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PubMed2006

Oxygen therapy in the pre-hospital setting for acute exacerbations of chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD), a leading cause of morbidity and mortality in the developed world, is characterised by acute deterioration in symptoms. During these exacerbations, people are prone to developing alveolar hypoventilation, which may be contributed to by the administration of high inspired oxygen concentrations. OBJECTIVES: The objective of the review was to determine the effect of different inspired oxygen concentrations ("high flow" compared to "controlled") in the pre-hospital setting on outcome for people with acute exacerbations of COPD. SEARCH STRATEGY: We searched the Cochrane Airways Group Specialised Register (August 2005), the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 3, 2005), MEDLINE (1966 to August 2005), EMBASE (1980 to wk 32, 2005), CINAHL (1982 to August wk 1, 2005) and reference lists of articles. We also contacted authors of identified RCTs for details of other relevant, published and unpublished studies. SELECTION CRITERIA: Randomised controlled trials comparing oxygen therapy at different concentrations or oxygen therapy versus placebo in the pre-hospital setting for treatment of acute exacerbations of COPD were eligible. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data. MAIN RESULTS: The search identified a total of 741 abstracts, of which 18 were selected as potentially relevant, only two of the 18 studies were randomised controlled trials and eligible for inclusion in the review, but were ongoing and had no data available for analysis. AUTHORS' CONCLUSIONS: No relevant trials have been published to date, so there is no evidence to indicate whether different oxygen therapies in the pre-hospital setting have an effect on outcome for people with acute exacerbations of COPD. There is an urgent need for robust, well-designed randomised controlled trials to investigate the effect of oxygen therapies in the pre-hospital setting for people with acute exacerbations of COPD.

Emergency Medical Services↗
PubMed2006

Treatment of latent tuberculosis in persons at risk for multidrug-resistant tuberculosis: systematic review.

SETTING: The emergence and spread of multidrug-resistant tuberculosis (MDR-TB), caused by Mycobacterium tuberculosis resistant to at least isoniazid (INH) and rifampicin, is a threat to global TB control. OBJECTIVE: To appraise evidence of the effectiveness of treatment of latent TB infection (LTBI) in people at risk for developing active MDR-TB. DESIGN: Systematic review of comparative studies of people treated and not treated for LTBI following exposure to MDR-TB. DATA SOURCES: PubMed, EMBASE, LILACS and the Cochrane Library (December 2004). RESULTS: Two observational studies met inclusion criteria. A prospective cohort study found individualised tailored treatment to be effective for preventing active TB in children (OR = 0.20, 95%CI 0.04-0.94), while a retrospective cohort study found INH not to be effective (OR = 0.46, 95%CI 0.07-2.32). CONCLUSION: Evidence of the effects of treatment of LTBI in people exposed to MDR-TB is extremely limited in both quantity and quality. The increasing global spread of MDR-TB and the difficulties in treating it emphasise the need for effective preventive measures. Ideally, this issue should be addressed in a randomised controlled trial. Until such a trial is conducted, routine clinical data collected as part of existing TB control programmes could be useful and can be generated relatively easily.

Antitubercular Agents↗
PubMed1995

Molecular genetics and the diagnostic mycology laboratory.

