Biomedical subjects

J A Wilson

Publications and source records attributed to J A Wilson.

At least 55 records · Page 3Linked to original sources

PubMed2001

Female gender exacerbates respiratory depression in leptin-deficient obesity.

Obese females are less predisposed to sleep-disordered breathing and have higher serum leptin levels than males of comparable body weight. Because leptin is a powerful respiratory stimulant, especially during sleep, we hypothesized that the elevated leptin level is necessary to maintain normal ventilatory control in obese females. We examined ventilatory control during sleep and wakefulness in male and female leptin-deficient obese C57BL/6J-Lep(ob) mice, wild-type C57BL/6J mice with dietary-induced obesity and high serum leptin levels, and normal weight wild-type C57BL/6J mice. Both male and female C57BL/6J-Lep(ob) mice had depressed hypercapnic ventilatory response (HCVR) in comparison with wild-type animals. In comparison with male C57BL/6J-Lep(ob) mice, female C57BL/6J-Lep(ob) mice had reduced HCVR and respiratory drive (a ratio of tidal volume to inspiratory time) both during non-rapid eye movement (NREM) sleep and wakefulness. In contrast, the HCVR did not differ between sexes in wild-type mice during NREM sleep and wakefulness, but was lower in females during REM sleep. Thus, leptin deficiency in female obesity is even more detrimental to hypercapnic ventilatory control during wakefulness and NREM sleep than in obese, leptin-deficient males.

Animals↗

PubMed2001

Is voice therapy an effective treatment for dysphonia? A randomised controlled trial.

OBJECTIVES: To assess the overall efficacy of voice therapy for dysphonia. DESIGN: Single blind randomised controlled trial. SETTING: Outpatient clinic in a teaching hospital. PARTICIPANTS: 204 outpatients aged 17-87 with a primary symptom of persistent hoarseness for at least two months. INTERVENTIONS: After baseline assessments, patients were randomised to six weeks of either voice therapy or no treatment. Assessments were repeated at six weeks on the 145 (71%) patients who continued to this stage and at 12-14 weeks on the 133 (65%) patients who completed the study. The assessments at the three time points for the 70 patients who completed treatment and the 63 patients in the group given no treatment were compared. MAIN OUTCOME MEASURES: Ratings of laryngeal features, Buffalo voice profile, amplitude and pitch perturbation, voice profile questionnaire, hospital anxiety and depression scale, clinical interview schedule, SF-36. RESULTS: Voice therapy improved voice quality as assessed by rating by patients (P=0.001) and rating by observer (P<0.001). The treatment effects for these two outcomes were 4.1 (95% confidence interval 1.7 to 6.6) points and 0.82 (0.50 to 1.13) points. Amplitude perturbation showed improvement at six weeks (P=0.005) but not on completion of the study. Patients with dysphonia had appreciable psychological distress and lower quality of life than controls, but voice therapy had no significant impact on either of these variables. CONCLUSION: Voice therapy is effective in improving voice quality as assessed by self rated and observer rated methods.

Adolescent↗

PubMed2001

Vaccine potential of Ebola virus VP24, VP30, VP35, and VP40 proteins.

Previous vaccine efforts with Ebola virus Zaire (EBOV-Z) emphasized the potential protective efficacies of immune responses to the surface glycoprotein and the nucleoprotein. To determine whether the VP24, VP30, VP35, and VP40 proteins are also capable of eliciting protective immune responses, these genes were expressed from alphavirus replicons and used to vaccinate BALB/c and C57BL/6 mice. Although all of the VP proteins were capable of inducing protective immune responses, no single VP protein protected both strains of mice tested. VP24, VP30, and VP40 induced protective immune responses in BALB/c mice, whereas C57BL/6 mice survived challenge only after vaccination with VP35. Passive transfer of immune sera to the VP proteins did not protect unvaccinated mice from lethal disease. The demonstration that the VP proteins are capable of eliciting protective immune responses to EBOV-Z indicates that they may be important components of a vaccine designed to protect humans from Ebola hemorrhagic fever.

