Biomedical subjects

S P Graham

Publications and source records attributed to S P Graham.

14 recordsLinked to original sources

PubMed2001

Anticoagulation and heart failure.

There are no clear data regarding whether to use warfarin, aspirin, or no therapy in patients with left ventricular systolic dysfunction. Aspirin use is widespread in patients with vascular disease but it can decrease renal blood flow in low output states. Warfarin may be used in patients with advancing heart failure due to the perceived risk of in situ thromboembolism. However, we know that ejection fraction and symptom class do not always match and that the regulation of warfarin dosing is more difficult in worsening heart failure. Drug use must be individualized, based on knowledge of underlying heart failure etiology, functional class, drug side effects, and renal function. We await ongoing studies to elucidate the differential effects of these drugs on global outcome as well as on the mechanisms by which they achieve their results.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed2000

Onchocerca volvulus: comparative analysis of antibody responses to recombinant antigens in two animal models of onchocerciasis.

Experimental infections of chimpanzees with Onchocerca volvulus and cattle with Onchocerca ochengi provide model systems for research in human onchocerciasis. These infections share many similarities from the standpoint of parasite biology, but little is known about the comparability of immune responses in the two systems. To make a direct comparison between the models in terms of immune responsiveness to defined parasite products, three recombinant antigens of O. volvulus (Ov7, Ov103, and B20) were used to analyze the kinetics of antibody production following experimental infection. Each of the antigens was derived from adult cDNA libraries following immunoscreening with sera from chimpanzees (Ov7, Ov103) or cattle (B20). All chimpanzees (n = 12) and cattle (n = 8) displayed responses to Ov7 and Ov103, and all cattle, but only 33% of chimpanzees, showed responses to B20. The dynamics of the response to individual antigens showed further similarities between the chimpanzees and the cattle, with responses to Ov7 and Ov103 peaking after, and B20 before, the onset of patent infections. We conclude that there is good preliminary evidence of concordance in the kinetics of serological responses in the two models. However, individual antigens many be more or less immunogenic in the two systems, making it inadvisable to extrapolate between models concerning the relative immunodominance of specific parasite products.

Animals↗

PubMed2000

Onchocerca ochengi infections in cattle as a model for human onchocerciasis: recent developments.

The bovine parasite Onchocerca ochengi is a nodule-dwelling filarial nematode, closely related to O. volvulus, the causal agent of human River Blindness, and, sharing with it, the same vector. This brief review, based on a presentation at the BSP Autumn Symposium 1999, describes recent work supported by the WHO Drug Development Research Macrofil programme and the Edna McConnell Clark Foundation vaccine development programme, to research the chemotherapy and immunology of onchocerciasis utilising this model system, with experimental infections in Liverpool and field infections in northern Cameroon. In a series of chemotherapeutic trials involving 10 compounds in 20 treatment regimes, the comparability of drug efficacy against O. ochengi with that described against O. volvulus has been demonstrated. Repeated, long-term treatment with oxytetracycline has been shown to be macrofilaricidal and the effect is hypothesized to be related to action on Wolbachia endobacteria, abundant in O. ochengi. Avermectins/milbemycins are not macrofilaricidal (even in high and repeated long-term treatments) but induce sustained abrogation of embryogenesis. In prospective, field exposure experiments with naive calves, prophylactic treatments with ivermectin and moxidectin prevented the development of adult worm infection, raising the possibility that drug-attenuated larval challenge infections may induce immunity. Putatively immune adult cattle exist in endemically exposed populations, and these have been shown to be significantly less susceptible to challenge than age-matched naive controls, whereas radically drug-cured, previously patently-infected cattle were not. Experimental infections with O. ochengi have revealed the kinetics of the immune response in relation to parasite development and demonstrate analogous responses to those reported in O. volvulus infection in humans and chimpanzees. In an immunization experiment with irradiated L3 larvae, cattle were significantly protected against experimental challenge--the first such demonstration of the experimental induction of immunity in a natural Onchocerca host-parasite system. Taken collectively, these studies not only demonstrate the similarity between the host-parasite relationships of O. ochengi in cattle and O. volvulus in humans, but promise to advance options for the control of human onchocerciasis.

Animals↗

PubMed2000

Distinct response kinetics of gamma interferon and interleukin-4 in bovine tuberculosis.

