in the mosquito stage of the life cycle. Analysis of 59 individual hybrid oocysts resulting from this cross clearly demonstrated that inheritance of the cytochrome b gene was uniparental. This observation makes it possible to investigate the inheritance and evolution of cytoplasmic traits, including certain forms of drug resistance, in natural populations of this parasite.

Animals↗
PubMed1993

Respiratory dysfunction after uncomplicated cardiopulmonary bypass.

Respiratory dysfunction is a well-recognized complication of cardiac operations. To quantify its current incidence and severity after uncomplicated cardiopulmonary bypass, serial measurements of arterial oxygen tension (PaO2), alveolar-arterial oxygen gradient (AaO2), and percentage pulmonary shunt fraction (%PSF) measured by a noninvasive technique were made in 129 patients (age, 59 +/- 8 years (mean +/- standard deviation) with good left ventricular function (left ventricular end-diastolic pressure < 15 mm Hg) undergoing isolated coronary artery operations (group 1) and 30 patients undergoing general surgical procedures (group 2). Measurements were made before operation and on the first, second, and sixth postoperative days. Seven patients in group 1 who required prolonged ventilation were excluded from further study. In group 1, between the preoperative and second postoperative days, there was a marked fall in PaO2 [89 +/- 11 versus 57 +/- 9 mm Hg; p < 0.001] and a marked increase in the AaO2 gradient [18 +/- 10 versus 50 +/- 11 mm Hg; p < 0.001)] and %PSF [3 +/- 1% versus 19 +/- 6%; p < 0.001)] with only modest improvement by the sixth postoperative day [PaO2, 67 +/- 11 mm Hg; AaO2, 45 +/- 11 mm Hg; %PSF, 15 +/- 4]. There were similar but less severe changes in PaO2 and AaO2 gradients in group 2 patients, with a return to baseline values by day 6.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