The laboratory diagnoses or confirmation of fungal diseases are extremely important considerations in the proper and efficient management of patients experiencing these infections. When an infectious process is suspected, suitable material must be collected and submitted to the pathologist for microscopic examination and to the diagnostic laboratory for culture. The practice of modern medicine dictates that the turn-around time be reduced to a minimum so that specific therapy can be rapidly instituted. Unfortunately, the classical procedures used in processing specimens for isolation and identification of fungi implicated in these diseases are technically time consuming and on occasion labor-intensive. More importantly, fungi are slow growing and cultures are frequently held for 3 to 4 weeks before they are discarded as negative. With the exception of coccidioidomycosis, most attempts to develop serological tests for rapid diagnosis of fungal infections have been hampered by poor specificity caused by immunologic cross reactivity. To some extent, such problems can be circumvented by application of molecular biological techniques to these problems. For example, procedures have been developed that allow efficient screening of DNA expression libraries to identify useful recombinant antigens and production of selected antigens in quantity. This is potentially a practical approach using molecular biological techniques for development of sensitive, specific and practical reagents useful in the serological diagnosis of fungal infections. In addition, nucleic acid hybridization techniques based on the ability of complementary nucleic acid strands to specifically align and associate to form stable double-stranded complexes have been put to use to develop confirmation tests for a variety of important fungal isolates.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens, Fungal↗
PubMed2005

Modifications in the myogenic program induced by in vivo and in vitro aging.

In this study, we have used high density cDNA arrays to assess age-related changes in gene expression in the myogenic program of human satellite cells and to elucidate modifications in differentiation capacity that could occur throughout in vitro cellular aging. We have screened a collection of 2016 clones from a human skeletal muscle 3'-end cDNA library in order to investigate variations in the myogenic program of myotubes formed by the differentiation of myoblasts of individuals with different ages (5 days old, 52 years old and 79 years old) and induced to differentiate at different stages of their lifespan (early proliferation, presenescence and senescence). Although our analysis has not been able to underline specific changes in the expression of genes encoding proteins involved in muscle structure and/or function, we have demonstrated an age-related induction of genes involved in stress response and a down-regulation of genes involved both in mitochondrial electron transport/ATP synthase and in glycolysis/TCA cycle. From this global approach of post-mitotic cell aging, we have identified 2 potential new markers of presenescence for human myotubes, both strongly linked to carbohydrate metabolism, which could be useful in developing therapeutic strategies.

Aged↗
PubMed2000

Depot perphenazine decanoate and enanthate for schizophrenia.

BACKGROUND: Anti-psychotic drugs are usually given orally but compliance with medication given by this route may be difficult to quantify. The development of depot injections in the 1960s gave rise to extensive use of depots as a means of long-term maintenance treatment. Perphenazine decanoate and enanthate are depot antipsychotics that belong to the phenothiazine family and have a piperazine ethanol side chain. OBJECTIVES: To assess the effects of depot perphenazine decanoate and enanthate versus placebo, oral anti-psychotics and other depot antipsychotic preparations for people with schizophrenia in terms of clinical, social and economic outcomes. SEARCH STRATEGY: Biological Abstracts (1982-1998), the Cochrane Library (Issue 2, 1998), the Cochrane Schizophrenia Group's Register (June 1998), EMBASE (1980-1998), MEDLINE (1966-1998), and PsycLIT (1974-1998) were searched. References of all identified trials were also inspected for more studies and industry contacted. SELECTION CRITERIA: Randomised clinical trials focusing on people with schizophrenia where depot perphenazine decanoate and enanthate, oral anti-psychotics or other depot preparations were compared. DATA COLLECTION AND ANALYSIS: Studies were reliably selected, quality rated and data extracted. For dichotomous data Peto odds ratios (OR) with the 95% confidence intervals (CI) were estimated. Where possible, the number needed to treat statistic (NNT) was calculated. Analysis was by intention-to-treat. MAIN RESULTS: One study of six months duration, compared perphenazine enanthate to clopenthixol decanoate. There was no differences between the two for outcomes of global improvement, relapse and leaving the study early. More people in the perphenazine enanthate group required anticholinergic drugs than those allocated to clopenthixol decanoate (OR 3.6 CI 1.2-10, NNT 10). A single study (n=64, duration six weeks) compared perphenazine enanthate and its longer acting decanoate ester. Data on relapse and leaving the study early failed to show convincing differences. The enanthate group, however, experienced more movement disorders (OR 0.2 CI 0.06-0.7) than those allocated the decanoate ester of the same drug (NNT 4.0) and required more anticholinergic drugs (OR 0.2 CI 0.08-0.7, NNT 3.7). REVIEWER'S CONCLUSIONS: Depot perphenazine is in clinical use in the Nordic countries, Belgium, Portugal and the Netherlands. At a conservative estimate a quarter of a million people suffer from schizophrenia in those countries and could be treated with depot perphenazine. The total number of participants in the two trials with useful data is 236. Neither study observes the effect of oral versus depot antipsychotic drugs. Until well conducted and reported randomised trials are undertaken clinicians will be in doubt as to the effects of perphenazine depots and people with schizophrenia should exercise their own judgement or ask to be randomised.

