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Biomedical subjects

M L Smith

Publications and source records attributed to M L Smith.

At least 289 records · Page 16Linked to original sources

Nalbuphine after major gynecologic surgery. Comparison of patient-controlled analgesia and intramuscular injections.

A randomized investigation compared the efficacy and safety of nalbuphine administered by two methods, a patient-controlled infuser system and intramuscular (IM) injections, after major gynecologic surgery. Forty-seven patients were randomly assigned to receive nalbuphine by either method. The 22 patients using the infuser were given a 2.0-mg, incremental dose with a 10-minute lock-out interval between doses. A similar group receiving 10-15 mg IM every three hours served as the control. Misprogramming, overdosage, depressed respiration and drug dependence were not encountered. Self-administration provided equally satisfactory sedation and more immediate pain relief without painful injections. Although patients with the infuser had the ability to self-administer more medication, they did not use higher doses of nalbuphine than did the IM group. The additional cost of the infuser system was offset by the satisfaction expressed by the patients and by the improved nursing efficiency. Nalbuphine administered with a patient-controlled infuser provided an effective balance between analgesia and sedation and offered advantages over IM injections.

Adult↗

The biochemical basis of ischemic brain lesions.

A major mechanism leading to ischemic damage is loss of cellular ion homeostasis. Energy failure with shortage of ATP is responsible for presynaptic release of glutamate, which then triggers rapid cellular efflux of K+, and influx of Ca2+, Na+, and Cl-, with osmotically obligated water. The neuronal damage occurring in ischemia is probably secondary to the influx of Ca2+, and/or to the intracellular release of Ca2+, with the subsequent activation of proteases and lipases. A delayed form of ischemic damage, observed after transient ischemia, may be caused by increased calcium cycling across metabolically perturbed membranes. Another type of damage, typically leading to pan-necrosis (infarction), seems related to excessive acidosis and to production of free radicals. The mechanisms may involve release of pro-oxidant iron-catalyzed free radical reactions. It has been proposed that free radical damage may preferentially affect microvessels, predisposing to vasogenic edema.

Animals↗

Toxicological findings in Federal Aviation Administration general aviation accidents.

Blood, urine, and tissue specimens were received from 377 Federal Aviation Administration (FAA) aviation fatalities during fiscal year 1989. Carbon monoxide at less than 10% saturation was found in 94% of the cases, and cyanide at less than 0.5 mg/L was found in 96% of the cases. Ethanol at greater than 10 mg/dL was found in 14.8% of the cases, but only 4.5% were determined to be due to ethanol ingestion from toxicological findings. Excluding nicotine and ethanol, 12.6% of the cases were positive for one or more drugs. Acetaminophen and salicylate were the most frequently found drugs. Cannabinoids were found in 1.3% of the cases and benzoylecgonine in 1.6%. There was minimal use of therapeutic drugs that cause central nervous system depression or stimulation. These results show no consistent pattern of drug involvement in civilian aviation fatalities.

Accidents, Aviation↗

Hemodynamic responses to 6 degree head-down rest in dogs: effect of aerobic conditioning.

The -6 degree head-down position is used in humans to produce fluid shifts that resemble those occurring in microgravity. Alternative animal models of microgravity may be helpful for extensive exploration of this unique condition. The dog may be a viable candidate. Sixteen dogs were assigned to one of three conditions: anesthetized open chest, anesthetized closed chest, and awake. Dogs in groups 1 (N = 6) and 2 (N = 6) were divided into an exercise or a sedentary treatment, and dogs in group 3 (N = 4) served as their own controls. Following instrumentation the dogs were put in the head-down position for 1 h. Measurements included right atrial pressure, heart rate, and mean arterial pressure for all groups, left ventricular pressure and LV dp/dt for group 1, and cardiac output and iliac flow for group 2. Right atrial pressure increased for all groups. Heart rate demonstrated non-significant changes over time or group. Significant differences were noted for mean arterial pressure, left ventricular pressure and LV dp/dt for exercise condition in response to HDR. It appears that -6 degrees of head-down rest produces similar cardiovascular responses in dogs as those observed in humans and that exercise has a minor effect on those responses.

