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Biomedical subjects

M Austin

Publications and source records attributed to M Austin.

At least 19 recordsLinked to original sources

Oxygen therapy in the pre-hospital setting for acute exacerbations of chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD), a leading cause of morbidity and mortality in the developed world, is characterised by acute deterioration in symptoms. During these exacerbations, people are prone to developing alveolar hypoventilation, which may be contributed to by the administration of high inspired oxygen concentrations. OBJECTIVES: The objective of the review was to determine the effect of different inspired oxygen concentrations ("high flow" compared to "controlled") in the pre-hospital setting on outcome for people with acute exacerbations of COPD. SEARCH STRATEGY: We searched the Cochrane Airways Group Specialised Register (August 2005), the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 3, 2005), MEDLINE (1966 to August 2005), EMBASE (1980 to wk 32, 2005), CINAHL (1982 to August wk 1, 2005) and reference lists of articles. We also contacted authors of identified RCTs for details of other relevant, published and unpublished studies. SELECTION CRITERIA: Randomised controlled trials comparing oxygen therapy at different concentrations or oxygen therapy versus placebo in the pre-hospital setting for treatment of acute exacerbations of COPD were eligible. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data. MAIN RESULTS: The search identified a total of 741 abstracts, of which 18 were selected as potentially relevant, only two of the 18 studies were randomised controlled trials and eligible for inclusion in the review, but were ongoing and had no data available for analysis. AUTHORS' CONCLUSIONS: No relevant trials have been published to date, so there is no evidence to indicate whether different oxygen therapies in the pre-hospital setting have an effect on outcome for people with acute exacerbations of COPD. There is an urgent need for robust, well-designed randomised controlled trials to investigate the effect of oxygen therapies in the pre-hospital setting for people with acute exacerbations of COPD.

Emergency Medical Services↗

Damage limitation.

Explore the source record for details and available documents.

Extravasation of Diagnostic and Therapeutic Materi↗

Pre-clinical development of cord blood-derived progenitor cell graft expanded ex vivo with cytokines and the polyamine copper chelator tetraethylenepentamine.

BACKGROUND: We have previously demonstrated that the copper chelator tetraethylenepentamine (TEPA) enables preferential expansion of early hematopoietic progenitor cells (CD34+CD38-, CD34+CD38-Lin-) in human umbilical cord blood (CB)-derived CD34+ cell cultures. This study extends our previous findings that copper chelation can modulate the balance between self-renewal and differentiation of hematopoietic progenitor cells. METHODS: In the present study we established a clinically applicative protocol for large-scale ex vivo expansion of CB-derived progenitors. Briefly, CD133+ cells, purified from CB using Miltenyi Biotec's (Bergisch Gladbach, Germany) CliniMACS separation device and the anti-CD133 reagent, were cultured for 3 weeks in a clinical-grade closed culture bag system, using the chelator-based technology in combination with early-acting cytokines (SCF, thrombopoietin, IL-6 and FLT-3 ligand). This protocol was evaluated using frozen units derived from accredited cord blood banks. RESULTS: Following 3 weeks of expansion under large-scale culture conditions that were suitable for clinical manufacturing, the median output value of CD34+ cells increase by 89-fold, CD34+CD38- increase by 30-fold and CFU cells (CFUc) by 172-fold over the input value. Transplantation into sublethally irradiated non-obese diabetic (NOD/SCID) mice indicated that the engraftment potential of the ex vivo expanded CD133+ cells was significantly superior to that of unexpanded cells: 60+/-5.5% vs. 21+/-3.5% CD45+ cells, P=0.001, and 11+/-1.8% vs. 4+/-0.68% CD45+CD34+ cells, P=0.012, n=32, respectively. DISCUSSION: Based on these large-scale experiments, the chelator-based ex vivo expansion technology is currently being tested in a phase 1 clinical trial in patients undergoing CB transplantation for hematological malignancies.

AC133 Antigen↗

The treatment of acute dacryocystitis using laser assisted endonasal dacryocystorhinostomy.

