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Biomedical subjects

P M Winter

Publications and source records attributed to P M Winter.

At least 19 recordsLinked to original sources

Fluorine-19 nuclear magnetic resonance imaging and spectroscopy of sevoflurane uptake, distribution, and elimination in rat brain.

BACKGROUND: Determination of macroscopic and microscopic distribution of general anesthetics can facilitate identification of anatomic, cellular, and molecular loci of anesthetic action. Previous attempts to measure brain anesthetic distributions with fluorine-19 (19F) nuclear magnetic resonance (NMR) imaging were conducted at magnetic field strengths lower than 2 Tesla. All have produced only silhouettes of brain tissue. Difficulties intrinsic to NMR imaging of anesthetics include higher anesthetic solubility in extracranial tissues and the lower limits to spin-echo delay times that can be used in conventional NMR imaging methods. So far, such methods have been unable to capture rapidly decaying brain 19F NMR signals. METHODS: 19F NMR imaging and spectroscopy were conducted at 4.7 Tesla using a specially developed NMR probe and new imaging methods. With the new techniques, it was possible to observe directly the uptake, distribution, and elimination in brain of sevoflurane, a fluorinated general anesthetic with special advantages for NMR investigations. RESULTS: 19F NMR images, acquired at different times after sevoflurane administration, clearly showed the distribution of a fluorinated general anesthetic within the brain. Based on continuous transverse relaxation time measurements, sevoflurane signals could be separated into two components, attributable respectively to sevoflurane in a mobile or immobile microenvironment. During washin, there was a delayed accumulation of anesthetic in the mobile microenvironment. During washout, there was a rapid elimination from the immobile microenvironment. CONCLUSIONS: At anesthetizing concentrations, sevoflurane distributes heterogeneously in the brain. Sevoflurane in the brain tissue contributes mostly to the immobile component of the 19F signal, whereas that in the surrounding adipose and muscle tissues contributes mostly to the mobile component. Imaging and spectroscopic results suggest that the immobile component of sevoflurane is associated with the general anesthetic effects of the agent.

Anesthetics

Mechanisms of cerebrovascular O2 sensitivity from hyperoxia to moderate hypoxia in the rat.

Cerebrovascular dilation over PaO2 ranging from hyperoxia to moderate hypoxia is unexplained. We hypothesize that tissue acidosis is the cause. Local cortical cerebral blood flow (LCBF), tissue hydrogen ion concentration [H+]t, and tissue PO2 (PtO2) were measured with microelectrodes in the parietal cortex of 18 rats during a 30-min steady state on 60 to 10% inspired O2 (PaO2, 300 to 40 torr) during 40% N2O analgesia. Five rats kept on 60% O2/40% N2O served as controls. In 18 rats at a PaO2 of 275 +/- 7 torr (mean +/- SEM) and PaCO2 of 35 +/- 1 torr, cerebral values were: LCBF = 129 +/- 23 (mean +/- SEM) ml.100 g-1.min-1; [H+]t = 62 +/- 6 nM; and PtO2 = 25 +/- 3 torr. As PaO2 was reduced from about 300 to 40 torr, changes in these variables in percentage of control with respect to PaO2, were described by the following equations, all at P less than 0.0001: LCBF = 85.9 + 5,572/Pao2; [H+]t = 97.15 + 1,012/PaO2; and PtO2 = 108.8 - 3,492/PaO2. Simultaneous solution of the LCBF and [H+]t equations at various PaO2 revealed a slope of 8.82%/nM. Direct correlation between LCBF in ml.100 g-1.min-1 and [H+]t in nM revealed a linear relationship defined by the equation Y = -7.472 + 1.6705X (r = 0.6426) for [H+]t between 56 and 160 nM (pH = 7.25 and 6.80) but no correlation at [H+]t values between 56 and 32 nM (pH = 7.25 to 7.50). Cerebrovascular tone is directly correlated with [H+]t during progressive, 30-min steady-state reduction in PaO2 from 350 to 40 torr.

Animals

A method to increase recovery of fentanyl from urine.

Fentanyl, a highly lipophilic drug (pk(a) 7.7), is a common drug of abuse. The current standard techniques to detect fentanyl in urine have low recovery rates and poor sensitivity. We report a modified solvent extraction technique that can recover between 63 and 86% of the drug with a detection limit of 0.2 ng/10 ml of urine. In addition, we report the duration of urinary fentanyl excretion in 11 adolescent patients administered either low (less than 10 mg/kg) or high (20-40 mg/kg) doses of fentanyl as part of anesthesia. The mean duration of urinary fentanyl excretion was similar in the two groups, with duration ranging from 1 to 5 days, and urine fentanyl concentration ranging from 0.1 ng to 10.3 ng/10 ml of urine.

Adolescent

Febrile transfusion reaction caused by AB0-incompatible platelet transfusion.