Animals↗

Chloroquine distribution in postmortem cases.

Chloroquine concentrations in blood and tissues were examined in overdose and non-overdose cases to determine appropriate ranges for interpretation. Twenty-nine literature overdose cases and 8 non-overdose literature cases were compared with this laboratory's findings. The results indicate significant postmortem redistribution of chloroquine. Combining this laboratory's results and the literature results indicates that using a liver concentration of 150 mg/kg as a cutoff between overdose and non-overdose concentrations properly identified 30 of the 34 published cases containing liver chloroquine and 19 of the 20 presented cases.

Accidents, Aviation↗

Subnormal parasympathetic activity after cardiac transplantation.

Heart period variability (standard deviation of 120 consecutive RR or PP intervals) was used to assess baseline parasympathetic activity in 18 patients with congestive heart failure before and after orthotopic cardiac transplantation, and was compared to that of 16 age-matched control subjects. Mean heart period variability (+/- standard error of the mean) was significantly greater (p less than 0.05) in control subjects (58 +/- 5 ms) than in the patients at any time before or after transplantation. Heart period variability of innervated recipient atria did not change significantly early (1 to 4 weeks) after transplantation (16 +/- 2 to 24 +/- 5 ms; p = 0.11), but increased significantly between weeks 15 and 37 after transplantation (30 +/- 5 ms, p less than 0.002 versus before transplantation). A stepwise regression model (R2 = 0.35; p = 0.01) showed that heart period variability was directly related to time after transplantation and inversely related to systolic arterial pressure after transplantation and degree of rejection. Heart period variability of the denervated donor atria did not change from early to late periods after transplantation, suggesting that vagal reinnervation of the donor heart had not occurred. These data indicate that baseline parasympathetic activity does not increase significantly during the first month after transplantation but increases significantly between months 3 and 6.

Atrial Function↗

Brain ischemia alters the density of binding sites for glibenclamide, a specific blocker of ATP-sensitive K+ channels.

Transient ischemia in normoglycemic animals leads to delayed neuronal damage which is confined to selectively vulnerable regions. In at least one of these, the CA1 sector of the hippocampus, cell death is preceded by neuronal hyperactivity, presumed to be caused by loss of inhibitory control. Hyperglycemic subjects develop postischemic seizures, and show enhanced damage. The ATP-sensitive K+ channel, which may be important in inhibitory control, is the target of antidiabetic sulfonylureas. We determined densities of sulfonylurea binding sites in rat brain after forebrain ischemia. Normoglycemic animals showed a decrease of glibenclamide receptor binding in the CA3 field, hilus and dentate gyrus of the hippocampus after 1 day of recovery. After 4 days of recovery, levels of sulfonylurea binding sites decreased mainly in the CA1 field and in the hilus, as well as in the substantia nigra. After 1 day of recovery, hyperglycemic animals did not show any significant variations of densities of sites compared to control animals. It is proposed that reduction of inhibitory control by ATP-sensitive K+ channels may be associated with delayed neuronal death.

Adenosine Triphosphate↗

Changes in regional adrenergic tone during sustained ventricular tachycardia associated with coronary artery disease or idiopathic dilated cardiomyopathy.

