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Biomedical subjects

J Gibson

Publications and source records attributed to J Gibson.

At least 127 records · Page 7Linked to original sources

Angioedema and swellings of the orofacial region.

OBJECTIVE: Patients may have various forms of angioedema and require dental treatment which can cause or contribute to the onset of an episode of angioedema. This paper seeks to highlight the causes and the management of this serious condition. DESIGN: An outline of the different types of angioedema is given here, along with three case reports which illustrate treatment and management. SUBJECTS AND METHODS: Three patients who presented to an Oral Medicine clinic with angioedema are presented to illustrate various types of angioedema and the different contributing factors that precipitated episodes of the condition. MAIN OUTCOME MEASURES: The three patients were all investigated for biochemical and allergic factors which may have caused their disease. RESULTS: Both drugs and dental materials were shown to be involved in the pathogenesis of angioedema in this short series of patients. CONCLUSIONS: Dental treatment or the use of some materials may promote or contribute to the disorder. Referral to hospital for specialist care is indicated for certain groups of patients who require invasive dental treatment. The multi-disciplinary team approach in the investigation and management of patients with angioedema is emphasised.

Aged↗

4-hydroxybenzoyl coenzyme A reductase (dehydroxylating) is required for anaerobic degradation of 4-hydroxybenzoate by Rhodopseudomonas palustris and shares features with molybdenum-containing hydroxylases.

The anaerobic degradation of 4-hydroxybenzoate is initiated by the formation of 4-hydroxybenzoyl coenzyme A, with the next step proposed to be a dehydroxylation to benzoyl coenzyme A, the starting compound for a central pathway of aromatic compound ring reduction and cleavage. Three open reading frames, divergently transcribed from the 4-hydroxybenzoate coenzyme A ligase gene, hbaA, were identified and sequenced from the phototrophic bacterium Rhodopseudomonas palustris. These genes, named hbaBCD, specify polypeptides of 17.5, 82.6, and 34.5 kDa, respectively. The deduced amino acid sequences show considerable similarities to a group of hydroxylating enzymes involved in CO, xanthine, and nicotine metabolism that have conserved binding sites for [2Fe-2S] clusters and a molybdenum cofactor. Cassette disruption of the hbaB gene yielded a mutant that was unable to grow anaerobically on 4-hydroxybenzoate but grew normally on benzoate. The hbaB mutant cells did not accumulate [14C]benzoyl coenzyme A during short-term uptake of [14C]4-hydroxybenzoate, but benzoyl coenzyme A was the major radioactive metabolite formed by the wild type. In addition, crude extracts of the mutant failed to convert 4-hydroxybenzoyl coenzyme A to benzoyl coenzyme A. This evidence indicates that the hbaBCD genes encode the subunits of a 4-hydroxybenzoyl coenzyme A reductase (dehydroxylating). The sizes of the specified polypeptides are similar to those reported for 4-hydroxybenzoyl coenzyme A reductase isolated from the denitrifying bacterium Thauera aromatica. The amino acid consensus sequence for a molybdenum cofactor binding site is in HbaC. This cofactor appears to be an essential component because anaerobic growth of R. palustris on 4-hydroxybenzoate, but not on benzoate, was retarded unless 0.1 microM molybdate was added to the medium. Neither tungstate nor vanadate replaced molybdate, and tungstate competitively inhibited growth stimulation by molybdate.

Amino Acid Sequence↗

Search for Mycobacterium paratuberculosis DNA in orofacial granulomatosis and oral Crohn's disease tissue by polymerase chain reaction.

BACKGROUND: Although intestinal Crohn's disease has long been suspected to have a mycobacterial cause, possible mycobacterial involvement in orofacial granulomatosis (OFG) and oral lesions of Crohn's disease has not yet been investigated. AIMS: As the slow growing Mycobacterium paratuberculosis has been implicated in the aetiology of intestinal Crohn's disease, the potential involvement of this mycobacterial species in OFG and oral lesions of Crohn's disease was investigated. PATIENTS: To attempt detection of the organism in OFG and oral Crohn's disease tissue samples, a polymerase chain reaction (PCR) assay was used on archival formalin fixed, paraffin wax embedded oral tissue sections from 30 patients with OFG, seven with Crohn's disease, and 12 normal controls. METHODS: The PCR assay used was based on primers targeting the 5' region of the multicopy IS900 DNA insertion element of the M paratuberculosis genome. In order to achieve maximum sensitivity, two rounds of PCR were carried out and amplicons confirmed by Southern blot hybridisation to a digoxigenin labelled IS900 DNA probe. RESULTS: None of the OFG and oral lesions of Crohn's disease samples were positive for M paratuberculosis and all normal controls were also negative. CONCLUSIONS: These results suggest that M paratuberculosis may not be a major aetiological agent in OFG or oral Crohn's disease lesions, although the use of paraffin wax embedded tissue as opposed to fresh tissue as a sample source could underestimate the true prevalence of the organism.

