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Biomedical subjects

T W Higenbottam

Publications and source records attributed to T W Higenbottam.

At least 109 records · Page 6Linked to original sources

Transplantation of the lungs.

Over the last eight years a completely new form of treatment has been introduced for end-stage pulmonary vascular disease and chronic lung disease, including cystic fibrosis. Lung transplantation and heart-lung transplantation have moved from an experimental and innovative stage to clinical treatments. The exclusion criteria for selecting potential recipients have become relaxed whilst preservation techniques have improved to allow ischaemic times of donor organs to be extended beyond 4 h. Monitoring of graft function with daily spirometry and use of transbronchial lung biopsy have enabled early diagnosis of lung rejection or infection and thus effective treatment. Lung transplantation and heart-lung transplantation, by their success, are providing new insight into lung disease and pulmonary physiology.

Heart-Lung Transplantation↗

Early experience of heart-lung transplantation.

We report our experience of heart-lung transplantation for the treatment of children with terminal respiratory disease. Between May 1987 and October 1988 we performed heart-lung transplantation in five children under the age of 16 (age range 11-15). All the patients were severely disabled by dyspnoea and hypoxia. Two had primary pulmonary hypertension, two cystic fibrosis, and one had Eisenmenger's syndrome. All five children are alive and well five to 17 months after operation and have returned to activities normal for their age. Three of the five patients had episodes of infection after operation. These were staphylococcal pneumonia, herpes simplex pneumonitis and, in one of the patients with cystic fibrosis, persistent purulent sputum. The mean number of episodes of rejection per child was 2.7 per half year. Heart-lung transplantation is a practical treatment for children in these disease groups with terminal respiratory failure.

Adolescent↗

Production of eosinophil-activating factor (EAF) by peripheral blood mononuclear cells from asthma patients.

Mononuclear cells from blood samples from asthmatic patients were tested for their ability to produce two eosinophil activating factors, EAF and TNF. High levels of EAF were produced by some but not by all patients. The influence of external factors on EAF production was evaluated. Patients receiving prednisolone (10-30 mg/day) tended to produce only low levels of EAF. Prednisolone has been shown to inhibit production of EAF in vitro by isolated mononuclear cells, at concentrations of 0.1-1 micrograms steroid/ml. Incubation of mononuclear cells with certain allergens enhances EAF production in sensitive individuals. Little or no production of TNF was observed in the patients examined.

Adult↗

The radiographic appearances of infection and acute rejection of the lung after heart-lung transplantation.

Thirty-two patients underwent combined heart and lung transplantation at Papworth Hospital between 1984 and 1987. The clinical and physiologic observations made at the time of episodes of infection and rejection together with the histopathology of lung tissue obtained by transbronchial lung biopsy were compared with pre- and postepisode chest radiographs. There were 45 episodes of rejection in 20 patients: 23 episodes during the first month after transplantation, and 22 after 1 month. Twenty-six episodes of infection occurred in 15 patients. The causative organisms included Aspergillus fumigatus, cytomegalovirus (CMV), herpes simplex, Pneumocystis carinii, and Staphylococcus aureus. When an abnormal chest radiograph is common during the first month after transplantation during acute rejection (74%), it may alternatively be due to lung infection (most commonly CMV pneumonitis). The chest radiograph during this period provides a useful indication for transbronchial biopsy and bronchial lavage. The chest radiograph is abnormal in the minority (23%) of episodes of rejection occurring later than 1 month after transplantation. Pulmonary function tests (FEV1 and VC) offered a more useful indication for transbronchial biopsy during this period.

Adolescent↗

Sites of deposition of aqueous aerosols: a study of efficiency of delivery systems for lung ventilation imaging in man.

A study was made of the deposition of 99Tcm-DTPA aerosol in the components of a jet nebulizer-based aerosol production system. Three impaction devices were compared: a ball-bearing separator, a virtual impactor and a step separator. In addition a comparison was made of two types of tubing which carried aerosol from nebulizer to mouthpiece: corrugated and smooth-walled tubing. The retention of aerosol following inhalation was measured in five normal volunteers using different patterns of breathing. Using an aerosol production system which included a ball-bearing separator only a mean of 11% of the radioactivity loaded into the nebulizer was emitted as an aerosol. Some 18% remained in the ball-bearing separator. The ball-bearing and step separators produced similar total outputs (7% and 6% minimum), the step separator producing marginally higher mean output/min. The virtual impactor produced a lower output than the other two impactors studied, only 1%. A larger proportion of the aerosol output was deposited on corrugated tubing (7%) compared with smooth-walled tubing (1%). The retained fraction of the aerosol inhaled by subjects ranged from 16% to 43%. A higher fraction was retained when subjects inhaled deeply and held their breath for 10 s between each breath. The efficiency of radionuclide deposition from aerosol generator to patient ranged from 1.1% to 6% and was determined more by the retention in the subject than by choice of separator or tubing.

