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Biomedical subjects

S Rea

Publications and source records attributed to S Rea.

At least 19 recordsLinked to original sources

Burns first aid information on the Internet.

The Internet is an increasingly important source of health-related information. However, the growth of the Internet and its use as a medical delivery tool should be viewed with caution. One of the key concerns is that although the volume of information is huge, the quality, accuracy and completeness of the information is questionable. The aim of this study was to evaluate burns first aid information on the Internet. The search term used was "first aid for burns" and the first 25 hits from each search engine were analysed by one of the observers. We gathered basic information on the web sites--such as the country of origin, language in which the information was offered, accessibility, relevance and whether the site was commercial, organisational or academic. Quality and technicality of the web sites were assessed and scored. The mean quality score was 4.7/15 (31.5%) The mean technical score was 6.1 of 12 (51.1%). When the total score was categorised by percentage, none of the web sites ranked in the excellent category, 1 was very good, 4 were good, 6 were fair and the majority, 36, were poor. Based on the quality score only, two web sites were in the excellent category and two were very good. For technicality one web site was excellent and three were very good. This study has shown first aid information on the Internet is largely of poor quality, that the technical information provided is inadequate and that the sites include a significant amount of grossly inaccurate information. The few sites that contain excellent technical information make up a very small proportion of what is available. Therefore, the average Internet user may not encounter these resources, instead gaining knowledge from sites of questionable value.

Burns↗

MSL proteins and the regulation of gene expression.

Epigenetics describes changes in genome function that occur without a change in the DNA sequence. Dosage compensation is a prime example of the regulation of gene expression by an epigenetic mechanism. Dosage compensation has evolved to balance the expression of sex-linked genes in males and females, which possess different numbers of sex chromosomes. However, the genetic sequence of the chromosomes is the same in both sexes. This mechanism therefore needs (1) to function in a sex-specific manner, (2) to target the sex chromosome from amongst the autosomes and (3) to establish and maintain through development a precise, equalised level of gene expression in one sex compared to the other. The process by which dosage compensation is orchestrated has been well characterised in fruit flies and mammals. Although each has evolved a specific dosage-compensation mechanism, these systems share some underlying themes; the molecular components that mediate dosage compensation in both include non-coding RNA molecules, which act as nucleation points for the compensation process. Both systems utilise chromatin-modifying enzymes to remodel large domains of a chromosome. This review will discuss the mechanism of dosage compensation in Drosophila in light of recent developments that have brought into question the previous model of dosage compensation.

Animals↗

The polymerase chain reaction and its application to clinical plastic surgery.

Molecular biology has become an essential component in many fields of modern medical research, including plastic surgery. Research into the molecular mechanisms underlying many disease processes offer increased understanding of the pathogenesis of disease and provide exciting therapeutic possibilities. Yet for many clinicians, the presentation of much research into molecular biological processes is couched in confusing terminology and based on scientific techniques, the basis of which are frequently difficult for the clinician to understand. The purpose of this review is to present an introduction to some of the molecular biological techniques currently in use, namely the polymerase chain reaction (PCR) and explore its applications to different aspects of plastic surgery. This review explores the role PCR now plays in all aspects of modern plastic surgery practise, with particular emphasis on normal and abnormal wound healing, the diagnosis of craniofacial anomalies, the diagnosis and treatment of cancer including melanoma and squamous cell carcinoma of the head and neck, and burns.

Burns↗

Minor burn injuries in adults presenting to the regional burns unit in Western Australia: a prospective descriptive study.

INTRODUCTION: Western Australia is the largest state in Australia, accounting for approximately one third of the Australian continent. The adult Burns Unit in Western Australia is at Royal Perth Hospital, which provides for the whole adult population of approximately 1.8 million, 80% of which live in and around the state capital city, Perth (approx. 1.4 million). The unit also offers a minor burn care facility. METHODS: The aim of this study was to perform the first prospective review of minor burn injuries in Western Australia, to classify patient demographics, injury patterns and primary treatment. RESULTS AND CONCLUSION: Two hundred and twenty seven patients were referred to the minor burn facility at Royal Perth Hospital (RPH) during the study period. One hundred and three patients (45%) sustained a scald, a further 44 (19%) received a flame burn. Thirty-seven (16%) patients sustained a contact burn, 18 (7.8%) patients attended the clinic with a chemical burn. Sixty percent of all patients reviewed had burns less than one percent. Only 39% of all our patients received adequate first aid. Sixty one percent of all patients received inadequate or inappropriate first aid. This study highlights a number of important issues. The over representation of metropolitan patients coupled with the low numbers of aboriginal patients reinforces the need for rural burns education. The best service we can provide is education on burns prevention and primary management. There are a number of other areas we hope to address in the future, the high incidence of domestic accidents, home safety must be a priority, coupled with seasonal promotional campaigns to address issues such as car radiator injuries. The most striking, and perhaps the most worrying finding in this study is the poor application of basic first aid principles. This is something that is unacceptable, needs further investigation and the lack of basic knowledge needs to be addressed at all levels of the community.

