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Biomedical subjects

P Brooks

Publications and source records attributed to P Brooks.

At least 91 records · Page 5Linked to original sources

Scleroderma and augmentation mammoplasty--a causal relationship?

BACKGROUND: The studies implicating a causal relationship between silicone and scleroderma, other autoimmune disease, and fibromyalgia-like symptoms have been largely descriptive with absence of appropriate controls and no consideration of potential confounders. This case control study of augmentation mammoplasty and scleroderma represents an attempt to answer these deficiencies. AIMS: To compare the frequency and temporal relationship of augmentation mammoplasty in interviewed and deceased cases and interviewed controls. To determine the frequencies of exposure to non-augmentation mammoplasty silicone, and to determine the frequencies of mastectomy and breast lumpectomy in interviewed cases and controls. METHODS: Scleroderma cases and age-stratified general practice controls were interviewed using a prepilotted telephone questionnaire. Self-reported date/s of augmentation mammoplasty were ascertained, as were dates of onset of first and second scleroderma symptom/s and scleroderma diagnosis, where relevant. Comparison of socioeconomically adjusted rates was expressed in terms of rate ratios. RESULTS: Augmentation mammoplasty rates were comparable between interviewed cases and controls. No augmentation mammoplasty procedures were documented in deceased scleroderma patients' medical records. Rates of exposure to non-mammoplasty silicone, mastectomy and breast lumpectomy were comparable in interviewed cases and controls. CONCLUSIONS: This study failed to demonstrate an association between silicone breast implantation and the subsequent development of scleroderma, to a relative risk level as low as 4.5 with 90% power.

Adult↗

Phanerochaete chrysosporium and its natural substrate.

We seek to define more fully how Phanerochaete chrysosporium degrades its natural substrate, lignocellulose. This contribution concerns several relevant topics. Mineralisation of [14C]DHP, as a model for lignin degradation, showed that a set of genetically defined meiotically derived products of strain ME446 differed in their degradative ability and also that, under optimum conditions for mineralisation, extracellular lignin peroxidase activity was absent. Xylanolytic and xylosidase/beta(1-->3) glucanase activities are also described. The complexity of the CBHI gene family is described and differential splicing of a CBHI gene transcript is proposed. In contrast to the multiplicity of CHBI genes there is a single CBHII gene. PCR methods were developed to analyse differential gene expression on different substrates. We have also developed a transformation system involving a reporter construct for the analysis of CBHI promoter function.

Basidiomycota↗

Nonsteroidal anti-inflammatory drugs. Differential use in older patients.

The nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used medications, particularly in elderly patients, for both rheumatic and nonrheumatic conditions. Elderly patients are more prone to the adverse effects of these agents. Adverse effects are seen in almost every organ system, but the gastrointestinal tract is most frequently affected. Elderly patients are more at risk of adverse effects from a wide range of pharmacokinetic and pharmacodynamic interactions compared with younger patients. By cautious prescribing, including giving due consideration to these factors, the risks associated with NSAIDs in elderly patients can be minimised.

Aged↗

The investigation and treatment of disorders of the knee: indications and a cost-comparison of arthroscopy and magnetic resonance imaging.

Results of a year-long prospective audit of all arthroscopies of the knee in one NHS Trust hospital indicate that selective magnetic resonance imaging (MRI) would be cost-effective in up to 40% of patients. However, to achieve such savings, at least 14% of patients who would otherwise need diagnostic arthroscopy would need to be excluded from surgery, the cost of MRI must be low, and the success rate of interpreting the scans should be known.

Adolescent↗

DC-ART: decreased inflammatory synovitis.

As part of the proposal for drug development using the SMARD/DC-ART definitions, "decreased inflammatory synovitis" needs to be defined. We review the literature with respect to each of the indirect, clinical measures of decreased inflammatory synovitis and recommend a preliminary, testable definition based on a per patient response. It includes minimum disease activity criteria for patients entering studies and improvement in at least 5 of the following 6 criteria: greater than 20% improvement in joint swelling count; greater than 20% improvement in joint tenderness count; greater than 20% improvement in erythrocyte sedimentation rate; greater than 30% improvement in physician/assessor global assessment; greater than 30% improvement in pain. While this definition is sensible within the confines of our knowledge to date, using these criteria prospectively in several clinical trials will allow better definition of the appropriate pooled index to define decreased inflammatory synovitis.

Antirheumatic Agents↗

Isozyme specific polymerase chain reaction analysis of differential gene expression: a general method applied to lignin peroxidase genes of Phanerochaete chrysosporium.

Analysis of differential expression of closely related genes is a general problem. The lignin peroxidase genes of Phanerochaete chrysosporium represent a typical case. They are differentially expressed according to the conditions encountered during growth. We show that the expression of two such genes, LIG1 and LIG5, can be differentiated at the mRNA level using a highly specific form of the polymerase chain reaction. This generally applicable method allows rapid and accurate analysis of complex and closely related mRNA populations.

Base Sequence↗

Disease-modifying antirheumatic drugs, including methotrexate, sulfasalazine, gold, antimalarials, and D-penicillamine.

Rheumatoid arthritis is a progressive inflammatory disease with evidence of early cartilage damage. Consequently, there is a trend toward earlier use of disease-modifying antirheumatic drugs. This review focuses on recent data on methotrexate, sulfasalazine, gold, hydroxychloroquine, D-penicillamine, and combination therapy. Methotrexate is focused on most, reflecting the increasing popularity of this agent; studies continue to show its good clinical efficacy. Combination therapy studies have been disappointing and are still marred by short duration and low power. Sulfasalazine has a fairly rapid onset of clinical effects and modulates immune function. Gold is still the subject of new studies, with evidence that clinical experience leads to improved patient efficacy. The beneficial effect of hydroxychloroquine in mild rheumatoid arthritis has been confirmed, and information on D-penicillamine suggests an effect on oxygen radical scavenging. Clinical studies are still required to ascertain the relative efficacy of these drugs, and potential long-term adverse effects remain a source of concern.

