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A2-agonists in sheep: a review.

OBJECTIVE: To review the use and adverse effects of alpha(2)-agonists in sheep. STUDY DESIGN: Literature review. MATERIAL AND METHODS: 'Pubmed' of the United States National Library of Medicine and 'Veterinary Science' of CAB International were searched for references relating sheep to alpha(2)-agonists. The bibliographies of retrieved articles were further scrutinized for pertinent references, and relevant articles were selected manually. RESULTS: Reports on the use of clonidine, xylazine, detomidine, romifidine, medetomidine and dexmedetomidine, MPV-2426 and ST-91 in sheep were found in the literature. Most of the studies described xylazine followed by medetomidine and clonidine. The literature on detomidine and romifidine in sheep was sparse. Reports included pharmacokinetic studies, evaluation of sedative, analgesic, and anaesthetic techniques with or without cardiovascular effects, and experimental investigations of adverse effects (mainly hypoxaemia) including the mechanisms of pulmonary oedema and impaired oxygenation after alpha(2)-agonist administration. CONCLUSIONS: A(2)-agonists are potent and effective analgesics in sheep. In combination with ketamine, they are frequently used for the induction and maintenance of anaesthesia, in this case analgesia is satisfactory. The degree of hypoxaemia which occurs with all commercially available alpha(2)-agonists is highly variable and depends on individual or breed-related factors; the most severe reactions occur after intravenous (IV) injection and during general anaesthesia. Clinical relevance Subclinical respiratory disease is common in sheep. Rapid IV injection of alpha(2)-agonists without supplementary oxygen should be avoided whenever hypoxaemia may be critical.

Adrenergic alpha-Antagonists↗

Duplication of 7p21.2-->pter due to maternal 7p;21q translocation: implications for critical segment assignment in the 7p duplication syndrome.

We describe a 1-year-old boy with mental and physical retardation, a large anterior fontanel, brachycephaly with flat occiput, short and stubby fingers, generalized hypotonia, ocular hypertelorism, low-nasal bridge, long philtrum, high-narrow palate, apparently low-set ears, and a small mandible. Cytogenetic analysis utilizing high resolution chromosome banding technique showed an unbalanced karyotype consisting of 46,XY,add(21)(q22.3) that originated from maternal balanced translocation between chromosomes 7 and 21. Fluorescence in situ hybridization (FISH) using micro-dissected library probe pool from chromosome 7 confirmed the additional material on 21q was derived from chromosome 7. Our results indicated that the patient had an unbalanced translocation, 46,XY, der(21)t(7;21)(p21.2;q22.3)mat, which resulted in duplication for distal 7p. Our patient is similar to reported cases with a 7p15-->pter or larger duplication of 7p, suggesting that the critical segment causing the characteristic phenotype of 7p duplication syndrome, including large anterior fontanel, exists at 7p21.2 or 7p21.2-->pter.

Abnormalities, Multiple↗

[Cloning and characterization of CMO gene from Atriplex hortensis].

Glycine betaine is a widespread osmopretectant existed in many organisms. In higher plant, glycine betaine is synthesized via a two-sep oxidation reaction: choline-->betaine aldehyde-->glycine betaine. The first step, also the speed-limiting step, is catalyzed by choline monooxygenase(CMO). Choosing halophyte Atriplex hortensis as material, we constructed a salt stress-induced cDNA library, and isolated a 1.77 kb length cDNA clone with spinach CMO cDNA as probe. The sequencing result showed a complete Open Reading Frame encoding a 438-amino-acid polypeptide which was 81% and 72% identified to CMO sequences of spinach and sugar beet in amino acid homology respectively. Compared with the CMO from spinach and sugar beet, the AhCMO had one conserved Rieske-Type [2Fe-2S] cluster-binding region and one conserved mononuclear Fe-binding motif. The expression pattern of AhCMO under salt stress was also stuied, the transcriptional level of AhCMO raised about three folds after the plant was treated with brine for 4 days. The AhCMO was then transfered into tobacco(Nictiana tabacum var. Xanthi) with 35S promotor and seven transgenic plants were certified by northern blot, these plants displayed some salt- and drought-stress tolerance when grew well on MS medium contained 1.2% NaCl or 10% PEG while the control was stagnated under the same cndition.

