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Biomedical subjects

J Adams

Publications and source records attributed to J Adams.

At least 163 records · Page 9Linked to original sources

Impact of troponins on the evaluation and treatment of patients with acute coronary syndromes.

Cardiac troponins possess superior sensitivity and specificity for the detection of cardiac injury. They can be used successfully to replace measurements of MB isoenzyme of creatine kinase or lactate dehydrogenase for the retrospective diagnosis of myocardial infarction. Measurement of these proteins confers powerful prognostic information that can be used to triage patients. An increasing body of data suggests that measurement of troponin proteins can be useful to guide therapeutic decisions in patients with acute coronary artery syndromes, especially regarding treatment with low-molecular-weight heparin or IIB/IIIA inhibitors. The absence of troponins in the circulation does not necessarily indicate the absence of coronary artery disease. With current assays, a significant diagnostic difference does not appear to exist between cardiac troponin I and T in patients with acute coronary artery syndromes.

Fibrinolytic Agents↗

An external landmark for the anterior commissure.

OBJECTIVE: The ability to predict the level of the true vocal cords based on external landmarks is crucial to the success of many laryngeal surgical procedures. This study examines the reliability of one such landmark on the thyroid cartilage. METHODS: Twenty-four cadaver larynges were examined. A pin was placed through the landmark, best described as a small diamond shaped area of color change and surface depression along the anterior midline of each thyroid cartilage through which travels a very small unnamed artery. The endolaryngeal position of the pin was checked with a flexible nasopharyngoscope. RESULTS: In all 24 cadavers, the pin entered the larynx at the anterior commissure, just above or at the level of the true vocal cords. CONCLUSIONS: This external landmark reliably predicts the position of the true vocal cords. It serves as a useful adjunct to existing external landmarks used to direct thyroid cartilage cuts in laryngeal procedures.

Arteries↗

Sports medicine in the new millennium: a vision for 2020.

Globalisation, empowerment and technological change will determine the emerging directions in sports medicine in the new millennium. Networks and alliances of scientist and clinician services, as well as electronic profiling of athletes' learning styles, genetic predisposition and other variables, will enhance the spectrum of sports medicine services. Visionary direction will require changes in the organisational paradigms employed, the communication of information to athletes and coaches and the methodologies of assessment. An emphasis on prevention science and clinical and educational interventions will require a clearer focus. The sports medicine scientist and clinician of today must utilise the endowments suggested by Covey and the multiple intelligence models advanced by Gardner in capturing the clarity of focus for sports medicine in the new millennium.

Humans↗

Academic emergency medicine's future. The SAEM Task Force on Emergency Medicine's Future. Society for Academic Emergency Medicine.

Emergency medicine (EM) will change over the next 20 years more than any other specialty. Its proximity to and interrelationships with the community, nearly all other clinicians (physicians and nonphysicians), and scientific/technologic developments guarantee this. While emergency physicians (EPs) will continue to treat both emergent and nonemergent patients, over the next decades our interventions, methods, and place in the medical care system will probably become unrecognizable from the EM we now practice and deliver. This paper, developed by the Society for Academic Emergency Medicine (SAEM) Task Force on Academic Emergency Medicine's Future, was designed to promote discussions about and actions to optimize our specialty's future. After briefly discussing the importance of futures planning, it suggests "best-case," "worst-case," and most probable future courses for academic EM over the next decades. The authors predict that EPs will practice a much more technologic and accurate form of medicine, with diagnostic, patient, reference, and consultant information rapidly available to them. They will be at the center of an extensive consultation network stemming from major medical centers and the purveyors of a sophisticated home health system, very similar to or even more advanced than what is now delivered on hospital wards. The key to planning for our specialty is for EM organizations, academic centers, and individuals to act now to optimize our possible future.

Academic Medical Centers↗

The proteasome inhibitor PS-341 in cancer therapy.