Accident Prevention↗

Burn first aid in Western Australia--do healthcare workers have the knowledge?

Burn injuries treated with adequate immediate first aid are associated with more favourable outcomes, limiting tissue damage and subsequent morbidity including the need for surgery. Cool running water at a temperature of between 10-15 degrees C for 20 to 30 minutes is considered adequate burn first aid treatment. A prospective audit of all new patients (n=227) with burns, attending the minor burn facility at Royal Perth Hospital showed only 88 (39%) patients received appropriate first aid. Fifty percent of patients receiving inappropriate first aid, had this delivered by his or her primary health care contact. This study aims to determine the knowledge of burns first aid among healthcare workers (HCW) and compare this to the general population. A customized survey was performed, four sample cases were included with 4 possible answers in a multiple choice format. All case studies asked the participant to record immediate first aid management. On a case by case basis, burn first aid knowledge was fair but overall knowledge very poor, only 18.8% of respondents achieving 4 correct responses. The uptake of first aid courses was high among HCW at 75% but particularly low among the NHCW at 28%. Our study has shown the value of performing such a course, with a statistically significant (p=0.00) difference between participants who had completed a first aid course and those that had not. The purpose of this study was to quantify knowledge of burns first aid with a view to providing directed education, studies have shown the success of multimedia campaigns. It has been shown that good first aid improves the outcome for the burn patient and this study demonstrates that participation in a first aid course improves knowledge. It is justifiable to progress toward compulsory first aid courses which include first aid of the burns patient to improve outcomes for the community as a whole.

Burns↗

Multicentre phase II study of bifractionated CPT-11 with bimonthly leucovorin and 5-fluorouracil in patients with metastatic colorectal cancer pretreated with FOLFOX.

This multicentre phase II study was designed to evaluate the antitumour activity and toxicity of bifractionated camptothecin (CPT-11) and 5-fluorouracil/ leucovorin (5-FU/LV) in the treatment of patients with metastatic colorectal cancer (MCC) who had been pretreated with 5-FU/LV-oxaliplatin (FOLFOX regimen). In all, 35 patients were enrolled in a two-stage trial. Treatment consisted of two daily doses of CPT-11, 90 mg m2 administered over 90 min, followed by LV, 200 mg m2 administered over 2 h plus 5-FU 400 mg m2 as a bolus and 600 mg m2 as a 22-h continuous infusion administered with disposable pumps as outpatient therapy. Toxicity was closely monitored. Response was evaluated by computed tomography scans every 8 weeks. All 35 patients were assessable for toxicity and response to treatment. Seven patients had a partial response, giving an overall response rate of 20%; 11 patients had stable disease (31.4%) and 17 progressed (48.5%). The median progression-free survival was 7.1 months and median survival was 14 months. A total of 10 patients (30%) experienced grade 3-4 toxicity, including nausea (15%), diarrhoea (12%) and neutropenia (15%), while seven patients (21%) had grade 2 alopecia. The bifractionated bimonthly schedule of CPT-11 plus 5-FU/LV showed substantial antitumour activity and was well tolerated in this group of patients with a poor prognosis, pretreated with the FOLFOX regimen.

Adult↗

Establishing a plastic surgery trauma clinic.

Trauma is an increasing burden on resources both in terms of personnel, operating time and bed occupancy. We describe the introduction of a plastic surgery trauma clinic. This clinic was established in an effort to streamline the increasing number of trauma referrals. Under the previous system inappropriate admissions were occurring using up a valuable resource. This audit was performed to see if the "see and treat" plastic surgery trauma clinic has made an impact on the service offered and provided by our unit. One of the aims in establishing this clinic was to ensure a more efficient bed occupancy rates. The "see and treat" aspect of this clinic has been very effective with regard to this as 21% of patients were treated in the minor operations area within the clinic. A further 26% of patients assessed in the clinic did not require admission or a surgical procedure. Prior to the establishment of this clinic both these groups of patients would have been admitted to the hospital and perhaps because of the delay to admission would have been managed in their own hospitals. From this audit we have proven that establishing a trauma clinic has enabled us to triage these patients in an effective manner, within a satisfactory time period and if appropriate, treat them at the time of review in the adjacent theatre.

