Biomedical subjects
A McLean
Publications and source records attributed to A McLean.
Immunopharmacological activity of Echinacea preparations following simulated digestion on murine macrophages and human peripheral blood mononuclear cells.
We have investigated the immunostimulatory, anti-inflammatory, and antioxidant activities of various Echinacea raw materials and commercially available products on murine macrophages and human peripheral blood mononuclear cells (PBMCs). To emulate oral dosing, a simulated digestion protocol was employed as a means of sample preparation. Echinacea-induced macrophage activation was used as a measure of immunostimulatory activity determined via quantitative assays for macrophage-derived factors including tumor necrosis factor alpha, interleukin (IL)-1alpha, IL-1beta, IL-6, IL-10, and nitric oxide. Echinacea herb and root powders were found to stimulate murine macrophage cytokine secretion as well as to significantly enhance the viability and/or proliferation of human PBMCs in vitro. In contrast, Echinacea extracts chemically standardized to phenolic acid or echinacoside content and fresh pressed juice preparations were found to be inactive as immunostimulatory agents but did display, to varying degrees, anti-inflammatory and antioxidant properties.
Peak inspiratory flow through Turbuhaler in chronic obstructive airways disease.
Many patients with chronic obstructive airways disease (COAD) receive therapy by the inhaled route. This study was performed to assess whether patients with severe COAD could generate sufficient peak inspiratory flow (PIF) through Turbuhaler (Astra, Sodertalje) to operate it effectively. One hundred patients (45 men, 55 women, mean age 69.1 years) with COAD (mean (SD) duration 17.7 (16.3) years) and peak expiratory flow (PEF) < or = 200 l min-1 or forced expiratory volume in 1 sec (FEV1) < or = 1 litre were studied. A series of randomly assigned inspiratory and expiratory lung function tests were contiguously performed, using portable spirometers, within 48 h of a screening visit. An empty Turbuhaler was used in the study. The patients' normal medication was not restricted. Sixty-six patients were previous smokers, eight occasional smokers, 19 habitual smokers and seven had never smoked. Mean (SD) FEV1 was 0.7 (0.2) 1 and mean PEF was 182 (68) l min-1. All patients were able to generate PIF through Turbuhaler (PIF-T) of 28 l min-1 (mean 53; range 28-78 l min-1). Eighty-three patients generated PIF-T of > or = 40 l min-1. PIF-T correlated with PIF without Turbuhaler (r = 0.35), PEF (r = 0.3), FEV1 (r = 0.2) and forced vital capacity (FVC) (r = 0.23) although the relationships were too weak to be used to predict PIF-T. The results suggest that patients with severely limited lung function caused by COAD can operate Turbuhaler effectively.
Diversity in the signalling and regulation of G-protein-coupled receptors.
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Intravenous therapy for women in labor: implementation of a practice change.
BACKGROUND: Intravenous therapy for women in labor has been routinely administered in many North American hospitals since the 1950s. The purpose of this study was to evaluate a change in intravenous therapy practice. METHODS: The evaluation study, using a posttest, quasi-experimental design, examined the responses of women in labor and nurses to a questionnaire. Proxy prestudy cohort data were used for comparison of some patient outcomes. The convenience sample comprised 219 women admitted to the labor and delivery unit of a community hospital in Toronto, Ontario, between August and October 1997. RESULTS: Under the new intravenous therapy protocol, 26 percent of the women in labor did not receive intravenous therapy compared with 100 percent under the old protocol. The primary reasons for therapy were to enable administration of prescribed medication and bolus intravenous administration associated with epidural anesthesia. At the first after-delivery void, 61 percent of study women-65 percent of those who received intravenous therapy and 50 percent of those who received no intravenous therapy-tested negative for ketonuria. All 119 comments from nurses indicated comfort with their judgments related to the initiation of intravenous therapy. CONCLUSIONS: The change in the intravenous therapy protocol was supported by the study findings. Nurses should increase patient education about drinking and eating adequately throughout labor if appropriate, and resuming adequate fluid and food intake as quickly as possible after childbirth.
Transabdominal bowel sonography in Crohn's disease.
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Study on scrapie resistance.
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An audit of patient acceptance of one-stop diagnosis for symptomatic breast disease.
AIMS: The impetus for optimizing outpatient provision of breast-care services has come both from the patient and management in order to reduce anxiety and make full use of scarce resources. The one-stop diagnostic clinic for the investigation of symptomatic breast lesions is a relatively recent concept with well-known service benefits. However, acceptance to the patient has not been previously investigated. RESULTS: The results of this prospective audit demonstrate a high level of patient satisfaction with the multi-disciplinary, one-stop breast clinic.
