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Biomedical subjects

I G Brown

Publications and source records attributed to I G Brown.

At least 19 recordsLinked to original sources

Bioactive surface coatings for nanoscale instruments: effects on CNS neurons.

A method is described for depositing onto medical instruments highly biocompatible and bioactive surface coatings that can promote and stabilize cell attachment. The coatings were made by first depositing thin films of materials, such as diamond-like carbon, or metals, including tantalum, tungsten, platinum, gold, iridium, palladium, and brass. These surfaces were further altered to either promote or inhibit cell growth and spreading by an additional overcoat of biological materials, including the extracellular matrix proteins, laminin, fibronectin, and collagen IV. The deposition technique used a metal or carbon plasma, and the important properties of film adhesion, hardness, density, and smoothness are tailored by control of the ion bombardment energy. The films are translucent enough to permit high resolution light microscopy for rapid and detailed examination of tissue response. These bioactive substrates have been tested on primary central nervous system neurons, and the growth response is excellent. Equally successful have been our attempts to anchor neurons, without associated proliferation of non-neuronal cells, using coatings of poly-d-lysine. The method and the materials could have important ramifications in a number of areas of research and biotechnology, for example for chronic implantation of microelectrode arrays in the cerebral cortex for neuroprosthetic and neural monitoring application and for research on the human central nervous system. Possible application in nonneuronal fields, such as for coronary artery stents and pacemaker electrodes, also are discussed.

Animals↗

Pleurectomy for persistent pain in benign asbestos-related pleural disease.

BACKGROUND: Persistent severe pain is a rare complication of benign asbestos-related pleural disease. METHODS: Four patients are described in whom pain persisted for more than one year (range 18 months to five years) which was incompletely relieved by opioid medication and nerve blocking procedures. All underwent pleurectomy in an attempt to relieve it. RESULTS: At operation the pleura was considerably thickened in all cases. Two of the four patients had successful relief of pain. The other two had a neuralgic component to their pain before surgery which persisted afterwards. One of these patients underwent successful cervical cordotomy. CONCLUSIONS: Pleurectomy may provide relief in patients with constant pleuritic pain due to benign asbestos-related pleural thickening. It seems, however, that patients in whom the pain has a neuralgic component are unlikely to benefit.

Adult↗

Successful treatment of disseminated strongyloidiasis.

OBJECTIVE: To report the successful treatment of Strongyloides stercoralis hyperinfection, which is usually lethal but in this case was diagnosed in its early stages. CLINICAL FEATURES: A 44-year-old woman, who had spent much of her life in Fiji and India, was treated with a high dose of prednisolone for rheumatoid arthritis complicated by gold lung. The onset of abdominal symptoms, an exacerbation of respiratory symptoms, and a persistent high eosinophil count and serum IgE level, led to the detection of numerous Strongyloides larvae in her faeces and sputum. INTERVENTION AND OUTCOME: She was treated with thiabendazole for five days, then mebendazole for one month, and the dose of prednisolone was reduced. Clinical symptoms and signs improved within days and after one week parasites could not be found in her faeces. After six months, enzyme-linked immunosorbent assay for Strongyloides infection gave a reading which was 40% of the initial level but still in the positive range. CONCLUSION: Steroid therapy in individuals with chronic, subclinical strongyloidiasis predisposes to the insidious development of hyperinfection syndrome, which has a high mortality rate. If detected early, this complication can be treated effectively. It can be prevented by actively seeking Strongyloides infection, by faecal microscopy and culture techniques and by serological tests, in high-risk individuals, such as immigrants from endemic areas.

Adult↗

Improvement in upper airway function after weight loss in patients with obstructive sleep apnea.