Adolescent↗

Firework injuries presenting to a national burn's unit.

The sale to the general public of fireworks is illegal in Ireland. However, many fireworks are readily available on the black market from illegal traders. The number of firework injuries presenting to our unit during the three week run-up to Hallowe'en October 2001 was recorded. In addition, each patient was contacted to determine how the fireworks were obtained, the average amount of money spent, and the level of adult supervision present at the time of injury. A total of 19 patients presented, 18 from the local catchment area, with a mean age of 16 yrs (range 5-46 yrs). Thirteen patients required admission. Sixteen patients sustained hand injuries including burns, and three sustained burns to other body areas. The amount of money spent varied between adults and children, the average amount among the paediatric group was Euro 2-4, but Euro 45 in the adult group. None were willing to identify the local source of their fireworks, but most fireworks originated in Northern Ireland. This small review highlights an ongoing problem in Ireland; fireworks are illegal, yet they are easily and cheaply available without quality or safety controls. Our public awareness campaign has failed to reach its target audience, and the illegal traders who sell these often inferior products are seldom charged. Children and adults will continue to sustain serious injuries as a result.

Adolescent↗

Low dose interleukin-2 and 13-cis-retinoic acid as maintenance therapy in patients with solid tumors responsive to chemotherapy.

After aggressive surgery and chemotherapy, patients (PTS) with advanced solid tumors have often an impaired immune function that may facilitate tumor relapse. We have demonstrated, in a phase IB study, that administering low-dose interleukin-2 (IL-2) and 13-cis retinoic acid (RA), there was a significant improvement of the immune function, with low toxicity, in PTS with advanced tumors that had been treated with aggressive surgery and chemotherapy (Clin Cancer Res 7: 1251-1257, 2001). A further A phase II study (International J Oncology 20: 1275-82, 2002) showed the efficacy of IL-2/RA in improving immunological parameters and in prolonging response in the same category of PTS. Aim of this study was evaluate the clinical and laboratory outcome of 214 patients, with advanced solid tumors, that, after aggressive surgery and chemotherapy, were treated with: subcutaneous IL-2 1.8 x 10(6) IU and oral RA, 0.5 mg/Kg for 5 days/week for 2 cycles of 3 weeks, with a 1-week rest, for up to 2 years. After a median follow-up time of 31 months, there was a statistically significant improvement in the number of lymphocytes, T4/T8 ratio, NK, with respect to baseline values. Responses were maintained for a median time of 36.4 months, while median survival was not reached yet (57% of PTS alive). These data show that the administration of low-dose IL-2/RA determines, with a low toxicity, a sustained increase in the immunological parameters known to be prognostically relevant.

Administration, Oral↗

CLK-1/Coq7p is a DMQ mono-oxygenase and a new member of the di-iron carboxylate protein family.

Strains of Caenorhabditis elegans mutant for clk-1 exhibit a 20-40% increase in mean lifespan. clk-1 encodes a mitochondrial protein thought to be either an enzyme or regulatory molecule acting within the ubiquinone biosynthesis pathway. Here CLK-1 is shown to be related to the ubiquinol oxidase, alternative oxidase, and belong to the functionally diverse di-iron-carboxylate protein family which includes bacterioferritin and methane mono-oxygenase. Construction and analysis of a homology model indicates CLK-1 is a 2-polyprenyl-3-methyl-6-methoxy-1,4-benzoquinone mono-oxygenase as originally predicted. Analysis of known CLK-1/Coq7p mutations also supports this notion. These findings raise the possibility of developing CLK-1-specific inhibitors to test for lifespan extension in higher organisms.

Aging↗

Ifosfamide, cisplatin, and 13-Cis retinoic acid for patients with advanced or recurrent squamous cell carcinoma of the head and neck: a phase I-II study.

