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Biomedical subjects

D Briggs

Publications and source records attributed to D Briggs.

At least 55 records · Page 3Linked to original sources

Developmental expression pattern screen for genes predicted in the C. elegans genome sequencing project.

Maximum use should be made of information generated in the genome sequencing projects. Toward this end, we have initiated a genome sequence-based, expression pattern screen of genes predicted from the Caenorhabditis elegans genome sequence data. We examined beta-galactosidase expression patterns in C. elegans lines transformed with lacZ reporter gene fusions constructed using predicted C. elegans gene promoter regions. Of the predicted genes in the cosmids analysed so far, 67% are amenable to the approach and 54% of examined genes yielded a developmental expression pattern. Expression pattern information is being made generally available using computer databases.

Animals↗

Renal artery stenosis managed by Palmaz stent insertion: technical and clinical outcome.

OBJECTIVE: To assess the technical and clinical outcome of Palmaz renal artery stent insertion in patients with renal artery stenosis. DESIGN: Twenty-nine patients with radiological evidence of renal artery stenosis and hypertension (16 patients, mean +/- SD diastolic blood pressure 100.5 +/- 8.16 mmHg) and/or renal impairment (17 patients, mean +/- SD serum creatinine 376 +/- 169 mu mol/l) were referred for radiological intervention. Of these, 22 had ostial atheromatous lesions, six had atheromatous non-ostial lesions and one patient had fibromuscular dysplasia. Palmaz stent insertion was performed where either previous or concomitant percutaneous transluminal renal angioplasty (PTRA) had been unsuccessful. Technical success was defined primarily as <30% residual stenosis. A prospective radiological and clinical follow-up was performed and the results compared with the outcome following PTRA alone in a similar group of patients from our centre. RESULTS: Immediate technical success was achieved in all 29 patients. Follow-up angiography in 24 patients after a mean of 7 months showed restenosis in four patients. The hypertension was not 'cured' in any patient; a blood pressure fall was observed in seven patients (44%) and no change in the remaining nine subjects (56%). Renal function improved in four patients (24%), two of whom had angiotensin converting enzyme inhibitor-exacerbated renal impairment. This compares with an immediate technical success of 81% for PTRA alone, with cure in 50% and improvement in 32% of patients with hypertension and improvement in renal function in 64.7% of patients with renal impairment. CONCLUSIONS: Palmaz renal artery stent insertion has a higher technical success rate than PTRA, but the clinical improvement is disappointing in our patient population.

Adult↗

Clinical benchmarking improves clinical paths: experience with coronary artery bypass grafting.

BACKGROUND: Clinical paths and clinical benchmarking are consistent with, and readily adaptable to, any health care organization that espouses the principles of continuous quality improvement. CLINICAL PATHWAY: In its initial clinical path project, Borgess Medical Center analyzed and streamlined the processes of caring for a coronary artery bypass graft (CABG) patient. Team discussions were driven by comparative data, specialty guidelines, peer review organization guidelines, patient financial statements, patient records, and the applicable literature. One year after the CABG clinical paths were implemented, average total charges to the patient dropped from $35,700 to $32,700. Average length of stay also dropped, from 11.1 to 9.7 days. The mortality rate held stable at 2.7%. CLINICAL BENCHMARKING: Recognizing the opportunity to further improve its CABG clinical path, Borgess participated in MediQual's CABG benchmarking project. The team followed MediQual's five phases of clinical benchmarking: focus and opportunity assessment, outcome analysis and comparison, clinical process documentation, benchmark process comparison, and action planning, implementation, and monitoring. Using benchmark data provided by MediQual, the CABG benchmark team focused on the high-risk population and identified further opportunities for streamlining the CABG clinical pathway. Several areas for improvement were identified by comparing Borgess's practices to the benchmark hospitals. CONCLUSION: Developing a clinical path before beginning to benchmark "forced" Borgess Medical Center to develop a clear understanding of its own processes. This allowed the benchmark team to easily identify variances between its CABG processes and those of the benchmark hospitals and to select which variations the hospital should adopt.

Clinical Protocols↗

Severe occupational traumatic injuries.

