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Biomedical subjects

B Richards

Publications and source records attributed to B Richards.

At least 37 records · Page 2Linked to original sources
PubMed1999

Creation of a stable human reporter cell line suitable for FACS-based, transdominant genetic selection.

Quality bioassays are central to all approaches directed at understanding or perturbing the function of proteins. One type of cell-based bioassay involves an engineered reporter whose transcriptional activity serves as a readout for upstream signals of a biochemical pathway(s) that feeds into the reporter. We describe a general strategy for creating a mammalian reporter line with attributes suitable for a high complexity, en masse transdominant genetic screen. The basic criteria required of the mammalian cells engineered with the reporter include ease of maintenance, ease of sorting by FACS, ability to be transduced by retroviruses, and high expression of transduced peptides or cDNAs. For maximal enrichment during selection, the reporter line should have a relatively homogeneous response and a high signal-to-background ratio. We use a melanoma cell line transduced with a retinoic-acid-responsive promoter coupled to a GFP reporter as a case study to demonstrate the strategy. We characterize an optimized retinoic-acid-responsive reporter clone to determine the kinetics of reporter induction and decay in the presence and absence of retinoids. Dose-response studies reveal that the reporter responds to all-trans retinoic acid with an EC50 of approximately 1 nM. The strategy described is general and may be applied to create other reporter lines that respond to a specific stimulus.

Base Sequence↗
PubMed1999

Presence of antibodies to canine distemper virus, canine parvovirus and canine adenovirus type 1 in free-ranging jackals (Canis adustus and Canis mesomelas) in Zimbabwe.

A survey of free-ranging jackals (Canis adustus and Canis mesomelas) in Zimbabwe was conducted to determine the prevalence of serum antibodies to canine distemper virus (CDV), canine parvovirus (CPV) and canine adenovirus type 1 (CAV-1). Sera from 16 Canis adustus and 22 Canis mesomelas were collected from 1990 to 1993 from various regions of Zimbabwe and assayed by means of immunofluorescent techniques. Seroprevalence in C. adustus and C. mesomelas respectively were 50% and 63.6% for CDV, 12.5% and 18.2% for CPV and 37.5 and 9.1 for CAV-1. These results demonstrate that jackals are infected with these viruses and may act as reservoirs of them, although their susceptibility to the viruses is not known.

Adenoviruses, Canine↗
PubMed1999

A computerised study on the results of in-vitro-fertilisation.

This project has been concerned with the comparison of children born as a result of fresh embryo transfer (IVF) with children conceived and born via the natural process. The former included children who were the single outcome of the birth (singletons) and children who were the result of a multiple birth (e.g. twins, triplets). A computer database was established into which was put 23 items of data on each child, making a total of 12,788 items overall. There were 278 "normally conceived" children (controls), 150 IVF Singletons, and 128 children from multiple births. The results show interesting differences in the gestational age at birth, the birth weight, the mode of delivery and the degrees of birth abnormalities and malformations.

Birth Weight↗
PubMed1999

Medical informatics educational tasks seen from practical perspective. Tempus-Phare Project CME-02555-96.

This paper tries to synthesize the discussion of a seminar on medical informatics educational tasks held in May 1998 in Sinaia, Romania, within the frame of the Tempus-Phare Project CME-02555-96 entitled "Know How Transfer from University to Industry" and coordinated by the University of Medicine and Pharmacy Timisoara, Romania. Special emphasis was paid to particular features of medical education requirements in East European countries, with particular reference to Romania.

Curriculum↗
PubMed1999

An Internet implementation of an international clinical study.

This paper describes a clinical study that is being conducted in 15 countries world-wide via the internet. The study concerns the removal of Factor VIII inhibitors in haemophilic children. The suitability of the Internet for this type of study is explored together with the technology (Active Server Pages, Secure Sockets Layer) that is involved in the creation of such a system.

Child↗
PubMed1999

A decision support system for cholinesterase genotyping.

Cholinesterase is a naturally occurring enzyme in the human body. Its importance became apparent when it was recognised that patients undergoing surgery and carrying abnormal genes for this enzyme were unable to recover from a dose of muscle-relaxant. It is therefore important to know the Genotype (the pair of genes) of a patient who might undergo surgery. The computer programme takes laboratory measurements and applies mathematical techniques and clinical judgements to determine the two genes present.

Acetylcholinesterase↗
PubMed1998

The current and future role of the Internet in patient education.