Amino Acid Sequence↗

Antigen-specific IgG antibodies in stage IV long-time survival breast cancer patients.

BACKGROUND: Profiling the immune responses in patients with cancer is expected to facilitate the design of diagnostic tests and therapeutic vaccines. Such studies usually require the parental antigens. We attempted to profile the immune responses in patients with breast cancer using a peptide phage display selection strategy, which identifies antibody specificities whether or not the antigens are known. MATERIALS AND METHODS: A panel of random peptide phage libraries was panned on serum IgG antibodies from breast cancer patients with stage IV, seeking for disease specific IgG epitopes. ELISA, immunoscreening, and Western blotting techniques were the main approaches used. RESULTS: Phage-displayed peptides were specifically enriched for binding to IgG antibodies from patients with breast cancer. Several peptides have been identified, in particular the SQRIPARIHHFPTSI peptide, which was recognized by IgG antibodies from breast cancer patients, but not from normals (p < 0.0004). In patients who responded to the selected peptides, in particular the SQRIPARIHHFPTSI peptide, antibodies against a 66 kDa cellular protein were found. Interestingly, three out of six patients with the strongest immunoreactivity are still alive, with a mean survival time from first recurrence until now of 2553 days. In contrast, all the nonresponders (n = 10) are deceased. The mean survival time of these patients was 784 days, whereas the mean survival time of the three deceased responders was 1050 days (p < 0.02). CONCLUSIONS: The data provide the first example in which panning of peptide phage display libraries on patient IgG antibodies results in the isolation of breast cancer specific IgG epitopes, some of which correlate with patient survival time. Thus, the identified B-cell epitopes should be of great interest in vaccine development.

Amino Acid Sequence↗

Critical care: how should we evaluate our progress?

OBJECTIVE: Review of the history and accomplishments of the Society of Critical Care Medicine (SCCM) to determine appropriate directions for the future. DATA SOURCES: Historical documents of the SCCM, Critical Care Medicine, bioethics and healthcare financing literature, Instant Library of Quotations. STUDY SELECTION: Identified (by the author) material containing specific statements concerning goals and objectives at the time of the founding of the SCCM and at intervals. Material supporting and criticizing predictive indices were identified and bioethical treatises concerning patient autonomy and quality-of-life decisions were chosen. DATA EXTRACTION: Presidential addresses of the first three SCCM presidents, material relevant to preservation of life and alleviation of suffering from bioethical and healthcare financing perspectives. Relevant quotations. DATA SYNTHESIS: Initial goals and objectives were identified. Societal and economic factors changing critical care were analyzed for their effect on current and future SCCM directions and objectives. CONCLUSIONS: The founding members set important goals for critical care and patient care, research, education, and organization. From a perspective of what was foreseeable, these goals have been accomplished to an admirable degree. The SCCM has responded to these goals by providing educational programs and fostering research, especially in its annual meetings and through the publication of guidelines in Critical Care Medicine. The SCCM members would do well to read the first three presidential addresses to experience the eloquence and foresight firsthand, particularly with respect to the founders' spirit, considerations of training, scope of care, humanism, organization and relations within and outside of critical care, integration of care, and development of the scientific process at the bedside. There have been major changes in society since the SCCM was founded: the maturation of the concept of patient's autonomy; recognition of quality-of-life values; healthcare financing; and legal and ethical aspects of care. The critical care profession in general, and the SCCM specifically, should seek to develop effective cost-containment strategies and severity of illness or predictive indices. The SCCM should also educate the professions with respect to ethical issues and provide information directly to the public, especially in the areas of advance directives and withholding and withdrawing care. Through these contributions, the SCCM can assume its proper leadership role within medicine, but, of greater importance, in society. In doing so, societal myths and misunderstandings of the capabilities, futility, role, and limitations of critical care can be corrected. The organization and structure of the SCCM are well developed to accomplish these ends. The SCCM leaders are both able and willing. The objectives seem reasonable and should be attainable.

Critical Care↗

The Cochrane Collaboration Pain, Palliative Care and Supportive Care Collaborative Review Group.