Aerosols↗

A simultaneous single breath measurement of pulmonary diffusing capacity with nitric oxide and carbon monoxide.

Pulmonary diffusing capacity (DL) for carbon monoxide (CO) and nitric oxide (NO) were simultaneously measured in man using the single breath method, by adding 4O ppm of NO to the inspired gas and analysing the expirate for NO by a chemiluminescent method. The mean ratio of DLNO to DLCO in thirteen subjects was 4.3 (SD 0.3), mean DLNO = 49 mmol.min-1.kPa-1 (SD 10) and mean DLCO = 11 mmol.min-1.kPa-1 (SD 2). An increase in alveolar oxygen concentration from a mean of 18 to 68% in five subjects was associated with a 54% fall in DLCO but no change in DLNO. A reduction of lung volume from total lung capacity (TLC) (mean of 7 l) to a mean volume of 3.9 l in five subjects caused a fall in both DLNO (by 34%) and DLCO (by 8%). With 175 watts cycle exercise in three subjects the DLCO rose by 45% and DLNO by 25%. Since NO reacts much faster with haemoglobin than CO, DLNO should be influenced much less by reaction with haemoglobin, and perhaps represents a better index for the diffusing capacity of the alveolar-capillary membrane (Dm) than DLCO.

Carbon Monoxide↗

Changes in factor VIII proteins after cardiopulmonary bypass in man suggest endothelial damage.

16 patients undergoing coronary artery bypass grafting using cardiopulmonary bypass (CPB) had blood samples taken at various times before, during and up to 1 week after surgery for estimation of beta-thromboglobulin (BTG), alpha-1-antichymotrypsin (ACT), factor VIII procoagulant protein (VIII:C), von Willebrand factor antigen (vWF:Ag) and ristocetin co-factor (vWF:RiCoF). vWF:Ag and vWF:RiCoF rose during and following surgery in a different manner to ACT. At 1 week there was a significantly disproportionate rise in vWF:Ag compared to vWF:RiCoF which suggested a degree of pulmonary endothelial damage. Prostacyclin, which was administered to 8 of the patients during CPB, reduced platelet activation as measured by a reduction in the release of BTG and also attenuated the consumption of VIII:C. It had no effect on pulmonary endothelial damage as measured by the ratio of vWF:Ag to vWF:RiCoF.

Adult↗

The relationship between pulmonary artery pressure and pulmonary artery diameter in pulmonary hypertension.

The pulmonary arteries dilate in response to many factors, principally increased pressure and flow. In patients who have pulmonary arterial hypertension but no increase in flow, we have compared main pulmonary artery size at computed tomography with pulmonary haemodynamic data obtained during right heart catheterisation. In patients with primary pulmonary hypertension and chronic thromboembolic pulmonary hypertension, dilatation correlated with raised pulmonary vascular resistance and reduced cardiac output but not with mean arterial pressure. In patients with chronic lung disease no correlations were shown though a trend between raised pressure and size was observed. We speculate that pulmonary artery compliance is an important factor which determines the degree of dilatation in response to raised pressure. Estimations of pressure cannot be made from measurements of pulmonary artery size without knowledge of the underlying lung disease.

Adult↗

Aerosol lung scintigraphy in the detection of bronchiectasis.

Twenty patients were studied to assess the value of aerosol ventilation scintigraphy, using 99Tcm diethylene triamine penta-acetic acid (DTPA) as a screening test for bronchiectasis. All patients had previously undergone bronchography for suspected bronchiectasis. Nine had cylindrical bronchiectasis and 11 had no demonstrable abnormality. Only two of the 20 patients had features suggestive of bronchiectasis on their chest radiographs. Segmental defects in ventilation were demonstrated by scintigraphy in five of the nine patients with bronchiectasis (56%). Regional ventilation appeared normal in 26 of the 27 lungs which were bronchographically normal (96%). Whilst the sensitivity of aerosol ventilation scintigraphy in detecting bronchiectasis is low (56%), it compares favourably with that of the chest radiograph (22%) in this group of patients with mild disease and non-specific symptoms. Thus, in some, it may obviate the need for bronchography.