Animals↗

PubMed2001

Modulation of gene expression by androgen and oestrogens in the testis and prostate of the adult rat following androgen withdrawal.

Androgens are important for the structural and functional integrity of the testis and the prostate and this may in part be mediated by the aromatisation of testosterone to oestradiol. The aim of the present study was to establish an in vivo model that would allow the identification of genes, the expression of which was regulated acutely by androgen and/or oestrogen in the male reproductive system. In rats in which the Leydig cells were ablated by administration of ethane dimethane sulfonate (EDS) 6 days earlier, testosterone esters (T) were administered from day 0 (To), and additional animals were administered either T, 17beta-oestradiol benzoate (EB) or diethylstilbestrol (DES) for 1 or 4 h on day 6 after EDS-treatment. Nuclear immunoexpression of the androgen receptor (AR) was reduced or absent from the testis but unaffected in the ventral prostate following these treatments. ERbeta immunoexpression in these tissues was unchanged. Northern blot analysis showed that EB and DES as well as T administration 4 h earlier could modulate mRNA expression of two androgen-responsive genes, C3 and SGP-2, in the prostate. The co-administration of T or EB with the AR antagonist, flutamide, or with the ER antagonist, ICI 182,780 (ICI), did not block the suppression of SGP-2 mRNA expression by T or EB. In contrast, the upregulation of C3 mRNA expression by T was successfully antagonised by both flutamide and by ICI. A preliminary evaluation of the expression of three Sertoli cell and five germ cell mRNAs revealed that their expression was not steroid regulated. Our results support the hypothesis that the action of testosterone in the male reproductive system may in part be mediated by its conversion to oestradiol. This in vivo model should prove of value in future studies to identify androgen and oestrogen regulated genes in the male reproductive system.

Androgen-Binding Protein↗

PubMed2001

Clinical evaluation of a new recombinant antigen-based cytomegalovirus immunoglobulin M immunoassay in liver transplant recipients.

BACKGROUND: Human cytomegalovirus (CMV) is a significant cause of morbidity and mortality among transplant recipients. Monitoring transplant recipients by CMV IgM serology has been questioned by several studies due to the reported insensitivity of serologic tests relative to antigen detection methods. METHODS: In this retrospective study, we have evaluated the performance of the new recombinant antigen-based Abbott AxSYM CMV IgM assay and compared it with CMV culture technique in a cohort of 40 liver transplant recipients who did not receive antiviral prophylaxis. RESULTS: The sensitivity, specificity, and positive and negative predictive values for detection of CMV disease by the AxSYM CMV IgM assay were 90.0%, 60.0%, 69.2%, and 85.7%, respectively, and by culture the values were 100%, 55.0%, 69.0%, and 100%, respectively. Detection of CMV IgM occurred before or at the time of CMV disease in only R+ recipients. CONCLUSION: Although this assay is a sensitive test for CMV-specific IgM, detection of CMV IgM preceded detection of virus by culture in patients only when the liver transplant recipient was CMV immune before transplantation (R+).

Antibodies, Viral↗

PubMed2001

Stereotactic proton beam therapy of skull base meningiomas.

