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Biomedical subjects

P D Allen

Publications and source records attributed to P D Allen.

At least 127 records · Page 7Linked to original sources
PubMed1988

Effects of milrinone on Ca++-sensitivity of myofibrillar Mg-adenosine triphosphatase isolated from normal human and canine hearts.

Sensitization or desensitization of cardiac actomyosin to calcium has been demonstrated with several pharmacological agents. The effect of milrinone on the sensitivity of cardiac Mg-adenosine triphosphatase (ATPase) activity to calcium was studied in purified myofibrils isolated from normal human hearts (after accidental death or trauma that caused no cardiac damage as established by the attending physician) and from normal canine hearts (established by echocardiography), over a range of calcium concentrations (pCa, 8 to 5). Caffeine, a cardiac stimulant that has been shown to increase the sensitivity of myofibrillar Mg-ATPase activity to calcium in rat ventricle, was used in this study to establish its effect on canine and human myofibrils in comparison with that of milrinone. Caffeine, at concentrations of 40 mM, caused statistically significant sensitization of canine and human myofibrils to calcium. In canine myofibrils, the calcium-dependent Mg-ATPase activity increased from 11.0 +/- 1.2 to 18.8 +/- 2.6 nmol of Pi per mg of protein per min at pCa 6.73 (N = 9, P less than .05) and from 32.9 +/- 2.1 to 37.3 +/- 2.2 nmol of Pi per mg of protein per min at pCa 6.16 (N = 9, P less than .05), whereas total Mg-ATPase activity increased from 23.4 +/- 1.5 to 33.6 +/- 2.6 nmol of Pi per mg of protein per min at pCa 6.73 (N = 9, P less than .05) and from 45.2 +/- 2.2 to 52.2 +/- 2.5 nmol of Pi per mg of protein per min at pCa 6.16 (N = 9, P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Is mammography painful? A multicenter patient survey.

Anecdotal reports of pain experienced during mammography have been a source of anxiety and concern for some women considering screening. To determine what asymptomatic women actually experience during mammography, a survey of 1847 women was performed at seven breast-imaging centers. Women recorded their experience on a six-point scale ranging from no discomfort to severe pain. Eighty-eight percent of the women experienced no discomfort (49%) or mild discomfort (39%). Only 9% experienced moderate discomfort; 1%, severe discomfort; and 1%, moderate pain. No woman had pain so severe that it would make her reconsider having a mammogram again. The degree of discomfort was slightly greater in women who complained of breast tenderness within three days prior to the mammogram but was not strongly related to age, menstrual status, or week of the menstrual cycle. We conclude that in a vast majority of women mammography causes no or mild physical discomfort and that actual pain is an uncommon occurrence.

Adult↗
PubMed1987

Comparison of contractile state and myosin isozymes of rat right and left ventricular myocardium.

We compared myocardial mechanics and myosin isozymes of right and left ventricular papillary muscles from adult (6 to 8 month old) male rats. Analysis of force velocity relations indicate that right ventricular papillary muscles contract more rapidly than left at light loads (2.68 +/- 0.13 vs 2.18 +/- 0.07 muscle lengths/s measured 75 ms following stimulation, at 0.5 g/mm2; P less than 0.01). Right ventricular papillary muscles had significantly more of the alpha heavy chain containing V1 myosin isozyme and less of the V3 containing beta heavy chain myosin isozyme than left ventricular preparations (P less than 0.05). Papillary muscle and ventricular free wall myosin isozyme distribution were not significantly different within their respective chambers. The presence of a relatively larger proportion of the alpha heavy chain containing myosin isozyme (V1) in right ventricle papillary muscles relative to left correlated with the more rapid velocities of shortening seen in right ventricular papillary muscles (r = 0.60; P less than 0.01).

Animals↗
PubMed1986

Epidural morphine provides postoperative pain relief in peripheral vascular and orthopedic surgical patients: a dose-response study.

A randomized double-blind study compared the dose-response relationship of epidural morphine for postoperative pain relief in two groups of patients whose surgical procedures would result in either moderate (femoral-popliteal bypass) or severe (total knee replacement) postoperative pain. Preservative-free morphine sulphate in doses of 0, 2, 5, or 10 mg in a volume of 10 ml saline were administered via lumbar epidural catheters. The epidural morphine was administered 1 hr after the last dose of intraoperative local epidural anesthetic in an effort to achieve a pain-free postoperative course. A significant relationship existed between the dose of epidural morphine and both time to first required pain medication and 24-hr weighted pain score. Five mg epidural morphine provided significant improvement in postoperative analgesia compared with the control in both groups. Further enhancement of analgesia occurred with 10 mg; however, late respiratory depression, demonstrated by an increased resting PaCO2 10 hr after administration, was seen only with the 10-mg dose in both surgical groups. Minor complications such as nausea, vomiting, pruritus, and urinary retention were uncommon and did not appear to be related to dose. We found that 5 mg epidural morphine provided long-lasting postoperative analgesia without serious adverse effects after peripheral vascular and orthopedic surgery.

