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Biomedical subjects

M L Smith

Publications and source records attributed to M L Smith.

At least 235 records · Page 13Linked to original sources
PubMed1993

Comparison of the post-Chernobyl 137Cs contamination of mushrooms from eastern Europe, Sweden, and North America.

A comparison was made of 134Cs and 137Cs contamination in fungi from eastern Europe and eastern North America. Mean activities of 25 Ukrainian, 6 Swedish, and 10 North American collections were 4,660, 9,750, and 205 Bq/kg (dry weight), respectively. Additional measurements were made on samples from the Moscow, southern Belarus, and Yugoslavia/Bulgaria regions. Activity values were found to vary by several orders of magnitude within all geographic areas, even for the same mushroom species. Significantly higher specific activities were observed in mycorrhizal species than in saprophytic and parasitic fungi. Unfortunately, many of the European mycorrhizal species considered as prized edibles contained unacceptably high levels of 137Cs (> 1,000 Bq/kg [dry weight]) and should be used sparingly as food. By contrast, no mushrooms collected in Ontario or northern Michigan exceeded 1,000 Bq of 137Cs per kg (dry weight). The excessive 137Cs contamination was evident in mushrooms from areas that had substantial fallout from the 1986 accident in reactor 4 at the Chernobyl nuclear power station. However, observations suggest that about 20% of the 137Cs in eastern Europe (Moscow area, Belarus, and Ukraine) is of non-Chernobyl origin.

Air Pollution, Radioactive↗
PubMed1993

Influence of cigarette smoking on human autonomic function.

BACKGROUND: Although cigarette smoking is known to lead to widespread augmentation of sympathetic nervous system activity, little is known about the effects of smoking on directly measured human sympathetic activity and its reflex control. METHODS AND RESULTS: We studied the acute effects of smoking two research-grade cigarettes on muscle sympathetic nerve activity and on arterial baroreflex-mediated changes of sympathetic and vagal neural cardiovascular outflows in eight healthy habitual smokers. Measurements were made during frequency-controlled breathing, graded Valsalva maneuvers, and carotid baroreceptor stimulation with ramped sequences of neck pressure and suction. Smoking provoked the following changes: Arterial pressure increased significantly, and RR intervals, RR interval spectral power at the respiratory frequency, and muscle sympathetic nerve activity decreased. Plasma nicotine levels increased significantly, but plasma epinephrine, norepinephrine, and neuropeptide Y levels did not change. Peak sympathetic nerve activity during and systolic pressure overshoots after Valsalva straining increased significantly in proportion to increases of plasma nicotine levels. The average carotid baroreceptor-cardiac reflex relation shifted rightward and downward on arterial pressure and RR interval axes; average gain, operational point, and response range did not change. CONCLUSIONS: In habitual smokers, smoking acutely reduces baseline levels of vagal-cardiac nerve activity and completely resets vagally mediated arterial baroreceptor-cardiac reflex responses. Smoking also reduces muscle sympathetic nerve activity but augments increases of sympathetic activity triggered by brief arterial pressure reductions. This pattern of autonomic changes is likely to influence smokers' responses to acute arterial pressure reductions importantly.

Adult↗
PubMed1993

Effects of dimethylthiourea on selective neuronal vulnerability in forebrain ischemia in rats.

BACKGROUND AND PURPOSE: Attempts have been made to characterize conditions under which oxygen free radicals contribute to ischemic brain damage. According to one hypothesis, free radicals are likely mediators of damage only when ischemia is of such long duration that infarction develops or when either preischemic hyperglycemia or hyperthermia is present. The objective of the present study was to explore whether 15 minutes of forebrain ischemia, an insult that leads to selective neuronal vulnerability but not to infarction, is accompanied by production of pathogenetically important free radicals. METHODS: Using a histopathological end point, we studied amelioration of damage by a free radical scavenger, dimethylthiourea, administered in a dose of 750 mg/kg i.p. 60 minutes before ischemia. To study whether this insult leads to detectable protein oxidation we assessed the activity of glutamine synthetase and of carbonyl compounds in the soluble protein fraction. RESULTS: In control animals, the transient ischemia resulted in the expected damage to vulnerable neurons in hippocampus, caudoputamen, and neocortex after 7 days of recovery. Glutamine synthetase activity in caudoputamen and hippocampus and carbonyl content in the soluble protein fraction after 90 minutes of recovery were not affected. However, dimethylthiourea significantly reduced damage to hippocampus and caudoputamen (p < 0.001) and neocortex (p < 0.005). CONCLUSIONS: Lack of evidence of protein oxidation supports the notion that 15 minutes of forebrain ischemia results in a limited insult, confined to the neurons. Provided that unspecific effects can be excluded, the results obtained with dimethylthiourea suggest that free radicals contribute to selective neuronal necrosis.