Adolescent↗

Effects of pH and osmolarity on aerosol-induced cough in normal volunteers.

1. The chemosensitivity of cough receptors stimulated by inhalation of aqueous aerosols was evaluated in 21 normal volunteers in three experiments. 2. The pH of isotonic saline was altered using small amounts of phosphate or glycine buffers to produce solutions with a pH range of 2.6-10.0. These solutions were nebulized ultrasonically and breathed for 1 min periods by seven subjects in random order and on separate days. Cough frequency during each 1 min inhalation was recorded. Only the two solutions of extreme pH (2.6 and 10.0) caused cough. 3. The effect of altering the osmolarity of the inhaled aerosol on cough was assessed using D-glucose over a range of 77-1232 mosmol/l. Saline solutions over the same range of osmolarity were also tested. The pH of D-glucose was raised to match that of saline by adding small amounts of sodium hydroxide. All solutions were nebulized and inhaled by seven subjects as described above for 1 min periods during which cough frequency was recorded. Forced expired volume in 1 s was recorded after each inhalation and did not alter in any subject by more than 10%. Subjects coughed when inhaling all the D-glucose solutions over the whole range of osmolarity. Cough occurred with saline solutions only at low chloride concentration and at the highest concentration. 4. In order to clarify whether the response to hypertonic saline was due to the high ionic content of the solutions or to its hypertonicity, two other solutions were tested. These were an isotonic and a hypertonic mixture of D-glucose and saline, containing 'normal' (150 mmol/l) ionic content.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Accurate measurement of airway thermal challenge.

Rapid and accurate measurement of air temperature is needed to determine both heat and water losses from the respiratory tract during breathing. We have designed, constructed and validated a low dead-space, two-channel valve/mouthpiece which prevents mixing of inspired and expired air outside the body. The effects of airflow on the thermocouple response time and of thermocouple position within the airstream on the temperature measured were assessed. The 63% thermocouple response time fell from 159 to 78.8 ms as airflow rose from 23.7 to 297 1 min-1, a range including the peak flows observed while breathing at rest and during exercise. Measurement of temperature profiles across the valve/mouthpiece at different flows indicated that thermocouples were best positioned at the centre of the airstream, though small deviations did not adversely affect accuracy.

Body Temperature Regulation↗

Clinical experience in the management of pulmonary opportunist infection and rejection in recipients of heart-lung transplants.

The main clinical problems that follow heart-lung transplantation are opportunist infections of the lungs and pulmonary rejection. Of 23 patients undergoing heart-lung transplantation, eight had opportunist infections and 12 had at least one episode of pulmonary rejection. Cardiac rejection occurred in only one patient, who did not need treatment. Of the 12 patients who had pulmonary rejection, nine recovered fully after augmented immunosuppression with high dose corticosteroids, although one patient required additional low dose corticosteroids for eight months before making a full recovery. Fatal opportunist lung infection followed treatment for rejection in two patients. One patient developed obliterative bronchiolitis. Of the eight patients with opportunist infections, five had primary cytomegalovirus pneumonitis, acquired from the donor. All three patients treated with acyclovir died, whereas the two treated with hyperimmune globulin and dihydroxy proxymethylguanine recovered fully. Two patients developed Pneumocystis carinii pneumonia, which was treated successfully in one patient with intravenous sulphadimidine and trimethoprim. The other patient died after a further episode of rejection and aspergillus bronchitis. One patient developed a tuberculous empyema. The calculated actuarial survival at one year was 78% and at two years 67.2%. Although it is still in its innovative stage heart-lung transplantation appears to have complications and results similar to those of transplantation of other organs.

Cytomegalovirus Infections↗

Effect of drugs used in the treatment of asthma on the production of eosinophil-activating factor by monocytes.

The cytotoxic activity of eosinophils, as measured by their ability to kill antibody-coated schistosomula of Schistosoma mansoni, is enhanced by a factor (eosinophil-activating factor, EAF) which is secreted by peripheral blood monocytes from certain moderately eosinophilic individuals. The secretion of this factor by monocytes is inhibited by methylprednisolone (1 microgram/ml), beclomethasone (10 micrograms/ml) and theophylline (100 micrograms/ml), but not by sodium cromoglycate or salbutamol. Methylprednisolone, beclomethasone and theophylline do not inhibit either eosinophil cytotoxic activity or enhancement of eosinophil cytotoxic activity by EAF at these concentrations.

Albuterol↗