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Biomedical subjects

C Lynch

Publications and source records attributed to C Lynch.

At least 127 records · Page 7Linked to original sources
PubMed1988

Calcitonin determination by a fast and highly sensitive enzyme amplified immunoassay.

A colorimetric enzyme amplification system was used to develop an immunoassay for human calcitonin (hCT) with a sensitivity of 6 pmol/l, and intra- and inter-assay CVs of 12% and 11.8% respectively for the low pool, and 10% and 11.2% for the high pool. The mean recovery of added synthetic hCT (58.5 pmol) from the plasma of 10 patients was 110% (64.4 pmol). The correlation coefficient between radioimmunoassay (RIA) and amplified enzymo-immunoassay was found to be 0.96 (p 0.001). The assay was successfully applied to the measurement of elevated calcitonin levels in plasma from patients with medullary carcinoma of the thyroid (MCT). AEIA offered a reliable and sensitive alternative to RIA for calcitonin determination with the added advantage of convenience as the label employed was much more stable.

Calcitonin↗
PubMed1988

Combined depressant effects of diltiazem and volatile anesthetics on contractility in isolated ventricular myocardium.

Because the volatile anesthetics depress the entry of calcium (Ca) into myocardial cells and also alter release of intracellular Ca stores, additional pharmacologic blockade of Ca entry could potentially enhance anesthetic-induced depression. The depressant effects of the calcium entry blocker diltiazem combined with the volatile anesthetics halothane, enflurane, or isoflurane were investigated in isolated guinea pig papillary muscle. Muscle contractions were studied in normal Tyrode solution after rest and at stimulation rates of 0.1, 0.25, 0.5, 1, 2, and 3 Hz. Anesthetics were studied in the presence of 0.1 and 1 microM diltiazem, which depressed tension to approximately 85 and 55% of control at 2-3 Hz, respectively; depression at the higher concentration was frequency-dependent. Depressant effects of enflurane were determined as previously done for equianesthetic concentrations (approximately 1 and 2 MAC) of halothane and isoflurane. At all stimulation rates, 1.7 and 3.5% enflurane depressed peak tension and dT/dt-max to approximately 73 and 50% of the mean control-recovery value, respectively. After control measurements of contractile characteristics, effects of 0.1 microM diltiazem were determined alone and then with the addition of halothane (0.75 or 1.5%), isoflurane (1.3 or 2.5%), or enflurane (1.7 or 3.5%), respectively. Recovery from anesthetic was then determined in the continued presence of diltiazem. After rest and at rates less than or equal to 0.5 Hz, equianesthetic concentrations of these volatile agents caused similar depression in the presence of diltiazem. At 3 Hz stimulation rate, 1.3% isoflurane caused significantly less contractile depression than did 1.7% enflurane or than 0.75% halothane. At 2-MAC concentrations, differences among the anesthetics were more apparent: 2.5% isoflurane depressed peak tension and dT/dt-max less than did halothane at 1-3 Hz stimulation rates, and depressed dT/dt-max less than 3.5% enflurane at 2-3 Hz. Similar frequency-dependent differences in depression by approximately 2 MAC anesthetics were observed in the presence of 1 microM diltiazem. The patterns of depressant action by the volatile anesthetics were similar to those previously observed in the absence of diltiazem. Furthermore, when the volatile anesthetic depression of contractions was combined with the depression due to diltiazem-induced blockade of Ca entry, the resulting contractile depression did not differ significantly from a prediction that assumed simply additive effects.

Animals↗
PubMed1988

Effects of halothane and isoflurane on isolated human ventricular myocardium.

Segments of viable human left ventricular trabeculae were obtained at the time of endocardial resection for intractable ventricular ectopy. Muscle segments which showed suitable and reproducible contractions in 26 mM K Tyrode solution with 1 microM isoproterenol were electrically stimulated after rest, and at frequencies of 0.1, 0.25, 0.5, and 1 Hz. Effects of 0.75% halothane and 1.3% isoflurane on peak tension, maximum rate of tension development (dT/dt-max), and on slow (calcium dependent) action potential (AP) characteristics were studied. Halothane depressed peak tension, dT/dt-max, and slow AP maximum rate of depolarization (Vmax) at all frequencies, and caused a significantly greater depression of peak tension and dT/dt-max at 0.5-1 Hz than after rest and at 0.1-0.25 Hz. Isoflurane did not significantly depress slow AP Vmax, showed no frequency dependent contractile depression, and depressed dT/dt-max less than halothane at 0.5 and 1 Hz. Halothane and isoflurane caused differing depression in the pattern of developed tension. The differential depression by halothane and isoflurane of human ventricular myocardium was similar to that previously observed in isolated animal ventricular tissue.

Action Potentials↗
PubMed1986

Differential depression of myocardial contractility by halothane and isoflurane in vitro.