Antipsychotic Agents↗
PubMed2005

The history of hiatal hernia surgery: from Bowditch to laparoscopy.

OBJECTIVE: This review addresses the historical evolution of hiatal hernia (HH) repair and reports in a chronological fashion the major milestones in HH surgery before the laparoscopic era. METHODS: The medical literature and the collections of the History of Medicine Division of the National Library of Medicine were searched. Secondary references from all sources were studied. The senior author's experience and personal communications are also reported. RESULTS: The first report of HH was published in 1853 by Bowditch. Rokitansky in 1855 demonstrated that esophagitis was due to gastroesophageal reflux, and Hirsch in 1900 diagnosed an HH using x-rays. Eppinger diagnosed an HH in a live patient, and Friedenwald and Feldman related the symptoms to the presence of an HH. In 1926, Akerlund proposed the term hiatus hernia and classified HH into the 3 types that we use today. The first elective surgical repair was reported in 1919 by Soresi. The physiologic link between HH and gastroesophageal reflux was made at the second half of the 20 century by Allison and Barrett. In the midst of a physiologic revolution, Nissen and Belsey developed their famous operations. In 1957, Collis published his innovative operation. Thal described his technique in 1965, and in 1967, Hill published his procedure. Many modifications of these procedures were published by Pearson and Henderson, Orringer and Sloan, Rossetti, Dor, and Toupet. Donahue and Demeester significantly improved Nissen's operation, and they were the first to truly understand its physiologic mechanism. CONCLUSION: Hiatal hernia surgery has evolved from anatomic repair to physiological restoration.

Fundoplication↗
PubMed2003

Forward & reverse chemical genetics using SPOS-based combinatorial chemistry.

Combinatorial chemistry is being applied to diverse problems in the biological and pharmaceutical sciences. This review will describe an emerging application called "chemical genetics" or "chemical genomics" - genetics and genomics are often used interchangeably in this context. In forward chemical genomics, chemical libraries are tested in living systems to discover compounds that cause a desirable effect. Subsequently, the protein target is identified using various biochemical and molecular biological tools. By this method, we gain insights into the inner workings of life, and indeed, in some forms this has been the path by which most of the pharmacopoeia was discovered. In reverse chemical genetics, proteins of interest are used to probe compound collections, and those compounds that bind the proteins of interest are used to treat living systems and observed for interesting biological responses. Plausible biological roles of these proteins are inferred from the effects of the compounds because they are assumed to generally inhibit, or more rarely, stimulate, the protein's functions. Interestingly, the reverse genetic approach is emerging as the leading model for drug discovery today. Different methods and cases will be described to illustrate forward and reverse paradigms, including those developed in the author's laboratory.

Combinatorial Chemistry Techniques↗
PubMed2001

James Wardrop (1782-1869): from Whitburn to Windsor Castle.