The hemodynamic tolerance of an episode of ventricular tachycardia (VT) can vary widely from no decrease in systolic blood pressure to severe hypotension. Little is known about the factors responsible for these different responses in man. Previous animal studies have suggested an important role for vasoconstriction mediated by the alpha-adrenergic nervous system. To determine the magnitude and time course of changes in alpha-adrenergic tone during symptomatic sustained monomorphic VT, VT cycle length, mean and phasic arterial pressure, forearm blood flow (by venous occlusion plethysmography) and forearm vascular resistance were measured in 15 patients. Nine of these patients were studied before and after regional intraarterial alpha blockade with phentolamine. After the induction of VT (350 +/- 68 ms), mean forearm blood flow decreased from 3.2 +/- 1.1 to 2.2 +/- 0.8 ml/min/100 ml (p = 0.0002) and the forearm vascular resistance increased from 32 +/- 14 to 40 +/- 14 units (p = 0.01). There were no significant differences for forearm vascular resistance during the first and last 30 seconds of VT (41.3 +/- 14 vs 37 +/- 13 units). After the infusion of intraarterial phentolamine, there were no significant changes in the VT cycle length or mean arterial pressure, but the forearm vascular resistance increase during VT was blunted by 60 to 70%. Most patients with symptomatic VT demonstrate sympathetic vasoconstriction and these changes are maximal during the first 30 seconds of VT. This sympathoexcitatory response is due largely to stimulation of alpha-adrenoreceptors and may be mediated by arterial baroreflexes.

Cardiomyopathy, Dilated↗

Increased vagal cardiac nerve traffic prolongs ventricular refractoriness in patients undergoing electrophysiology testing.

Stimulation of the vagus nerve in animals causes prolongation of sinus cycle length, atrioventricular nodal conduction and ventricular refractoriness. Vagal stimulation appears to have a protective effect in animal models of sudden death. The electrophysiologic effects of enhanced vagal activity on right ventricular (RV) refractoriness in man have not been studied previously. The comparative effects of enhanced vagal tone (neck suction to -60 mm Hg) on sinus cycle length and RV refractoriness were assessed in 26 patients. The electrophysiologic effects of vagal activation by stimulation of carotid baroreceptors with neck suction were compared to the effect of carotid and aortic baroreceptor stimulation with phenylephrine infusion in 12 patients. During neck suction, mean sinus cycle length (819 +/- 32 ms) was prolonged by 146 +/- 20 ms (p less than 0.0001). The mean RV effective refractory period (ERP) and functional refractory period (FRP) were prolonged by 4 +/- 1 ms and 5 +/- 1 ms (p = 0.0001 and 0.0002, respectively). The mean change in RV ERP and FRP correlated with the peak change in sinus cycle length during neck suction (r = 0.46 and r = 0.58, respectively). During intravenous phenylephrine infusion, the mean change in RV ERP and FRP was 5 +/- 2 ms (p less than 0.04) and 10 +/- 3 ms (p less than 0.01), respectively. These results show that reflex vagal stimulation with neck suction or phenylephrine infusion causes a small but significant prolongation in RV refractoriness. These findings imply that the potential benefits of enhanced vagal tone in preventing sudden death may be indirectly mediated by changes in ventricular refractoriness.

Cardiac Pacing, Artificial↗

The effect of mild hyperthermia and hypothermia on brain damage following 5, 10, and 15 minutes of forebrain ischemia.

The present study examines the effects of mild hypothermia and hyperthermia on the density and distribution of ischemic brain damage, and compares these effects to those induced by variations in the duration of ischemia. Body temperatures were maintained at 35 degrees C, 37 degrees C, and 39 degrees C, before, during, and after ischemia, and brain temperatures were held at similar values with a technique that in preliminary experiments proved to avoid intracerebral temperature gradients or overheating of surface structures. In all animals, brain damage was assessed by histopathological analysis of perfusion-fixed brains after six to seven days of recovery. Our results confirm previous findings showing that a decrease in temperature of only 2 degrees C significantly reduces damage to several selectively vulnerable neuronal populations. The results also showed that an increase in temperature of 2 degrees C significantly enhances brain damage. In general, a rise in temperature had effects similar to an increased duration of the ischemia. In some areas, such as the CA1-subiculum sectors of the hippocampus, temperature and ischemic duration altered damage in a gradual manner, but in others, such as the caudoputamen, there was a steplike change from virtually no to virtually complete damage. In some areas, the effects of hypothermia and hyperthermia appeared symmetrical around the normal temperature of 37 degrees C. Hyperthermia had some seemingly "specific" effects, however, notably the tendency to induce pannecrosis ("infarction") in the neocortex and caudoputamen, and to cause damage to the substantia nigra pars reticulata. The results underscore the potentially devastating effects of fever in patients with cerebrovascular disease.

