Search PubMed⌕ Search

Biomedical subjects

G F Mitchell

Publications and source records attributed to G F Mitchell.

At least 37 records · Page 2Linked to original sources
PubMed1997

Comparison of techniques for measuring pulse-wave velocity in the rat.

We evaluated methods for measuring average and regional pulse-wave velocity along the full length of the aorta in 18-mo-old ether-anesthetized male spontaneously hypertensive rats. Catheter-tip manometers were placed in the ascending and descending thoracic aorta via the right carotid and left femoral arteries, respectively. As the distal catheter was withdrawn at 1-cm intervals, the relationship between the distal catheter insertion distance and distance between transducers was determined from the intercept of the insertion distance vs. transmission delay regression line. Methods that assessed the foot-to-foot time delay between pressures accurately predicted the separation between catheters (measured distance of 1.43 cm; intercept of 1.40 +/- 0.5 cm; P = not significant) were highly reproducible (coefficient of variation of 2.3% for repeated measurements) and showed minimal variability (range 509 +/- 30 to 600 +/- 29 cm/s) along the full length of the aorta. Methods that made use of the pressure-pressure transfer function were spatially (range of values along the aorta 367 +/- 17 to 722 +/- 39 cm/s) and temporally more variable, especially during vasoconstriction with methoxamine, due to the effects of reflected waves.

Animals↗
PubMed1996

Equipotent antihypertensive agents variously affect pulsatile hemodynamics and regression of cardiac hypertrophy in spontaneously hypertensive rats.

BACKGROUND: Converting enzyme inhibitors are more effective than arteriolar vasodilators at regressing left ventricular hypertrophy in spontaneously hypertensive rats (SHR), possibly because of nonhemodynamic factors. However, the pulsatile component of hemodynamic load has not been evaluated in this model. METHODS AND RESULTS: We measured pulsatile hemodynamics in 18-month-old male SHR after 6 months of therapy with either zofenopril (Z), hydralazine (H), or water (W). Hydralazine and zofenopril reduced mean arterial pressure comparably (W, 106 +/- 23 versus H, 81 +/- 12 versus Z, 84 +/- 18 mm Hg, P = .002) yet had a differential effect on the ratio of left ventricular weight to body weight (W, 3.9 +/- 0.5 versus H, 3.3 +/- 0.4 versus Z, 2.4 +/- 0.2 g/kg, P < .005). Hydralazine-treated SHR had increased characteristic impedance (P = .0011) and a persistently low ratio of the reflected-wave transit time to left ventricular ejection time (P < .001), which contributed to early and late systolic loading, respectively, of the left ventricle. Consequently, only zofenopril-treated SHR had a significant reduction in left ventricular systolic force-time integral (P = .02), a measure of total ventricular load. There were no differences in systolic stress-time integral, suggesting that mass was appropriate to load when all elements of steady-flow and pulsatile load were considered. CONCLUSIONS: A blunted reduction in total left ventricular load, due to increased pulsatile load in SHR treated with hydralazine, provided a hemodynamic basis for the differential regression of hypertrophy in this model of genetic hypertension.

Animals↗
PubMed1996

ISCOMs (immunostimulating complexes): the first decade.

A little over a decade ago, novel immunostimulating complexes (ISCOMs) were described. This review examines the position and progress that ISCOM technology has achieved in the fields of vaccine research and medicine over this period. Much of the work on ISCOMs has remained in the area of vaccine research where there is still an urgent need for improved adjuvants to help combat important diseases such as AIDS, malaria and influenza. Currently the only widely licensed adjuvants for human use are the aluminium salts, but with the trend towards highly purified subunit vaccines, which are inherently less immunogenic than some of the older vaccines, potent adjuvants capable of promoting specific immune responses are required. ISCOMs are one such technology that offers many of these requirements and as their use in vaccines enters its second decade clinical trials are commencing that will establish whether these submicron, non-living particles composed of saponin, cholesterol, phospholipid and in many cases protein, are useful components for a range of human vaccines.

Adjuvants, Immunologic↗
PubMed1996

Removal of the protruding retention wire via a femoral approach while leaving the active-fixation atrial "J" lead in situ: a technique for the management of class III atrial "J" leads.

The Telectronics Accufix Atrial "J" pacing lead poses a mechanical risk to patients of retention wire fracture and protrusion. Standard lead extraction techniques include percutaneous approaches, which are associated with significant risk of morbidity and mortality, and open procedures, which necessitate thoracotomy. In nine patients referred with Class III retention wire fractures, attempts were made to snare the protruding retention wire from a femoral approach using snare devices and bioptomes. In six cases, the retention wire was successfully removed, leaving the lead body in place. In four patients with lead function that was able to be evaluated, the atrial lead remained functional after the procedure. There were no complications. Snare removal of the protruding retention wire via a femoral approach should be considered as an option in the management of patients with Class III Accufix leads.