The medical career of a Scottish doctor, James Wardrop, in the 19th century is described. An early interest in the developing science of Pathology in the Royal College of Surgeons of Edinburgh was expanded further when he moved to London, due to financial needs. Despite being outside the London teaching hospital scene, he continued to publish and teach in the private schools of the time. His interest in ophthalmology led him to describe what we now know as retinoblastoma, with recommendation for treatment. He also described sympathetic ophthalmitis and performed paracentesis in acute angle-closure glaucoma. He became surgeon to the Prince of Wales, later King George IV, but his criticism of other medical men at court led to his exclusion from the King at the scene of his death. He owned a notable collection of pictures and presented two of them to the National Gallery of Scotland on its foundation in 1850. In recent years, his work has been recognised by leading ophthalmologists, particularly in the USA. The Library of the Royal College of Surgeons of Edinburgh contains several of his works, and his portrait hangs in the College.

Famous Persons↗
PubMed1996

An assessment of practice support and continuing medical education needs of rural Pennsylvania family physicians.

Family physicians provide the greatest proportion of care in rural communities. Yet, the number of physicians choosing family practice and rural practice has continued to decline. Undesirable aspects of rural practice, such as professional isolation and a lack of or inadequate resources, are assumed to be associated with this decline. This article reports on the practice support and continuing medical education needs of rural family physicians. A mail survey was conducted in 1993 on a purposive sample of family physicians in 39 of 67 rural-designated or urban Pennsylvania counties with low population densities. The physicians identified needs that included patient education materials and programs, community health promotion, federal regulation updates, technical assistance with computers and business management, database software and a videotape lending library, a drug hotline, and mini-fellowships on clinical skill development. A majority of respondents were willing to participate in clinical educational experiences for students and residents. Some physicians indicated a lack of interest in access to information through telecommunications, e.g., video conference referrals and consultations. Overall, findings revealed that family physicians need and are receptive to a variety of practice support and continuing education programs. A practice support program coupled with policy coordination among public and private organizations is likely to lessen complaints by rural primary care physicians.

Clinical Competence↗
PubMed2006

Vaccines for preventing malaria (SPf66).

BACKGROUND: A malaria vaccine is badly needed. SPf66 was one of the earliest vaccines developed. It is a synthetic peptide vaccine containing antigens from the blood stages of malaria linked together with an antigen from the sporozoite stage, and is targeted mainly against the blood (asexual) stages. OBJECTIVES: To assess the effect of SPf66 malaria vaccines against Plasmodium falciparum, P. vivax, P. malariae, and P. ovale in preventing infection, disease, and death. SEARCH STRATEGY: We searched the Cochrane Infectious Diseases Group Specialized Register (September 2005), CENTRAL (The Cochrane Library 2005, Issue 3), MEDLINE (1966 to September 2005), EMBASE (1980 to September 2005), LILACS (1982 to September 2005), Science Citation Index (1981 to September 2005), and reference lists of articles. We also contacted organizations and researchers in the field. SELECTION CRITERIA: Randomized and quasi-randomized controlled trials comparing SPf66 vaccine with placebo or routine antimalarial control measures in people of any age receiving an artificial challenge or natural exposure to malaria infection (any species). DATA COLLECTION AND ANALYSIS: Two people independently assessed trial quality and extracted data, including adverse events. Results were expressed as relative risks (RR) with 95% confidence intervals (CI). MAIN RESULTS: Ten efficacy trials of SPf66 involving 9698 participants were included. Results with SPf66 in reducing new episodes of P. falciparum malaria were heterogeneous: it was not effective in four African trials (RR 0.98, 95% CI 0.90 to 1.07; 2371 participants) or in one Asian trial (RR 1.06, 95% CI 0.90 to 1.25; 1221 participants). In four trials in South America the number of first attacks with P. falciparum was reduced by 28% (RR 0.72, 95% CI 0.63 to 0.82; 3807 participants). It did not reduce episodes of P. vivax malaria or admission to hospital with severe malaria. Trials have not indicated any serious adverse events with SPf66 vaccine. AUTHORS' CONCLUSIONS: There is no evidence for protection by SPf66 vaccines against P. falciparum in Africa. There is a modest reduction in attacks of P. falciparum malaria following vaccination with SPf66 in South America. There is no justification for further trials of SPf66 in its current formulation. Further research with SPf66 vaccines in South America or with new formulations of SPf66 may be justified.