Animals↗

Tomographic views of normal and abnormal hearts: the anatomic basis for various cardiac imaging techniques. Part I.

Recent developments have taken place in the diagnosis of cardiovascular disorders in the area of cardiac imaging techniques. From a previous era of imaging by silhouettes (chest roentgenography, fluoroscopy, angiocardiography), we have emerged into an era of imaging by tomographic scanning (echocardiography, radionuclide tomography, computed tomography, magnetic resonance). A basic understanding of tomographic cardiac anatomy is the foundation for proper use and interpretation of these new imaging modalities. The present report provides a description of the techniques of tomographic cutting of necropsy cardiac specimens and illustrates some of the pathologic cardiac abnormalities cut in these tomographic planes. Part I of this report describes position of the heart and tomographic axis planes, preparation of the heart and methods of cutting at necropsy, and the short-axis, two-chamber, and four-chamber views of the heart.

Heart↗

Tomographic views of normal and abnormal hearts: the anatomic basis for various cardiac imaging techniques. Part II.

Recent developments have enhanced the diagnosis of cardiovascular disorders in the area of cardiac imaging techniques. From an era of imaging by silhouettes (chest roentgenography, fluoroscopy, angiocardiography), we have emerged into an era of imaging by tomographic scanning (echocardiography, radionuclide tomography, computed tomography, magnetic resonance). A basic understanding of tomographic cardiac anatomy is the foundation for proper use and interpretation of these new imaging modalities. The present report provides a description of the techniques of tomographic cutting of necropsy cardiac specimens and illustrates some of the pathologic cardiac abnormalities cut in these tomographic planes. Part II of this report describes the long-axis method, methods using the body rather than the heart as the reference axis, and includes transverse, frontal, and parasagittal methods of imaging the heart.

Autopsy↗

Event-related potential evidence of sex differences in verbal and nonverbal memory tasks.

ERPs were recorded from 19 scalp electrodes while 48 subjects (24 females) performed visual recognition tasks for recurring verbal items and recurring abstract figures. Reaction times were longer in the figures than verbal task; the latencies of the ERP components (P2, N4, P3, P4) were also longer for the figures. A nonreversing asymmetry (R greater than L) was seen in both tasks. Significant task by electrode interactions (for P3, P4) were found, due to larger amplitudes anteriorly for the figures, but larger amplitudes posteriorly for the verbal task. All ERP latencies were longer for males than females. There were sex by task by electrode interactions in the amplitudes, due to larger ERPs (P2, N4) for females anteriorly for the figures, but slightly larger posteriorly for the verbal task. These results suggest that sex differences in cognitive abilities may be based on differences in biological mechanisms.

Adult↗

Imaging peripheral benzodiazepine receptors in brain tumors in rats: in vitro binding characteristics.

Peripheral benzodiazepine binding constants for transplanted RG-2 gliomas and HD and LK Walker 256 tumors (metastatic breast carcinoma) were determined in Wistar rats using autoradiography. In addition, Kd and Bmax parameters for peripheral benzodiazepine receptors on RG-2 tumors were directly visualized using digital image analysis of autoradiograms. High specific binding of [3H]PK11195, a selective peripheral benzodiazepine ligand, had excellent topographical correlation to areas of histologically verified tumor. Scatchard analysis suggested a single class of peripheral binding sites with similar binding affinities in RG-2 and LK Walker 256 tumors and normal cortex. Bmax was 20-fold greater in glial tumors and 11.6- and 10.6-fold greater in LK and HK Walker 256 tumors, respectively, compared to normal cortex. The location of metastatic tumors, either intracerebrally or subcutaneously, did not effect their Kd or Bmax values. Kd and Bmax values for RG-2 tumors were similar whether determined densitometrically or by direct visualization with image analysis. Binding parameters within normal brain were difficult to visualize by image analysis due to the low level of specific binding. The ability to label specifically intracerebral tumor cells and to characterize the binding parameters shown in this study suggest that peripheral benzodiazepine receptor ligands could be utilized by PET to analyze directly a variety of tumors in humans.

