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Biomedical subjects

J Richardson

Publications and source records attributed to J Richardson.

At least 163 records · Page 9Linked to original sources

Knockout of the two ldh genes has a major impact on peptidoglycan precursor synthesis in Lactobacillus plantarum.

Most bacteria synthesize muramyl-pentapeptide peptidoglycan precursors ending with a D-alanyl residue (e.g., UDP-N-acetylmuramyl-L-Ala-gamma-D-Glu-L-Lys-D-Ala-D-Ala). However, it was recently demonstrated that other types of precursors, notably D-lactate-ending molecules, could be synthesized by several lactic acid bacteria. This particular feature leads to vancomycin resistance. Vancomycin is a glycopeptide antibiotic that blocks cell wall synthesis by the formation of a complex with the extremity of peptidoglycan precursors. Substitution of the terminal D-alanine by D-lactate reduces the affinity of the antibiotic for its target. Lactobacillus plantarum is a lactic acid bacterium naturally resistant to vancomycin. It converts most of the glycolytic pyruvate to L- and D-lactate by using stereospecific enzymes designated L- and D-lactate dehydrogenases, respectively. In the present study, we show that L. plantarum actually synthesizes D-lactate-ending peptidoglycan precursors. We also report the construction of a strain which is deficient for both D- and L-lactate dehydrogenase activities and which produces only trace amounts of D- and L-lactate. As a consequence, the peptidoglycan synthesis pathway is drastically affected. The wild-type precursor is still present, but a new type of D-alanine-ending precursor is also synthesized in large quantities, which results in a highly enhanced sensitivity to vancomycin.

Anti-Bacterial Agents↗

Double jeopardy, the equal value of lives and the veil of ignorance: a rejoinder to Harris.

Harris levels two main criticisms against our original defence of QALYs (Quality Adjusted Life Years). First, he rejects the assumption implicit in the QALY approach that not all lives are of equal value. Second, he rejects our appeal to Rawls's veil of ignorance test in support of the QALY method. In the present article we defend QALYs against Harris's criticisms. We argue that some of the conclusions Harris draws from our view that resources should be allocated on the basis of potential improvements in quality of life and quantity of life are erroneous, and that others lack the moral implications Harris claims for them. On the other hand, we defend our claim that a rational egoist, behind a veil of ignorance, could consistently choose to allocate life-saving resources in accordance with the QALY method, despite Harris's claim that a rational egoist would allocate randomly if there is no better than a 50% chance of being the recipient.

Australia↗

Another peep behind the veil.

Harris argues that if QALYs are used only 50% of the population will be eligible for survival, whereas if random methods of allocation are used 100% will be eligible. We argue that this involves an equivocation in the use of "eligible", and provides no support for the random method. There is no advantage in having a 100% chance of being "eligible" for survival behind a veil of ignorance if you still only have a 50% chance of survival once the veil is lifted. A 100% chance of a 50% chance is still only a 50% chance. We also argue that Harris provides no plausible way of dealing with the criticism that his random method of allocation may result in the squandering of resources.

Australia↗

Varicella-zoster virus DNA in CSF and arteries in delayed contralateral hemiplegia: evidence for viral invasion of cerebral arteries.

A 78-year-old woman presented with a right basal ganglia infarct 6 weeks after a left herpes zoster ophthalmicus. MR angiography showed focal segmental stenosis of the proximal segments of the anterior, middle, and posterior cerebral arteries. Varicella DNA was detected in the CSF by polymerase chain reaction (PCR). Treated with dexamethasone and acyclovir without improvement, she died 1 month later. There was focal endarteritis in the left anterior, middle, and posterior cerebral arteries at autopsy. Varicella DNA was detected by PCR of extracts from these vessels but not from the arteries on the right side. This study provides further evidence that the vasculopathy after herpes zoster ophthalmicus results from direct viral invasion of the vessel wall.

Aged↗

Results of surgical treatment of stage I and II lung cancer.

