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Biomedical subjects

C Lynch

Publications and source records attributed to C Lynch.

At least 91 records · Page 5Linked to original sources
PubMed1993

Profound deafness treated by the Ineraid multichannel intracochlear implant.

Twelve deaf adults and two deaf children were treated with the Ineraid (formerly Symbion) four channel intracochlear implant between September 1989 and October 1991 at Addenbrooke's Hospital in Cambridge. All were post-lingually totally deaf and had found themselves beyond the reach of hearing aids. The effect of the implant upon the patients ability to lip-read was tested with the speech tracking test, BKB sentences (comparable to CID sentences) and Boothroyd word lists (comparable to NU6 word lists). All patients showed an improvement in their ability to understand speech with the help of the implant. Discrimination of speech without lip-reading was tested with Boothroyd word lists and BKB sentences, eight patients (57 per cent) demonstrated some 'open set' speech discrimination. The acceptability of the carbon percutaneous pedestal is discussed from the patient's, audiologist's and surgeon's points of view.

Adolescent↗
PubMed1993

Cellular electrophysiological effects of hyperthermia on isolated guinea pig papillary muscle. Implications for catheter ablation.

BACKGROUND: The primary mechanism of tissue injury by radiofrequency catheter ablation is presumed to be thermally mediated. However, the myocardial cellular electrophysiological effects of hyperthermia are not well characterized. We used an in vitro model of isolated guinea pig right ventricular papillary muscle to investigate the acute cellular electrophysiological effects of hyperthermia. METHODS AND RESULTS: Excised guinea pig right ventricular papillary muscles were pinned in a high-flow tissue bath and superfused with Tyrode's solution at 37.0 +/- 0.5 degrees C. The superfusate temperature was rapidly changed to 38.0 to 56.0 degrees C for 60 seconds and then returned to 37.0 degrees C. Conventional microelectrodes were used to measure membrane potential (Vm), maximum rate of rise of the action potential (dV/dtmax), and action potential (AP) amplitude and AP duration at 50% (APD50) and 90% (APD90) repolarization. Hyperthermia resulted in (1) a progressive depolarization of Vm at temperatures > or = 40.0 degrees C, which became more prominent at temperatures > or = 45.0 degrees C; (2) changes in the AP characterized by a temperature-dependent increase in dV/dtmax and a temperature-dependent decrease in AP amplitude, APD50, and APD90; (3) reversible loss of cellular excitability within a temperature range of 42.7 to 51.3 degrees C (median, 48.0 degrees C); (4) irreversible loss of cellular excitability and tissue injury at temperatures > or = 50.0 degrees C; and (5) the development of abnormal automaticity at temperatures > 45.0 degrees C. CONCLUSIONS: Hyperthermia causes significant changes in myocardial cellular electrophysiological properties that include membrane depolarization, reversible and irreversible loss of excitability, and abnormal automaticity. There appear to be specific temperature ranges for reversible and irreversible electrophysiological changes. These observations may have important implications for tissue temperature monitoring during radiofrequency catheter ablation.

Animals↗
PubMed1993

Inhalational anesthetic actions on voltage-gated ion currents of bovine adrenal chromaffin cells.

The effects of the inhalational anesthetics halothane and isoflurane on voltage-gated ionic currents in bovine adrenal chromaffin cells were examined using patch-clamp techniques. Halothane (1.5% atmospheres, 0.90 mM in solution) and isoflurane (2.5% atmospheres, 0.78 mM in solution) diminished the Ca(2+)-dependent K+ current (IK(Ca)) "hump" by 52 +/- 3% (n = 16 cells) and 40 +/- 4% (n = 6), respectively. These concentrations of halothane and isoflurane had virtually no effect on the rapid inward Na+ current and exerted only minor effects on outward K+ currents in the absence of external Ca2+. The effectiveness of halothane (0.90 mM) was reduced by increasing the external Ca2+ concentration ([Ca2+]o); IK(Ca) was decreased by 64 +/- 4% (n = 4) with 1 mM [Ca2+]o but by only 37 +/- 4% (n = 4) with 10 mM [Ca2+]o. Voltage-activated Ca2+ current (ICa), isolated by intracellular perfusion with Cs+ and tetraethylammonium in the presence of 15-30 microM external tetrodotoxin, was insensitive to 0.90 mM halothane and partially reduced by 0.78 mM isoflurane (24 +/- 7%, n = 9). Halothane at 1.4 mM decreased ICa by approximately 30 +/- 5% (n = 7), with a slight enhancement of the rate of activation and no change in the voltage dependence of activation. Higher levels of halothane produced a clear enhancement of the rates of both activation and deactivation of ICa. Detailed examination of the Na+ current showed that excessive levels of halothane (approximately 3 mM) decreased the peak amplitude by 26 +/- 7% (n = 6) and enhanced the rates of activation and inactivation, while shifting the voltage dependence of activation by 8.3 +/- 2.3 mV (n = 3) and the steady state inactivation by 6 mV towards hyperpolarized levels. Excised membrane patch-clamp measurements were performed to assess the direct effect of halothane on the large conductance "BK" channels underlying IK(Ca). Halothane (0.90 mM) with approximately 900 nM free Ca2+ at the cytoplasmic side of the patch decreased the probability of opening (Po) by 42 +/- 10% (n = 8), with no alteration in the open channel amplitude. With the cytoplasmic [Ca2+] reduced to approximately 100 nM, halothane diminished po by 65 +/- 8% (n = 8), suggesting that Ca2+ can antagonize the effect of halothane on BK channels, consistent with whole-cell experiments. Although these results show that several channel types in chromaffin cells are affected by inhalational agents, BK channels appear to be more sensitive than other voltage-dependent channels.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenal Medulla↗
PubMed1993