PURPOSE: To review outcomes for patients with skull base meningiomas treated using the stereotactic proton beam at the National Accelerator Center (NAC), Republic of South Africa. METHODS AND MATERIALS: Since 1993, 27 patients with intracranial meningiomas have been treated stereotactically with protons at NAC. Of those, 23 were located on the skull base, were large or had complex shapes, and were treated with radical intent. Both stereotactic radiotherapy (SRT, 16 or more fractions) and hypofractionated stereotactic radiotherapy (HSRT, 3 fractions) were used. Eighteen patients underwent proton HSRT, while 5 patients were treated with SRT. The mean target volume for the HSRT group was 15.6 cm(3) (range 2.6-63 cm(3)). The mean ICRU reference dose was 20.3 cobalt Gray equivalent (CGyE), and the mean minimum planning target dose was 16.3 CGyE. The mean clinical and radiologic follow-up periods were 40 and 31 months respectively. The mean volume in the SRT group was 43.7 cm(3), with ICRU reference doses ranging from 54 CGyE in 27 fractions to 61.6 CGyE in 16 fractions. RESULTS: In the HSRT group, 16/18 (89%) of patients remained clinically stable or improved, while 2/18 (11%) deteriorated. Radiologic control was achieved in 88% of patients, while 2 patients had a marginal failure. Among the 5 SRT patients, 2 were clinically better, and 3 remained stable. All SRT patients achieved radiologic control. Three patients (13%), 2 of them in the HSRT group, suffered permanent neurologic deficits. Analyzing different dose/fractionation schedules, an alpha/beta value of 3.7 Gy for meningiomas is estimated. CONCLUSION: Proton irradiation is effective and safe in controlling large and complex-shaped skull base meningiomas.

Adult↗

PubMed2001

Ebola virus: the search for vaccines and treatments.

Ebola viruses belong to the family Filoviridae, which are among the most virulent infectious agents known. These viruses cause acute, and frequently fatal, hemorrhagic fever in humans and nonhuman primates. Currently, no vaccines or treatments are available for human use. This review describes Ebola viruses, with a particular focus on the status of research efforts to develop vaccines and therapeutics and to identify the immune mechanisms of protection.

Animals↗

PubMed2001

Nasal septal surgery: evaluation of symptomatic and general health outcomes.

Although septoplasty and submucous resections are common procedures, there have been very few studies on the outcome of nasal septal surgery. This prospective study of two hundred patients undergoing septal surgery used the Fairley nasal symptom score, the Nottingham health profile, a general health questionnaire and clinical examination of nasal cavities to assess the outcome. A wide range of baseline severity scores was observed. Almost 40% of patients failed to attend for review. Analysis of the outcomes in the remaining 121 patients revealed significant improvement in (a) nasal obstruction in 74%, (b) facial pain in 72%, and (c) catarrh in 64% of patients. There was a lack of correlation between observed postoperative reduction in the number of nasal septal areas deviated and improvement in nasal obstruction. The Nottingham health profile and general health questionnaire scores remained unchanged in a large majority of patients. Postoperative improvement in nasal obstruction was independent of grade of surgeon or concomitant lateral nasal wall surgery. The principal benefits of septal surgery relate to improvement in nasal symptoms. The generic quality-of-life measures such as the Nottingham health profile and general health questionnaire did not show significant improvement in quality of life. Our results support the use of disease-specific instruments to evaluate the outcome of septal surgery.

Adolescent↗

PubMed2001

Expression of MUC1 and MUC2 glycoproteins in laryngeal cancer.

The aim of this study was to examine the expression of MUC1 and MUC2 glycoproteins in laryngeal cancer and to determine if mucin expression is related to prognosis. The study included laryngeal specimens from 57 patients comprising of 36 laryngeal carcinomas and 21 normal controls. High MUC1 expression was found in both carcinomas and normal control groups (P = 0.689, Fisher's exact test). High levels of MUC2 expression were only detected in carcinomas versus controls (P = 0.009, Fisher's exact test). Using multivariate analysis neither MUC1 nor MUC2 expression significantly related to survival. MUC1 expression however, did correlate with T stage. Advanced T stage was associated with prognosis (P = 0.001).

Adult↗

PubMed2001

Pattern of ambulatory pharyngo-oesophageal motility and pH-metry in healthy volunteers.