Aged↗
PubMed1995

Arrhythmias and death after coronary artery occlusion in the rat. Continuous telemetric ECG monitoring in conscious, untethered rats.

BACKGROUND: The onset of acute myocardial infarction (MI) is accompanied by a rapid increase in electrical instability and often fatal ventricular arrhythmias. The aim of this study was to assess the continuous arrhythmia profile during the initial 48 hours after coronary artery ligation in the rat in relation to time course, mortality, and infarct size. METHODS AND RESULTS: Continuous ECG recording were obtained in 26 conscious, untethered rats for 24 hours before and 48 hours after coronary ligation by use of an implantable telemetry system. All episodes of ventricular tachycardia and fibrillation were counted and their durations summed. Infarct size was measured at 48 hours after MI or after spontaneous death. After ligation, two distinctly active arrhythmogenic periods developed (A1, 0 to 0.5 hours; A2, 1.5 to 9 hours), each followed by a quiescent phase of low ectopy (Q1, 0.5 to 1.5 hours; Q2, 10 to 48 hours). The total mortality rate of 65% was found within the two active periods, with 13 of 15 deaths occurring in A2. Rats with larger infarcts (> or = 50%) and nonsurvivors tended to have increased arrhythmia frequency and duration compared with both animals with smaller MIs (< 50%) and survivors. CONCLUSIONS: Two distinct arrhythmogenic periods occur in rats with acute MI that may be caused by different mechanisms and correspond to the bimodal arrhythmia time course seen in dogs and humans after acute MI. Telemetric monitoring of the ECG in the conscious rat after infarction will be useful in assessment of the differential effects of therapeutic interventions on these two arrhythmogenic periods and in the study of potential mechanisms for the spontaneous resolution of ventricular ectopy and risk of sudden death.

Animals↗
PubMed1995

Recovery of hepatic function and latent mortalities in sheep exposed to the blue-green alga Microcystis aeruginosa.

Seventeen sheep died, and many others showed signs of hepatogenous photosensitivity after being exposed to Microcystis aeruginosa at Lake Mokoan, Victoria, Australia. Two groups of sheep were observed, and their hepatic recovery was monitored by means of serum biochemical tests during the subsequent six months. During the first three weeks, their serum gamma-glutamyl transferase activity and bilirubin concentration declined rapidly to normal levels, and the signs of hepatogenous photosensitivity disappeared. Serum bile acid concentrations were above normal for almost three months. Thirty-four per cent of the sheep died during the observation period, and the serum biochemical tests provided no clear indication of the cause of these delayed mortalities. This study suggests that sublethal exposure to microcystins may cause prolonged morbidity and delayed mortality.

Animals↗
PubMed1995

Serum levels of circulating anodic antigen and circulating cathodic antigen detected in mice infected with Schistosoma japonicum or S. mansoni.

Serum concentrations of circulating anodic antigen (CAA) and circulating cathodic antigen (CCA) were studied in mice infected with either Schistosoma japonicum or S. mansoni cercariae. Sera from uninfected mice were negative for both antigens. CAA was detectable in the S. japonicum-infected mice as early as at 2 weeks post-infection (p.i.), and levels were higher in these animals than in the S. mansoni-infected group during the full study period. At the moment of perfusion, 10 weeks p.i., a median of 9 and 29 worms, respectively, were recovered from the S. japonicum- and S. mansoni-infected mice, and the median CAA levels were 326 and 27 ng/ml, respectively. In contrast, CCA levels were much lower in the S. japonicum-infected group (27 ng/ml) as compared with the S. mansoni-infected mice (282 ng/ml). These results suggest an important difference between S. japonicum and S. mansoni infections in CAA and CCA production and/or clearance and indicate a significant role for CAA in the diagnosis of human schistosomiasis japonicum.

Animals↗
PubMed1994

A biochemical profile for predicting the chronic exposure of sheep to Microcystis aeruginosa, an hepatotoxic species of blue-green alga.

