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Biomedical subjects

M L Smith

Publications and source records attributed to M L Smith.

At least 217 records · Page 12Linked to original sources
PubMed1994

Postoperative effects of fentanyl, ketorolac, and piroxicam as analgesics for outpatient laparoscopic procedures.

OBJECTIVE: To compare postoperative analgesia and side effects of intramuscular ketorolac, intravenous fentanyl, and oral piroxicam on healthy women undergoing laparoscopic surgery. METHODS: The study was a randomized double-blind clinical trial of three analgesic drugs. An initial 100-micrograms dose of fentanyl was given at induction, with 25-micrograms boluses after 45 and 90 minutes of operating time. Piroxicam, 40 mg, and ketorolac, 60 mg, were administered 90 and 30 minutes before induction, respectively. RESULTS: Eighty-four subjects were included in the analysis. Ketorolac patients (N = 29) spent significantly less time in the recovery room (median 96 minutes) than those receiving fentanyl (N = 27) (median 121 minutes; P < .01) or piroxicam (N = 28) (median 124 minutes; P < .01) or a verbal descriptive scale, more fentanyl patients (38%) experienced moderate pain at discharge than ketorolac (11%; P < .05) or piroxicam (4%; P < .01) patients. The incidence of measured side effects did not differ significantly between groups. CONCLUSIONS: Intramuscular ketorolac was associated with shorter recovery room stays while providing analgesia equal to intravenous fentanyl or the oral nonsteroidal antiinflammatory drug piroxicam.

Adult↗
PubMed1993

Potassium-induced changes in excitability in the hippocampal CA1 region of immature and adult rats.

Orthodromic and spontaneous population spike activity was measured in vitro in the CA1 region of rat hippocampal slices to determine maturational differences in excitability and susceptibility to K(+)-induced seizures. Several indices of excitability in the CA1 region changed in a non-monotonic fashion during maturation, in response to step-wise increases in bath [K+]. Slices from rats 18-22 days old, showed a greater probability of both spontaneous epileptiform activity and episodes of seizure-like activity followed by spreading depression, and more prolonged durations of evoked seizure-like events. Elevation of [K+] in the bathing medium increased these indices in a similar manner in older rats but not to the same degree as in 18- to 22-day-old rats. However, the threshold level of bath [K+] resulting in evoked bursts of population spikes was lower in adult and 28- to 32-day-old rats than in 18- to 22-day-old rats, suggesting that excitability is not uniformly greater at any given age. In 10- to 15-day-old rats, elevation of bath [K+] either produced persistent blockade of population responses, or increased the amplitude of the initial population spike, without producing bursts. Basal levels of [K+] in the interstitium of the slices corresponded to the various levels of [K+] placed in the bathing medium and there were no differences among age groups. Therefore, differences in basal [K+]o cannot account for the maturational changes in excitability and seizure activity. The period from 18-22 days of age in the rat is a useful focal point for investigating mechanisms underlying maturational changes in propensity to develop seizures.

Action Potentials↗
PubMed1993

Abnormalities in the p53 gene in tumors and cell lines of human squamous-cell carcinomas of the head and neck.

Abnormalities in the p53 gene were studied in a series of cell lines of human squamous-cell carcinoma of the head and neck (SCCHN) and in tumor tissues. Restriction-fragment-length polymorphism (RFLP), quantitative hybridization and immunochemical analysis of mutant p53 proteins were combined to detect and characterize 3 different phases in the p53 gene alteration: mutation (in 9/9 cases), 17p13 deletion (9/10 cases) and amplification of the non-deleted allele (9/31 cases). In SCCHN, deletion of the p53 gene was nearly always accompanied by mutation, only one cell line studied having mutation without deletion. Alterations in the p53 gene are common in SCCHN, and involve a series of genetic events which occur in sequence during tumor progression.

Alleles↗
PubMed1993

Lack of mutations of the p53 tumor suppressor gene in hepatocellular carcinomas induced in rats by a peroxisome proliferator.

Immunohistochemical, immunoblotting, and DNA-sequencing analyses were performed on hepatocellular carcinomas induced in rats chronically fed BR931, a peroxisome proliferator, to determine whether the tumors carried mutations or other alterations of the p53 gene. None were detected. Inactivation of this tumor suppressor gene does not appear, therefore, to be involved in the carcinogenicity of BR931, a nongenotoxic chemical hepatocarcinogen.

Animals↗
PubMed1993

Low frequency of retinoblastoma gene alterations in rat hepatocellular carcinomas.

