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Biomedical subjects

J P Payne

Publications and source records attributed to J P Payne.

At least 19 recordsLinked to original sources
PubMed1998

The myelotoxicity of chloramphenicol: in vitro and in vivo studies: II: In vivo myelotoxicity in the B6C3F1 mouse.

1. Chloramphenicol continues to be widely used in many parts of the world despite its known haematotoxicity. Until now, elucidation of the mechanisms involved and any attempt at amelioration of the toxic effects have been hampered by the lack of an animal model. 2. In this study neither acute nor chronic administration of chloramphenicol as its succinate ester in the drinking water produced anaemia in mice as assessed by changes in peripheral blood parameters. 3. Chloramphenicol could not be detected in the bone marrow when the antibiotic was administered either in the drinking water or by gavage, although it was detected in the serum. 4. In marrow taken from mice after chloramphenicol succinate administration and cultured in vitro, depression of the differentiation of immature committed erythroid progenitors occurred 15 min after administration of the antibiotic by gavage. However, recovery was beginning to occur at 48 h after administration of chloramphenicol succinate at 50 and 200 mg/kg and this was then followed by an 'overshoot' response at the higher dose. A toxic effect was therefore achieved in the bone marrow but this was probably masked in the peripheral blood by enhanced proliferation. 5. Morphological evidence of apoptosis was seen in erythroid and myeloid precursors in mice treated with 200 mg/kg. 6. The data suggest that the effect of chloramphenicol was at the differentiation stage of the committed marrow progenitor cells rather than at the replication stage of the stem cells and therefore this response appears to mimic the reversible bone marrow depression seen in the treated patient.

Animals↗
PubMed1997

Physiologic estradiol replacement therapy and cardiac structure and function in normal postmenopausal women: a randomized, double-blind, placebo-controlled, crossover trial.

OBJECTIVE: To assess the effect of estradiol (E2) replacement therapy on cardiac structure and function in healthy postmenopausal women. METHODS: We conducted a randomized, double-blind, placebo-controlled, crossover study of 31 healthy postmenopausal female volunteer study subjects (55-65 years) using 12 weeks of micronized E2 replacement therapy (2 mg/day). Echocardiography and Doppler techniques were used to assess the cardiac effects of E2 at rest and during graded bicycle ergometry. RESULTS: Crossover analysis demonstrated no carryover effects of estrogen treatment (which increased serum E2 15-fold to 37.6 pmol/L) on the cardiac characteristics measured. Estradiol treatment did not affect measurements of systolic function, diastolic function, left ventricular mass, or pulmonary artery pressure at rest or during bicycle ergometry. Left ventricular end-diastolic volume at rest was slightly higher with E2 treatment (P = .03). However, this change was not reflected by changes in stroke volume, ejection fraction, or cardiac output. CONCLUSIONS: Estrogen replacement therapy, which results in physiologic serum concentrations, does not affect cardiac structure or function in normal postmenopausal women after 12 weeks of treatment.

Aged↗
PubMed1995

Blockade of multiple human cardiac potassium currents by the antihistamine terfenadine: possible mechanism for terfenadine-associated cardiotoxicity.

Use of the antihistamine terfenadine has been associated with QT prolongation and torsade de pointes. One possible mechanism is blockade of cardiac potassium channels. We therefore characterized the effects of terfenadine on potassium currents recorded from isolated human cardiac myocytes. We demonstrated terfenadine block of the transient outward current and a novel, ultra-rapidly activating, delayed rectifier K+ current (IKur), which is very sensitive to 4-aminopyridine. IKur is probably produced by the protein product of Kv1.5a, a Shaker-like potassium channel cDNA cloned from human heart. We also compared terfenadine blockade of fHK (Kv1.5a) currents stably expressed in a human embryonic kidney cell line with terfenadine blockade of IKur in human atrial myocytes. Using the patch-clamp technique, we found that terfenadine produced a time-dependent reduction in Kv1.5a current that was consistent with blockade from the cytoplasmic side of the channel. The terfenadine-sensitive Kv1.5a current in human embryonic kidney cells was similar to the 4-aminopyridine-sensitive current in human atrial myocytes. In addition to blockade of the transient outward current and IKur, terfenadine at clinically relevant concentrations blocked both the rapidly and slowly activating components of the delayed rectifier in human atrial myocytes. Blockade of these K+ currents may contribute to the cardiotoxicity associated with terfenadine usage.