Sheep which grazed on the shoreline of a fresh-water lake which had a toxic bloom of Microcystis aeruginosa were studied for evidence of chronic poisoning, and a serum biochemical profile was developed to indicate sub-lethal, chronic poisoning in the sheep which had been exposed to microcystins. The profile included measurements of glutamate dehydrogenase (GLDH), gamma-glutamyl transferase (gamma GT), bile acids, bilirubin and albumin. Of 18 sheep which were exposed to M aeruginosa for more than three months, 100 per cent had high serum concentrations of bile acids, 94 per cent had high activities of GLDH and gamma GT, 83 per cent had high bilirubin and 72 per cent had low albumin concentrations compared with the median values of unexposed animals. Other sheep which were exposed for shorter periods, showed evidence of hepatic injury after one week of exposure. The majority of the sheep showed no preference for an alternative, uncontaminated source of water.

Animals↗
PubMed1994

Measurement of aortic input impedance in rats.

Measurement of aortic input impedance in the rat is complicated by a high basal heart rate but is possible if appropriate compensation is made for frequency-dependent errors in modulus and phase resulting from analog filters in the equipment and from nonalignment of pressure and flow sensors. Because input impedance is a complex quantity, accurate values for both phase and modulus are required before meaningful interpretation of the data can be made. We measured aortic pressure and electromagnetic ascending aortic blood flow in mature, ether-anesthetized, open-chest male Wistar rats. Pressure and flow waveforms were averaged in the time domain and converted to Fourier series. Flow moduli were corrected for the measured frequency response of the flowmeter. Phase spectra were corrected by the classic frequency-domain and two new time-domain methods. Compensation for instrumentation errors was assessed at two different flowmeter filter settings in five animals. Reproducibility, variability, and the effects of vasoconstriction were assessed in 43 animals. Three methods of estimating characteristic impedance from the impedance spectra were evaluated and found to produce comparable results at baseline and following pharmacological elevation of blood pressure with graded methoxamine infusion. Physiologically equivalent values for phase, as assessed by comparing oscillatory power calculated from the impedance spectra, were obtained with each of the phase-correction techniques. The new time-domain methods facilitate the assessment of aortic input impedance in this small animal model because they do not require measurement of the spatial separation between pressure and flow transducers and pulse wave velocity in the proximal aorta.

Analysis of Variance↗
PubMed1993

Ventricular remodeling after myocardial infarction.

Acute transmural myocardial infarction initiates a series of changes in left ventricular (LV) volume, regional function and geometry. This process, known as post-infarction LV remodeling, may continue for months or years following the initial ischemic event. To characterize the components of late ventricular remodeling, biplane left ventriculography was performed in 52 patients at 3 weeks and repeated at 1 year after first anterior myocardial infarction. Biplane circumference and contractile and noncontractile segment lengths were measured. Global geometry was evaluated by calculating a sphericity index and regional geometry was assessed by measurement of endocardial curvature. End-diastolic (ED) volume was increased at 3 weeks and enlarged further at one year. This late enlargement was accompanied by an increase in the length of the contractile segment and an increase in sphericity, whereas the length of the noncontractile segment decreased. Curvature analysis revealed that this late increase in sphericity resulted from flattening of regions of presumably high tension negative curvature at the infarct border zone and from less bulging of the infarcted anterior wall. Even in patients selected for late ventricular enlargement (change in ED volume > 20 ml, n = 19), this increase in volume resulted from both lengthening of the contractile segment and an increase in sphericity without a change in the noncontractile segment length. Thus, late ventricular enlargement after anterior myocardial infarction results from an increase in contractile segment length and a change in ventricular geometry and is not a result of progressive infarct expansion.

Adult↗
PubMed1993

Female-specific genomic PCR sequences from Schistosoma mansoni as probes for hybridization histochemistry.

Rapid methods for sexing single larval or egg stages of schistosomes have been difficult to establish. Such methods would be of value for assessing changes in sex ratios at different stages of the life cycle and studying diseases processes of schistosomiasis. We describe the use of hybridization histochemistry for identification of female eggs of Schistosoma mansoni in sections of infected mouse liver using a highly repetitive genomic DNA sequence generated by the polymerase chain reaction with primers spanning a known female-specific sequence (W1) of S. mansoni. In an initial study, approximately half of the eggs in each liver section from mice infected for 50 days labelled heavily with this probe. Further studies will evaluate the sensitivity and specificity of the probe on clonal populations (either male or female) or larvae in host tissue.

Animals↗
PubMed1992

Left ventricular remodeling in the year after first anterior myocardial infarction: a quantitative analysis of contractile segment lengths and ventricular shape.

