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Biomedical subjects

C Griffiths

Publications and source records attributed to C Griffiths.

At least 19 recordsLinked to original sources

Fatal poisoning in childhood, England & Wales 1968-2000.

We analysed deaths certified as due to poisoning in England & Wales, 1968-2000, in children aged <10 years by age, sex, circumstances of death, intent, and agents involved. The number of deaths fell from 165 (20.6 per million children) in 1968 to 30 (4.6 per million) in 2000, a decrease of approximately 80%. The age-specific death rates were similar in boys and girls. The rate was initially much higher, and fell more, in those aged <5 years. Most deaths (n=1923) occurred in fires, and had been attributed to inhaling combustion products. A small number (n=104) occurred in fires resulting from motor vehicle and other transport accidents. From 1979 (use of ICD-9) the coding of some of these deaths changed from poisoning with carbon monoxide to poisoning with 'other gases, fumes or vapours'. These 'fire deaths' do not appear as poisonings in mortality statistics based on a single underlying cause of death, and cannot be tabulated as poisoning in many countries. Fire deaths and deaths coded to accidental, deliberate, or undetermined poisoning (n=702) decreased substantially with time, and by 2000 numbered 14 and 10, respectively. Accidental deaths declined from 151 in 1968 to 23 in 2000, but homicides and open verdicts varied from 5 to 20 per year, with no clear trend. Deaths attributed to carbon monoxide and to 'other gases, fumes or vapours' (mostly fire-related) totalled 2431 (84% of all poisoning deaths). Overall, 10% of these deaths were either certified as homicides or open verdicts. However, homicide or open verdict was recorded in half of the 47 fatal opiate poisonings. Opioids have now superseded antidepressants as the commonest agents encountered in fatal poisoning with drugs in children.

Accidents↗

Leukocyte extravasation as a target for anti-inflammatory therapy - Which molecule to choose?

In view of the central pathogenic importance of leukocyte extravasation in inflammatory skin diseases, therapeutic interference with this - surprisingly complex - process is clearly a promising new approach for treating these dermatoses. Despite some disappointments during the clinical use of these agents and despite their crippling price tag, the recent incorporation of biologicals that target defined molecular controls of leukocyte extravasation into dermatological and rheumatological practise, consequently, has greatly enriched our therapeutic options for battling major, chronic, inflammatory dermatoses such as psoriasis. However, the - as yet unresolved and still rather controversially discussed - critical question is: Which of the multiple steps that control leukocyte extravasation in the human system really offer the most promising, most pragmatic, and safest molecular targets for therapeutic intervention for which disease entity? The current debate intends to stimulate public and rational debate of this crucial issue, beyond the evident commercial interests that are touched by whatever stand one takes.

Anti-Inflammatory Agents↗

The DNA sequence and comparative analysis of human chromosome 10.

The finished sequence of human chromosome 10 comprises a total of 131,666,441 base pairs. It represents 99.4% of the euchromatic DNA and includes one megabase of heterochromatic sequence within the pericentromeric region of the short and long arm of the chromosome. Sequence annotation revealed 1,357 genes, of which 816 are protein coding, and 430 are pseudogenes. We observed widespread occurrence of overlapping coding genes (either strand) and identified 67 antisense transcripts. Our analysis suggests that both inter- and intrachromosomal segmental duplications have impacted on the gene count on chromosome 10. Multispecies comparative analysis indicated that we can readily annotate the protein-coding genes with current resources. We estimate that over 95% of all coding exons were identified in this study. Assessment of single base changes between the human chromosome 10 and chimpanzee sequence revealed nonsense mutations in only 21 coding genes with respect to the human sequence.

Animals↗

DNA sequence and analysis of human chromosome 9.

Chromosome 9 is highly structurally polymorphic. It contains the largest autosomal block of heterochromatin, which is heteromorphic in 6-8% of humans, whereas pericentric inversions occur in more than 1% of the population. The finished euchromatic sequence of chromosome 9 comprises 109,044,351 base pairs and represents >99.6% of the region. Analysis of the sequence reveals many intra- and interchromosomal duplications, including segmental duplications adjacent to both the centromere and the large heterochromatic block. We have annotated 1,149 genes, including genes implicated in male-to-female sex reversal, cancer and neurodegenerative disease, and 426 pseudogenes. The chromosome contains the largest interferon gene cluster in the human genome. There is also a region of exceptionally high gene and G + C content including genes paralogous to those in the major histocompatibility complex. We have also detected recently duplicated genes that exhibit different rates of sequence divergence, presumably reflecting natural selection.

Base Composition↗

The DNA sequence and analysis of human chromosome 13.

