Controversy in neurology: the Canadian study on TIA and aspirin. A critique of the Canadian TIA study. Reply.
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Aspirin↗
Biomedical subjects
D W Taylor
Publications and source records attributed to D W Taylor.
Determination of static pulmonary volumes after bronchodilator therapy.
Increased (more positive) end-expiratory and decreased (more negative) end-inspiratory values for intrapleural pressure (PpI) invariably accompany acute bronchoconstriction. We hypothesize that both the increase in vital capacity (VC) and the decrease in residual volume (RV) observed after dilation of the central airways in patients with reversible obstruction of the airways result, in part, from a restoration of normal PpI during unforced exhalation. To test this hypothesis, we examined the end-expiratory PpI during breathing at rest in ten emphysematous and eight asthmatic subjects before and after inhalation of isoproterenol. The VC increased by 0.38 L after therapy, and the specific airway resistance and the RV decreased by 6.8 cm H2O.sec and 0.63 L, respectively. Total lung capacity was unchanged. The response of the VC to administration of isoproterenol is an important sequel to dilation of the large airways. Bronchioles close at a critical PpI during exhalation. Because PpI normalizes with administration of isoproterenol, this closure may be delayed to a lower pulmonary volume even if improvement in the function of peripheral airways does not occur.
Asthma↗
Observer variation in the interpretation of lower limb venograms.
After agreeing on diagnostic criteria and after a pilot study, two experienced radiologists twice independently reviewed 40 lower limb venograms performed by a standard technique in patients suspected or known to have venous thrombosis. The observers reviewed 20 examinations at a time, their analysis requiring separate identification of 11 major veins. At each site observers stated whether thrombus was "absent," "doubtful," "presumed," or "definite," or declared "no opinion possible." They then rediscussed criteria of diagnosis and, using the same experimental design, examined another 40 venograms. To correct for agreement expected by chance, data were analyzed by using the kappa statistic. In general, levels of agreement were higher than those reported for many other clinical and radiologic investigations, probably because of refinement of criteria after the pilot study. Nonetheless, observers disagreed about the probable presence or absence of thrombus at some site in the limb in about 10% of examinations. Observer variation should be considered when venography is used as a reference standard to evaluate other methods of diagnosing thrombi.
Adult↗
Susceptibility of owl monkeys to Plasmodium falciparum infection in relation to location of origin, phenotype, and karyotype.
The relationship among geographic origin, phenotype, karyotype, and susceptibility of owl monkeys to 2 strains of Plasmodium falciparum was investigated. Owl monkeys from Columbia and Panama were both susceptible to fatal infections with the Asian FVO (Vietnam-Oak Knoll) strain of P. falciparum. However, when inoculated with the African FUP (Uganda-Palo Alto) strain, most Colombian owl monkeys developed fatal or potentially fatal (bled out with parasitemias of over 25%) infections, but Panamanian monkeys generally survived. Colombian and Panamanian monkeys that spontaneously recovered from malaria infection were phenotypically indistinguishable from those which died. Karyotype analysis revealed that animals considered in this study were either Karyotype II (54 chromosomes) or II (53 chromosomes). Karyotype differences between individual monkeys did not correlate with increased susceptibility or resistance to malaria. Thus, the country of origin of owl monkeys appears to play a more important role in host susceptibility to malaria infection than karyotype.
Animals↗
Immunization of experimental monkeys against Plasmodium falciparum: use of synthetic adjuvants.
The replacement of Freund's adjuvant by a possible safe adjuvant for effective immunization of owl monkeys (Aotus trivirgatus griseimembra) against a human malaria parasite, Plasmodium falciparum, has been investigated. Experiments involved the use of two synthetic adjuvants: MDP (N-acetylmuramyl-L-alanyl-D-isoglutamine) and stearoyl-MDP (6-O-stearoyl-N-acetylmuramyl-L-alanyl-D-isoglutamine). In both cases, P. falciparum merozoites obtained through short-term in vitro cultivation were used as antigen. MPD was used as adjuvant in 5 owl monkeys; 2 control monkeys died and of the 3 experimental monkeys only 1 survived. In contrast, in another experiment where stearoyl-MDP was used as adjuvant, there was 100% protection of 4 immunized monkeys against a challenge with the homologous strain of P. falciparum. The results of the second experiment are encouraging for the development of an effective and safe vaccine for human malaria.
Acetylmuramyl-Alanyl-Isoglutamine↗
A study of cellular and humoral immune responses in owl monkeys (Aotus trivirgatus) following vaccination against Plasmodium falciparum.