Infarct expansion after myocardial infarction results in early ventricular enlargement and distortion of ventricular geometry. To characterize the components of late volume enlargement, biplane left ventriculography was performed in 52 patients 3 weeks and 1 year after a first anterior myocardial infarction. Biplane diastolic circumference and contractile and noncontractile segment lengths were measured. Global geometry was evaluated by using a sphericity index (angiographic volume of the ventricle divided by the volume of a sphere with the same circumference). Regional geometry was assessed by measurement of endocardial curvature, an important determinant of wall tension. End-diastolic volume was enlarged at baseline and increased at 1 year (230 +/- 42 to 244 +/- 55 ml, p = 0.01) as a result of increases in contractile segment length (34 +/- 5 to 37 +/- 5 cm, p less than 0.001) and sphericity index (0.74 +/- 0.07 to 0.76 +/- 0.08, p less than 0.001), whereas the noncontractile segment length decreased (15 +/- 6 to 12 +/- 6 cm, p less than 0.005). Curvature analysis revealed a flattening of presumably high tension concavity at the anterobasal (-6.0 +/- 4.0 to -4.5 +/- 3.7, p less than 0.01) and inferior (-4.5 +/- 2.0 to -3.6 +/- 2.1, p less than 0.005) margins of the infarct and less bulging of the anterior wall (9.4 +/- 2.5 to 8.2 +/- 2.3, p less than 0.001). Patients selected for late enlargement (diastolic volume increase greater than 20 ml, n = 19) had an increase in sphericity (0.75 +/- 0.05 to 0.80 +/- 0.08, p less than 0.005) and in diastolic circumference (54 +/- 3 to 56 +/- 4 cm, p less than 0.001) secondary to elongation of the contractile segment (32 +/- 4 to 36 +/- 4 cm, p = 0.001) at 1 year. Thus, late ventricular enlargement after anterior infarction results from an increase in contractile segment length and a change in ventricular geometry and is not a result of progressive infarct expansion. In the group of patients at high risk for late ventricular enlargement because of persistent occlusion of the infarct-related vessel, captopril therapy attenuated late volume enlargement by preventing these changes in contractile segment length and chamber geometry.

Adult↗
PubMed1992

Cyclophilin of Schistosoma japonicum.

A 623-bp cDNA molecule encoding cyclophilin, a specific cyclosporin A-binding protein, has been isolated from Schistosoma japonicum using a heterologous cDNA probe from Echinococcus granulosus. The nucleotide sequence of this molecule has been determined, and the deduced amino acid sequence has revealed extensive homology with homologues of other species. Southern blot analysis suggests that S. japonicum cyclophilin is the product of a single-copy gene. The cloning of this cDNA will allow an investigation of cyclophilin as a possible target of the antischistosome effects of cyclosporin A.

Amino Acid Isomerases↗
PubMed1991

Serologic reactivities of the 23-kDa integral membrane proteins of schistosomes.

The 23-kDa integral membrane proteins of Schistosoma mansoni and Schistosoma japonicum (Sm23 and Sj23) are Ag of some interest in terms of both antiparasite vaccination and immunodiagnosis. We have raised an antiserum against a recombinant fusion protein expressing the extracellular hydrophyllic domain of Sm23 (Sm23HD-pGEX) and used this serum, as well as other antibody reagents reacting with Sm/Sj23, in immunochemical analyses. The immunogenicity and antigenicity of Sm23HD-pGEX, and the surprising lack of cross-reactivity between Sm23 and Sj23 support the hypothesis that Sm/Sj23 are host-like molecules with a very limited number of B cell epitopes that are likely to reside in the extracellular hydrophilic domain. We also present evidence that, unlike the highly immunogenic Sj23, Sm23 is not immunogenic in chronically infected mice. Moreover, we confirm a surface location for Sj23 in adult worms, in S. japonicum.

Animals↗
PubMed1991

Further characterisation of the Schistosoma japonicum protein Sj23, a target antigen of an immunodiagnostic monoclonal antibody.

Sj23, the 23-kDa target antigen in Schistosoma japonicum adult worms of the hybridoma monoclonal antibody (mAb) I-134, has been identified and cloned from cDNA libraries, mAb I-134 has been successfully used in immunodiagnostic assays to detect S. japonicum infection in Philippine patients. Sequence analysis has shown that Sj23 is the homologue, with 84% amino acid identity, of Sm23, a 23-kDa molecule from S. mansoni worms previously described from our laboratory. The domain structures of Sj23 and Sm23 are strikingly similar to the human membrane proteins ME491, CD37, CD53 and TAPA-1, which may suggest a functional role for the schistosome molecules in cellular proliferation.

Amino Acid Sequence↗