Animals↗
PubMed1993

Cholinesterase activity in postmortem blood as a screening test for organophosphate/chemical weapon exposure.

This study was undertaken to determine whether postmortem blood cholinesterase activity could be used as a screening test for exposure to nerve agents. Whole blood cholinesterase activity at 25 degrees C was analyzed for a one week period in order to simulate the battle field collection problems of: hemolyzed blood samples, delayed recovery of the specimen, and unrefrigerated transfer to the testing facility. A total of 53 nonpreserved post-mortem whole blood specimens were analyzed in triplicate for cholinesterase activity by the delta pH method of Michel. There was a negligible loss of cholinesterase activity by the seventh day of the study. The enzyme activities of the specimens had a mean value (range) of 0.48 (0.20 to 0.74) initially and 0.45 (0.07 to 0.70) pH units after one week. Whole blood from five healthy adults remained essentially unchanged during this period, with an initial value 0.59 (0.52 to 0.67) and a final value of 0.52 (0.46 to 0.62) pH units. To compare postmortem and simulated nerve agent values, aliquots from 18 of the original 53 postmortem specimens were frozen during day one of the study, thawed on day seven and a cholinesterase inhibitor added. These specimens were then analyzed with the other specimens. All values from inhibited specimens were essentially zero (0.0 to 0.01) pH units compared to a range of 0.07 to 0.61 pH units for matched, uninhibited, day seven postmortem specimens. Fifteen actual nonpreserved specimens from the battlefield were analyzed as verification of screen performance. Their results fell within the uninhibited postmortem range above.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Preservation↗
PubMed1993

Two deaths involving isoflurane abuse.

Two deaths due to isoflurane abuse are reported. One case was a suicide and the other a multiple drug death including isoflurane. A simple headspace gas chromatographic method was used for isoflurane quantitation. A review of the literature did not reveal blood and tissue concentrations of isoflurane. Drug tissue distributions and a discussion of the toxicological findings are presented.

Adult↗
PubMed1993

Interpretation of low postmortem concentrations of ethanol.

The interpretation of postmortem blood ethanol concentrations (BAC), especially those less than 0.05 g/dL can be complicated by postmortem ethanol formation. One method used by the toxicologist to respond to this possibility is to analyze multiple specimens for ethanol. Two useful specimens to analyze are vitreous humor and urine, because they are less susceptible to the putrefaction process. A negative vitreous humor and/or urine ethanol would suggest that the measured ethanol resulted from postmortem formation. Data were collected from the Office of the Chief Medical Examiner, State of Maryland and the Armed Forces Institute of Pathology on blood specimens with ethanol concentrations less than 0.05 g/dL to develop a reasonable threshold for interpretation in the absence of other specimens. A total of 381 cases with a BAC between 0.01 and 0.04 g/dL were studied over a 2 year period. Urine and vitreous humor specimens were tested where available. At a BAC of 0.01 g/dL, 54% of the cases were associated with a positive vitreous humor and/or urine ethanol concentration. This percentage increased to 63% when BAC equals 0.02 g/dL. Seventy-three percent and 92% of the cases had a positive alternate specimen if the BAC was 0.03 g/dL and 0.04 g/dL, respectively. In addition, 90% of the cases where both vitreous humor and urine were analyzed showed consistent results, that is both specimens were positive or negative. This suggests that in the absence of additional information, a BAC of 0.04 g/dL or higher probably resulted from ethanol consumption.

Alcohol Drinking↗
PubMed1992

Measurement of azacyclonol in urine and serum of humans following terfenadine (Seldane) administration using gas chromatography-mass spectrometry.

