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Biomedical subjects

P Gannon

Publications and source records attributed to P Gannon.

At least 19 recordsLinked to original sources
PubMed2004

Validating the subcutaneous model of injectable autologous cartilage using a fibrin glue scaffold.

PURPOSE: To create and validate an injectable model for autologous in vivo cartilage engineering with ultimate clinical applicability in human subjects. HYPOTHESIS: Cartilage can be generated subcutaneously using fibrin glue and autologous chondrocyte components. BACKGROUND: To date, cartilage engineering studies have been limited by several factors. Immunocompromised animals and nonautologous chondrocytes have been successfully used to create cartilage, but results using identical designs failed in immunocompetent subjects. Recent studies using more biocompatible tissues and matrices have been performed with both in vitro and in vivo steps. Although successful, several problems are notable. In vitro cartilage displays a poor modulus of elasticity, even after in vivo implantation. Variable deformation and volume loss occurs when in vitro specimens are matured in vivo. These concerns limit the clinical utility of these methods. We therefore set out to create autologous cartilage using a model that was clinically feasible, easy to create, and could be performed with very low patient harvest morbidity. MATERIALS AND METHODS: Eight New Zealand white rabbits underwent a unilateral harvest of ear cartilage. Samples were then digested using standard methods. Cell counts and survival assays were performed before implantation. One sample of fibrin glue (Tisseel) and chondrocytes was injected subcutaneously into each donor rabbit and then left in situ for 3 months. A second sample with both basic fibroblast growth factor (b-FGF) and insulin-like growth factor (IGF)-1 in the injection suspension was also assessed (for a total of 16 samples). After harvest, analysis of overall volume, histology, and chondrocyte drop out counts was performed. RESULTS: Cartilage formation occurred in 8 of 14 (57%) specimens that were obtained at the time of sacrifice. Of note, 6 of 7 (85%) non-growth-factor containing samples yielded positive results. Comparison with the success rate using concomitant growth factors (2/7) showed a negative effect on cartilage yield (P = .015). Chondrocyte survival, based on chondrocyte dropout counts, was not effected. Angiogenesis appeared to correlate with cartilage formation in the central regions of the implant. Alcian blue demonstrated the presence of active matrix deposition, and elastin Verhoff-van Geison (EVG) stains were positive, showing an elastic cartilage phenotype. Very limited osteoid formation was seen in successful implants. Failed implants demonstrated avascular necrosis, giant cell reactions, and inflammatory infiltrates. CONCLUSIONS: This study validates the subcutaneous site as a recipient bed for the engineering of autologous cartilage in vivo. It also represents the first subcutaneous implantation of fibrin glue and chondrocytes in an immunocompetent host as well as the first published report of elastic cartilage generation in vivo. Although the model needs to be further streamlined to increase yields and overall volume, this study clearly demonstrates the feasibility of in vivo chondrogenesis (85% success). The addition of FGF and IGF-1 at the concentrations used negatively influenced cartilage yield. However, extrapolation of these results to other combinations or concentrations can not be done, and this issue deserves further investigation.

Animals↗
PubMed2002

Interpretation of occupational peak flow records: level of agreement between expert clinicians and Oasys-2.