BACKGROUND: Ifosfamide (IFO) and cisplatin (CDDP) are active drugs in the treatment of patients with squamous cell carcinoma (SCC) of the head and neck. 13-Cis retinoic acid (RA), along with its antiproliferative and differentiating activity on SCC cell lines, has immunomodulatory and chemopreventive effects. The objective of the current Phase I-II study was to evaluate the combination of CDDP, IFO, and RA in patients with advanced or recurrent SCC of the head and neck. METHODS: Patients with measurable recurrent, metastatic, or locally advanced SCC of the head and neck were eligible. Patients received a fixed dose of 20 mg/m(2) CDDP, and IFO was administered with sodium mercaptoethanesolfonate in three-dose increments (1000 mg/m(2), 1200 mg/m(2), and 1500 mg/m(2)) up to dose limiting toxicity. Both drugs were given for 5 consecutive days every 3 weeks. RA (0.5 mg/kg) was given orally for 5 days per week. RESULTS: Fifty-two patients either with locoregional recurrence or distant metastases (50%) or with locally advanced SCC of the head and neck beyond surgery or radiation therapy (50%) were entered into the trial. Fifteen patients were enrolled in the Phase I study, during which the maximum tolerated dose of IFO was 1500 mg/m(2). In the Phase II study (CDDP 20 mg/m(2) and IFO 1200 mg/m(2)), the response rate was 72% (95% confidence interval, 57-83%). After a median follow-up of 23 months, the median time to disease progression was 10.4 months (range, 2.9-47.2+ months), and the median overall survival was 12.95 months (range, 1.7-47.2+ months). Two patients were converted from a partial response to a complete response with RA. Toxicity was relatively well tolerated and caused no deaths. Grade 3-4 neutropenia was observed in 16 patients, and Grade 2-3 diarrhea toxicity occurred in 9 patients. CONCLUSIONS: The dose and schedule for the combination of CDDP, IFO, and RA that were used in this study are feasible and active in the treatment of patients with SCC of the head and neck, with durable responses and a relatively well tolerated toxicity.

Adult↗

Why only time will tell.

The nematode Caenorhabditis elegans has become a model system for the study of the genetic basis of aging. In particular, many mutations that extend life span have been identified in this organism. When loss-of-function mutations in a gene lead to life span extension, it is a necessary conclusion that the gene normally limits life span in the wild type. The effect of a given mutation depends on a number of environmental and genetic conditions. For example, the combination of two mutations can result in additive, synergistic, subtractive, or epistatic effects on life span. Valuable insight into the processes that determine life span can be obtained from such genetic analyses, especially when interpreted with caution, and when molecular information about the interacting genes is available. Thus, genetic and molecular analyses have implicated several genes classes (daf, clk and eat) in life span determination and have indicated that aging is affected by alteration of several biological processes, namely dormancy, physiological rates, food intake, and reproduction.

Aging↗

Methylation of histone H3 lysine 9 creates a binding site for HP1 proteins.

Distinct modifications of histone amino termini, such as acetylation, phosphorylation and methylation, have been proposed to underlie a chromatin-based regulatory mechanism that modulates the accessibility of genetic information. In addition to histone modifications that facilitate gene activity, it is of similar importance to restrict inappropriate gene expression if cellular and developmental programmes are to proceed unperturbed. Here we show that mammalian methyltransferases that selectively methylate histone H3 on lysine 9 (Suv39h HMTases) generate a binding site for HP1 proteins--a family of heterochromatic adaptor molecules implicated in both gene silencing and supra-nucleosomal chromatin structure. High-affinity in vitro recognition of a methylated histone H3 peptide by HP1 requires a functional chromo domain; thus, the HP1 chromo domain is a specific interaction motif for the methyl epitope on lysine9 of histone H3. In vivo, heterochromatin association of HP1 proteins is lost in Suv39h double-null primary mouse fibroblasts but is restored after the re-introduction of a catalytically active SWUV39H1 HMTase. Our data define a molecular mechanism through which the SUV39H-HP1 methylation system can contribute to the propagation of heterochromatic subdomains in native chromatin.

Amino Acid Sequence↗

Flotillin-1-enriched lipid raft domains accumulate on maturing phagosomes.

Flotillin-1 was recently shown to be enriched on detergent-resistant domains of the plasma membrane called lipid rafts. These rafts, enriched in sphingolipids and cholesterol, sequester certain proteins while excluding others. Lipid rafts have been implicated in numerous cellular processes including signal transduction, membrane trafficking, and molecular sorting. In this study, we demonstrate both morphologically and biochemically that lipid rafts are present on phagosomes. These structures are enriched in flotillin-1 and devoid of the main phagosomes membrane protein lysosomal-associated membrane protein (LAMP1). The flotillin-1 present on phagosomes does not originate from the plasma membrane during phagocytosis but accumulates gradually on maturing phagosomes. Treatment with bafilomycin A1, a compound that inhibits the proton pump ATPase and prevents the fusion of phagosomes with late endocytic organelles, prevents the acquisition of flotillin-1 by phagosomes, indicating that this protein might be recruited on phagosomes from endosomal organelles. A proteomic characterization of the lipid rafts of phagosomes indicates that actin, the alpha- and beta-subunits of heterotrimeric G proteins, as well as subunits of the proton pump V-ATPase are among the constituents of these domains. Remarkably, the intracellular parasite Leishmania donovani can actively inhibit the acquisition of flotillin-1-enriched lipid rafts by phagosomes and the maturation of these organelles. These results indicate that specialized functions required for phagolysosome biogenesis may occur at focal points on the phagosome membrane, and therefore represent a potential target of intracellular pathogens.

