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Biomedical subjects

S Holmes

Publications and source records attributed to S Holmes.

At least 19 recordsLinked to original sources
PubMed2006

The DNA sequence and biological annotation of human chromosome 1.

The reference sequence for each human chromosome provides the framework for understanding genome function, variation and evolution. Here we report the finished sequence and biological annotation of human chromosome 1. Chromosome 1 is gene-dense, with 3,141 genes and 991 pseudogenes, and many coding sequences overlap. Rearrangements and mutations of chromosome 1 are prevalent in cancer and many other diseases. Patterns of sequence variation reveal signals of recent selection in specific genes that may contribute to human fitness, and also in regions where no function is evident. Fine-scale recombination occurs in hotspots of varying intensity along the sequence, and is enriched near genes. These and other studies of human biology and disease encoded within chromosome 1 are made possible with the highly accurate annotated sequence, as part of the completed set of chromosome sequences that comprise the reference human genome.

Base Sequence↗
PubMed2006

Skin-cancer awareness in Scottish cardiac transplant recipients.

BACKGROUND: Cardiac transplant recipients have a greatly increased risk of nonmelanoma skin cancer, with a relative risk of up to 108. Skin cancer is more aggressive in transplant patients and results in substantial morbidity and mortality. It is therefore important that these patients understand this risk and take adequate sun-protection measures. AIM: To assess awareness of skin cancer risk and sun protection measures used by cardiac transplant recipients and determine the impact of patient education. METHODS: Using a detailed questionnaire, we surveyed 118 patients attending the cardiac transplant clinic at our centre to quantify knowledge of skin cancer risk (maximum total score 10) and behaviour in the sun (maximum total score 15). Of these patients, 50 were then seen by a dermatologist for education about skin cancer risk, sun protection measures and skin cancer screening. Six months later, we asked them to complete the same questionnaire again. RESULTS: The mean knowledge score was 7.3/10 and the mean behaviour score was 11.2/15. In the group that received education, the mean knowledge score improved from 7.2/10 before the dermatology consultation to 7.8/10 after the consultation (P < 0.03). The mean score for the behaviour questions improved even more, from 11.2/15 before to 13.5/15 after the consultation (P < 0.0001). CONCLUSIONS. This study demonstrates that specialist advice can improve self-reported knowledge of skin cancer risk and sun protective behaviour in cardiac transplant recipients. It is hoped that this may reduce the risk of nonmelanoma skin cancer in these patients.

Adolescent↗
PubMed2006

An audit of the management of melanoma patients at Glasgow Royal Infirmary 1998-2003.

BACKGROUND: Melanoma is an important cause of morbidity and mortality. Recently published Scottish Intercollegiate Guideline Network (SIGN) guidelines outline standard management for melanoma patients in Scotland. METHODS: We audited the management of consecutive patients diagnosed with melanoma in Glasgow Royal Infirmary (1998-2003), using the SIGN guidelines as a gold standard. RESULTS: Of 102 patients, 41% were male and 59% were female. The mean ages of men and women were 58 and 50 years respectively. Fifty five per cent of all patients had a superficial spreading melanoma, and the median Breslow thickness was 0.64 mm. The most commonly affected site was the head and neck (29%). Most patients (87%) were referred by their general practitioner, but only 30% were marked as urgent by the referrer, and accordingly the median time to first appointment varied between 20 days (1998) and 52 days (2001). The most frequently noted suspicious feature was irregular pigmentation. The median time to biopsy was 6 days. Seventy-one per cent of patients had an excision biopsy, and of those who did not, most (71%) had lesions on the head and neck. There was poor recording of surgical margins (13%) and histological margins were used to determine the need for re-excision. The SIGN guidelines for re-excision and sentinel lymph node biopsy were closely followed. CONCLUSION: The SIGN guidelines for melanoma have been adhered to in our department, although time to first appointment exceeded national recommendations.

Adult↗
PubMed2004

Humanized animal models for autoimmune diseases.

