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Biomedical subjects

A F Wilson

Publications and source records attributed to A F Wilson.

At least 19 recordsLinked to original sources

Tidal breath flow-volume curves in obstructive sleep apnea.

Because of the gravitational position during sleep and the associated relaxed state, we hypothesized that passive expiration in the supine position might reflect upper airway pathophysiology in obstructive sleep apnea (OSA). We prospectively enrolled and tested 92 subjects with several clinical conditions. Maximal comfort and relaxation during expiration was achieved by connecting subjects to a ventilator via a mouthpiece. An initial respiratory rate of 16 breaths/min and tidal volume of 10 ml/kg were selected. Fine adjustments were then made to achieve maximal subject relaxation. Using this method, we obtained reproducible tidal breath flow-volume curves (TBFVC). Testing was performed in both sitting and supine positions. Standard pulmonary function tests, including spirometry and lung volume measurements, were also obtained in both sitting and supine positions. Of 86 patients who could be evaluated, 12 (60%) of 20 subjects with documented OSA (respiratory disturbance index: mean, 64.8; range, 10 to 120.5) demonstrated a positional change in the terminal portion of the TBFVC; 10 (32%) of 31 with a history of snoring also tested positive, but only three (9%) of 35 subjects with no OSA, by polysomnography (n = 8) or questionnaire (n = 27), demonstrated such a positional change. This positional change in TBFVC, which was significantly more frequent in subjects with OSA, could not be attributed to any measurable pulmonary function abnormality or body mass index. We believe this positional change in TBFVC reflects upper airway functional narrowing induced by assumption of supine position and decreasing airflow rates.

Female

Thoracoscopic carbon dioxide laser treatment of bullous emphysema.

A new technique of thoracoscopic laser ablation of pulmonary bullae suitable for patients with multiple bullae and diffuse emphysema was developed and assessed in 22 patients. 20 of 22 patients survived. Pre-operative and postoperative functional evaluation is available for the 11 patients followed up for more than a month; at 1 to 3 months postoperatively there were increases in FVC (mean 2.0 litres pre-operatively to 2.7 litres postoperatively, p less than 0.001), in FEV1 (0.74 to 1.06 litres, p = 0.01), and in maximum exercise treadmill times (5.4 min to 8.0 min, p less than 0.01). Postoperative air leaks lasted a mean of 13 days and usually resolved spontaneously. Other complications were bleeding (1 patient) and unilateral acute lung injury (1 patient). These results suggest that selected patients with diffuse emphysema and pulmonary bullae may benefit from thoracoscopic carbon dioxide laser ablation.

Cysts

Corticotropin releasing hormone and gonadotropin secretion in physically active males after acute exercise.

Plasma concentrations of corticotropin releasing hormone (CRH) and the serum concentrations of luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone, adrenocorticotropic hormone (ACTH) and cortisol were measured in seven physically active males after acute exercise on a treadmill using the Bruce protocol. Measurements were made in the basal pre-exercise state, immediately after exercise, and at 30-min intervals for 3 h after exercise. Serum LH concentrations declined following exercise reaching nadir values between 60 and 180 min after exercise (90 min post exercise in the group). The nadir values in individual volunteers were significantly lower than both the baseline and post-exercise levels. This fall in serum LH concentration appeared to follow a slight but significant elevation of the plasma concentration of CRH which reached peak levels when measured immediately post exercise. Plasma ACTH concentrations paralleled the rise in CRH, but fell to undetectable levels of below 13.8 nmol.l-1 (less than 5 ng.l-1) 60 min after exercise. Plasma cortisol concentrations peaked approximately 30 min after the rise in ACTH, after which they gradually declined to baseline levels. Plasma testosterone concentrations paralleled the concentrations of LH. The data suggest that CRH, on the basis of its previously described gonadotropin-depressant property, may be the hormone involved in the exercise-mediated decline in serum LH. Alternatively, some as yet unidentified factor(s), may be involved in producing the altered concentrations of both LH and CRH.

Adrenocorticotropic Hormone

Effect of canister temperature on performance of metered-dose inhalers.

We studied the effects of ambient temperatures between 0 degrees C and 42 degrees C in an anatomically realistic model of the upper airway ventilated with warm, moist air. Metered-dose inhalers of metaproterenol maintained at the experimental temperatures were activated in the mouth of the model at the onset of inspiration. We measured the amount of drug released and that which was able to penetrate the model at each temperature. At low canister temperatures considerably more drug was released than at higher temperatures. However, at higher temperatures much more drug was able to traverse the upper airway, raising lower airway deposition from 17.7% at 4 degrees C to 32.2% at 37 degrees C. Aerosol size became progressively smaller as temperature was raised: mass median diameter (MMD) was 3.65 microns at 0 degrees C and 2.50 microns at 37 degrees C. These findings are most likely due to greater canister vapor pressures at higher temperatures. We conclude that patients should probably be instructed to prewarm metered-dose inhaler canisters prior to use when canister temperatures are low.