Severe occupational traumatic injuries represent a challenge to workers and physicians. Efforts to prevent occupational injuries, such as education, protective equipment, adherence to safety procedures, and personal responsibility, are of critical importance. The physician's role as educator, consultant, and on-site manager of these injuries forms the basis for effective management of severe occupational traumatic injuries. Rapid assessment and treatment by coworkers trained in first aid can be vital in preventing more serious sequelae.

Accidents, Occupational↗

Static secondary ion mass spectrometric investigation of the surface chemistry of organic plasma-deposited films created from oxygen-containing precursors. 3. Multivariate statistical modeling.

Partial least squares (PLS) multivariate statistical models were developed to predict the surface composition and chemistry of a set of model homopolymers based on their static SIMS fragmentation patterns. In the calibration or model-building step, the positive and negative ion static SIMS spectra of different classes of model homopolymers were related to specific chemical attributes of the polymers. The models were then used to examine the surface chemistry of oxygen-containing plasma-deposited films prepared from a variety of precursors. PLS models were developed to predict the surface oxygen concentration and H/C ratios. The results obtained from the PLS models were compared with experimental results.

Analysis of Variance↗

A molecular and serologic analysis of the major histocompatibility complex and complement component C4 in systemic sclerosis.

OBJECTIVE: To investigate the contributions of the major histocompatibility complex (MHC) and C4 alleles to systemic sclerosis (SSc), and to pulmonary fibrosis and autoantibody expression in SSc, by analysis at the DNA level. METHODS: One hundred fifteen patients with SSc were tested serologically for alleles of the class I MHC loci, and were tested for class II alleles (DRB, DQA, and DPB) by a combination of restriction fragment length polymorphism (RFLP) analysis and oligonucleotide probes with polymerase chain reaction amplification. C4 was studied by protein phenotyping and RFLP analysis in 80 patients. Correlations were made between disease status, pulmonary fibrosis, and expression of anticentromere antibodies (ACA) and anti-Scl-70. RESULTS: The C4A-null phenotype was found to provide the strongest disease association factor of the MHC region (P = 0.000064, relative risk [RR] = 2.8, etiologic fraction [EF] = 32.1). The primary MHC susceptibility allele was found to be DQA2 (Pcorr = 0.0009, RR = 2.5, EF = 35.6), which is in linkage disequilibrium with both DR3 and DR11. DR2 was protective, but only for female patients (P = 0.0021, RR = 0.42, protective fraction = 19.4). DR52a was the primary MHC allele associated with pulmonary fibrosis in SSc patients. Expression of ACA was associated with the presence of either DR1 or DR4 (P = 0.0015, RR = 6.7, EF = 78.0). Anti-Scl-70 expression correlated with an acidic residue of DP beta (DPB1:69:E) (P = 0.0063, RR = 4.6, EF = 53.1). CONCLUSION: Of all the potential markers of disease susceptibility analyzed, the C4A locus was the strongest. C4AQ0 and DQA2 are independent susceptibility factors for SSc. The development of pulmonary fibrosis in SSc patients can be predicted using combined MHC and autoantibody analysis. The MHC alleles associated with the expression of disease-specific autoantibodies are not markers for disease susceptibility.

Alleles↗

Hepatitis B prevalence in local authority employees.

Prevalence of hepatitis B infection was determined in 420 employees from three local authorities by testing for hepatitis B core antibody (anti-HBc). Five (1.2 per cent) were positive: this included a hepatitis BsAg carrier, three with antibody to hepatitis BsAg (anti-HBs) and one who had only anti-HBc. The prevalence of hepatitis B was not significantly different (P > 0.05) from a control group of blood donors. However, four out of five anti-HBc positive individuals worked with mentally or physically handicapped individuals or those discharged into the community after long-term institutionalized care.

Adolescent↗

Connective tissue disease and autoantibodies in the kindreds of 63 patients with systemic sclerosis. The United Kingdom Systemic Sclerosis Study Group.

