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Biomedical subjects

R Fletcher

Publications and source records attributed to R Fletcher.

At least 127 records · Page 7Linked to original sources

Methylxanthines reduce in vitro human overall platelet metabolism as measured by microcalorimetry.

The effect in vitro of caffeine, theophylline and enprofylline on overall platelet metabolism was investigated by a sensitive microcalorimetric method. Platelet heat production rate was found to be decreased significantly in the presence of any of the three methylxanthines in mM concentrations. Also lower caffeine concentration, as occurring during normal coffee intake, reduced platelet metabolism. These results show that, firstly, methylxanthines have a direct influence on platelet metabolism, and secondly, microcalorimetry can be used as a new and sensitive tool for investigating the influence of drugs on blood cell metabolism.

Blood Platelets↗

The effects on gas exchange of a large mediastinal tumour.

A 14-year-old boy with a mediastinal tumour large enough to cause dyspnoea at rest was anaesthetised for a biopsy. The tumour was believed to compress the tracheal bifurcation. After tracheal intubation, the expiratory breath sounds were heard to be intermittent. The expiratory flow pattern showed irregularities synchronous with the electrocardiogram. With constant flow inflation, the inspiratory pressure profile was suggestive of mechanical obstruction with a resistance which decreased during inspiration. The airway deadspace was greatly reduced, suggesting that the obstruction was near the tracheal tube opening and that there was pooling of carbon dioxide behind this obstruction. The alveolar deadspace fraction was increased and the shape of the carbon dioxide single breath test suggested severe airway obstruction. These findings can be explained on the basis of large airway obstruction, partly intermittent because of the heart's movement, and also reduced lung volume and uneven gas distribution caused by the tumour and pleural fluid.

Adolescent↗

Clonidine and the sympatico-adrenal response to coronary artery by-pass surgery.

Clonidine was administered intravenously in an attempt to limit sympatico-adrenal activity and thereby reduce the incidence of arterial hypertension associated with coronary artery by-pass graft surgery (CABG). Forty patients scheduled for CABG were assigned to two groups. Twenty patients received clonidine 4 micrograms kg-1 before surgery, 2 micrograms kg-1 after cardiopulmonary by-pass and 1 microgram kg-1 when the skin was sutured. The other 20 patients served as controls. All patients were anesthetized with fentanyl, droperidol, nitrous oxide and alcuronium. During surgery 5 min after sternotomy, mean arterial pressure was 13 mmHg lower (P less than 0.01) in the clonidine group, while after operation the difference between the groups was negligible. Both during and after surgery the plasma catecholamine concentrations were significantly lower in the clonidine group (P less than 0.01). The greatest difference between the groups was seen 90 min after operation, when plasma noradrenaline and plasma adrenaline concentrations in the clonidine group were less than 1/3 of those in the control group (P less than 0.01). As judged by catecholamine concentrations clonidine was effective in attenuating sympatico-adrenal hyperactivity during and after surgery. Postoperative arterial hypertension was not reduced, however, and it is concluded that other factors besides sympatico-adrenal hyperactivity must be important.

Adrenocorticotropic Hormone↗

On-line measurement of gas-exchange during cardiac surgery.

This paper describes an on-line system for continuously monitoring expired CO2 during controlled ventilation. Signals from a Servo ventilator 900B or C and a CO2 Analyzer 930 are processed and corrected by the computer to produce a CO2 single breath test (SBT-CO2). This is the tracing of expired CO2 concentration or fraction against expired volume, from which the computer calculates the airway deadspace (VDaw). If a value for arterial PCO2 is supplied, the computer will calculate the physiological deadspace (VDphys) and the alveolar deadspace (VDalv) for each breath. The system was used to make measurements at four stages during coronary artery by-pass grafting in 13 male patients. When the sternum was opened there was a 32% increase in VDaw, and the physiological deadspace fraction therefore increased. There were reductions in VDaw after extra-corporeal circulation and again after sternal suture. By the end of surgery, the alveolar deadspace fraction had increased significantly. VDaw at this stage was smaller than pre-operatively, and so there was no net change in the physiological deadspace fraction at the end of surgery. Arterial PO2 was, however, reduced at this stage.

Aged↗

Investigation of malignant hyperthermia in Sweden.

One hundred and thirty patients from 52 families were investigated for susceptibility to malignant hyperthermia (MH). The diagnosis of MH susceptibility (MHS) was made by in vitro exposure of muscle to halothane and to caffeine, according to the protocol established by the European malignant hyperpyrexia group. In addition, 13 normal control biopsies were obtained from the same muscle and with the same anaesthesia as in the MH patients. These control results agree with and confirm the criteria formulated in the European MH group. The results are compared with our first 85 investigations performed prior to the establishment of the protocol. The main difference compared to the earlier material is the addition of an equivocal group (MHE), whose muscle reacted in vitro to either halothane or caffeine, but not both. All the families referred because of a fulminant MH reaction contained MHS or MHE members. There was a greater incidence of MH-negative families, suggesting an increased suspicion of MH amongst the clinicians.

