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Biomedical subjects

C McLean

Publications and source records attributed to C McLean.

At least 19 recordsLinked to original sources

Thrombolysis in Myocardial Infarction frame count in saphenous vein grafts.

BACKGROUND: Although the Thrombolysis in Myocardial Infarction flow grade system is a widely used index of coronary blood flow, it has important limitations. We recently described a new continuous measure of blood flow in native coronary arteries, the Thrombolysis in Myocardial Infarction frame count (TFC), and sought to extend this method to coronary artery bypass grafts. METHODS: We retrospectively analyzed cinefilms of patients' status after coronary artery bypass grafting, excluding patients with recent myocardial infarction and grafts with stenoses in the graft or native vessel. We counted the cineframes required for dye to travel from the ostium of the graft to the graft anastomotic site (TFCg) and to a standardized distal coronary landmark (TFC). RESULTS: For all vein grafts combined, TFCg was 19.2+/-5.7 frames (mean+/-SD, n = 93) and the TFC was 33.9+/-8.0 frames (n = 67). The upper limits for "normal" flow, calculated from the 95% confidence intervals, were 31 frames for TFCg and 50 frames for TFC. CONCLUSIONS: The Thrombolysis in Myocardial Infarction frame counting method has now been extended to normal saphenous vein grafts, and normal reference values are provided.

Cardiac Catheterization

The enantiomer-specific kinetics and dynamics of verapamil after rapid intravenous administration to sheep: physiological analysis and modeling.

The lung, myocardial and systemic kinetics of the enantiomers of verapamil, and their myocardial effects, were measured after administration of 10 mg of racemic verapamil during 2 min to chronically instrumented sheep; the data were used to develop a physiological model of the process. Verapamil was characterized by relatively slow transit through the lungs and heart. The lung kinetic values were membrane limited, whereas the tissue/blood equilibrium half-life for the heart was approximately 8 min. There was little difference between the kinetic values of the enantiomers, with the exception of their extent of deep distribution into the lung. The time course of the increase in myocardial blood flow caused by verapamil was best related to the time course of the arterial verapamil concentrations, whereas the time course of increases in the interval between P and R waves of the electrocardiogram and decreases in the maximum rate of rise of left ventricular pressure were best related to the time course of its myocardial concentrations. Thus, the observed hysteresis for these effects compared with arterial blood was largely caused by the time required for the myocardial equilibration. The model predicted that the myocardial concentrations of verapamil were relatively insensitive to the duration of injection of a given bolus dose, but that rapid injection caused transient, high arterial concentrations. It also predicted that the bolus dose of verapamil should be modified over a 2-fold range to account for physiologically plausible variations in base-line cardiac output and myocardial blood flow.

Animals

Angioplasty guidewire velocity: a new simple method to calculate absolute coronary blood velocity and flow.

The Thrombolysis In Myocardial Infarction (TIMI) frame count is a relative index of coronary flow that measures time by counting the number of frames required for dye to travel from the ostium to a standardized coronary landmark in a cineangiogram filmed at a known speed (frames/s). We describe a new method to measure distance along arteries so that absolute velocity (length divided by time) and absolute flow (area x velocity) may be calculated in patients undergoing percutaneous transluminal coronary angiography (PTCA). After PTCA, the guidewire tip is placed at the coronary landmark and a Kelly clamp is placed on the guidewire where it exits the Y-adapter. The guidewire tip is then withdrawn to the catheter tip and a second Kelly clamp is placed on the wire where it exits the Y-adapter. The distance between the 2 Kelly clamps outside the body is the distance between the catheter tip and the anatomic landmark inside the body. Velocity (cm/s) may be calculated as this distance (cm) divided by TIMI frame count (frames) x film frame speed (frames/s). Flow (ml/s) may be calculated by multiplying this velocity (cm/s) and the mean cross-sectional lumen area (cm2) along the length of the artery to the TIMI landmark. In 30 patients, velocity increased from 13.9 +/- 8.5 cm/s before to 22.8 +/- 9.3 cm/s after PTCA (p <0.001). Despite TIMI grade 3 flow both before and after PTCA in 18 patients, velocity actually increased 38%, from 17.0 +/- 5.4 to 23.5 +/- 9.0 cm/s (p = 0.01). For all 30 patients, flow doubled from 0.6 +/- 0.4 ml/s before to 1.2 +/- 0.6 ml/s after PTCA (p <0.001). In the 18 patients with TIMI grade 3 flow both before and after PTCA, flow increased 86%, from 0.7 +/- 0.3 to 1.3 +/- 0.6 ml/s (p = 0.001). Distance along coronary arteries (length) can be simply measured using a PTCA guidewire. This length may be combined with the TIMI frame count to calculate measures of absolute velocity and flow that are sensitive to changes in perfusion. TIMI grade 3 flow is composed of a range of velocities and flows.