This study shows that gamma interferon (IFN-gamma) and interleukin-4 (IL-4) cytokine responses are produced by peripheral blood cells in cattle infected with Mycobacterium bovis. The different kinetics of the IFN-gamma and IL-4 responses to bovine tuberculin and to ESAT-6 following experimental intratracheal infection with M. bovis are described. An early increase in IFN-gamma was observed that was maintained throughout the period studied. In contrast, the IL-4 response was delayed and confined to a peak of activity lasting 6 to 8 weeks. Interestingly, an experimental challenge of cattle with a lower dose of M. bovis which did not result in the development of lesions, positive DTH skin test, or substantial IFN-gamma responses nevertheless generated strong specific IL-4 responses. Investigation of naturally infected M. bovis field reactors showed increased IFN-gamma and IL-4 responses compared to uninfected cattle and that both of these cytokines were equally able to differentiate infected from uninfected animals. The magnitude of the M. bovis-induced IL-4 responses were found to be similar to the antigen-specific IL-4 responses of cattle infected with the parasitic nematode Onchocerca ochengi, further supporting the presence of this type 2 cytokine in bovine tuberculosis.

Animals↗

PubMed1999

Patterns of Onchocerca volvulus recombinant antigen recognition in a bovine model of onchocerciasis.

The antibody responses of 8 cattle experimentally infected with Onchocerca ochengi to 18 recombinant O. volvulus antigens were measured by ELISA. In addition to establishing antigenic cross-reactivity between the species, the dynamics of antigen-specific responses were examined to assess how the recognition of the antigens compared to the known stage-specificity of expression. Six cattle responded to all of the antigens and 2 animals responded to all but 1. The dynamics of the recognition of 4 antigens (B20, MOv-2, MOv-14 and OvNHR2 02E1) were characterized by rapid seroconversion following infection. Antibody levels to 2 antigens (Ov7 and OvALT-1) increased gradually over the course of infection. Antibody levels to 4 antigens (OvTPX-2, OvL3Chitinase, Ov103 and Ov9m) reached maximum levels coincident with the onset of patency. The levels to 3 antigens (OvProalf C50, OvAldolase, Ov39) varied little over the course of infection. Responses to antigens with functional similarities (OvSOD1, OvSOD2 and OvSOD3 or OvGST1 and OvGST2) showed comparable temporal profiles. This study demonstrates the high degree of immunological cross-reactivity between the antigens of O. volvulus and O. ochengi. The immunogenicity of antigens varied over the course of infection in an antigen-specific manner, which not always reflected developmentally regulated expression of the corresponding gene, possibly owing to cross-reactive epitopes on distinct parasite products.

Animals↗

PubMed1996

Comparison of long-term patency of "horseshoe" saphenous vein grafts with and without valves.

OBJECTIVE: The paper analyzes the long-term patency of valveless and valvular limbs of reversed saphenous veins. METHODS: Between 1983 and 1988, 335 patients underwent isolated coronary artery bypass grafting (CABG) with 1,329 grafts. Eighty-three patients had follow-up angiography over 8-12 years. The side-to-side saphenous vein to aortic "horseshoe" anastomosis was created just before the first valve from the ankle (naturally a valveless portion). The valveless (ankle end) was depicted in every case. These patients with angiography were similar to 252 patients without angiography in terms of age, gender, number of grafts, diseases vessels, single (A) and sequential (B) grafts and actuarial survival. In the 83 patients, graft patency was 75%. Overall patency was the same in B versus A grafts (76% versus 74.6%); valveless patency (78.7%) was slightly better than valvular patency (73.3%). RESULTS: In patients with B grafts (88.6%) valveless patency was significantly better than valvular patency (71.9%) (P < 0.02). The patency of B-valveless to the left coronary bed was also better, (86.8% versus B-valvular 70.5%, P < 0.04). Attrition of the B-valveless and B-valvular grafts was similar up to 8 years, but by the 12th year it had become significantly different (P < 0.05). The 12-year actuarial survival rate of the patients was 87.7%. CONCLUSIONS: We recommended the use of valveless vein segments when possible.

Actuarial Analysis↗

PubMed1995

Recombinant ovine interferon gamma inhibits the multiplication of Chlamydia psittaci in ovine cells.

The local production of interferon-gamma (IFN-gamma) in sheep in response to Chlamydia psittaci was measured by cannulation of the efferent lymph duct draining the site of challenge inoculation. Peak production of IFN-gamma (256 U/ml) was detected 24 h after challenge. Based on these physiological data, functional studies were carried out in vitro to determine the effect of recombinant ovine (rOv) IFN-gamma on the multiplication of C. psittaci in ovine fibroblasts. IFN-gamma inhibited the multiplication of C. psittaci in ovine cells over a range of concentrations (250 U/ml to 2.5 U/ml) in a dose-dependent manner. The inhibition of chlamydial multiplication was most pronounced when cells were treated with rOvIFN-gamma for 24 h before infection. The addition of exogenous L-tryptophan (500 micrograms/ml) to cultures within 48th of infection abrogated the anti-chlamydial effect of rOvIFN-gamma thus suggesting that tryptophan deprivation is an anti-chlamydial mechanism induced by rOvIFN-gamma in these ovine cells.