A febrile transfusion reaction caused by strong isoagglutinins in the patients serum is reported. The reaction resulted from a transfusion of group A platelets in a group 0 patient; the recipients' serum contained high titered isohemagglutinin (Anti-A 1:8192) capable of lysing bloodgroup A1 red cells up to a titer of 1:8. Moreover, the serum showed a strong positive thrombocytotoxic reaction with the platelets of the donor and some other group A individuals, but remained negative with group 0, and turned to negative reaction with group A samples after neutralization with bloodgroup substance. We conclude that pretransfusion testing of group 0 donors and recipients for isohemolysins combined with platelet crossmatching may prevent febrile reactions.

ABO Blood-Group System

The frequency of IgA-deficiency in the Austrian population. A protocol for large-scale screening by ELISA and a study on 3056 blood donors.

A protocol for large scale screening of blood donors for IgA-deficiency with the help of an ELISA is described. The ELISA method proved to be fast and reliable, the obtained data can be managed by electronic data processing. Donors were regarded as IgA-deficient when their serum level was below 10 mg/dl (normal values 90 to 450 mg/dl). At this concentration ELISA shows acceptable reproducibility (within +/- 15% limits). We found 8 deficient donors, i.e. one in 382 or 0.26%. Seven of these donors were totally deficient by ELISA, 2 of them having a strong anti-IgA in their serum. We conclude that ELISA is a simple, reliable, and inexpensive method for screening blood donors for IgA-deficiency.

Blood Donors

[Detection and quantification of erythrocyte-associated immunoglobulins using immunoenzyme technic--enzyme immunometric assay (EIMA)].

A new technique is described for the quantification of erythrocyte-associated immunoglobulin G (EAIgG). Enzyme immunometric assay (EIMA) measures the consumption of enzyme-labelled anti-human globulin. Thus, the release of cellular enzymes is avoided and, thereby also falsification of the results owing to the antigen-antibody reaction taking place in media of differing molarity and ionic strength (as is inevitable in red cell lysis assays). This consumption technique is more sensitive than simple "sandwich" procedures. The measurement of minimal amounts of physiologically bound EAIgG is, moreover, possible.

Anemia, Hemolytic, Autoimmune

Mechanisms of cerebrovascular dilation by ether in monkeys.

We hypothesized that when the depth of ether anesthesia is increased from 2 to 5%, cerebral vessels dilate secondary to circulating catecholamine stimulation of cerebral metabolism. Cerebral blood flow (CBF) by 133Xe clearance and cerebral metabolic rate for oxygen (CMRO2) were measured on 2% and then 5% ether in air in two groups of seven monkeys each during mechanical ventilation. Propranolol, 0.5 mg/kg i.v., was infused over 5 min in one group, and the other received saline. All measurements were repeated on 5% and 2% ether. Cerebrovascular resistance (CVR) fell by 30%, from 2.28 +/- 0.61 (mean +/- SD) to 1.51 +/- 0.28 mm Hg ml-1 100 g-1 min-1 (p less than 0.01), with the increase in ether from 2 to 5%. CBF and CMRO2 were unaltered from values of about 45 ml 100 g-1 min-1 and 2.3 ml 100 g-1 min-1, respectively. During 5% ether anesthesia, propranolol had no effect on CBF, CMRO2, or CVR. On 2% ether, it increased CVR twofold, from 1.5 +/- 0.30 to 3.0 +/- 1.0 mm Hg ml-1 100 g-1 min-1, and decreased CBF by 33%, from 48 +/- 8 to 32 +/- 10 ml 100 g-1 min-1. Plasma epinephrine was two-fold higher on 2% compared to 5% ether, both before and after saline or propranolol infusion. In monkeys, cerebrovascular dilation by ether at 5% compared to 2% is not secondary to catecholamine stimulation of CMRO2. It may result from a direct effect of either plasma catecholamines or ether on the cerebrovasculature.

Animals

Absence of beta-adrenergic receptor involvement in cerebrovascular dilation by halothane in monkeys.

We determined, in monkeys, whether halothane-induced cerebrovascular dilation is mediated by beta-adrenergic receptors and whether cerebrovascular tone progressively returns to baseline values during prolonged halothane anesthesia. Total cerebral blood flow (CBF), cerebral perfusion pressure, plasma halothane concentration, and arterial blood gas tensions and pH were measured in 14 rhesus monkeys mechanically ventilated with 0.5% (inspired) halothane, 33% O2 and balance N2O. Halothane was increased to 2.0% and the measurements repeated 30 and 60 min later. Then either 0.9% NaCl (controls n = 6) or propranolol (n = 8), 1.0 mg/kg was infused intravenously over 10 min, and the measurements repeated at 70, 90, 120, and 150 min. After 30 min at 2.0% halothane, CBF increased in the controls by 50% (P less than 0.05) from 92 +/- 8 (mean +/- SD) to 137 +/- 39 ml X 100 g-1 X min-1 and in the propranolol group by 30% (P less than 0.05) from 106 +/- 33 to 137 +/- 28 ml X 100 g-1 X min-1. After 2.5 hr of 2.0% halothane anesthesia, CBF remained elevated above baseline levels, but by only 28 and 23% in the control and propranolol groups, respectively. Cerebrovascular resistance was identical in both groups (0.55 +/- 0.33 vs 0.53 +/- 0.13 mm Hg X ml-1 X 100 g 1 X min 1). The results show that there is only a 10-20% return of CBF toward baseline levels after up to 2.5 hr of 2% halothane anesthesia. The results also indicate that halothane-induced cerebrovascular dilation is not mediated by beta-adrenergic receptors.

