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Biomedical subjects

L Frey

Publications and source records attributed to L Frey.

At least 37 records · Page 2Linked to original sources

Global tissue oxygenation during normovolaemic haemodilution in young children.

Sixteen patients (1-8 years) scheduled for major general surgery were chosen for the study. They were divided into two groups according to the replacement solution used for haemodilution (HD); whether 6% middle molecular weight hydroxyethyl starch (HES) or 6% dextran 60 (DEX). After induction of general anaesthesia and pulmonary artery catheterization, a precalculated amount of autologous blood was withdrawn while the patient's autologous blood was simultaneously replaced by either HES or DEX. Autologous blood was retransfused at a minimum haematocrit (Hct.) of 17% or at the end of surgery. The following parameters were measured and/or calculated before and after HD, every 20 min intraoperatively and hourly for 6 h postoperatively: heart rate (HR), mean arterial pressure (MAP), Cardiac index (CI), Hct., arterial and mixed venous oxygen content (CaO2, CvO2) and arterio-venous difference of oxygen content (avDO2), oxygen delivery index (DO2I), oxygen consumption index (VO2I). The cardiovascular system remained stable. There was no significant difference as regards SvO2, despite a significant decrease in CaO2 to 10.8 and 10.0 ml.dl-1 (median values) due to reduction of haemoglobin concentration in the HES and DEX groups respectively. In spite of the low hct. values during surgery DO2I remained in normal range (median value 602 and 710 ml.min-1.m-2) in HEX and DEX group respectively. There was no significant change in VO2I after haemodilution (median value 212 and 243 ml.min-1.m-2) in either group. No statistically significant difference was noticed between either groups regarding: CaO2, CvO2, DO2I, VO2I, and no side effects of the colloids were observed. Isovolaemic haemodilution (Hct. approximately 17%) is well tolerated by young children undergoing major elective surgery; global tissue oxygenation was preserved throughout the procedure and both solutions used for haemodilution were equally effective.

Anesthesia, General↗

Effect of hypertonic saline/dextran on post-stenotic myocardial perfusion, metabolism, and function during resuscitation from hemorrhagic shock in anesthetized pigs.

Resuscitation using small volumes of hypertonic saline solutions normalizes cardiac output without fully restoring arterial pressure. This study compared the efficacy of either 7.2% saline/10% dextran 60 (HSDex) or the identical sodium load of normal saline (NS) to improve regional myocardial blood flow (MBF), contractile function, and oxygen metabolism in the presence of a critical coronary stenosis. Fourteen anesthetized, open-chest pigs (25 +/- 3.6 kg) were instrumented to assess left anterior descending coronary artery (LAD) flow, post-stenotic oxygen, and lactate metabolism, regional myocardial segment shortening (SS, sonomicrometry), and MBF (radioactive microspheres). After implementation of a critical LAD-stenosis, shock was induced by hemorrhage (mean arterial pressure (MAP) 45-50 mmHg for 75 min). Resuscitation was started by infusion (2 min) of either HSDex (n = 7,10% of blood loss) or NS (n = 7, 80% of blood loss); 30 min later 6% dextran 60 (10% of blood loss) was administered in both groups. The LAD-stenosis did not affect myocardial metabolism, SS, or MBF at rest. After hemorrhage, MBF remained unchanged from baseline in non-stenotic but decreased by 53% in post-stenotic myocardium (p < .05). The endo-epicardial flow ratio fell below 1.0 in both areas. SS decreased by 10-15% only in post-stenotic myocardium (p < .05). Resuscitation with both HSDex and NS restored cardiac index (CI) but not MAP. MBF increased above baseline values with either solution in non-stenotic while it remained at shock levels in post-stenotic myocardium, where ischemia persisted as evidenced by lactate production and depressed SS. Neither in non-stenotic nor in post-stenotic myocardium was the epi-endocardial flow ratio normalized upon resuscitation with HSDex or NS. We conclude that in the presence of a flow-limiting coronary stenosis, initial fluid resuscitation with both HSDex and the identical sodium load of NS failed to restore perfusion pressure, redistributed MBF in favor of normally perfused myocardium, and did not reverse ischemia in post-stenotic myocardium.

Animals↗

Arginine biosynthesis and regulation in Lactobacillus plantarum: the carA gene and the argCJBDF cluster are divergently transcribed.

