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Biomedical subjects

J E Baker

Publications and source records attributed to J E Baker.

At least 91 records · Page 5Linked to original sources
PubMed1990

Is protection of ischemic neonatal myocardium by cardioplegia species dependent?

Hypothermia combined with pharmacologic cardioplegia protects the globally ischemic adult heart, but this benefit may not extend to children, resulting in poor postischemic recovery of function and increased mortality. The relative susceptibilities to ischemia modified by hypothermia alone and by hypothermia plus cardioplegia were assessed in isolated perfused neonatal (3- to 4-day-old) rabbit and pig hearts. Hearts were perfused aerobically with Krebs buffer solution in the working mode for 30 minutes and aortic flow was recorded. This was followed by 3 minutes of hypothermic (14 degrees C) coronary perfusion with either Krebs or St. Thomas' Hospital cardioplegic solution No. 2 followed by hypothermic (14 degrees C) global ischemia (rabbits 2, 4, and 6 hours; pigs 2 and 4 hours). Hearts were reperfused for 15 minutes in the Langendorff mode and 30 minutes in the working mode, and recovery of postischemic aortic flow was measured. Hypothermia alone provided excellent protection of the ischemic neonatal rabbit heart, with recovery of aortic flow after 2 and 4 hours of ischemia at 91% +/- 4% and 87% +/- 5% (mean +/- standard deviation) of its preischemic value. Recovery after 6 hours of ischemia was depressed to 58% +/- 9% of its preischemic value. Ischemic neonatal pig hearts protected with hypothermia alone recovered 94% +/- 3% of preischemic aortic flow after 2 hours; none was able to generate flow after 4 hours. St. Thomas' Hospital solution No. 2 decreased postischemic aortic flow after 4 hours of ischemia in rabbit hearts from 87% +/- 5% to 70% +/- 7% (p less than 0.05, hypothermia alone versus hypothermia plus cardioplegia) but improved postischemic recovery of aortic flow in pig hearts after 4 hours of ischemia from 0 to 73% +/- 13% (p less than 0.0001, hypothermia alone versus hypothermia plus cardioplegia). This effect was dose related in both species. We conclude that the neonatal pig heart is more susceptible to ischemia modified by hypothermia alone than the neonatal rabbit and that St. Thomas' Hospital solution No. 2 improves postischemic recovery of function in the neonatal pig but decreases it in the neonatal rabbit. This species-dependent protection of the neonatal heart may be related to differences in the extent of myocardial maturity at the time of study.

Animals↗
PubMed1989

Ischemia-induced changes in myocardial paramagnetic metabolites: implications for intracellular oxy-radical generation.

Evidence to identify the cellular sources of oxy-radical generation in myocardium has been of an indirect nature. We have used low-temperature ESR spectroscopy to identify and characterize ischemia-induced changes in myocardial paramagnetic metabolites. Iron-sulfur proteins associated with the NADH or succinate dehydrogenases of the mitochondrial electron-transport chain were progressively reduced with the onset and development of ischemia. This study provides direct evidence for ischemia-induced changes in an intracellular source of superoxide radical generation that may contribute to oxy-radical production during reperfusion.

Animals↗
PubMed1989

Loss of residual hearing after cochlear implantation.

Many cochlear implant recipients have some measurable hearing prior to implantation. Animal studies have demonstrated some loss of viable neural elements resulting from both mechanical insertion trauma and long-term electrical stimulation. The effect of implantation of a long intracochlear multichannel electrode array and subsequent electrical stimulation on residual hearing was evaluated. Forty consecutive cochlear implant recipients were assessed by audiometry at the Colorado Ear Clinic between July 1985 and June 1988. Twelve of these patients (30%) had some measurable residual hearing before implantation, although all had profound hearing loss, with no understanding of speech. All patients received a multichannel cochlear implant with all 22 electrodes inserted in each patient by an experienced cochlear implant surgeon. Audiometric testing was repeated between 2 and 24 months after implantation. Pure-tone threshold responses in the implanted ear were significantly reduced postimplant, while pure-tone threshold responses in the nonimplanted ear were stable.

Adult↗
PubMed1988

Myocardial ischemia and reperfusion: direct evidence for free radical generation by electron spin resonance spectroscopy.