Systemic sclerosis (SSc) tends to occur in a sporadic fashion and familial occurrence of the disease is unusual. Nevertheless, reports of related connective tissue diseases (CTD), autoantibodies, or both in family members together with associations of certain HLA class II phenotypes with SSc suggest that genetic factors might play a part in susceptibility to the disease. Because of the relative rarity of SSc only a small number of family pedigrees have been studied previously. This report represents the largest study to date, to our knowledge, of family members of patients with scleroderma, and provides the opportunity to investigate the relative importance of genetic and environmental factors operating in the disease. The family pedigrees of 63 patients with systemic sclerosis were examined with respect to clinical, serologic, and immunogenetic features. Multiple cases of SSc were seen only in 1 family, in which the disease affected a father and daughter. Disease expression in these 2 individuals was very similar both clinically and serologically; relatives with other connective tissue diseases were found in 9 families, and nonspecific features of CTD such as Raynaud phenomenon, and arthralgia or arthritis, occurred commonly, especially in female relatives. Antinuclear antibodies (ANA) were also detected more frequently in relatives than in controls. However, antibodies previously demonstrated to have a high degree of specificity for SSc were confined to patients with this disease. Probands had an increase in the frequency of HLA-DR3, DR5, and C4AQO. Patients with diffuse scleroderma had an increased frequency of HLA-DR3, while those with the limited form of the disease had an increased frequency of HLA-DR5.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Variations between Biomer lots. I. Significant differences in the surface chemistry of two lots of a commercial poly(ether urethane).

We have studied the surface chemistry of two lots of Biomer (BSP067 and BSUA001), a widely used commercial poly(ether urethane) (PEU). Although transmission infrared adsorption studies revealed no differences in the bulk chemistry of the two lots, the surface chemistry, as seen by x-ray photoelectron spectroscopy (XPS) and static secondary ion mass spectrometry (SIMS), was different. Lot BSP067 showed soft-segment enrichment at the surface, which is typical of PEU. Lot BSUA001 showed no evidence of either hard- or soft-segment PEU components at the surface. The surface of this lot was completely covered with a nonextractable additive identified as poly(diisopropyl amino ethyl methacrylate). Small amounts of a low-molecular-weight antioxidant were observed at the surface of both samples. Because the biological response to polymers is dependent on surface structure, these results are of considerable importance to biomaterials research.

Antioxidants↗

Analysis of complement C4 loci in Caucasoids and Japanese with idiopathic membranous nephropathy.

Deletion of the HLA class III complement gene, C4A, has been linked with susceptibility to a number of autoimmune diseases. In this study, we show a strong positive association between C4A gene deletion and development of idiopathic membranous nephropathy (IMN) in European Caucasoids [patients, 17/27 (63%); healthy controls, 13/65 (20%); RR 6.8; P = 0.003]. To clarify whether C4A deletion is an independent risk factor for IMN or is increased secondarily to the Caucasoid HLA A1, B8, DR3 extended haplotype, we examined the frequency of C4A deletion in Japanese patients, in whom the disease is associated with another HLA haplotype (DR2-DQw1). Analysis of 31 Japanese patients and 46 healthy controls showed that C4A deletion was present in only one patient (3%) and one control (2%). In addition, examination of the C4B locus in Japanese patients showed that there was no significant increase in the estimated frequency of C4B deletion in patients against controls (31 vs. 27%) and no difference in the frequency of the C4B long gene (73 vs. 87%) or C4B short gene (77 vs. 78%). We conclude that although C4A deletion confers significant risk of IMN in Caucasoids, there is no significant association between C4 polymorphism, as detected here, and risk of IMN in Japanese. This suggests that either C4A deletion is irrelevant to the pathogenesis of IMN or that more than one genetic mechanism is involved.

Asian People↗

The immunogenetic background of scleroderma--an overview.