Adult↗
PubMed1985

The creatine kinase system in normal and diseased human myocardium.

We measured creatine kinase activity, isozyme composition, and total creatine content in biopsy samples of left ventricular myocardium from 34 adults in four groups: subjects with normal left ventricles, patients with left ventricular hypertrophy due to aortic stenosis, patients with coronary artery disease without left ventricular hypertrophy, and patients with coronary artery disease and left ventricular hypertrophy due to aortic stenosis. As compared with specimens of normal left ventricles, those from all patients with left ventricular hypertrophy had lower creatine kinase activity, higher MB creatine kinase isozyme content and activity, and lower creatine content. Specimens from the patients without left ventricular hypertrophy had normal creatine kinase activity, increased MB creatine kinase isozyme content and activity, and decreased total creatine content. The normal ventricles showed almost no MB isozyme content or activity. These data suggest that changes in the creatine kinase system occur in both pressure-overload hypertrophy and coronary artery disease. Patients with myocardial infarction who have mild or no preexisting fixed coronary artery disease or pressure-overload hypertrophy would not be expected to have elevation of serum MB creatine kinase.

Adult↗
PubMed1985

23Na and 39K nuclear magnetic resonance studies of perfused rat hearts. Discrimination of intra- and extracellular ions using a shift reagent.

High-resolution 23Na and 39K nuclear magnetic resonance (NMR) spectra of perfused, beating rat hearts have been obtained in the absence and presence of the downfield shift reagent Dy(TTHA)3- in the perfusing medium. Evidence indicates that Dy(TTHA)3- enters essentially all extracellular spaces but does not enter intracellular spaces. It can thus be used to discriminate the resonances of the ions in these spaces. Experiments supporting this conclusion include interventions that inhibit the Na+/K+ pump such as the inclusion of ouabain in and the exclusion of K+ from the perfusing medium. In each of these experiments, a peak corresponding to intracellular sodium increased in intensity. In the latter experiment, the increase was reversed when the concentration of K+ in the perfusing medium was returned to normal. When the concentration of Ca2+ in the perfusing medium was also returned to normal, the previously quiescent heart resumed beating. In the beating heart where the Na+/K+ pump was not inhibited, the intensity of the intracellular Na+ resonance was less than 20% of that expected. Although the data are more sparse, the NMR visibility of the intracellular K+ signal appears to be no more than 20%.

Animals↗
PubMed1984

Kinetic studies of Ca2+ release from sarcoplasmic reticulum of normal and malignant hyperthermia susceptible pig muscles.

The time-course of Ca2+ release from sarcoplasmic reticulum isolated from muscles of normal pigs and those of pigs susceptible to malignant hyperthermia were investigated using stopped-flow spectrophotometry and arsenazo III as a Ca2+ indicator. Several methods were used to trigger Ca2+ release: (a) addition of halothane (e.g., 0.2 mM); (b) an increase of extravesicular Ca2+ concentration ([Ca2+0]); (c) a combination of (a) and (b), and (d) replacement of ions (potassium gluconate with choline chloride) to produce membrane depolarization. The initial rates of Ca2+ release induced by either halothane or Ca2+ alone, or both, are at least 70% higher in malignant hyperthermic sarcoplasmic reticulum than in normal. The amount of Ca2+ released by halothane at low [Ca2+0] in malignant hyperthermic sarcoplasmic reticulum is about twice as large as in normal sarcoplasmic reticulum. Membrane depolarization led to biphasic Ca2+ release in both malignant hyperthermic and normal sarcoplasmic reticulum, the rate constant of the rapid phase of Ca2+ release induced by membrane depolarization being significantly higher in malignant hyperthermic sarcoplasmic reticulum (k = 83 s-1) than in normal (k = 37 s-1). Thus, all types of Ca2+ release investigated (a, b, c and d) have higher rates in malignant hyperthermic sarcoplasmic reticulum than normal sarcoplasmic reticulum. These results suggest that the putative Ca2+ release channels located in the sarcoplasmic reticulum are altered in malignant hyperthermic sarcoplasmic reticulum.

Animals↗
PubMed1984

Determinants of cardiovascular stability during abdominal aortic aneurysmectomy (AAA).