Electron spin resonance spectroscopy has recently been used by others to detect directly radical species in isolated perfused hearts. Sample processing prior to spectroscopy in this study involved pulverization of tissue, which can artifactually generate radical species. We assessed in isolated perfused hearts the influence of tissue pulverization on the identity of radical species detected by spectroscopy and then, using a processing technique less likely to induce artifacts, whether myocardial ischemia and reperfusion generate radical species. Rat and rabbit hearts (n = 8) were perfused aerobically for 10 min and freeze-clamped to -196 degrees C. Frozen tissue was processed at -196 degrees C for spectroscopic analysis by pulverization vs. chopping. Spectra of pulverized tissue consisted of three components: a semiquinone (g = 2.004), a lipid peroxy radical (g [ = 2.04 and g = 2.006), and a carbon-centered radical that is possibly a lipid radical (giso = 2.002 and AHzz approximately equal to 50 G). Chopped tissue consisted of a single component, a semiquinone (g = 2.004). Rat hearts (n = 8 per group) also underwent 10-min global no-flow normothermic ischemia followed by 5-60 sec of either aerobic or anaerobic reperfusion, with frozen tissue chopped prior to spectroscopy. Spectra of ischemic tissue consisted of an iron-sulfur center and a semiquinone. Aerobic reperfusion resulted in a spectrum similar to the control but with increased amplitude that peaked after 10-15 sec of reflow. Anaerobic reperfusion yielded a spectrum identical to that of ischemic tissue. We conclude that pulverization of frozen myocardial tissue arti-factually generates radical species. Using a nonpulverization technique for tissue processing, we found that myocardial ischemia and reperfusion produce radical species but that molecular oxygen is necessary for the burst of radical production during reflow.

Aerobiosis↗
PubMed1988

Alpha adrenoceptor subtypes and receptor reserve in human versus canine saphenous vein: sensitivity to blockade by nitroglycerin.

The purpose of this investigation was to determine the subtypes of alpha adrenoceptors present in human saphenous vein and to determine if there is a large receptor reserve for phenylephrine as has been demonstrated in canine saphenous vein. The subtypes of alpha adrenoceptors found in isolated human saphenous vein were determined using selective alpha-1 and alpha-2 adrenoceptor agonists and antagonists. Prazosin, a selective alpha-1 antagonist, produced a parallel shift of the concentration response curve to phenylephrine, a selective alpha-1 agonist, with no significant reduction in the maximal response. Yohimbine, a selective alpha-2 antagonist, produced a parallel shift of the concentration response curve to B-HT 920, a selective alpha-2 agonist, with no reduction in the maximal response. The pA2 values obtained for prazosin and yohimbine in human saphenous vein agreed closely with corresponding values obtained in canine saphenous vein. These results demonstrate that both alpha-1 and alpha-2 adrenoceptors exist in human saphenous vein. Phenoxybenzamine (10(-7) M), an irreversible alpha-1 adrenoceptor antagonist, markedly reduced the maximal response produced by phenylephrine, an agonist with high intrinsic activity, with no significant shift in the concentration response curve in human saphenous vein, suggesting that there was little or no alpha-1 receptor reserve for phenylephrine. The sensitivity of alpha-1 versus alpha-2 adrenoceptor-mediated vasoconstrictor responses to nitroglycerin were compared in human and canine saphenous veins. In both species, nitroglycerin blocked the vasoconstrictor response produced by stimulation of alpha-2 adrenoceptors to the same degree.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Agonists↗
PubMed1988

Age-related changes in the ability of hypothermia and cardioplegia to protect ischemic rabbit myocardium.

Hypothermia combined with pharmacologic cardioplegia protects the globally ischemic adult heart, but this benefit may not extend to children; poor postischemic recovery of function and increased mortality may result when this method of myocardial protection is used in children. The relative susceptibilities to ischemia-induced injury modified by hypothermia alone and by hypothermia plus cardioplegia were assessed in isolated perfused immature (7- to 10-day-old) and mature (6- to 24-month-old) rabbit hearts. Hearts were perfused aerobically with Krebs-Henseleit buffer in the working mode for 30 minutes, and aortic flow was recorded. This was followed by 3 minutes of hypothermic (14 degrees C) coronary perfusion with either Krebs or St. Thomas' Hospital cardioplegic solution No. 2, followed by hypothermic (14 degrees C) global ischemia (mature hearts 2 and 4 hours; immature hearts 2, 4, and 6 hours). Hearts were reperfused for 15 minutes in the Langendorff mode and 30 minutes in the working mode, and recovery of postischemic function was measured. Hypothermia alone provided excellent protection of the ischemic immature rabbit heart, with recovery of aortic flow after 2 and 4 hours of ischemia at 97% +/- 3% and 93% +/- 4% (mean +/- standard deviation) of the preischemic value. Mature hearts protected with hypothermia alone recovered only minimally, with 22% +/- 16% recovery of preischemic aortic flow after 2 hours; none were able to generate flow at 4 hours. St. Thomas' Hospital solution No. 2 improved postischemic recovery of aortic flow after 2 hours of ischemia in mature hearts from 22% +/- 16% to 65% +/- 6% (p less than 0.05), but actually decreased postischemic aortic flow in immature hearts from 97% +/- 3% to 86% +/- 10% (p less than 0.05). To investigate any dose-dependency of this effect, we subjected hearts from both age groups to reperfusion with either Krebs solution or St. Thomas' Hospital solution No. 2 for 3 minutes every 30 minutes throughout a 2-hour period of ischemia. Reexposure to Krebs solution during ischemia did not affect postischemic function in either age group. Reexposure of immature hearts to St. Thomas' Hospital solution No. 2 caused a decremental loss of postischemic function in contrast to incremental protection with multidose cardioplegia in the mature heart. We conclude that immature rabbit hearts are significantly more tolerant of ischemic injury than mature rabbit hearts and that, unexpectedly, St. Thomas' Hospital solution No. 2 damages immature rabbit hearts.