Prevalence of sensitization to aeroallergens in California patients with respiratory allergy. Allergy Skin Test Project Team.
BACKGROUND: The number of allergy skin tests required to evaluate patients with respiratory allergy has recently been challenged by the managed care community. OBJECTIVES: The purpose of this study was to determine which aeroallergens are prevalent in patients with respiratory allergy (allergic rhinitis and bronchial asthma) in California. METHODS: Utilizing aeroallergens thought to be relevant from recent aerobiologic and botanic data, 141 allergic and 17 asymptomatic control subjects were tested for the prevalence of 103 allergens. A standardized prick puncture technique and standardized interpretation of wheal/flare responses were utilized using the same lot of allergen for 13 allergy practices distributed throughout California. Frequency curves based on prevalence were established to determine the number of tests required to give up to 90% of positive responses for tree, weed and grass pollen, mold spores, and miscellaneous allergens which included house dust mite, cat, dog, and cockroach allergens. RESULTS: Positive responses in allergic subjects for grasses ranged from 46% to 54%, for weeds 19% to 37%, and for trees 10% to 42%. For molds the range was from 11% to 22%. The response rate for Dermatophagoides pteronyssinus was 53%, for Dermatophagoides farinae 42%, for cat pelt 39% and cat hair 37%, for cockroach 23% and dog dander 19%. Asymptomatic control subjects responded to only 4% of all allergens tested. Ninety percent of all positive tests required three miscellaneous allergens (house dust mite, cat, and cockroach), 9 molds, 2 grasses, 16 weeds, and 27 trees for a total of 57 allergens (56% of total tested). There was no clear relationship between locale and specific allergen response, probably related to the limited number of subjects tested and variability within the same geographic region. Several seldom tested tree and weed allergens showed a higher prevalence rate than several commonly tested for allergens. CONCLUSIONS: This preliminary study suggests that approximately 57 aeroalleroens might be adequate to detect 90% of all positive responses in patients with respiratory allergy in California. This study was limited by subject number and variability between study sites. It is hoped a standardized model can be developed from this pilot study to definitively determine which aeroallergens are relevant in the United States.
Hemorrhagic necrotic schwannoma presenting as purulent meningitis.
BACKGROUND: Intracranial schwannoma involving the XIIth cranial nerve is rare. We report an unusual clinical presentation and pathological verification of a schwannoma, which had become haemorrhagic and necrotic, simulating acute purulent meningitis. METHODS: A literature review of intracranial tumors presenting as acute purulent meningitis, with emphasis on schwannomas, was undertaken. RESULTS: Few cases of hypoglossal schwannoma have been reported; the association with purulent meningitis has not been previously documented. CONCLUSION: In patients presenting with sterile purulent meningitis, a necrotic tumor should be considered as a possible etiology.
Effect of the nitric oxide donor, glyceryl trinitrate, on human gall bladder motility.
BACKGROUND: Nitric oxide is a major neurotransmitter in non-adrenergic, non-cholinergic (NANC) pathways. NANC inhibitory innervation has been shown in human gall bladder muscle in vitro; the role of nitric oxide in human gall bladder emptying however is undefined. AIMS: To study the effect of glyceryl trinitrate, a nitric oxide donor, on gall bladder emptying in healthy subjects using a randomised, double blind, cross-over, placebo controlled design. METHODS: Ultrasonographic gall bladder volume was measured in the fasting state in eight healthy volunteers after randomised administration of either glyceryl trinitrate 1200 micrograms buccal spray or placebo spray. On two further occasions, after randomised administration of either glyceryl trinitrate 1200 micrograms buccal spray or placebo spray, gall bladder volumes were also measured after a liquid test meal. RESULTS: Glyceryl trinitrate significantly increased fasting gall bladder volume to a mean of 114% (SEM 5%) of pretreatment volume (p = 0.039). Glyceryl trinitrate also significantly impaired gall bladder emptying between five and 40 minutes postprandially. Gall bladder ejection fraction was also reduced after glyceryl trinitrate compared with placebo (43 (6.9)% versus 68.4 (6.5)%, p = 0.016). CONCLUSIONS: This study shows that glyceryl trinitrate produces gall bladder dilatation in the fasting state and reduces postprandial gall bladder emptying, suggesting that nitric oxide mechanisms may be operative in the human gall bladder in vivo.
Criteria for the predictably restorable endodontically treated tooth.