Currently it may be stated that the MHC associations in scleroderma support the classification of disease subsets, but in no ethnic group is the overall association strong enough for clinical use. In different ethnic groups, the distribution of MHC alleles varies, as does the degree of linkage disequilibrium between alleles of the linked loci. This concept is even relevant to relatively close populations. Thus Whiteside noticed that, if those patients referred from more than 100 miles from the study centre were excluded, then the strength of the DR1 association increased. The environmental contribution to scleroderma is unknown, except in the case of toxin or solvent associated disease. Different causal environmental agents found in different global regions might result in separate MHC associations and hence explain the discrepancies noted above. There are indications that associations between specific subsets of SSc patients and genetic markers will assume greater importance both diagnostically and prognostically. The lung fibrosis group look prime candidates, for example. Genetic markers are also a useful means of relating chemically-induced SSc-like disorders to the classical disease. Vinyl chloride disease provides an example. There is much heterogeneity within the disease, in terms of extent of skin involvement, severity, and of organ involvement. It is clear that the different clinical subsets of scleroderma are characterized by different associated MHC alleles. There are also many cases of clinical overlap with related diseases, and certain of these diseases have a different HLA association, which could detract from the primary HLA type associated with SSc.(ABSTRACT TRUNCATED AT 250 WORDS)

Autoantibodies↗

Surface characterization of 2-hydroxyethyl methacrylate/styrene copolymers by angle-dependent X-ray photoelectron spectroscopy and static secondary ion mass spectrometry.

The surface composition and structure of three structurally distinct amphiphilic copolymers of 2-hydroxyethyl methacrylate (HEMA) and styrene have been examined with angle-dependent X-ray photoelectron spectroscopy (XPS) and static secondary ion mass spectrometry (SIMS). The phase-separated block copolymer made by anionic living polymerization, HSH-A50, showed significant surface enrichment of styrene. The outermost 2-3 A appeared to be approximately 100% styrene, with the styrene concentration decreasing to its bulk value at a depth of approximately 50 A from the surface. However, HEMA was detected in the outer 20 A of this copolymer. The presence of HEMA in the surface region implies this copolymer may undergo significant restructuring when hydrated in a hydrophilic environment (as opposed to the hydrophobic environment in which the sample was prepared and analyzed). The phase-separated block copolymer made by telechelic coupling of free radical polymerized functionalized oligomers, HSH-B60, showed only slight styrene enrichment at the surface. Both HEMA and styrene were detected at all sampling depths, including the outermost surface layer, consistent with the presence of discrete HEMA and styrene domains at the copolymer surface. Since both components are already present at the surface under hydrophobic conditions, the degree of restructuring this copolymer may undergo upon hydration should be minor. The random HEMA--styrene copolymer made by conventional free radical initiation techniques, HS-RAN50, had a surface composition that was similar to the bulk composition and independent of depth, as expected for a homogeneously mixed copolymer film.

Biocompatible Materials↗

Psychopathic disordered, mentally ill, and mentally handicapped sex offenders: a comparative study.

Although there currently exists a large amount of research on the characteristics and treatment of psychopathic disordered (PD) sex offenders, little if any empirical studies have addressed the mentally ill (MI) and mentally handicapped (MH) offender populations. A total of 106 PD, MI, and MH sex offender records from Rampton (Special) Hospital were reviewed for the study. Offender categories were compared by age of first documented sex offence, IQ at the time of admission, sex offence type, frequency of each offence type, history of violence during sex offences, age and gender of sex offence victims and number of victims for age and gender. Results revealed that 88 per cent of PD, 98 per cent of MI, and only 56 per cent of MH offenders' victims were female. Further analysis revealed that PD and MI offenders' victims were primarily female, with the largest proportion being pubescent and adult females. MH offender victims were primarily males and females under the age of 16. IQ correlated positively with history of violence during sexual assault and mean IQs were higher for 'violent' than 'non-violent' offenders in each offender category. A discussion of these and other significant findings, as well as implications for clinical treatment, is presented.

Adolescent↗

Homoeopathy.

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Homeopathy↗

Static secondary-ion mass spectrometric investigation of the surface structure of organic plasma-deposited films prepared from stable-isotope-labeled precursors. 1. Carbonyl precursors.