Atrial Function↗
PubMed1994

Rescue of lethal subunits into functional K+ channels.

In a chimeric, voltage-dependent K+ channel (CHM), the valine at position 369 and the leucine at position 374 interact within the pore or P-region to regulate ion permeation and block. Here we show that the point mutation, CHM V369L, abolished channel function whereas previous experiments showed that CHM V369 and CHM V369I are functional. Coinjection of "lethal" CHM V369L cRNA with CHM L374V cRNA but not CHM cRNA generated functional heteromultimers. The whole-cell Rb+/K+ conductance ratio was 2.98 +/- 0.43 for CHM L374V and was reduced to 0.87 +/- 0.04 for the coexpressed CHM V369L and CHM L374V subunits. When single-channel currents were recorded, a single class of CHM V369L/CHM L374V heteromultimers was identified. This class was readily distinguishable from CHM L374V homomultimers by K+ conductance, gating, and blockade by internal tetraethylammonium. Coinjection experiments at various RNA ratios suggest that the CHM V369L/CHM L374V heteromultime, assuming it to be a tetramer, was composed of three CHM L374V subunits and one CHM V369L subunit. It appears that in the critical P-region of CHM position 369 may tolerate only one leucine.

Amino Acid Sequence↗
PubMed1989

The use of pulse oximetry in post-operative hypoxaemia in patients after propofol induction of anaesthesia.

Pulse oximetry was used to measure changes in oxygen saturation in the early post-operative phase in three groups of 50 patients in whom anaesthesia was induced with propofol. One group breathed room air during induction and anaesthesia was maintained with halothane whereas the other two groups both breathed oxygen during induction and anaesthesia was maintained with either halothane inhalation or a propofol infusion. In 59 patients distributed fairly evenly between the three groups the oxygen saturation fell below 90%; the mean minimum oxygen saturation was 91.7 +/- 0.3 and the mean time at which it occurred was 3.9 +/- 0.4 min after the anaesthetic was withdrawn. Neither the inhalation of oxygen during induction nor the anaesthetic technique affected the decrease in postoperative oxygen saturation but the infusion group took significantly longer to recover consciousness.

Adolescent↗
PubMed1987

Recovery of respiration after neuromuscular blockade with alcuronium.

Alcuronium 0.2 mg kg-1 was given to six patients to investigate the simultaneous recovery of breathing and peripheral neuromuscular function. Anaesthesia was maintained with 66% nitrous oxide in oxygen supplemented with 0.5% halothane, and the patients were ventilated to normocarbia. Patients were disconnected from the ventilator after the reappearance of the tetanic response. This response returned at a mean time of 19.2 min after the injection of alcuronium and oxygenation was maintained thereafter by means of apnoeic diffusion. Spontaneous breathing returned at a mean time of 23.6 min after the injection of alcuronium. Sixty minutes after the administration of alcuronium, respiratory exchange was judged adequate, and at that time neuromuscular function was still markedly depressed with a tetanic height less than 25% of control. It was concluded that, because of the slow recovery of neuromuscular function, alcuronium should be reserved for the longer surgical procedure.

Adolescent↗
PubMed1987

Electrical and mechanical responses after neuromuscular blockade with vecuronium, and subsequent antagonism with neostigmine or edrophonium.

Six unpremedicated patients who had given their informed consent were given vecuronium 0.08 mg kg-1 before elective surgery. Recovery from neuromuscular blockade was measured electrically and mechanically. Neuromuscular blockade was antagonized 1 h after the administration of vecuronium with two doses of neostigmine 2.5 mg (three patients) or edrophonium 0.5 mg kg-1 (three patients). Although the onset of initial recovery was similar, subsequent recovery was faster when measured electrically (EMG) than when measured mechanically. Recovery appeared to be faster in younger patients. Reintroduction of neuromuscular blockade occurred after the second dose of neostigmine 2.5 mg, given to antagonize the block. This did not occur after either dose of edrophonium 0.5 mg kg-1.

