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Biomedical subjects

B Richards

Publications and source records attributed to B Richards.

At least 19 recordsLinked to original sources

Characterization and rapid analysis of the highly polymorphic VNTR locus D4S125 (YNZ32), closely linked to the Huntington disease gene.

The highly polymorphic VNTR locus pYNZ32 has been more extensively characterized, and its analysis converted to a rapid PCR-based format. DNA sequencing in the areas within and flanking the repeated segment allowed the design of specific amplification primers. The repeated region of pYNZ32 consists of an imperfectly duplicated 27-bp motif, 16 bases of which are more highly conserved. Allelic products from PCR amplification were resolved into nine different size classes ranging from approximately 1400 to 2200 bp. Additional polymorphism was revealed when the amplified products were analyzed by restriction enzyme digestion. Both the overall size variation and the internal sequence polymorphism were used to determine a heterozygosity value of 86% for YNZ32 in 50 unrelated individuals. The rapid analysis and improved resolution of amplified alleles on agarose gels, and the internal variability within YNZ32, increase its diagnostic utility as a VNTR and as a linkage marker for the nearby Huntington disease gene.

Base Sequence

Interpretation of biopsies of "normal" urothelium in patients with superficial bladder cancer. MRC Superficial Bladder Cancer Sub Group.

In the course of a Medical Research Council trial of intravesical chemotherapy, biopsies were taken from apparently normal bladder urothelium near to newly diagnosed superficial bladder cancers in 417 patients. Differences were noted in the rates at which histological features were described in different centres. To gain more information about the reproducibility of the pathological findings, a group of 6 pathologists (5 from the UK and 1 from the USA), all having a special interest in urological pathology, were asked to examine a representative sample of 92 slides. They were then asked to re-examine 30 of them after an interval of at least 6 months. At first examination and at re-examination the slides were assessed using a standard proforma. However, the definitions of the categories were left unspecified for the pathologists to use their own criteria. The 5 UK pathologists then met to establish a consensus view of each slide. The results indicated that: (1) The reporting of non-dysplastic changes varied so much between pathologists as to render it of little value to clinical practice. (2) There were wide variations between different pathologists in the reported incidence of dysplastic change. (3) On a second review the pathologists reproduced their own assessment on only 62% of occasions. (4) Even after discussion between pathologists there was no consensus on the diagnosis of mild as opposed to moderate dysplasia. Consensus was reached on all biopsies which showed either severe dysplasia or carcinoma in situ. (5) In adopting a policy of taking urothelial biopsies, urologists should be aware of the imprecision and lack of reproducibility in the interpretation of such biopsies. (6) Biopsies of cystoscopically normal urothelium may not be a useful guide in defining therapy.

Biopsy

Results of Medical Research Council phase II study of low dose cisplatin and methotrexate in the primary treatment of locally advanced (T3 and T4) transitional cell carcinoma of the bladder.

A series of 49 previously untreated patients with category T3 or T4 bladder cancer underwent treatment with low dose methotrexate and cisplatin; 44 patients were eligible for assessment of response. Complete response (CR) was seen in 5 patients (11%) and partial response in 15 (34%) (overall response rate 45%). Treatment was reasonably well tolerated with no major morbidity and no treatment-related deaths. After a median follow-up of 3.5 years, the 1-year and 2-year survival rates were 70 and 30% respectively. Ten patients remain recurrence-free without having received "definitive local therapy" (cystectomy and/or radiotherapy) at follow-up extending from 20 to 50 months.

Adult

The technical aspects of computers.

This chapter is concerned with the technical aspects of computers. It is therefore concerned with how computers came about in the way they did, and who were the people who pioneered their development--what they were like in the early years, what they are like now, and what are likely to be the future developments. The emphasis is always on giving information to the readers so that they may know what questions to ask of the experts and, equally important, which experts to spend time with. In consequence of this last statement it becomes necessary to present a panorama showing the range of computers both size-wise and cost-wise; such scenario will therefore cover the vista from large main-frames (which must inevitably be needed in District Health Authorities and District General Hospitals) to the desk-top personal computers which all clinicians of the future will find essential. Because readers will be experiencing the impact and, hopefully, the benefits of the computer at the lower end of the size and price scale, considerable space has been devoted to explaining the various items (disc drives, monitors, printers) that pervade the microcomputer scene. New terminology must be introduced to readers if they are to discuss intelligently their computer needs to the providers of such facilities. Just as an automobile is no use without oil, petrol, water and a competent user, so the computer hardware needs computer software and a competent user. The chapter therefore continued with some considerable space being devoted to software (operating systems, programming languages, utilities and expert systems) so that the user will have clear guidance as to which path to follow in order to become a competent user of the present and future technology. Because of the rapid advances in data storage, in networking and in computer programs, the clinicians of tomorrow will have vast sources of information at their disposal. This latter will include not only patient records, but also drug data-sheets, textbooks, journals and research reports. Finally, lack of space has prevented some topics receiving more than a cursory mention. This is known but, like real life, one has to make judgements as to the relative importance of the topics and include those which come out top. It is hoped that the readers will not be too disappointed: if they absorb all that is here they will be very knowledgeable indeed.

Computer Peripherals

Impact and value of junior rotation in radiology.