A cluster of citrulline biosynthetic genes has been cloned and sequenced from a fragment of Lactobacillus plantarum CCM 1904 (ATCC 8014) DNA isolated as complementing a Bacillus subtilis argF mutation. The gene order was carA-argCJBDF, with carA transcribed divergently from the arg cluster. Although other gram-positive bacteria show similar arg clusters, this arrangement for carA is thus far unprecedented. Downstream from the arg cluster, two open reading frames (ORF7 and ORF8) having unknown functions were found. Sequence analysis of the end of a 10.5-kb cloned DNA fragment showed that argF was 3.5 kb from the ldhL gene coding for L-(+)-lactate dehydrogenase. A tree representation of amino acid sequence clustering relationships of 31 ornithine carbamoyltransferases (OTCases) from various organisms revealed two prokaryotic groups: one with ArgF of L. plantarum and one with ArgF of B. subtilis, which are paralogous. This divergence was not observed in vivo because an L. plantarum argF mutant (AM 1215) harboring no OTCase activity was complemented by the argF genes of L. plantarum and B. subtilis. No OTCase activity was detectable when L. plantarum was grown in the presence of saturating amounts of arginine or citrulline. Arginine may repress the citrulline biosynthetic genes in L. plantarum by using 11 identified DNA motifs which resemble the Escherichia coli ARG box consensus and which are in most cases separated by multiples of 11 bp, corresponding to a DNA helical turn. The carA and argCJBDF genes are divergently transcribed. Their putative promoters are 6 bp apart and are partially overlapped by putative ARG boxes, suggesting concerted transcription regulation.

Arginine↗

Reference intervals of CD3, CD4, CD8, CD4/CD8, and absolute CD4 values in Asian and Non-Asian populations.

A study to determine reference intervals in normal Asian and non-Asian populations for CD3 (T cells), CD4 (T helper/inducer cells), CD8 (T suppressor/cytotoxic cells), and for the CD4/CD8 ratio and absolute CD4 lymphocyte count was performed. Coulter Clone/Cytostat reagents were used. The samples were lysed using the Coulter Q-Prep and analyzed on the Coulter Profile II flow cytometer. The Asian population appeared to have a lower mean percentage of CD3 and CD4 cells, a lower CD4/CD8 ratio, and lower absolute CD4 lymphocytes. These findings indicate that race should be a consideration in determining reference intervals for immunophenotyping for CD3, CD4, and CD8.

Adult↗

Assessment of splanchnic tissue oxygenation by gastric tonometry in patients undergoing laparoscopic and open cholecystectomy.

This experimental study compared the effects of laparoscopic (n = 31) and open (n = 32) cholecystectomy on gastric intramucosal pH (pHi). For this purpose, pHi was measured tonometrically before induction of anaesthesia, at 30-min intervals during surgery, and 1, 2 and 4 h after operation in otherwise healthy patients undergoing elective cholecystectomy. Additionally, perioperative arterial pH (pHa), arterial carbon dioxide tension (PaCO2), intramucosal carbon dioxide tension, arterial bicarbonate concentration, end-tidal carbon dioxide pressure (PECO2), levels of serum lactate, lactate dehydrogenase (LDH) and gamma-glutamyl transferase (GGT), haematocrit and arterial blood pressure were recorded. In the two groups no significantly different changes occurred in pHi, pHa, serum lactate concentration or haematocrit at any of the observation times. PECO2 and PaCO2 were significantly raised during the laparoscopic procedure, whereas levels of LDH and GGT and arterial blood pressure rose during and after open cholecystectomy. In spite of the increased intra-abdominal pressure and the peritoneal carbon dioxide absorption related to the creation of a pneumoperitoneum, no decrease in pHi was detectable during laparoscopic cholecystectomy.

Adult↗

Quantitative evaluation of manganese-52m as a myocardial perfusion tracer in pigs using positron emission tomography.

There is a need for a quantitative myocardial perfusion agent that does not require an on-site cyclotron. Early studies with manganese demonstrated that this trace metal is of potential use for myocardial imaging. 52mMn can be produced in a 52Fe-52mMn generator and is suitable for positron emission tomographic (PET) imaging. The purpose of this study was to evaluate 52mMn with regard to its potential to quantitatively assess myocardial perfusion. Dynamic PET imaging was performed in six pigs with various doses of dipyridamole to increase blood flow. Retention (R) and model-based K1 values were correlated with microsphere blood flow. The models consisted of one (K1, k2) and two (K1, k2, k3) tissue compartments. Anterior, lateral and septal regions showed a good myocardium-to-background ratio; the evaluation of the inferior wall was impaired by high liver uptake. Linear regression yielded the following equations: K1=1.152 flow+0.059 (r=0.92), R=0.069 flow+0.034 (r=0.84). Based on these regressions, K1 increased 2.7-fold and R 2.6-fold in the examined flow range of 0.5-2 ml/min/g (fourfold increase), demonstrating an underestimation of higher flow rates by both measures. It is concluded that 52mMn allows the qualitative assessment of myocardial perfusion but does not meet the requirements of a quantitative myocardial perfusion agent.

