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Biomedical subjects

R Carter

Publications and source records attributed to R Carter.

At least 163 records · Page 9Linked to original sources
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↗
PubMed1993

Insulin binding and degradation by rat liver Kupffer and endothelial cells.

The liver is the major site of insulin metabolism. Previous studies have suggested that hepatocytes were chiefly responsible for this activity, while contributions of Kupffer and other nonparenchymal liver cells remained controversial. In this study, we compared 125I-insulin binding and degradation by rat hepatocytes with insulin binding and degradation by sinusoidal Kupffer and endothelial cells. Kupffer cells were separated from endothelial cells by centrifugal elutriation. Hepatocytes had approximately 3.5 times more insulin binding sites than Kupffer cells and approximately eight times more binding sites than endothelial cells. In addition, wheat germ agglutinin (WGA)-purified solubilized receptors from all three cell types bound insulin in proportions similar to whole cells. Moreover, all three cell types were shown with a ribonuclease (RNase) protection assay to express insulin receptor mRNA. Hepatocytes degraded approximately four times more insulin than Kupffer cells, while endothelial cells degraded only negligible amounts of insulin. Based on morphometric data available in the literature, we estimated that nonparenchymal cells could account for approximately 10% to 15% of hepatic insulin degradation. We concluded that rat hepatocytes, Kupffer cells, and endothelial cells all have specific insulin receptors, and that nonparenchymal cells play a small but significant role in insulin degradation.

Animals↗
PubMed1993

Respiratory dysfunction following cardiopulmonary bypass: verification of a non-invasive technique to measure shunt fraction.

Respiratory dysfunction is a well recognized complication of cardiopulmonary bypass. The size of the pulmonary shunt fraction is the best indicator of respiratory dysfunction but its measurement conventionally requires use of a pulmonary artery catheter to measure mixed venous oxygen content. We compared pulmonary shunt fraction, based on a non-invasive technique using a previously described mathematical model, with shunt fraction measured invasively using a pulmonary artery catheter in 22 patients undergoing elective coronary artery surgery. The mean shunt fraction measured by the invasive technique was 19.6 +/- 2.0 (18.8-20.4)% of cardiac output at 24 h (+/- 1 SD and 90% confidence intervals) and 20.9 +/- 2.9 (19.8-22.0)% of cardiac output at 44 h post-surgery. There was good agreement between the two methods of measurement. The mean difference was 0.21 percentage points with 95% confidence interval -0.01 to 0.43. The limits of agreement (-1.17 to 1.59) are small enough to be confident that the non-invasive method can be used to give the same result as that obtained using a pulmonary artery catheter. The values for shunt fractions obtained by the non-invasive technique were 19.7 +/- 2.3 (18.8-20.6)% of cardiac output at 24 h and 20.7 +/- 2.5 (19.7-21.6)% of cardiac output at 44 h. The non-invasive measurement of the shunt fraction provided us with a simple, practical method for following a further ten patients over an extended period of time where prolonged catheterization is impractical.

Aged↗
PubMed1993

Ploidy and proliferative index in medulloblastoma: useful prognostic factors?

Paraffin sections from 32 patients with primary medulloblastoma were analysed by flow cytometry for DNA ploidy and proliferative index to assess the value of these measurements in determining prognosis. Twenty-seven samples were informative. Of these 27 patients, 8 had had a total resection. The tumors were diploid in 13 patients and aneuploid in 14. Neither ploidy nor S-phase fraction were prognostic factors for survival, even when considered in conjunction with the type of surgery performed. This is in contrast to other published data, emphasising the need for large multicentre studies of biological prognostic factors in this rare tumour.

Adolescent↗
PubMed1993

Frequency of cross-fertilization in the human malaria parasite Plasmodium falciparum.

Two clones of the human malaria parasite Plasmodium falciparum, denoted 3D7 and HB3, were grown in vitro under conditions permitting the development of gametocytes. The two clones differ in their allelic forms of two antigen genes MSP1 and MSP2. The alleles can be distinguished as size differences of polymerase chain reaction (PCR) amplified fragments of repetitive regions of each gene. Mosquitoes (Anopheles stephensi) were fed on a mixture of these gametocytes. A total of 128 oocysts was isolated from the midguts of infected mosquitoes from 9 crossing experiments between the clones. DNA extracted from these oocysts was amplified by PCR. Oocysts which contained both alleles of each gene (MSP1 and MSP2) had developed from heterozygotes produced by cross-fertilization events between 3D7 and HB3 gametes. The remaining oocysts contained single alleles of each gene, in parent clone combinations, and these had developed from homozygotes formed by self-fertilizations. The results suggest that gametes in the original mixture fed to mosquitoes had undergone random mating.

Alleles↗
PubMed1993

Cost-effectiveness of mammographic screening in Australia.