Aging↗
PubMed1987

Transport and Compartmentation of 1-Aminocyclopropane-1-Carboxylic Acid and Its Structural Analog, alpha-Aminoisobutyric Acid, in Tomato Pericarp Slices.

The uptakes of 1-aminocyclopropane-1-carboxylic acid (ACC), the immediate precursor to ethylene, and its structural analog, alpha-aminoisobutyric acid (alphaAIB) by tomato pericarp slices were investigated. Both uptakes show a biphasic (saturable-linear) dependence on external concentration of the transported amino acid. At low concentrations, ACC uptake is competitively inhibited by alphaAIB and vice versa. Both uptakes also are inhibited by other neutral amino acids but not by acidic or basic amino acids. ACC and alphaAIB uptakes are metabolically dependent and are increased with time of tissue incubation. alphaAIB efflux patterns from pericarp slices indicated three distinct alphaAIB compartments having efflux kinetics consistent with those for cell wall, cytoplasm, and vacuole. The bulk of the alphaAIB taken up by pericarp tissue is sequestered into the vacuole. The ability of pericarp tissue to accumulate alphaAIB in the vacuole declines with fruit development.

Journal Article↗
PubMed1986

Risk of hypothermia in elderly patients with diabetes.

The incidence of admissions of patients with hypothermia was determined to examine whether hypothermia was more common in elderly patients with diabetes than in the general population after diabetic metabolic emergency cases had been excluded. A prospective survey of three accident and emergency departments identified 134 cases of hypothermia admitted from a catchment population of almost 157,000 aged 65 or over during the winters of 1981-2 to 1983-4. The predicted number of patients with diabetes in the population was nearly 5600 (3.5%). Twenty three admissions for hypothermia (17%) occurred in 20 patients with previously diagnosed diabetes. Women made up 87% of the diabetic admissions; the ratio of diabetic to non-diabetic admission rates in women was 7.9 (95% confidence interval 5.3 to 12.0). After excluding diabetic metabolic emergency admissions the ratio was 6.4. The ratio in men was 2.4, but the small number of admissions produced wide confidence intervals. Ten of the admissions with diabetes (43%) had pathological disorders that are associated with an increased risk of hypothermia. The frequency of these conditions is higher in patients with diabetes than in the general population and partly explains the increased risk of hypothermia in these patients.

Aged↗
PubMed1986

Morphology of bronchogenic carcinoma in workers formerly exposed to crocidolite at Wittenoom Gorge in Western Australia.

Cytology and histology material from 46 bronchogenic carcinomas occurring in ex-workers from the Wittenoom crocidolite mine and mill in Western Australia and a matched random sample of 234 other bronchogenic carcinomas occurring in Western Australia over the same period were reviewed by a single histopathologist without knowledge of asbestos exposure status. Squamous-cell carcinomas formed 45.7% of the cancers in the asbestos-exposed group but only 32.5% of the cancers in the comparison group. This difference could not be explained by differences in smoking history between the two groups of lung cancer patients or in the type of histopathological material available for review. The excess of squamous-cell cancers was observed in subjects both with and without parenchymal asbestosis.

Adult↗
PubMed1986

Community hospitals in Oxfordshire: their effect on the use of specialist inpatient services.

About one-third of the general practices in the Oxfordshire Health District have access to beds in community hospitals as well as district general hospitals. Hospital Activity Analysis data were used to calculate the average number of hospital beds occupied daily by patients registered with each general practice in the district. Practices with and without access to community hospitals were compared to determine whether such access was associated with a reduction in the use of beds in general medical, geriatric, and other specialties, and an increase in overall utilisation rates. The rate of use of general medical and geriatric beds in district general hospitals by practice populations with access to community hospitals was about half that of populations without such access. Utilisation rates overall, combining the use of beds in both district general hospitals and community hospitals, were a little higher in populations with access to both community hospitals and district general hospitals than in those with access to district general hospitals only.