The anticancer activity of the boronic acid dipeptide proteasome inhibitor PS-341 was examined in vitro and in vivo. PS-341 was a potent cytotoxic agent toward MCF-7 human breast carcinoma cells in culture, producing an IC90 of 0.05 microM on 24 h of exposure to the drug. In the EMT-6 tumor cell survival assay, PS-341 was equally cytotoxic administered p.o. or by i.p. injection up to a dose of 2 mg/kg. PS-341 was also toxic to the bone marrow colony-forming unit-granulocyte macrophage. PS-341 increased the tumor cell killing of radiation therapy, cyclophosphamide, and cisplatin in the EMT-6/Parent tumor, but was not able to overcome the in vivo resistance of the EMT-6/CTX and EMT-6/CDDP tumors. In the tumor growth delay assay, PS-341 administered p.o. had antitumor activity against the Lewis lung carcinoma, both primary and metastatic disease. In combination, regimens with 5-fluorouracil, cisplatin, Taxol and adriamycin, PS-341 seemed to produce primarily additive tumor growth delays against the s.c. tumor and was highly effective against disease metastatic to the lungs. The proteasome is an interesting new target for cancer therapy, and the proteasome inhibitor PS-341 warrants continued investigation in cancer therapy.

Adenocarcinoma↗

Documentation on trial: nine ways to protect your agency.

In today's environment, home care professionals are often overwhelmed with documentation requirements. Licensure and certification surveyors, Office of Inspector General staff, third-party payors, fraud and abuse inspectors, courtroom attorneys, and others seem to scrutinize home care documentation constantly. In short, home care documentation is always "on trial." These tips can help agencies protect themselves in this environment.

Confidentiality↗

Fibromyalgia: a risk factor for osteoporosis.

OBJECTIVE: To investigate associations of bone mineral density (BMD) and osteoporosis in patients with fibromyalgia (FM) and healthy controls. METHODS: Twenty-four women meeting the American College of Rheumatology criteria for FM (23 Caucasians, one Asian) were each compared to 2 age (+/-3 years) and ethnically matched controls by bone densitometry of the femoral neck and lumbar spine. The patients' ages were 33 to 60 years. No patient or control used steroids or other bone demineralizing agents. Simple T tests were used to compare hip and lumbar spine BMD of FM cases to controls by 3 decades (31-40, 41-50, 51-60 years). RESULTS: The patients with FM in all 3 decades had a lower mean BMD of the spine (p<0.05). The femoral neck BMD were also lower, but reached significance (p<0.05) only in the 51-60 age group. CONCLUSION: FM in this pilot study was frequently associated with osteoporosis. Early detection and implementation of appropriate nutritional supplementation (calcium/vitamin D), resistive and weight bearing exercise, and specific bone mineral enhancing pharmacological therapy may be indicated in pre, peri, and postmenopausal subjects.

Absorptiometry, Photon↗

Role of the proteasome and NF-kappaB in streptococcal cell wall-induced polyarthritis.

The transcription factor NF-kappaB activates a number of genes whose protein products are proinflammatory. In quiescent cells, NF-kappaB exists in a latent form and is activated via a signal-dependent proteolytic mechanism in which the inhibitory protein IkappaB is degraded by the ubiquitin-proteasome pathway. Consequently, inhibition of the proteasome suppresses activation of NF-kappaB. This suppression should therefore decrease transcription of many genes encoding proinflammatory proteins and should ultimately have an anti-inflammatory effect. To this end, a series of peptide boronic acid inhibitors of the proteasome, exemplified herein by PS-341, were developed. The proteasome is the large multimeric protease that catalyzes the final proteolytic step of the ubiquitin-proteasome pathway. PS-341, a potent, competitive inhibitor of the proteasome, readily entered cells and inhibited the activation of NF-kappaB and the subsequent transcription of genes that are regulated by NF-kappaB. Significantly, PS-341 displayed similar effects in vivo. Oral administration of PS-341 had anti-inflammatory effects in a model of Streptococcal cell wall-induced polyarthritis and liver inflammation in rats. The attenuation of inflammation in this model was associated with an inhibition of IkappaBalpha degradation and NF-kappaB-dependent gene expression. These experiments clearly demonstrate that the ubiquitin-proteasome pathway and NF-kappaB play important roles in regulating chronic inflammation and that, as predicted, proteasome inhibition has an anti-inflammatory effect.