BACKGROUND: Oasys-2 is a validated diagnostic aid for occupational asthma that interprets peak expiratory flow (PEF) records as well as generating summary plots. The system removes inconsistency in interpretation, which is important if there is limited agreement between experts. A study was undertaken to assess the level of agreement between expert clinicians interpreting serial PEF measurements in relation to work exposure and to compare the responses given by Oasys-2. METHOD: 35 PEF records from workers under investigation for suspected occupational asthma were available for review. Records included details of nature of work, intercurrent illness, drug therapy, predicted PEF, rest periods, and holidays. Simple plots of PEF and the Oasys-2 generated plots were available. Experts were advised that approximately 1 hour was available to review the records. They were asked to score each work-rest-work (WRW) period and each rest-work-rest (RWR) period for evidence of occupational effect. At the end of each record scores of 0-100% were given for evidence of "asthma" and "occupational effect" for the whole record. Kappa values were calculated for each scored period and for the opinions on the whole record. The scores were converted into four groups (0-25%, 26-50%, 51-75%, 76-100%) and two groups (0-50% and 51-100%) for analysis. This is relevant to scores produced by Oasys-2. Agreement between Oasys-2 scores and each expert was calculated. RESULTS: 24 of 35 records were analysed by seven experts in the allotted time. For whole record occupational effect, median kappa values were 0.83 (range 0.56-0.94) for two groups and 0.62 (0.11-0.83) for four groups. For asthma, median kappa values were 0.58 (0-0.67) and 0.42 (0.15-0.70) for two and four groups respectively. For all WRW and RWR periods kappa values were 0.84 (0.42-0.94) and 0.70 (0.46-0.87) respectively. Agreement between Oasys-2 and individual experts showed a median kappa value of 0.75 (0.50-0.92) for two groups and 0.50 (0.39-0.70) for four groups. Kappa values for the median expert score v Oasys-2 were 0.75 for two groups and 0.67 for four groups. Agreement was poor for records with intermediate probability, as defined by Oasys-2. CONCLUSION: Considerable variation in agreement was seen in expert interpretation of occupational PEF records which may lead to inconsistencies in diagnosis of occupational asthma. There is a need for an objective scoring system which removes human variability, such as that provided by Oasys-2.

Asthma↗
PubMed1999

Genetic testing and employee protection.

Given advances in the science of genetics it is increasingly possible for individuals to acquire an increased understanding about their DNA. Employers may wish to access such information or may request that employees participate in genetic testing. An examination of the UK legislative framework to accommodate or to prevent such demands raises concern about the need to balance the employer's economic interests and the autonomy of the employee.

Persons with Disabilities↗
PubMed1998

Characterizing the antigenic profile of the human trachea: implications for tracheal transplantation.

BACKGROUND: Tracheal transplantation may be a viable alternative in select situations of long-segment tracheal stenosis. Issues concerning human tracheal antigenicity and the requirement for systemic immunosuppression need to be addressed. This study examined the distribution of the major transplantation antigens on fresh human trachea. METHODS: Frozen sections of 10 human tracheas were examined for class I (HLA [human leukocyte antigen]-A, -B, -C) and class II (HLA-DR) histocompatibility antigens using mouse monoclonal antibodies in an indirect immunoperoxidase assay. The tracheal mucosa, perichondrium, cartilage matrix, and chondrocytes were examined and assigned a semiquantitative score for HLA class I and class II expression. RESULTS: The tracheal mucosa was strongly antigenic for HLA class I and class II antigens, whereas the perichondrium contained only scattered fibroblasts that were positive for both classes. The polysaccharide matrix was consistently devoid of class I or class II expression. The chondrocytes of all 10 specimens expressed diffuse class I positivity; only two specimens contained chondrocytes that expressed class II positivity. CONCLUSIONS: The human trachea contains "compartments" of highly antigenic tissue that are morphologically distinct from regions of lesser antigenicity.

Biopsy↗
PubMed1998

Frequency of cerebral vasospasm in patients treated with endovascular occlusion of intracranial aneurysms.

