Understanding and using the medical subject headings (MeSH) vocabulary to perform literature searches

The United States National Library of Medicine's (NLM) MEDLINE database is the largest and most widely used medical bibliographic database. MEDLINE is manually indexed with NLM's Medical Subject Headings (MeSH) vocabulary. Using MeSH, a searcher can potentially create powerful and unambiguous MEDLINE queries. This article reviews the structure and use of MeSH, directed toward the nonexpert, and outlines how MeSH may help resolve a number of common difficulties encountered when searching MEDLINE. The increasing importance of the MEDLINE database as an information resource and the trend toward individuals performing their own bibliographic searches makes it crucial that health care professionals become familiar with MeSH.     

Corneal endothelial involvement in pseudoexfoliation syndrome

Information on corneal manifestation in pseudoexfoliation syndrome is restricted to specular microscopic studies. We investigated morphologic changes of the posterior cornea of two corneal buttons with Fuchs' endothelial dystrophy obtained at penetrating keratoplasty and of one enucleated glaucomatous eye from three patients with ocular pseudoexfoliation syndrome. By transmission electron microscopy, large clumps of typical pseudoexfoliation material were found adhering to the corneal endothelium and masses of pseudoexfoliation material were incorporated into the posterior Descemet's membrane. In the affected areas, the endothelial layer appeared irregular and discontinuous, with loosely adherent, degenerating cells producing pseudoexfoliation fibers and fibroblastic cells spreading to cover denuded Descemet's membrane. The present findings indicate that the pseudoexfoliation material is initially formed by degenerative endothelial cells and that it becomes subsequently buried by overgrowing cells. The corneal endothelial involvement may potentiate complications of cataract surgery and open angle glaucoma in patients with pseudoexfoliation syndrome.     

A streptavidin mutant with altered ligand-binding specificity

The biotin-binding site of streptavidin was modified to alter its ligand-binding specificity. In natural streptavidin, the side chains of N23 and S27 make two of the three hydrogen bonds with the ureido oxygen of biotin. These two residues were mutated to severely weaken biotin binding while attempting to maintain the affinity for two biotin analogs, 2-iminobiotin and diaminobiotin. Redesigning of the biotin-binding site used the difference in local electrostatic charge distribution between biotin and these biotin analogs. Free energy calculations predicted that the introduction of a negative charge at the position of S27 plus the mutation N23A should disrupt two of the three hydrogen bonds between natural streptavidin and the ureido oxygen of biotin. In contrast, the imino hydrogen of 2-iminobiotin should form a hydrogen bond with the side chain of an acidic amino acid at position 27. This should reduce the biotin-binding affinity by approximately eight orders of magnitude, while leaving the affinities for these biotin analogs virtually unaffected. In good agreement with these predictions, a streptavidin mutant with the N23A and S27D substitutions binds 2-iminobiotin with an affinity (Ka) of 1 x 10(6) M-1, two orders of magnitude higher than that for biotin (1 x 10(4) M-1). In contrast, the binding affinity of this streptavidin mutant for diaminobiotin (2.7 x 10(4) M-1) was lower than predicted (2.9 x 10(5) M-1), suggesting the position of the diaminobiotin in the biotin-binding site was not accurately determined by modeling.     

Vegetational association of host-seeking adult blacklegged ticks, Ixodes scapularis Say (Acari: Ixodidae), on dairy farms in northwestern Wisconsin

