Search PubMedSearch

Biomedical subjects

W D Smith

Publications and source records attributed to W D Smith.

At least 19 recordsLinked to original sources

Wakeful response to command indicates memory potential during emergence from general anesthesia.

OBJECTIVE: An important aspect of assessing anesthetic depth is determining whether a patient will remember events during surgery. We looked for a clinical sign that would indicate a patient's potential for memory formation during emergence from anesthesia. A clinical sign indicating memory potential could be a useful endpoint for measuring the performance of anesthetic depth monitors and for titrating administration of anesthetic agents. METHODS: We evaluated patients' responses to commands to open the eyes, squeeze the hand four times, and count 20 numbers. These responses were correlated with results on recall, cued recall, and multiple-choice memory tests. MAIN RESULTS: Patients did not have evidence of memory formation until they sustained wakefulness sufficiently long to complete at least four hand squeezes or count four numbers. Of 28 patients, 13 (46%) with this sustained wakeful response had memory. Of 22 patients, 0 (0%) had evidence of memory formation when they demonstrated a brief wakeful response, defined as being responsive to command but unable to complete more than one hand squeeze or count, or an intermediate response, defined as two or three hand squeezes or counts. CONCLUSIONS: We conclude that a brief wakeful response to command indicates that a patient is unlikely to form memories, while a sustained wakeful response indicates that a patient may form memories. Thus, a patient's wakeful response to command could be a useful indicator of potential for memory.

Adult

Brief wakeful response to command indicates wakefulness with suppression of memory formation during surgical anesthesia.

OBJECTIVE: In a previous study of patients emerging from anesthesia following surgery, we found that a brief wakeful response to command of an eye opening or single hand squeeze or count was not associated with memory formation, while the response of four hand squeezes or counts was associated with memory. We wanted to determine the anesthetic requirements for obtaining this brief wakeful response endpoint during surgery and to determine if memory occurred at this endpoint during surgical anesthesia. METHODS: Six different combinations of isoflurane, 70% N2O, and fentanyl were administered to 326 patients undergoing pelvic laparoscopy. After insertion of the trocar, anesthesia was reduced while patients were given verbal commands, and they were observed for movement responses to surgery and to command. Patients were classified as either not arousing, arousing with a movement response to surgery, or arousing with a wakeful response to command. For the patients who aroused, we calculated the percentage of arousal responses that were wakeful responses to command. The effect of fentanyl dosage upon the percentage of arousal responses that were wakeful responses to command was determined by using a Mann-Whitney test to compare a group of patients receiving fentanyl 2 micrograms/kg or less, with a group receiving fentanyl 4 micrograms/kg. In a subset of 39 patients, the potential for memory formation was evaluated by presenting a target sound to 29 patients during a period of either no arousal, movement response to surgery, or wakeful response to command; for a control group of 10 patients, no target sound was presented. All 39 patients were tested for memory of the target sound; the results from each group receiving a target sound were compared with the results of the control group, using a Mann-Whitney test. MAIN RESULTS: A total of 68 patients aroused with either a movement response or a wakeful response to command. Wakeful responses occurred with only 1 of 39 patients (3%) receiving fentanyl 2 micrograms/kg or less; but, wakeful responses occurred with 17 of 29 patients (59%) receiving fentanyl 4 micrograms/kg. The difference between the groups was significant at p = 0.01. None of the 68 patients had recall of intraoperative events or unpleasant dreams. None of these patients who were in the multiple-choice memory subset recalled the target sound. There were no statistically significant differences on the multiple-choice memory test between the groups presented with the target sound and the control group. Patient anecdotes suggested that some patients may have had memory of the target sound; but, memory was no more likely in patients with a brief wakeful response to command than in those who responded with a movement to surgical stimulation or those who did not have an arousal response. CONCLUSIONS: A brief wakeful response to a command of opening the eyes or squeezing the hand was not associated with increased memory formation during surgery. A brief wakeful response to command was found during surgery when patients received fentanyl 4 micrograms/kg; but it was rarely found at fentanyl dosages of 2 micrograms/kg or less.