Pulmonary resection remains the most appropriate treatment for localised bronchogenic carcinoma, since prognosis and outcome are currently dependent on surgical resectability. A retrospective analysis of our experience with three hundred and thirteen stage I (n=250) and stage II (n=63) patients treated surgically form the basis of this report. The initial pulmonary resection was lobectomy in 173 patients, bilobectomy in 38, sleeve lobectomy in 12, pneumonectomy in 59, wedge excision or segmentectomy in 31. The overall operative mortality was 3.2%; 4.03% for lobectomy and 1.6% for pneumonectomy. Morbidity was observed in 21 (6.7%) patients. Four out of sixteen small cell carcinoma patients had postoperative adjuvant chemotherapy. Survival in patients with stage I tumours was 71% at 5 years and 61% at 10 years compared with 41% at 5 years and 35% at 10 years for patients with stage II disease. The five year survival after pneumonectomy was significantly (p<0.05) better for both stage I and stage II lung cancer than after lobectomy. Five year survival in stage I carcinoma was not influenced by histological type, while there was statistically significant difference (p<0.05) in survival between adenocarcinoma (0%) and squamous cell carcinoma (46%) in stage II disease. We conclude that an aggressive surgical approach can provide an excellent prognosis for recovery and long term cure in most patients with early stage lung cancer.

Carcinoma, Bronchogenic↗

Domestic violence: a hidden problem for general practice.

Domestic violence is a common problem that may affect more than a quarter of women. It is a complex area in which to undertake research. Studies often focus on selected populations and exhibit a diversity of design, making comparison difficult. This review focuses on physical violence by men against women partners or ex-partners, and exemplifies important issues for general practitioners. Domestic violence frequently goes undetected. This may be the result of doctor's fears of exploring an area perceived as time-consuming, where knowledge is lacking and where they feel powerless to 'fix' the situation. Women may not reveal that they are experiencing violence, sometimes because doctors are unsympathetic or hostile. Nevertheless, women wish to be asked routinely about physical abuse and want to receive immediate advice and information about their options if necessary. Women experience a range of health and social problems in association with domestic violence, including depression, anxiety, substance abuse and pregnancy complications. However, none of these features is specific enough to be useful as an indicator of violence. Therefore, doctors should routinely ask all women direct questions about abuse. This recommendation can be incorporated into guidelines, which should be implemented widely in the UK, to improve the care of women experiencing domestic violence. In parallel with this, the educational needs of general practitioners should be addressed. Further research is needed to establish the prevalence of domestic violence in women presenting to general practice and to investigate how the problem is currently being addressed. If progress is to be made in tackling domestic violence, action within primary care is just one part of this: a fundamental change in the attitudes of men towards women is required.

Family Practice↗

Results of surgical treatment of oesophageal cancer.

Oesophagogastrectomy is the best available treatment for patients with carcinoma of the oesophagus or cardia. A retrospective analysis of our experience with 485 patients who were treated surgically forms the basis of this report. Of the 317 patients who underwent resection (resectability rate of 65%) only 210 were considered to be potentially curative. Overall, the 5-year survival rate for oesophageal cancer was 3%, whilst curative resection had a 5-year survival rate of 22% and varied according to stages. Five-year survival rate was 67.7% for patients with Stage I disease compared with 27.6, 9.4 and 6.4% for Stages IIa, IIb and III disease respectively. There were no 5-year survivors with Stage IV disease or with those patients who underwent an incomplete resection. Curative resection carried a mortality rate of 3.8%, whereas incomplete resection or palliative procedure carried higher mortality rates of 14 and 20.7% respectively. Adequate post-operative analgesia was provided by continuous extrapleural intercostal nerve block. Morbidity, mainly caused by respiratory complications, occurred in 30 patients (6.2%), with three patients requiring ventilatory support. Outcome was influenced mostly by the extent of the disease and the completeness of surgical resection rather than by histological type. We conclude that surgical treatment provides better longevity than any other type of therapy and remains the standard against which combined modality treatment should be compared. Our experience suggests that surgical treatment can be achieved with minimal morbidity and mortality.

Aged↗

Pax-6 is essential for lens-specific expression of zeta-crystallin.

Pax-6 is essential for normal eye development and has been implicated as a "master gene" for lens formation in embryogenesis. Guinea pig zeta-crystallin, a taxon-specific enzyme crystallin, achieves high expression specifically in lens through use of an alternative promoter. Here we show that Pax-6 binds a site in this promoter, which is essential for lens-specific expression. Lens and lens-derived cells exhibit a tissue-specific pattern of alternative splicing of Pax-6 transcripts and Pax-6 is expressed in adult lenses and cells that support zeta-crystallin expression. These results suggest that zeta-crystallin is a natural target gene for Pax-6 and that this Pax family member has a direct role in the continuing expression of tissue-specific genes.

Animals↗

Personal and behavioral predictors of automobile crash and injury severity.