Animals↗

Hypovolemic shock and cardiac contractility: assessment by end-systolic pressure-volume relations.

The end-systolic pressure-volume relation (ESPVR) is accepted as a load-independent measure of cardiac contractility. Potential curvilinearity of the ESPVR, dependency on coronary perfusion pressure (CPP) and sensitivity to the type of loading intervention might limit its use in hemorrhagic shock. This study compared ESPVRs obtained by caval and aortic occlusion under physiological loading conditions at baseline with those obtained during hemorrhagic shock (mean arterial pressure 45 mmHg). The left ventricular (LV) pressure (tip manometer) and volume (conductance catheter) were measured in ten anesthetized pigs. ESPVRs were fitted to linear and quadratic models. Within end-systolic pressure (Pes) ranges obtained under baseline conditions, ESPVR displayed only minimal curvilinearity (second-order coefficient a < 0.007) and could be accurately described by a linear model. However, nonlinearity of ESPVRs obtained over wider load ranges is suggested by negative volume axis intercepts of the linear model. Steeper ESPVR with aortic than with caval occlusion (2.28 +/- 0.22 vs 3.41 +/- 0.51 mmHg/ml, ns) could not be proven owing to the large interindividual variance of ESPVR slopes with both loading interventions. During shock the Pes range obtained by caval occlusion decreased to very low levels (from 49 +/- 2 to 34 +/- 1 mmHg), ESPVR did not adequately fit either of the two models (mean R < 0.66), and critical reduction of CPP induced negative ESPVR slope in four of ten experiments. In contrast, aortic occlusion at shock resulted in linear ESPVR (R = 0.927 +/- 0.029), Pes ranges (92 +/- 3 to 58 +/- 4 mmHg) comparable to the ones obtained by caval occlusion at control (113 +/- 5 to 73 +/- 6 mmHg), and steeper ESPVR than at control (3.41 +/- 0.51 to 7.38 +/- 1.0 mmHg/ml, P < 0.05). Interpretation of the increased ESPVR slope obtained with aortic occlusion as due to increased contractility in shock is, however, complicated by different Pes ranges. It is concluded that within Pes ranges obtained with caval or aortic occlusion in situ the ESPVR can be adequately fitted to a linear model. For assessment of the inotropic response to shock the ESPVR is of limited value because (1) caval occlusion is not suitable to generate ESPVR during shock, and (2) Pes ranges obtained with identical loading interventions differ greatly between baseline and shock and, therefore, apparent ESPVR changes are influenced by the potential nonlinearity of the ESPVR. Combining caval occlusion at baseline with aortic occlusion at shock would result in comparable Pes ranges. Interpretation of results is, however, complicated by diverging effects of the different loading interventions on the shape and slope of the ESPVR.

Animals↗

Perioperative mucosal pH and splanchnic endotoxin concentration in orthotopic liver transplantation.

Although impairment of splanchnic perfusion may induce mucosal hypoxia and endotoxaemia during orthotopic liver transplantation (OLT), little is known about the changes in mucosal oxygenation during and after the procedure. To study the effects of liver surgery itself on mucosal pH (pHi) and the response of pHi to acute changes in portal flow, we measured gastric pHi during six liver resections using tonometry: in two patients, after clamping of the hepatoduodenal ligament, pHi decreased within 30 min and recovered promptly after reperfusion. We then investigated gastric and sigmoid pHi (pHig, pHis) during the perioperative phase in 18 OLT. Median pHi values were low before surgery (pHig 7.28 (first/third quartiles 7.22/7.34); pHis 7.27 (7.12/7.36)). Although global oxygen delivery and haemodynamic variables remained constant and veno-venous bypass (VVB) was used to maintain portal flow, pHi declined during the anhepatic phase (pHig 7.19 (7.13/7.23), P < 0.01; pHis 7.13 (7.06/7.24), P < 0.05). After reperfusion of the graft, pHi recovered and did not differ from baseline values by the end of OLT. After operation pHig increased further, reaching the highest values 30 h after ICU admission (7.34 (7.26/7.38)). In the intraoperative period, no significant endotoxaemia was observed either in portal or systemic blood. The maximum reduction in pHi was related neither to the duration of VVB and OLT nor to the number of red cell units transfused. pHi after reperfusion did not correlate with graft viability or dysfunction of the lung or kidney. We conclude that pHi indicates mucosal ischaemia during OLT which is not necessarily associated with endotoxaemia, and intraoperative pHi monitoring does not appear to be a valuable predictor of postoperative graft failure and organ dysfunction.