The Pain, Palliative and Supportive care group is one of 50 collaborative review groups that make up the Cochrane Collaboration, an international organization with the task of preparing, maintaining and disseminating systematic reviews of the effects of healthcare. Cochrane reviews are published cumulatively four times a year on the Cochrane library (CD-ROM and Web-based), along with other useful material such as a register of some 300,000 randomized controlled trials. The group has identified some 20,000 randomized trials in pain and 1,200 in palliative care. Reviews in progress are also published on the library as protocols. Full peer-review is undertaken for protocols and reviews. The Pain, Palliative and Supportive care group is an informal international team involving some 100 people from some 18 countries. The group has published 26 protocols and 17 full reviews with a further 50 reviews in progress. The task is huge and there is scope for further volunteers to help with the various tasks of writing reviews, peer reviewing and literature searching.

Databases, Factual↗

Chemical synthesis of TASP arrays and their application in protein design.

A combinatorial synthesis of de novo proteins is described. The concept of template-assembled synthetic proteins (TASP) has been adapted to an orthogonal assembly of small libraries of purified peptide building blocks. It is combined with the spot synthesis of peptides which is exploited to array cyclic decapeptide templates on cellulose membranes. A cleavable linker on the cellulose allows control of the synthesis. The hydrophilic proteins are constructed by successive cleavage of orthogonal protecting groups on the template, followed by coupling of amphipathic helices in a predefined orientation and finally by incorporation of a cofactor. Libraries of peptides with variation of the amino acids expected to be close to the cofactor were coupled to the cellulose-bound template in all combinations, yielding up to 500 variants of a protein. Cofactors have been inserted either at non-covalent binding sites as heme and Cu2+ or by covalent modification of amino acids as Ru-bipyridine or flavin. The proteins were screened by recording their UV-vis spectra directly on the solid support. The properties screened include the redox potential of heme proteins, charge transfer bands indicating the ligation of Cu-centers, enzymatic activity, and folding stability. Synthesis of the best hits as soluble variants was used for detailed characterization. Iterative improvement in a second screening cycle was efficient in finding novel copper proteins. We discuss the prospects of synthesizing proteins by extending the concept to beta-sandwich proteins and construction of efficient peptide libraries with computer-supported design, as well as the possible usage of improved solid phase materials.

Amino Acid Sequence↗

DXplain: a Web-based diagnostic decision support system for medical students.

DXplain is a diagnostic decision support program, with a new World Wide Web interface, designed to help medical students and physicians formulate differential diagnoses based on clinical findings. It covers over 2000 diseases and 5000 clinical manifestations. DXplain suggests possible diagnoses, and provides brief descriptions of every disease in the database. Not all diseases are included, nor does DXplain take into account preexisting conditions or the chronological sequence of clinical manifestations. Despite these limitations, it is a useful educational tool, particularly for problem-based learning (PBL) cases and for students in clinical rotations, as it fills a niche not adequately covered by MEDLINE or medical texts. The system is relatively self-explanatory, requiring little or no end-user training. Medical libraries offering, or planning to offer, their users access to Web-based materials and resources may find this system a valuable addition to their electronic collections. Should it prove popular with the local users, provision of access may also establish or enhance the library's image as a partner in medical education.

Clinical Clerkship↗

[Development of GC/MS library for analyzing pesticides and drugs].

To analyze the root components of compounds causing drug addiction, we have developed our own GC/MS libraries(PESTICID.LIB consisting of 20 pesticides and Herbicides, and DRUG.LIB with 57 drugs). We have usually utilized standardized agents, but gastric contents, gastric specimens, serum and urine samples from patients were also used for the analyses. We were able to add libraries of various difficult to purchase psychotropic drugs and legally restricted agents by extracting them from the patient samples. Comments about the retention time, the base peak of the mass spectrum and 5 typical ion chromatograms in the libraries have been useful for laboratory analysis, and consequently have improved the accuracy of detection and identification. They were also found to be a useful guideline for discrimination of the unchanged materials and the metabolites. We are attempting to improve the accuracy of the library to avoid the effects of GC column conditions such as the column size, column temperature and different inserts by using a retention time index.

Gas Chromatography-Mass Spectrometry↗

Reference books and computerized information services: partners in librarianship.

