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Biomedical subjects

N A Smith

Publications and source records attributed to N A Smith.

At least 37 records · Page 2Linked to original sources
PubMed1998

Cytomegalovirus pp65 antigenaemia as an indicator of end-organ disease in AIDS.

We aim to assess the usefulness of the cytomegalovirus (CMV) pp65 antigenaemia test, also called the CMV direct antigen test (DAT), in the management of patients with advanced human immunodeficiency virus (HIV) infection; we studied all patients who had pp65 assays between 8 September 1995 and 30 August 1996. Twenty-three patients had 31 tests. The mean CD4 cell count was 20/mm3. The tests were negative in 16 patients, of whom 12 have not developed CMV end-organ disease after a mean follow up of 114 days (range 14-269 days), whilst the remaining 4 patients had previously treated CMV disease. Eleven patients had positive tests: 4 had active CMV disease, 2 subsequently developed CMV retinitis, 2 died within a fortnight of multi-drug resistant tuberculosis (MDR-TB), one was lost to follow up and 2 have remained disease-free. This test has a positive predictive value of 43% and a negative predictive value of 94%, Fisher's exact test P=0.03. The pp65 antigenaemia assay can be performed in a standard virology laboratory avoiding the problems associated with polymerase chain reaction (PCR), a result is available within 5 h, and it is semi-quantifiable. However, a large prospective study is required to determine the comparative value and roles of the pp65 antigenaemia assay and DNA PCR in the management of CMV disease, especially with regard to the use of primary prophylaxis and pre-emptive therapy.

AIDS-Related Opportunistic Infections↗
PubMed1997

Biochemical assessment of pancreatic disease in human immunodeficiency virus infected men.

AIM: To determine the usefulness of measuring amylase activity as an indicator of pancreatic disease in human immunodeficiency virus (HIV) positive patients. METHODS: A prospective study of 129 ambulant HIV positive males. Total amylase, pancreatic amylase, and lipase activities were assayed using commercial test kits on an automated analyser. Samples with raised amylase were examined for the presence of macroamylasaemia using cellulose acetate electrophoresis. RESULTS: Thirty six (28%) of the subjects had raised total amylase activities compared with healthy, age matched blood donors. However, almost half of these were because of an increase of the salivary fraction. Four subjects were found to have macroamylasaemia. Pancreatic amylase and lipase assays, more specific indicators of pancreatic disease, produced significantly fewer abnormal results. There was no association between abdominal symptoms and elevated enzyme levels. CONCLUSIONS: Total amylase is a poor indicator of pancreatic disease in HIV infected outpatients. Specific assays for pancreatic amylase offer advantages over the traditional total amylase assay. The lipase assay produced the least number of abnormal results and its use could improve the biochemical identification of patients with possible pancreatic disease and allow a more selective investigation of these cases.

Adult↗
PubMed1996

Prospective validation of a decision rule for the use of radiography in acute knee injuries.

OBJECTIVE: To validate a previously derived decision rule for the use of radiography in patients with acute knee injury. DESIGN: Prospectively administered survey. SETTING: Emergency departments of two university hospitals serving adults. PATIENTS: Convenience sample of 1096 of 1251 eligible adults with acute knee injuries; 124 patients were examined by two physicians. MAIN OUTCOME MEASURES: Attending emergency physicians assessed each patient for standardized clinical variables and determined the need for radiography according to the decision rule. Patients who did not have radiography underwent a structured telephone interview at day 14 to determine the possibility of a fracture. The rule was assessed for ability to correctly identify the criterion standard, fracture of the knee. An attempt was made to refine the rule by means of univariate and recursive partitioning analyses. RESULTS: The decision rule had a sensitivity of 1.0 (95% confidence interval [CI], 0.94 to 1.0) for identifying 63 clinically important fractures. Physicians correctly interpreted the rule in 96% of cases, and the k value for interpretation was 0.77 (95% CI, 0.65 to 0.89). The potential relative reduction in use of radiography was estimated to be 28%. The probability of fracture, if the decision rule were "negative," is estimated to be 0% (95% CI, 0% to 0.4%). Attempts to refine the rule led to a model with improved specificity but with an unacceptable loss of sensitivity. CONCLUSION: Prospective validation has shown this decision rule to be 100% sensitive for identifying fractures of the knee, to be reliable and acceptable, and to have the potential to allow physicians to reduce the use of radiography in patients with acute knee injury.

Adult↗
PubMed1995

Molecular modeling studies of HIV-1 reverse transcriptase nonnucleoside inhibitors: total energy of complexation as a predictor of drug placement and activity.