VACCINATION OF ANIMALS AGAINST MALARIA PARASITES IS THOUGHT TO INDUCE TWO BASIC IMMUNOLOGICAL RESPONSES: (i) specific recognition of parasite antigens by the host, and (ii) a generalized immune enhancement due to the presence of adjuvant. Immunological techniques were used in this study to monitor cellular and humoral immune changes in owl monkeys prior to and following immunization with a vaccine consisting of merozoite-enriched schizonts of Plasmodium falciparum and one of three adjuvants: N-acetylmuramyl-L-alanyl-D-isoglutamine (muramyl dipeptide), Freund's complete adjuvant, or 6-O-stearoyl-N-acetylmuramyl-L-alanyl-D-isoglutamine. The results showed that most of the immunized animals responded specifically to malarial antigens as demonstrated by the fact that peripheral blood lymphocytes underwent blast transformation in vitro in the presence of parasite antigens and that substantial antibody titres were produced as detected by indirect immunofluorescence. By use of the in vitro inhibition test, it was found that sera from immunized owl monkeys collected after challenge greatly inhibited merozoite reinvasion. Generalized nonspecific immune responses observed in owl monkeys following vaccination included an increase in the number of white blood cells and the proportion of T and B cells in the peripheral blood. Responses to mitogen stimulation with phytohaemagglutinin, concanavalin A, and pokeweed mitogen, however, did not appear to be appreciably affected by immunization.
Animals↗
Isolation and characterization of surface antigens from Schistosoma mansoni. I. Evaluation of techniques for radioisotope labeling of surface proteins from adult worms.
Radiolabeled surface proteins of adult Schistosoma mansoni were prepared by in vitro labeling of whole worms, and by labeling freeze-thaw surface membrane extracts. Incorporation of 125I into surface proteins was attempted using the lactoperoxidase, chloramine-T, iodosulfanilic acid, and Bolton-Hunter methods. Radiolabeling of whole worms with lactoperoxidase, chloramine-T and iodosulfanilic acid yielded a single protein peak (mol wt greater than 100,000) on SDS-PAGE, and showed considerable incorporation of label in the lipid fraction. Bolton-Hunter labeling of whole worms yielded four major peaks with molecular weights of 100,000, 60,000, 30,000 and 21,000, and minor peaks with molecular weights of 26,000, 36,000, 43,000, 68,000 and 78,000; three of the four major peaks corresponded to prominent bands in Coomassie blue-stained gels. Although carbohydrate-labeling techniques were not successful, a single carbohydrate band, molecular weight greater than 100,000, was detected was PAS staining. Radiolabeling of freeze-thaw extracts yielded results similar to those obtained with whole worms. Electron microscopy revealed the tegument to be left intact and undamaged after labeling with the Bolton-Hunter reagent.
Animals↗
Isolation and characterization of surface antigens from Schistosoma mansoni. II. Antigenicity of radiolabeled proteins from adult worms.
Adult Schistosoma mansoni were radiolabeled in vitro with 125I Bolton-Hunter reagent. Surface membrane antigens were solubilized with non-ionic detergent, then reacted with infection or normal serum. The antigen-antibody complexes were then precipitated with staphylococcal protein A immunoadsorbent, eluted with urea and SDS, and fractionated by SDS-PAGE. The results indicated the presence of 6 to 8 tegument antigens, depending on the type of antisera used. Human antisera to S. japonicum and S. haematobium reacted with some but not all of the antigens identified with human S. mansoni infection serum; this implies the presence of species-specific tegument antigens. The molecular weights of the radiolabeled antigens ranged from 10,000 to 100,000. A large (greater than 100,000) molecular weight glycoprotein and an uncharacterized lipid fraction appeared to be precipitated nonspecifically. Immunoprecipitation methods with anti-mouse IgG and anti-mouse whole serum failed to detect the presence of hostlike antigens in the labeled extracts. Several of the labeled proteins from S. mansoni were found to react with serum from patients infected with either S. haematobium or with S. japonicum.
Animals↗
Self-recording of blood pressure in the management of hypertension.
The efficacy of self-recording of blood pressure in the management of hypertension was assessed in a randomized clinical trial involving 140 persons who had been receiving antihypertensive therapy for a year or more, but whose diastolic blood pressure had remained at 95 mm Hg or higher. To control for the increased attention implicit in self-recording, which might affect blood pressure, the patients were assigned at random to one of the four groups: self-recording and monthly home visits, self-recording only, monthly home visits only, and neither self-recording nor monthly home visits. This design also permitted assessment of the effect of home visits. During the 6-month experiment no significant differences were apparent between the groups in either compliance or diastolic blood pressure. However, both self-recording and monthly home visits produced a reduction in blood pressure among patients who admitted to difficulty remembering to take their pills; a reduction was not seen among patients who said they had no such difficulty. This confirmed an earlier observation suggesting that this easily identified group of patients may be the most responsive to intervention programs.
Adult↗
Increased absenteeism from work after detection and labeling of hypertensive patients.