AIMS: To determine whether acute dacryocystitis complicated by abscess formation can be successfully treated using laser assisted endonasal dacryocystorhinostomy. METHODS: A protocol was adopted for the management of acute dacryocystitis presenting to an ophthalmology department. All patients were assessed jointly by an ophthalmologist and otolaryngologist for their suitability for primary internal drainage via a nasal endoscopic approach. All suitable patients during the study period August 1999 to November 2000 were managed by intravenous antibiotics and holmium:YAG laser dacryocystorhinostomy. RESULTS: Nine patients were studied (mean age 72 years (range 38-82 years), three men, six women). A history of chronic epiphora was found in 78% of patients, and recurrent nasolacrimal infections in the same 78%. Resolution of symptoms and signs of acute dacryocystitis occurred in all nine patients. No recurrence of acute dacryocystitis occurred during the median follow up period of 11 months (range 6-31 months). Ostium patency defined as the absence of epiphora and the observation of irrigated lacrimal fluorescein at the ostium was achieved in 67% of patients. Epiphora recurred in 33% of cases. CONCLUSION: Laser assisted endonasal dacryocystorhinostomy is an effective primary treatment in cases of acute dacryocystitis complicated by abscess formation. In addition, pre-existing symptoms of epiphora and recurrent nasolacrimal infections are relieved in the majority of patients.

Abscess↗

Assessment of risk for type 2 diabetes mellitus in a Caribbean population with high diabetes-related morbidity.

Diabetes mellitus is a major cause of morbidity in Trinidad and Tobago. Screening programmes are not incorporated in the health sector and the population at risk remains unaware of the benefits of screening. We investigated the risk of developing Type 2 diabetes mellitus in office workers with one risk factor. Participants were randomly selected from the urban corporate sector in Port of Spain. Fasting capillary blood glucose and the American Diabetes Association (ADA) questionnaire for major diabetes risk factors were used to assess risk. Student pharmacists approached 482 persons, of whom 317 consented to participate (66% response rate). There were 101 (32%) men and 216 (68%) women, 37 (39%) were of African ancestry and 28% each were of East Indian and mixed ancestry. Family history was positive in 54%. Thirty per cent (95) of the volunteers were at risk of developing Type 2 diabetes mellitus (41 men; 54 women). Based on the ADA questionnaire, 82% (78) of volunteers were at high risk for developing Type 2 diabetes mellitus. The ADA risk test and Impaired Fasting Glucose were both positive in 13 (14%) volunteers. In subjects at risk, Body Mass Index (BMI) was > 25 kg/m2 in 74% (78) and the waist/hip ratio was 0.85. Approximately 30% of office staff was at risk of developing diabetes mellitus. The ADA questionnaire is a useful non-invasive measure which pharmacists can use to assess risk for Type 2 diabetes mellitus. The glucometer can be used for risk assessment providing that it is associated with a quality assurance programme and that diagnosis is confirmed with laboratory testing.

Adult↗

A dose- and schedule-finding study of darbepoetin alpha for the treatment of chronic anaemia of cancer.

A multicentre study evaluated the efficacy and safety of darbepoetin alpha administered weekly (QW), every 3 weeks (Q3W), and every 4 weeks (Q4W) to anaemic patients with cancer not concurrently receiving chemotherapy or radiotherapy. The QW portion (n=102) was an open-label, sequential, dose-escalation design; cohorts received darbepoetin alpha QW by subcutaneous (s.c.) injection at 0.5, 1.0, 2.25, or 4.5 micro g kg(-1) week(-1) for 12 weeks. The 12-week placebo-controlled, double-blind Q3W (6.75 micro g kg(-1)) and Q4W (6.75 or 10.0 micro g kg(-1)) schedules (n=86), which enrolled different patients, took place after the QW schedule and were followed by a 12-week, open-label phase. Patients were evaluated for change in haemoglobin end points and red blood cell transfusions, serum darbepoetin alpha concentration, and safety. Selected domains of health-related quality of life (HRQOL) were measured. With QW dosing, at least 70% of each cohort had a haemoglobin increase from baseline of > or =2 g dl(-1) or a concentration > or =12 g dl(-1) (haematopoietic response). In the 4.5 micro g kg(-1) QW cohort, all patients achieved a haematopoietic response (100%; 95% confidence interval (CI)=100, 100). In the Q3W and Q4W schedules, all cohorts had at least 60% of patients who achieved a haematopoietic response. Darbepoetin alpha effectively increases haemoglobin concentration when given QW, Q3W, or Q4W. Less-frequent administration may benefit patients with chronic anaemia of cancer and their caregivers alike.