Depressant effects of halothane and isoflurane on isolated right ventricular guinea pig papillary muscle bathed in Tyrode's solution at 37 degrees C were examined. Contractions were elicited by stimulation through external field electrodes while tension was recorded continuously and the intracellular cardiac action potential (AP) was monitored simultaneously by microelectrodes. The time differential of tension (dT/dt) and of membrane potential (V) was determined electronically and recorded also. Contractions after rest and at stimulation rates of 0.1, 0.25, 0.5, 1, 2, and 3 Hz were studied. With normal APs, isoflurane (1.3 and 2.5%) depressed peak tension significantly less at high frequencies than did equivalent doses of halothane (0.75 or 1.5%). Isoflurane depressed dT/dt max less than halothane at all frequencies. At 0.3 Hz stimulation, isoflurane (1-4%) significantly increased the normal AP duration by 7-11%. Slow calcium-dependent APs and accompanying contractions were studied in partially depolarized muscles (-40 to -45 mV resting potential in 26 mM K+ Tyrode's solution) stimulated with 0.1 microM isoproterenol. Following rest and at 0.1, 0.25, 0.5, 1, 2, and 3 Hz, both isoflurane (1.3% or 2.5%) and enflurane (1.7% or 3.5%) markedly depressed the late-peaking slow AP contraction observed with low-frequency stimulation. Halothane (0.75% or 1.5%) caused a similar contractile depression (40-60%) at all frequencies. In contrast, isoflurane depressed early peaking tension and the dT/dt max at frequencies greater than 1 Hz significantly less than did halothane or enflurane. At 0.3 Hz, 2% and 4% isoflurane caused 9% and 17% depression of slow AP maximum rate of depolarization (Vmax), but significantly prolonged the AP duration. Isoflurane altered the pattern of tension development in a different manner than halothane, suggesting differing mechanisms of myocardial depression by these anesthetics.

Action Potentials↗
PubMed1986

A mother and baby unit in a psychiatric hospital.

Two rooms where women with puerperal psychiatric illness could be admitted together with their babies were provided in a general psychiatric unit. Over a 21-month-period demand for joint admission far exceeded capacity and most referrals could not be accepted. Women with various psychiatric disorders were referred to and managed in the unit. Greatest demand was for young women suffering from psychosis following childbirth.

Breast Feeding↗
PubMed1986

Depression of myocardial contractility in vitro by bupivacaine, etidocaine, and lidocaine.

The effects of local anesthetics in depressing myocardial contractility were studied in isolated guinea pig right ventricular papillary muscles. Bupivacaine and etidocaine, 4 and 10 microM, showed reverse frequency-dependent depression of contractility, that is, less significant depression of contractility at higher stimulation frequencies (2-3 Hz) than at lesser frequencies (less than 1 Hz). Lidocaine, 40 microM, demonstrated a similar trend. In contrast, the normal action potential maximum rate of depolarization (Vmax), a measure of sodium channel conductance, was significantly more depressed at 2-3 Hz by bupivacaine and etidocaine than by lidocaine. Consequently, contractile depression could be overcome only at higher stimulation frequencies, at which conduction was depressed. To explore the mechanism of the contractile depression, local anesthetic effects were studied on slow (calcium channel-mediated) action potentials in partially depolarized papillary muscles. Etidocaine and bupivacaine, 4 and 10 microM, and lidocaine, 40 and 100 microM, caused a marked depression of the late-peaking contractile responses, attributed to Ca2+ release from the sarcoplasmic reticulum. In contrast, only 10 microM bupivacaine caused any significant depression of the slow action potential rate of depolarization (to 89% of control), consistent with a possible small depression of Ca2+ entry.

Acetanilides↗
PubMed1986

Effects of dantrolene and verapamil on atrioventricular conduction and cardiovascular performance in dogs.

The effects of intravenous dantrolene sodium, alone and in combination with verapamil, upon atrioventricular conduction, cardiovascular function, and neuromuscular function were studied in chloralose-urethane anesthetized dogs. Hemodynamic variables (systemic arterial, central venous, and pulmonary arterial pressures and cardiac output) and His-bundle electrograms were monitored, and measurements were made during atrial pacing at 175 beats/min, as well as at the spontaneous heart rate. In one part of the study animals received dantrolene sodium incrementally at 30-min intervals to cumulative doses of 1, 2.5, 5, and 10 mg/kg. Subsequently, verapamil was administered incrementally at 30-min intervals to cumulative doses of 0.1, 0.2, 0.4, and 0.6 mg/kg. In the second part of the study, dogs received identical dosage sequences, but verapamil preceded dantrolene administration. Dantrolene caused no significant depression of atrioventricular conduction or cardiac performance but did increase systemic vascular resistance at doses above 2.5 mg/kg. Verapamil alone (greater than or equal to 0.2 mg/kg) or with dantrolene (greater than or equal to 0.1 mg/kg) increased the atrial-His-bundle conduction interval. In the presence of verapamil, dantrolene (greater than or equal to 2.5 mg/kg) decreased cardiac index and increased pulmonary artery occlusion pressure. Although 0.6 mg/kg verapamil depressed cardiac index and increased pulmonary artery occlusion pressure, this effect was observed at 0.4 mg/kg after prior treatment with dantrolene. Verapamil did not augment the dose-dependent twitch depression observed with dantrolene. Dantrolene alone had no apparent effect on atrioventricular conduction and caused little enhancement of the effects of verapamil. However, each drug appeared to enhance the myocardial depressant effects of the other.

