Biomedical subjects

J B Gavin

Publications and source records attributed to J B Gavin.

At least 55 records · Page 3Linked to original sources

PubMed1989

Uneven host tissue ongrowth and tissue detachment in stent mounted heart valve allografts and xenografts.

Following explanation from the mitral position because of primary tissue failure, 30 human antibiotic sterilised stent mounted aortic valve allografts and 28 glutaraldehyde treated porcine xenografts were examined for evidence of tissue detachment from the stents. These grafts had been in situ for 34 to 166 months. Graft detachment had occurred from one or two stent posts with displacement of the commissures and central valvular incompetence in 12 (67%) of 18 allografts supported on rigid stainless steel stents, in six (50%) of 12 allografts mounted on flexible acetal copolymer stents, but in only one (4%) of 28 xenografts mounted on polypropylene stents. In regions of detachment the aortic remnant of the graft was infiltrated by components of blood and phagocytic cells which had removed not only fibrin but also graft tissue. Detachment did not occur from stent posts where the graft margin had become coated by collagenous host tissue. This intimal fibrous sheath appeared not only to strengthen the attachment of the graft but also to limit the entry of fibrin and phagocytes into the graft tissue.

Animals↗

PubMed1989

Differences between heart valve allografts and xenografts in the incidence and initiation of dystrophic calcification.

Following surgical removal because of primary tissue failure, 30 antibiotic-sterilized human aortic valve allografts and 27 glutaraldehyde-treated porcine aortic valve xenografts were examined for macroscopic and microscopic evidence of dystrophic calcification. These grafts had been mounted on stents and used for from 34 to 166 months to replace diseased mitral valves. After explantation the grafts were carefully examined then prepared for light microscopy, for transmission electron microscopy and for energy dispersive X-ray microanalysis. Gross calcification occurred significantly (p = 0.002) more frequently in xenografts (89%), and was more extensive than in allografts (53%). Calcification usually appeared as nodular excrescences on the cusps, although occasionally it formed plates within them. This reduced tissue pliability and was usually associated with either valvular stenosis or regurgitation. The calcified deposits contained calcium and phosphate in ratios approaching those of hydroxyapatite. In xenograft valves the smallest discrete deposits of calcification were spherical and usually associated with membranous debris of porcine donor fibroblasts, but allografts did not contain donor cell remnants and early calcification was linearly arranged along collagen fibres.

Adolescent↗

PubMed1989

Endocardial damage induced by lactate, lowered pH and lactic acid in non-ischemic beating hearts.

The left ventricular lumen of isolated perfused beating hearts was perfused for up to 8 h with either Krebs Henseleit buffer (KHB, pH 7.4), KHB including 33 mumol/ml of lactic acid at pH 7.4 or 6.4, or with KHB including hydrochloric acid to reduce the pH to 6.4. Scanning and transmission electron microscopy showed that whereas control hearts maintained an intact endocardium, those groups exposed to increased concentrations of lactate, hydrogen ions or both, developed endothelial cell separation and exfoliation with exposure first of basal lamina and then of endocardial collagen. The underlying myocytes also showed evidence of irreversible cell injury. The extent and severity of damage was greater in hearts exposed to lactic acid than to either lactate or lowered pH alone. These findings suggest that the increased concentrations of metabolites which accumulate in developing myocardial infarcts can diffuse through and damage the endocardium in ways which are likely to predispose in vivo to the development of mural thrombosis.

Acidosis↗

PubMed1989

Early follow-up of patients with the Medtronic Intact porcine valve. A new cardiac bioprosthesis.