Patients undergoing abdominal aortic aneurysmectomy (AAA) develop depressed cardiac function during aortic clamping. The importance of volume status and thromboxane (Tx) mediated declines in cardiac contractility in determining this event was studied. In a blinded fashion, patients received the cyclo-oxygenase inhibitor ibuprofen 12 mg/kg by mouth (n = 11) or a placebo (n = 15), 1.5 hours prior to surgery. In the placebo group levels of 6-keto-PGF1 alpha, the hydrolysis product of prostacyclin (PGI2) rose from 20 +/- 10 to 1170 +/- 80 pg/ml (p less than 0.05) soon after incision. Concentrations of TxB2, the stable hydrolysis product of TxA2, were unchanged until 30 minutes after the aorta was clamped when arterial TxB2 concentrations rose from 90 +/- 20 to 230 +/- 30 pg/ml (mean +/- SEM) (p less than 0.05). A pulmonary source for PGI2 and TxA2 was indicated by the observation that arterial 6-keto-PGF1 alpha and TxB2 levels exceeded those in pulmonary arterial blood by 180 +/- 50 and 110 +/- 30 pg/ml, respectively (p less than 0.05). Levels of TxB2 in circulating platelets remained unchanged from baseline in the placebo group. During aortic clamping, cardiac index (CI) fell 0.7 +/- 0.2 1/min X m2 (p less than 0.05) in placebo treated patients, and there was a 6% decline in plasma contractility as bioassayed with a rat papillary muscle (p less than 0.05). Placebo patients entered surgery with a PAWP greater than or equal to 10 mmHg (mean 13 mm). Ibuprofen suppressed production of TxB2, such that 30 minutes after aortic clamping TxB2 was 70 +/- 30 pg/ml, a value lower than control patients (p less than 0.05). Further, plasma no longer depressed contractility of the papillary muscle. Five patients given ibuprofen had an initial pulmonary arterial wedge pressure (PAWP) of 10 mmHg or greater (mean 12 mmHg). During aortic clamping there was an insignificant decrease in CI of 0.2 +/- 0.1 1/min X m2. This was in contrast to the CI decrease in six other ibuprofen treated patients of 0.9 +/- 0.2 1/min X m2 whose PAWP at the start of surgery was less than 10 mmHg (mean 6 mmHg) (p less than 0.05), and to placebo patients whose initial PAWP was greater than or equal to 10 (p less than 0.05). Platelet counts fell from 185,000 to 121,000/mm3 in placebo patients (p less than 0.05), but did not fall when ibuprofen was given. Creatinine concentrations were unaffected by ibuprofen. Blood replacement in placebo and ibuprofen patients was similar, 1.90 +/- 0.20 and 0.65 +/- 0.15 1, respectively. Results indicate that CI will not decrease during AAA if sufficient volume is given before surgery to increase PAWP above 10 mmHg, and secondly, if TxB2 synthesis is inhibited.

Aged↗
PubMed1984

Physostigmine: effectiveness as an antagonist of respiratory depression and psychomotor effects caused by morphine or diazepam.

Each of six healthy volunteers was studied on three different occasions to determine the interactions of placebo-physostigmine, diazepam-physostigmine, and morphine-physostigmine with respect to respiration and psychomotor function. Respiratory measurements were made using the steady state and isohypercapnic techniques. Psychomotor function was assessed by the Trieger Dot Test (TDT) and compared with the Continuous Performance Test (CPT). Administration of physostigmine alone (3 mg, iv) did not affect ventilation. Diazepam (0.29 mg/kg, iv) did not cause a significant depression of ventilation in all subjects, although psychomotor function was impaired as measured by the CPT. The latter was unaffected by physostigmine. Administration of morphine (0.21 mg/kg, iv) caused a significant decrease in ventilation that was not antagonized by physostigmine. Morphine did not impair psychomotor function. The authors conclude that physostigmine is an ineffective antagonist of narcotic-induced respiratory depression and that the CPT correlates well with the TDT.

Adult↗
PubMed1983

Dextroamphetamine with morphine: respiratory effects.

The combination of dextroamphetamine and morphine has been shown to be synergistic for analgesia and antagonistic for most other effects. However, the claim that dextroamphetamine antagonizes the respiratory depression caused by morphine has not been well substantiated. In this double-blind study, we investigated respiratory effects, including resting respiration, isohypercapnic ventilation, CO2 response, dose response, and duration of these effects with dextroamphetamine alone and in combination with morphine. Dextroamphetamine alone (0.215 mg/kg) caused increases in minute ventilation and a leftward shift of the CO2 response curve that lasted for less than 2 hours. Dextroamphetamine combined with low-dose morphine (0.15 mg/kg) antagonized respiratory depression throughout the 5-hour observation period. Dextroamphetamine combined with high-dose morphine (0.30 mg/kg) was unable to completely antagonize depressed ventilation, and some residual effects of morphine persisted at 23 hours.