A gas chromatographic-mass spectrometric (GC-MS) method is presented for the analysis of azacyclonol (AZA), a metabolite of terfenadine in serum and urine specimens. Following an alkaline extraction, AZA and an internal standard were derivatized using heptafluorobutyric anhydride. Fourier transform infrared spectrometry suggested that two sites on the AZA molecule were derivatized. GC-MS of the extracts had a limit of quantitation (LOQ) of 1 ng/ml and linear range of 1-1000 ng/ml in urine. Four volunteers were administered a therapeutic regimen of terfenadine followed by urine and serum specimen collection(s) during the next seven days. The results indicated that following a 60-mg dose of terfenadine each 12 h for five days, (1) AZA appears in urine within 2 h, (2) urine AZA concentrations were above the LOQ 72 h following the last dose, (3) peak urine concentrations were as high as 19,000 ng/ml, and (4) mean serum concentration following the ninth dose was 59 ng/ml.

Adult↗
PubMed1992

Differential regulation of mRNAs for nerve growth factor, brain-derived neurotrophic factor, and neurotrophin 3 in the adult rat brain following cerebral ischemia and hypoglycemic coma.

In situ hybridization was used to study expression of mRNAs for members of the nerve growth factor (NGF) family in the rat brain after 2 and 10 min of forebrain ischemia and 1 and 30 min of insulin-induced hypoglycemic coma. Two hours after the ischemic insults, the level of brain-derived neurotrophic factor (BDNF) mRNA was markedly increased in the granule cells of the dentate gyrus, and at 24 h it was still significantly elevated. NGF mRNA showed a pronounced increase 4 h after 2 min of ischemia but had returned to a control level at 24 h. Both 2 and 10 min of ischemia caused a clear reduction of the level of mRNA for neurotrophin 3 (NT-3) in the dentate granule cells and in regions CA2 and medial CA1 of the hippocampus 2 and 4 h after the insults. The increase of BDNF mRNA could be partially blocked by the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist NBQX but was not influenced by the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801. Both NBQX and MK-801 attenuated the decrease of NT-3 mRNA after ischemia. One and 30 min of hypoglycemic coma also induced marked increases in BDNF and NGF mRNA in dentate granule cells with maximal levels at 2 h. If the changes of mRNA expression lead to alterations in the relative availability of neurotrophic factors, this could influence functional outcome and neuronal necrosis following ischemic and hypoglycemic insults.

Animals↗
PubMed1992

Pediatric euthanasia.

Pediatric euthanasia is currently practiced in the Netherlands on newborns, infants, children, and adolescents, although exact numbers are not known. Euthanasia in the Netherlands is generally assumed to be active and voluntary, but some cases of pediatric euthanasia would have to be characterized as nonvoluntary. Much of the motivation behind the euthanasia movement and the performance of pediatric euthanasia in the Netherlands is a genuine, compassionate desire to alleviate pain and suffering. In this study, we review the Dutch experience, with particular attention to the current practice of euthanasia on newborns, infants, children, and adolescents. We discuss pediatric euthanasia from an ethical point of view. We assert that more effective pain control, better symptom management, and psychosocial support of the dying and their families would alleviate the perception of suffering, and reduce the perceived need to resort to euthanasia.

Adolescent↗
PubMed1992

Ischemic penumbra in a model of reversible middle cerebral artery occlusion in the rat.

It has become increasingly clear that a stroke lesion usually consists of a densely ischemic focus and of perifocal areas with better upheld flow rates. At least in rats and cats, some of these perifocal ("penumbral") areas subsequently become recruited in the infarction process. The mechanisms may involve an aberrant cellular calcium metabolism and enhanced production of free radicals. In general, though, the metabolic perturbation in the penumbra requires better characterization. The objective of this article was to define flow distribution in a rat model of reversible middle cerebral artery (MCA) occlusion, so as to allow delineation of the metabolic aberrations responsible for the subsequent infarction. We modified the intraluminal filament occlusion model recently developed by Koizumi et al. (1986), and described in more detail by Nagasawa and Kogure (1989), adopting it for use in both spontaneously breathing and artificially ventilated rats. Successful occlusion of the MCA (achieved in about 9/10 rats) was judged by unilateral EEG depression in ventilated rats, and neurological deficits, such as circling, in spontaneously breathing ones. CBF in the ipsilateral hemisphere was reduced to nearly constant values after 20, 60, and 120 min of occlusion, flow rates in the focus being about 10% and in the perifocal ipsilateral areas about 15-20% of control (contralateral side). When the filament was left in place (permanent occlusion) 2,3,5-triphenyl tetrazolium chloride (TTC) staining and histopathology after 24 h showed a massive infarct on the occluded side, extending from caudoputamen and overlaying cortex to the occipital striate cortex. Animals recirculated after 60 min of MCA occlusion, and allowed to survive 7 days for histopathology, showed infarction of the caudoputamen (lateral part or whole nucleus) in 5/6 animals and selective neuronal necrosis in one animal. The neocortex showed either infarcts, selective neuronal necrosis, or no damage. There was some overlap between neocortical areas which were infarcted and those which were salvaged by reperfusion. In general, though, both the CBF data and the recovery studies with a histopathological endpoint define large parts of the neocortex as perifocal (penumbral) areas which lend themselves to studies of metabolic events leading to infarction.