UNLABELLED: The purpose of this study was to retrospectively compare a group of 19 patients treated with craniotomy and aneurysmal clipping with a group of 18 patients who were treated via endovascular occlusion with Guglielmi detachable coils in regard to frequency and severity of cerebral vasospasm. METHODS: All patients were treated within 48 hours of ictus. In the endovascular group, nine patients had Hunt and Hess grade I subarachnoid hemorrhage, five patients had grade II aneurysms, and four patients had grade III. According to the Fisher classification, one aneurysm was grade I, nine were grade II, and eight were grade III. Twelve of the aneurysms were on the anterior circulation and seven were on the posterior circulation. In the surgical group, 10 patients had Hunt and Hess grade I hemorrhage, seven had grade II aneurysms, and two had grade III. Nine of these were Fisher grade II and 10 were grade III. Eighteen aneurysms were on the anterior circulation and one was on the posterior circulation. Endovascularly treated patients were medically treated identically to those in the surgical group, with prophylactic volume expansion and hemodilution immediately after endovascular occlusion, except that they also received 48 hours of full heparinization followed by 24 hours of dextran infusion after endovascular occlusion. RESULTS: All four patients in the endovascular group in whom delayed neurologic deficits developed as a result of vasospasm responded to elevation of blood pressure and did not require either mechanical or chemical angioplasty to reverse their symptomatology. In the surgical group, 14 of 19 developed clinical vasospasm, with elevation of their transcranial Doppler velocities, and required maximum triple-H (hypertensive, hypervolemic, hemodilutional) therapy. Three of these patients required mechanical and pharmacologic angioplasty. No surgical complications were incurred as a direct result of the craniotomy. One patient in the endovascular group developed a femoral pseudoaneurysm as a complication of the procedure and postocclusion anticoagulation. No thromboembolic events were noted in this group. CONCLUSION: In patients with similar Hunt and Hess grades and Fisher grades, preliminary data suggest that the frequency and severity of cerebral vasospasm may be reduced in those treated by endovascular occlusion of their aneurysm as compared with those treated by direct surgical clipping.

Adult↗
PubMed1997

Undergraduate training in the European Union. Convergence or divergence?

A survey of dental schools in the European Union was carried out for two main reasons. Firstly to promote the exchange of information in respect of curriculum objectives in the different countries and secondly to ascertain the differences in the interpretation of the 1978 EU sectoral directives for dental education and training. Out of 127 schools, only 30 responded, yet the information provided is of considerable importance. It demonstrates wide divergence in the interpretation of the 1978 Directives and methods of assessment of clinical competence. There is a considerable difference throughout Europe in hours devoted to the various subjects included in the Dental Directives. There is little evidence of convergence in methods of assessment or quality assurance. The survey demonstrates the difference in resources, levels of staff, availability of clinical training places, output in research and patient treatments throughout the European Union. The results question the effectiveness of the 1978 Dental Directives in promoting convergence of standards. As there is free movement of dentists throughout the European Union, it is concluded that a different approach may be necessary to ensure that all European Union dental graduates achieve comparable standards in their education and training.

Curriculum↗
PubMed1994

The effect of polyethylene glycol gavage on plasma volume.

This study examines the hypothesis that whole gut irrigation with polyethylene glycol-electrolyte gavage solution (PEG-ELS) increases intravascular volume. Seventeen patients drank 6 to 8 liters of PEG-ELS in preparation for elective colonoscopy. The patients were weighed and serum electrolytes, albumin, hematocrit, blood urea nitrogen, and creatinine were obtained prior to the gavage and 8 hr following gavage. Plasma volume was measured before and after gavage using an isotope dilution technique involving 125I-human serum albumin. No patients developed symptoms of intravascular volume excess or depletion following gavage. There was no significant change in body weight, serum sodium, chloride, potassium, bicarbonate, blood urea nitrogen, or creatinine following gavage with PEG-ELS. When measured by the isotope dilution technique, the mean plasma volume increased from 3174 +/- 117 ml before gavage to 3365 +/- 160 ml following gavage (P = 0.03). This represented a mean percentage change in plasma volume of 5.88 +/- 2.4%. The percentage change in plasma volume associated with gavage ranged from -9.8 to +29.8%. This data supports the hypothesis that gavage with polyethylene glycol-electrolyte solution is associated with an increase in plasma volume. Although in most patients the increase in plasma volume is minimal, there is significant variability in this response, with some patients experiencing substantial increases in plasma volume.

Colon↗
PubMed1993

Evaluation of i.v. ceftriaxone usage in a community-based hospital.

Ceftriaxone is primarily used for the treatment of gram-negative nosocomial pneumonia and for gram-negative bacteremias. The following study examines whether ceftriaxone, a broad spectrum parenteral cephalosporin antibiotic, was being administered appropriately based on pre-established hospital criteria.

Ceftriaxone↗
PubMed1992

Preliminary development of a live drug-controlled vaccine against bovine babesiosis using the Mongolian gerbil, Meriones unguiculatus.