The development of transgenic mice expressing human DR and DQ major histocompatibility complex (MHC) class II molecules has been of value in studying the immunopathology of human MHC class II-associated autoimmune diseases such as rheumatoid arthritis, multiple sclerosis, insulin-dependent diabetes mellitus and celiac disease. Such mice have been used to identify the target antigens that are involved in the initiation of these diseases. Many of the mice develop aspects of the human diseases, either spontaneously or following immunization with the relevant antigen, thus providing an in vivo disease model, which may be used as a tool for further understanding the disease mechanisms and testing novel immunotherapies.

Animals↗
PubMed2004

Bupropion as an aid to smoking cessation: a review of real-life effectiveness.

Clinical trials rigorously demonstrate the efficacy of new products and justify their marketing. However, it is only after use in real-life settings that the clinical value (effectiveness) of a new treatment is fully known. The purpose of this review was to summarise the effectiveness data for bupropion SR as an aid to smoking cessation. Available reports of effectiveness data for bupropion SR were obtained from the literature, presentations at smoking cessation meetings and from the manufacturer. Twelve sources of effectiveness data were found and included clinical practice trials, observational studies/surveys, motivational support programme results and employer-based cessation programme results. The 6-month point prevalence smoking cessation rates ranged from 25 to 49%. There is a growing body of evidence supporting the effectiveness of bupropion SR as an aid to smoking cessation. Real-life quit rates for bupropion SR are similar to those seen in the original clinical trial programme.

Bupropion↗
PubMed2003

Complications with use of the Epistat in the arrest of midfacial haemorrhage.

Control of midfacial haemorrhage can be difficult, especially in the multiply injured patient, either at the scene of injury, or in the Accident and Emergency Department. The use of Epistats has proven invaluable in this setting. Potential problems exist with their use and this is illustrated with examples, together with strategies for overcoming them. A summary of the didactic method of safe use of this life saving technique is insert the Epistat, aiming for a fingertip placed at the soft palate;inflate the posterior cuff;withdraw the Epistat slightly, to position the posterior cuff within the nasal choanae;inflate the anterior (intranasal) cuff.

Adolescent↗
PubMed2003

Incidence of clinically significant lymphoedema as a complication following surgery for primary operable breast cancer.

There has recently been considerable interest for the need for specialist lymphoedema nurses to be appointed in the NHS. However, we had noticed in our cancer follow-up clinics that the incidence of lymphoedema appeared to be very low. Treatment for primary breast cancer (>5 cm) has been surgery and low axillary sampling (ANS). Radiotherapy (RT) or axillary clearance is subsequently performed in patients found to be node positive. The patients are followed-up in the primary breast cancer (PBC) clinic weekly. Follow-up is initially at 3-month intervals up to 2 years and then 1 yearly indefinitely. We conducted a two phased study in patients being followed up in our post cancer clinic in order to identify the incidence of LE in these patients. Phase 1 involved symptomatic patients identified at routine follow up in a 15-week period and the number of patients reporting arm swelling was recorded. The aim of this was to provide an estimate to power a phase 2 study (prospective questionnaire based). Phase 2 was conducted over a 13-week period. All patients attending the clinic were administered modified FACT B4, EQ-50 and Speilberger questionnaires. A total of 1242 patients were examined and lymphoedema found in 5 (0.04%). Of these 5, 3 had undergone axillary clearance, 1 ANS plus radiotherapy and only 1 had ANS alone. A policy of ANS, with prophylactic treatment for lymph node positivity either by surgery or RT alone, gives a very low rate of lymphoedema.

Arm↗
PubMed2003

The role of therapeutic antibodies in drug discovery.

The last 5 years have seen a major upturn in the fortune of therapeutic monoclonal antibodies (mAbs), with nine mAbs approved for clinical use during this period and more than 70 now in clinical trials beyond phase II. Sales are expected to reach $4 billion per annum worldwide in 2002 and $15 billion by 2010. This success can be related to the engineering of mouse mAbs into mouse/human chimaeric antibodies or humanized antibodies, which have had a major effect on immunogenicity, effector function and half-life. The issue of repeated antibody dosing at high levels with limited toxicity was essential for successful clinical applications. Emerging technologies (phage display, human antibody-engineered mice) have created a vast range of novel, antibody-based therapeutics, which specifically target clinical biomarkers of disease. Modified recombinant antibodies have been designed to be more cytotoxic (toxin delivery), to enhance effector functions (bivalent mAbs) and to be fused with enzymes for prodrug therapy and cancer treatment. Antibody fragments have also been engineered to retain specificity and have increased the penetrability of solid tumours (single-chain variable fragments). Radiolabelling of antibodies has now been shown to be effective for cancer imaging and targeting. This article focuses on developments in the design and clinical use of recombinant antibodies for cancer therapy.