Humans↗
PubMed2002

Identification of cut rose (Rosa hybrida) and rootstock varieties using robust sequence tagged microsatellite site markers.

In this study a DNA fingerprinting protocol was developed for the identification of rose varieties based on the variability of microsatellites. Microsatellites were isolated from Rosa hybrida L. using enriched small insert libraries. In total 24 polymorphic sequenced tagged microsatellite site (STMS) markers with easily scorable allele profiles, from six different linkage groups, were used to characterize 46 Hybrid Tea varieties and 30 rootstock varieties belonging to different species (Rosa canina L., Rosa indica Thory., Rosa chinensis Jacq., Rosa rubiginosa L., and Rosa rubrifolia glauca Pour.). Clones and known flower color mutants were identified as being identical, all other varieties were differentiated by a unique pattern with as few as three STMS markers. The high discriminating power of the loci suggests that a selection of the most-robust STMS markers may be able to differentiate any two varieties within rootstocks or Hybrid Teas except for mutants. The selected STMS markers will be useful as a tool for reference collection management, for assessing essential derivation of varieties and illegal propagation.

Alleles↗
PubMedDate not supplied

[A review of the clinical application of dyes in gastrointestinal chromoendoscopy, and their magistral formulation].

OBJECTIVE: To review the drug compounding of dyes employed in chromoendoscopy, and their clinical effectiveness. METHOD: A literature search in Medline, Cochrane Library, and Micromedex was carried out with the term chromoendoscopy as a keyword, and the search was then repeated for each dye found in association with the term endoscopy. A number of monographs, scientific journals, and references quoted in selected papers were also reviewed. Papers collected were then classified according to their methodology. RESULTS: Ninety-six references were found, their original article being recovered for only 57 of these - 13 clinical trials, 21 case series, and 11 reviews. References were found for 7 dyes. Main indications, evidence of effectiveness, administration route, and drug formulation are described for each dye. CONCLUSIONS: The number of papers involved is high, but their accessibility is limited. Evidence is overall scarce, but high in cases such as methylene blue for Barrett s esophagus, lugol in the detection of esophageal carcinoma, and indigo carmine for colonic hyperplastic polyp differentiation. Drug compounding is rather simple, but scarcely developed.

Coloring Agents↗
PubMed2002

High-throughput methods for culturing microorganisms in very-low-nutrient media yield diverse new marine isolates.

Microbial diversity studies based on the cloning and sequencing of DNA from nature support the conclusion that only a fraction of the microbial diversity is currently represented in culture collections. Out of over 40 known prokaryotic phyla, only half have cultured representatives. In an effort to culture the uncultured phylotypes from oligotrophic marine ecosystems, we developed high-throughput culturing procedures that utilize the concept of extinction culturing to isolate cultures in small volumes of low-nutrient media. In these experiments, marine bacteria were isolated and cultivated at in situ substrate concentrations-typically 3 orders of magnitude less than common laboratory media. Microtiter plates and a newly developed procedure for making cell arrays were employed to raise the throughput rate and lower detection sensitivity, permitting cell enumeration from 200-microl aliquots of cultures with densities as low as 10(3) cells/ml. Approximately 2,500 extinction cultures from 11 separate samplings of marine bacterioplankton were screened over the course of 3 years. Up to 14% of the cells collected from coastal seawater were cultured by this method, which was 14- to 1,400-fold higher than the numbers obtained by traditional microbiological culturing techniques. Among the microorganisms cultured were four unique cell lineages that belong to previously uncultured or undescribed marine Proteobacteria clades known from environmental gene cloning studies. These cultures are related to the clades SAR11 (alpha subclass), OM43 (beta subclass), SAR92 (gamma subclass), and OM60/OM241 (gamma subclass). This method proved successful for the cultivation of previously uncultured marine bacterioplankton that have consistently been found in marine clone libraries.

