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Biomedical subjects

R A Miller

Publications and source records attributed to R A Miller.

At least 199 records · Page 11Linked to original sources
PubMed1994

Using POSTDOC to recognize biomedical concepts in medical school curricular documents.

Recognition of the biomedical concepts in a document is prerequisite to further processing of the document: medical educators examine curricular documents to discover the coverage of certain topics, detect unwanted redundancies, integrate new content, and delete old content; and clinicians are concerned with terms in patient medical records for purposes ranging from creation of an electronic medical record to identification of medical literature relevant to a particular case. POSTDOC (POSTprocessor of DOCuments) is a computer application that (1) accepts as input a free-text, ASCII-formatted document and uses the Unified Medical Language System (UMLS) Metathesaurus to recognize relevant main concept terms; (2) provides term co-occurrence data and thus is able to identify potentially increasing correlations among concepts within the document; and (3) retrieves references from MEDLINE files based on user identification of relevant subjects. This paper describes a formative evaluation of POSTDOC's ability to recognize UMLS Metathesaurus biomedical concepts in medical school lecture outlines. The "precision" and "recall" varied over a wide range and were deemed not yet acceptable for automated creation of a database of concepts from curricular documents. However, results were good enough to warrant further study and continued system development.

Curriculum↗
PubMed1994

From hospital to production line: the price of modern surgical bed management?

A global analysis of surgical bed dynamics in a District General Hospital over a typical 18 working day period is presented. All surgical specialties are represented. A total of 2,484 bed days were studied. Bed occupancy was 92 per cent. Seven per cent of bed capacity was occupied by acute medical patients. The operation cancellation rate was 7 per cent. Fifteen per cent of beds were closed for financial reasons. The study of admission and the stay and discharge policies of different specialties indicated that potential cost improvements could be made by the introduction of more day surgery, day of surgery admission, efficient discharge, ring fencing of beds and improved hospital data collection. While these recommendations are financially desirable, their impact on patients and staff remains to be seen.

Bed Occupancy↗
PubMed1993

The development of response strategies in preparation for sudden loading to the torso.

Sudden and unexpected loading to the torso has been reported in the literature as a potential cause of low-back disorders. When such loadings occur, it is hypothesized that the body's response is designed to minimize the destabilizing postural disturbance, and to minimize the mechanical loading of the musculoskeletal system. This study tested hypotheses regarding the role of task experience in the development of preparatory strategies that potentially minimize the postural disturbance to the body and minimize the mechanical loading of the spine. These strategies were hypothesized to consist of muscle pretensioning, postural changes, and intra-abdominal pressure (IAP). Four subjects participated in five to six experimental sessions in which a sudden load was applied by dropping a weight once a minute for 30 minutes. Electromyographic (EMG) data from 10 trunk muscles, IAP data, and postural data were collected during the initial session and final sessions for each subject. The results indicate where each subject developed a unique preparatory strategy. The preparation always involved the pretensioning of the erector spinae muscles, although the coactivation of the other trunk muscles was quite variable across subjects. During the sudden loading the overall postural disturbance was not consistently reduced; however, the trunk flexion was significantly reduced in most subjects. Furthermore, the estimated spinal compression due to muscle loading was significantly reduced in all subjects.

Abdomen↗
PubMed1993

Complete primary structure and biochemical properties of gilatoxin, a serine protease with kallikrein-like and angiotensin-degrading activities.

The activity and the complete primary structure of gilatoxin, a glycoprotein component from the venom of the Mexican beaded lizard (Heloderma horridum horridum) has been elucidated. Gilatoxin, a serine protease, showed kallikrein-like activity, releasing bradykinin from kininogen; toxin-treated kininogen also produced lowered blood pressure in rats and contraction of isolated rat uterus smooth muscle. Gilatoxin catalyzed the hydrolysis of various arginine ester substrates for trypsin and thrombin and degraded both angiotensin I and II by cleavage of the dipeptide Asp-Arg from the NH2-terminal end. Fibrinogen was degraded but a fibrin clot was not produced, indicating that gilatoxin has specificities different from thrombin and snake venom thrombin-like proteases. The complete amino acid sequence of gilatoxin (245 residues) was deduced from NH2-terminal sequencing of overlapping peptide fragments cleaved from the reduced and alkylated toxin by enzymatic and chemical methods. The toxin is extensively glycosylated, containing approximately 8 mol of monosaccharide/mol of toxin, but appears to lack O-glycosylation sites. Amino acid sequence alignment of gilatoxin with batroxobin, crotalase, kallikrein, thrombin, trypsin, and several partial sequences of other Heloderma toxins reveals that there is considerable homology between these enzymes, particularly in the regions of the presumed catalytic site. Gilatoxin contains an additional 7 residues in the highly conserved catalytic region of serine proteases (including Asp-96, in the basic specificity pocket of thrombin) which may contribute to the unusual substrate specificity of the toxin.