Computer modeling studies have been carried out on three nonnucleoside inhibitors complexed with human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT), using crystal coordinate data from a subset of the protein surrounding the binding pocket region. Results from the minimizations of solvated complexes of 2-cyclopropyl-4-methyl-5,11-dihydro-5H-dipyrido[3,2-b :2',3'-e][1,4] diazepin-6-one (nevirapine), alpha-anilino-2, 6-dibromophenylacetamide (alpha-APA), and 8-chloro-tetrahydro-imidazo(4,5,1-jk)(1,4)-benzodiazepin-2(1H)-thi one (TIBO) show that all three inhibitors maintain a very similar conformational shape, roughly overlay each other in the binding pocket, and appear to function as pi-electron donors to aromatic side-chain residues surrounding the pocket. However, side-chain residues adapt to each bound inhibitor in a highly specific manner, closing down around the surface of the drug to make tight van der Waals contacts. Consequently, the results from the calculated minimizations reveal that only when the inhibitors are modeled in a site constructed from coordinate data obtained from their particular RT complex can the calculated binding energies be relied upon to predict the correct orientation of the drug in the pocket. In the correct site, these binding energies correlate with EC50 values determined for all three inhibitors in our laboratory. Analysis of the components of the binding energy reveals that, for all three inhibitors, solvation of the drug is endothermic, but solvation of the protein is exothermic, and the sum favors complex formation. In general, the protein is energetically more stable and the drug less stable in their complexes as compared to the reactant conformations. For all three inhibitors, interaction with the protein in the complex is highly favorable. Interactions of the inhibitors with individual residues correlate with crystallographic and site-specific mutational data. pi-Stacking interactions are important in binding and correlate with drug HOMO RHF/6-31G* energies. Modeling results are discussed with respect to the mechanism of complex formation and the design of nonnucleoside inhibitors that will be more effective against mutants of HIV-1 RT that are resistant to the currently available drugs.

Acetamides↗
PubMed1995

Derivation of a decision rule for the use of radiography in acute knee injuries.

STUDY OBJECTIVE: To derive a highly sensitive decision rule for the selective use of radiography in acute knee injuries. DESIGN: Prospectively administered survey. SETTING: Emergency departments of two university hospitals. PARTICIPANTS: Convenience sample of 1,047 adults with acute knee injuries. RESULTS: Attending emergency physicians assessed each patient for 23 standardized clinical findings, which were recorded on data collection forms. A total of 127 patients was examined independently by two physicians to determine interobserver agreement. The outcome measure was fracture of the knee. Any patients who did not have ED radiography underwent a structured telephone interview to determine the possibility of a missed fracture. Those variables found to be both reliable (highest kappa values) and strongly associated with a fracture (highest chi 2 values) were further analyzed by a recursive-partitioning multivariate technique. The derived decision rule included the following variables: (1) age 55 years or older, (2) tenderness at the head of the fibula, (3) isolated tenderness of the patella, (4) inability to flex to 90 degrees, and (5) inability to bear weight both immediately and in the ED (four steps). The presence of one or more of these findings would have identified the 68 fractures in the study population with a sensitivity of 1.0 (95% confidence interval [Cl], .95 to 1.0) and a specificity of .54 (95% Cl, .51 to .57). Application of the rule would have led to a 28.0% relative reduction in the use of radiography from 68.6% to 49.4% in the study population. CONCLUSION: A practical, highly sensitive, and reliable decision rule for the use of radiography in acute knee injuries has been derived. Clinical application should await prospective validation of the rule.

Adult↗
PubMed1994

Autoimmune thrombocytopenia: anti-glycoprotein IIb/IIIa auto antibodies are reduced after human anti-D immunoglobulin treatment.

In chronic autoimmune thrombocytopenic purpura (AITP), an indirect monoclonal antibody immobilised platelet antigen (MAIPA) assay detected serum glycoprotein (GP) IIb/IIIa antibodies in 16/39 (41%) cases. In patients with clinically active AITP, a direct MAIPA assay detected platelet-associated GP IIb/IIIa kantibodies in 8/13 (62%) cases. Platelet bound and serum antibody concentrations suggested a high antibody affinity for platelet membrane glycoprotein IIb/IIIa. Five AITP patients with platelet associated glycoprotein IIb/IIIa antibodies were treated with intravenous anti D immunoglobulin. All showed an increase in platelet counts and a decrease in platelet associated autoantibody. These responses could be due to immunosuppressive anti-idiotype antibodies in anti D immunoglobulin.

Autoantibodies↗
PubMed1994

Better medication compliance is associated with improved control of childhood asthma.

Our previous studies have shown that medication compliance in children prescribed continuous treatment for asthma is poor, and that an intervention can improve the level of compliance. The present study examined the effects of an intervention on the clinical course of moderately severe asthma. At each of six clinic visits, spirometry was performed, medication compliance was assessed by questionnaire, and the physicians made an overall assessment of asthma severity (Severity Score) and provided a score for asthma control (Control of Asthma Score). Peak expiratory flow rates were measured twice daily for one month prior to each clinic visit, and the coefficient of variation (% CV) was calculated. Subjects received the intervention after at least two visits, and 53 of the 78 recruits completed the study. Following the intervention, % CV, Control of Asthma Score, Severity Score and % compliance improved, showing that better medication compliance was associated with better control of moderately severe asthma.

Adolescent↗
PubMed1992

Platelet loss during plasma exchange is unaffected by in-line filters.

15 patients underwent plasma exchange using a standard 170-microns in-line filter with or without an additional 40-microns microaggregate filter in the return circuit. The mean platelet count fall immediately after plasma exchange in 15 patients was (54 +/- 6) x 10(9)/l and 48 h later was (23 +/- 8) x 10(9)/l representing a mean total platelet loss immediately after plasma exchange of (253 +/- 31) x 10(9) with no difference in the 40-microns filtered procedures. The mean platelet loss in the discarded plasma was (60 +/- 8) x 10(9), and a mean of 52 x 10(9) platelets were recovered from machine harness washings. The platelet loss in the removed plasma and in the harness therefore accounted for only 42-44% of the total loss of platelets. The inclusion of 40-microns microaggregate filters did not reduce platelet loss, and it is therefore unlikely that the thrombocytopenia is induced by reinfused microaggregates. It is likely that platelets are activated in the machine and sequestered in the spleen.

Humans↗