Animals

Cardiovascular depression secondary to ionic hypocalcemia during hepatic transplantation in humans.

Cardiovascular function, serum ionized calcium (Ca+2), and serum citrate were measured intraoperatively in patients (n = 9) undergoing orthotopic hepatic homotransplantation. Serum citrate increased 20-fold (P less than 0.0006) following transfusion of citrated blood products in the absence of a functional liver. Serum ionized calcium decreased (P less than 0.003) with concomitant decreases in cardiac index (P less than 0.005), stroke index (P less than 0.004), and left ventricular stroke work index (P less than 0.001). Hemodynamic depression and ionic hypocalcemia were reversed following the administration of CaCl2. In contrast to patients with normal hepatic function, who may tolerate large amounts of citrated blood, patients with end-stage liver disease demonstrate acute ionic hypocalcemia with concomitant hemodynamic depression when receiving citrated blood products during the course of hepatic transplantation.

Calcium Chloride

Naloxone does not antagonize the analgesic effects of inhalation anesthetics.

A previous demonstration that the ratio of analgesic to anesthetic endpoints is not constant across inhalation anesthetic agents implies that more than one mechanism of action may be operant in general anesthesia. We hypothesized that the endogenous opiate systems might account for this observed disparity in ratios. The tail flick ED50 (TFED50) in response to a heat stimulus, as an index of analgesia, and MAC as an index of anesthesia, were determined in rats treated with either saline or naloxone, 20 mg/kg, and exposed to halothane, enflurane, or isoflurane. Our findings confirmed those of Deady et al., showing a lack of uniformity of ratios of TFED50/MAC, with values of 0.90 +/- 0.03 for halothane, 0.80 +/- 0.04 for enflurane, and 0.70 +/- 0.04 for isoflurane. Naloxone had no effect on TFED50, MAC, or their ratio. If the endogenous opiate system were involved in the analgesic effect of general anesthetics, naloxone would have affected the ratios. We conclude that opiate systems are not involved in the analgesic action of general anesthetics.

Analgesia

Anesthesiology.

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Anesthesia, General

Intraoperative changes in blood coagulation and thrombelastographic monitoring in liver transplantation.

The blood coagulation system of 66 consecutive patients undergoing consecutive liver transplantations was monitored by thrombelastograph and analytic coagulation profile. A poor preoperative coagulation state, decrease in levels of coagulation factors, progressive fibrinolysis, and whole blood clot lysis were observed during the preanhepatic and anhepatic stages of surgery. A further general decrease in coagulation factors and platelets, activation of fibrinolysis, and abrupt decrease in levels of factors V and VIII occurred before and with reperfusion of the homograft. Recovery of blood coagulability began 30-60 min after reperfusion of the graft liver, and coagulability had returned toward baseline values 2 hr after reperfusion. A positive correlation was shown between the variables of thrombelastography and those of the coagulation profile. Thrombelastography was shown to be a reliable and rapid monitoring system. Its use was associated with a 33% reduction of blood and fluid infusion volume, whereas blood coagulability was maintained without an increase in the number of blood product donors.

Adult

Continuous monitoring of arterial oxygen saturation with pulse oximetry during transfer to the recovery room.

The incidence of hypoxemia in the immediate postoperative period was determined using a pulse oximeter for continuous monitoring of arterial oxygen saturation (SaO2) in 95 ASA class I or II adult patients breathing room air during their transfer from the operating room to the recovery room. Hypoxemia was defined as 90% SaO2 (arterial oxygen partial pressure (PaO2) approximately equal to 58 mm Hg). Severe hypoxemia was defined as 85% SaO2 (PaO2 approximately equal to 50 mm Hg). Hypoxemia occurred in 33 (35%) patients; severe hypoxemia occurred in 11 (12%). Postoperative hypoxemia did not correlate significantly with anesthetic agent, age, duration of anesthesia, or level of consciousness. There was a statistically significant correlation (P less than 0.05) between hypoxemia and obesity. All three patients with a history of mild asthma became severely hypoxemic even though none had perioperative evidence of obstructive disease, also a statistically significant (P less than 0.003) finding.

Adult

Field endotracheal intubation by paramedical personnel. Success rates and complications.

One-hundred thirty mobile intensive care unit paramedics were trained in the technique of direct laryngoscopic endotracheal intubation of cardiac arrest or deeply comatose patients. Three attempts at intubation were permitted. Of the 779 patients studied, 701 (90.0 percent) were successfully intubated: 57.9 percent on the first attempt, 26.1 percent and 5.5 percent on the second and third respectively. Reported and observed complications of the procedure numbered 74 (9.5 percent) of the 779 patients included in the study. There were three unrecognized esophageal intubations. The success rate rose to more than 94 percent toward the end of the study. It is concluded that endotracheal intubation of deeply comatose patients is a field procedure safely and skillfully performed by well-trained and monitored paramedical personnel, with success and complication rates at least comparable to other invasive airway techniques.

Allied Health Personnel