Animals↗

Catalytic defects in mutants of class II histidyl-tRNA synthetase from Salmonella typhimurium previously linked to decreased control of histidine biosynthesis regulation.

The expression of histidine biosynthetic genes in enteric bacteria is regulated by an attenuation mechanism in which the level of histidyl-tRNA serves as a key sensor of the intracellular histidine pool. Among the early observations that led to the formation of this model for Salmonella typhimurium were the identification of mutants in the gene (hisS) encoding histidyl-tRNA synthetase. We report here the detailed biochemical characterization of five of these S. typhimurium bradytrophic mutants isolated by selection for resistance to histidine analogs, including identification of the deduced amino acid substitutions and determination of the resulting effects on the kinetics of adenylation and aminoacylation. Using the crystal structure of the closely related Escherichia coli histidyl-tRNA synthetase (HisRS) as a guide, two mutants were mapped to a highly conserved proline residue in motif 2 (P117S, P117Q), and were correlated with a fivefold decrease in the kcat for the pyrophosphate exchange reaction, as well as a tenfold increase in the Km for tRNA in the aminoacylation reaction. Another mutant substitution (A302T) mapped to a residue adjacent to the histidine binding pocket, leading to a tenfold increase in Km for histidine in the pyrophosphate exchange reaction. The remaining two mutants (S167F, N254T) substitute residues in or directly adjacent to the hinge region, which joins the insertion domain between motif 2 and motif 3 to the catalytic core, and cause the Km for tRNA to increase four- to tenfold. The kinetic analysis of these mutants establishes a direct link between critical interactions within the active site of HisRS and regulation of histidine biosynthesis, and provides further evidence for the importance of local conformational changes during the catalytic cycle.

Amino Acid Sequence↗

Novel nonnucleoside inhibitors of HIV-1 reverse transcriptase. 7. 8-Arylethyldipyridodiazepinones as potent broad-spectrum inhibitors of wild-type and mutant enzymes.

Like other nonnucleoside inhibitors of HIV-1 reverse transcriptase, the dipyridodiazepinone nevirapine (Viramune, 1) selects for drug resistant variants of HIV-1, both in cell culture and in patients. In particular, the mutation of residue 181 from tyrosine to cysteine (Y181C) is associated with resistance to most reported nonnucleoside inhibitors. Introduction of an arylethyl substituent at the 8-position of the tricyclic dipyridodiazepinone skeleton confers enhanced potency against Y181C RT. Several analogues of this series display good broad spectrum potency against a panel of mutant enzymes.

Amino Acid Substitution↗

Potent and selective inhibitors of the proteasome: dipeptidyl boronic acids.

Potent and selective dipeptidyl boronic acid proteasome inhibitors are described. As compared to peptidyl aldehyde compounds, boronic acids in this series display dramatically enhanced potency. Compounds such as 15 are promising new therapeutics for treatment of cancer and inflammatory diseases.

Boronic Acids↗

Thy-1 is a component common to multiple populations of synaptic vesicles.

Thy-1, a glycosylphosphatidylinositol-linked integral membrane protein of the immunoglobulin superfamily, is a component of both large dense-core and small clear vesicles in PC12 cells. A majority of this protein, formerly recognized only on the plasma membrane of neurons, is localized to regulated secretory vesicles. Thy-1 is also present in synaptic vesicles in rat central nervous system. Experiments on permeabilized PC12 cells demonstrate that antibodies against Thy-1 inhibit the regulated release of neurotransmitter; this inhibition appears to be independent of any effect on the Ca2+ channel. These findings suggest Thy-1 is an integral component of many types of regulated secretory vesicles, and plays an important role in the regulated vesicular release of neurotransmitter at the synapse.

Animals↗

Rice body formation in bicipito-radial bursitis: ultrasound, CT, and MRI findings.

The bicipito-radial bursa, which lies at the biceps tendon insertion on the radial tuberosity, is a rare site of chronic bursitis. We describe the clinical, radiological, and pathological findings in a case complicated by multiple rice body formation. In so doing, we describe MR appearances that allow discrimination of this entity from both synovial chondromatosis and pigmented villonodular synovitis.

Adult↗