Blotting, Southern↗

Disease progression in patients with multiple myeloma is associated with a concurrent alteration in the expression of both oncogenes and tumour suppressor genes and can be monitored by the oncoprotein phenotype.

The dysregulation of specific oncogenes due to either mutation or activation has previously been reported in a small number of patients with myeloma but the extent of oncogene dysregulation during the course of the disease is not known. The oncoprotein phenotype of plasma cells in 146 bone marrow samples from 81 patients with multiple myeloma was determined by dual colour flow cytometry using a predetermined panel of 8 monoclonal antibodies. High intensity CD38 expression was used to distinguish the plasma cell population and the cells were permeabilised to detect intracellular antigen expression. In situ hybridization using biotinylated cDNA probes for c-myc and bcl-2 was used to determine mRNA expression and to validate the flow cytometric assay. The normal range of expression for each of 6 oncoproteins (c-myc, c-fos, c-neu, bcl-2, p-ras, p53 mutant) and 2 tumour suppressor gene products (p53 wild and Rb) was determined in plasma cells from 33 normal bone marrows. Disease progression was associated with the concurrent abnormal expression of at least one oncogene and one tumour suppressor gene where as stable disease was associated with a normal expression of at least one or both (chi2 = 34.1; p < 0.001). At diagnosis there was a correlation between serum beta2 microglobulin and the concurrent overexpression of both an oncoprotein and a tumour suppressor gene product. Longitudinal studies of 33 different patients over 4 years, suggests that the progressive evolution of myeloma is a multistep process of genomic instability producing ongoing alterations in the expression of both oncogenes and tumour suppressor genes.

Adult↗

The functional phenotype of the primitive plasma cell in patients with multiple myeloma correlates with the clinical state.

The malignant plasma cells from patients with multiple myeloma display considerable phenotypic heterogeneity. All plasma cells express high intensity CD38 (CD38++), cytoplasmic immunoglobulin and either kappa or lambda light chains. Subpopulations of mature (CD45-), immature (CD45+) and primitive (CD45++, CD19+) plasma cells can be defined but little is known about the functional differences and clinical significance of these subpopulations. Three colour flow cytometry and permeabilisation was used to determine the expression of functionally important antigens in plasma cell subpopulations. These antigens included the labelling index (LI, bromodeoxyuridine), number of nucleoside transporter per cell, p-glycoprotein (JSB-1), and oncoprotein expression (c-myc, c-fos, c-neu, bcl-2, p-ras, p53m, p-53w, and Rb). In progressive disease there was an increase in the absolute number but not the percentage of CD45++ plasma cells. There was a significant difference in the mean LI of the CD38++, CD45++ population in progressive disease compared with stable disease (9.2% vs 2.2%; z = 19.9, p < 0.001). The LI of CD45++ cells ranged up to 45% and provided a better correlation with disease status than the LI of the total cell population. Any increase in nucleoside transporters or p-glycoprotein expression was almost entirely attributable to an increase in the primitive plasma cell population. In 96% (n = 28) of samples from patients in progressive disease there was at least one abnormality in the functional phenotype of the primitive plasma cells. This is in contrast with 44% of samples from patients in stable disease (n = 58). These studies suggest that the functional phenotype of the primitive plasma cell determines the clinical phenotype of patients with myeloma.

ADP-ribosyl Cyclase↗

An audit of antibiotic prescribing in general dental practice.

Clinical audit is widely recognised as the systematic and critical analysis of the quality of clinical care, including treatment regimes, the associated use of resources, and the resulting outcome and quality of life for the patient. The prescribing of antibiotics in general dental practice is an area 'wide open' for audit analysis since the profession must clearly accept its responsibility to use antibiotics sensibly; however, the definition of 'sensibly' is likely to vary from practitioner to practitioner. This audit reviews the need for antibiotic prescribing in general dental practice over two consecutive four-month periods. A consensus was achieved on the rationale for antibiotic prescribing and the number of prescriptions fell by 50% as a result.

Anti-Bacterial Agents↗

The Ontario trial of active compression-decompression cardiopulmonary resuscitation for in-hospital and prehospital cardiac arrest.