Adolescent

Haemopoietic cell responses in the blood and bone marrow of sheep infected with the abomasal nematode Telodorsagia circumcincta.

The generation of bone marrow and blood haemopoietic progenitor colony-forming cells (CFCs) in sheep given primary or challenge infections with the nematode parasite Telodorsagia circumcincta is described. Ten days after a primary infection, the frequency of early multipotential-CFCs, eosinophil-CFCs, macrophage-CFCs and mast cell or basophil-CFCs was greater than in controls. These frequencies then declined to pre-infection levels by day 21. Blood CFCs (mainly macrophage-CFCs and eosinophil-CFCs) also increased after infection, indicating a migration of CFCs, presumably to the site of infection. Ten days after challenge infection there was less marked myelopoiesis than in the primary infection on day 10, though both eosinophil-CFCs and mast cell or basophil-CFCs were significantly above control values. Blood CFC output (mainly macrophage-CFCs and eosinophil-CFCs) reached a peak 2-6 days after challenge, evidence of rapid recruitment to the site of infection. Telodorsagia circumcincta infection is therefore associated with an increase in myelopoiesis, particularly for the cell types characteristic of the local inflammatory response to abomasal nematodes. There was no correlation between any of the haemopoietic cell responses measured and worm burdens in individual animals after either primary or challenge infection.

Animals

Ingestion of host immunoglobulin by three non-blood-feeding nematode parasites of ruminants.

Host immunoglobulin was detected in homogenates of adult worms or fourth stage larvae of Haemonchus contortus, Ostertagia ostertagi, O circumcincta and Dictyocaulus viviparus, but not in preparasitic third stage larvae of H contortus. All the worms had been washed in detergent before being homogenised to remove any immunoglobulin adhering to the cuticle. This procedure, the concentrations of immunoglobulin detected and observations on sections of the worms stained with fluorescent anti-sheep immunoglobulin, all suggested that the immunoglobulin had been ingested, even by the non-blood-feeding species. This finding suggests that the Ostertagia species and D viviparus may be susceptible to vaccination by the gut antigen approach, a method with considerable promise for blood-feeding parasites like H contortus and Boophilus microplus.

Animals

Protection studies with integral membrane fractions of Haemonchus contortus.

Techniques for targetting glycoproteins integral to the luminal membrane of the intestinal cells of Haemonchus contortus were used to isolate fractions of whole parasites with protective antigen potential. Sheep immunization trials with various candidate fractions revealed one which selectively bound to lectins with specificity for N-acetylgalactosamine and which reduced mean challenge worm burdens by up to 72% and mean faecal egg counts by up to 93%. The luminal surface of the intestines of the Haemonchus recovered from sheep immunized with this antigen were coated with host immunoglobulin, suggesting that the protective effect was due to antibodies interfering with the function of the gut. Further biochemical characterization of this fraction, which has been termed Haemonchus galactose-containing glycoprotein complex (H-gal-GP complex), showed that it could be distinguished from previously described protective antigens of this parasite and that it was only detectable in detergent extracts of the worms.

Acetylgalactosamine

Local eosinophil- and mast cell-related responses in abomasal nematode infections of lambs.