The purpose of this research was to estimate the cost-effectiveness of mammographic screening to supplement the results of the National Evaluation of Breast Cancer Screening which identified the mortality benefit as the most sensitive parameter. This appraisal used a different computer model, MISCAN, which models the effects of introducing a national screening program into a previously unscreened population, rather than basing estimates on the assumption of a fully established program. For the 40 to 49 age group a mortality reduction of 8 per cent was assumed, rather than the 30 per cent estimate utilised in the National Evaluation. The revised estimate is based on the two Swedish trials (Malmo and WE). New estimates for treatment costs were also incorporated into the MISCAN model. The cost-effectiveness of the policy recommended in the National Evaluation Report, $11,000 per life year saved with two-yearly screening of women over 40, is estimated by the MISCAN model to be $20,300. These differences arise partly from the difference in mortality effects for the 40 to 49 age group, but also from differences inherent in the steady-state and dynamic population approaches to modelling premature deaths averted. The MISCAN results confirm that screening for women over 50 is more cost-effective than screening women under 50. Screening all women aged 50 to 69 every two to three years is reasonable value for money. For women aged 40 to 49 the mortality benefit and cost-effectiveness is less clear, and it would be prudent to allow screening in this group until further evidence is available.

Adult↗
PubMed1993

Use of a combined oxygen and carbon dioxide transcutaneous electrode in the estimation of gas exchange during exercise.

BACKGROUND: Accurate and reliable measurement of gas exchange during exercise has traditionally involved arterial cannulation. Non-invasive devices to estimate arterial oxygen (O2) and carbon dioxide (CO2) tensions are now available. A method has been devised and evaluated for measuring gas exchange during exercise with a combined transcutaneous O2 and CO2 electrode. METHODS: Symptom limited exercise tests were carried out in 24 patients reporting effort intolerance and breathlessness. Exercise testing was performed by bicycle ergometry with a specifically designed protocol involving gradual two minute workload increments. Arterial O2 and CO2 tensions were measured at rest and during exercise by direct blood sampling from an indwelling arterial cannula and a combined transcutaneous electrode heated to 45 degrees C. The transcutaneous system was calibrated against values obtained by direct arterial sampling before each test. RESULTS: In all tests the trend of gas exchange measured by the transcutaneous system was true to the trend measured from direct arterial sampling. In the 140 measurements the mean difference between the O2 tensions estimated by direct sampling and the transcutaneous method was 0.08 kPa (0.62 mm Hg, limits of agreement 4.42 and -3.38 mm Hg). The mean difference between the methods for CO2 was 0.02 kPa (0.22 mm Hg, limits of agreement 2.20 and -1.70 mm Hg). There was no morbidity associated with the use of the transcutaneous electrode heated to 45 degrees C. CONCLUSIONS: A combined transcutaneous O2 and CO2 electrode heated to 45 degrees C can be used to provide a reliable estimate of gas exchange during gradual incremental exercise in adults.

Adult↗
PubMed1993

Altered exercise gas exchange and cardiac function in patients with mild chronic obstructive pulmonary disease.

Patients with advanced COPD have significantly reduced gas exchange and pulmonary function; however, little is known regarding physical work capacity and exercise gas exchange in patients with mild COPD. A total of 39 individuals (20 men and 19 women) without evidence of COPD (controls) and 51 individuals (29 men and 22 women) with mild COPD (FEV1 > or = 60 percent of predicted; and ratio of FEV1 over forced vital capacity of 60 to 70 percent) were tested to determine resting pulmonary function and resting and peak exercise gas exchange in response to progressive maximal cycle ergometer testing. In general, those with mild COPD had similar smoking histories and essentially equivalent resting gas exchange studies as compared to the controls. Measured maximal oxygen consumption was less in both the male (p < 0.003) and the female patients (p < 0.001). This was due, in part, to a lower maximal ventilation in the men with obstruction (p < 0.04), resulting from a significant reduction in tidal volume (p < 0.05). Women presented with similar decreases in maximal ventilation (p < 0.04) and maximal tidal volume (p < 0.01), while no difference in maximal respiratory rate was noted in either group (p > 0.05). Breathing reserve was 32 percent and 53 percent less for the male and female patients with obstruction than for controls. Maximal heart rates were less in the individuals with obstruction, where they reached 93 percent (p < 0.02) and 96 percent (p < 0.003) of the age- and sex-specific maximal heart rates for men and women as compared to 101 percent and 99 percent obtained in the controls. Achieved absolute work loads for men and women (in kilogram.meters per minute) were lower in the groups with obstruction (p < 0.002 and 0.0003) as well. These results demonstrate that work capacity and gas exchange are significantly decreased in individuals with even mild COPD. The reduction in functional work capacity is secondary to a loss of pulmonary function, as well as chronic deconditioning. Increased dyspnea may be responsible for the premature cessation of exercise observed in patients with mild COPD. Thus, early intervention with exercise training may be warranted to counter the deleterious effects of deconditioning and declining pulmonary function in patients with mild COPD.