Effect of temperature on volatile anesthetic depression of myocardial contractions.

Anesthetics are studied and used under conditions of hypothermia both experimentally and clinically. To determine if myocardial contractile depression by anesthetics is equivalent at different temperatures, depressant effects on guinea pig papillary muscle contractions were compared at 37 degrees C vs 30 degrees C. Stimulation after rest and at rates from 0.1 to 3 Hz was used. After control measurements were established at one temperature, effects due to equi-anesthetic concentrations (equivalent to approximately 0.9 minimum alveolar concentration) of halothane, isoflurane, or enflurane were determined, followed by recovery measurements. The same procedure was then applied at the other temperature. Hypothermia itself had positive inotropic effects: contractions at 30 degrees C developed about twice the tension as at 37 degrees C; the maximum rate of tension development (dT/dt-max) at 30 degrees C was about 50% greater than at 37 degrees C (1-3 Hz stimulation). When anesthetic contractile depression was assessed by the fractional decrease in dT/dt-max, the anesthetics were more depressant at 30 degrees C than at 37 degrees C, an effect which was most prominent at 0.5 Hz. In contrast to the anesthetics, 1 microM ryanodine which decreases sarcoplasmic reticulum (SR) Ca2+ release, and 0.1 microM nifedipine which decreases Ca2+ entry, both depressed dT/dt-max less at 30 degrees C than at 37 degrees C. Furthermore, ryanodine, nifedipine, and a decrease in external [Ca2+] all exhibited distinct rate-dependent contractile depression at 37 degrees C (typically greatest at 2-3 Hz) not seen with anesthetics.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Barbiturate anesthetics depress the resting K+ conductance of myocardium.

The intravenous anesthestic thiopental has been previously shown to increase the incidence of ventricular arrhythmias, particularly when combined with epinephrine and halothane. Recent work based on microelectrode and tension measurements has indicated that thiopental may diminish membrane K+ permeability. Utilizing the whole-cell patch-clamp technique, we investigated the effect of thiopental on the current associated with the resting membrane conductance, the anomalous or inward rectifying K+ current (IK1). External application of 30 microM thiopental to frog atrial myocytes resulted in a 56 +/- 2% (mean +/- S.E.M.; n = 12 cells) reduction in the magnitude of IK1 elicited by a hyperpolarization to -110 mV. The outward current component through IK1 channels, evoked by depolarizing voltages above the resting potential, was decreased to same extent. The effect of thiopental on IK1 was concentration-dependent and the time courses of onset and recovery were rapid (tau = 10-14 sec). Ramp command potentials from -120 to +60 mV at a rate of 20 mV/sec revealed that 30 microM thiopental also depressed the delayed outward K+ current by 25 +/- 4% (n = 4). Examination of other barbiturates revealed that the potency in the suppression of IK1 was related to the octanol/water partition coefficient, suggesting a lipophilic site of action. Utilizing guinea pig ventricular myocytes, we observed a similar level of IK1 depression with thiopental, however the rates of onset and recovery were considerably slower than with frog atrial myocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1992

Effects of enflurane on the voltage-gated membrane currents of bovine adrenal chromaffin cells.