As a basis for thoughts on the roles of reference books and computerized information services in general, a comparison is made of the value to medical libraries of a comprehensive reference tool (the new dual media publication Biomedical Research in Progress) and a comprehensive information center file (the Smithsonian Science Information Exchange, the national resource for information on research in progress). It is concluded that a detailed reference tool which is physically present for library users has several advantages, in particular the provision of both detailed and comprehensive retrieval of all biomedical research information at substantially less annual cost and with faster access time than is possible with comparable questions put to an information center. On the other hand, the information center is able to provide more up-to-date material in more flexible combinations. The recommendation is made that medical libraries avoid treating the comprehensive reference tool and the computerized information file as alternatives and instead view both as necessary and complementary to each other.

Computers↗

The reorganization of a monographic reference collection.

Reference monographs in the Health Sciences Library of the College of Medicine and Dentistry of New Jersey were reorganized recently according to form, in order to enable both librarians and patrons to utilize these materials more efficiently. This reorganization reflects the unique characteristics of reference books as differentiated from the regular monographic collection, since reference materials are frequently consulted for quick "look-ups." A reference category scheme was developed and implemented, based on observations of and comparisons with reference collections of eight medical libraries in the New York metropolitan area. The reorganization enhances the retrievability of materials from this collection.

Book Classification↗

High-resolution cosmid mapping of the left arm of Saccharomyces cerevisiae chromosome XII; a first step towards an ordered sequencing approach.

For the sequencing of the left arm of chromosome XII of Saccharomyces cerevisiae, we fine-mapped the entire 450 kb fragment between the ribosomal DNA (rDNA) and the left telomere. Total yeast DNA in agarose blocks was digested with I-PpoI, which exclusively cuts once in each repeat unit of the rDNA. The resulting fragment was isolated from pulsed-field gels, together with the equally sized chromosome IX. A cosmid library of some 30-fold chromosome coverage was generated from this material, with the cloning efficiency being around 20,000 clones per microgram genomic DNA. The chromosome XII and IX specific clones were identified by complementary hybridizations with the respective chromosomes. For the left arm of chromosome XII, a contiguous cosmid array (contig) with an average map resolution better than 9 kb was generated by clone hybridization procedures. The ordered library serves as a tool for the physical mapping of genetic markers. Also, a minimal set of 15 clones was selected that covers the entire fragment. This subset forms the basis for the generation of a template map of much higher resolution for a directed sequencing of the left arm of chromosome XII.

Chromosome Mapping↗

A note on the Philadelphia Regional Medical Library Committee.

No rigid library plan can fullfil the needs of every region. The Philadelphia Regional Medical Library Committee, composed of representatives of the five medical schools, the College of Physicians, and other medical organizations, was formed to determine cooperative activities that best suit its own needs. The committee has reviewed plans for new libraries at several medical schools to avoid duplication of library resources. It envisions, also, cooperative storage of little-used materials, messenger service, an acquisition program to expand regional resources, improved communication by means of mechanical devices, and the establishment of a regional center and distribution of bibliographies from regionally located MEDLARS tapes.

Electronic Data Processing↗

Detection of diverse bacterial signatures in atherosclerotic lesions of patients with coronary heart disease.

BACKGROUND: Bacterial infection has been discussed as a potential etiologic factor in the pathophysiology of coronary heart disease (CHD). This study analyzes molecular phylogenies to systematically explore the presence, frequency, and diversity of bacteria in atherosclerotic lesions in patients with CHD. METHODS AND RESULTS: We investigated 16S rDNA signatures in atherosclerotic tissue obtained through catheter-based atherectomy of 38 patients with CHD, control material from postmortem patients (n=15), and heart-beating organ donors (n=11) using clone libraries, denaturating gradient gel analysis, and fluorescence in situ hybridization. Bacterial DNA was found in all CHD patients by conserved PCR but not in control material or in any of the normal/unaffected coronary arteries. Presence of bacteria in atherosclerotic lesions was confirmed by fluorescence in situ hybridization. A high overall bacterial diversity of >50 different species, among them Staphylococcus species, Proteus vulgaris, Klebsiella pneumoniae, and Streptococcus species, was demonstrated in >1500 clones from a combined library and confirmed by denaturating gradient gel analysis. Mean bacterial diversity in atheromas was high, with a score of 12.33+/-3.81 (range, 5 to 22). A specific PCR detected Chlamydia species in 51.5% of CHD patients. CONCLUSIONS: Detection of a broad variety of molecular signatures in all CHD specimens suggests that diverse bacterial colonization may be more important than a single pathogen. Our observation does not allow us to conclude that bacteria are the causative agent in the etiopathogenesis of CHD. However, bacterial agents could have secondarily colonized atheromatous lesions and could act as an additional factor accelerating disease progression.