Angioplasty, Balloon, Coronary

Relation between injections before 90-minute angiography and coronary patency: results of the thrombolysis in myocardial infarction 4 trial.

The current goal of thrombolytic therapy is to achieve both full (Thrombolysis in Myocardial Infarction [TIMI] grade 3) and early reperfusion. Newer reperfusion strategies may now achieve a high degree of reperfusion even earlier than the traditional 90-minute end point. To determine whether injections before 90 minutes affect this traditional end point, the relation between the number of injections before 90-minute angiography and patency was examined in the TIMI 4 trial. The number of injections before 90-minute angiography was no different between occluded arteries (TIMI grade 0/1 flow) (2.46 +/- 1.78; n = 94) and patent arteries (TIMI grade 2/3 flow) (2.71 +/- 2.42; n = 295) (p = 0.24). The incidence of any injections before 90 minutes was no different in patent versus closed arteries (80.6% [77/98] vs 72.4% [22/304]; p = 0.10). The number of injections before 90 minutes was insignificantly smaller in patients with TIMI grade 3 flow (2.53 +/- 2.53 [n = 184] vs 2.76 +/- 2.03 [n = 204]; p = 0.31), but the incidence of any injections before 90 minutes was significantly smaller in patients with TIMI grade 3 flow (68.8% [132/192] vs 79.5% [167/210]; p = 0.01). No relation was identified between the number of injections before 90-minute angiography and patency at this traditional time point. This observation justifies the judicious use of a limited number of "earlier snapshots" of the infarct-related artery before 90 minutes to ascertain just how rapidly newer thrombolytic regimens achieve patency. Patients with TIMI grade 3 flow had a slightly lower incidence of injections before 90 minutes, perhaps because they did not require as urgent a definition of coronary anatomy.

Aged

Perivascular T cells express the pro-inflammatory chemokine RANTES mRNA in multiple sclerosis lesions.

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS), characterized by accumulation of mononuclear cells. The pathogenesis of MS is complex and probably involves soluble immune mediators, particularly cytokines, and activated memory T cells, that are thought to migrate into the CNS. During lesion formation in MS, cytokines regulate cell functions, such as cell recruitment and migration. Because the chemokine RANTES play a role in both activating and recruiting leucocytes, particularly memory T cells into inflammatory sites, the authors have assessed RANTES mRNA levels at the site of lesions. Expression levels were analysed in brain samples and compared with neurological, infectious and other controls. RANTES was expressed by activated perivascular memory T cells, predominantly located at the edge of active plaques. While RANTES mRNA was detected in all 17 MS brains analysed, it was only found in six of the 14 control patients and generally at a lower expression level. In view of the regulatory and chemotactic properties of RANTES, these results imply that RANTES in MS lesions may play an important role in the activation and/or selective accumulation of memory T cells and, thereby, in the pathogenic events associated with MS.

Adult

Pharmacokinetics of EMLA cream 5% application to oral mucosa.

Plasma concentrations of lidocaine and prilocaine were measured following the application of a 5% eutectic mixture of local anesthetics (EMLA) topical anesthetic cream to the oral mucosa of twelve subjects. For each subject, a total of 8 g of EMLA was occluded to 18 cm2 of buccal mucosa for 30 min. Analysis was carried out by high-pressure liquid chromatography, and results showed peak concentrations at 40 min for lidocaine and prilocaine. The maximum concentration measured in any subject was 418 ng/ml for lidocaine and 223 ng/ml for prilocaine, well below known toxic levels. No adverse local effects were observed from a 30-min application of EMLA. A follow-up pilot study assessing the clinical efficacy of EMLA for achieving sufficient analgesia for restorative procedures showed that the cream was successful in 75% of subjects tested.

Administration, Topical

Control of expression of the I factor, a LINE-like transposable element in Drosophila melanogaster.

