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Biomedical subjects

C Burke

Publications and source records attributed to C Burke.

At least 55 records · Page 3Linked to original sources

Regional cerebral blood flow during memory recognition and neuropsychological performance in patients referred for investigation of dementia.

Regional cerebral blood flow was studied at rest and during a memory recognition activation task in a preliminary investigation carried out in patients with mild to moderate dementia of Alzheimer type and in 2 control groups of subjects. There were differences in the sites of activation-increased blood flows between the normal controls and the controls with major depression, while the Alzheimer's disease subjects showed more variable patterns of flow response, which differed overall from those present in the 2 control groups.

Alzheimer Disease↗

Ocular hazards of nebulized bronchodilators.

Three cases of pupillary dilatation associated with the development of acute glaucoma, precipitated by the use of nebulized bronchodilators are described. We suggest measures to reduce the risk of this complication.

Adult↗

Hepatic transplants. Liver transplantation: an OR nurse's perspective.

1. Advanced surgical technique, improved immunosuppressive drug therapy, and an increased public awareness of the need for donor organs has resulted in liver transplantation being recognized as an available option for the treatment of end-stage liver disease. 2. The evaluation process is extensive. Medical and surgical assessments are done through a complete history and physical examination; diagnostic testing ranges from blood typing and serologies to radiologic and consultant procedures; and psychological and psychosocial evaluations are done for the patient and family. 3. Ongoing research in organ preservation, immunosuppressive drug therapy, and surgical technique has helped to make liver transplantation programs successful.

Anastomosis, Surgical↗

T-cell dominated inflammatory reactions in the bronchi of asthmatics are not reflected in matched bronchoalveolar lavage specimens.

Samples of bronchoalveolar lavage (BAL) and endobronchial biopsies were obtained from five patients with clinically diagnosed asthma (ATS criteria). A comparison was made of the presence and distribution of immunocompetent lymphocytes and macrophages within each sample. Significantly raised numbers of T lymphocytes, CD45RO+ lymphocytes, RFD1+ macrophage-like cells and RFD7+ macrophages were seen in the bronchial biopsies. In contrast four out of five of the BAL specimens showed a normal differential cell count, the one exception being a patient exhibiting a degree of lymphocytosis. Further, immunocytological investigation demonstrated a normal distribution of T-cell subsets and macrophage subsets in asthmatic BAL with the exception that in four out of five of these patients a raised number of macrophage-like cells exhibiting phenotypic markers of monocytes was observed. Correlation between BAL and biopsy data was seen in the number of CD45RO+ T-cells present. No other parameters exhibited a significant correlation. Raised expression of HLA-DR was recorded in all asthmatic biopsies, yet lavage cells from the same patients failed to exhibit any increase of HLA-DR density over normal. It is concluded that the immune-associated inflammation present in endobronchial biopsies of clinically stable asthmatics is not reflected in bronchoalveolar lavage samples taken from the same patients.

Acute-Phase Reaction↗

Lung function and immunopathological changes after inhaled corticosteroid therapy in asthma.

Six patients with asthma (American Thoracic Society (ATS) criteria), maintained on inhaled beta 2-agonists alone, were treated with inhaled corticosteroid (budesonide 400 micrograms b.d.) for a period of three months. Prior to steroid therapy, baseline spirometry, bronchodilator response and bronchial hyperresponsiveness were documented and endobronchial biopsies were obtained for immunopathological analysis. Frozen sections of the biopsies were investigated using immunoperoxidase methods, with a panel of monoclonal antibodies selected to reveal the presence and distribution of lymphocyte and macrophage subsets and HLA-DR expression. After three months the studies were repeated. Studies before steroid therapy revealed a T-cell-dominated inflammation in the bronchial wall of all subjects. Baseline airway obstruction, median (range) forced expiratory volume in one second (FEV1) 78.5 (61-109)% of predicted, with a significant bronchodilator response 20.8 (14-33)% and bronchial hyperresponsiveness to histamine geometric mean (SD) PC20FEV1 0.69 (2.5) mg was documented. Steroid therapy caused a significant reduction in bronchial hyperresponsiveness to histamine, with an increase in geometric mean PC20FEV1 to 2.22 (3.2) mg post steroid (p less than 0.03). Concurrent with a reduction in bronchodilator response and an increase in spirometric variables (improved forced midexpiratory flow (FEF25-75) p less than 0.03), there were marked reductions observed in the overall numbers of T-lymphocytes (CD 2, 5, 8), the numbers of CD45RO+ T-cells, and the numbers of macrophages (RFD1+) with the phenotype of antigen presenting cells. In all six subjects, reductions in the quantitative expression of HLA-DR molecules were also seen.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗

1H NMR and CD secondary structure analysis of cell adhesion promoting peptide F-9 from laminin.