Carbon Dioxide↗
PubMed1982

Energy spectra of secondary neutrons produced by high-energy bremsstrahlung in carbon, nitrogen, oxygen and tissue.

The energy spectra of secondary neutrons produced when bremsstrahlung of end-point energy in the range 10-30 MeV is incident on oxygen, carbon and nitrogen have been calculated. Photonuclear reactions of the type (gamma, n) and (gamma, pn)( have been included. The respective contributions of various nuclear reactions have been adjusted using the published values of experimentally determined cross-sections, or branching-ratios, where these are available. Where no such information exists in the literature, the values have been empirically estimated. Agreements has been obtained between the calculated photoneutron spectra from C, N and O at various energies and the available experimentally-measured spectra. The photoneutron spectra from C, N and O have been combined in the right proportion (C5H40O18N) to compute the spectra of secondary neutrons from tissue irradiated with bremsstrahlung of end-point energy from 10-30 MeV. Mean neutron energies and kerma factors for these spectra have been calculated.

Carbon↗
PubMed1981

Maintenance of cardiodynamics with aspirin during abdominal aortic aneurysmectomy (AAA).

The importance of prostacyclin (PGI2) and thromboxane (Tx) medication of depressed cardiac performance during abdominal aortic aneurysm operative surgery was studied by contrasting the effects of 650 mg aspirin administered 12 hours before operation to that of a placebo. In 11 patients who received a placebo, the stable metabolite of PGI2, 6-keto-PGF1 alpha rose from 0.050 +/- 0.032 eta grams/ml to 0.419 +/- 0.257 eta grams/ml (p less than 0.01) 30 minutes after the skin incision. The stable metabolite of TxA2, TxB2 did not increase until the aorta was clamped when TxB2 rose from 0.089 +/- 0.054 eta grams/ml to 0.193 +/- 0.138 eta grams/ml (p less than 0.05); this was prior to blood transfusion. During aortic clamping cardiac output decreased 27% (p less than 0.001). In vitro testing of patient plasma showed: 1) depressed developed tension (Tpd) of a rat papillary muscle by 16% (p less than 0.05); 3) reduction of Ca++-ATPase and Mg++-ATPase activity in a rat myocardial subfraction of sarcoplasmic reticulum (p less than 0.05); 3) reduction of Ca++-ATPase in a rat myocardial subfraction of myofibrils (p less than 0.01). Aspirin administered to 11 patients produced no measurable changes in blood loss or fluid requirements. Aspirin lowered preoperative 6-keto-PGF1 alpha and TxB2 levels (p less than 0.01) and prevented an increase of either agent during operation. The low Tx levels were associated with a stable cardiac output during aortic clamping. Further, plasma obtained from aspirin-treated patients did not depress papillary muscle contractility nor decrease ATPase activity of either myocardial subfraction. The observation that TxB2 when added to a papillary muscle or myocardial subfractions, did not decrease Tpd or ATPase suggests that TxB2 plays an indirect role in altering cardiac muscle activity. The results indicate that Txs modulate cardiac depression, which can be prevented with 650 mg aspirin before operation.

6-Ketoprostaglandin F1 alpha↗
PubMed1977

Perceived exertion associated with breathing hyperoxic mixtures during submaximal work.

The effect of an enriched inspired oxygen concentration on perceived exertion (RPE) was investigated while running at two submaximal treadmill loads. Twelve males (VO2 max = 49.3 ml/kg-min) worked at 50% and 80% VO2 max, breathing either air or 80% O2-20% N2 in random order using a single blind technique. Subjects were evaluated while running for 10 min and during a 20 min recovery. Heart rate (HR), ventilation (VE), respiration rate (RR), tidal volume (VT) and RPE were measured before, during and after work. Blood lactate was measured 1 min after work. Oxygen concentration did not statistically affect HR, VE, RR or VT during exercise or recovery. At both loads, RPE at the end of exercise was significantly reduced breathing the hyperoxic mixture. At 50% VO2 max, mean RPE decreased from 11.2 breathing room air to 9.6 breathing 80% O2 and, 80% VO2 max, from 13.8 to 11.7 (P less than 0.01). Blood lactates were significantly reduced breathing 80% O2; from 23.4 mg to 13.3 at 50% VO2 max and from 55.5 to 36.5 at 80% VO2 max (P less than 0.01). The RPE correlated with lactate (r=0.64) at the end of work. Results indicate that during moderate and heavy work RPE is significantly affected by the inspired O2 concentration and there is a significant relationship between RPE and blood lactate.

Adult↗