Age Factors↗
PubMed1985

Differing potencies and dose-response characteristics in the ability of slow-calcium-channel blockers to reduce enzyme leakage in the calcium paradox.

In studies of the calcium paradox, we have used an isolated rat heart preparation to investigate the relationship between myocardial creatine kinase leakage and the concentration of slow-calcium-channel blockers (nifedipine or verapamil) in the perfusion fluid during a cycle of calcium reduction and repletion. The results indicated that enzyme leakage could be further reduced to a degree greater than that seen under conditions of a full calcium paradox (complete calcium depletion). Detailed dose-response studies with verapamil and nifedipine at a calcium concentration of 1.0 mM during a 20-min period of calcium repletion following a 10-min period of calcium reduction (12 microM calcium) revealed complex dose-response characteristics for each drug. In the dose range studied (0-20 microM), nifedipine was able to reduce enzyme leakage maximally by 57 +/- 8% and verapamil by 37 +/- 4%. Optimal concentrations for verapamil and nifedipine were 4.0 and 2.0 microM, respectively. Both drugs exhibited bell-shaped dose-response curves without a loss of efficacy at higher concentrations. There was no resumption in contractile activity in the drug-treated groups. Simultaneous use of verapamil and nifedipine at their optimal concentrations failed to improve the reduction in enzyme leakage to a reduction greater than that observed with one drug alone.

Animals↗
PubMed1984

Epidemiology of malignant mesothelioma in Western Australia.

Crocidolite was mined and milled at Wittenoom Gorge in Western Australia from 1943 to 1966. Between 1960-1964 and 1980-1982, the estimated incidence of malignant mesothelioma in Western Australia rose from 0.6/100 000 in men and less than 0.1/100 000 in women, aged 35 years or older, to 6.6/100 000 in men and 0.7/100 000 in women in this age group. Overall, 97 (70%) of 138 patients with malignant mesothelioma had definite or probable exposure to asbestos; 76 of these (55%) to Western Australian crocidolite. Of the latter 76 patients, 56 had worked in the mine or mill at Wittenoom and 4 had non-occupational exposure in the Wittenoom area; the remaining 16 had been exposed to crocidolite elsewhere in the State. There were only 4 (3%) patients with malignant peritoneal mesothelioma, of whom three had been exposed to crocidolite.

Adult↗
PubMed1984

Calcium delivery and time: factors affecting the progression of cellular damage during the calcium paradox in the rat heart.

Using an isolated rat heart preparation we have investigated the influence of calcium delivery and time upon the induction of cellular injury during the calcium paradox. Hearts were subjected to 10 min of calcium depletion. This was followed by calcium repletion for up to 20 min during which time the calcium concentration in the perfusate was varied between 0.025 and 1.00 mmol X litre-1. For the lowest calcium repletion concentration, cumulative leakage of creatine kinase activity was small and linear with time over the 20 min repletion period, and relatively few damaged cells were observed, these being situated around coronary vessels. For calcium concentrations of 0.05 mmol X litre-1 and above the progression of structural injury was dependent on both increasing calcium concentration and time. After 1 min of repletion with 0.10 mmol calcium X litre-1 the percentage damaged cells was 2%, this sharply increased to 95% after 10 min of repletion but without a parallel increase in the profile for creatine kinase leakage. For calcium repletion at 0.05 mmol X litre-1 morphological injury was shown to be highly heterogeneous both within and between hearts. Uniform cellular damage (ie greater than 95%) in the concentration range 0.25 to 1.00 mmol calcium X litre-1 was only seen after 10 min of calcium readmission. Maximal cumulative creatine kinase activity only occurred after 15 to 20 min of repletion with 0.50 and 1.00 mmol calcium X litre-1. Our results show calcium delivery and time can both modulate the progression of cellular injury and allow a dissociation between indices of tissue damage.

Animals↗
PubMed1983

Slow calcium channel blockers and the calcium paradox: comparative studies in the rat with seven drugs.