Adult↗

Combinatorial approaches as a component of high-throughput experimentation (HTE) in catalysis research.

We consider the application of high-throughput experimentation (HTE), including combinatorial methods, to catalyst discovery and early-phase optimization. While combinatorial- and parallel-testing methods have an already substantial history in catalysis, recent work by several groups promises significant efficiency gains. In molecular catalysis, progress is noted in library design, library synthesis by pooled, parallel, and discrete formats, catalyst testing and reaction optimization; the prime constraint for organometallic catalysts is the limited scope of synthesis procedures for non-peptide-based ligand libraries. Routes described for the synthesis of heterogeneous catalysts include hydrothermal synthesis, arraying of solution precursors, automated impregnation and precipitation, and arraying of solid precursors. The key challenge in applying HTE to heterogeneous catalysis is testing; we distinguish here between Stage 1, or "discovery" testing and Stage 2, optimization testing, and describe techniques with potential in each case. Recent examples from the literature and our own work are used to illustrate these principles and the prospects for HTE applied to catalysis.

Catalysis↗

[The first decades of pharmaceutical training at the Royal Hungarian University in the XVIIIth century].

This is the second part of the author's former article; the previous one was published in the last issue of our journal. The author gives an overview on the education of pharmacists in 18th-century Hungary. She attempts to provide a complete list of the sources of medical and pharmaceutical education, with a special regard on subjects lacking any textbook published in Hungary at that time. Based on the analysis of hand-written and archival data author concludes that students during their courses borrowed the required exsiccated material or manuscripts and even the herbal items from the University itself. Author calls our attention to the hitherto neglected fact, that the possibility of acquiring botanical knowledge was actually given at the University, while former researches emphasized only the difficulties. Even the library of the university at Buda and Pest possessed a rather valuable material. Author concludes, that the pharmaceutical education in Hungary presented the average level of the age.

Education, Pharmacy↗

Recombinant polyclonal antibody libraries.

We describe a technology for generating recombinant polyclonal antibody libraries (PCALs) that enables the creation and perpetuation of standardized mixtures of polyclonal whole antibodies specific for a multiantigen (or polyantigen). Therefore, this technology combines the advantages of targeting multiple antigenic determinants -- high avidity, low likelihood of antigen 'escape variants', and efficient mediation of effector functions, with the advantages of using monoclonal antibodies -- unlimited supply of standardized reagents and the availability of the genetic material for desired manipulations. The technology for generating recombinant polyclonal antibody libraries begins with the creation of phage display Fab (antibody) libraries. This is followed by selection of sublibraries with desired antigen specificities, and mass transfer of the variable region gene pairs of the selected sublibraries to a mammalian expression vector for generation of libraries of polyclonal whole antibodies. We review here our experiments for selection of phage display antibody libraries against microbes and tumor cells, as well as the recent literature on the selection of phage display antibody libraries to multiantigen targets.

Animals↗

Children in hospital: II. Reading therapy and children in hospital.

Following the survey of book and library services described in the first of these two articles (Health Libraries Review, 8, 210-219), a research project funded by BNB Research Fund in 1991 investigated the theory and practice of reading therapy with children in hospital. Hospital play staff had been identified as the therapists most commonly involved and a number of them were interviewed using advance notice questionnaires and structured discussion. The following aspects were investigated: definitions of reading therapy, children in hospital, the reading therapy process, materials used, evaluation, services to facilitate and promote reading therapy, training and the role of libraries and librarians. Recommendations relate to practice, to provision and listing of materials, to evaluation procedures and to training. The final conclusions relate to the role of librarians in the processes and development of reading therapy with children in hospital.

Bibliotherapy↗