Search PubMed⌕ Search

Biomedical subjects

M B Smith

Publications and source records attributed to M B Smith.

At least 109 records · Page 6Linked to original sources
PubMed1992

Does glycine antagonism underlie the excitatory effects of methohexitone and propofol?

We have investigated the pharmacological basis of CNS excitation that occurs in association with general anaesthesia in mice. Propofol produced sustained clonic movements during anaesthesia. Methohexitone produced intermittent non-rhythmic jerking during anaesthesia. Ethanol and pentobarbitone produced anaesthesia without associated clonic movements. Doses of all anaesthetic drugs were equipotent. Surface EEG recordings showed paroxysmal discharges consistent with interictal manifestations of cortical seizures with methohexitone or propofol, but not with ethanol or pentobarbitone. Strychnine, a glycine antagonist without effects on the cerebral cortex, and bicuculline, a GABAA antagonist with effects on the cerebral cortex, were used in doses that were equipotent-0.5 log units less than the ED10 for clonic convulsions. Strychnine potentiated both excitatory behaviour and EEG paroxysmal discharges when given with methohexitone or propofol, but not with ethanol or pentobarbitone. Bicuculline did not affect either behaviour or EEG with any of the anaesthetic drugs. Our data show that methohexitone and propofol produced CNS excitation, while pentobarbitone and ethanol did not. We propose that the pharmacological basis of this excitation may be glycine antagonism occurring in subcortical structures.

Anesthesia, General↗
PubMed1992

Splitting tubes.

Explore the source record for details and available documents.

Anesthesiology↗
PubMed1992

Hydrogen ion concentration is not the sole determinant of muscle metaboreceptor responses in humans.

We examined the effects of exercise conditioning on muscle sympathetic nerve activity (MSNA) during handgrip and posthandgrip circulatory arrest (PHG-CA). Two conditioning stimuli were studied: forearm dominance and bodybuilding. Static handgrip at 30% maximal voluntary contraction followed by PHG-CA led to a rise in MSNA smaller in dominant than in nondominant forearms (99% vs. 222%; P less than 0.02) and in body builders than in normal volunteers (28% vs. 244%; P less than 0.01). Separate 31P NMR experiments showed no effect of dominance on forearm pH but a pH in bodybuilders higher (6.88) than in normal volunteers (6.79; P less than 0.02) during PHG-CA. Our second goal was to determine if factors besides attenuated [H+] contribute to this conditioning effect. If differences in MSNA during exercise were noted at the same pH, then other mechanisms must contribute to the training effect. We measured MSNA during ischemic fatiguing handgrip. No dominance or bodybuilding effect on pH was noted. However, we noted increases in MSNA smaller in dominant than nondominant forearms (212% vs. 322%; P less than 0.02) and in bodybuilders than in normal volunteers (161% vs. 334%; P less than 0.01). In summary, MSNA responses were less during exercise of conditioned limbs. Factors aside from a lessening of muscle acidosis contribute to this effect.

Adult↗
PubMed1992

Baclofen effect on quadriceps strength in multiple sclerosis.

Weakness has been reported by patients as one side effect of baclofen. We evaluated torque production as a measure of contractile strength in 30 subjects with clinically definite multiple sclerosis. Participants, with minimal to moderate spasticity, were titrated onto baclofen by 5mg increments every other day for seven days and maintained at 20mg for one week. Using a KinCom isokinetic unit set at 60 degrees per second, subjects performed maximal concentric quadriceps contractions; three consecutive trials were recorded. Results indicated no significant difference in maximum torque production between sessions. Although torque values remained unchanged, the angle at which peak torque production occurred moved closer to normal values. Subjective reports of weakness do not appear related to physiologic properties of contraction, but may be a subjective interpretation that less stiffness is weakness because of less resistance to muscle contraction.

Activities of Daily Living↗
PubMed1992

Effect of pH and inorganic phosphate on creatine kinase inactivation: an in vitro 31P NMR saturation-transfer study.