Aerosols

Use of the robust sib-pair method to screen for single-locus, multiple-locus, and pleiotropic effects: application to traits related to hypertension.

Robust sib-pair linkage analysis can be used as a screening tool in the search for the potential involvement of single-loci, multiple-loci, and pleiotropic effects of single loci underlying phenotypic variation. Four large families were each ascertained through one adult white male with essential hypertension. The robust sib-pair method was used to screen these families for evidence of linkage between 39 quantitative traits related to hypertension and 25 genetic marker loci. All traits were analyzed on the untransformed, square-root and log-transformed scales. Among other findings, there is a suggestion of linkage between the 6-phosphogluconate dehydrogenase locus on chromosome 1p36 and mean fifth-phase diastolic blood pressure. There may also be linkage between the following markers and traits: the adenylate kinase-1 marker and/or the Lewis blood group marker and the traits height, weight, and biacromial breadth; the glyoxylase I marker and the traits upper-arm circumference and suprailiac skinfold thickness; the ABO blood group and adenylate kinase-1 markers on chromosome 9q34 and the third component of complement marker on chromosome 19p13 and dopamine-beta-hydroxylase; and the P1 blood group and the traits weight and 1-h postload serum glucose level.

Alleles

Evidence for mendelian inheritance in the pathogenesis of lung cancer.

Segregation analyses that allowed for variable age of onset of lung cancer and smoking history were performed on 337 families, each ascertained through a lung cancer proband. Results indicated compatibility of the data with mendelian codominant inheritance of a rare major autosomal gene that produces earlier age of onset of the cancer. Segregation at this putative locus could account for 69% and 47% of the cumulative incidence of lung cancer in individuals up to ages 50 and 60, respectively. The gene was involved in only 22% of all lung cancers in persons up to age 70, a reflection of an increasing proportion of noncarriers succumbing to the effects of long-term exposure to tobacco.

Adult

Stepwise oligogenic segregation and linkage analysis illustrated with dopamine-beta-hydroxylase activity.

A stepwise oligogenic method is developed that can be used to adjust the phenotype of a quantitative trait for the effects of a previously identified single-locus component. This method assumes that a single-locus component can be adequately identified through the use of segregation and/or linkage analysis under a 1-locus model and that the variation due to that locus can be removed from the phenotype leaving a residual that can be parameterized in terms of an additional single-locus component. Segregation and/or linkage analysis can then be used in an attempt to identify an additional single-locus component in the residual phenotype. This stepwise process can be repeated until no further single-locus effects are identified. The method is illustrated using family data on the specific activity of dopamine-beta-hydroxylase (DBH), which a number of studies have suggested may be due either to the combined effects of single-locus and multifactorial components or to the combined effects of 2 loci.

Crossing Over, Genetic

Treatment of refractory Parkinson's disease with adrenal medullary autografts utilizing two-stage surgery.

Treatment of refractory PD with autologous adrenal medullary implants utilizing two-stage surgery warrants further investigation. This transplantation technique is associated with prolonged transplant area BBB disruption which may require a change in medical treatment strategies including the withdrawal of peripheral dopa decarboxylase inhibitors and possible intravenous or intraventricular dopamine therapy. Of 5 patients receiving adrenal medullary transplants, 3 have demonstrated varying degrees of clinical improvement which has persisted for the duration of the study. The positive correlation between clinical outcome and caudate function (i.e., 6-fluorodopa PET scans) suggests a positive influence of the transplantation procedure on the diseased striatum. Whether or not the grafted tissue remains viable for an extended period is currently being investigated utilizing 6-FDG-PET studies. Because of the presence of persistent BBB disruption, we surmise that at least viability of implanted fenestrated adrenal medullary capillaries exists. We conclude that this prolonged leakage is the result of the implanted tissue rather than the cavitation procedure as prolonged BBB disruption was not witnessed in a control group of patients with post-traumatic cerebral contusions or in Parkinson's patients subjected to thalamotomies. Whether two-stage surgery results in increased graft viability, and host neuronal sprouting, leading to prolonged clinical improvement and slowing the progression of PD awaits continued longitudinal (greater than 24 months) studies.

Adrenal Medulla

Dose-response effects of two sizes of monodisperse isoproterenol in mild asthma.

The dose-response effect of monodispersed isoproterenol of two different sizes (diameters 2.5 and 5 microns) was examined in eight mild asthmatic subjects (baseline FEV, 81.5% of predicted). Pulmonary and cardiovascular variables were measured before and following 1, 2, 4, 8, and 16 cumulative min of aerosol inhalation. Subjects inhaled 1 to 30 micrograms (2.5-microns particles) or 2 to 50 micrograms (5-microns particles) of isoproterenol. Pulmonary but not cardiac responses were significantly greater for the 2.5-microns particles as compared to equivalent doses of 5-microns particles. Pulmonary dose-related response differences were particularly marked for variables associated with small airway function (FEF25-75 and FEF75-85). These findings suggest that small particles penetrate more deeply into the lung and thereby more effectively dilate small airways and that small amounts of appropriately sized inhaled bronchodilator may produce considerable therapeutic effects.