The effects of the volatile anesthetic enflurane on voltage-gated ionic currents of bovine adrenal chromaffin cells were studied using the patch clamp technique. Bath application of 3.5% (1.7 mM) enflurane decreased the outward Ca(2+)-dependent K+ current (IK(Ca)) 'hump' by 88 +/- 6% (mean +/- S.E.M., n = 5 cells) and the peak inward Ca2+ current by 60 +/- 3% (n = 5), whereas the Ca(2+)-independent K+ current fell by only 34 +/- 3% (n = 5) and peak inward Na+ current was unchanged. Exposure of excised patch 'BK' Ca(2+)-dependent K+ channels to 3.5% enflurane revealed that the anesthetic directly suppressed the channel probability of opening by 68 +/- 10% (n = 4) with no effect on open state conductance. The differential sensitivity of depolarizing and hyperpolarizing current pathways may contribute to the biphasic response, excitation and depression, observed in certain neuronal systems in response to this inhalational anesthetic.

Anesthesia↗
PubMed1992

Pregnancy and HIV.

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AIDS Serodiagnosis↗
PubMed1992

Mobilization of peripheral blood progenitor cells by chemotherapy and granulocyte-macrophage colony-stimulating factor for hematologic support after high-dose intensification for breast cancer.

High-dose therapy with autologous marrow support results in durable complete remissions in selected patients with relapsed lymphoma and leukemia who cannot be cured with conventional dose therapy. However, substantial morbidity and mortality result from the 3- to 6-week period of marrow aplasia until the reinfused marrow recovers adequate hematopoietic function. Hematopoietic growth factors, particularly used after chemotherapy, can increase the number of peripheral blood progenitor cells (PBPCs) present in systemic circulation. The reinfusion of PBPCs with marrow has recently been reported to reduce the time to recovery of adequate marrow function. This study was designed to determine whether granulocyte-macrophage colony-stimulating factor (GM-CSF)-mobilized PBPCs alone (without marrow) would result in rapid and reliable hematopoietic reconstitution. Sixteen patients with metastatic breast cancer were treated with four cycles of doxorubicin, 5-fluorouracil, and methotrexate (AFM induction). Patients responding after the first two cycles were administered GM-CSF after the third and fourth cycles to recruit PBPCs for collection by two leukapheresis per cycle. These PBPCs were reinfused as the sole source of hematopoietic support after high doses of cyclophosphamide, thiotepa, and carboplatin. No marrow or hematopoietic cytokines were used after progenitor cell reinfusion. Granulocytes greater than or equal to 500/microL was observed on a median of day 14 (range, 8 to 57). Transfusion independence of platelets greater than or equal to 20,000/microL occurred on a median day of 12 (range, 8 to 134). However, three patients required the use of a reserve marrow for slow platelet engraftment. In retrospect, these patients were characterized by poor baseline bone marrow cellularity and poor platelet recovery after AFM induction therapy. When compared with 29 historical control patients who had received the same high-dose intensification chemotherapy using autologous marrow support, time to engraftment, antibiotic days, transfusion requirements, and lengths of hospital stay were all significantly improved for the patients receiving PBPCs. Thus, autologous PBPCs can be efficiently collected during mobilization by chemotherapy and GM-CSF and are an attractive alternative to marrow for hematopoietic support after high-dose therapy. The enhanced speed of recovery may reduce the morbidity, mortality, and cost of high-dose treatment. Furthermore, PBPC support may enhance the effectiveness of high-dose therapy by facilitating multiple courses of therapy.

Adolescent↗
PubMed1992

Halothane and isoflurane effects on Ca2+ fluxes of isolated myocardial sarcoplasmic reticulum.

To elucidate better the differential myocardial depressant actions of halogenated volatile anesthetics, anesthetic-induced changes in Ca2+ accumulation, release, and Ca-ATPase (Ca2+ pump) activity of isolated canine cardiac sarcoplasmic reticulum (SR) vesicles were examined. An initial crude microsomal fraction of homogenized canine ventricle was subfractionated on a discontinuous sucrose gradient after Ca2+ loading in the presence of phosphate. Junctional SR (JSR) enriched with terminal cisternae was identified by its content of an electrophoretically verified approximately 450-kDa protein, the Ca(2+)-release channel (CaRC). When the CaRC of JSR was blocked by 1 microM ruthenium red (RR), the rate of Ca2+ uptake increased 47% as measured spectrophotometrically using the Ca-sensitive dye antipyrylazo III. A second fraction was identified as primarily longitudinal SR (LSR) based on its trace content of 450-kDa protein and 11% increase of Ca2+ uptake with RR. Halothane (0.75-2.5%) or isoflurane (2.5-4%) decreased net Ca2+ accumulation rate by either LSR or JSR, and the decrease in uptake rate of JSR was only partially reversed by addition of 1 microM RR (27% increase for isoflurane, 7% increase for halothane). Both halothane and isoflurane increased JSR ATP consumption as measured by a coupled-enzyme assay. 45Ca2+ efflux from passively loaded SR vesicles was then determined to verify that the decreased net uptake rate was due to enhanced Ca2+ efflux from vesicles. Both anesthetics increased passive Ca2+ efflux from SR vesicles in which the CaRC was blocked by 10 microM RR as well as those in which Ca2+ release via the CaRC was activated by 10 microM Ca2+.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Effects of propofol and thiopental in isolated rat aorta and pulmonary artery.