The pseudo-first-order rate constant of rabbit muscle creatine kinase (CK), in the direction of ATP synthesis (kf), was determined by saturation-transfer 31P NMR. When pH was varied between 6.0 and 7.4, kf increased linearly at both 20 degrees C and 37 degrees c. The corresponding flux is very small between pH 6.0 and 6.5, in contrast to previous studies. Up to 50 h exposure of the CK enzyme to high concentrations of inorganic phosphate (Pi), a known inhibitor in certain situations, had negligible effect on enzymatic flux in the physiological pH range. Thus under in vivo conditions, such as in stroke, where pH falls as low as 6.2 and Pi rises to high levels, the rate of the CK reaction may be severely reduced due to pH but not due to high Pi concentrations.

Adenosine Triphosphate↗
PubMed1991

31P NMR saturation-transfer study of the in situ kinetics of the mitochondrial adenine nucleotide translocase.

The exchange of intramitochondrial ATP (ATP(in)) for extramitochondrial ATP (ATP(out)) was measured by using 31P NMR spectroscopy over a range of temperatures in isolated rat liver mitochondria oxidizing glutamate and succinate in the presence of external ATP but no added ADP (state 4). The rate of this exchange is more than an order of magnitude faster than rates reported previously that were determined by using isotopic techniques in the presence of oligomycin, the potent ATPase inhibitor. Differences are ascribed in part to the low levels of matrix ATP present in oligomycin-treated mitochondria. The addition of oligomycin to mitochondrial suspensions decreases intramitochondrial ATP levels from 17 +/- 3 (SEM) nmol/mg of protein in state 4 to 1.51 +/- 0.1 nmol/mg of protein in the presence of inhibitor at 8 degrees C. Simultaneously, transporter flux falls from 960 +/- 55 nmol/min.mg to undetectable levels (less than 300 nmol/min.mg). Although transport rates are much faster when measured by saturation-transfer than by conventional isotopic methods, the enthalpy values obtained by determining the effect of temperature on flux are very similar to those reported in the past that were determined by using isotopic techniques. Intramitochondrial ATP content regulates the rate of the ATP(in)/ATP(out) exchange. At 18 degrees C, the concentration of internal ATP that produces half-maximal transport rate is 6.6 +/- 0.12 nmol/mg of mitochondrial protein. The relationship between substrate concentration and flux is sigmoidal and is 90% saturated at 11.3 +/- 0.18 nmol/mg of mitochondrial protein.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1991

Rates of various reactions catalyzed by ATP synthase as related to the mechanism of ATP synthesis.

The forward and reverse rates of the overall reaction catalyzed by the ATP synthase in intact rat heart mitochondria, as measured with 32P, were compared with the rates of two partial steps, as measured with 18O. Such rates have been measured previously, but their relationship to one another has not been determined, nor have the partial reactions been measured in intact mitochondria. The partial steps measured were the rate of medium Pi formation from bound ATP (in state 4 this also equals the rate of medium Pi into bound ATP) and the rate of formation of bound ATP from bound Pi within the catalytic site. The rates of both partial reactions can be measured by 31P NMR analysis of the 18O distribution in Pi and ATP released from the enzyme during incubation of intact mitochondria with highly labeled [18O]Pi. Data were obtained in state 3 and 4 conditions with variation in substrate concentrations, temperature, and mitochondrial membrane electrical potential gradient (delta psi m). Although neither binding nor release of ATP is necessary for phosphate/H2O exchange, in state 4 the rate of incorporation of at least one water oxygen atom into phosphate is approximately twice the rate of the overall reaction rate under a variety of conditions. This can be explained if the release of Pi or ATP at one catalytic site does not occur, unless ATP or Pi is bound at another catalytic site. Such coupling provides strong support for the previously proposed alternating site mechanism. In state 3 slow reversal of ATP synthesis occurs within the mitochondrial matrix and can be detected as incorporation of water oxygen atoms into medium Pi even though medium [32P]ATP does not give rise to 32Pi in state 3. These data can be explained by lack of translocation of ATP from the medium to the mitochondrial matrix. The rate of bound ATP formation from bound Pi at catalytic sites was over twice the rate of the overall reaction in both states 4 and 3. The rate of reaction at the catalytic site is considerably less sensitive to the decrease in membrane potential and the concentration of medium ADP than is the rate of medium ATP formation. This supports the view that the active catalytic site is occluded and proceeds at a rapid rate which is relatively independent of delta psi m and of media substrates.

Adenosine Triphosphate↗
PubMed1991

Magnetic susceptibility measurement using a double-DANTE tagging (DDT) sequence.

