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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
PubMed1998

Quantitation of intracellular [Na+] in vivo by using TmDOTP5- as an NMR shift reagent and extracellular marker.

A method is presented to measure the absolute concentration of intracellular Na+ ([Na+]i) in vivo by using interleaved 23Na- and 31P-nuclear magnetic resonance (NMR) spectroscopy and TmDOTP5- as shift reagent and chemical marker of tissue extracellular space (ECS). The technique was used to determine [Na+]i and relative ECS in livers of control rats (21 +/- 3 and 0.11 +/- 0.02 mM, respectively) and in rats exposed to carbon tetrachloride (103 +/- 29 and 0.23 +/- 0.03 mM, respectively). The NMR measurements were confirmed independently on excised tissue samples by using atomic absorption spectroscopy. The results confirm that TmDOTP5- can be used as a combined cation shift reagent and ECS marker, thereby allowing quantitation of [Na+]i in vivo by NMR.

Animals↗
PubMed1997

Regional brain activity changes associated with fentanyl analgesia elucidated by positron emission tomography.

Recent positron emission tomography (PET) studies have demonstrated areas of pain processing in the human brain. Given the inhibitory effects of opioids on neuronal activity, we predicted that fentanyl's analgesic effects would be associated with suppression of pain-evoked responses in these distinct brain areas. To test this, PET was used to measure cerebral blood flow responses, as reflections of regional neuronal activity, to painful and nonpainful thermal stimuli both in the absence and presence of fentanyl in humans. During each PET scan in nine healthy volunteers a tonic heat source was placed against the subject's left forearm, delivering a preset temperature of either 40 degrees C (nonpainful) or 47-48 degrees C (painful). Subjects underwent eight blood flow studies, each consisting of 50 mCi [15O]water injection and a PET scan. The first four studies were performed during placebo administration in the stimulus sequence: nonpainful, painful, painful, nonpainful. This sequence was then repeated during intravenous (i.v.) administration of fentanyl 1.5 micrograms/kg [corrected]. Significant differences in regional cerebral blood flow (rCBF) between the placebo and the fentanyl conditions during nonpainful and painful stimuli were identified using statistical parametric mapping. It was found that pain increased rCBF in the anterior cingulate, ipsilateral thalamus, prefrontal cortex, and contralateral supplementary motor area. Fentanyl increased rCBF in the anterior cingulate and contralateral motor cortices, and decreased rCBF in the thalamus (bilaterally) and posterior cingulate during both stimuli. During combined pain stimulation and fentanyl administration, fentanyl significantly augmented pain-related rCBF increases in the supplementary motor area and prefrontal cortex. This activation pattern was associated with decreased pain perception, as measured on a visual analog scale. In contrast to our hypothesis, these data indicate that fentanyl analgesia involves augmentation of pain-evoked cerebral responses in certain areas, as well as both activation and inhibition in other brain regions unresponsive to pain stimulation alone.

Adult↗
PubMed1997

In vivo imaging of nitrous oxide-induced changes in cerebral activation during noxious heat stimuli.

BACKGROUND: Although previous studies have provided some insight into the pharmacologic aspects of nitrous oxide analgesia, the neural circuits mediating its antinociceptive effect remain relatively unexplored. Position emission tomography was used in nine volunteers to identify the loci of nitrous oxide-modulated cerebral responses to a peripheral noxious stimulus. METHODS: Nitrous oxide-pain interactions were studied by comparing regional cerebral blood flow responses to a 48 degrees C tonic heat stimulus, applied to each volunteer's left forearm, during room air inhalation with those obtained while 20% nitrous oxide was administered. Two cerebral blood flow scans were obtained with the 15O-water technique during each condition. Locations of specific regional activation related to pain, and nitrous oxide, were identified using the statistical parametric mapping method, with a significance level of P < 0.01. Pain was rated by visual analog scale and the values were compared using Wilcoxon rank sum analysis. RESULTS: Pain produced cerebral activation in the contralateral thalamus, anterior cingulate, and supplementary motor area. Adding nitrous oxide during pain stimulation abolished activation in these areas but was associated with activation in the contralateral infralimbic and orbitofrontal cortices. In parallel, mean visual analog scale scores decreased significantly from 67 +/- 4 (SEM) to 54 +/- 5 (P < 0.05). CONCLUSIONS: Nitrous oxide, at 20% concentration, appears to modulate pain processing in the brain's medial pain system, and also activates the infralimbic and orbitofrontal cortices. The potential contribution of the affected brain areas to nitrous oxide analgesia is discussed.