This study investigated the practicality and potential of the gerbil, Meriones unguiculatus, as a source of live Babesia divergens vaccine and also as a model for the use of the vaccine in cattle. A series of experiments with gerbils concerning vaccine infectivity, immunogenicity and safety were carried out. It was concluded that the use of RPMI medium/40% foetal calf serum as a diluent improved vaccine infectivity, but that the parasitaemia of the blood obtained from donor gerbils had little or no effect. The immunostimulants levamisole and killed Corynebacterium parvum improved vaccine immunogenicity and it was also shown that the subcutaneous route of infection resulted in the greatest host response. Control of vaccine virulence with drugs was only possible when drugs with prophylactic properties, such as imidocarb and long-acting oxytetracycline, were used. More studies are required on all these topics, particularly with regard to their applicability to cattle, and also concerning the possible attenuation of the parasite by manipulation in the gerbil host.

Adjuvants, Immunologic↗
PubMed1989

Vaccination against bovine babesiosis with drug-controlled live parasites.

Live Babesia divergens derived from gerbils were used to vaccinate cattle that had previously been treated with imidocarb dipropionate. Drug doses ranged from 1 to 2 mg/kg and animals were infected subcutaneously three to seven days later. After a further 35 days, vaccinated and control animals were given a heavy heterologous intravenous challenge. This regimen was effective for both avirulent and virulent strains in 12- to 18-month-old cattle. However, at low drug doses some animals reacted to the virulent vaccine strain and at high doses animals infected with the avirulent strain failed to seroconvert although they were still resistant to challenge. The variable infectivity of vaccine strains was a minor problem which can be overcome by strain selection and optimisation of infectivity using gerbils as experimental animals. Gerbils would also be useful as a source of parasites for the further development of in vitro cultures which could ultimately produce the vaccine.

Animals↗
PubMed1984

Acutely thrombosed aneurysm of the middle cerebral artery presenting as intracranial hemorrhage in a 3-year-old child. Case report.

Spontaneous thrombosis of aneurysms occurs rarely in children, and, to our knowledge, there are no reports of aneurysms presenting as an embolic event in a child. We describe the case of a 3-year-old boy whose symptoms initially suggested an ischemic event to the dominant hemisphere. Initial computerized tomography scans indicated an intracranial hemorrhage. Subsequent radiographic study revealed evidence of emboli and, at exploration, a large acutely thrombosed aneurysm of the left middle cerebral artery associated with arterial occlusion was found. Entrapment of the aneurysm and thrombectomy provided excellent operative results.

Cerebral Angiography↗
PubMed1983

The ultrastructural localization of serotonin immunoreactivity in myelinated and unmyelinated axons within the medial forebrain bundle of rat and monkey.

Myelinated and unmyelinated serotonin-containing axons were demonstrated in the medial forebrain bundle of rats and monkeys with an antibody against serotonin (5-HT) conjugated to hemocyanin. The level of 5-HT in the brain was increased by pretreatment of animals with pargyline and L-tryptophan. The addition of nickel salts to the diaminobenzidine-peroxidase reaction mixture increased the intensity of the reaction product. Specific 5-HT immunoreactivity was observed to be localized to membrane-enclosed and membrane-attached compartments. 5-HT immunoreactivity was seen predominantly in unmyelinated axons (0.2 to 1.25 micron in diameter) surrounded by unlabeled processes. More than half of these 5-HT-immunoreactive fibers were in apposition with unreactive myelinated axons in the hypothalamus of both the rat (55%) and the monkey (54%). These appositions may provide the anatomical substrate for the observations that sprouting serotonergic fibers in the adult brain use myelinated axons for contact guidance. In addition to the unmyelinated fibers, intensely labeled myelinated axons (1.0 to 2.1 micron) were seen in the medial forebrain bundle of both rats and monkeys. The percentage of 5-HT-immunoreactive myelinated axons appeared greater in the monkey than in the rat (25.4% versus 0.7% of the total number of 5-HT-immunoreactive fibers, respectively). the observation of an increased number of myelinated 5-HT-immunoreactive axons in the monkey hypothalamus as compared to the rat supports the general hypothesis of a trend toward increased myelination during evolution.

Animals↗