Preliminary results are presented for the nuclear magnetic resonance (NMR) measurement of field gradients generated by differences in magnetic susceptibility. The DDT technique maps the resonant frequency throughout the sample in a single image. Regions of paramagnetic and diamagnetic susceptibility are differentiated with a single magnitude-calculated image.

Humans↗
PubMed1991

Predicting outcome following pulmonary resection in cystic fibrosis patients.

A small subset of cystic fibrosis (CF) patients develop pulmonary disease primarily limited to one lobe or lung segment requiring prolonged recurrent hospitalizations with intensive medical therapy. Although surgery has been advocated for patients who do not respond to medical therapy, very little is known about criteria for selection of patients who might benefit from resection of the involved parenchyma. In an attempt to further define criteria for pulmonary resection in these patients, we retrospectively reviewed our experience at Tulane Medical Center over the past 10 years. Fourteen patients with CF, ranging from 3 to 30 years of age, underwent 17 pulmonary resections. Indications for surgery were persistent lobar or pulmonary atelectasis and bronchiectasis requiring multiple hospitalizations and unresponsive to medical therapy (n = 13), bronchopleural fistula (n = 2), or hemoptysis not responding to medical therapy or selective embolization (n = 2). Thirteen lobectomies and four pneumonectomies were performed. Only two resections were on the left side and 11 right upper lobectomies were performed. Postoperative hospitalization ranged from 5 to 21 days (mean, 8.5 days). Preoperative pulmonary function tests showed widely divergent function in these patients. Forced expiratory volume (FEV1) ranged from 11% to 88% whereas forced vital capacity (FVC) ranged from 20% to 100% of predicted values. Oxygen saturation ranged from 86% to 99%. Although there was no significant difference in preoperative and postoperative FVC or O2 saturation, there was a significant (P less than .003) decrease in the postoperative FEV1. In the 12 surviving patients followed for at least 1 year, there was also a significant reduction (P less than .001) in the number of hospitalizations required due to pulmonary exacerbations from an average 2.2 admissions per year (range, 0.44 to 3.5 admissions per year) to 1.1 admissions per year (range, 0 to 8).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

Skeletal muscle metaboreceptor exercise responses are attenuated in heart failure.

BACKGROUND: Resting sympathetic nervous system activity is increased in heart failure. Whether sympathetic nervous system responses during exercise are increased is controversial. Furthermore, the role of muscle metaboreceptors and central command in regulating sympathetic outflow has been largely unexplored. METHODS AND RESULTS: Muscle sympathetic nerve activity (MSNA, peroneal nerve) was measured in nine heart failure subjects and eight age-matched control subjects during static exercise (30% maximal voluntary contraction) for 2 minutes and during a period of posthandgrip regional circulatory arrest. This maneuver isolates the metaboreceptor contribution to sympathetic nervous system responses. MSNA responses were similar during static exercise in the two groups. During posthandgrip regional circulatory arrest we observed a marked attenuation in MSNA responses in the heart failure subjects (15% increase in heart failure versus 57% increase in control subjects). A cold pressor test demonstrated a normal MSNA response to a potent nonspecific stimulus in the heart failure subjects (heart failure subjects, 141% increase; control subjects, 215% increase; NS). Nuclear magnetic resonance spectroscopy studies in five separate heart failure subjects and five control subjects suggested that the attenuated metaboreceptor response in heart failure was not due to reduced H+ production. CONCLUSIONS: Skeletal muscle metaboreceptor responses are impaired in heart failure. Because MSNA responses during static exercise are similar in the two groups, mechanisms aside from metaboreceptor stimulation must be important in increasing sympathetic nervous system activity.

Exercise↗
PubMed1991

Intraoperative colonic lavage: failure to decrease mucosal microflora.

Few data exist concerning the ability of intraoperative colonic lavage to decrease colonic bacterial counts, and nothing is known about its effect on the recently described mucosa-associated bacteria. The goal of our study was to determine the impact of intraoperative colonic lavage on both the intraluminal and mucosal microflora. After intraoperative colonic washout in 10 adult male Sprague-Dawley rats, quantitative and qualitative aerobic and anaerobic cultures of the intraluminal and mucosal bacteria were obtained. Tissue was also removed for scanning electron microscopic examination of the colon wall. Whereas 1000-fold to 10,000-fold reductions of aerobic and anaerobic intraluminal flora were achieved with mechanical lavage, reductions of aerobic or anaerobic mucosal bacteria were not significant. Failure to diminish bacterial colonization in this ecologic niche may be partly responsible for the persistently high infection rate after emergency colorectal surgery.