Animals↗

The influence of mild body and brain hypothermia on ischemic brain damage.

The influence of brain and body temperature on ischemic brain damage, notably on the density and distribution of selective neuronal vulnerability, was studied in SPF-Wistar rats subjected to 15 min of forebrain ischemia induced by bilateral occlusion of the common carotid arteries combined with arterial hypotension (50 mm Hg) in a room air environment. In one group of animals, the body temperature was maintained at 37 degrees C but no attempt was made to prevent heat losses from the ischemic brain; i.e., the head was not heated during ischemia. Under those conditions the temperature of the caudoputamen and at a subcutaneous site over the skull bone spontaneously fell to approximately 32 degrees C. In four other groups, both the rectal and the subcutaneous skull temperatures were maintained at 38, 37, 35, and 33 degrees C during the ischemia. Our results confirm those recently reported when brain temperature was varied during 20 min of ischemia, with body temperature kept constant. Thus, the histopathological outcome of the brain damage, as assessed after 7 days of recovery, was strongly temperature dependent. Whereas ischemia at 37-38 degrees C consistently caused neuronal necrosis in the hippocampus, neocortex, and caudoputamen, spontaneous cooling of the brain during ischemia at a rectal temperature of 37 degrees C significantly reduced the ischemic damage. Intentional lowering of temperature to 35 degrees C markedly reduced and to 33 degrees C virtually prevented neuronal necrosis in some but not all of the regions studied. While damage to the caudoputamen was extremely temperature sensitive, that affecting the CA1 sector of the hippocampus, and particularly the lateral reticular nucleus of the thalamus, was less so. Our results suggest that whatever biochemical events are responsible for selective neuronal vulnerability, they are temperature sensitive; however, since there are differences in sensitivity between different parts of the brain, more than one mechanism may be involved.

Animals↗

Mitochondrial genetics in a natural population of the plant pathogen armillaria.

Transmission and propagation of mitochondrial genotypes in fungi have not been previously investigated in the field. This study examined the distribution of nuclear and mitochondrial genotypes in a natural, local population of the fungal (Basidiomycetes) root-rot pathogen, Armillaria. Six vegetative clones, ranging in size up to 635 m, were identified on the basis of mating-type alleles. Mitochondrial DNA (mtDNA) restriction fragment patterns indicated that each vegetative clone has one, unique mtDNA type. However, as in other basidiomycetous fungi, biparental transmission of mitochondria following laboratory matings of sexually compatible haploid isolates of Armillaria resulted in a uniformly diploid mycelium that was a mosaic for both parental mitochondrial types. Therefore, either matings between monosporous, haploid isolates are uncommon in nature, or when mating does occur, cytoplasmic markers of one partner predominate during subsequent vegetative growth.

Basidiomycota↗

Lung scanning for pulmonary embolism: clinical and pulmonary angiographic correlations.

A group of 78 patients with suspected pulmonary embolism was studied by both ventilation perfusion lung scanning and pulmonary angiography. Symptoms and clinical signs were analysed using Bayesian techniques to produce pre-test odds for pulmonary embolism in individual patients. While, as a group, those with embolism could be discriminated from those without on this basis, major overlap existed between the groups, invalidating the use of this approach for individual patients. Strict diagnostic criteria for interpretation of lung scans were accurate using pulmonary angiography as the 'gold standard', but at the expense of a significant number of patients (38 per cent) in the indeterminate (non-diagnostic) group. In the 48 patients in whom the test yielded a diagnostic result, there was a sensitivity of 100 per cent (15/15) and a specificity of 97 per cent (32/33). In the series as a whole, the likelihood of lung scanning correctly diagnosing pulmonary embolism was 55 per cent (15/27) and of correctly excluding embolism, 63 per cent (32/51). By the use of strict criteria for interpretation of lung scanning, reliable information can be obtained on the presence or absence of pulmonary embolism in a large proportion of patients suspected of having the condition. Such information is more discriminating than clinical signs and symptoms.

Adult↗