Aged↗

The effects of single-dose fexofenadine, diphenhydramine, and placebo on cognitive performance in flight personnel.

BACKGROUND: Sedation and functional impairments are side effects associated with the use of first-generation antihistamines that preclude their use in aviation. Selected second-generation antihistamines do not have such side effects and have been proposed for use in aircrew. METHODS: Forty-two healthy naval aviation personnel served as subjects in this double-blind, randomized, placebo-controlled crossover study. Subjective drowsiness, cognitive performance, and vigilance were measured under three conditions: 180 mg fexofenadine (F), 50 mg diphenhydramine (D) as a positive control, or placebo (P). RESULTS: Subjects receiving F vs. D tended to have a faster mean hit reaction time (adjusted mean difference +/- SE, -10.5 +/- 6.8 ms, p = 0.127). Subjects performed faster and better with F vs. D on measures of omission errors and commission errors (p < 0.05). Variable symbol digit coding delayed recall accuracy was better for F vs. D (p = 0.023), and approached significance for shifting attention and divided attention tasks (p = 0.062 and p = 0.057, respectively). Subjects reported significantly more drowsiness (p < 0.005) with D than F. CONCLUSIONS: Diphenhydramine administration resulted in significant psychomotor decrements compared with fexofenadine, while the effects of fexofenadine were similar to placebo. These results provide additional support for the safe use of fexofenadine by aviation personnel.

Administration, Oral↗

Pigment dispersion with elevated intraocular pressure after AcrySof intraocular lens implantation in the ciliary sulcus.

A 45-year-old white woman had phacoemulsification with intraocular lens (IOL) implantation. The surgery was routine except for a linear tear in the posterior capsule; there was no disruption of the anterior vitreous face. After residual soft lens matter was removed, an AcrySof IOL was placed in the ciliary sulcus. One month postoperatively, the patient presented with an intraocular pressure (IOP) of 30 mm Hg and signs of pigment dispersion with 360 degrees of heavy pigmentation of the trabecular meshwork and iris transillumination defects. Intraocular pressure was controlled with a topical beta-blocker. The optic disc appearance and visual field remained normal, but the uniocular hyperpigmentation of the trabecular meshwork was still present. We hypothesize that the sharp square edge of the AcrySof IOL increases the risk of a chafing effect on the posterior iris pigment and advocate that this IOL be placed in the capsular bag and ideally have 360 degrees of protective overlapping of the anterior capsule over the edge of the optic.

Acrylic Resins↗

Antibiotic resistance patterns of group B streptococci in late third-trimester rectovaginal cultures.

OBJECTIVE: Our purpose was to determine the antibiotic sensitivity patterns of rectovaginal group B streptococcal isolates obtained from a heterogeneous obstetric population in the late third trimester. STUDY DESIGN: We performed a prospective observational study of rectovaginal group B streptococcal isolates obtained in the late third trimester during routine screening over a 12-month period. All cultures were prepared in a selective broth medium for 18 to 24 hours before plating onto sheep blood agar. Susceptibility testing of all isolates was performed for ampicillin, cefazolin, clindamycin, erythromycin, penicillin G, and vancomycin with the E-test method. RESULTS: A total of 2111 consecutive rectovaginal cultures were performed in which group B streptococci were isolated from 574 (27.2%) different patients. The "antibiogram" of the susceptible percentage is as follows: vancomycin, 100%; ampicillin, 98.2%; penicillin G, 98.2%; cefazolin, 98.1%; clindamycin, 92%; erythromycin, 81%. Ten isolates (1.8%) demonstrated intermediate susceptibility to both ampicillin and penicillin G. CONCLUSION: Routine susceptibility testing of group B streptococcal isolates collected during pregnancy should be considered because of the emergence of antibiotic resistance among group B streptococcal strains.

Adult↗

GABA transporter-1 mRNA in the prefrontal cortex in schizophrenia: decreased expression in a subset of neurons.