Chromosome 13 is the largest acrocentric human chromosome. It carries genes involved in cancer including the breast cancer type 2 (BRCA2) and retinoblastoma (RB1) genes, is frequently rearranged in B-cell chronic lymphocytic leukaemia, and contains the DAOA locus associated with bipolar disorder and schizophrenia. We describe completion and analysis of 95.5 megabases (Mb) of sequence from chromosome 13, which contains 633 genes and 296 pseudogenes. We estimate that more than 95.4% of the protein-coding genes of this chromosome have been identified, on the basis of comparison with other vertebrate genome sequences. Additionally, 105 putative non-coding RNA genes were found. Chromosome 13 has one of the lowest gene densities (6.5 genes per Mb) among human chromosomes, and contains a central region of 38 Mb where the gene density drops to only 3.1 genes per Mb.

Chromosome Mapping↗

Biological therapies in the systemic management of psoriasis: International Consensus Conference.

Psoriasis is a chronic, immune-mediated disorder that usually requires long-term treatment for control. Approximately 25% of patients have moderate to severe disease and require phototherapy, systemic therapy or both. Despite the availability of numerous therapeutic options, the long-term management of psoriasis can be complicated by treatment-related limitations. With advances in molecular research and technology, several biological therapies are in various stages of development and approval for psoriasis. Biological therapies are designed to modulate key steps in the pathogenesis of psoriasis. Collectively, biologicals have been evaluated in thousands of patients with psoriasis and have demonstrated significant benefit with favourable safety and tolerability profiles. The limitations of current psoriasis therapies, the value of biological therapies for psoriasis, and guidance regarding the incorporation of biological therapies into clinical practice are discussed.

Age Factors↗

The DNA sequence and analysis of human chromosome 6.

Chromosome 6 is a metacentric chromosome that constitutes about 6% of the human genome. The finished sequence comprises 166,880,988 base pairs, representing the largest chromosome sequenced so far. The entire sequence has been subjected to high-quality manual annotation, resulting in the evidence-supported identification of 1,557 genes and 633 pseudogenes. Here we report that at least 96% of the protein-coding genes have been identified, as assessed by multi-species comparative sequence analysis, and provide evidence for the presence of further, otherwise unsupported exons/genes. Among these are genes directly implicated in cancer, schizophrenia, autoimmunity and many other diseases. Chromosome 6 harbours the largest transfer RNA gene cluster in the genome; we show that this cluster co-localizes with a region of high transcriptional activity. Within the essential immune loci of the major histocompatibility complex, we find HLA-B to be the most polymorphic gene on chromosome 6 and in the human genome.

Animals↗

Can a self-management programme delivered by a community pharmacist improve asthma control? A randomised trial.

BACKGROUND: No randomised studies have addressed whether self-management for asthma can be successfully delivered by community pharmacists. Most randomised trials of asthma self-management have recruited participants from secondary care; there is uncertainty regarding its effectiveness in primary care. A randomised controlled study was undertaken to determine whether a community pharmacist could improve asthma control using self-management advice for individuals recruited during attendance at a community pharmacy. METHODS: Twenty four adults attending a community pharmacy in Tower Hamlets, east London for routine asthma medication were randomised into two groups: the intervention group received self-management advice from the pharmacist with weekly telephone follow up for 3 months and the control group received no input from the pharmacist. Participants self-completed the North of England asthma symptom scale at baseline and 3 months later. RESULTS: The groups were well matched at baseline for demographic characteristics and mean (SD) symptom scores (26.3 (4.8) and 27.8 (3.7) in the intervention and control groups, respectively). Symptom scores improved in the intervention group and marginally worsened in the control group to 20.3 (4.2) and 28.1 (3.5), respectively (p<0.001; difference adjusted for baseline scores=7.0 (95% CI 4.4 to 9.5). CONCLUSIONS: A self-management programme delivered by a community pharmacist can improve asthma control in individuals recruited at a community pharmacy. Further studies should attempt to confirm these findings using larger samples and a wider range of outcome measures.

Administration, Inhalation↗

Existential concerns in late stage cancer.

In health care, it is generally acknowledged that individuals experiencing cancer illness and dying of cancer face a challenging time. Oncology and palliative care have responded by developing an expertise of treatment and care. The opportunity to receive the best of health care is accepted as an important concern to patients. However, recent research explains that many areas of dying cancer patients' concerns remain undisclosed and unresolved (Heaven & Maguire 1997). The purpose of this qualitative study was to identify dying cancer patients' concerns with the aim of developing a Concerns Questionnaire to further explore the relationship between patients' concerns and psychological and physical distress. In-depth interviews were carried out with 21 patients with advanced cancer who had been told they were no longer to receive curative treatments. Content analysis of the interview transcripts showed that existential concerns were a significant issue for these patients. Furthermore, patients' opportunity for reflection, personal change and inner discovery at the end of their illness could be enhanced by earlier experiences of holistic cancer care.

Journal Article↗

The shaping of nitric oxide signals by a cellular sink.