Animals↗
PubMed1985

Calcitonin gene-related peptide: potent vasodilator and major product of calcitonin gene.

In addition to calcitonin and katacalcin, the human calcitonin gene encodes a novel peptide--calcitonin gene-related peptide (CGRP)--a potent vasodilator. A sensitive and specific radioimmunoassay was developed to study plasma levels of CGRP in normal subjects. CGRP circulates at five times the concentration of calcitonin, suggesting that it may be an important physiological regulator of vascular tone and blood flow.

Adult↗
PubMed1985

Ionic conductances in frog short skeletal muscle fibres with slow delayed rectifier currents.

Short (0.8-1.6 mm) lumbricalis fibres of Rana pipiens were voltage clamped by a two-micro-electrode technique at 5 degrees C in sucrose hypertonic Ringer solution (SHR). Terminated linear cable analysis suggests that if the current electrode is placed near the centre of the fibre length and the voltage-sensing electrode is placed 0.19 times the fibre length from the current electrode, the fibre can be adequately voltage clamped and the conductance may be simply calculated as I/V for fibre length constants from 1.0 to 0.15 mm. In SHR solution lumbricalis fibres have action potentials with peak amplitudes of only +2 to 7 mV and a slow, gradual repolarization, distinct from the action potentials observed in sartorius muscle. In 60 mM-Na+ SHR the inward Na current could be adequately controlled over the fibre length, providing an estimated Na conductance (GNa) of 8.9 mS/cm2. The magnitude of GNa and GK (delayed rectifier) in lumbricalis fibres was approximately 20% of that reported for sartorius and semitendinosus, although the resting conductances were similar. Fibres demonstrated delayed rectifier currents with complex patterns of activation suggesting two components of conductance (fast, GK,f and slow, GK,s) which were combined together in varied amounts: (a) GK,f activated rapidly to a maximum within 80 ms at 0 mV as previously described (Adrian, Chandler & Hodgkin, 1970a); (b) GK,s activated gradually with depolarizations below -50 mV and achieving peak currents at about 400 ms at 0 mV. In about 10% of lumbricalis fibres studied, GK,s occurred in isolation with a peak magnitude of 1.4 +/- 0.4 mS/cm2 (+/- S.D.). GK,s activation kinetics and tail currents are described by a squared two-state (l2) Hodgkin-Huxley model and have a Q10 of 2.8. These currents inactivated with a time constant of 5-7 s at 0 mV. Isolated GK,s with identical kinetics was also observed in certain sartorius fibres studied with the three-electrode voltage clamp. The fractional amount of GK,s in the combined delayed rectifier (GK,s + GK,f) currents could be estimated from analysis of the late activation phase with depolarization. Combined delayed currents were described by summing GK,f currents using a n4 model with GK,s currents defined by the l2 model.

Action Potentials↗
PubMed1985

Biochemical separation of delayed rectifier currents in frog short skeletal muscle fibres.

Frog short (1-1.5 mm) skeletal muscle fibres in sucrose hypertonic Ringer at 5 degrees C were voltage clamped employing a two-electrode technique. Decreasing pH from 7.0 to 5.0 dramatically increased the rate of turn on of the slow delayed rectifier (GK,s) current, so that it became similar to the rapidly activated form. The accelerating effects of decreased pH upon slow current kinetics had a pKa of 5.8. Decreased pH also appeared to shift the voltage dependence of fast and GK,s gating to more positive potentials. In addition, a decrease in pH from 7.0 to 5.0 shifted the reversal potential of GK,s by over 11 mV in the positive direction. GK,s was selectively and irreversibly abolished by applying 1 mM-diethylpyrocarbonate (DEP), a histidine reagent. This effect occurred even after GK,s had been accelerated by low pH. DEP had no effect upon fast delayed rectifier current except for a small positive shift in voltage dependence. Application of 1 or 2 mM-N-ethylmaleimide, a sulphydryl reagent, depressed the fast delayed rectifier while sparing the GK,s currents. However, the muscle fibres also developed markedly increased leakage currents.

Action Potentials↗