Eosinophil numbers in peripheral blood and eosinophil potentiating activity (EPA) and sheep mast cell protease (SMCP) in efferent gastric lymph were monitored in lambs during infections with Ostertagia circumcincta. Worm burdens, eosinophil numbers in bone marrow, abomasal mucosa and gastric lymph node, as well as mast cell numbers and SMCP concentrations in mucosa and mucus, were determined in post mortem samples. In naive lambs, high and relatively uniform worm burdens were present 10 days after primary infection and these were associated with only mild blood and tissue eosinophilia. By day 21 worm burdens were markedly lower and more variable. There was more evidence of eosinophil and mast cell accumulation in mucosa, and numbers in bone marrow were also higher than on day 10. However, neither EPA nor SMCP were detectable in lymph. By contrast, EPA and SMCP were present in substantial amounts in draining lymph within 48 h of challenge (secondary) infection of previously exposed lambs. EPA was inversely related to worm burdens recovered on day 10, as were abomasal mucosal and mucus SMCP concentrations. Elevated eosinophil numbers were also consistently detected in blood, bone marrow, mucosa and gastric lymph node. The results suggest that host immune defence against secondary, but not primary, exposure to O. circumcincta involves a rapidly mobilised local inflammatory component.

Abomasum

Evaluation of the VMM turbine for spirometry in the applied physiology laboratory.

The volume measurement module turbine (VMM) was evaluated in 51 subjects for spirometry in applied physiology against the Stead-Wells spirometer (SW) and Wright peak flow meter (WM). The volume and flow ranges (VMM) were, FEV1 1.32 to 3.94 L (mean 2.62, confidence interval [CI] 2.46 to 2.78); forced vital capacity (FVC) 1.97 to 5.06 L (mean 3.50, CI 3.29 to 3.71); and peak expiratory flow rate (PEFR) 290 to 624 L.min-1 (mean 434, CI 407 to 461). The mean difference for FEV1 was 0.09 L (CI 0.05 to 0.14), FVC 0.04 L (CI -0.02 to 0.10), and PEFR 18.0 L min-1 (CI 8.7 to 27.3) less than SW or WM. Bias with FEV1 and FVC was not significant, though PEFR demonstrated a significant proportional error. The repeatability coefficients for FEV1 and FVC were 0.18 and 0.20, comparable to the SW; but for PEFR they were greater, 58.4 versus 33.8 L.min-1 by WM. The VMM turbine is accurate and reliable for the measurement of FEV1 and FVC over the ranges studied; however, care should be taken when interpreting PEFR.

Adult

Ventilatory sensitivity to CO2 in hyperoxia and hypoxia in older aged humans.

Findings from studies of the effects of aging on the human respiratory controller are equivocal. This study assessed the ventilatory response to CO2 in hyperoxia and hypoxia in groups of younger (YS) and older (OS) humans. Two protocols were used. In the first, end-tidal PCO2 (PETCO2) was clamped at 1-2 Torr above rest (eucapnia), and, in the second, PETCO2 was clamped at 7-8 torr above resting PETCO2 (moderate hypercapnia). End-tidal PO2 was clamped at 100 Torr throughout except for two 2-min periods at 500 and 50 Torr. The ventilatory responses for each subject at each PO2 were fitted to the linear equation, VE = S(PETCO2 - B), where VE is minute ventilation, S is the response curve slope, and B is the response curve threshold. In eucapnia, there were no differences in hypoxic and hyperoxic VE between YS and OS. In hypercapnia, hypoxic VE was 24% lower in OS [39.93 +/- 2.71 (SE) l/min] than in YS (52.16 +/- 3.17 l/min). In hypoxia, S was significantly lower in OS (3.25 +/- 0.38 l.min-1.Torr-1) than in YS (4.76 +/- 0.37 l.min-1.Torr-1). We conclude that, in older humans, VE is lower in hypoxia during moderate hypercapnia, resulting mainly from a decreased peripheral chemoreflex CO2 sensitivity.

Adult

Physiological responses of young and elderly men to prolonged exercise at critical power.