Administration, Inhalation↗
PubMed1996

Anesthetics modulate phospholipase C hydrolysis of monolayer phospholipids by surface pressure.

Anesthetics are believed to produce anesthesia through the reversible inhibition of synaptic transmission but how this is accomplished is unknown. Based on earlier studies of anesthetic-enzyme-phospholipid interaction, we surmised that anesthetics may inhibit synaptic transmission by increasing synaptic membrane lateral pressure thereby inhibiting phospholipid hydrolysis, membrane transduction and synaptic transmission. As a first approximation towards investigating this concept, we hypothesized that anesthetics modulate the rate of phospholipase C hydrolysis of a lipid monolayer through its effects on surface pressure. The relationship between the hydrolysis rate of a monolayer of dipalmitoylphosphatidylcholine [14C-choline] (DPPC) by phospholipase C (Plase C) and monolayer surface pressure (SP) as altered by either halothane, isoflurane, or by physical compression at 37 degrees C was studied. The decline in surface 14C-activity as the [14C]choline diffuses into the Krebs-Ringer bicarbonate buffer aqueous subphase is estimated as the rate of DPPC hydrolysis measured by the initial slope method. DPPC hydrolysis was about 300 cpm/min and constant between SP of 0 to 20 dynes/cm. Higher SP between 25 and 30 dyne/cm, whether induced by halothane, isoflurane or physical compression, increased the rate of hydrolysis by 5-fold to a peak rate of about 1600 cpm/min at 25-30 dynes/cm. At a SP above 32 dynes/cm, DPPC hydrolysis abruptly ceased. We conclude that anesthetics can reversibly inhibit synaptic transmission through their effects on synaptic membrane lateral pressure. We also speculate that membrane lateral pressure may be a highly sensitive means of controlling membrane function through alteration in membrane lipid composition, membrane enzyme activity, receptor affinity and ion channel permeability.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1996

Human brain activity response to fentanyl imaged by positron emission tomography.

Positron emission tomography (PET) is a noninvasive imaging technique that can be used to observe drug actions on human brain in vivo. We used 15O-water PET scanning in six volunteers to examine the effects on regional cerebral activity as reflected by regional cerebral blood flow (rCBF) of a small intravenous bolus of fentanyl. rCBF was compared between scans obtained after fentanyl or a placebo using three separate statistical criteria including a pixel-by-pixel t statistic; significance was stringently defined at P values < 0.01. Anatomic locations of regional cerebral activity changes were verified by aligning rCBF PET scans with cranial magnetic resonance images using mathematical coregistration. Fentanyl administration was associated with significant increases in rCBF consistent with regional neuronal activation in both cingulate and orbitofrontal and medial prefrontal cortices, as well as caudate nuclei. These areas are responsive to nociceptive stimuli and are involved in avoidance learning, reward and addiction, visceromotor control, maintenance of attention, and pain-related affective behavior. Significant decreases were noted in both frontal and temporal areas and the cerebellum, a distribution far less extensive than that of opiate receptors in general. These data indicate that fentanyl's effects are highly localized and specifically affect cerebral regions associated with a range of pain-related behaviors.

Adult↗
PubMed1996

In vivo imaging of human limbic responses to nitrous oxide inhalation.