The purpose of this paper is to develop a statistical model explaining the relationships between certain driver characteristics and behaviors, crash severity, and injury severity. Applying techniques of categorical data analysis to comprehensive data on crashes in Hawaii during 1990, we build a structural model relating driver characteristics and behaviors to type of crash and injury severity. The structural model helps to clarify the role of driver characteristics and behaviors in the causal sequence leading to more severe injuries. From the model we estimate the effects of various factors in terms of odds multipliers--that is, how much does each factor increase or decrease the odds of more severe crash types and injuries. We found that driver behaviors of alcohol or drug use and lack of seat belt use greatly increase the odds of more severe crashes and injuries. Driver errors are found to have a small effect, while personal characteristics of age and sex are generally insignificant. We conclude with a discussion of our modeling approach and of the implications of our findings for appropriate traffic safety interventions and future research.

Accidents, Traffic↗

Who cares about cost? Does economic analysis impose or reflect social values?

In a two-stage survey, a cross-section of Australians were questioned about the importance of costs in setting priorities in health care. Generally, respondents felt that it is unfair to discriminate against patients who happen to have a high cost illness and that costs should therefore not be a major factor in prioritising. The majority maintained this view even when confronted with its implications in terms of the total number of people who could be treated and their own chance of receiving treatment if they fall ill. Their position cannot be discarded as irrational, as it is consistent with a defensible view of utility. However, the results suggest that the concern with allocative efficiency, as usually envisaged by the economists, is not shared by the general public and that the cost-effectiveness approach to assigning priorities in health care may be imposing an excessively simple value system upon resource allocation decision-making.

Attitude to Health↗

Maximizing health benefits vs egalitarianism: an Australian survey of health issues.

Economists have often treated the objective of health services as being the maximization of the QALYs gained, irrespective of how the gains are distributed. In a cross section of Australians such a policy of distributive neutrality received: (a) very little support when health benefits to young people compete with health benefits to the elderly; (b) only moderate support when those who can become a little better compete with those who can become much better; (c) only moderate support when smokers compete with non smokers; (d) some support when young children compete with newborns; and (e) wide spread support when parents of dependent children compete with people without children. Overall, the views of the study population were strongly egalitarian. A policy of health benefit maximization received very limited support when the consequence is a loss of equity and access to services for the elderly and for people with a limited potential for improving their health.

Adult↗

Increased physiological dead space/tidal volume ratio during exercise in burned children.

Exercise testing enables the simultaneous evaluation of the cardiovascular and respiratory systems' ability to perform gas exchange. The physiological responses to exercise have not been previously reported in the postburn child. This investigation was designed to evaluate residual cardiopulmonary impairment in patients convalescing from severe burns. Spirometry, lung volumes and exercise stress testing were completed on 40 children with a mean time postburn injury of 2.6 +/- 1.9 years and mean burn size of 44 +/- 22 per cent TBSA. Respiratory variables studied during exercise included expired volume, tidal volume and respiratory rate, and physiological dead space/tidal volume (VD/VT) ratios. Stress testing revealed an increased VD/VT ratio consistent with uneven ventilation-perfusion relationships. The data indicate that patients who survive thermal injury may not regain normal cardiopulmonary homeostasis.

Burns↗

Comparison of serological tests for the diagnosis of feline immunodeficiency virus infection of cats.

A new enzyme-linked-immunosorbent assay (ELISA) for the detection of antibodies to feline immunodeficiency virus was compared with previously described ELISAs. Serum samples from 184 infected or uninfected cats were tested using a whole virus lysate kit and ELISAs based on recognition of one of two synthetic peptides (P237 and P253) localized in the transmembrane domain of the viral envelope. The whole virus lysate commercial kit led to the detection of 6% false positive and 4.3% false negative sera. The ELISA based on peptide P253 gave no false positive result and failed to detect only one serum that was subsequently shown to be positive by radio-immunoprecipitation assay. A sandwich-ELISA test using Galanthus nivalis agglutinin, a lectin that specifically binds terminal mannose groups of the envelope proteins was used as a confirmatory test for equivocal results with peptide ELISA and gave similar results. This study indicates that recognition of P253 could serve as a sensitive and specific test for the diagnosis of seropositivity to feline immunodeficiency virus, and moreover that the Galanthus nivalis ELISA could be useful in equivocal cases as a confirmatory test.

Amino Acid Sequence↗