Stable-isotope-labeled carbonyl precursors (acetaldehyde, acetone, and 2-butanone) were used to create plasma-deposited films (PDFs), which were then examined by positive- and negative-ion static SIMS. This allowed hydrocarbon (HC) fragments to be distinguished from oxygen-containing fragments in the static SIMS spectra of these PDFs. Both the positive- and negative-ion static SIMS fragmentation patterns of conventional HC and oxygen-containing polymers were qualitatively examined in order to assign structural units on the PDF surface that could account for the sallent features in the static SIMS fragmentation patterns of these PDFs.

Hydrocarbons↗

A pause site for RNA polymerase II is associated with termination of transcription.

Termination of transcription by RNA polymerase II has been postulated to involve a pausing process. We have identified such a pause signal, 350 bp into the 3' flanking region of the human alpha 2 globin gene at a position where termination is thought to occur. We show that this pause signal enhances the utilization of an upstream poly(A) site which is otherwise out-competed by a stronger downstream poly(A) site. We also demonstrate that the pause site rescues a poly(A) site that is inactive due to its location within an intron. Using nuclear run-on analysis we show that elongating RNA polymerase II molecules accumulate over this pause signal. Furthermore we show that when the pause site is positioned immediately downstream of a strong poly(A) signal, significant levels of transcription termination take place.

Base Sequence↗

Critical care nurses' roles--traditional or expanded/extended.

The concept of role is an important one and an issue which should be more often addressed within the so called high technology areas. The unique environment within specialist critical care units means that nurses are frequently in danger of becoming pseudo medics. The intention in this paper is to explore the issue of nurses' role--traditional, extended/expanded and futuristic from an intensive care perspective.

Critical Care↗

Major histocompatibility complex class II genes and systemic sclerosis.

1. In no ethnic group is the overall association between systemic sclerosis and the MHC strong enough for direct clinical use. MHC associations do support the classification of the disease into limited cutaneous systemic sclerosis and diffuse cutaneous systemic sclerosis. 2. Indications are that associations between specific subsets of patients with systemic sclerosis and genetic markers will assume greater importance both diagnostically and prognostically. The group with lung fibrosis look prime candidates, for example. 3. Genetic markers are useful means of relating chemically induced systemic sclerosis like disorders with the classical disease. Vinyl chloride disease provides an example. 4. Evidence is emerging of strong associations between certain genetic markers and autoantibody production; a similar story has emerged in systemic lupus erythematosus. We believe that, eventually, genetic tests will be used to influence treatment in at least a subset of patients with systemic sclerosis but that a dramatic breakthrough will not be made until we know how the genetics of the disease relate to the primary biochemical disease characteristic--that is, the overproduction of collagen. In this respect it has been suggested that the 5' flanking DNA of dermal collagen genes is particularly susceptible to the action of Scl-70 (topoisomerase I). A problem is how to tie this and the other observations discussed above together. The association of autoantibodies with topoisomerase I provides a tentative link between the MHC and collagen gene expression. Although the role and reason for anti-Scl-70 in systemic sclerosis is unknown, humoral autoimmunity, at least in systemic lupus erythematosus, seems to be strongly dependent on specific HLA genes. With an understanding of the function of MHC products at the molecular level, HLA and disease associations can now be analysed on a mechanistic level. For insulin dependent diabetes mellitus it has been shown that the MHC determined susceptibility to the disease is conferred by neutral residues (Val, Ser, Ala), at position 57 of the DQ beta chain, while Asp at this position correlates with resistance. A similar phenomenon has been described in rheumatoid arthritis. Although DR4 in general is associated with rheumatoid arthritis, it is heterogeneous, but a subtype of DR4 which is characterised by positively charged residues at positions 70 and 71 of the beta chains is not found in patients with rheumatoid arthritis (Wordsworth B P et al, unpublished data). A similar approach applied to the study of systemic sclerosis is likely to be similarly rewarding. The precise subtyping of the class II genes and the characterisation of their associated haplotypes is therefore required for a complete understanding of the contribution of the MHC to the disease. Additional genes linked to the MHC must not be overlooked, and are relevant to associations of haplotypes with the disease. Of particular interest are the recent reports of a new class of proteins, which are determined by genes in the MHC and which are considered to play a part in the assembly of the antigen peptide/MHC molecule complex.

Environmental Exposure↗