A heparin binding, cell adhesion promoting domain, termed peptide F-9, from the B1 chain of human laminin, residues 641 to 660, i.e. RYVVLPRPVCFEKGMNYTVR, has been investigated by 1H NMR (500 MHz) spectroscopy and CD spectropolarimetry. While small linear peptides in water solution normally exist in a number of fluctuating conformational states, CD data analysis of peptide F9 indicates the existence of some preferred average structural populations consisting of about 30% beta-sheet, 22% beta-turn, and 6% alpha-helix. NMR structural analysis supports this observation and indicates specific sequences of preferred structural populations. Evidence for these is indicated by the presence of dNN nuclear Overhauser effect (NOE) populations and attenuated or absent d alpha N NOEs at short mixing times (0.1 s), 3J alpha N coupling constants of 5 and 10 Hz, and chemical shifts significantly removed from random coil positions. The NH2-terminal VVL sequence primarily exists in an extended chain conformation by virtue of large d alpha N NOEs and 9-10 Hz 3J alpha N coupling constants. Residues C10-N16 have turn-like or helix character with a run of dNN and d beta N NOEs and attenuated d alpha N NOEs. These midchain reversals include the lysine and asparagine residues proposed to be involved in heparin binding and N-glycosylation, respectively, to laminin peptide F-9.

Amino Acid Sequence↗

T cell dominated inflammatory reactions in the bronchioles of asymptomatic asthmatics are also present in the nasal mucosa.

Endobronchial and nasal mucosa biopsies were obtained from 5 patients with clinically-stable, diagnosed asthma (ATS criteria). A comparison was made of the presence and distribution of immunocompetent lymphocytes and macrophages within each sample. The distribution of immunocompetent cells within the nasal biopsies of the asthmatic patients reflected a very similar inflammatory infiltrate to that seen in the bronchial biopsies. Significantly raised numbers of T lymphocytes, CD45RO + lymphocytes, RFD1 + macrophage-like cells and RFD7 + macrophages were seen in both the nasal mucosa and the bronchial biopsies. Increases in HLA-DR expression were also seen in the nasal mucosa biopsies from asthmatics although the increases over normal did not reach statistical significance. It is concluded that inflammation present in the nasal mucosa of asymptomatic asthmatics exhibits cellular characteristics also seen in endobronchial biopsies. This observation offers the possibility that mucosal biopsy may be an alternative and less invasive approach for studying the cells involved in the bronchial inflammatory reaction that possibly predisposes asthmatics to bronchial hyper-responsiveness.

Adolescent↗

Propofol as an anaesthetic agent for ECT: effect on outcome and length of course.

Recent reports of reduced seizure duration with ECT under propofol anaesthesia have led to concerns that propofol may diminish the efficacy of this treatment. To investigate the effect of propofol on the response to ECT, we reviewed records of 66 patients with primary depression treated with ECT, 37 of whom had been assessed prospectively with pre- and post-ECT Hamilton and Zung depression severity ratings. Despite demonstrating that the individual seizure duration was significantly reduced with propofol compared to thiopentone we found no evidence of reduced ECT efficacy with propofol. Courses under propofol anaesthesia were on an average two treatments longer than with thiopentone. Although this difference was not statistically significant this may have been due to a type II error. These results suggest that it is premature to abandon the use of this new anaesthetic agent in ECT without controlled prospective outcome studies.

Adult↗

Regional cerebral blood flow and recognition memory in elderly normals: potential application to Alzheimer's disease.

Regional cerebral blood flow, a physiological measure of brain function, has been used for the assessment of cognitive dysfunction in Alzheimer's disease. A number of studies have found diminished temporo-parietal regional cerebral blood flow (RCBF) in Alzheimer's disease patients at rest and have differentiated these patients from normal subjects with a high degree of sensitivity. However the majority of the Alzheimer's disease patients have been in the moderate to severe stages of the disorder. Few studies have assessed RCBF in the early stages of Alzheimer's disease. With increasing emphasis now being placed on the early detection of such patients we chose to examine RCBF during a task which made demands on those cognitive processes which are impaired in the early stages of the disease, viz. a recognition--memory task. Using a 32-channel RCBF system, we examined 20 normal control subjects over the age of 60 years and 10 patients with early to moderate Alzheimer's disease. RCBF was examined during a task of recognition--memory, and also at rest. Normal subjects showed a global increase in RCBF, with marked left frontal activation, as compared with when at rest. Resting perfusion was decreased in the Alzheimer's subject, and there appeared to be a greater degree of intersubject variability in flow during activation.