Animals↗
PubMed1992

The influence of hypothermia on hypoglycemia-induced brain damage in the rat.

The effects of hypothermia on hypoglycemic brain damage were studied in rats after a 30-min period of hypoglycemic coma, defined as cessation of spontaneous EEG activity. The rats were either normothermic (37 degrees C) or moderately hypothermic (33 degrees C). Morphological brain damage was evaluated after various periods of recovery. Hypothermic animals with halothane anesthesia never resumed spontaneous respiration, thus requiring artificial ventilation during recovery (maximally 8 h). In contrast, when isoflurane was used as the anesthetic agent, all animals survived and were examined after 1 week of recovery. There was a tendency towards gradually higher arterial plasma glucose levels during hypoglycemia with lower body temperature. The time period from insulin injection until isoelectric EEG appeared was gradually prolonged by hypothermia, and was shorter when isoflurane was used for anesthesia. Brain damage was examined within the neocortex, caudoputamen and hippocampus (CA1, subiculum and the tip of the dentate gyrus). Damage to neurons was found to be of two types, namely condensed dark purple neurons (pre-acidophilic) and shrunken bright red-staining neurons (acidophilic). In the neocortex, no clear influence of temperature on the degree of injury was seen. In the caudoputamen, the number of injured neurons clearly decreased at lower temperature (33 degrees C, P less than 0.001) when halothane was used, while no such difference was seen when isoflurane was used as the anesthetic agent. Likewise, a protective effect of hypothermia was seen in subiculum (P less than 0.01) when halothane, but not isoflurane was used.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Sympathoinhibition and hypotension in carotid sinus hypersensitivity.

Carotid sinus reflex hypersensitivity is a known cause of syncope in humans. The condition is characterized by cardioinhibition and vasodepression, each to varying degrees. The extent and importance of sympathoinhibition has not been determined in patients with carotid sinus hypersensitivity. This study reports on the extent of sympathoinhibition measured directly directly during carotid massage with and without atrioventricular sequential pacing, in a patient with symptomatic carotid sinus reflex hypersensitivity. Carotid massage elicited asystole, hypotension and complete inhibition of muscle sympathetic nerve activity. Carotid massage during atrioventricular pacing produced similar sympathoinhibition, but with minimal hypotension. Therefore, sympathoinhibition did not contribute importantly to the hypotension during carotid massage in the supine position in this patient. Further investigations are required to elucidate the relation of sympathoinhibition to hypotension in patients with carotid sinus hypersensitivity in the upright position.

Carotid Sinus↗
PubMed1992

Frontal cortex lesion prior to hyperglycemic ischemia: no decrease in ensuing substantia nigra pars reticulata damage or fatal post-ischemic seizures.

Preischemic hyperglycemia worsens brain damage after ischemia, and characteristically leads to post-ischemic seizures and a pan-necrotic lesion in substantia nigra pars reticulata (SNPR). The excitatory input to SNPR could contribute to the damage observed. By performing a unilateral frontal cortex lesion 6-19 days prior to the ischemia, we wanted to explore whether a decrease in excitatory input to the ipsilateral SNPR ameliorate the seizures or alter the light microscopical damage in SNPR. Our results demonstrate that unilateral frontal cortex lesion did not alter the development of fatal post-ischemic seizures after 10 min of ischemia in hyperglycemic subjects. Thus, 7/8 animals developed seizures and died within 20 h of recovery. This study also failed to show any difference between the left and right side in post-ischemic SNPR damage after 15 h of recovery in animals with preischemic unilateral frontal cortex lesion. Furthermore, no side difference was observed in any other brain region evaluated. The results thus suggest that the pan-necrotic lesion in SNPR after hyperglycemic ischemia is not caused by excessive excitatory input from frontal cortex. A decrease in the GABA-ergic inhibitory input from caudoputamen to SNPR may be a more important mechanism for the ensuing excitotoxic post-ischemic SNPR damage, and for seizure development.

Amino Acids↗