Overweight patients with obstructive sleep apnea (OSA) are improved by weight reduction, although the underlying mechanisms are not clear. We tested the hypothesis that improvement in OSA after weight loss is associated with improvement in pharyngeal function. Consequently, we measured pharyngeal area at functional residual capacity (AFRC) and at residual volume (ARV), the percent change in pharyngeal area between FRC and RV (delta Aph%) defined as (AFRC - ARV)/AFRC x 100, and lung volume dependence of pharyngeal area (LVD) defined as the difference between AFRC and ARV normalized for the expiratory reserve volume (ERV)--in 12 overweight apneic patients before and after weight loss. We found that after a 26 +/- 18 kg weight loss, there was a significant reduction in the apnea/hypopnea index from 57 +/- 29 to 14 +/- 10 (p less than 0.0005) and increase in the lowest nocturnal oxygen saturation from 54 +/- 20% to 80 +/- 8% (p less than 0.001). This improvement was associated with a significant reduction in delta Aph% from 25 +/- 15% to 9 +/- 18% (p less than 0.05) and a significant decrease in LVD from 1.98 +/- 1.52 cm2/L to 0.16 +/- 0.88 cm2/L (p less than 0.005). There were four patients in whom baseline LVD was low and relatively unchanged after weight loss. Three of these patients exhibited paradoxical inspiratory narrowing of the glottis, which reversed after weight loss; these glottic abnormalities were not present in the rest of the patients with OSA. We conclude that improvement in obstructive sleep apnea after weight loss may be related to improvement in pharyngeal and glottic function.

Adult↗

Differences in pharyngeal properties between snorers with predominantly central sleep apnea and those without sleep apnea.

The underlying cause of idiopathic central sleep apnea syndrome is not well understood. We therefore examined the possibility that patients with idiopathic central sleep apnea may have abnormalities of upper airway mechanics that might contribute to the pathogenesis of central apneas. The acoustic reflection technique was used to assess pharyngeal size, lung volume dependence, and pharyngeal "compliance" in 8 patients with idiopathic central sleep apnea, all of whom were snorers, and in 8 weight-matched, snoring control subjects with normal sleep studies. Patients with central sleep apnea when compared with control subjects exhibited markedly increased specific pharyngeal "compliance" (0.12 +/- 0.05 versus 0.03 +/- 0.01 cm H2O-1; p less than 0.001), increased change in pharyngeal area from FRC to RV (0.8 +/- 0.5 versus 0.03 +/- 0.3 cm2; p less than 0.05), and a larger pharyngeal area at FRC (4.7 +/- 0.9 versus 3.8 +/- 0.8 cm2; p less than 0.03). We conclude that increased pharyngeal "compliance" and lung volume dependence may play a role in the etiology of central apneas in this syndrome.

Brain Diseases↗

Pharyngeal size in snorers, nonsnorers, and patients with obstructive sleep apnea.

We measured pharyngeal cross-sectional area and its change with alterations in lung volume in 10 subjects who snored and had obstructive sleep apnea, 6 subjects who snored and did not have obstructive sleep apnea, and 9 subjects who did not snore. Pharyngeal area was measured with use of an acoustic-reflection technique. We found that snorers with and without sleep apnea had a significantly smaller mean (+/- SE) pharyngeal cross-sectional area (4.1 +/- 0.2 and 3.7 +/- 0.9 cm2, respectively) at functional residual capacity than nonsnorers (5.4 +/- 0.5 cm2, P less than 0.025). When lung volume decreased from functional residual capacity to residual volume, both nonsnorers and snorers with sleep apnea had a decrease in pharyngeal area (from 5.4 +/- 0.5 to 4.5 +/- 0.4 cm2 and 4.1 +/- 0.2 to 3.4 +/- 0.2 cm2, respectively), whereas snorers without sleep apnea had no such decrease, suggesting that their pharynxes were less collapsible at low lung volumes. We conclude that snorers with and without sleep apnea have smaller pharyngeal cross-sectional areas than nonsnorers and that snorers with sleep apnea have a further decrease as lung volume falls.

Adult↗

Changes in tracheal cross-sectional area during Mueller and Valsalva maneuvers in humans.