The critical power (CP) of a muscle group or individual may represent the highest rate of work which can be performed for an extended period. We investigated this concept in young (n = 13, 24.5 years) and elderly (n = 12, 70.7 years) active men by first determining CP and then comparing responses elicited by 24 min of cycle exercise at power outputs (omega) corresponding to CP. Values from the final 2 min of the 24-min ride were expressed relative to maximal values established in a ramp test. CP for the elderly was only 65% that for the young, but on a relative basis, it was significantly higher both in terms of omega (67 vs 62% of omega max) and oxygen consumption (VO2) (91.5 vs 85.2% of maximum oxygen consumption). There were no group differences in relative values for ventilation (VE), heart rate or respiratory exchange ratio (R). During the 24-min ride, VO2 and R achieved a plateau in both groups, while VE, blood lactate and arterial PCO2 continued to change in the young. It was concluded that CP can be determined in active elderly men, but that CP may not represent a true non-fatiguing work rate in either young or elderly men.

Adult

Forced expiratory volume, height, and demispan in Canadian men and women aged 55-86.

In a random cross-sectional study in London, Canada, forced expiratory volume in 1 second (FeV1.0), height, and demispan (fingerweb to central sternal notch) were measured on 182 men and 212 women of mean ages 70.4 (SD 8.5) and 71.3 (8.2). The mean FeV1.0 for men was 2.55 (0.66) l, and for women 1.80 (0.48) l and declined 29 ml.year-1 and 25 ml.year-1, respectively. The mean FeV1.0 standardized for measured height and calculated height for men was 2.54 (0.61) l and 2.55 (0.62) l in men, and 1.80 (0.46) l and 1.79 (0.45) l in women. There was no significant difference between the two methods of standardization, and the relationship of height to demispan in this independent elderly population was constant across age for both men (2.16) and women (2.17). Linear and proportional regression coefficients to predict FeV1.0 from height and demispan have been generated for this random sample aged 55 to 86 years.

Aged

Further observations on the phagocytosis of Candida albicans by hamster and human oocytes.

Pathogenic yeast, Candida albicans, were incubated with hamster and human oocytes for up to 21 hours in order to determine the nature and time course of phagocytosis of these organisms. Aliquotes of the interacting cells were taken at various time intervals for electron microscopic examination. Some specimens had their zona pellucidae enzymatically removed prior to incubation with yeast, and these specimens showed the most extensive interaction and phagocytosis of Candida. The zona pullucida appears to be an effective barrier to yeast, at least over the time span studied. The observations are consistent with the hypothesis of an initial attachment of yeast via a surface component to oocyte microvilli followed by phagocytic uptake into an endosome. There is no compelling evidence of lysosomal degradation of the yeast over the time course of this study; however, the oocytes appear to undergo some degenerative changes at long incubation times.

Animals

Parasite-specific T cell responses of sheep following live infection with the gastric nematode Haemonchus contortus.

Helper T cell lines recognizing antigen in the context of MHC Class II molecules were generated from peripheral blood mononuclear cells (PBMC) of sheep undergoing a primary or secondary infection with the nematode parasite Haemonchus contortus. The lines were used to identify 15-18, 25-29, 70-80 and greater than 100 kD immunodominant parasite larval antigens fractionated by SDS-PAGE under reducing conditions. Non-specific mitogenic activity in the antigen fractions was not detected. During primary infection PBMC did not respond to soluble antigens or those fractionated on SDS-PAGE, whereas T cell lines generated from these PBMC responded well. T cell lines and PBMC derived after a secondary infection responded similarly to fractionated larval antigen. This indicated that (a) the T cell lines had retained their antigen specificities (as represented by autologous PBMC reactivity) in spite of in-vitro cycles of restimulation with whole larval soluble antigen and subsequent expansion in recombinant human IL-2, and (b) proliferation of the antigen-specific PBMC was predominantly due to helper T cells. Variations between individual sheep in response to fractionated larval antigens was also observed. The pattern of helper T cell reactivity to SDS-PAGE larval antigens correlated poorly with B cell reactivity in the same animals by serum antibody Western blot analysis. These results demonstrate that helper T cell epitopes can be mapped in complex parasite antigen preparations in sheep and that this approach will be useful in the identification of parasite protective antigens in helminthiasis where the cellular or humoral nature of protection is not clearly defined.

Animals