The Internet technology known as the World Wide Web is rapidly emerging as the most powerful medium of mass communication this century and it can be harnessed to dispense global, cost-effective, high-quality, multimedia patient education material. This paper reviews how the Internet has progressed from delivering simple static, text-based material to sophisticated interactive Web sites based on CGI Technology. Interactive Web sites can be used to deliver health assessment questionnaires and Web-based decision-support systems can give patients advice on the emergency management of acute medical problems. The advantages and drawbacks of this new technology, including information regulation and quality are discussed. The role of the Hospital Intranet as a patient education resource is described. The paper concludes by illustrating how patients can appreciate the 3-D structure of bones and organs using virtual reality in a VRML Web environment.

Decision Support Techniques↗
PubMed1998

Mutation at the phenylalanine hydroxylase gene (PAH) and its use to document population genetic variation: the Quebec experience.

We describe variation at the PAH locus in the population of Quebec. We successfully analyzed 135 of 141 chromosomes from phenylketonuria (PKU) probands (95.7% of the sample), and eight additional chromosomes from a small number of probands with non-PKU hyperphenylalaninemia (HPA). The full set of chromosomes harboured 45 different PAH mutations: i) seven polymorphisms (IVS2nt19, IVS3nt-22, IVS6nt-55, Q232Q, V245V, L385L, Y414Y); ii) four mutations causing non-PKU HPA (T92I, E390G, R408Q, D415N); iii) 34 mutations causing PKU. Only six mutations (M1V, R261Q, F299C, S349P, R408W and IVS12nt1) occurred in the whole province at relative frequencies > 5%: most are rare and probably identical by descent. By studying associations of mutations with polymorphic haplotype alleles, we found examples of mutations on different haplotypes that were identical by state, but not by descent because they were recurrent mutations (E280K and R408W); and examples of mutations identical both by state and by descent because of intragenic recombination (S67P, G218V, V245A and IVS12nt1). Ten mutations were first described in Quebec and five are still unique there; three of these 'Quebec' mutations are reported here for the first time (c.125A-->T (K42I); [c.470G-->A; c.471A--C] (R157N); c.707nt-55 (IVS6nt-55). The PAH mutations stratify by geographic region and population, their distributions validating hypotheses about European range expansion to North America during three separate phases of immigration and demographic expansion in the Quebec region over the past four centuries. The PAH homozygosity value (j) is 0.06 for the total Quebec sample (0.5-0.08 by regions), and the corresponding homoallelic fraction of mutant PAH genotypes is 24%. These findings are a documentation of genetic diversity in the Quebec population.

Alleles↗
PubMed1998

The use of antimicrobials in ten Australian and New Zealand intensive care units. The Australian and New Zealand Intensive Care Multicentre Studies Group Investigators.

A prospective standardized collection of clinical, microbiological and pharmaceutical information on antibiotic use was conducted in Australia and New Zealand intensive care units (ICUs) involving 481 consecutive critically ill patients who were receiving antibiotics for any reason while in ICU. Patients had a mean SAPS II score of 34.1 +/- 17.8 with an expected mortality of 15.6% (actual mortality 12%). Of these, 292 (60.8%) were admitted to the ICU within 72 hours of surgery. Among such surgical patients, 233 (79.9%) received antibiotics for "surgical prophylaxis" while in ICU (48% of sample population). The second largest group of patients treated with antibiotics in ICU included those with systemic inflammatory response syndrome and clinical suspicion of infection (38%). Antibiotics were prescribed for the treatment of clinically diagnosed infection in 268 patients. Clinical response was apparent in 62.6% and in most (71%) was achieved in the first 72 hours of treatment. The incidence of antimicrobial-related side-effects was 4%, mostly in the form of diarrhoea or rash (75% of all side-effects). The most commonly prescribed antimicrobials were gentamicin (n = 146), ceftriaxone (n = 98), vancomycin (n = 94) and metronidazole (n = 111). Three times daily prescription of aminoglycosides was uncommon (< 1%). Forty-one patients had a documented infection (positive culture) with a gram-negative organism. Of these, 17 received therapy with a single antibiotic and 24 received therapy with two antibiotics. Despite similar illness severity, there were six deaths in the former group and only two in the latter.

Anti-Bacterial Agents↗
PubMed1997

Conditional mutator phenotypes in hMSH2-deficient tumor cell lines.

Two human tumor cell lines that are deficient in the mismatch repair protein hMSH2 show little or no increase in mutation rate relative to that of a mismatch repair-proficient cell line when the cells are maintained in culture conditions allowing rapid growth. However, mutations accumulate at a high rate in these cells when they are maintained at high density. Thus the mutator phenotype of some mismatch repair-deficient cell lines is conditional and strongly depends on growth conditions. These observations have implications for tumor development because they suggest that mutations may accumulate in tumor cells when growth is limited.

Cell Count↗
PubMed1997

Children conceived by in vitro fertilisation after fresh embryo transfer.