Oesophago-pharyngeal reflux is widely accepted as an aetiological factor in many laryngeal and lower respiratory tract diseases. This study aims to establish normal reference ranges for pharyngo-oesophageal pH and pressure. Twenty-five asymptomatic healthy volunteers underwent ambulatory pharyngo-oesophageal pressure and pH-metry. Acid exposure times were very low. Only one subject showed any evidence of oesophago-pharyngeal reflux during recumbency. Two distinct upper oesophageal sphincter pressure patterns were observed during recumbency-one with episodic dry swallows and moderate tonic pressures, the other with almost complete manometric quiescence. Negative results, i.e. the exclusion of abnormal cervical reflux, appear to be more achievable than quantifiable positive results, but this is not absolutely clear from our results. Categorisation of an individual as having abnormal upper pH-metry requires use of a synchronous pharyngeal probe. pH-metry is likely to be of value in establishing the role of reflux in relation to laryngeal or respiratory disease.

Adult↗

PubMed2001

The development of a General Nasal Patient Inventory.

Most available clinical outcome measures for rhinology patients relate to specific nasal disease or general quality of life. Fairley's validated 12-item questionnaire measures general nasal symptoms, but is a 'physician-derived' clinical tool and may not reflect all the problems that rhinology patients experience. Our aims were to develop a patient-orientated questionnaire, representing the concerns of a large number of rhinology patients, called the General Nasal Patient Inventory (GNPI) and compare this with the Fairley nasal questionnaire (FNQ). The GNPI was developed from the open-ended problem lists of 211 rhinology patients, from the 45 most frequent complaints. Both questionnaires were then administered to 153 general rhinology patients and the results compared. The highest-ranking items for each questionnaire were different, but the total scores were highly correlated (r = 0.79, P < 0.0001). Factor analysis showed six factors to account for 75% of FNQ variance and 18 factors for 78% of GNPI variance. The 45-item GNPI, the first patient-derived, comprehensive nasal questionnaire could be a time-saving tool in rhinology clinics and more sensitive to change after intervention than other available measures.

Adolescent↗

PubMed2001

Altered MUC1 and MUC2 glycoprotein expression in laryngeal cancer.

The purpose of this study was to determine whether mucin expression is altered in laryngeal cancer. MUC1 and MUC2 mucin expression was examined in biopsy specimens from 80 patients that comprised 23 laryngeal dysplasias, 36 laryngeal carcinomas, and 21 normal larynx control specimens. High MUC1 expression was found in all 3 groups (P = 0.689, Fisher exact test). However, significantly higher levels of MUC2 expression were detected in carcinomas compared with dysplasias and control specimens (P = 0.009, Fisher exact test). Altered MUC2 expression may be an important step in carcinogenesis in laryngeal cancer.

Adult↗

PubMed2001

Pharyngoesophageal pressure monitoring in sleep apnea syndrome.

OBJECTIVES: This study tests the sensitivity and the specificity of overnight pharyngoesophageal pressure measurement for identification and classification of obstructive sleep apnea (OSA). METHODS: Fifty-nine snoring patients undergoing polysomnography were invited to have simultaneous pharyngoesophageal manometry. We used a soft silicone catheter with 4 microtip pressure sensors at different levels. RESULTS: The apnea hypopnea indexes (AHIs) measured by the 2 methods were highly correlated (r = 0.971). Manometry was 100% sensitive and specific in excluding OSA and identifying severe OSA. It was 90% sensitive in identifying moderate OSA and 80% sensitive in identifying mild OSA. CONCLUSION: Overnight ambulatory pharyngoesophageal manometry is a reliable tool for the exclusion of OSA and identification of severe OSA. It has additional advantages of localizing the level of obstruction and identifying the upper airway resistance syndrome and can be performed at home. It is cost-effective when compared with polysomnography and may aid in treatment selection for individual patients.

Adult↗

PubMed2001

The clinical features of functional dysphonia.