A new-generation porcine valve fixed in glutaraldehyde at zero pressure and mounted on an acetal copolymer flexible stent was inserted in 97 patients between August 1983 and October 1986. The mean age of the patients was 51 years (range 10 to 76) and eight were under the age of 20 years. There were 57 mitral, 33 aortic, and 10 tricuspid valve replacements. Concomitant coronary artery bypass grafting was performed in 9% of patients, 40% underwent multiple valve operations, and in 40% the procedure was a reoperation. Mean follow-up was 26 months (range 12 to 49) and was 99% complete. There were no examples of primary tissue failure, and only to reoperations have been undertaken for infective endocarditis alone. The early mortality rate was 8.2% and the late mortality rate, 12.1%. Four late deaths were valve related (two caused by infective endocarditis and two by embolism). The actuarial 3-year survival rate was 70%, freedom from infective endocarditis 879%, freedom from embolism 87%, freedom from reoperation 90%, and freedom from valve-related complications 77%. All but three surviving patients were in New York Heart Association class I or II. Doppler echocardiography, performed in 62 of 76 survivors, showed thin and mobile leaflets in all patients and trivial or mild regurgitation in four (6%). The mean gradient across the Medtronic Intact valves (Medtronic Blood Systems Inc., Minneapolis, Minn.) in the aortic position was 17 +/- 5.2 mm Hg, in the mitral position 3.8 +/- 1.33 mm Hg, and in the tricuspid position 4.1 +/- 1.14 mm Hg. We conclude that early results with the Intact valve are encouraging.

Adolescent↗

PubMed1988

Strategies for research: active or passive.

This paper provides an introduction to a symposium on challenges for medical research held to mark the golden jubilee of the Medical Research Council of New Zealand. It provides some historical, international and national perspectives for the papers which follow and discusses the interrelationships which exist between society, health care and medical research and also between medical research workers, the institutions in which they work and the agencies which provide funds for research. The point is made that in basic research, where the final applications of the new knowledge cannot be predicted, the initiative and direction may equally well be determined by the investigators or by the institutions which support them. It is considered that the research funding agencies, however, have a major responsibility to actively encourage research in fields where specific needs for improved health care can be defined or predicted.

Global Health↗

PubMed1988

Mechanism of resistance of noncycling mammalian cells to 4'-(9-acridinylamino)methanesulfon-m-anisidide: comparison of uptake, metabolism, and DNA breakage in log- and plateau-phase Chinese hamster fibroblast cell cultures.

Resistance of noncycling cells to amsacrine (m-AMSA) has been widely reported and may limit the activity of this drug against solid tumors. The biochemical mechanism(s) for this resistance have been investigated using spontaneously transformed Chinese hamster fibroblasts (AA8 cells, a subline of Chinese hamster ovary-cells) in log- and plateau-phase spinner cultures. In early plateau phase most cells entered a growth-arrested state with a G1-G0 DNA content and showed a marked decrease in sensitivity to cytotoxicity induced by a 1-h exposure to m-AMSA or to its solid tumor-active analogue, CI-921. Studies with radiolabeled m-AMSA established that similar levels of drug were accumulated by log- and plateau-phase cells and that there was no significant drug metabolism in either of these cultures after 1 h. However, marked differences in sensitivity to m-AMSA-induced DNA breakage were observed using a fluorescence assay for DNA unwinding (Kanter P.M., and Schwartz, H.S., Mol. Pharmacol., 22: 145-151, 1982). Changes in sensitivity to DNA breakage occurred in parallel with changes in sensitivity to m-AMSA-induced cell killing. DNA breaks disappeared rapidly after drug removal (half-time approximately 4 min), suggesting that these lesions were probably mediated by DNA topoisomerase II. Resistance to m-AMSA may therefore be associated with changes in topoisomerase II activity in noncycling cells.

Amsacrine↗

PubMed1988

Effects of glutamic acid on cardiac function and energy metabolism of rat heart during ischaemia and reperfusion.

The effects of exogenous glutamate (20 mM) on myocardial energy metabolism and cardiac function during low-flow ischaemia and subsequent reperfusion were studied in isolated working rat hearts. Hearts were made severely ischaemic for 60 min by reducing the perfusion rate to 0.17 ml/min, and then reperfused for 30 min. Low-flow ischaemia resulted in a 50% reduction of myocardial ATP, a 70% reduction of both creatine phosphate (CP) and GTP, and a 250% rise in AMP. After reperfusion, CP was restored to normal levels but ATP and GTP remained significantly low. All hearts failed completely to recover cardiac pump function. The addition of glutamate to the perfusate during low-flow ischaemia had no significant effect on myocardial high-energy phosphates (HEP) but slightly increased succinate production. Subsequent reperfusion without added glutamate resulted in the recovery of 62% of pre-ischaemic aortic flow rate, as well as restoration of myocardial ATP and GTP to 70% of their control values and of creatine phosphate to supranormal levels. Reperfusion with added glutamate did not raise HEP levels any further but did increase recovery of cardiac function to 92% or more of pre-ischaemic values. Thus, by mechanism(s) which are not yet clear but which may include an increase in HEP via anaerobic succinate production, elevated levels of exogenous glutamate exert a highly beneficial effect on the post-ischaemic recovery of cardiac function.