Abnormalities of the retinoblastoma (Rb) gene have been reported in some human cancers, including hepatocellular carcinomas (HCCs). We examined by Southern blotting the status of the Rb gene in HCCs induced in rats in four experimental models. A low frequency of Rb gene alterations, detected as novel hybridizing bands unique to each tumor, was observed. Expression of the Rb protein product was examined in the HCCs and in seven established rat hepatoma cell lines studied. It appears, therefore, that alterations in the structure or expression of the Rb gene do occur but probably do not contribute in a major way to hepatocarcinogenesis in the rat.

Alleles↗
PubMed1993

Free radicals and brain damage due to transient middle cerebral artery occlusion: the effect of dimethylthiourea.

The objective of this study was to assess whether dimethylthiourea (DMTU), an established free radical scavenger, ameliorates ischaemic damage due to 2-3 h of transient middle cerebral artery (MCA) occlusion, induced by an intraluminal filament. A major point addressed was whether DMTU given before MCA occlusion only delayed the "maturation" of the damage, or if it had a lasting effect on infarct size. The end point was morphological, and either encompassed triphenyltetrazolium chloride (TTC) staining of tissue slices after 24 h or 48 h of recovery, or histopathological assessment of infarct size after 7 days of recovery. In a preliminary series of experiments, rats were subjected to 3 h of MCA occlusion, and infarct volume was assessed by TTC staining after 24 h of recovery. DMTU in a dose of 750 mg/kg reduced infarct volume by more than 50%. However, due to a high mortality rate, that protocol was not subsequently pursued. When the ischaemia duration was reduced to 2 h and the DMTU dose to 400 mg/kg, a similar amelioration of the tissue damage was observed. However, since DMTU reduced a spontaneous rise in body temperature to 39.0-39.5 degrees C, DMTU-treated animals in the main series of experiments with 24 and 48 h of recovery were treated so that they had the same temperature rise as the saline controls. Under such constant temperature conditions, the effect of DMTU at 24 h of recovery was borderline (P = 0.052) and at 48 h it was nil. The lack of a lasting effect of DMTU was supported by the findings on evaluation of infarct area after 7 days of recovery. The results raise the important question whether DMTU, and perhaps other free radical scavengers, delay rather than ameliorate the ischaemic lesion developing after transient MCA occlusion.

Animals↗
PubMed1993

Naloxone does not prevent vasovagal syncope during simulated orthostasis in humans.

The mechanism of vasovagal syncope during orthostasis in humans is unknown. Opioid receptors have been implicated in the vasovagal-like responses to hemorrhagic hypotension in conscious animals. We sought to determine if opioid receptor blockade with naloxone (mu receptor antagonist) would prevent or delay the onset of vasovagal syncope in humans. Three protocols were performed in which heart rate, arterial pressure, sympathetic nerve activity, thoracic impedance and forearm vascular resistance were measured during stepwise steady-state increments of lower body negative pressure (LBNP) in nine healthy volunteers. In protocol 1, duplicate trials of LBNP to syncope or -60 mmHg were performed with a 30-45 minute rest period separating the trials. No significant differences in any physiologic responses or cumulative stress tolerance were found. In protocol 2, graded LBNP was repeated after administration of saline or naloxone (0.1 mg/kg) in six subjects in which vasovagal syncope occurred prior to -60 mmHg LBNP. The peak increase of sympathetic nerve activity during LBNP was augmented after naloxone (P = 0.02), but the occurrence of vasovagal syncope was not prevented nor was the cumulative stress tolerated affected (P = 0.42). The heart rate and arterial pressure responses to LBNP were not affected by naloxone. Similarly, in protocol 3, naloxone given just prior to the onset of pre-syncopal symptoms did not alter the physiologic response or the occurrence of vasovagal syncope. These data show that naloxone does not prevent or delay the onset of vasovagal syncope in humans which suggests that mu opioid receptors do not mediate the vasovagal response.

Adult↗
PubMed1993

Abnormalities of baroreflex control in heart failure.

This brief review summarizes abnormalities of arterial and cardiopulmonary baroreflex control of heart rate and sympathetic nerve activity. The potential role of these abnormalities in the development of the neurohumoral excitatory state associated with heart failure is discussed. Major emphasis is placed on the identification of important issues still to be investigated in this area. The potential importance of altered cardiovascular reflexes in the context of the interaction of the patient with heart failure and environmental stresses is discussed. The use of the canine rapid ventricular pacing model of biventricular failure in the investigation of abnormalities of baroreflexes in heart failure is emphasized. Insights obtained from this model should be extended to human investigations.

Animals↗
PubMed1993

Increased production of the TrkB protein tyrosine kinase receptor after brain insults.