Aged↗

Transcription factor IIA of wheat and human function similarly with plant and animal viral promoters.

Eucaryotic transcription initiation by RNA polymerase II involves protein:DNA interactions during the formation of a transcription complex. In addition to RNA polymerase II there are at least five other general transcription factors necessary for initiation with the adenovirus major late promoter. One of these, TFIIA, is involved in the earliest events during transcription complex assembly. We have purified TFIIA from wheat germ and characterized it in an in vitro transcription system. Wheat TFIIA is a single polypeptide of Mr approximately 35 kd which functionally replaces human (HeLa) TFIIA to form a wheat/HeLa transcription system. [This polypeptide can be eluted from a SDS-polyacrylamide gel, refolded to a native conformation, and will function as wheat TFIIA in the heterologous system.] The heterologous system requires a lower optimal incubation temperature than the HeLa system. Biochemical characterization, using the adenovirus major late promoter, indicates that transcription reaction parameters for both wheat and HeLa TFIIA are similar but the kinetics of transcription for both TFIIAs are somewhat dissimilar. A plant viral promoter, the cauliflower mosaic virus 35S promoter, accurately and efficiently directs in vitro transcription in both the wheat/HeLa and HeLa systems with identical transcription kinetics. We conclude that TFIIA function has been conserved during evolution.

Chromatography, Gel↗

Transcription factor IIA of wheat and human interacts similarly with the adenovirus-2 major late promoter.

Transcription factor IIA (TFIIA) is a necessary component of many RNA polymerase II transcription complexes. Assembly of the transcription complex begins when TFIIA interacts with the promoter. We have previously purified wheat germ TFIIA to homogeneity and demonstrated that it substitutes for human TFIIA in a human in vitro transcription system which utilizes the adenovirus-2 major late promoter (Ad-2 MLP). We now show, by gel retardation assays, that wheat TFIIA interacts with the Ad-2 MLP. Extensively purified human (HeLa) TFIIA interacts with the Ad-2 MLP similarly. Both wheat and human TFIIA interact with a DNA fragment comprising the minimal promoter region (-51/+32) but not with upstream or downstream regions. With both TFIIAs multiple complexes form; the fastest wheat TFIIA/DNA complex appears to be larger than the corresponding human TFIIA/DNA complex. Limited point mutation analysis of the Ad-2 MLP demonstrates that changes at -30 (TATAA region), +1, and -1 diminish TFIIA binding, but a change at -40 does not. DNA footprint analysis of this region is not definitive, but does indicate that following TFIIA binding there are changes in the pattern of hypersensitive sites.

Adenoviridae↗

1H NMR sequential assignments and secondary structure analysis of human fibrinogen gamma-chain C-terminal residues 385-411.

The human fibrinogen gamma-chain, C-terminal fragment, residues 385-411, i.e., KIIPFNRLTIGEGQQHHLGGAKQAGDV, contains two biologically important functional domains: (1) fibrinogen gamma-chain polymerization center and (2) platelet receptor recognition domain. This peptide was isolated from cyanogen bromide degraded human fibrinogen and was investigated by 1H NMR (500 MHz) spectroscopy. Sequence-specific assignments of NMR resonances were obtained for backbone and side-chain protons via analysis of 2D NMR COSY, double quantum filtered COSY, HOHAHA, and NOESY spectra. The N-terminal segment from residues 385-403 seems to adopt a relatively fixed solution conformation. Strong sequential alpha CH-NH NOESY connectivities and a continuous run of NH-NH NOESY connectivities and several long-lived backbone NH protons strongly suggest the presence of multiple-turn or helix-like structure for residues 390 to about 402. The conformation of residues 403-411 seems to be much less constrained as evidenced by the presence of weaker and sequential alpha CH-NH NOEs, the absence of sequential NH-NH NOEs, and the lack of longer lived amides. Chemical shifts of resonances from backbone and side-chain protons of the C-terminal dodecapeptide, residues 400-411, differ significantly from those of the parent chain, suggesting that some preferred C-terminal conformation does exist.

Amino Acid Sequence↗

Pseudomonas aeruginosa meningitis treated with ceftazidime.

A case of pseudomonas aeruginosa meningitis secondary to chronic otitis media was successfully treated with ceftazidime and gentamicin intravenously. No intrathecal antibiotics were necessary. Treatment of pseudomonas meningitis has been simplified with the advent of third generation cephalosporins.

Aged↗

The relationship between bronchial immunopathology and hyperresponsiveness in asthma.