Bacteriological Techniques↗
PubMed1997

[An entire rain forest can be screened at pharmaceutical industry's laboratories].

The pharmaceutical industry has long been heavily reliant on natural products, and today more than half of the twenty best-selling pharmaceuticals are derived from natural sources. Hitherto sample collection from fauna and flora has been based on an ethnobotanical approach involving traditional healers and oral histories of indigenous peoples as sources of information on folk uses of plants and organisms. In the future, however, random sampling combined with automated high-throughput screening (HTS) may come to the forefront in drug design, enabling extensive libraries of active compounds to be built up, and rendering local knowledge largely irrelevant. New technological advances in chemistry, molecular biology and data processing are combined in automated systems whereby HTS, based on bioassay-guided fractionation procedures, is used to isolate active compounds, and enabling the chemical structure of isolated compounds to be determined within 24 hours. The combination of the speed of HTS, and a remarkable decrease in the amount of sample required for the isolation and structure determination of natural compounds, has improved our ability to find unique natural products for drug development. Moreover, it has already been demonstrated that, owing to the relatively minute amounts of material required for HTS, this random sampling approach to bioprospecting for the purposes of drug will benefit efforts to conserve such sensitive biosystems as the rain forests and marine ecosystems. Thus, this technology would seem to be more compatible with the needs of modern drug design in the pharmaceutical industry that the ethnobotanical approach.

Drug Industry↗
PubMed2004

Face washing promotion for preventing active trachoma.

BACKGROUND: Trachoma remains a major cause of avoidable blindness among underprivileged populations in many developing countries. It is estimated that about 146 million people have active trachoma and nearly six million people are blind due to complications associated with repeat infections. OBJECTIVES: The objective of this review is to assess the effects of face washing on the prevalence of active trachoma in endemic communities. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials - CENTRAL (which contains the Cochrane Eyes and Vision Group trials register) on The Cochrane Library (Issue 2, 2004), MEDLINE (1966 to February 2004), EMBASE (1980 to February 2004), the reference lists of identified trials and the Science Citation Index. We also contacted investigators and experts in the field to identify additional trials. SELECTION CRITERIA: We included randomised or quasi-randomised controlled trials, comparing face washing with no treatment or face washing combined with antibiotics against antibiotics alone. Participants in the trials were people normally resident in endemic trachoma communities. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and assessed trial quality. Study authors were contacted for additional information. Two clinically heterogeneous trials are included, therefore a meta-analysis was considered inappropriate. MAIN RESULTS: This review includes two trials with data from a total of 2560 participants. Face washing combined with topical tetracycline was compared to topical tetracycline alone in three pairs of villages in one trial. The trial found a statistically significant effect for face washing combined with topical tetracycline in reducing 'severe' active trachoma compared to topical tetracycline alone. No statistically significant difference was observed between the intervention and control villages in reducing ('non-severe') active trachoma. The prevalence of clean faces was higher in the intervention villages than the control villages and this was statistically significant. Another trial compared eye washing to no treatment or to topical tetracycline alone or to a combination of eye washing and tetracycline drops in children with follicular trachoma. The trial found no statistically significant benefit of eye washing alone or in combination with tetracycline eye drops in reducing follicular trachoma amongst children with follicular trachoma. REVIEWERS' CONCLUSIONS: There is some evidence that face washing combined with topical tetracycline can be effective in reducing severe trachoma and in increasing the prevalence of clean faces. Current evidence does not however support a beneficial effect of face washing alone or in combination with topical tetracycline in reducing active trachoma.

Anti-Bacterial Agents↗
PubMed2002

Computation of the physio-chemical properties and data mining of large molecular collections.