The protein-tyrosine kinases Trk, TrkB, and TrkC are signal-transducing receptors for a family of neurotrophic factors known as the neurotrophins. Here we show that seizures induced by hippocampal kindling lead to a rapid, transient increase of trkB mRNA and protein in the hippocampus. TrkB is a component of a high affinity receptor for brain-derived neurotrophic factor (BDNF). No change was detected in mRNAs for Trk or TrkC, components of the high affinity nerve growth factor or neurotrophin-3 receptors, respectively. trkB mRNA was also transiently increased in the dentate gyrus following cerebral ischemia and hypoglycemic coma; these treatments had no effect on trk and trkC mRNAs. The increase in trkB mRNA and protein showed the same time course and distribution as the increase in BDNF mRNA. These data suggest that BDNF and its receptor may play a local role within the hippocampus in kindling-associated neural plasticity and in neuronal protection following epileptic, ischemic, and hypoglycemic insults.

Animals↗
PubMed1993

Does ischemia with reperfusion lead to oxidative damage to proteins in the brain?

Recent results suggest that even relatively brief periods of ischemia in gerbils (10 min) lead to oxidative damage to brain proteins, reflected in an increased carbonyl content in the soluble protein fraction and a decreased glutamine synthetase (GS) activity. Since we failed to reproduce these findings in rats subjected to 15 min of transient ischemia, we explored whether oxidative damage to proteins could be observed after longer ischemic periods. To that end, one middle cerebral artery was occluded in rats for either 1 or 3 h, with recirculation periods of 0 min, 15 min, 1 h, and 6 h. Protein carbonyl content and GS activity were determined in focal and perifocal tissues and compared with values obtained in the same areas on the contralateral side. Ischemia, particularly of 3-h duration, followed by various reperfusion periods was accompanied by a significant (16-35%) decrease in the concentration of proteins of the soluble protein fraction. However, in no group was there an increased carbonyl content of the remaining proteins in this fraction. When expressed per milligram of protein, GS activity remained unchanged or rose somewhat. An inconsistent (and moderate) decrease in GS activity was present only if GS activity was expressed per milligram of wet tissue. The present findings, which fail to document oxidative damage to proteins following focal ischemia of 1- or 3-h duration, are thus radically different from those obtained in gerbils. The results suggest that appreciable species differences exist and raise the question of whether free radical-mediated oxidation of proteins is an invariable component of ischemic brain damage.

Animals↗
PubMed1993

Computer simulation of selection in a hypothetical crop species.

A computer simulation model demonstrating the effect of directional selection upon a simplified quantitative genetic character, is presented. Complementary homozygous parents were crossed to generate a fully heterozygous F1 population. Phenotypic truncation selection was effected upon the F2 and subsequent generations, and genotypic and phenotypic response to selection, as well as the change in population heterozygosity, was monitored to generation F9. The model simulates selection for alternative breeding regimes, modes of allelic interaction, selection pressure, population size and levels of environmental variation. Three alternative methods for the simulation of the environmental component of phenotypic variance are incorporated, and mechanisms and relative merits of the rival methods are discussed. Data generated by the model conformed closely to theoretical expectation, lending support to the use of the model as a platform for development of more comprehensive simulation models. Potential improvements to the model are discussed.

Algorithms↗
PubMed1993

p53 mutations in hepatocellular carcinomas induced by a choline-devoid diet in male Fischer 344 rats.

Analyses were performed on livers and hepatocellular carcinomas from male Fischer 344 rats fed a choline-devoid diet, to assess whether they carried alterations of the p53 tumor suppressor gene. The analyses consisted of immunoperoxidase staining of tissue sections with monoclonal antibodies to p53, Western blotting and cDNA sequencing. Immunostaining revealed the presence of mutant p53 proteins in 22/27 tumors analyzed and immunoblotting in 18/20. Immunochemical evidence was obtained that occurrence of the mutations precedes tumor development. cDNA sequencing was performed on 11 hepatocellular carcinomas that expressed mutant p53 gene proteins. Seven were found to contain point mutations within the 120-290 codon region of the gene, and one a microdeletion in the same region. No mutational hot spot was observed. It is concluded that mutations within the p53 gene, along with a c-myc gene amplification previously detected in these tumors, most likely contribute to the neoplastic transformation of liver cells in this nutritional model of hepatocarcinogenesis. The results are discussed also in view of recent literature on the presence of p53 mutations in human hepatocellular carcinomas.

Animals↗
PubMed1993

Detection of amphetamine and methamphetamine in urine by gas chromatography/Fourier transform infrared (GC/FTIR) spectroscopy.