Amino Acid Sequence↗
PubMed1993

Age-associated decline in IL-4 production by murine T lymphocytes in extended culture.

Aging leads to an increase in the proportion of cells that have the surface phenotype (CD45RBlo, CD44hi) characteristic of memory T lymphocytes and also to a decline in both the production of IL-2 and the response to this lymphokine. Several groups have reported an increase, with age, in the secretion of IL-4 in short-term T cell cultures and have suggested that this increase could reflect the age-dependent accumulation of memory T cells, which are thought to be principally responsible for IL-4 production in young mice. Because the response to IL-2 declines with age, we hypothesized that IL-4 production would also decline with age if tested under conditions that promoted IL-2-driven expansion and maturation of IL-4-secreting effectors. Using a culture system in which T cells are first activated by immobilized anti-CD3 antibody for 2 days, and then cultured with anti-CD3 plus IL-2 for an additional 9-11 days, we found a 3-fold decline with age in IL-4 production by murine splenic CD4 T cells. Under these conditions memory (CD45RBlo) CD4 T cells from young mice produced 22-fold more IL-4 than the reciprocal naive (CD44lo) subset. Production of IL-4 by old T cells was also largely attributable to memory T cells, but memory cells from these old donors generated 6-fold less IL-4 in extended cultures than memory cells from young donors. Cultured memory (but not naive) T cells increase in number over a 9-day interval, but the amount of expansion by young memory cells is 4-fold higher than that for old cells. We conclude that the production of IL-4 by memory T cells declines with age under conditions that promote IL-2-driven proliferation and differentiation.

Aging↗
PubMed1993

Suramin, an experimental chemotherapeutic drug, irreversibly blocks T cell CD45-protein tyrosine phosphatase in vitro.

Suramin has long been used for the treatment of Gambian and Rhodesian trypanosomiasis and oncocerciasis. More recently, the demonstration that suramin inhibits DNA polymerases, reverse transcriptase and the lymphocyte terminal deoxynucleotidyl transferase has led to its clinical trials for the treatment of AIDS and cancer. The precise nature of suramin's anti-neoplastic action is not clear at this time. Suramin rapidly alters the tyrosine-specific phosphorylation of cellular proteins in many cancer cell lines. Here we demonstrate that suramin strongly inhibits the activity of CD45, the principal tyrosine specific protein phosphatase of T lymphocytes. Suramin-induced inactivation of CD45 is noncompetitive, irreversible and complete within 10 min. The ability of suramin to block CD45 mediated phosphatase function provides both new insight into the mechanism of action of this agent and a useful new probe for studies of T cell activation.

Animals↗
PubMed1993

Differential tyrosine-specific protein phosphorylation in mouse T lymphocyte subsets. Effect of age.

We have previously reported that activation of normal murine T lymphocytes with either anti-CD3 or Con A leads to increased phosphorylation of three phosphotyrosine-containing proteins with molecular masses of 120, 80, and 40 kDa, that antibody to the alpha beta TCR heterodimer induces phosphorylation of the 120- and 80-kDa species, and that aging impairs phosphorylation of all three substrates. In our study we determine if phosphorylation of these substrates differs among T cell subsets in old and young mice. In young mice, we found that the induced levels of all three phosphorylated substrates, 10 min after addition of the mitogenic stimulus, were significantly higher in CD8 than in CD4 cells for anti-CD3 and Con A stimulation; responses to anti-TCR were also higher in CD8 than in CD4 cells for the 80 kDa, although not the 120-kDa substrate. Aging led to significant declines in the ability to phosphorylate all three substrates in the CD8 population, and also of the 80-kDa substrate in CD4 cells. Comparison of unfractionated CD4 to purified CD4 memory T cells showed that the age-dependent shift from naive to memory T cells could explain the loss with age in p80 phosphorylation, in that memory cells were significantly less able to phosphorylate p80 than were the unseparated CD4 preparations. Phosphorylation of p40 also was significantly lower in CD4 memory cells, as was phosphorylation of p120 in responses to anti-CD3. We conclude that subsets of mouse splenic T cells display different patterns of tyrosine-specific protein phosphorylation in the first 10 min after activation, and that the accumulation of memory T cells with age can account for at least some of the age-dependent decline in tyrosine protein kinase pathways.

Aging↗
PubMed1993

Increased function of P-glycoprotein in T lymphocyte subsets of aging mice.