All junior medical students at the authors' institution are enrolled in a 2-week combined rotation in diagnostic radiology and anesthesia, with the time divided equally between the departments. The purpose of this rotation is to familiarize students with various imaging modalities and to introduce interpretation of conventional radiographs. The rotation is offered five times during the academic year, and each includes the same enrollment (about 20 students), educational structure (lectures, self-study, and case review) and method of evaluation (multiple choice examination). To assess the educational benefits of this short exposure to radiology, we gave a preexamination and postexamination at the beginning and the end of each rotation. Comparison of scores between the pretest and post-test showed a significant learning gain for all rotations (P less than 0.01). There was no difference between groups scheduled early in the academic year compared with those with more clinical experience at the end of the year. We conclude that a well-structured brief junior rotation in radiology can effectively improve students' knowledge of imaging and its role in clinical evaluation.

Curriculum

Characterization and rapid diagnostic analysis of DNA polymorphisms closely linked to the cystic fibrosis locus.

Six genetic polymorphisms, closely linked to the cystic fibrosis gene and useful in clinical linkage analysis, have been characterized and converted to a more rapid form of assay. Sequences flanking the metD (Ban I), metH (Msp I), XV-2c (Taq I), KM.19 (Pst I), MP6d-9 (Msp I), and J3.11 (Msp I) polymorphic restriction sites have been determined and used to design specific polymerase chain reaction (PCR) amplification primers and allele-specific oligonucleotide probes. All six of these polymorphisms were found to involve single-base alterations, and the XV-2c polymorphism was found to lie within an Alu repeat segment. These PCR-based tests, in conjunction with the CS.7 (Hha I) assay described elsewhere (Stanier P et al. Hum Genet 1988;80:309-10; Williams C et al. Lancet 1988;ii:102-3), provide a convenient, rapid, and reliable method of haplotype and linkage analysis, clinically useful in those situations where direct detection of mutations is not possible.

Base Sequence

Perspective of the patient with rheumatoid arthritis on issues related to missed medication.

In order to better understand issues surrounding missed medication doses, 140 patients with rheumatoid arthritis in a tertiary care clinic were interviewed about their medication-taking behavior and beliefs. Findings from work in memory and attention and concepts from Ajzen and Fishbein's theory of reasoned action were used to guide the development of questions. Key findings included: (a) some ignorance about their regimen, (b) a tendency to rely just on their memories rather than environmental cues to remember doses, (c) variation in responses to a missed dose, and (d) the use of an inferential process for judging a medication's efficaciousness. These findings suggest several areas that physicians and allied health professionals can investigate with patients to help minimize missed doses.

Arthritis, Rheumatoid

Missed medication doses in rheumatic arthritis patients: intentional and unintentional reasons.

A survey of 200 rheumatoid arthritis (RA) patients was conducted to identify the kinds and frequencies of intentional and unintentional reasons for missed medication dose. Planned and unplanned changes in usual activity routines accounted for most of the unintentionally missed doses, while side effects attributed to the medication accounted for most of the intentionally missed doses. Patients who did not miss medication doses were different from those who did by tending to have more financial resources and social support available to them.

Anti-Inflammatory Agents

Bibrachial palsy due to paraneoplastic encephalomyelitis.

Bibrachial palsy is a distinctly unusual pattern of muscular weakness. We have described a woman who had a slowly progressive clinical course, with profound bibrachial palsy and neurogenic respiratory failure, but neurologically normal lower extremities. Autopsy revealed encephalomyelitis and a small previously undetected oat cell carcinoma with inflammatory infiltration. The pathologic features are consistent with an autoimmune process.

Brachial Plexus

Long-term therapy with a depot luteinizing hormone-releasing hormone analogue (Zoladex) in patients with advanced prostatic carcinoma.

We treated 191 patients with histologically proved locally advanced stage (T3 or T4) and/or metastatic prostate cancer with a biodegradable depot formulation of a luteinizing hormone-releasing hormone analogue (Zoladex). After an initial increase in serum testosterone in week 1 of therapy a continuous decrease of testosterone to castrate levels was obtained. With a monthly injection of the luteinizing hormone-releasing hormone analogue 4 patients (2 per cent) experienced a transient increase in bone pain, 1 had ureteral obstruction and 1 suffered paraplegia during the first few weeks of therapy. Over-all objective and subjective responses were similar to those obtained by castration or estrogen therapy. The absence of local and systemic (long-term) side effects proves the validity of this approach for patients with advanced prostatic cancer.

Aged

Multichannel digital recording of intraluminal temperature in the upper gastrointestinal tract of man: techniques and analyses.

A recording system has been developed to measure intraluminal temperature changes from six sites simultaneously in the upper gastrointestinal tract at rates up to 10 Hz from each site. The temperature probe contains six type K thermocouples mounted in 14 French gauge orogastric tube. The data is logged, after digital conversion and signal multiplexing, onto disc storage by a dedicated microcomputer. The fluctuating temperature profile, defined as temperature spikes, has been subjected to novel computer analysis to allow definition of temperature load and dissipation within the oesophagus, stomach and duodenum. This system enables the effects of drinking and eating hot and cold foods on the physiological functions of the gastrointestinal tract to be studied accurately.

Body Temperature