This paper outlines criteria which allow the clinician to identify endodontically treated teeth that can be restored with a high level of predictability. The intent of the article is not to preclude the restoration of teeth that do not meet these criteria; it is to provide a science-based approach for identifying those teeth with a high probability of long-term success upon restoration. For an endodontically treated tooth not requiring a post, the requirements are for biologic width + ferrule length, (i.e. 4.5 mm of supra-bony solid tooth--dentin a minimum of 1 mm thick after preparation). A tooth requiring a post needs, in addition, enough root length to allow a 4 mm apical seal and a post length--apical to the crown margin, equal to the length of the crown. It is essential to assess the functional loads to which the restored tooth would be subjected. Teeth that are endodontically treated, or are likely to be in future, should be avoided as abutments supporting precision attachment RPDs, distal extension RPDs or cantilever FPDs.
Predictably restoring endodontically treated teeth.
Endodontically treated teeth can be restored with a wide range of techniques of varying complexity. This paper presents a straightforward technique for the restoration of endodontically treated teeth that meet certain standards. Criteria are provided for the utilization of crowns, composite resins, cast gold post cores, amalgam or composite build-ups, and passive, parallel, small diameter stainless steel posts to restore these teeth. Consideration is given to ferrule design and its importance in achieving success.
Computed tomography in chronic inflammatory bowel disease.
In children with complicated inflammatory bowel disease, conventional ultrasound imaging may not define the extent of extraluminal disease and the involvement of other viscera. Three children with chronic inflammatory bowel disease are presented, where computed tomography was well tolerated and provided valuable information on extraluminal disease, involvement of other organs, and the state of the bowel wall and mesentery. In children in whom ultrasound examination is inconclusive or limited by gas or tenderness, computed tomography can provide important information that may determine clinical management.
Correlation of peak systolic velocity and angiographic measurement of carotid stenosis revisited.
BACKGROUND AND PURPOSE: Recent observations from the North American Symptomatic Carotid Endarterectomy Trial (NASCET) questioned the reliability of peak systolic velocity (PSV) criteria for grading carotid stenosis. We compared PSV and angiographic measurements at our center together with known physiological relationships to investigate the accuracy of ultrasound. METHODS: Consecutive patients who underwent both color-coded duplex ultrasound and intra-arterial digital subtraction angiography were studied. PSV was determined with angle correction at the site of the tightest internal carotid artery narrowing. Carotid stenosis was measured on angiograms with the North American (N) and common carotid (C) methods. Variables for the stepwise multiple linear regression analysis were selected from an axisymmetrical flow model. RESULTS: Eighty bifurcations were imaged in 40 patients. PSV did not exceed 140 cm/s in normal vessels. In diseased arteries, PSV increased proportionally with increasing stenosis and decreased to 0 cm/s at occlusion. In stepwise selection of polynomial terms, the linear, quadratic, and cubic correlations of .38, .17, and .22 for N and .45, .24, and .03 for C were found to be significant (P < .02). When only stenosed vessels were evaluated, PSV increase was found with greater scatter for the N measurement: r2 = .73 for N and r2 = .85 for C (n = 50; P = .03 for the difference between two correlated correlation coefficients). CONCLUSIONS: At our laboratory PSV consistently correlates well with N and C angiographic measurements, as determined with a simple flow model. The complex nature of these correlations and greater variability of the N measurement should be taken into account when data from different centers are compared.
Systemic corticosteriod rapidly reverses bronchodilator subsensitivity induced by formoterol in asthmatic patients.