Very large data sets of molecules screened against a broad range of targets have become available due to the advent of combinatorial chemistry. This information has led to the realization that ADME (absorption, distribution, metabolism, and excretion) and toxicity issues are important to consider prior to library synthesis. Furthermore, these large data sets provide a unique and important source of information regarding what types of molecular shapes may interact with specific receptor or target classes. Thus, the requirement for rapid and accurate data mining tools became paramount. To address these issues Pharmacopeia, Inc. formed a computational research group, The Center for Informatics and Drug Discovery (CIDD).* In this review we cover the work done by this group to address both in silico ADME modeling and data mining issues faced by Pharmacopeia because of the availability of a large and diverse collection (over 6 million discrete compounds) of drug-like molecules. In particular, in the data mining arena we discuss rapid docking tools and how we employ them, and we describe a novel data mining tool based on a ID representation of a molecule followed by a molecular sequence alignment step. For the ADME area we discuss the development and application of absorption, blood-brain barrier (BBB) and solubility models. Finally, we summarize the impact the tools and approaches might have on the drug discovery process.

Algorithms↗
PubMed2004

Development, utilisation, and importance of accident and emergency department derived assault data in violence management.

OBJECTIVES: To develop formal processes for the collection, disclosure, and effective use of accident and emergency (A&E) department derived assault injury data for city violence reduction. METHODS: Over a four year period, managed by a multi-agency steering group, A&E data collection, collation, and disclosure processes were developed, instituted, and refined. Consultations and negotiations between agencies identified the most effective and ethical methods, appropriate recipients, and the nature of the information of most use. RESULTS: Disclosure of A&E data to city authorities, the police, and local media drew substantial attention and crime prevention resources to the locations of violence. As a result, a police task force responsible for targeting city street crime was funded, which analysed both A&E and police information. Monthly, electronic transfer of raw, anonymous data to the task force crime analyst informed and prompted violence prevention initiatives by several agencies. Police mounted overt and covert interventions targeted at violence hotspot licensed premises and used the data to oppose, on injury grounds, drinks/entertainment licence applications. Transport authorities established new half hourly night time city centre bus services. The local authority mounted an assault awareness campaign in schools and public libraries, and licensing magistrates used the data to measure, for example, the impact of continuous 36 hour drinks licensing on public safety. CONCLUSIONS: The principal finding of this evaluation was that judicious sharing of unique information about locations and times of violence derived from A&E patients was a powerful and effective means of targeting police and other local resource to bring about violence reduction.

Adult↗
PubMed1996

Isolation, characterization, and expression of cDNAs encoding the medaka (Oryzias latipes) ovarian follicle cytochrome P-450 aromatase.

Two cDNA clones of cytochrome P-450 aromatase (P-450arom) were isolated from a medaka (Oryzias latipes, a daily spawner) ovarian follicle cDNA library using a medaka P-450arom genomic DNA fragment as a probe. The first, 1,809-bp insert (S81f) contains an 1,554-bp open reading frame encoding a 518-amino-acid polypeptide. The second, 1,852-bp (S52f) insert possesses an open reading frame identical to that of the S81f insert, except for the absence of the heme-binding region as the result of an additional A residue at the position of nucleotide 1,827. Expression of the S81f cDNA, but not of the S52f cDNA, in nonsteroidogenic COS-1 cells leads to production of a steroidogenic enzyme which is capable of converting exogenous testosterone to estrogen. The P-450arom genomic DNA fragment hybridizes to a single mRNA in medaka ovarian follicle RNA. Changes in level of P-450arom transcripts and P-450arom enzyme activity were determined in medaka ovarian follicles collected at 16 stages of development. A close correlation was found between these two profiles, both being high in midvitellogenic follicles and low in postvitellogenic follicles collected during oocyte maturation. These findings, together with those of our previous study showing that actinomycin D prevented gonadotropin-induced aromatase activation by medaka ovarian follicles, suggest that aromatase activity is regulated at the transcriptional level in medaka vitellogenic follicles.

Animals↗