Aged↗
PubMed1993

Plasmodium vivax malaria in Sri Lanka: transmission, disease and immunity.

We have established a study site in a malaria endemic region around Kataragama in the south of Sri Lanka. A population of about 3,000 individuals in a group of villages around Kataragama have been provided with access to a small field clinic enabling us to monitor aspects of malarial infection under conditions of natural transmission. At the present time, both Plasmodium falciparum and Plasmodium vivax are prevalent to a similar degree although prior to about five years ago P. falciparum had been virtually absent for most of the previous ten years.

Animals↗
PubMed1993

Reinduction of remission of chronic myeloid leukemia by donor leukocyte transfusion following relapse after bone marrow transplantation: recovery complicated by initial pancytopenia and late dermatomyositis.

A significant proportion of patients relapse after allogeneic BMT for CML. These relapses have been treated by induction of a graft-versus-leukemia effect by transfusing donor leukocytes. We have treated a 27-year-old woman with interferon and donor leukocyte transfusion and a complete haematological and cytogenetic remission was obtained coincident with the onset of GVHD. Her course was complicated by prolonged and profound pancytopenia which was fully reversed by the administration of rGM-CSF. She remains in CR with mild dermatomyositis due to chronic GVHD 17 months after the procedure.

Adult↗
PubMed1993

Cytokine-mediated inactivation of malarial gametocytes is dependent on the presence of white blood cells and involves reactive nitrogen intermediates.

Supernatants of human peripheral blood mononuclear cells (PBMC) incubated for 24 hr in the presence of extracts of freeze-thawed blood stage parasites of Plasmodium vivax or P. falciparum mediate inactivation of gametocytes of either species when incubated in vitro with whole human blood cells. Cultured P. falciparum gametocytes incubated with these malaria extract-stimulated PBMC supernatants in the presence of human blood from which white blood cells (WBC) had been removed were not inactivated. Thus the effects of the PBMC supernatants on gametocyte infectivity were dependent upon the presence of WBC. The suppressive effects mediated in the presence of WBC could be partially reversed in the presence of concentrations of 1 mM or higher of the L-arginine analogue NGL-monomethyl arginine acetate (L-NMMA). Our results indicate that the effects of WBC in inactivating gametocytes are due, at least in part, to a mechanism involving an L-arginine-dependent pathway. Previous studies have shown that the mediators of gametocyte inactivation in the stimulated PBMC supernatants comprised tumour necrosis factor (TNF) acting in conjunction with unidentified, but essential, 'complementary factors'. In the present study we show that these mediators, TNF and complementary factors, affect gametocytes indirectly through their interaction with WBC.

Animals↗
PubMed1992

Dynamics of fever and serum levels of tumor necrosis factor are closely associated during clinical paroxysms in Plasmodium vivax malaria.

Paroxysms are sharp episodes of high fever accompanied by chills and rigors that occur periodically, once in every 48 hr in Plasmodium vivax infections. We have measured the changing levels of serum tumor necrosis factor (TNF) during paroxysms in non-immune patients infected with P. vivax malaria. The changes in TNF levels closely paralleled the rise and fall in temperature during the paroxysms but tended to precede them by 30-60 min. These observations suggest that the rise and fall in temperature during P. vivax paroxysm may be directly related to the periodic changes in TNF levels induced during these infections. The peak TNF levels reached during P. vivax infections were much higher than even those which have been recorded during severe and fatal P. falciparum infections in which TNF has been postulated to contribute to the severe manifestations of this disease.

Activity Cycles↗
PubMed1992

Laser recanalization versus endoscopic intubation in the palliation of malignant dysphagia: a randomized prospective study.

Forty patients with histologically confirmed malignant dysphagia were randomized to either endoscopic intubation or laser recanalization. Age, sex, tumour histology and site were evenly distributed between the groups. Results were analysed on an 'intention to treat' basis. All patients treated by laser achieved patency; there was one failed intubation. The best swallowing grade achieved was significantly better with laser recanalization (median 4 (range 3-4)) than with intubation (median 3 (range 2-4)) (P < 0.001). The median survival was 21.5 (range 4-62) weeks in the group receiving laser treatment, compared with 14.5 (range 7-102) weeks in the intubated group (P = 0.09). The median inpatient stay as a proportion of survival time was 14 per cent in the group receiving laser treatment compared with 15 per cent in the intubated group (P > 0.05). The median weight loss was less in the laser-treated patients (2.0 (range 2-8) versus 3.0 (range 0-10) kg, P = 0.04). These results indicate that laser recanalization provides better palliation of dysphagia than does intubation, but this is not reflected in an improvement in survival time.