Adult

A new method for measurement of airway occlusion pressure.

Airway occlusion pressure correlates with central respiratory drive. The airway occlusion pressure (P0.1) may be an excellent predictor of the ability of patients with obstructive lung disease to wean from mechanical ventilation. We describe a new method for measuring P0.1 using digitized signals generated from standard respiratory equipment and a computer program to automatically determine P0.1 values. The accuracy of this new method was tested by comparison with standard analog recorder methods using a mechanical lung model, in ventilated patients in an intensive care unit, and in normal volunteers. In all settings, excellent correlation was obtained between P0.1 measurements by the digital Servo and standard analog methods (r = 0.99). This new method permits accurate and automatic determination of P0.1 in ventilated patients using standard respiratory equipment. The rapid response and ease of use of this method should enable evaluation of a number of physiologic variables involved in respiratory control in ventilated and nonventilated patients.

Airway Resistance

Thoracoscopic treatment of spontaneous pneumothorax using carbon dioxide laser.

In an effort to improve the success rate of the previously described thoracoscopic electrocautery ablation technique of spontaneous pneumothorax, the carbon dioxide laser was evaluated in 12 patients. The recurrent (5 patients) or persistent (7 patients) spontaneous pneumothoraces were caused by rupture of (1) blebs in 6 patients, (2) intrapulmonary apical type II bullae in 3 patients, and (3) diffuse bullous emphysema, type III, in 3. The air leaks were successfully sealed in all but 1 patient with ruptured type II bulla. Surgical specimen from this single failure suggested that the entire inner lining of the bullae must be thermocoagulated. This technical modification led to successful outcome in 2 subsequent cases. With the use of carbon dioxide laser, it was possible to treat not only small blebs but all types of bullae causing spontaneous pneumothorax. Laser thoracoscopy is effective and safe in treating spontaneous pneumothorax.

Adolescent

Linkage analysis of depression spectrum disease.

As part of a study of the possible subgroups of unipolar affective disease, 27 families were ascertained as depression spectrum disease (DSD) families. The purpose of this study was an investigation of the linkage relationships between DSD and 30 genetic markers using the robust sib-pair and lod-score methods. Using the sib-pair methods, evidence for linkage was found with orosomucoid (ORM) on chromosome 9q (p = 0.006), regardless of whether only individuals with unipolar depression, alcoholism, or antisocial personality were considered to be affected, or whether individuals with any psychiatric disorder were considered to be affected. Weak evidence of linkage with ORM was corroborated using lod-score methods when a narrow definition of depression spectrum disease was used, although stronger evidence of linkage was found with ORM when any psychiatric disorder was considered to be affected. The maximum lod-score for ORM was 1.68 at a male recombination fraction of 0.23 and a female recombination fraction of 0.01.

Adult

Linkage analysis of pure depressive disease.

In a study of the subgroups of unipolar affective disease, 13 families were ascertained as pure depressive disease (PDD) families. Here we investigate linkage relationships between PDD and 30 genetic markers in these families. Using the robust sib-pair method of linkage analysis, evidence for possible linkage or association was found with five loci: the ABO and MNS blood groups, immunoglobulin kappa (IGK), proline rich parotid salivary protein (PR) and glyoxylase-1 (GLO1). Weak evidence of linkage with ABO was supported using the lod score method of analysis. The maximum lod score between PDD and ABO was 1.42 at a male recombination fraction of 0.09 and a female recombination fraction of 0.03. When these results from the sib-pair analysis were combined with the results from two previous sib-pair studies on PDD, the ABO, MNS and IGK loci were found to be significant (P = 0.05, P = 0.005, P = 0.05, respectively, not allowing for multiple tests).

Adolescent

Double-blind cross-over placebo controlled study of flunarizine in patients with therapy resistant epilepsy.

Twenty-five patients with long-standing therapy resistant epilepsy were studied in an eight-month double-blind cross-over add-on trial with a daily dose of 15 mg flunarizine. In five patients the seizure frequency decreased 50% or more. The mean seizure frequency reduction in the patients on flunarizine was 35%. Particularly the control of secondary generalized seizures improved. Flunarizine did not significantly alter the plasma levels of the regular anticonvulsant drugs. Minimal adverse side effects were reported equally in the flunarizine and the placebo group. In three patients depressive symptoms improved and two patients became free of postictal headaches. Flunarizine appears to be a safe adjuvant anticonvulsant.

Adolescent