Antibodies↗
PubMed2003

Scalp necrosis in temporal arteritis.

Giant cell arteritis is a systemic disease of the elderly which affects large and medium-sized arteries and which may occur in association with polymyalgia rheumatica. Scalp necrosis is a rare cutaneous complication of giant cell arteritis, and this dermatological presentation is not commonly reported.1-4 Giant cell arteritis should be considered in all elderly patients with scalp ulceration. We describe two patients who presented in this manner.

Aged↗
PubMed2003

Antibodies as therapeutic agents: vive la renaissance!

Until recently, the concept of antibodies as in vivo therapeutics was still considered to be an exceedingly ambitious goal. However, in 2003, the situation has been completely transformed, with 14 FDA-approved monclonal antibodies (mAbs), 70 in late stage clinical (Phase II+) trials and > 1000 in preclinical development. The driving force behind this reversal in fortune has been advances in antibody engineering and the emergence of novel discovery techniques which overcame stability and immunogenicity issues that had blighted previous clinical trials of murine antibodies. For indications as diverse as inflammation, cancer and infectious disease, it is clear that unique properties of antibodies make them safe, effective and versatile therapeutics. These drugs can be used to neutralise pathogens, toxins and endogenous mediators of pathology. As cell targeting reagents, antibodies can be used to modulate cytoplasmic cascades or to 'tag' specific cells for complement- or effector-mediated lysis. Antibodies can also be modified to deliver toxic or modulatory payloads (small molecules, radionuclides and enzymes) and engineered to bind multiple epitopes (bispecifics) or even to have novel catalytic activity (abzymes). The modular structure of immunoglobulins and the availability of antibody fragment libraries also make it possible to produce variable-domain therapeutics (Fab, single-chain and domain antibodies). Although exhibiting less favourable kinetics in vivo, these fragments are simple to express and have an increased tissue penetration, making them especially useful as neutralising agents or in the delivery of payload. The number of approved antibodies is expected to increase arithmetically in the near term, as the platform is adopted as a valid alternative to small molecule discovery. This review provides an introduction to the antibody discovery process and discusses the past, present and future applications of therapeutic antibodies, with reference to several FDA-approved precedents.

Animals↗
PubMed2002

Sema7A is a potent monocyte stimulator.

Sema7A is a recently described member of the semaphorin family that is associated with the cell surface via a glycophosphatidylinositol linkage. This study examined the mRNA expression and biological properties of this protein. Although the expression of Sema7A was demonstrated in lymphoid and myeloid cells, no stimulation of cytokine production or proliferation was evident in B or T cells. In contrast, Sema7A is an extremely potent monocyte activator, stimulating chemotaxis at 0.1 pm and inflammatory cytokine production (interleukin-1 (IL-1beta), tumour necrosis factor-alpha (TNF-alpha), IL-6 and IL-8) and superoxide release at 1-10 pm. Sema7A is less effective at stimulating neutrophils. Sema7A also significantly increases granulocyte-macrophage colony-stimulating factor (GM-CSF) production from monocytes but has no consistent effect on IL-10, IL-12 or IL-18. Sema7A can also induce monocytes toward a dendritic cell morphology. Sema7A is expressed in monocytes and probably released through proteolysis and acts as a very potent autocrine activator of these cells.

Animals↗
PubMed2002

Use of an orthopaedic fixator for external fixation of the mandible.

A patient presented with a chronically infected, non-united fracture of the mandible, with considerable bone loss. He was treated with a metacarpal fixator, the miniPennig external fixator. The fixator is stable and smaller than conventional mandibular fixators. It can be applied and removed under local anaesthesia, if necessary, requires little maintenance and produces minimal scarring. The successful outcome in this patient is encouraging and we commend the use of the fixator in similar difficult cases.

Adult↗