Anastomosis, Surgical↗
PubMed1991

Evaluation of treatment protocols on minimal to moderate spasticity in multiple sclerosis.

Thirty men and women diagnosed with definite multiple sclerosis (MS) were treated for ten weeks in a blinded, cross-over study. Patients with minimal to moderate spasticity were randomized to one of three sequences to evaluate the effects on MS-related spasticity of baclofen alone, stretching regimen with placebo, placebo alone, and stretching regimen with baclofen. The Cybex II isokinetic unit, timed gait, Ashworth scale, and subject's assessment of function were objective and subjective measures used to evaluate changes in hypertonicity. There was significant correlation between the Cybex and Ashworth as methods of measuring spasticity. Overall, treatment with baclofen alone significantly improved moderate quadriceps spasticity as measured by Cybex flexion scores. A trend, indicative of enhancing the beneficial effects of baclofen, was noted when stretching exercises were added to the treatment.

Adult↗
PubMed1990

A DANTE tagging sequence for the evaluation of translational sample motion.

A magnetic resonance imaging sequence that is sensitive to translational motion such as that seen with cardiac contraction is presented. The sequence employs DANTE radio-frequency excitation with a continuous magnetic field gradient to generate a grid pattern of lines. There is improved line resolution and reduced eddy-current formation over current techniques.

Heart↗
PubMed1990

Another complication of intravenous catheterization: a case report.

The list of possible complications following central vein catheterization has been well described. A technique for placement of a catheter into a central vein has to be learned by the individual following guidelines dictated by anatomical understanding, literature reporting, and other practitioners' previous experience. We report here another complication of intravenous catheterization where the first catheter is severed completely by a second, larger needle.

Adult↗
PubMed1990

Assessing the risk of kernicterus using nuclear magnetic resonance.

Kernicterus is the end result of injury to the central nervous system by bilirubin and other factors. Serum bilirubin levels alone are poor predictors of kernicterus especially in sick preterm infants. We need a rapid noninvasive indicator of neurotoxicity and impending cell injury. Bilirubin first seems to affect neuronal conduction before energy metabolism is impaired. Unchecked, this may lead to failure of ATP synthesis, resulting in the breakdown of all active intracellular processes. It is now possible to measure energy metabolism in vivo and noninvasively by surface coil 31P NMR spectroscopy. Recent animal studies demonstrate perturbations in energy metabolism when hyperbilirubinemia is associated with an open BBB. Perhaps the further developments in NMR spectroscopy and imaging will permit regional assessment of impending or actual bilirubin neurotoxicity and allow us to identify those infants in need of immediate treatment.

Adenosine Triphosphate↗
PubMed1989

Comparison of propofol and midazolam for sedation in critically ill patients.

101 critically ill patients admitted to five intensive-care units were allocated randomly to receive a continuous intravenous infusion of either propofol or midazolam for sedation for up to 24 h. In addition, morphine was given to provide analgesia. The mean duration of infusion was 20.2 h (range 3.0-24.5) in the propofol group and 21.3 h (4.0-47.0) in the midazolam group and infusion rates were 1.77 mg/kg/h (range 0.40-5.00) and 0.10 mg/kg/h (0.01-0.26), respectively. The infusion rates were adjusted as necessary, and the desired level of sedation was achieved easily in most patients in both groups. There were slight falls in arterial pressure, but there were no significant differences between the groups. Heart rate was lower in patients who received propofol. Some small changes occurred in biochemical and haematological variables in both groups, but they were not clinically significant. There was no indication that either drug substantially impaired adrenal steroidogenesis. When the infusion was discontinued, there was less variability in recovery of consciousness in patients who had received propofol. In a subgroup of patients, weaning from mechanical ventilation was achieved significantly faster after discontinuation of propofol than of midazolam. Propofol proved to be a satisfactory agent for sedation of these critically ill patients and compared favourably with midazolam.

Adolescent↗