Pressure-area behavior of the excised trachea is well documented, but little is known of tracheal compliance in vivo. Extratracheal tissue pressures are not directly measurable, but transmural pressure for the intrathoracic trachea is inferred from intra-airway and pleural pressure differences. Extramural pressure of the cervical trachea is assumed to be atmospheric. The difference in transmural pressure between the intra- and extrathoracic tracheal segments should be exaggerated during Mueller and Valsalva maneuvers. We used the acoustic reflection technique to measure tracheal areas above and below the thoracic inlet during these isovolume-pressure maneuvers. We found that 10 cmH2O positive pressure increased tracheal area in the extrathoracic segment by 34 +/- 16% (mean +/- SD) and in the intrathoracic segment by 35 +/- 15%. There was a reduction in area of 27 +/- 16 and 24 +/- 14%, respectively, for the extra- and intrathoracic segments with 10 cmH2O negative pressure. We conclude that the effective transmural pressure gradients do not vary significantly between intra- and extrathoracic tracheal segments.

Adult↗

Pharyngeal cross-sectional area in normal men and women.

Pharyngeal size and the dynamic behavior of the upper airway may be important factors in modulating respiratory airflow. Patients with obstructive sleep apnea are known to have reduced pharyngeal cross-sectional area. However, no systematic measurements of pharyngeal area in healthy asymptomatic subjects are available, in part due to the lack of simple, rapid, and noninvasive measurement techniques. We utilized the acoustic reflection technique to measure pharyngeal cross-sectional area in 24 healthy volunteers (14 males, 10 females). Pharyngeal area was measured during a continuous slow expiration from total lung capacity (TLC) to residual volume (RV). We compared pharyngeal cross-sectional areas in males and females at three lung volumes: TLC, 50% of vital capacity (VC), and RV. In males, pharyngeal areas (means +/- SD) were 6.4 +/- 1.3 cm2 at TLC, 5.4 +/- 0.9 cm2 at 50% VC, and 4.1 +/- 0.8 cm2 at RV. In females, pharyngeal areas were 4.8 +/- 0.6 cm2 at TLC, 4.2 +/- 0.5 cm2 at 50% VC, and 3.7 +/- 0.6 cm2 at RV. The difference in area between males and females was statistically significant at TLC and 50% VC but not at RV. However, when the pharyngeal cross-sectional area was normalized for body surface area, this difference was not significant. In males there was a negative correlation of pharyngeal area with age. We conclude that sex differences in pharyngeal area are related to body size, pharyngeal area shows a similar variation with lung volumes in males and females, and in males pharyngeal area reduces with age.

Adult↗

Lung volume dependence of esophageal pressure in the neck.

There is conflicting evidence in the literature regarding tissue pressure in the neck. We studied esophageal pressure along cervical and intrathoracic esophageal segments in six healthy men to determine extramural pressure for the cervical and intrathoracic airways. A balloon catheter system with a 1.5-cm-long balloon was used to measure intraesophageal pressures. It was positioned at 2-cm intervals, starting 10 cm above the cardiac sphincter and ending at the cricopharyngeal sphincter. We found that esophageal pressures became more negative as the balloon catheter moved from intrathoracic to cervical segments, until the level of the cricopharyngeal sphincter was reached. At total lung capacity, esophageal pressures were -10.5 +/- 2.9 (SE) cmH2O in the lower esophagus, -18.9 +/- 3.0 just within the thorax, and -21.3 +/- 2.73 within 2 cm of the cricopharyngeal sphincter. The variation in mouth minus esophageal pressure with lung volume was similar in cervical and thoracic segments. We conclude that the subatmospheric tissue pressure applied to the posterior membrane of the cervical trachea results in part from transmission of apical pleural pressure into the neck. Transmural pressure for cervical and thoracic tracheal segments is therefore similar.

Adult↗

Pharyngeal compliance in snoring subjects with and without obstructive sleep apnea.