Animals↗

Use of duplex polymerase chain reaction (duplex-PCR) technique to identify bovine and water buffalo milk used in making mozzarella cheese.

Molecular biology techniques have been used for species identification in food of animal origin in relatively recent years. A polymerase chain reaction (PCR) based method, the multiplex PCR, was recently applied to species identification in meat and meat products. It allows co-amplification of separate regions of a single gene or specific fragments, each typical of a different animal species in a single PCR reaction, using different pairs of primers in the same reaction mix. In the present paper, the duplex-PCR technique is proposed to identify bovine and water buffalo DNA in a single PCR assay in milk and mozzarella cheese (a typical Italian cheese, originally made from pure water buffalo milk). Because of its lower cost, undeclared bovine milk is added to water buffalo milk for making different kinds of mozzarella cheese. The results of this experiment indicate the applicability of this method, which showed an absolute specificity for the two species and a high sensitivity even down to low DNA concentrations (1 pg). In bovine and water buffalo mixtures of both milk and mozzarella cheese, the minimum concentration tested was 1% of bovine in water buffalo milk and water buffalo in bovine milk. The importance of the somatic cell content in raw milk is also discussed with special reference to the evaluation of mixtures (milk or cheese) of the two species.

Animals↗

Metastatic bone pain palliation with 89-Sr and 186-Re-HEDP in breast cancer patients.

AIM: The study evaluates the therapeutic efficacy of Strontium-89-chloride (89Sr) and 186Re-1,1-hydroxyethylidene diphosphonate (186Re-HEDP) in the palliation of painful bone metastases from breast cancer. PATIENTS AND METHODS: Fifty patients with painful multifocal bone metastases from breast cancer entered the study and were randomized into two groups according to the radiopharmaceutical used: 148 MBq 89Sr i.v. (Group A: 25 patients) and 1406 MBq 186Re-HEDP i.v. (Group B: 25 patients). Pain palliation was evaluated on the basis of the Wisconsin pain test improvement at two months and response was graded as complete, partial, minimal or absent. Hematological toxicity and side effects were reported according to WHO guidelines. RESULTS: The global response rate was 84% (21/25) for 89Sr and 92% (23/25) for 186Re-HEDP, respectively. The onset of pain palliation appeared significantly earlier in Group B (p < 0.0001). The duration of pain relief ranged from two months to 14 months (mean of 125 days with a median value of 120 days) in Group A and from one month to 12 months (mean of 107 days with a median value of 60 days) in Group B (p = 0.39). A moderate hematological toxicity was apparent in both groups. Platelet and white blood cell counts returned to baseline levels within 12 weeks after 89Sr administration and 6 weeks after 186Re-HEDP administration (p < 0.01). CONCLUSIONS: Both 89Sr and 186Re-HEDP are effective and safe in bone pain palliation in breast cancer with the latter showing a significantly faster onset of pain relief.

Adult↗

Phase II study of epirubicin, mitomycin C, and 5-fluorouracil in hormone-refractory prostatic carcinoma.

Management of metastatic prostatic carcinoma when it becomes refractory to hormonal therapy is controversial, and no standard treatment exists. Nevertheless, chemotherapy for hormone-refractory prostatic carcinoma (HRPC) has shown some advantages compared with the best supportive care. In a prospective phase II study, we evaluated the combination of epirubicin (E), mitomycin C (MMC), and 5-fluorouracil (5-FU) in patients with HRPC. Twenty-eight patients with HRPC were treated with a combination of E (30 mg/m2), 5-FU (750 mg/m2), and MMC (5 mg/m2) day 1 and 2, every 4 weeks. Treatment was continued until evidence of disease progression or excessive toxicity. Patients were monitored with serial measurements of prostate-specific antigen (PSA). Forty-seven percent of the patients exhibited a reduction of serum PSA concentration and an objective response; 38% exhibited disease stability, and 15% had disease progression. Toxicity was substantial. The median time to progression was 7.3 months (range, 1.7-16.8 months) and median survival was 14.5 months (range, 1.6-38.4 months). Performance status improved in 80% of patients, and bone pain was relieved in 70%. Thus the combination of E, MMC, and 5-FU shows activity in the treatment of HRPC, giving substantial palliation of symptoms. In one patient, PSA values remained low even when the tumor had progressed.

Adenocarcinoma↗