A study of hypertension in an industrial setting allowed us to confirm and explore an earlier retrospective finding that the labeling of patients as hypertensive resulted in increased absenteeism from work. After screening and referral, we found that absenteeism rose (mean +/- 1 S.E.) 5.2 +/- 2.3 days per year (P less than 0.025); this 80 per cent increase greatly exceeded the 9 per cent rise in absenteeism in the general employee population during this period. The main factors associated with increased absenteeism were becoming aware of the condition (P less than 0.01) and low compliance with treatment (P less than 0.001). Subsequent absenteeism among patients unaware of their hypertension before screening was not related to the degree of hypertension, whether the worker was started on therapy, the degree of blood-pressure control achieved or exposure to attempts to promote compliance. These results have major implications for hypertension screening programs, especially since absenteeism rose among those previously unaware of their condition, regardless of whether antihypertensive therapy was begun.
Absenteeism↗
Vaccination of experimental monkeys against Plasmodium falciparum: a possible safe adjuvant.
Owl monkeys (Aotus trivirgatus griseimembra) were effectively immunized against a human malaria parasite, Plasmodium falciparum. Two injections of antigen, primarily mature segmenters with fully developed merozoites, mixed with adjuvant (6-O-stearoyl-N-acetylmuramyl-L-alanyl-D-isoglutamine and liposomes) were administered intramuscularly at a 4-week interval. Approximately 2 weeks after the second vaccination, the monkeys were challenged with the homologous strain of P. falciparum. All immunized monkeys survived the challenge. The substitution of Freund's complete adjuvant is an encouraging step toward the development of an effective and safe vaccine for human malaria.
Acetylmuramyl-Alanyl-Isoglutamine↗
Compliance with antihypertensive drug therapy.
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Antihypertensive Agents↗
Schistosoma mansoni: analysis of surface membrane carbohydrates using lectins.
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Animals↗
Lymphocyte isolation, rosette formation, and mitogen stimulation in Rhesus monkeys.
Over 70% of rhesus monkey peripheral mononuclear cells were isolated on sodium metrizoate-ficoll gradients with greater than 98% purity. Rhesus blood contained 47.8% active E, 58.2% total E, and 30.2% EAC rosette forming cells. Optimal conditions for mitogen studies were determined using phytohemagglutinin, concanavalin A, pokeweed mitogen, lipopolysaccharide and streptolysin O.
Animals↗
The manuscript lecture-notes of Alexander Monro, secundus (1733-1817).
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Education, Medical↗
Suppression of lymphocyte transformation by plasma from owl monkeys acutely infected with Plasmodium falciparum.
Plasma collected from owl monkeys during the acute phase of Plasmodium falciparum infection was shown to adversely affect several in vitro responses which are considered to be correlates of cell-mediated immune functions of normal monkeys. In the presence of acute-phase plasma, response of normal monkey peripheral blood lymphocytes to stimulation with phytohemagglutinin, concanavalin A, and pokeweed mitogen was severely reduced, as was the ability of peripheral blood lymphocytes to respond to allogenic and xenogenic histocompatible antigens. The transformation response of peripheral blood lymphocytes from normal humans to phytohemagglutinin and concanavalin A was also suppressed. Since acute-phase plasma was not cytotoxic for peripheral blood lymphocytes, decreased responsiveness did not result from cell destruction. Acute-phase plasma appears to block initial steps in lymphocyte transformation.
Animals↗
Impedance plethysmography: the relationship between venous filling and sensitivity and specificity for proximal vein thrombosis.
We investigated the hypothesis that the diagnostic accuracy of impedance plethysmography (IPG) for thrombosis of the popliteal or more proximal veins increases with enhanced venous filling. Venous filling was increased by prolonging cuff occlusion and by sequential testing. IPG and vengography were performed on 169 legs with and 317 legs without proximal vein thrombosis. The sensitivity and specificity of IPG rose significantly with increased venous filling. Changes in venous filling were associated with corresponding changes in emptying in normal legs, but not those with proximal vein thrombosis, so that the regression lines relating venous filling and emptying in normal and abnormal legs diverged significantly (P less than 0.001). If the IPG sequence had been terminated after only a single 45 second occlusion time test, sensitivity would have deteriorated by 10% and specificity by 20%. These observations indicate that the accuracy of IPG can be significantly enhanced if optimal venous filling is obtained.
Evaluation Studies as Topic↗
Partial protection of Plasmodium falciparum-vaccinated Aotus trivirgatus against a challenge of a heterologous strain.
Two Aotus trivirgatus griseimenbra monkeys which had been immunized with the merozoite-enriched FUP strain of Plasmodium falciparum were protected against a primary challenge with the homologous strain. The results described here show that these two monkeys were protected against a subsequent challenge with a heterologous strain (FVO) of P. falciparum. The unimmunized control monkey died of FVO infection by day 18.
Animals↗