OBJECTIVE: This report aims to study the prevalence of features of laryngeal muscle tension in a population of patients with functional dysphonia (FD) and nondysphonic control subjects. STUDY DESIGN: Prospective control-blinded, cross-sectional study. METHODS: We reported on a prospective control-blinded, cross-sectional study of the prevalence of the six features described by Van Lawrence and the six features incorporated in the Morrison-Rammage classification. A senior laryngologist and senior speech pathologist independently rated sound-free, random-sequence video laryngoscopies of 51 patients with FD and 52 nondysphonic control subjects. Assessments were made of the presence or absence of the 12 laryngoscopic features of laryngeal dysfunction, and an overall rating made of the vocal technique as "normal" or "abnormal." RESULTS: More than 60% of the control population demonstrated 1 or more of the 12 features of hyperfunction. There was no significant difference in the prevalence of the six Van Lawrence features, the six Morrison-Rammage features, or the total number of abnormal features between patients with FD and control subjects. On overall assessment, both assessors noted a high prevalence (50% and 36%, respectively) of abnormal vocal technique in the control population. There was no statistical difference in the total number of abnormal features observed between patients with FD and control subjects. Positive predictive value calculations showed that the presence of a clinical feature, at best, presented a 75% chance of correctly identifying a patient with FD and, at worst, a 50% chance. CONCLUSION: The laryngoscopy features commonly associated with FD are frequently prevalent in the nondysphonic population and fail to distinguish patients with FD from normal subjects.

Adolescent↗

PubMed2001

Rheolytic catheter and thrombolysis of dural venous sinus thrombosis: a case series.

OBJECTIVE: The high morbidity and mortality rates associated with dural sinus thrombosis may be heightened by a delay in diagnosis, which necessitates prompt and effective treatment. Traditional treatment consists of the initiation of systemic anticoagulation with heparin and, more recently, regional thrombolysis with direct endovascular infusion of thrombolytic agents. We report our experience in a series of five patients in whom we accomplished mechanical clot lysis with the combination of a rheolytic device and balloon catheters. METHODS: Five patients with dural sinus thrombosis were treated with a combination of pharmacological and mechanical thrombolysis with the 5-French Angiolet rheolytic catheter (Possis Medical, Minneapolis, MN) and balloon catheters. The success of the procedure was determined by resolution of or improvement in the patient's neurological examination results and imaging features. RESULTS: All five patients demonstrated immediate improvement as observed on imaging studies or in terms of neurological status. Three patients required more than one intervention, and all but one patient continued to improve after the final intervention. Two of the five patients continued to experience mild residual neurological deficits, and two patients experienced complete recovery. The fifth patient had a delayed recurrence of thrombosis that required multiple interventions, and the patient has significant neurological deficits. Navigation of the dural sinuses was possible in all patients with the use of a microcatheter and was possible to a variable degree with the rheolytic catheter. Known complications of the procedures included two pseudoaneurysms at the femoral puncture site. CONCLUSION: Mechanical clot lysis is a powerful technique for immediate restoration of antegrade venous flow in dural sinus thrombosis. In most patients, the superior sagittal sinuses and contralateral transverse sinuses could be accessed with the 5-French rheolytic catheter.

Adult↗

PubMed2001

Protection from Ebola virus mediated by cytotoxic T lymphocytes specific for the viral nucleoprotein.

Cytotoxic T lymphocytes (CTLs) are proposed to be critical for protection from intracellular pathogens such as Ebola virus. However, there have been no demonstrations that protection against Ebola virus is mediated by Ebola virus-specific CTLs. Here, we report that C57BL/6 mice vaccinated with Venezuelan equine encephalitis virus replicons encoding the Ebola virus nucleoprotein (NP) survived lethal challenge with Ebola virus. Vaccination induced both antibodies to the NP and a major histocompatibility complex class I-restricted CTL response to an 11-amino-acid sequence in the amino-terminal portion of the Ebola virus NP. Passive transfer of polyclonal NP-specific antiserum did not protect recipient mice. In contrast, adoptive transfer of CTLs specific for the Ebola virus NP protected unvaccinated mice from lethal Ebola virus challenge. The protective CTLs were CD8(+), restricted to the D(b) class I molecule, and recognized an epitope within amino acids 43 to 53 (VYQVNNLEEIC) in the Ebola virus NP. The demonstration that CTLs can prevent lethal Ebola virus infection affects vaccine development in that protective cellular immune responses may be required for optimal protection from Ebola virus.