The age-associated decline in T lymphocyte function can be attributed in part to shifts between subsets (in particular the accumulation of memory T cells at the expense of naive T cells), and in part to alterations of function within the different T lymphocyte subsets. We show that the fluorochrome rhodamine-123 (R123) can distinguish further subdivisions within the naive and memory populations of both CD4 and CD8 T cells in the mouse. Aging leads to a progressive increase in the proportion of T cells in each subset that stain dimly with R123, and a corresponding decrease in the proportion of R123hi T cells, which are typical in young mice. We show that differential R123 staining between T cell subsets is due to variation in the activity of P-glycoprotein (P-Gp), the 170 kDa, ATP-dependent plasma membrane pump that mediates multiple-drug resistance. All T cells initially take up equivalent amounts of R123, but some T cells then can extrude the dye in a temperature-dependent process that is blocked by each of four pharmacologically disparate inhibitors of P-Gp function. Immunofluorescence experiments suggest that T cells from old and young mice have equal amounts of the P-Gp molecule itself, suggesting that differences in R123 extrusion may depend on posttranslational regulation of P-Gp activity.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1993

Consistency enforcement in medical knowledge base construction.

Some aspects of knowledge base creation can be partially or completely automated, resulting in higher quality and smaller effort. Computer assistance is particularly valuable in ensuring the internal consistency of a knowledge base. The article describes several techniques for consistency enforcement in QMR-KAT, an interactive knowledge base editor for the INTERNIST-I/QMR medical knowledge base. Two strategies that improve consistency are applicable to a wide range of situations. The first strategy prevents simple (but common) inconsistencies. The second strategy reveals facts that are potentially (but not necessarily) inconsistent with known data, and may require further evaluation. Both strategies use the contents of the existing knowledge base in the evaluation of new facts.

Artificial Intelligence↗
PubMed1993

Sleeve insertion and collagen coating improve nerve regeneration through vein conduits.

Vein grafts have been used as conduits for nerve regeneration in both research protocols and clinical situations. Results to date are encouraging. This study investigated several variations in the vein graft model in an attempt to enhance peripheral nerve regeneration. Results showed that the jugular vein, with an improved suture technique made possible by its larger diameter, is superior to the femoral vein as a conduit for regeneration of the sciatic nerve in the rat. The larger diameter of the jugular vein and its lack of valves provided less hinderance to regenerating axons. Results also showed that coating the luminal epithelium of the jugular vein with type I collagen gel greatly improved regeneration.

Animals↗
PubMed1993

Infection of an arterial prosthesis as the presenting manifestation of disseminated coccidioidomycosis: control of disease with fluconazole.

We describe an elderly man whose presenting manifestation of disseminated coccidioidomycosis was bilateral infection of femoral arterial prosthetic grafts. After the patient failed to respond to both ketoconazole and amphotericin B, treatment with fluconazole brought about clinical resolution of meningitis and pulmonary disease and, in combination with repeated percutaneous aspiration, control of the arterial infection. The unusual clinical features of this case, along with the incidence and management of prosthetic arterial infections caused by fungi, are discussed.

Aged↗
PubMed1993

Temporary prostatic stenting and androgen suppression: a new minimally invasive approach to malignant prostatic retention.

Urinary retention secondary to carcinoma of the prostate is usually treated by 'channel' transurethral resection of the prostate either performed alone or in combination with hormone manipulation. The combination of temporary prostatic stenting and androgen suppression may reduce the morbidity and mortality associated with this treatment. We report on our initial experience using the combination of a temporary prostatic stent with the oral anti-androgen Flutamide in 10 patients with urinary retention or severe bladder outflow obstruction secondary to prostatic carcinoma. Eight of the ten patients successfully voided and maintained normal voiding after stent removal. There were two treatment failures requiring prostatic resection. We believe the cost of stenting and medication is entirely justified by patient preference and clearance of hospital beds.

Aged↗
PubMed1993

Comparing contents of a knowledge base to traditional information sources.

Physicians rely on the medical literature as a major source of medical knowledge and data. The medical literature, however, is continually evolving and represents different sources at different levels of coverage and detail. The recent development of computerized medical knowledge bases has added a new form of information that can potentially be used to address the practicing physician's information needs. To understand how the information from various sources differs, we compared the description of a disease found in the QMR knowledge base to those found in two general internal medicine textbooks and two specialized nephrology textbooks. The study shows both differences in coverage and differences in the level of detail. Textbooks contain information about pathophysiology and therapy that is not present in the diagnostic knowledge base. The knowledge base contains a more detailed description of the associated findings, more quantitative information, and a greater number of references to peer-reviewed medical articles. The study demonstrates that computerized knowledge bases, if properly constructed, may be able to provide clinicians with a useful new source of medical knowledge that is complementary to existing sources.

Artificial Intelligence↗