This study was performed to determine if direct arterial dilating actions of propofol contribute to the drug's hypotensive actions. The effects of propofol were compared with those of thiopental on isolated vascular ring preparations from rat thoracic aorta and pulmonary artery. Thoracic aortic ring responses were evaluated in the presence and absence of endothelium, indomethacin, and N omega-nitro-L-arginine methyl ester (LNAME; a specific inhibitor of endothelium-derived relaxing factor-nitric oxide [EDRF/NO] synthase). Pulmonary artery responses were investigated with intact endothelium. After the induction of active isometric force by a predetermined EC50 dose of phenylephrine for each ring, effects of propofol (30, 100, 300 microM) and thiopental (10, 30, 100 microM) were examined. Propofol caused significant vasodilation in endothelium-intact, endothelium-denuded, and LNAME-treated aortic rings. In the endothelium-intact aortic and pulmonary artery rings, the initial vasodilation due to 30 and 100 microM propofol showed gradual and partial recovery over 15 min; 300 microM propofol caused sustained vasodilation. Endothelium-denuded rings and LNAME-pretreated endothelium-intact rings showed constant and sustained vasodilation with all propofol concentrations. Propofol also caused marked vasodilation in pulmonary arteries. In contrast, thiopental had no vasodilating effect in aortic or pulmonary artery preparations. In control experiments, propofol vehicle (Intralipid) also had no effect on vascular rings. Indomethacin pretreatment induced a dose-dependent vasoconstriction by thiopental in endothelium-intact rings and decreased the vasodilation due to propofol.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Propofol and thiopental depression of myocardial contractility. A comparative study of mechanical and electrophysiologic effects in isolated guinea pig ventricular muscle.

The purpose of the study was to compare the actions of propofol and thiopental on myocardial contractility and cellular electrophysiologic behavior. Isometric tension of isolated guinea pig right ventricular papillary muscle was studied in normal and 26 mM potassium Tyrode's solutions at various stimulation rates (after rest up to 3 Hz). Normal and slow action potentials were also recorded by conventional microelectrodes. Propofol (30, 100, and 300 microM) applied in the commercial 10% Intralipid emulsion caused dose-dependent depression of contractions at all stimulation rates, whereas Intralipid alone had no effect. Thiopental (10, 30, and 100 microM) caused depression similar to the threefold greater concentrations of propofol. Although neither drug altered the normal action potential (AP) amplitude or dV/dt max, thiopental (30 microM) increased AP duration. In the partially depolarized (26 mM potassium) beta-adrenergically stimulated myocardium, propofol and thiopental caused dose-dependent contractile depression similar to that in normal Tyrode's solution. Whereas propofol did not alter slow AP characteristics, 30-100 microM thiopental increased slow AP duration (consistent with decreased potassium conductance), and 100 microM thiopental depressed dV/dt max (consistent with decreased calcium channel ionic influx). Comparing the clinical plasma concentration ranges required for an equivalent anesthetic effect, propofol depresses myocardial contractility less than thiopental.

Action Potentials↗
PubMed1992

Effects of the fitting parameters of a two-channel compression system on the intelligibility of speech in quiet and in noise.

These experiments were carried out to assess how accurately the gains and compression ratios in a two-channel compression system needed to be set. We used as a research tool a laboratory version of a two-channel full-dynamic-range compression system. The system was initially adjusted to suit each hearing-impaired subject according to the manufacturer's recommendations. Then, further adjustments were made to ensure that speech stimuli were both audible and comfortable over a wide range of sound levels. Finally, the settings of the gains and compression ratios were systematically varied from the adjusted values and the effects of this on the intelligibility of speech in quiet and in noise (12-talker babble, levels of 65 and 75 dB SPL) were measured. The results indicated that speech reception thresholds (SRTs) in quiet were significantly adversely affected by decreases in low-level gain. However, SRTs in noise were relatively unaffected by changes in low-level gain. An exception occurred at the higher noise level used, where increases in the low-level gains (with corresponding increases in compression ratios) had a significant adverse effect on the SRTs. It is concluded that, provided excessive low-level gains (associated with high compression ratios) are avoided, the main criteria for fitting such a system should be listening comfort (i.e. achieving an acceptable tonal balance, and avoiding uncomfortably loud sounds) and an appropriate value of the threshold for detecting speech in quiet (which should be a little below 50 dB SPL).