Adult↗

Hypertonic saline dextran does not increase cardiac contractile function during small volume resuscitation from hemorrhagic shock in anesthetized pigs.

Small volumes of hypertonic saline dextran (10% of shed blood volume [SBV] restore cardiac output (CO) and increase arterial pressure in hemorrhagic shock. Besides rapid expansion of plasma volume, a positive inotropic effect has been proposed as an additional mechanism for the immediate onset of the cardiovascular response. This study compares the effects of 7.2% saline/10% dextran 60 (HSDex, n = 8) and normal saline (NS; n = 6) on central hemodynamics and cardiac contractility assessed by end-systolic elastance (Ees; conductance technique) and segmental preload recruitable stroke work (sPRSW; sonomicrometry). In anesthetized open chest pigs (28 +/- 1 kg, mean +/- SEM) shock was induced by blood withdrawal (40% of blood volume) to maintain mean arterial pressure (MAP) at 45 mm Hg for 75 min. Resuscitation was started by bolus infusion (2 min) of either HSDex (10% of SBV) or the identical sodium load of NS (80% of SBV); 30 min later both groups received 6% dextran (10% of SBV). Hemorrhagic shock reduced CO (-45%) and left ventricular end-diastolic volume (Ved; -70%) while Ees increased (NS:2.2 +/- 0.4 to 7.5 +/- 1.8 mm Hg/mL, P < 0.05; HSDex: 1.9 +/- 0.2 to 9.1 +/- 2.6 mm Hg/mL, P = 0.085). Within 5 min after infusion of either solution CO returned to baseline values and MAP (NS +55%, HSDex +64%) and Ved (+100%) increased. Neither HSDex nor NS increased Ees above shock levels (NS, 8.7 +/- 4.9 mm Hg/mL; HSDex, 7.3 +/- 2.6 mm Hg/mL) and no group differences occurred in other measurements of contractility (dP/dt40,sPRSW). Plasma osmolality increased to 328 +/- 3 mOsmol/kg with HSDex.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Is sodium acetate dextran superior to sodium chloride dextran for small volume resuscitation from traumatic hemorrhagic shock?

Small volumes (4 mL/kg body weight (bw)) of hypertonic sodium chloride dextran effectively restore cardiac output and nutritional blood flow and increase arterial pressure in severe hemorrhagic shock. It has been suggested that the chloride anion be replaced with acetate to provide a solution that avoids the risk of hyperchloremia and has the advantage of supplying a buffering base to optimize hypertonic resuscitation. This study compares the effects of hypertonic sodium chloride dextran solution (7.2% NaCl/10% dextran 60 [NaCl-Dx]; n = 7) with sodium acetate dextran (10.4% Na-Ac/10% dextran 60 [NaAc-Dx]; n = 6) on hemodynamic, oxygen transport, and metabolic variables. Both solutions had the identical osmolality (2400 mOsmol/kg). Dogs (16.9 +/- 1.9 kg) were anesthetized and mechanically ventilated. Shock was induced by exteriorization of intestine and blood withdrawal (50% of blood volume) to maintain mean arterial blood pressure (MAP) at 40 mm Hg for 75 min. Thereafter, resuscitation was performed either with NaCl-Dx (4 mL/kg over 2 min) or NaAc-Dx (4 mL/kg over 4 min). During hypertonic resuscitation, there was a short-lasting decrease in MAP, which was more pronounced in the NaAc-Dx group (delta MAP -7.3 +/- 2.5 mm Hg). Cardiac index and oxygen consumption were normalized within 5 min after resuscitation with both solutions. In NaAc-Dx-treated animals, MAP remained at lower values as compared to NaCl-Dx-treated dogs at 5 and 30 min after resuscitation (52 +/- 3 vs 74 +/- 6, and 61 +/- 7 vs 79 +/- 12 mm Hg; P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Acetates↗

Biodistribution and estimated radiation burden for a new 123I-labelled monoamine oxidase-B inhibitor, Ro 43-0463: a preliminary report.