OBJECTIVE: To compare the impact of active compression-decompression (ACD) cardiopulmonary resuscitation (CPR) and standard CPR on the outcomes of in-hospital and prehospital victims of cardiac arrest. DESIGN: Randomized controlled trial with blinding of allocation using a sealed container. SETTINGS: (1) Emergency departments, wards, and intensive care units of 5 university hospitals and (2) all locations outside hospitals in 2 midsized cities. PATIENTS: A total of 1784 adults who had cardiac arrest. INTERVENTION: Patients received either standard or ACD CPR throughout resuscitation. MAIN OUTCOME MEASURES: Survival for 1 hour and to hospital discharge and the modified Mini-Mental State Examination (MMSE). RESULTS: All characteristics were similar in the standard and ACD CPR groups for the 773 in-hospital patients and the 1011 prehospital patients. For in-hospital patients, there were no significant differences between the standard (n = 368) and ACD (n = 405) CPR groups in survival for 1 hour (35.1% vs 34.6%; P = .89), in survival until hospital discharge (11.4% vs 10.4%; P = .64), or in the median MMSE score of survivors (37 in both groups). For patients who collapsed outside the hospital, there were also no significant differences between the standard (n = 510) and ACD (n = 501) CPR groups in survival for 1 hour (16.5% vs 18.2%; P = .48), in survival to hospital discharge (3.7% vs 4.6%; P = .49), or in the median MMSE score of survivors (35 in both groups). Exploration of clinically important subgroups failed to identify any patients who appeared to benefit from ACD CPR. CONCLUSIONS: ACD CPR did not improve survival or neurologic outcomes in any group of patients with cardiac arrest.

Adolescent↗

Flagellin gene profiling of Campylobacter jejuni heat-stable serotype 1 and 4 complex.

Flagellin gene (flaA) sequence polymorphisms were used to discriminate amongst 167 strains of Campylobacter jejuni serotype HS1 and the HS4 complex. Direct PCR of cell suspensions provided a rapid method for analysing DNase-negative strains, whereas purified DNA was necessary for the DNase-positive strains. Nine different PCR-RFLP patterns (genotypes) were identified by analysis with Hinfl and 12 with Ddel, giving a total of 19 combined flaA profile types. The most common combined fla types were H1D1 (35%) and H1D2 (20%) for serotype HS1, and H1D2 (23%) and H4D7 (43%) for serotype HS4. Comparison of flaA typing with other key subtyping methods for C. jejuni showed it to be less discriminatory than pulsed field gel electrophoretic (PFGE) profiling, but more so than ribotyping. Fla types provided a useful indication of strain diversity, but as some were conserved across different serotypes, ribotypes and PFGE types, the same fla type could not be used as the sole basis for grouping strains. We provide evidence for several distinct subgroups based on conserved multiple genomic criteria within the HS1 and HS4 strains, and conclude that monitoring of such subgroups could provide a novel basis for future epidemiological surveillance of C. jejuni.

Campylobacter jejuni↗

The labelling index of primitive plasma cells determines the clinical behaviour of patients with myelomatosis.

For patients with multiple myeloma the most important laboratory correlate of prognosis and disease activity is the bromodeoxyuridine (BrdUrd) plasma cell labelling index (LI). However, the traditional immunofluorescent microscope LI technique, like other manual enumeration assays, can suffer from poor precision and accuracy. In this study the LI of different subpopulations of plasma cells (CD38++) as determined by flow cytometry was correlated with disease state. The mean LI of the total CD38++ population was significantly higher (2.7 +/- 0.4%) than the LI determined by the traditional slide technique (0.6 +/- 0.1%) for 65 samples tested. Primitive plasma cells (CD38++, CD45++) had a higher labelling index than mature plasma cells (CD38++, CD45-) (7.0 +/- 1.3% v 1.8% +/- 0.3%) and in one patient the LI of the primitive plasma cells was 46%. In addition, the LI of the mature plasma cells was lower than the total plasma cell population. As expected, there was a significant difference between the LI of patients in plateau phase and progressive disease but this difference was greatest when the LI of the primitive plasma cells was studied (9.2 +/- 2.9% v 2.2 +/- 0.7%; z = 19.9, P < 0.001). This study has raised some concerns about the sensitivity and accuracy of the traditional labelling index and has shown that the increased LI associated with progressive disease is almost entirely attributable to an increase in the LI of the primitive plasma cell subpopulation and that the LI of primitive plasma cells provides a more clinically significant correlation with disease status than the traditional assay.

ADP-ribosyl Cyclase↗

Rapid quantitation of mixed red cell populations using flow cytometry.

Methods are described for the identification and quantitation of mixed red cell populations using flow cytometry. Antibodies specific for a wide range of blood group antigens have been used and examples are given in which these analyses have proved to be of clinical use. These examples include monitoring of erythropoiesis following engraftment in allogeneic bone marrow transplant recipients and the detection of chimaeric states months or years after transplantation. The techniques involved are fast, simple and inexpensive.

Bone Marrow Transplantation↗