OBJECTIVE: Within the prefrontal cortex of schizophrenic subjects, alterations in markers of gamma-aminobutyric acid (GABA) neurotransmission, including decreased immunoreactivity for the GABA membrane transporter GAT-1, may be most prominent in a subset of inhibitory neurons. In the present study, the authors sought to determine whether the alterations in GAT-1 protein could be attributed to a reduction in GAT-1 mRNA expression. METHOD: Tissue sections containing prefrontal cortex area 9 from 10 matched pairs of schizophrenic and comparison subjects were processed for in situ hybridization histochemistry with (35)S-oligonucleotide probes for GAT-1 mRNA. RESULTS: In the schizophrenic subjects, the relative density of labeled neurons was 21%-33% lower in layers 1-5 of the prefrontal cortex but was unchanged in layer 6. In contrast, cellular levels of GAT-1 mRNA expression, as reflected in grain density per labeled neuron, did not differ by more than 11% between subject groups in any layer. These findings indicate that GAT-1 mRNA expression is relatively unaltered in the majority of prefrontal cortex GABA neurons in schizophrenic subjects but is reduced below a detectable level in a subset of GABA neurons. Furthermore, the magnitude and laminar pattern of these results were strikingly similar to those found in a previous study of mRNA expression for the synthesizing enzyme of GABA, glutamic acid decarboxylase(67), in the same subjects. CONCLUSIONS: Both GABA synthesis and reuptake appear to be altered at the level of gene expression in a subset of GABA neurons, and the resulting changes in GABA neurotransmission may contribute to prefrontal cortex dysfunction in schizophrenia.

Adult↗

A major gene effect on fasting insulin and insulin sensitivity in familial combined hyperlipidemia.

The most common inherited dyslipidemia, familial combined hyperlipidemia (FCHL), is associated with insulin resistance. Whether insulin sensitivity in these families is inherited is not known. Therefore, we investigated the inheritance of insulin sensitivity in 352 nondiabetic family members from 37 families with FCHL, 105 of whom had undergone testing using the hyperinsulinemic-euglycemic clamp technique for the measurement of insulin sensitivity. First, complex segregation analysis of fasting insulin levels (both unadjusted and age-, age(2)-, and BMI-adjusted) was used for modeling of the variance in fasting insulin levels. In these analyses, Mendelian codominant inheritance (P = 0.320 for unadjusted and P = 0.295 for adjusted insulin values) was not rejected over the most general model and fit the data significantly better than the sporadic model (P < 0.001). Polygenic and environmental models were rejected (P < 0.001). The Mendelian codominant model explained 44 and 45% of the variance in unadjusted and adjusted fasting insulin levels, respectively. The proposed genotypes of this locus, based on segregation analysis, were associated with directly measured insulin sensitivity in 105 FCHL family members who underwent the hyperinsulinemic-euglycemic clamp (P < 0.001). These results provide evidence for a major gene regulating insulin sensitivity in FCHL families. Possible pleiotropic effects of this insulin sensitivity locus on dyslipidemias in FCHL remain to be elucidated.

Adult↗

Validity of leg-to-leg bioelectrical impedance measurement in males.

BACKGROUND: This study determined the validity of the leg-to-leg bioelectrical impedance analysis (BIA) system (Tanita Body Fat Analyzer, TBF 105, Tanita Corporation of America, Inc., Arlington Heights, IL) in estimating body composition in males. METHODS EXPERIMENTAL DESIGN: Fat-free mass (FFM) was estimated using BIA and underwater weighing, and compared. SETTING: Subjects were recruited from the community. PARTICIPANTS: Heterogeneous group of males (N=192) was recruited, with a mean+/-SD age of 39.0+/-16.8 yrs; body mass index, 26.0+/-4.0 kg/m2, percent body fat, 18.1+/-8.9 percent. MEASURES: Prior to BIA testing, subjects were required to adhere to standard BIA testing guidelines, and bioelectrical impedance was measured in subjects standing erect with bare feet on the analyzer's footpads, and wearing a swimsuit. Underwater weighing was conducted using standard procedures, with direct measurement of residual volume. RESULTS: A Bland-Altman plot of difference between FFM measured by underwater weighing and BIA versus average FFM by the two methods showed no systematic difference (mean difference, 0.07+/-3.5 kg). FFM was estimated at 66.3+/-8.6 kg with underwater weighing, and 66.2+/-7.7 kg with BIA (r=0.92, p<0.001; SEE 3.5 kg). CONCLUSIONS: These data indicate that the leg-to-leg bioelectrical impedance system accurately assesses FFM in a heterogenous group of males when compared to underwater weighing.