In studies of the calcium paradox, the isolated perfused rat heart was used to characterize the relationship between myocardial protein leakage and the concentration of calcium antagonist (verapamil and D600) or calcium in the perfusion fluid during a cycle of calcium depletion and repletion. The results indicated a dose-dependency such that protein leakage could be progressively reduced by decreasing the concentration of calcium during calcium repletion and/or by increasing the concentrations of drug. Detailed dose-response studies with seven calcium antagonists (verapamil, D600, nifedipine, terodiline, diltiazem, fendiline and prenylamine) and a calcium concentration of 1.0 mmol/l during a 20 min period of calcium repletion following a 10 min period of calcium depletion revealed complex dose-response characteristics for each drug. In the dose range studied (0 to 40 mumol/l) all drugs with the exception of prenylamine were able to reduce protein leakage by up to 25 to 30% Optimal concentrations for verapamil, nifedipine, D600, diltiazem and terodiline were all between 2.0 and 4.0 mumol/l. With the exception of D600, which provided a constant reduction of protein leakage at all concentrations above this optimum, all drugs exhibited bell-shaped dose-response curves with a loss of efficacy at higher concentrations. Fendiline also had a bell-shaped dose-response curve with 23% as a maximal reduction of leakage; however, the optimal concentration for this drug was 21.0 mumol/l. Additional studies with verapamil revealed that the drug acted during the calcium repletion phase and did not influence events during calcium depletion. Simultaneous use of two drugs, verapamil and nifedipine, at their optimal concentrations failed to improve the reduction in protein leakage over and above that observed with one drug alone.

Animals↗
PubMed1983

The temperature dependence of the calcium paradox: enzymatic, functional and morphological correlates of cellular injury.

An isolated rat heart preparation was used to characterize the temperature dependence of the calcium paradox and also to assess the validity of various indices of hypothermic protection. Hearts were subjected to 10-min periods of calcium depletion at various degrees of hypothermia followed by 20 min of normothermic calcium repletion. Using enzyme or protein leakage during calcium repletion as an index of hypothermic protection during calcium depletion, paradox injury was reduced extensively by relatively moderate hypothermia. Thus, depletion at 29 degrees C reduced total creatine kinase leakage by 57 +/- 4% from 1585 +/- 24 IU/g dry wt to 677 +/- 63 IU/g dry wt and at 25 degrees C leakage was reduced by 85 +/- 4% from 1585 +/- 24 IU/g dry wt to 237 +/- 71 IU/g dry wt. However, upon calcium repletion there was no recovery of contractile function. It was not until the myocardial depletion temperature was reduced to 20 degrees C that some functional recovery occurred. Under these circumstances cumulative creatine kinase leakage was reduced to below 88 IU/g dry wt, 6% of its normothermic value and protein leakage was undetectable. Functional recovery was not complete until the temperature was reduced to 15 degrees C or below. Correlation of cumulative enzyme leakage with functional recovery suggested a narrow release threshold (50 to 100 IU/g dry wt) above which no recovery occurred and below which a full recovery could be confidently predicted. Morphological assessments an all-or-none phenomenon; thus although increasingly severe hypothermia progressively reduced the percent of cells that sustained damage (as opposed to the degree of damage in all cells), it was not until 100% of cells appeared ultrastructurally undamaged that functional recovery was observed. Calcium-free perfusion at 4 degrees C protected the intercalated discs from gross lesions and prevented the separation of the external lamina from the surface coat. Our results also stress the heterogeneity of tissue injury and hypothermic protection and in addition shed further light upon the component mechanisms contributing to calcium injury.

Animals↗
PubMed1983

The temperature-sensitivity of slow channel calcium blockers in relation to their effect upon the calcium paradox.

The isolated perfused rat heart preparation was used to investigate the interrelationship between temperature and the ability of calcium antagonists to reduce protein leakage in the calcium paradox. Exploiting the fact that although the calcium depletion phase of calcium paradox-injury is highly temperature sensitive, the calcium repletion phase, during which time the injury is manifested, is temperature independent. Verapamil (4 mumol l-1) included in a 10 min period of calcium depletion (37 degrees C) and a 20 min period of calcium repletion (37 degrees C) was known to reduce cumulative protein leakage by 22 +/- 3%. With calcium depletion again at 37 degrees C but repletion at 21 degrees C verapamil failed to achieve any reduction in protein leakage despite the fact that leakage in the 21 degrees C control group did not differ significantly from that in the 37 degrees C control group. Temperature-response studies (repletion temperature of 4, 10, 21, 23, 25, 28, 31, 34 and 37 degrees C) revealed an abrupt loss of drug effect below 25 degrees C. Studies with D600 (10 mumol l-1), nifedipine (4 mumol l-1), terodiline (4 mumol l-1) fendiline (20 mumol l-1) and diltiazem (2 mumol l-1) revealed that while all of these drugs reduced protein leakage at 37 degrees C (24 +/- 3%, 31 +/- 2%, 31 +/- 3%, 23 +/- 3% and 29 +/- 3%, respectively), like verapamil they had no effect at 21 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