The selective, reversible inhibitor of monoamine oxidase B (MAO-B), Ro 19-6327 (Lazabamide) N-aminoethyl-5-chloro-picolinamide, inhibits the enzyme with an initial competitive phase, followed by a time-dependent inhibition of MAO-B; i.e. Ro 19-6327 is a substrate for MAO-B, and after its oxidation it is activated into an intermediate form which remains tightly bound to the enzyme's active site. Our radiopharmaceutical is a new 123I-labelled derivative of Ro 19-6327, N-aminoethyl-5-[123I]iodo-picolinamide, which seems to be a potentially useful SPECT tracer for the imaging of the MAO-B enzyme distributions. The first biodistribution of this compound was measured in rats at 6 different points in time (10, 25, 40, 60, 180 and 900 minutes post-injection). For each point the average from three animals was taken. In the brain there was an activity plateau over the first hour. In the first hour post-injection the brain-to-blood ratio was over 1, with a maximum ratio of 1.24 at 25 minutes post-injection. Because MAO-B is abundant in the ependyma, pineal and cerebellar Bergmann glia cells, this ratio of 1.24 over the whole brain is encouraging. At first, radioactivity was principally and rapidly accumulated in the liver. After 1 hour, about 37% of the injected activity is accumulated there. The elimination of the compound seemed to take place mainly through the hepatobiliary system (about 75%), but also via the kidneys (about 25%). Fifteen hours post-injection, only 4% (corrected for decay) of the injected radioactivity was left in the body.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

A comparative study of prothrombinase and thrombin inhibitors in a novel rabbit model of non-occlusive deep vein thrombosis.

A quantitative and non-occlusive deep vein thrombosis model was developed in rabbits. We used this model to test the antithrombotic activity of the prothrombinase complex inhibitors factor rXai and its chemical analog glutamyl-glycyl-arginyl chloromethyl ketone inactivated human factor Xa (EGR-Xai), along with the thrombin inhibitors D-phenylalanyl-prolyl-arginyl chloromethyl ketone (PPACK) and heparin. Dose dependent effects of the inhibitors during constant infusion were monitored. Measurements included thrombus weights, hemostatic parameters and both cuticle and ear bleeding times. In this model, factor rXai and EGR-Xai had comparable in-vivo efficacy, and showed 80%-93% inhibition at plasma levels of 6.5 nM (rXai) and 8 nM (EGR-Xai). Effects on ex-vivo clotting times varied among the inhibitors. At 80-100% thrombus inhibition, factor rXai and EGR-Xai had no statistically significant effect, while PPACK extended thrombin clotting time (TCT) times 2.3-fold, and heparin prolonged both activated partial thromboplastin time (APTT), prothrombin time (PT) and TCT ex-vivo clotting times 6.9-, 1.2-, and 7-fold respectively. At these dosages, cuticle and ear bleeding times were prolonged for all inhibitors and showed increases of 177%-389% (cuticle) and 45%-129% (ear). Our results demonstrate that direct inhibition of prothrombinase complex assembly is effective in arresting venous thrombosis.

Amino Acid Chloromethyl Ketones↗

A rural emergency department.

The appropriate use of emergency departments is of growing concern. By knowing which patients are more likely to make inappropriate visits to these departments, efforts can be directed to encourage more suitable care. Our study was done in a rural county hospital in eastern New Mexico. Data were collected from all emergency department visits over a 4-week period. Patient and physician questionnaires were administered to assess aspects of emergency department use, including appropriateness based on published criteria, physicians' opinion of appropriateness, groups who made inappropriate visits, and the perception of the need for and the urgency of a visit. We found that 32% of visits were inappropriate based on published criteria and 24% were considered inappropriate by physician opinion. Two groups with a high rate of inappropriate visits were Hispanics and Medicaid recipients. Patients and physicians have differing opinions of the urgency of a visit and of how soon medical treatment is required. To decrease the frequency of inappropriate use of emergency departments, educational efforts should be focused on the subgroups with high rates of such use.

Adolescent↗

Filament lengths in frog semitendinosus and tibialis anterior muscle fibres.

In frog semitendinosus muscle the descending limb of the length-tension curve is shifted rightward relative to that of tibialis anterior. Both the plateau right corner and the zero-force intercept are equally shifted. To investigate the reason for this shift, we compared filament lengths in the two muscles. Single fibres were mechanically skinned, stretched to reveal filaments clearly, incubated in a solution containing one of several antibodies to enhance filament visualization, and examined by electron microscopy. We found no differences of filament length. Thick filament lengths were 1.62 and 1.61 microns, respectively. I-segment lengths were measured by two methods. With the first, filament length was the same for both muscles, 1.95 or 1.98 microns, depending on the value taken for the troponin repeat; with the second it was 1.92 and 1.94 microns, respectively, for the two muscles. These differences are insignificant. Thus, the reported differences of shape of the length-tension curve are not explainable in terms of differences of filament length.

Actin Cytoskeleton↗