Non-obese diabetic NOD/SCID mice have been used to grow human leukaemia as a systemic disease. The animals were inoculated with leukaemic cells obtained from a 36-year-old male with early B-cell precursor acute lymphoblastic leukaemia and on day 15 were given the first of three weekly injections of 1 mg/kg vincristine or equimolar liposomal vincristine. The development of leukaemia in the mice was monitored by taking weekly blood samples and measuring the cell content by flow cytometry. The median time to 50% human cells in the peripheral blood of mice treated with free vincristine was 41 d from the start of treatment compared with 49 d for mice treated with liposomal vincristine (P < 0.01). The median day of death for mice treated with free vincristine was 47 d from the start of treatment and 57 d for mice receiving liposomal vincristine (P<0.01), thus providing a 21% increase in lifespan for animals treated with the liposomal preparation. There was slightly greater weight loss in mice treated with free vincristine than those given liposomal vincristine. Measurement of in vitro colony forming bone marrow progenitor cells in similarly treated, tumour-free mice, showed no difference in progenitor cell survival between mice that received either type of vincristine. We conclude that encapsulating vincristine in liposomes improves the therapeutic index of this drug measured in mice bearing human leukaemia. This may lead to use of the drug in conventional combination chemotherapy with greater safety or, in this setting, at higher dosage.     

Serious infections due to Pseudomonas aeruginosa

Infections due to Ps. aeruginosa are a problem in the tropics as in other parts of the world. Over a four year period, 15 patients attending University College Hospital, Ibadan, were proved to have septicaemia due to this organism and 13 patients died rapidly as a direct result of the infection. The two patients who survived the acute episode had received immediate treatment with at least one antibiotic active against Ps. aeruginosa: a third patient, who received immediate appropriate antibiotic therapy, was already suffering from aplastic anaemia and died rapidly despite treatment. The remaining patients received inappropriate antibiotic therapy because pseudomonas infection was not suspected at the time the diagnosis of septicaemia was made. Patients most at risk appear to be the very young and those with pre-existing malignant or other conditions affecting the defence mechanisms of the body: it is suggested that routine initial management of such patients should include a blood culture, followed by immediate treatment with an antibiotic combination that includes at least one agent likely to be active against Ps. aeruginosa. The development of medical services can lead to the introduction of ophthalmic or other operations on tissues that are highly susceptible to infection before facilities are provided for the maintenance of a pathogen-free environment. Following an outbreak of eye infection after cataract extractions, carried out in an old and unsatisfactory theatre, wide-spread room contamination was demonstrated with the same strains of Ps. aeruginosa that had been responsible for the clinical infections. Chemical disinfection of the theatre floor failed to eliminate the organisms, although other experiments suggested that the drying effect of air-conditioning would be successful in this respect. The wisdom of introducing such operations before the provision of adequate facilities is seriously questioned.     

Studies on long chain cis- and trans-acyl-CoA esters and Acyl-CoA dehydrogenase from rat heart mitochondria

A quantitative counterimmunoelectrophoresis technique has been applied to evaluation of RNA antibodies in serum and unconcentrated CSF. Serum anti-RNA antibodies have been found at high dilutions in some patients with infectious diseases, subacute panencephalitis and multiple sclerosis. RNA antibodies in CSF are significantly linked to oligoclonal aspect, i.e. to a synthesis of IgG inside the CNS.     

Remote atmospheric breakdown for standoff detection by using an intense short laser pulse

A remote atmospheric breakdown is a very rich source of UV and broadband visible light that could provide an early warning of the presence of chemical-biological warfare agents at extended standoff distances. A negatively chirped laser pulse propagating in air compresses in time and focuses transversely, which results in a rapid laser intensity increase and ionization near the focal region that can be located kilometers away from the laser system. Proof-of-principle laboratory experiments are performed on the generation of remote atmospheric breakdown and the spectroscopic detection of mock biological warfare agents. We have generated third harmonics at 267 nm and UV broadband radiation in air from the compression and focusing of femtosecond laser pulses. Fluorescence emission from albumin aerosols as they were illuminated by the femtosecond laser pulse has been observed.     

Instrumentation problems for physicians

The physician has, for whatever reasons, diminished his or her level of involvement on the team dedicated to developing, refining, and evaluating medical technology. As a result, the challenge confronting the physician and the technology development team today is to orchestrate a team structure that will ensure the greatest input and commitment from physicians and other professionals during current and future technology development. The charges of cost escalation and dehumanization in our system of health care delivery will also be discussed, as will the lack of, or confusion about, access to data concerning cost of a given instrument, and fuzzy semantics and perspectives on technology and instrumentation. The author suggests answers to, or means to ameliorate, the problems.