Adipose Tissue↗

Increased DNA vaccine delivery and immunogenicity by electroporation in vivo.

DNA vaccines have been demonstrated to be potent in small animals but are less effective in primates. One limiting factor may be inefficient uptake of DNA by cells in situ. In this study, we evaluated whether cellular uptake of DNA was a significant barrier to efficient transfection in vivo and subsequent induction of immune responses. For this purpose, we used the technique of electroporation to facilitate DNA delivery in vivo. This technology was shown to substantially increase delivery of DNA to cells, resulting in increased expression and elevated immune responses. The potency of a weakly immunogenic hepatitis B surface Ag DNA vaccine was increased in mice, as seen by a more rapid onset and higher magnitude of anti-hepatitis B Abs. In addition, the immunogenicity of a potent HIV gag DNA vaccine was increased in mice, as seen by higher Ab titers, a substantial reduction in the dose of DNA required to induce an Ab response, and an increase in CD8+ T cell responses. Finally, Ab responses were enhanced by electroporation against both components of a combination HIV gag and env DNA vaccine in guinea pigs and rabbits. Therefore, cellular uptake of DNA is a significant barrier to transfection in vivo, and electroporation appears able to overcome this barrier.

AIDS Vaccines↗

Serous retinal detachment at the macula in sarcoidosis.

PURPOSE: To report an unusual case of serous retinal detachment at the macula in a patient with a history of sarcoidosis. METHOD: Case report. In a 44-year-old Caucasian man, the history, clinical features, fluorescein angiography, laboratory and radiological investigations, treatment, and lung autopsy findings are presented. RESULTS: A serous detachment of the retina in the macula of his left eye was observed. He had pulmonary hypertension secondary to active sarcoid granulomas that caused pulmonary angiitis. CONCLUSION: Serous retinal detachment at the macula may occur in association with pulmonary angiitis secondary to sarcoidosis.

Adult↗

Hospital- and community-based surveillance of methicillin-resistant Staphylococcus aureus: previous hospitalization is the major risk factor.

OBJECTIVE: The purpose of the study was to determine the incidence and risk factors for the acquisition of methicillin-resistant Staphylococcus aureus (MRSA) in our community. DESIGN: This study used a cross-sectional design to assess patients colonized or infected with MRSA. PATIENTS: The study population consisted of residents of London, Ontario, Canada, who were identified as MRSA-positive for the first time in 1997. SETTING: All acute- and chronic-care hospitals, long-term healthcare facilities, and community physicians' offices in the city of London participated in the study. MAIN OUTCOME MEASURE: Incidence of MRSA in the community, risk factors for acquisition, especially previous hospitalization over a defined period, and strain type were evaluated. RESULTS: In 1997, 331 residents of London were newly identified as MRSA-positive, representing an annual incidence of 100/100,000 persons (95% confidence interval, 88.8-110.7). Thirty-one (9.4%) individuals were not healthcare-facility patients in the previous month, and 11 (3.3%), 10 (3.0%), and 6 (1.8%) individuals had no such contact in the previous 3, 6, and 12 months, respectively. One hundred seventy-seven strains, including five of the isolates from patients with no healthcare-facility contact in the previous year, were typed. One hundred sixty (90.3%) of these isolates, including all typed strains from patients with no healthcare facility contact, belonged to a single clone. CONCLUSION: These findings demonstrate that the incidence of MRSA is higher than previously reported and that hospital contact is the single most important risk factor for the acquisition of MRSA in our community. Screening for MRSA in previously hospitalized patients at the time of hospitalization may reduce nosocomial spread and indirectly reduce the incidence of MRSA in the community.

Adult↗