There is evidence that downregulation and desensitization of airway beta 2-adrenoceptors (beta 2-AR) develops after continuous exposure to long-acting beta 2-agonists such as formoterol and salmeterol. To investigate the facilitatory effects of acute administration of systemic corticosteroid on bronchodilator subsensitivity, as might occur in the setting of acute asthma, 12 subjects with moderately severe asthma, with a mean FEV1 of 66% predicted, of whom were all receiving inhaled corticosteriod, were randomized to receive either inhaled placebo (PL) or inhaled formoterol (FM) 24 micrograms twice daily for 4 wk in a double-blind crossover study. Subjects were also genotyped in terms of beta 2-Ar polymorphism at loci 16 and 27. A dose-response curve (DRC) and duration-time profile for FM (12 to 108 micrograms) was produced 1 h after administration of placebo tablets and after injection at 3 wk, and 1 h after administration of oral prednisolone, 50 mg, and intravenous hydrocortisone, 200 mg, at 4 wk. Comparisons between treatments were made with area-under-curve (AUC) measurements as the change from baseline. There was a significant rightward shift in the DRC after FM as opposed to placebo for delta FEV1 (as AUC, L.h): 2.51 versus 4.22 (95% CI: 0.54 to 2.89; p = 0.01) and delta FEF25-75 (as AUC, L x 10(3)): 11.30 versus 19.94 (95% CI: 2.12 to 15.12; p = 0.01). This was significantly reversed by steroid (S) for FEV1 (FM versus FM+5): 2.51 versus 3.57 (95% CI: 0.11 to 2.27; p = 0.03) and for FEF25-75: 11.30 versus 18.47 (95% CI: 2.52 to 11.70; p = 0.005). Lymphocyte beta 2-AR density (log Bmax; fmol/10(6) cells) showed significant upregulation 3 h after steroid (FM+5 versus FM): 0.34 versus 0.24 (95% CI: 0.02 to 0.18; p = 0.01). For heart-rate response (as AUC, beats), there was subsensitivity with FM versus PL: 2,700 versus 5,200 (95% CI: 40 to 5,000; p < 0.001), and this was reversed by steroid (FM+5 versus FM): 9,600 versus 2,700 (95% CI: 4,900 to 8,800; p < 0.001). This reversal by systemic corticosteroid appears to be generally independent of beta 2-AR polymorphism at loci 16 and 27. In conclusion, we have demonstrated that bronchodilator subsensitivity occurs after regular inhaled FM in asthmatic patients, and is rapidly reversed by systemic corticosteroid. Thus, in acute asthma, systemic corticosteroid should be administered a soon as possible, in order to restore normal airway beta 2-AR sensitivity, particularly in patients who are receiving regular long-acting beta 2-agonists.
Comparative efficacy and potency of ipratropium via Turbuhaler and pressurized metered-dose inhaler in reversible airflow obstruction.
Ipratropium bromide (IB), typically delivered by pressurized metered dose inhaler (pMDI), is used to treat patients with reversible airways obstruction. Use of the pMDI, unlike the Turbuhaler (TH), demands co-ordination of actuation with inspiration for efficient use. Two studies were carried out to compare the relative efficacy and potency of IB delivered by TH or pMDI. Both studies were of a randomized, double-blind and cross-over design. For the efficacy study, 15 patients received a cumulative dose of 160 microg IB via TH or pMDI as doses of 20, 20, 40 and 80 microg at 45 min intervals on two days. Forced expiratory volume in one second (FEV1) was measured prior to and 40 min after dosing. For the potency study, 33 patients received 10, 20 or 40 microg of IB via TH, 20 microg IB via pMDI, or placebo, on five days. FEV1 was recorded prior to and 15-360 min after dosing. For the efficacy study, there was no difference in FEV1 response to a cumulative dose of IB via pMDI and TH. More than 80% of the maximum effect was seen at the lowest dose (20 microg of IB). Regarding the potency study, the FEV1 response to 20 microg IB administered via pMDI was similar to that of 10 microg via TH; 20 microg via TH was significantly more effective than 20 microg via pMDI (p<0.05). In conclusion, the efficacy study showed that maximum FEV1 occurred at low doses of IB, negating any opportunity to identify differences between devices. The potency study indicated that the 10 microg dose via TH was of similar efficacy to the 20 microg dose via pMDI, confirming an efficacy ratio of 1.5-2.0:1 for the TH device.
Comparative psychophysical evaluation in cochlear implantation: electrical and magnetic stimulation.
Transtympanic electrical stimulation, either in the form of round window or promontory placement of electrode prior to cochlear implantation is an accepted and commonly used psychophysical tool. Certain response parameters have been identified as predictors of outcome. This study compared the subjective auditory responses generated by promontory electrical stimulation (PES) with those from two noninvasive modalities, namely peritympanic electrical stimulation (PTES) and transcranial magnetic stimulation (TMS). Ten postlingually deafened adult cochlear implant candidates were studied. Standard psychophysical parameters were obtained from patients undergoing PES and PTES. A more subjective form of evaluation was conducted for TMS. Subsequently, nine patients received the multichannel Nucleus (Cochlear Corp., Denver, CO, U.S.A.) implant and one patient a Clarion (Advanced Bionics, Sylmar, CA, U.S.A.) implant. Compared with PES. PTES elicited increased threshold responses with similar dynamic ranges between 50 and 400 Hz of stimulation. The differences were, by and large, insignificant. PTES appeared to be a useful alternative in selected individuals owing to its noninvasiveness. TMS, on the other hand, was incapable of clearly inducing auditory percepts. It also produced concomitant facial and trigeminal stimulation, limiting its potential use as a prognostic tool.