Physiological and Immunopathological parameters were investigated in 15 patients with diagnosed asthma, and 6 non-asthmatics presenting with other chest symptoms. The 15 symptom-free asthmatics expressed bronchohyperresponsiveness with a mean provocative dose producing a 20% fall in forced expiratory volume in one second (PD20FEV1) of 1 mg histamine. None of the non-asthmatics responded to 16 mg histamine. Twenty four hours later bronchoscopy was performed and endobronchial biopsies were obtained. Histological staining of frozen biopsy sections revealed a mononuclear cell infiltrate in all 15 asthmatics, while only 1 of the 6 non-asthmatics showed mild inflammation. Monoclonal antibodies were used to identify subsets of lymphocytes, activation markers, macrophages, and HLA-DR expression within the peribronchial infiltrates. In all samples, activated T-cells and macrophages were identified and HLA-DR expression was found to be raised, but the CD4: CD8 ratio was highly variable. No clear relationship was found between cellular distribution and measured lung function parameters. A highly significant correlation was found between the level of HLA-DR expression on the infiltrating cells (quantified microdensitometrically) and bronchial hyperresponsiveness. These results show for the first time that a chronic T-cell-mediated immune response is present in the bronchial tissue of asymptomatic asthmatics, and that the HLA-DR expression promoted correlates with the hyperresponsive status. These data promote the hypothesis that a T-cell-mediated response contributes to a predisposition to bronchial hyperresponsiveness in asthmatics.

Adolescent↗

Epidermal growth factor receptor binding is not a simple one-step process.

The binding kinetics of 125I-labeled mouse epidermal growth factor (EGF) to receptors on human fibroblast cells in monolayer culture were measured at 4 degrees C. Initial binding rates as a function of hormone concentration allowed estimation of simple two-state on-off rate constants of 1.2 x 10(6) M-1 s-1 and 4.9 x 10(-3) s-1, respectively. These two-state parameters gave inadequate computer fits to long term kinetic and equilibrium-binding data, suggesting that an additional process(es) was occurring. Nonlinear equilibrium Scatchard plots and transient "pseudo-Scatchard" plots taken at pre-equilibrium times support the idea that at least one other process is occurring during receptor binding. 125I-EGF-receptor dissociation kinetic plots were biphasic, yielding rate constants of 1.5 x 10(-2) s-1 and 5.6 x 10(-5) s-1 with the ratio of the two components changing with the time of initial incubation with 125I-EGF. Application of a ternary complex model which assumed complexation of the bound receptor with a cell surface interaction molecule gave satisfactory fits to all data.

Animals↗

Risk factors in onychocryptosis.

A study is described in which the normal toes of 50 patients with unilateral ingrowing toenails were compared with those of 50 healthy subjects matched for age and sex. Twenty-one potential risk factors were compared between the groups. All measurements on patients were derived from unaffected toes in order to avoid anatomical distortion due to the disease process. Statistical analysis revealed significant differences between the groups for three anatomical measures, namely nail fold width (P less than 0.001), medial rotation (eversion) of the great toe (P less than 0.02) and nail thickness (P less than 0.03). Possible discriminating variables were assessed using linear discriminant function analysis and a mathematical equation was derived based on these three factors. This equation was found to possess a potentially high predictive value in that it correctly classified 86 per cent of the patients and 77 per cent of the controls. A further group of 62 unselected patients presenting with unilateral onychocryptosis and 35 unaffected controls were assessed for these three parameters. Of these, 80 per cent of controls and 85 per cent of patients could be classified correctly by the equation. It is thus proposed that, in the majority of subjects with onychocryptosis, a discrete anatomical predisposition exists and that the other factors act only as triggers in the development of the condition. This study provides a rationale for less traumatic surgical approaches to ingrown nail than nail avulsion, with or without nail bed ablation and may also provide a means of identifying high-risk groups.

Adolescent↗

Long-term results of silicone trapezial implant arthroplasty.

The senior author has performed the Swanson implant arthroplasty for arthritis of the basal joint of the thumb for the past 12 years. Fifty-two patients with a total of 64 arthroplasties of the thumb were reviewed, with follow-up periods of 12-156 months (average, 4.4 years). The majority (80%) of the arthroplasties were performed for osteoarthritis; 11% were performed for rheumatoid arthritis, 6% for traumatic arthritis, and 3% for mixed connective tissue disease. Subjective and objective hand functional measurements and radiographic examinations were performed in the majority of patients (77%). The overall results were good both subjectively and objectively. Although degenerative changes involving the implant occurred with increasing frequency as the follow-up period increased, these changes were not symptomatic in the majority of cases.

Adult↗