Acoustic Stimulation↗
PubMed1992

Umbilical artery velocimetry in predicting perinatal outcome with intrapartum fetal distress.

The aim of this study was to see whether umbilical artery Doppler velocimetry predicts intrapartum fetal distress evidenced by poor perinatal outcome. Umbilical velocimetry was performed on 102 parturients with a presumptive diagnosis of fetal distress based on fetal heart rate (FHR) patterns. A mean systolic-diastolic ratio (S/D) of 3 or more after 30 weeks' gestation was considered abnormal. Poor perinatal outcome was defined by any of the following: small for gestational age, low Apgar score, acidosis, meconium below the vocal cords, prolonged neonatal hospital stay, neonatal intensive care unit admission, and neonatal morbidity. Eighty-two patients had normal S/Ds and 20 had abnormal ratios. Eighteen neonates (90%) in the abnormal-SD group had at least one adverse outcome, compared with only 13 (15.8%) of those with a normal S/D, a statistically significant difference (P less than .001). Umbilical artery S/D used as a screening tool to detect poor perinatal outcome had a sensitivity of 65-100%, specificity of 83-92%, positive predictive value of 20-81%, negative predictive value of 91-100%, and a kappa index of 0.24-0.63. These findings suggest that umbilical artery Doppler velocimetry may be useful as an adjunct in the assessment of intrapartum FHR patterns suggesting fetal distress.

Adult↗
PubMed1991

Pharmacological evidence for two types of myocardial sarcoplasmic reticulum Ca2+ release.

Contractions of guinea pig papillary muscles were studied at 37 degrees C under a variety of conditions and stimulation rates that markedly alter the pattern of tension development. When rested-state contractions (RSCs) were enhanced by treatments that increase intracellular adenosine 3',5'-cyclic monophosphate (0.1-1 microM isoproterenol, 1-10 microM forskolin), a markedly enhanced late peak tension developed after a 100-ms delay. Such late peak tension was selectively depressed by local anesthetics (200-400 microM procaine, 4-10 microM tetracaine, or 0.5-1 mM ethyl aminobenzoate). In contrast, 0.1-1 microM ryanodine had little effect on late peak tension, whereas 5 mM caffeine reduced the delay before tension development. Inotropic interventions such as increased external Ca2+ concentration or the Ca2+ channel agonist BAY K 8644 did not elicit such distinct late peaking RSCs. Rapid initial tension development observed under a variety of situations (short cycle lengths, stimulation rates of 0.25 Hz plus isoproterenol, decreased external Na+ concentration) was markedly depressed by 0.01-1 microM ryanodine and by caffeine, whereas local anesthetics had little effect. These results suggest two pharmacologically distinct types of sarcoplasmic reticulum Ca2+ release: 1) Ca2+ that accumulates during prior depolarizations is released immediately upon depolarization and decreased by ryanodine and caffeine; 2) extracellular Ca2+ that enters the myocyte is accumulated and released after an initial delay and is selectively depressed by low concentrations of local anesthetics.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1991

Expression of rat renal Na/H antiporter mRNA levels in response to respiratory and metabolic acidosis.

The mammalian proximal tubule is an important mediator of the renal adaptive response to systemic acidosis. In chronic metabolic and respiratory acidosis the bicarbonate reabsorptive (or proton secretory) capacity is increased. This increase is mediated, at least in part, by an increase in Vmax of the luminal Na/H antiporter. To determine whether this adaptation involves increased mRNA expression, Na/H antiporter mRNA levels were measured by Northern analysis in renal cortex of rats with metabolic (6 mmol/kg body wt NH4Cl for 2 or 5 d) and respiratory (10% CO2/air balanced for 2 or 5 d) acidosis and of normal, pair-fed rats. Na/H antiporter mRNA levels were unchanged after 2 d of both metabolic and respiratory acidosis. After 5 d, however, Na/H antiporter mRNA expression was increased 1.76 +/- 0.12-fold in response to metabolic acidosis (P less than 0.005, n = 8), but was not different from normal in response to respiratory acidosis: 1.1 +/- 0.2 (NS, n = 8). Thus, the renal adaptive response to metabolic acidosis involves increased cortical Na/H antiporter mRNA levels. In contrast, the enhanced proximal tubule Na/H antiporter activity and bicarbonate reabsorption in respiratory acidosis seem to involve mechanisms other than increased Na/H antiporter gene expression.

Acidosis↗