Anti-Inflammatory Agents↗

The changing role of volunteerism.

As the number of Americans who volunteer grows, the definition of "volunteer" is becoming more broad. In addition to the traditional volunteer opportunity, there are community service, student internship, and court-ordered service programs, all of which pose a set of complicated managerial questions for those charged with designing and running volunteer programs. Today, volunteers' motives may extend further than the simple desire to help their neighbor. For example, given the tough job market, some individuals are volunteering as a possible bridge to employment, and are eager to learn skills and gain experience that they might transfer to a new work setting. The growth in the number of volunteers is not without its down side, however. As governments have cut back on service programs, some responsibilities traditionally assumed by government are being shunted to volunteer organizations, an inappropriate solution. Although volunteer programs deserve support, governments cannot be let off the hook. Volunteers cannot and should not replace paid staff. There are a number of exciting and innovative approaches to recruiting, managing, and motivating volunteers. Some programs are responding to the new kinds of volunteers by restructuring the volunteer opportunity to make it more accessible to those who work from 9 to 5. Others are responding to the diversity of the communities they serve by seeking training in cultural sensitivity and recruiting volunteers from the community. Whatever the volunteer opportunity, the screening and placement interview is a crucial first step. It should be used to clarify expectations--of the volunteer and of the volunteer administrator. Once volunteers are on board, the key to managing and retaining volunteers is to recognize what motivates the individual volunteer--whether it is the desire to acquire job-related skills, to socialize, or simply to learn new things--and to provide the volunteer with these opportunities. Continuing education, training, and feedback are essential ingredients of any volunteer program. Another key to retaining volunteers is appropriate recognition. Although volunteers may appreciate the traditional pin or letter of thanks, volunteer administrators should explore other means of recognition that are tied in to the individual volunteer's motives for volunteering in the first place. Involving volunteers in the development and refinement of the volunteer program and considering their suggestions for improvements are important ways of keeping them involved and signaling recognition of their expertise and value.(ABSTRACT TRUNCATED AT 400 WORDS)

Acquired Immunodeficiency Syndrome↗

The chondroprotective drugs, Arteparon and sodium pentosan polysulphate, increase collagenase activity and inhibit stromelysin activity in vitro.

The effects of the chondroprotective drugs, sodium pentosan polysulphate (SP54) and Arteparon (glycosaminoglycan polysulphate), on the in vitro activities of the purified matrix metalloproteinases interstitial collagenase (matrix metalloproteinase 1, MMP1) and stromelysin (MMP3) were examined. Both drugs produced concentration-dependent enhancement of the degradation of type I collagen fibrils by purified human fibroblast collagenase and rat tumour collagenase. Rat collagenase activity was increased by drug concentrations above 0.5 microgram/mL, whereas human collagenase activity was only increased by higher drug concentrations, above 5 micrograms/mL. The concentration dependence of the increase in rat collagenase activity was similar for both drugs, with a maximal 3-fold increase at 50 micrograms/mL. In contrast, human collagenase activity was increased to a greater extent by SP 54 compared to Arteparon, with maximal increases at 5000 micrograms/mL of 6-fold and 2-4-fold, respectively. Both drugs produced concentration-dependent inhibition of the proteoglycan-degrading activity of both human fibroblast stromelysin and rat tumour stromelysin. Rat and human stromelysin activities were inhibited at drug concentrations above 0.005 microgram/mL, with a similar concentration dependence for both drugs. Fifty percent inhibition of rat stromelysin was produced by concentrations of each drug in the 0.5-5 microgram/mL range. The pattern of inhibition of human stromelysin was similar, except that drug concentrations in the 500-5000 micrograms/mL range produced 50% inhibition. The possible modes of action for these drug effects and their possible pharmacological significance are discussed.

Animals↗

Current issues of methotrexate and cyclosporine.

Methotrexate given in weekly oral-pulse regimens is rapidly becoming the most popular of the antirheumatic drugs. It seems to act relatively quickly (within 6 to 8 weeks) and patients continue to take it for a longer period of time than other antirheumatic drugs. This issue of long-term hepatotoxicity still has not been clarified, and concerns are now being raised regarding increased infection rates and whether methotrexate should be stopped before joint replacement surgery. Methotrexate, however, remains a very easy drug to use, although in the future it will probably be used as part of combination therapy. Although several clinical trials have demonstrated efficacy for cyclosporine in active rheumatoid arthritis, problems with renal toxicity are still significant. The majority of patients exhibit a rise in the serum creatinine level, although this returns to a normal level when cyclosporine is ceased. In view of this, cyclosporine is likely to remain a drug used in selected, severe cases not responding to other agents.

Arthritis, Rheumatoid↗

Transient ischemia attenuates neuronal afterdischarges induced in the absence of synaptic transmission.

In vitro hippocampal slices were prepared from animals previously subjected to a 10-min period of transient forebrain ischemia. Electrophysiological responses were examined in the selectively vulnerable CA1 region in the presence of standard (2.0 mM) and reduced (0.2 mM) calcium concentrations. Synaptic responses evoked by orthodromic stimulation in standard calcium were intact following ischemia. In contrast, repetitive neuronal discharges, which are normally evoked by antidromic stimulation in the presence of low calcium concentrations, were attenuated or eliminated following ischemia. The possible contributions of presynaptic and postsynaptic mechanisms to post-ischemic hyperexcitability are discussed.

Animals↗