Adult↗
PubMed1986

Halothane and the liver.

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Chemical and Drug Induced Liver Injury↗
PubMed1986

Antagonism of atracurium-induced neuromuscular blockade by neostigmine or edrophonium.

Antagonism of atracurium-induced neuromuscular blockade by neostigmine or edrophonium has been studied using the tetanic (50 Hz) and train-of-four (2 Hz) or single twitch responses of the adductor pollicis muscle in 22 anaesthetized patients. A further nine patients not given an anticholinesterase acted as a control group. In two groups (six patients for each anticholinesterase) in whom antagonism was attempted at 95-98% blockade of the tetanic response, recovery of the tetanic response after two or three doses of edrophonium 0.75 mg kg-1 i.v. was not statistically different from that in the control group; recovery after two doses of neostigmine 2.5 mg i.v. was significantly faster (P less than 0.001). Recovery of the single twitch response after antagonism with edrophonium, although longer than that with neostigmine (P less than 0.01), was significantly shorter than in the control group (P less than 0.05). When edrophonium is given at the commencement of recovery, the initial rapid antagonism of tetanic block is not sustained, whereas antagonism by neostigmine is more persistent and the recovery phase is significantly shortened. In a further two groups of patients (n = 5) given atracurium 0.3 mg kg-1 i.v., antagonism was not attempted until the peak height of the tetanic contraction had reached approximately 50% of the control value.(ABSTRACT TRUNCATED AT 250 WORDS)

Atracurium↗
PubMed1986

Recovery of spontaneous breathing following neuromuscular blockade with atracurium.

Atracurium 0.3 mg kg-1 was given to two groups of patients to compare the recovery of spontaneous breathing with that of peripheral neuromuscular function. Anaesthesia was maintained in one group (n = 6) with an infusion of etomidate (mean flow rate 24 micrograms kg-1 min-1) and in the other group (n = 5) with 0.5% halothane. From the time of discontinuing ventilation, about 5 min after the reappearance of the tetanic response, spontaneous breathing returned in an average time of 135 s (range 18-300) in the patients given etomidate and in 68 s (range 0-123) in the patients who received halothane (ns). The duration of action of atracurium was not significantly prolonged by halothane, probably because of the low concentration used. Adequate recovery of respiratory muscle function occurred within 30 min of administration of atracurium at a time when there was less than 25% recovery of the tetanic response of the adductor pollicis muscle. It was concluded that recovery of the muscles of respiration from neuromuscular blockade by atracurium occurred more rapidly than recovery of the muscles of the hand, but an adequate tidal volume in the absence of other clinical signs should not be regarded as a reliable indicator of complete return of neuromuscular function.

Adult↗
PubMed1986

Recovery of respiration following neuromuscular blockade with atracurium and alcuronium.

Eleven fit unpremedicated patients took part in the study. Group I (five patients) received atracurium 0.3 mg kg-1 and group II (six patients) received alcuronium 0.2 mg kg-1. The simultaneous recovery of respiration, judged by serial measurements of the tidal volume and blood-gas values, and peripheral neuromuscular function, judged by the response of the adductor pollicis muscle, were studied. Anaesthesia was maintained with 66% nitrous oxide in oxygen, supplemented by 0.5% halothane. The tetanic response reappeared 17.6 +/- 0.92 min (group I) and 19.2 +/- 2.6 min (group II) after the administration of the drug, and spontaneous breathing at 24.0 +/- 2.08 min (group I) and 23.6 +/- 2.1 min (group II). Adequate recovery of respiratory muscle function was present in group I within 15 min of the onset of spontaneous respiration, whereas in group II this recovery took 30 min. At this time there was marked peripheral neuromuscular blockade with the peak tetanic height value less than 25% of control in both groups. It was concluded that recovery of the respiratory muscles from neuromuscular block by atracurium and alcuronium occurred more rapidly than the recovery of the small muscles of the hand, but that adequate tidal volume, in the absence of other clinical signs, should not be regarded as a reliable indication of complete return of neuromuscular function.

Adolescent↗