Adenine Nucleotides↗

PubMed1988

The intestinal and diffuse types of gastric carcinoma in Maori and non-Maori patients in Auckland.

Histologic specimens of gastric carcinoma from 128 Maori, Pacific Island Polynesian, and European patients in Auckland, New Zealand, were classified into intestinal or diffuse type. The ratio of intestinal to diffuse type (ID) was lowest (0.3) in the female Maori patients and highest (1.4) in the male Maori. The higher ID ratio reflects the increased risk of gastric carcinoma in the Maori men as compared with the other groups studied.

Adult↗

PubMed1988

Transmural differences in the postischemic recovery of cardiac energy metabolism.

After 25 minutes of ischemia, in the isolated rat preparation, hearts fail to reestablish adequate contractile function. To determine whether this failure was associated with a transmural variation in the metabolic response of myocardial cells to reperfusion, the authors subjected hearts to 25 minutes of global ischemia with and without 5 or 20 minutes of reperfusion. After freeze-drying the left ventricular myocardium was divided into subepicardial (EPI) and subendocardial (ENDO) regions before estimating the lactate, total adenine pool metabolites, and creatine phosphate (CP) and phosphate concentrations in each region. Other groups of hearts were perfusion-fixed with glutaraldehyde then injected with nuclear track emulsion to demonstrate that a high proportion of capillaries in both the subendocardial (89%) and subepicardial (95%) myocardium transmitted perfusate after 5 minutes of reperfusion. Reperfusion removed lactate equally from each region. Thus the differences in the capacity of reperfusion of these regions to recover CP (ENDO, 100%; EPI, 168% of preischemic values), to elevate adenosine triphosphate (ATP) (ENDO, 32%; EPI, 63%), or to retain adenosine monophosphate (AMP) (ENDO, 625%; EPI, 277%) were unlikely to be due to regional differences in microvascular function. Despite the better preservation of both structure and metabolism in the subepicardium, there was, during reperfusion, a progressive loss of purine precursors from cells in both regions of the myocardium. These results suggest that the loss of ability of the myocardium to recover significant function after relatively short periods of ischemia is due to their inability, on reperfusion, to synthesise sufficient ATP from the available precursors. This capacity for resynthesis of ATP is lost more rapidly in the subendocardial than in the subepicardial myocardium.

Adenine Nucleotides↗

PubMed1987

Back-scattered electron imaging of sections through the cochlea: a new technique for studying cochlear morphology.

A new technique for studying the morphology of the cochlea is described. The development of back-scattered electron (BSE) detectors has allowed the examination of heavy-metal stained tissues by scanning electron microscopy. Comparison with light microscopy on adjacent resin sections through whole decalcified cochleae demonstrated that the back-scattered electron technique provides equal or superior clarity and resolution throughout the light microscope range of magnification, allows identification of lysosomes, mitochondria and endoplasmic reticulum, and extends useful magnification into the range previously associated only with transmission electron microscopy. Back-scattered electron imaging enables the study of sections of the undissected cochlea at high magnifications and resolution.

Animals↗

PubMed1986

Preservation of mucus in situ in rat colon.

Mucus, a hydrated complex consisting mainly of glycoproteins, forms a layer over the epithelial surface of the gastrointestinal tract. The usual preparative procedures for histological and scanning electron microscopic examination of the gut result in the loss or distortion of this mucus layer. Careful evaluation of two new methods reported to stabilize the mucus layer showed that acrolein vapor did not provide adequate fixation, but application of heat-inactivated antiserum raised in rabbits against rat colon mucus reliably preserved a continuous layer closely adherent to the epithelium. This stabilized layer is continuous with the mucus in the colonic crypts.