I factors are LINE-like transposable elements in the genome of Drosophila melanogaster. They normally transpose infrequently but are activated in the germline of female progeny of crosses between males of a strain that contains complete elements, an I or inducer strain and females of a strain that does not, an R or reactive strain. This causes a phenomenon known as I-R hybrid dysgenesis. We have previously shown that the I factor promoter lies between nucleotides 1 and 30. Here we demonstrate that expression of this promoter is regulated by nucleotides 41-186 of the I factor. This sequence can act as an enhancer as it stimulates expression of the hsp7O promoter in ovaries in the absence of heat-shock. Within this region there is a site that is required for promoter activity and that is recognized by a sequence-specific binding protein. We propose that this protein contributes to the enhancer activity of nucleotides 41-186 and that reduced I factor expression in inducer strains is due to titration of this protein or others that interact with it.

Animals

Malignant granular cell tumour of the sciatic nerve.

A case of malignant granular cell tumour of the sciatic nerve is presented. Computed tomography demonstrated isodensity with muscle and minimal enhancement. Magnetic resonance demonstrated T1 isointensity with muscle with marked enhancement, and isointensity with fat on proton and T2 images. Pathological evidence is presented for its probable Schwann cell histogenesis.

Aged

The effect of oral cisapride premedication on fasting gastric volumes.

The aim of this study was to determine whether fasting gastric volumes could be reduced by preoperative administration of cisapride. One hundred and twenty-one patients undergoing elective general anaesthesia were randomly allocated to receive either cisapride 20 mg plus diazepam 10 mg or placebo tablets plus diazepam 10 mg, two hours prior to induction. Immediately following induction blind gastric aspiration was performed using a 16Fr multiorificed orogastric tube. Gastric volume, pH, and cisapride blood concentration were measured at this time. Gastric volumes were significantly smaller in the cisapride group, 20.5 (SD 22.2) ml compared to placebo 28.2 (SD 26.0) ml but there was no significant difference with respect to pH. Some patients in both groups had large gastric volumes despite fasting. No significant adverse effects were noted with cisapride.

Adjuvants, Anesthesia

DNA heterogeneity in prostatic adenocarcinoma. A DNA flow cytometric mapping study with whole organ sections of prostate.

BACKGROUND: The degree of DNA heterogeneity varies between tumors arising at different sites. The presence of a significant degree of variability within a given tumor may result in problems in the interpretation of DNA flow cytometric findings. This study evaluated the degree of DNA heterogeneity in prostatic adenocarcinoma. METHODS: A total of 122 3-mm punch biopsy specimens were evaluated from single representative whole organ sections from nine cases of prostate cancer (range, 4-18 samples per case; mean, 12 samples; median, 14 samples). Individual punch biopsy specimens were graded and reviewed to confirm the presence of carcinoma and processed for DNA ploidy analysis. RESULTS: Assessable histograms, defined as having a coefficient of variation of the diploid G0/G1 peak of 7.5% or less, were available for 111 (91%) of the samples. Of the nine cases studied, five (56%) showed heterogeneity in the DNA pattern (diploid plus aneuploid, n = 1; diploid plus tetraploid, n = 2; and diploid plus tetraploid plus aneuploid, n = 2). All four cases having a homogeneous DNA content were DNA diploid in all samples. In those cases with a heterogeneous pattern, the areas having abnormal DNA patterns could not be predicted by histologic pattern or grade. CONCLUSIONS: From this study, the authors conclude that a significant degree of DNA heterogeneity exists within individual cases of prostatic adenocarcinoma, and this may be an important confounding factor in DNA ploidy studies.

Adenocarcinoma

An evaluation of 4% prilocaine and 3% mepivacaine compared with 2% lidocaine (1:100,000 epinephrine) for inferior alveolar nerve block.

The purpose of this study was to measure the degree of anesthesia obtained with 4% prilocaine and 3% mepivacaine compared with 2% lidocaine (1:100,000 epinephrine) for inferior alveolar nerve block. Using a repeated measures design, 30 subjects randomly received an inferior alveolar injection using masked cartridges of each solution at three successive appointments. The first molar, first premolar, lateral incisor, and contralateral canine (control) were blindly tested with an Analytic Technology pulp tester at 3-min cycles for 50 min. Anesthetic success was defined as no subject response to the maximum output of the pulp tester (80 reading) within 16 min and maintenance of this reading for 50 min. Although subjects felt numb subjectively, anesthetic success as defined here occurred in 43 to 63% of the molars, in 53 to 67% of the premolars, and in 30 to 37% of the lateral incisors. No statistically significant differences in onset, success, or failure were found among the solutions. We conclude that the three preparations are equivalent for an inferior alveolar nerve block of 50-min duration.

Adult