Animals↗

PubMed1991

Comparison of angiographic findings and demographic variables in patients with coronary artery disease presenting with acute pulmonary edema versus those presenting with chest pain.

One hundred nineteen patients admitted to the coronary care unit with pulmonary edema were retrospectively reviewed to identify the demographic characteristics and underlying cardiac disorders of this population. The patients with pulmonary edema were compared with 119 patients admitted to the coronary care unit with chest pain. Cardiac catheterization in 71 patients with pulmonary edema and 93 with chest pain showed left main and 3-vessel coronary artery diseases to be equally common in both groups, although anginal pain was infrequent in patients with pulmonary edema (n = 28, 24%). Left ventricular function was reduced in the patients with pulmonary edema compared with those with chest pain (mean ejection fraction 42 vs 59%; p less than 0.001). More patients with pulmonary edema were black, and had diabetes and preexisting hypertension than those with chest pain. The results of cardiac catheterization were the same for black and white patients with pulmonary edema. In conclusion, patients with pulmonary edema have a high incidence of cardiac disease, and pulmonary edema may be 1 manifestation of silent myocardial ischemia. Important demographic differences exist between patients admitted with pulmonary edema and those who present with chest pain.

Adult↗

PubMed1991

Percutaneous intravascular ultrasound imaging: validation of a real-time synthetic aperture array catheter.

This study was designed to validate the dimensional accuracy and ability to characterize atherosclerotic vessel morphology of a new percutaneously passed ultrasound catheter. The 5.5F catheter used for this study has a synthetic aperture array transducer providing a radial field of view perpendicular to the catheter and can be passed over a standard 0.014-in guide wire. Initial in vitro studies were performed to assess accuracy of dimensional and morphologic information. In vitro images of fixed human vessels demonstrated good boundary definition, and dimensional measurements were closely correlated with histological samples (luminal area, r = .97; maximal lumen diameter, r = .95; maximal wall thickness, r = .83). Morphological subtypes were also closely correlated, with increasing severity of histological atherosclerosis characterized by predictable changes in the ultrasound images. Subsequently, the catheter was passed percutaneously in 28 patients to obtain images of coronary (n = 20) and pelvic (n = 12) vessels. Ultrasound images were compared with simultaneous digital angiograms. Correlation between ultrasonic and angiographic estimations of vessel diameters was good (r = .92). We conclude that intravascular ultrasound imaging will be useful for dimensional and morphological characterization of vascular disease, for the study of regression or progression of atherosclerosis, and, potentially, for guidance of therapeutic interventions such as atherectomy and angioplasty.

Adult↗

PubMed1990

Estimation of coronary flow reserve by intracoronary Doppler flow probes and digital angiography.

This prospective study investigated two different methods used clinically to estimate coronary flow reserve during cardiac catheterization. First, the relationship between simultaneous digital angiography and intracoronary Doppler velocity measurements was determined in 61 patients. The correlation coefficient for 233 simultaneous pairs of papaverine-induced flow reserve was 0.70 (Doppler = 0.41 digital + 0.93, P less than 0.0001). Repeated basal flow determinations showed little variability (Doppler: 2 +/- 5% (mean +/- 95% confidence intervals); digital: 3 +/- 10%). Repeated hyperemic flow estimates by the Doppler technique were more reproducible (10 +/- 2%) than those by the digital method (26 +/- 6%). Second, estimates of coronary flow reserve by side-mounted and end-mounted Doppler catheters were compared in vitro and in patients. In vitro measurement of blood velocity was linear for both catheter designs and was highly correlated with volume flow determined by electromagnetic flow meter (r = 0.99 side-mounted; r = 0.96 end-mounted). In patients (n = 20), average coronary flow reserve for the side-mounted Doppler crystal was 2.64 +/- 0.15 and for the end-mounted Doppler crystal was 2.40 +/- 0.14 (P less than 0.02). When flow reserve was determined twice for each catheter, there was greater variability in repeated measurements using the side-mounted Doppler crystal (21 +/- 10%, n = 14) than using the end-mounted Doppler crystal (12 +/- 4%, n = 32).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1990

Percutaneous intracoronary ultrasound imaging: initial applications in patients.