Adoptive Transfer↗

PubMed2001

A model of sleep-disordered breathing in the C57BL/6J mouse.

To investigate the pathophysiological sequelae of sleep-disordered breathing (SDB), we have developed a mouse model in which hypoxia was induced during periods of sleep and was removed in response to arousal or wakefulness. An on-line sleep-wake detection system, based on the frequency and amplitude of electroencephalograph and electromyograph recordings, served to trigger intermittent hypoxia during periods of sleep. In adult male C57BL/6J mice (n = 5), the sleep-wake detection system accurately assessed wakefulness (97.2 +/- 1.1%), non-rapid eye movement (NREM) sleep (96.0 +/- 0.9%) and rapid eye movement (REM) sleep (85.6 +/- 5.0%). After 5 consecutive days of SDB, 554 +/- 29 (SE) hypoxic events were recorded over a 24-h period at a rate of 63.6 +/- 2.6 events/h of sleep and with a duration of 28.2 +/- 0.7 s. The mean nadir of fraction of inspired O(2) (FI(O(2))) on day 5 was 13.2 +/- 0.1%, and 137.1 +/- 13.2 of the events had a nadir FI(O(2)) <10% O(2). Arterial blood gases confirmed that hypoxia of this magnitude lead to a significant degree of hypoxemia. Furthermore, 5 days of SDB were associated with decreases in both NREM and REM sleep during the light phase compared with the 24-h postintervention period. We conclude that our murine model of SDB mimics the rate and magnitude of sleep-induced hypoxia, sleep fragmentation, and reduction in total sleep time found in patients with moderate to severe SDB in the clinical setting.

Animals↗

PubMed2001

Predictors of successful extubation in neurosurgical patients.

A respiratory therapist-driven weaning protocol incorporating daily screens, spontaneous breathing trials (SBT), and prompts to caregivers has been associated with superior outcomes in mechanically ventilated medical patients. To determine the effectiveness of this approach in neurosurgical (NSY) patients, we conducted a randomized controlled trial involving 100 patients over a 14-mo period. All had daily screens of weaning parameters. If these were passed, a 2-h SBT was performed in the Intervention group. Study physicians communicated positive SBT results, and the decision to extubate was made by the primary NSY team. Patients in the Intervention (n = 49) and Control (n = 51) groups had similar demographic characteristics, illness severity, and neurologic injuries. Among all patients, 87 (45 in the Control and 42 in the Intervention group) passed at least one daily screen. Forty (82%) patients in the Intervention group passed SBT, but a median of 2 d passed before attempted extubation, primarily because of concerns about the patient's sensorium (84%). Of 167 successful SBT, 126 (75%) did not lead to attempted extubation on the same day. The median time of mechanical ventilation was 6 d in both study groups, and there were no differences in outcomes. Overall complications included death (36%), reintubation (16%), and pneumonia (9%). Tracheostomies were created in 29% of patients. Multivariate analysis showed that Glasgow Coma Scale (GCS) score (p < 0.0001) and partial pressure of arterial oxygen/fraction of inspired oxygen ratio (p < 0.0001) were associated with extubation success. The odds of successful extubation increased by 39% with each GCS score increment. A GCS score > or = 8 at extubation was associated with success in 75% of cases, versus 33% for a GCS score < 8 (p < 0.0001). Implementation of a weaning protocol based on traditional respiratory physiologic parameters had practical limitations in NSY patients, owing to concerns about neurologic impairment. Whether protocols combining respiratory parameters with neurologic measures lead to superior outcomes in this population requires further investigation.

Adolescent↗