Animals↗

PubMed1986

Microvascular function at the margins of early experimental myocardial infarcts in isolated rabbit hearts.

Injection of low-viscosity resin was used to identify in situ functional blood vessels at the margins of developing regional myocardial infarcts. The ventral interventricular branch (VIB) of the left coronary artery was occluded for 0-240 min in 20 isolated perfused rabbit hearts. After perfusion fixation with glutaraldehyde, resin was injected into the coronary arteries--that injected into the VIB contained dispersed lead dioxide and that injected into the remainder of the heart contained Fat Red 7B dye. This allowed macroscopic and microscopic identification of functional blood vessels. Following transmural freeze fracture, left ventricles were examined using back-scattered electron imaging in a scanning electron microscope. Close to 60% of capillaries in nonischemic myocardium allowed the passage of resin. Thirty minutes of ischemia produced a hyperemic increase to 80%-90% in the proportion of filled vessels. After 60 min, however, a severe reperfusion defect corresponding to the "no-reflow" phenomenon had developed, with virtually all vessels collapsed and less than 10% functional. Among the structurally normal myocytes adjacent to the infarct margin there was a significant reduction (to 30%-40%) in the proportion of functional capillaries. This was due to groups of dilated vessels which were not accessible to arterial supply. Although these marginal "low-flow" regions were of small volume at any one point in time, they seem likely to contribute to the progression of ischemic necrosis, and are probably nonfunctional due to the compression of their venous drainage traversing the infarct.

Animals↗

PubMed1986

The pathogenesis of stereocilia abnormalities in acoustic trauma.

Stereocilia abnormalities develop in anesthetized guinea pigs within two minutes of exposure to loud sound (3 kHz, 125 dB SPL). Displacement, fracture, fusion and membrane rupture were observed well before the development (after 10 or more minutes) of fine structural changes to other cytoplasmic organelles within the hair cells. Thus stereocilia abnormalities can arise very rapidly due to the direct effects of noise on their microfilaments, cross linkages and limiting membranes. Such abnormalities are thus not necessarily secondary to changes in the body of the affected hair cells.

Actin Cytoskeleton↗

PubMed1986

Effects of ischaemia on vasculature.

The effects of ischaemia on the structure and function of coronary vessels have been evaluated most thoroughly in the open-chest anaesthetised dog. In the beating heart the flow into the capillary bed is controlled by precapillary sphincters in the terminal arterioles. Short periods (up to 20 min) of ischaemia result during reperfusion in vasodilatation which is mediated through increased tissue adenosine levels. Longer periods of ischaemia (60 or more min) result in degenerative vascular changes and no-reflow during reperfusion. Endothelial cells swell, lose their pinocytotic vesicles and form spherical cytoplasmic protrusions into the capillary lumina. Prolonged ischaemia (over 3 hours) causes ruptures in microvascular walls. Such vessels become permeable to large tracers, e.g. carbon particles, and reperfusion results in haemorrhage. Capillaries in ischaemic myocardium are collapsed by compression resulting from intra- and extracellular oedema and contracture of myocytes. Erythrocytes plug collapsed microvessels. However, in vitro observations have shown that no-reflow may result from ischaemia even without erythrocyte plugging. Capillary compression is the main determinant of no-reflow after ischaemia. Degenerative ischaemic changes in vascular walls further contribute to vascular incompetence in vivo.

Animals↗

PubMed1986

Location of bacteria in the mid-colon of the rat.

The distribution of microorganisms in the mid-colon of the rat was studied by light and scanning electron microscopy. An antiserum against rat colon mucus was used to stabilize the mucus in situ. In samples not incubated with antiserum, the mucus disintegrated and contracted into patchy strands only partly covering the luminal surface of the colon. Bacteria were seen within fecal pellets, tangled among the strands of mucus, and scattered on the epithelial surface. However, when incubated with antiserum, mucus almost completely filled the lumen and coated the fecal pellets. Bacteria in these stabilized preparations were limited mainly to the fecal pellets, and there were small numbers scattered in the luminal mucus, but none were observed on the epithelial surface or within the crypts. Latex particles introduced into the lumen with the antiserum or with phosphate-buffered saline showed the same distribution as the bacteria. These findings are at variance with previous reports that organisms occur in abundance in the mucous layer, adjacent to cell surfaces, and inside crypts. Our results suggest that conventional preparation for microscopy without prior stabilization of the mucus in situ may lead to artifactual redistribution of microorganisms and emphasize the importance of mucus in maintaining mucosal-floral homeostasis in the colon.