Adolescent↗

Increased alveolar deadspace after closure of cardiac septal defects: pulmonary air embolism or failure of homeostasis?

During surgery for closure of atrial or ventricular septal defects (ASD, VSD), we used a computerized on-line system to follow changes in the alveolar deadspace fraction. We observed a large increase in the alveolar deadspace immediately following septal defect closure. No increase had been observed post-cardio-pulmonary bypass in children operated upon because of aortic or pulmonary stenosis, or in adults undergoing myocardial revascularization. The increase in deadspace is probably a result of the lung's failure to adjust to the large decrease in pulmonary blood flow following septal defect closure. An alternative cause for the finding, that of pulmonary artery air embolism occurring intraoperatively, appears to be less likely.

Adult↗

Clinical and muscle biopsy findings in malignant hyperthermia susceptibility.

Patients (155) were investigated for malignant hyperthermia susceptibility (MHS), by in vitro testing of muscle taken from the vastus medialis muscle. Histopathological and histochemical investigation of muscle was also performed. Ultrastructural investigation was performed in 13 MHS patients; 90% of the patients replied to a questionnaire concerning present or previous neuromuscular symptoms. The majority of MHS and MH negative (MHN) patients had no or only minor histopathological and histochemical abnormalities. Core-targetoid fibres were the only potentially important abnormalities found in MHS patients. There were no differences in neuromuscular symptoms between MHS, MHN and control patients, and most patients in both the MHS and MHN group were normal on clinical examination.

Adolescent↗

Gas exchange during controlled ventilation in children with normal and abnormal pulmonary circulation: a study using the single breath test for carbon dioxide.

Carbon dioxide single breath tests (SBT-CO2) were obtained during anesthesia and controlled ventilation in 42 children about to undergo thoracic surgery. The tests were obtained with a computerized system based on the Servo ventilator. The system made on-line corrections for compressed volume, apparatus deadspace, and rebreathing. Children with normal pulmonary circulation had excellent gas exchange with high PaO2 values, a mean alveolar deadspace fraction (VDalv/VTalv) of 0.10, and a gently sloping phase III of SBT-CO2. Children with pulmonary hyperperfusion (left to right shunting) due to an atrial septal defect or a ventrical septal defect had significantly lower PaO2 values, steeper phase III slopes, and a greater spread of values for VDalv/VTalv. Children with pulmonary hypoperfusion due to pulmonary stenosis in combination with intracardiac right to left shunting had extremely low PaO2 values, and "adult" values for VDalv/VTalv. They required increased ventilation to maintain CO2 homeostasis. In the pooled material, the airway deadspace was strongly correlated to height, weight, and age. The airway deadspace was unaffected when tidal volume was increased by 37%, and ventilatory frequency simultaneously reduced by 30%, a maneuver that left alveolar ventilation unchanged. This is probably because an end-inspiratory pause was used; when frequency is reduced the length of the end-inspiratory pause increases, allowing proximal diffusion of the alveolar/fresh gas interface.

Anesthesia↗

Microcalorimetric studies in malignant hyperpyrexia susceptible individuals.

In an attempt to develop a diagnostic test for malignant hyperpyrexia (MH) without the need for open muscle biopsy, we have investigated the change in heat production brought about when platelets and muscle are exposed to halothane and caffeine. Halothane 3% caused platelet aggregation, which was itself associated with heat production. Caffeine 4 mmol litre-1 decreased heat production in platelets from both MH susceptible and non-susceptible individuals. Muscle exposed to 4% halothane showed an increase in heat production in both types of tissue. There were no significant differences in heat production between MH-susceptible and non-susceptible tissue in any of the tests.

Blood Platelets↗

Malignant hyperpyrexia and sudden death.

Two teenage boys, brothers, died suddenly within 2 months of each other. No clear cause of death could be identified in either case. Because of previous reports of the association between malignant hyperpyrexia and sudden death in otherwise healthy young men, we examined the parents. The father was found to be malignant hyperpyrexia-susceptible.

Adolescent↗

Gas exchange in the partially atelectatic lung.

An 11-month-old girl was anaesthetised for resection of a coarctation of the aorta. The child took part in a research project in which functional residual capacity (FRC) and alveolar deadspace were being monitored on-line. Initial measurements during controlled ventilation showed an unexpectedly low PaO2 and an alveolar deadspace more than double the normal value. After manual hyperventilation and tracheal suction, FRC increased by 25% and PaO2 and the alveolar deadspace fraction reverted towards normal values for an infant. We therefore had strong grounds for suspecting atelectasis, although the shunt through the atelectatic lung was, in theory, too small to account for the increase in alveolar deadspace. We also noted that the shape of the expired CO2 trace was improved after hyperinflation, as was the time needed to wash out SF6 (the tracer gas used to measure FRC) from the lung. From these observations, we conclude that atelectasis may be associated with more widespread disturbances of gas exchange than is generally realised, perhaps because of distension of adjacent lung regions.

Anesthesia, General↗