Recent studies have demonstrated a reduction in pharyngeal cross-sectional area and in upper airway muscle tone in patients with obstructive sleep apnea. These findings suggest that the pharynx in such patients may be more compliant than normal even in the awake state. We have tested this hypothesis by examining the pressure-area relationship of the pharynx in 13 patients and in 7 control subjects. Measurements were performed during wakefulness, with the subject seated, and at a constant lung volume near functional residual capacity. Pharyngeal area was measured by an acoustic reflection technique. Pharyngeal pressure was varied by having the subject perform gradual inspiratory and expiratory isovolume maneuvers against a distally occluded airway while mouth pressure was recorded. Specific compliance of the pharynx was calculated as the fractional change in pharyngeal area between a pressure of 0 and -10 cm H2O and and between 0 and 10 cm H2O. Specific pharyngeal compliance was 0.036 +/- 0.004 cm H2O-1 (mean +/- SE) in the control group and 0.094 +/- 0.012 cm H2O-1 in patients with OSA (p less than 0.01). These findings indicate that patients with obstructive sleep apnea have increased pharyngeal compliance. This abnormality predisposes to pharyngeal occlusion during sleep when negative transmural pressures are generated in the pharynx.

Acoustics↗

Hydrocortisone-induced anaphylaxis.

Two patients with asthma developed an anaphylactic reaction after the intravenous administration of hydrocortisone. In both cases, the reaction included the rapid development of airflow obstruction. Previous reports have suggested that the allergenic component may be hydrocortisone itself, rather than the diluents or preservatives. When administering hydrocortisone, one should be aware of the possibility of such a reaction, even though it is uncommon. Although potentially life-threatening, particularly in an asthma sufferer, this reaction should be reversible with prompt recognition and appropriate management.

Aged↗

Bronchodilator responses to nebulised ipratropium and salbutamol singly and in combination in chronic bronchitis.

A placebo controlled study compared the magnitude and duration of bronchodilatation produced by nebulised salbutamol (5 mg) and ipratropium (0.5 mg) singly and in combination in twenty patients with chronic bronchitis (mean baseline FEV1 was 33% predicted). The onset of action, of both nebulised salbutamol and ipratropium given singly, occurred within 15 min. Both agents produced a similar degree of bronchodilatation. In combination both the magnitude and duration of the bronchodilatation produced was significantly greater than with either agent alone.

Aged↗

Assessment of the clinical usefulness of nebulised ipratropium bromide in patients with chronic airflow limitation.

The effect of adding nebulised ipratropium bromide to bronchodilator treatment was studied in 20 patients with severe chronic airflow limitation. Maintenance theophylline with or without a steroid preparation was continued and comparison made between placebo, nebulised salbutamol, and a combination of nebulised salbutamol and ipratropium. Although the mean FEV1 values showed the combination to produce a small but significant increase in peak bronchodilatation over the effect of salbutamol alone, there were eight patients in whom no clinically useful improvement occurred. The remaining 12 patients did obtain clinically useful improvement in the magnitude or the duration of bronchodilatation (or both) as a result of the added ipratropium. The conclusion is that individual patients with chronic airflow limitation responded to the addition of nebulised ipratropium bromide in a variable way. Patients who could obtain additional benefit from ipratropium need to be identified by an appropriate reversibility study before its inclusion in their bronchodilator treatment.

Aerosols↗

Pharyngeal and glottic changes following methacholine challenge in normal subjects.

Recent evidence indicates that some normal subjects exhibit glottic narrowing following experimentally induced bronchospasm. Similar findings have been observed during episodes of bronchospasm in asthmatics. The exact mechanism of this effect is unknown but it is thought to occur as part of a generalized reflex response associated with constriction of intrapulmonary airways. We tested the hypothesis that in addition to the glottic changes, coincident with intrapulmonary airway constriction which occurred after inhalation of methacholine, the pharynx would show similar changes. Pharyngeal and glottic cross-sectional areas were measured using the acoustic reflection technique in seven healthy subjects before and after inhalation of metacholine. Before methacholine, pharyngeal and glottic areas (mean +/- SE) were 5.0 +/- 0.2 cm2 and 2.4 +/- 0.3 cm2 respectively. After inhalation of methacholine, these areas were reduced to 4.6 +/- 0.3 cm2 and 1.9 +/- 0.3 cm2 respectively (p less than 0.05). We conclude that inhalation of methacholine induces similar reductions in glottic and pharyngeal areas. The role of local or reflex mechanisms accounting for this reduction remains unclear.

Adult↗