Human behavioral studies have shown that nitrous oxide, in subanesthetic concentrations, impairs psychomotor function, cognitive performance, and learning and memory processes. However, the cerebral mechanisms of such effects remain unknown. Positron emission tomography (PET) was used to map the brain areas associated with nitrous oxide effects. Regional cerebral blood flow (rCBF) was measured in eight volunteers, during room air (control) or 20% nitrous oxide (nitrous oxide) inhalation using 15(O)-water, to reflect regional neuronal activity. To control for the possibility that 20% nitrous oxide uncoupled cerebral blood flow and metabolism, in four of the subjects, regional cerebral metabolic rate (rCMR) was also measured using 18F-deoxyglucose during the two experimental conditions. Results of rCBF and rCMR scans were compared between conditions using the statistical parametric mapping method, and areas of nitrous oxide-related activation or deactivation were identified at a significance level of 0.005. Percent changes in rCBF scan pixels from these activated or deactivated areas were then compared with those of stereotactically corresponding rCMR scan pixels with t statistics (P < 0.05 was defined as a significant difference). It was found that cerebral blood flow and metabolism were not uncoupled by 20% nitrous oxide, since percent changes in rCBF and rCMR, detected during nitrous oxide inhalation, did not differ significantly from each other (P < 0.05). Nitrous oxide inhalation was associated with significant activation in the anterior cingulate cortex, a limbic area known to mediate psychomotor and cognitive processes. Deactivation was found in the posterior cingulate, hippocampus, parahippocampal gyrus, and visual association cortices in both hemispheres; the former two regions are known to mediate learning and memory. These areas identified by PET in vivo may provide the neuroanatomical basis for the behavioral responses associated with subanesthetic nitrous oxide inhalation.

Adult↗
PubMed1996

Funding resuscitation research.

The present trend in managed care has meant downsizing expectations concerning the availability of support for resuscitation research. This trend applies to funding possibilities from industry, governmental agencies, and nongovernmental agencies (Table 1). There will be increasing barriers to making innovations. Truth, science, and good patient care alone will not make potential donors give grants. Investigators must also understand the potential donors' expectations and be persuasive. "Delight your donor". Industries' concerns include intellectual property rights and publications. The National Institutes of Health, recently favoring molecular biology over lifesaving therapies or integrated physiologic research, is an anomaly. The current peer review system propagates itself without having advocates for resuscitation research. This system has become a self-fulfilling prophecy. The American Heart Association is only recently, after 30 yrs of educational activities concerning cardiopulmonary resuscitation, considering putting some basic research money into resuscitation research. In university hospitals, where clinical departments have made significant contributions to innovative, clinically relevant life-support research, funded with incomes from patient care, the sky is beginning to fall. Resuscitation researchers need persuasive advocates with clout and hard data to convince funding agencies to give support to multilevel research and development in areas of pathophysiology and reversibility of terminal states and clinical death--to give these topics a higher priority than is currently available.

American Heart Association↗
PubMed1995

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↗
PubMed1993

Volatile anesthetic requirements differ in mice selectively bred for sensitivity or resistance to diazepam: implications for the site of anesthesia.

One approach to elucidating the general anesthetic target has used genetic selection procedures, wherein animals are bred for sensitivity or resistance to general anesthetics and correlations are sought with a specific neuronal structural or functional defect. For example, murine strains have been developed that are either sensitive or resistant to the obtunding effects of diazepam, as assessed by their ability to maintain balance on a rotating rod. The present study explored whether diazepam-sensitive (DS) and diazepam-resistant (DR) mice might also be similarly divergent in the obtunding response to general anesthetics, by testing the requirements for halothane and enflurane in these strains. Using a carousel enclosed in a chamber, the end-point of loss-of-righting reflex was defined. For both anesthetics, the DS groups had a lower median effective dose (ED50, %atm) than did the DR group, and the reductions paralleled diazepam susceptibility. For example, with halothane, the ED50 for the DS group was 0.72 +/- 0.022 (SE); the ED50 for the DR group was 0.87 +/- 0.030 (P < 0.0001). Similar results were obtained with enflurane. Such findings associate an inbred difference in response to diazepam with altered volatile anesthetic requirement, suggesting that these two phenotypes are mediated by a common underlying mechanism.

Anesthesia, Inhalation↗
PubMed1989

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↗
PubMed1989

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↗
PubMed1988

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↗
PubMed1988

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↗
PubMed1987

[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↗
PubMed1987

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↗