Animals↗

PubMed1986

Scanning electron microscopy of heart muscle freeze-dried from dimethylsulfoxide for simultaneous demonstration of cell morphology and microvascular function.

Scanning electron microscopy was used to examine cryofracture surfaces of ventricular myocardium from glutaraldehyde fixed rat and rabbit hearts subjected to intravascular injection of polymerizing acrylic resin. This allowed simultaneous observation of morphological features of cardiac muscle cells and the functional state of their associated small blood vessels. Because the resin injected to identify capillaries accessible to flow might be soluble in commonly used tissue dehydrating agents, alternative preparation methods using the cryoprotectants dimethylsulfoxide (DMSO) and glycerol were investigated. Provided a high performance backscattered electron detector and simple environmental cell were used to abolish specimen charging and circumvent potential instrument contamination, immersion in 2.82 M DMSO for 12 hr prior to cryofracture and freeze-drying gave the best results. The SEM appearance of specimens dehydrated in this way differed little from that of specimens prepared by ethanol dehydration and freeze-drying or by acetone dehydration and critical-point drying. Tissue shrinkage was 26.5 +/- 9.4%, comparable to that found after standard methods using solvent dehydration and critical-point drying.

Acetone↗

PubMed1985

The development and progression of myocyte injury at the margins of experimental myocardial infarcts.

Distinct differences in the extent and progression of the lateral and epicardial boundaries of evolving regional infarcts were demonstrated in isolated rabbit hearts. Ischemia was produced by interrupting (0-240 minutes) flow in the ventral interventricular branch of the left coronary artery, whilst the remainder of the heart was continuously perfused with oxygenated Krebs-Henseleit bicarbonate buffer. Perfusion fixed blocks were freeze-fractured then examined using back-scattered electron imaging in a scanning electron microscope. Control myocytes showed relatively smooth, continuous internal fracture faces. After 30 min of ischemia myocytes showed evidence of mild, probably reversible, injury in the form of prominence of pits and channels. Severe injury, characterized by separation of organelles and prominent intracellular spaces, developed after 60 or more min of ischemia, first in the subendocardial two thirds, and after 120 min across the full thickness of the ventricular wall. At the lateral margins of infarcts there was a distinct cell-to-cell boundary between control and severely injured myocytes, with only a few scattered mildly injured cells within 30 mu of the infarct. Although transmural progression of necrosis provides the potential for recovery of the external aspect of the myocardium in the ischemic zone by reperfusion, corresponding regions of salvageable myocytes at lateral infarct margins are very narrow.

Animals↗

PubMed1985

Reversal of the no reflow phenomenon in globally ischemic rat hearts by ventricular dilation.

Changes in the contracture and stiffness of ventricular walls during ischemia and their effect on vascular reperfusion were studied in isolated rat hearts. Global ischemia was induced by stopping the flow of oxygenated perfusate for 60 min. Contracture pressures generated against water-filled left ventricular balloons maintained at diastolic volume increased between 8 and 25 min of ischemia and declined thereafter. On the other hand, left ventricular wall stiffness, estimated from the pressure required to periodically inflate otherwise uninflated balloons to diastolic volume, increased rapidly between 20 and 30 min of ischemia, and more slowly thereafter. Inflation of balloons following 30 or more min of ischemia caused significant reductions in left ventricular wall stiffness. Similar brief inflation after 60 min of ischemia allowed aqueous sodium fluorescein to perfuse the subendocardial half of the left ventricular wall which was otherwise not accessible to reperfusion. This reversal of the no reflow phenomenon was accompanied by a reduction in myocardial wall stiffness, stretching of myocytes and increased patency of myocardial capillaries.

Animals↗