New methods for identification of amphetamines have been employed using gas chromatography/Fourier transform infrared spectroscopy (GC/FTIR). These methods have provided identification of the drug and its metabolites, with detection at the low picogram levels or less than 10 ng/mL. Developments in cryogenic sample deposition for GC/FTIR spectroscopy have increased the sensitivity of GC/FTIR to levels that match or surpass that of gas chromatography/mass spectrometry (GC/MS). This advancement in technology has allowed the highly selective ability of infrared spectroscopy to be used for identification and quantitation in studies where the analytes are in low concentrations. The limits of detection (LOD), quantitation (LOQ), and linearity (LOL), and precision have been determined in this study, and these instrumental parameters have been compared with those of established techniques.

Amphetamine↗
PubMed1993

An intoxication involving BRON and verapamil.

A case is presented in which the body of a 19-year-old white male was found in his family's quarters by his mother. An autopsy failed to determine the cause of death, and specimens were sent out for toxicologic analysis. No ethanol or volatile substances were detected in the blood, urine, or vitreous fluid. Comprehensive drug testing of the urine identified chlorpheniramine, dihydrocodeine, methylephedrine, salicylate, and verapamil. The first three drugs listed appear together in an over-the-counter cold medication in Japan, under the trade name BRON. Blood quantitations (in mg/L) were as follows: chlorpheniramine, 2.6; dihydrocodeine, 4.7; methylephedrine, 5.6; salicylate, 150; and verapamil, 6.0. The cause of death was multiple drug intoxication, and the manner of death was suicide.

Adult↗
PubMed1993

A multiple drug intoxication involving cyclobenzaprine and ibuprofen.

A 19-year-old black man presented to the emergency room with superficial cuts on the anterior wrists, lethargy, tachycardia, and metabolic acidosis. Multiple containers of medication were found at the scene. Dysrhythmias developed and the patient died 7 h after admission. No anatomic cause of death was identifiable at autopsy. Toxicologic analysis identified the following drugs in the blood (mg/L): cyclobenzaprine (0.3), phenylpropanolamine (2.5), chlorpheniramine (0.2), lidocaine (6.6), phenytoin (19), and ibuprofen (130). Lidocaine and phenytoin had been administered therapeutically. The major symptoms displayed by the patient were tachycardia and metabolic acidosis, symptoms consistent with cyclobenzaprine and ibuprofen intoxication, respectively. Therefore, the medical examiner ruled that the cause of death was multiple drug intoxication and that the manner of death was suicide.

Adult↗
PubMed1993

Renal sympathetic responses to conflicting baroreceptor inputs: rapid ventricular pacing in dogs.

1. Ventricular tachycardia generates complex changes in baroreceptor input to the central nervous system: arterial baroreceptors are unloaded while cardiopulmonary receptors are stimulated. In humans with heart diseases, muscle sympathetic nerve activity increases during ventricular tachycardia. This suggests that arterial baroreceptor-mediated sympathoexcitation overrides cardiopulmonary receptor-mediated sympathoinhibition. However, the relative roles of each reflex are difficult to determine in humans. 2. We measured efferent renal sympathetic neural responses to simulated ventricular tachycardia, to determine what pathophysiological mechanisms are invoked when inputs from different baroreceptive areas change in opposite directions. In alpha-chloralose anaesthetized, mechanically ventilated dogs, we recorded the electrocardiogram, mean left atrial and arterial pressures and multifibre efferent renal sympathetic nerve activity (RSNA) during 1 min of right ventricular pacing at 214 beats min-1. Pacing was repeated after either sinoaortic or vagal cardiopulmonary denervation and again after both sinoaortic and cardiopulmonary denervation. 3. With all afferent baroreceptor pathways intact, right ventricular pacing elicited transient sympathoinhibition (delta RSNA, -19 +/- 10%, mean +/- S.E.M.). After sinoaortic denervation (cardiopulmonary receptors intact), right ventricular pacing elicited abrupt and sustained sympathoinhibition (delta RSNA, -53 +/- 8%, P < 0.05 vs. intact). After vagal cardiopulmonary denervation (sinoaortic receptors intact), right ventricular pacing elicited abrupt and sustained sympathoexcitation (delta RSNA, + 56 +/- 19%, P < 0.05 vs. intact). After both sinoaortic and vagal cardiopulmonary denervation, right ventricular pacing elicited a gradual increase in sympathetic outflow (delta RSNA, + 16 +/- 6%, P < 0.05 vs. intact). 4. We conclude that interactions between vagal cardiopulmonary and arterial baroreflexes determine renal sympathetic outflow during simulated ventricular tachycardia. In healthy anaesthetized dogs, the balance of the two opposing reflexes is weighted towards vagal cardiopulmonary-mediated sympathoinhibition.

Animals↗