This study was designed to evaluate the feasibility and potential clinical utility of intracoronary ultrasound imaging in patients using a 5.5 F synthetic aperture array, over-a-wire ultrasound catheter. Thirty patients underwent percutaneous intracoronary (n = 22) or peripheral (n = 8) ultrasound imaging at the time of cardiac catheterization. Ultrasound images were compared to simultaneous digital angiograms. Correlation between ultrasonic and angiographic estimation of coronary diameters was good (r = 0.80). Morphological analysis of ultrasound images obtained in patients revealed a pattern consistent with mild-to-minimal atherosclerosis, as defined by prior in vitro studies. In 15 patients, imaging was performed during intracoronary infusion of vasoactive medications (papaverine 15 mg, nitroglycerine 100 mugm, and acetylcholine 2 x 10 -5 or 2 x 10 -6M). These medications were also infused during continuous intracoronary Doppler catheter monitoring of velocity and pressure, thus allowing calculation of volume flow and coronary resistance indices. Serial determination of ultrasound-derived epicardial vessel cross-sectional area demonstrated no change (-1 +/- 1%) after papaverine, an 8 +/- 2% increase after nitroglycerine, and a 9 +/- 3% decrease after acetylcholine. Calculated resistance fell 53 +/- 4% after acetylcholine and 60 +/- 3% after papaverine. Preliminary in vitro studies using a combination angioplasty balloon/ultrasound catheter demonstrated the ability to visualize vessel dilation in real time. We conclude that intravascular ultrasound imaging will be useful for dimensional and morphological characterization of vascular disease, for beat-to-beat monitoring of vasomotion, and potentially as a real-time adjunct to therapeutic interventions.

Adult↗

PubMed1989

Accelerated aortic stenosis.

A 56 year-old woman presented in congestive heart failure 4 weeks after cardiac catheterization. By repeat catheterization, the mean gradient across the native aortic valve had progressed from 10 mm Hg to 51 mm Hg. In patients with calcific-degenerative valvular disease, the rapid worsening of aortic stenosis should be considered in the differential diagnosis of recurrent heart failure.

Aortic Valve Stenosis↗

PubMed1989

Clinical percutaneous imaging of coronary anatomy using an over-the-wire ultrasound catheter system.

This manuscript describes initial applications of a unique new intravascular ultrasound imaging catheter. This 5.5F catheter uses an over-the-wire design and incorporates a phased array transducer at its tip. There are no moving parts. A 360 degree image is produced perpendicular to the catheter axis using a 20 MHz center frequency. A dedicated minicomputer is used for initial image processing, as well as enhancement and analysis. Initial studies using phantoms demonstrated excellent accuracy for linear dimensions (r = 0.99, range 3.0 to 7.6 mm, image = 1.0 phantom + 0.1). Serial imaging of the same arterial segment in vitro showed good reproducibility (coefficients of variance 2.5-5.2%). Likewise, intra- and inter-observer variability in image analysis was minimal (r = 0.92-0.99). Initial in vivo studies were performed in dogs. The catheter was easily passed over a wire into mesenteric, cerebral and coronary vessels without evidence of significant vessel trauma. Subsequently, 20 patients had percutaneous coronary imaging performed during cardiac catheterization. Cardiac motion was rarely a problem and acceptable images were obtained in all but two patients. Areas of calcification, mild stenoses, branching vessels and graft atherosclerosis could be identified. We conclude that intracoronary ultrasound imaging will be useful for assessing vascular pathology, for studying both rapid change in vessel size as well as chronic progression or regression of atherosclerosis, and for assisting with new therapeutic interventions.

Angioplasty, Balloon↗

PubMed1980

Effect of chemical sympathectomy on myocardial cell division in the newborn rat.

Myocardial chemical sympathectomy was achieved by daily SC injection of 100 micrograms/g body weight of 6-OH-dopamine to each of 239 Holtzman newborn rat pups for the first seven days of life. Effective sympathectomy was verified by identifying a decrease in ventricular myocardial norepinephrine concentrations to 31% +/- 12 S.E. of control at 20 days of age. Activity of DNA polymerase was used to indicate the extent of myocardial cell division. Beginning at eight days of age, DNA polymerase activity was increased in the sympathectomized pups relative to control. The DNA polymerase activity was highest relative to control at 16 days (235% +/- 31 S.E.) and remained elevated beyond 20 days (188% +/- 30 of control). The DNA polymerase data was analyzed by covariance and was significantly greater in the 6-OH-dopamine rat pups (P < 0.001).

Animals↗