AIMS: To compare the outcome in in vitro fertilisation (IVF) children (after fresh embryo transfer) from multiple and singleton births with one another, and with normally conceived control children. METHODS: A cohort of 278 children (150 singletons, 100 twins, 24 triplets and four quadruplets), conceived by IVF after three fresh embryos had been transferred, born between October 1984 and December 1991, and 278 normally conceived control children (all singletons), were followed up for four years after birth. They were assessed for neonatal conditions, minor congenital anomalies, major congenital malformations, cerebral palsy and other disabilities. Control children, all born at term, were matched for age, sex and social class. RESULTS: The ratio of male:female births was 1.03. Forty six per cent of IVF children were from multiple births; 34.9% were from preterm deliveries; and 43.2% weighed less than 2500 g at birth. The IVF singletons were on average born one week earlier than the controls, weighed 400 g less, and had a threefold greater chance of being born by caesarean section. The higher percentage of preterm deliveries was largely due to multiple births and they contributed to neonatal conditions in 45.0% of all IVF children. The types of congenital abnormalities varied: 3.6% of IVF children and 2.5% of controls had minor congenital anomalies, and 2.5% of IVF children and none of the controls had major congenital malformations. The numbers of each specific type of congenital abnormality were small and were not significantly related to multiple births. IVF children (2.1%) and 0.4% of the controls had mild/moderate disabilities. They were all from multiple births, including two children with cerebral palsy who were triplets. CONCLUSIONS: The outcome of IVF treatment leading to multiple births is less satisfactory than that in singletons because of neonatal conditions associated with preterm delivery and disabilities in later childhood. A reduction of multiple pregnancies by limiting the transfer of embryos to two instead of three remains a high priority.

Cerebral Palsy↗
PubMed1997

The Chernobyl accident: predicting cardio-vascular disease in the ex-workers.

This paper describes a computer package that has been used to predict the likelihood of the onset of cardiovascular diseases in these patients who were former workers (liquidators) on the Chernobyl site in the Ukraine, Chernobyl being the place where the Nuclear Power Station was destroyed when the atomic reactor got out of control and spread radiation over a very wide area both on the ground and into the atmosphere. The programme predicts the future morbidity in those patients with an accuracy of 90%.

Adult↗
PubMed1996

Sleep history is neglected diagnostic information. Challenges for primary care physicians.

Sleep problems are treatable causes of morbidity and mortality, but little is known about how often the history fundamental to diagnosis is obtained. We recorded the frequency of sleep histories during encounters with simulated patients by 20 experienced primary care practitioners, 23 uninstructed medical interns, and 22 interns who had previous instruction about sleep disorders. Sleep histories were uncommonly obtained by uninstructed physicians (0% of practitioners, 13% of interns), but trained interns more often (81.8%) asked about sleep. If sleep problems are to be prioritized, major changes in physician education and behaviors are essential. Focused instruction about sleep influences physician behavior.

Education, Medical, Continuing↗
PubMed1996

The quality of life of patients with newly diagnosed M1 prostate cancer: experience with EORTC clinical trial 30853.

This study was undertaken to evaluate the quality of life (QoL) of previously untreated patients with M1 prostate cancer before and during androgen-suppressive treatment. Assessment of QoL was included as an optimal component of EORTC protocol 30853, a phase III trial comparing LH-RH (luteinising hormone-releasing hormone) analogue combined with a non-steroidal anti-androgen versus orchiectomy in patients with M1 prostate cancer. At pretreatment and during the follow-up period, patients were asked to complete a questionnaire assessing their physical and psychosocial functioning, and their symptom levels. Physicians rated the patients' performance status, pain, urological symptoms and erectile function. Due to its optional nature, only a minority of the patients in the trial were recruited for the QoL investigation. 63 patients completed a pretreatment questionnaire, of whom 49 completed a second questionnaire at least once during the initial 15 month follow-up period. While statistically significant correlations were observed between patients' and physicians' ratings of physical functioning and pain, these were of only a moderate magnitude (r = 0.43 and 0.30, respectively). No significant association was observed between physicians' and patients' ratings of micturation problems or of erectile function. Before treatment, fatigue, pain and decreased social role and sexual functioning were the problems most frequently reported by patients. With an average of approximately 1 year follow-up, statistically significant improvements were observed in patients' self-reported urological symptoms and metastatic pain. No significant changes were noted for the other QoL domains assessed. The results of this study confirm earlier findings that physicians' ratings may not reflect accurately the functional health and symptom experience of their patients. Patient-based QoL questionnaires offer the most direct means of evaluating the subjective morbidity associated with prostate cancer and its treatment. To increase participation and compliance rates in future studies, it is recommended that QoL assessment be made mandatory in those clinical trials in which QoL is considered to be an important study endpoint.

Aged↗