1. The functioning of nitric oxide (NO) as a biological messenger necessitates that there be an inactivation mechanism. Cell suspensions from a rat brain region rich in the NO signalling pathway (cerebellum) were used to investigate the existence of such a mechanism and to determine its properties. 2. The cells consumed NO in a manner that could not be explained by reaction with O(2), superoxide ions or contaminating red blood cells. Functionally, the mechanism was able to convert constant rates of NO formation into low steady-state NO concentrations. For example, with NO produced at 90 nM min(-1), the cells (20 x 10(6) ml(-1)) held NO at 20 nM. Various other cell types behaved similarly. 3. The influence of NO inactivation on the ability of NO to access its receptor, soluble guanylyl cyclase, was explored by measuring cGMP accumulation in response to the clamped NO concentrations. The extrapolated steady-state EC(50) for NO was 2 nM, a concentration readily achieved by low NO release rates, despite inactivation. 4. When confronted by higher NO release rates for several minutes, the clamping mechanism failed, resulting in a progressive rise in NO concentration. While the clamp was maintained, cellular respiration was unaffected but, as it failed, respiration became inhibited by NO. The IC(50) was measured to be 120 nM (at 100-140 microM O(2)). 5. It is concluded that cerebellar (and other) cells possess a powerful NO inactivation mechanism that, extrapolated to the whole tissue, would impose on NO a half-life of around 100 ms. This and other properties of the device appear ideal for shaping low-level NO signals for activating its receptor, soluble guanylyl cyclase, whilst avoiding adverse effects on mitochondrial function. The exhaustibility of the mechanism provides a scenario for NO to become toxic.

Algorithms↗

Influences on hospital admission for asthma in south Asian and white adults: qualitative interview study.

OBJECTIVE: To explore reasons for increased risk of hospital admission among south Asian patients with asthma. DESIGN: Qualitative interview study using modified critical incident technique and framework analysis. SETTING: Newham, east London, a deprived area with a large mixed south Asian population. PARTICIPANTS: 58 south Asian and white adults with asthma (49 admitted to hospital with asthma, 9 not admitted); 17 general practitioners; 5 accident and emergency doctors; 2 out of hours general practitioners; 1 asthma specialist nurse. MAIN OUTCOME MEASURES: Patients' and health professionals' views on influences on admission, events leading to admission, general practices' organisation and asthma strategies, doctor-patient relationship, and cultural attitudes to asthma. RESULTS: South Asian and white patients admitted to hospital coped differently with asthma. South Asians described less confidence in controlling their asthma, were unfamiliar with the concept of preventive medication, and often expressed less confidence in their general practitioner. South Asians managed asthma exacerbations with family advocacy, without systematic changes in prophylaxis, and without systemic corticosteroids. Patients describing difficulty accessing primary care during asthma exacerbations were registered with practices with weak strategies for asthma care and were often south Asian. Patients with easy access described care suggesting partnerships with their general practitioner, had better confidence to control asthma, and were registered with practices with well developed asthma strategies that included policies for avoiding hospital admission. CONCLUSIONS: The different ways of coping with asthma exacerbations and accessing care may partly explain the increased risk of hospital admission in south Asian patients. Interventions that increase confidence to control asthma, confidence in the general practitioner, understanding of preventive treatment, and use of systemic corticosteroids in exacerbations may reduce hospital admissions. Development of more sophisticated asthma strategies by practices with better access and partnerships with patients may also achieve this.

Adult↗

Dental complications of head and neck radiotherapy: Part 2.

Radiotherapy for head and neck tumours is a viable treatment modality. However, a wide range of potentially debilitating dental complications may accompany the treatment. In Part 2 of this article, prevention and management strategies available to the dental practitioner to stave off the dental side effects of radiotherapy are explored and particular attention is given to the management of xerostomia and radiation caries.

Candidiasis, Oral↗

Dental complications of head and neck radiotherapy: Part 1.

Radiotherapy for head and neck tumours is a viable treatment modality. However, a wide range of potentially debilitating dental complications may accompany this treatment. The nature and impact of these complications are outlined in this first part of a two-part article. In Part 2, prevention and management strategies available to the dental practitioner to stave off the dental side effects of radiotherapy will be explored.

Candidiasis, Oral↗

Patient satisfaction with store-and-forward teledermatology.

We assessed patient satisfaction with a nurse-led store-and-forward teledermatology service in Manchester. A teledermatology nurse obtained the patient's history, took digital photographs of the patient's skin lesion and then sent the information to a hospital dermatologist, who responded with management advice the following week. Of 141 patients who attended their teledermatology appointment, 123 (50 male, 73 female) completed the study questionnaire (87%). The average age of respondents was 42 years (SD 17, range 18-90 years). Ninety-three per cent reported that they were happy with the teleconsultation while 86% reported that it was more convenient than going to the outpatient clinic. Forty per cent agreed that they would feel more comfortable seeing the dermatologist in person while only 58% were comfortable with not speaking to the dermatologist about their skin condition. The absence of interaction with the dermatologist and the delay in receiving management advice may have contributed to the somewhat low satisfaction rates.

Adolescent↗