Adult↗
PubMed1992

Gene inactivation of Pf11-1 of Plasmodium falciparum by chromosome breakage and healing: identification of a gametocyte-specific protein with a potential role in gametogenesis.

We report the identification of the product of the Plasmodium falciparum Pf11-1 gene and demonstrate that it is a gametocyte-specific protein that has a potential role in the rupture of the host erythrocyte and emergence of the gametes (gametogenesis). The Pf11-1 gene is a large locus (30 kb) whose sequence predicts a glutamic acid-rich polypeptide. Our identification of the Pf11-1 gene product as gametocyte specific was greatly facilitated by the isolation of a mutant parasite clone in which greater than 90% of the Pf11-1 gene was deleted. Molecular analysis of the mutant locus suggests that the underlying genetic mechanism is chromosome breakage and subsequent healing by the addition of telomere repeats. PCR-based analysis showed that similar DNA rearrangements occur commonly in small subpopulations of most laboratory strains, suggesting that the Pf11-1 locus represents a fragile chromosome region. Northern blot analysis demonstrates that a large Pf11-1 gene-specific transcript (much greater than 10 kb) is present in gametocytes but not in asexual blood stage parasites. The Pf11-1 protein was localized by electron microscopy to granules in the cytoplasm of gametocytes adjacent to the membrane of the parasitophorous vacuole. Following in vitro stimulation of gametogenesis, the Pf11-1 protein was found in the membrane of lysed erythrocytes, suggesting a role for Pf11-1 in erythrocyte rupture within the mosquito gut.

Animals↗
PubMed1992

Protein-DNA interactions at the H4-site III upstream transcriptional element of a cell cycle regulated histone H4 gene: differences in normal versus tumor cells.

Upstream sequences of the H4 histone gene FO108 located between nt -418 to -213 are stimulatory for in vivo transcription. This domain contains one protein/DNA interaction site (H4-Site III) that binds factor H4UA-1. Based on methylation interference, copper-phenanthroline protection, and competition assays, we show that H4UA-1 interacts with sequences between nt -345 to -332 containing an element displaying sequence-similarity with the thyroid hormone response element (TRE). Using gel retardation assays, we also demonstrate that H4UA-1 binding activity is abolished at low concentrations of Zn2+ (0.75 mM), a characteristic shared with the thyroid hormone (TH) receptor DNA binding protein. Interestingly, phosphatase-treatment of nuclear proteins inhibits formation of the H4UA-1 protein/DNA complex, although a complex with higher mobility (H4UA-1b) can be detected; both complexes share identical protein-DNA contacts and competition behaviors. These findings suggest that phosphorylation may be involved in the regulation of H4-Site III protein/DNA interactions by directly altering protein/protein associations. H4-Site III interactions were examined in several cell culture systems during cell growth and differentiation. We find that H4UA-1 binding activity is present during the cell cycle of both normal diploid and transformed cells. However, during differentiation of normal diploid rat calvarial osteoblasts, we observe a selective loss of the H4UA-1/H4-Site III interaction, concomitant with an increase of the H4UA-1b/H4-Site III complex, indicating modifications in the heteromeric nature of protein/DNA interactions during downregulation of transcription at the cessation of proliferation. Transformed cells have elevated levels of H4UA-1, whereas H4UA-1b is predominantly present in normal diploid cells; this alteration in the ratio of H4UA-1 and H4UA-1b binding activities may reflect deregulation of H4-Site III interactions in transformed cells. We propose that H4-Site III interactions may contribute, together with protein/DNA interactions at proximal regulatory sequences, in determining the level of H4-FO108 histone gene transcription.

Base Sequence↗
PubMed1992

Assessment of costs and benefits in the introduction of digital radiology systems.

A discussion is presented of cost and benefit considerations in establishing digital radiology systems and an approach to assessment of such factors. Costs of digital radiology systems need to be defined and compared appropriately. Assessments should consider capital and replacement costs, but also less tangible items such as effects on staff and training requirements, hospital infrastructure, productivity, file integrity and diagnostic accuracy. Benefits of digital radiology systems could be assessed using cost-benefit and social audit analysis techniques, yielding a matrix of monetary items and also summaries of non-monetary benefits. Such analysis would define the major participants in the digital radiology process and the nature of their interests and assess the costs and benefits impacting on each of them. Economic evaluation of digital radiology to date has focused on the cost side of the appraisal. Analyses of benefits of digital radiology systems have been limited and have given inconclusive results. There is a need for better definition of comparative costs and benefits to inform interested parties, including hospital staff and health policy makers. Such economic analysis is an important way of asking the right questions about resource usage and could usually be carried out in a pilot setting before there is wider diffusion of digital radiology systems.

Cost-Benefit Analysis↗