Biomedical subjects

S Houle

Publications and source records attributed to S Houle.

At least 109 records · Page 6Linked to original sources

PubMed1992

In vitro stability of EDTA and DTPA immunoconjugates of monoclonal antibody 2G3 labeled with indium-111.

Monoclonal antibody 2G3 directed against a high molecular weight glycoprotein on breast and ovarian cancer cells was conjugated with bicyclic DTPA (or EDTA) anhydride or benzyl isothiocyanate DTPA (benzyl DTPA) and labeled with 111In. DTPA anhydride was more reactive with the antibody than benzyl DTPA, and kinetics of labeling with 111In were more rapid for DTPA substituted 2G3 than for benzyl DTPA substituted 2G3. On the other hand, 111In-2G3 conjugates prepared using DTPA anhydride were subject to more extensive dimerization and higher losses in immunoreactivity than those prepared using benzyl DTPA. On the basis of measurement of transchelation to transferrin, the stability of 111In-2G3 prepared using DTPA anhydride or benzyl DTPA did not differ during incubation in human plasma for 6 days at 37 degrees C. These results suggest that an important advantage of benzyl DTPA over DTPA anhydride for preparing 111In-labeled antibodies is the prevention of intermolecular (and intramolecular) crosslinking during conjugation which ultimately leads to alterations in conformation and losses in immunoreactivity of the radioimmunoconjugate.

Antibodies, Monoclonal↗

PubMed1992

Quantification of skeletal muscle necrosis in the lower extremities using 99Tcm pyrophosphate with single photon emission computed tomography.

No non-invasive quantitative method is currently available for measuring the amount of regional skeletal muscle necrosis in humans. A threshold method using 99Tcm pyrophosphate (PPi) with single photon emission computed tomography (SPECT) has been reported to quantify muscle necrosis successfully in a canine model. This method has been modified to measure muscle necrosis in the lower extremities of human patients. Modifications include adding background subtraction and using the contralateral unaffected lower extremity as background region. A region of interest was also manually drawn around the affected lower extremity muscle to exclude the tibia. In order to identify the group of patients with no significant necrosis and with diffuse hyperaemia, nine control subjects were studied. The variance of the counts within the pixels of the lower extremities was 132 (S.D. = 27). A variance of greater than 159 was considered as being significant for necrosis. Thirteen patients were studied. Six patients had significant muscle necrosis (462 ml, S.D. = 280 ml). All except one patient (who had a small amount of muscle necrosis) developed foot drop. Seven patients had no significant necrosis. All patients had normal ankle dorsiflexion. It is possible to quantify regional muscle necrosis using PPi with SPECT. Volume of necrosis determined by this method can also predict clinical outcome.

Aged↗

PubMed1992

Rapid quality control of 99Tcm-sestamibi.

The thin layer chromatographic (TLC) method for determining the radiochemical purity of 99Tcm-sestamibi suggested by the manufacturer of the kit is slow and inconvenient. In this study a more rapid reversed phase chromatography (Sep-Pak) technique is compared with the TLC method for measurement of the radiochemical purity of 99Tcm-sestamibi. The levels of free 99Tcm-pertechnetate in 99Tcm-sestamibi were accurately determined using the Sep-Pak technique. However, due to binding of variable amounts of reduced-hydrolysed unbound 99Tcm to the chromatography cartridge, the Sep-Pak method overestimated the radiochemical purity of the radiopharmaceutical by approximately 3%. In practice, this overestimation is not important and the Sep-Pak technique can be used as a rapid method of determining radiochemical purity of 99Tcm-sestamibi.

Quality Control↗

PubMed1991

Prospective assessment of cardiac function in patients with Kaposi's sarcoma and the acquired immune deficiency syndrome.

Prospective evaluation of cardiac function was undertaken in 21 patients with Kaposi's sarcoma (KS) and the acquired immune deficiency syndrome (AIDS) as part of a phase II clinical trial of 4'epirubicin. All patients were homosexual or bisexual males of median age 34 years (range 23-65). All patients had disseminated cutaneous involvement by KS and seven had systemic organ involvement. No patient had a history of cardiac symptoms, and physical examination of the cardiovascular system was within normal limits for all patients. The baseline ECG was normal in only nine patients (45%). Five had non-specific S-T segment and T-wave changes. Two had poor R-wave progression, and one patient each had incomplete right bundle branch block, left axis deviation, and voltage criteria suggestive of left ventricular hypertrophy. Radionuclide angiography was performed on all patients and compared to 12 age-matched, low-likelihood male controls. The mean ejection fraction (EF) at rest was 61.0 +/- 8.4%, and was not significantly different from the normal control value of 62.4 +/- 7.0%. Similarly the EF during exercise was 66.7 +/- 5.0%, again not significantly different from the control value of 67.8 +/- 5.8%. A drop in EF during exercise was seen in five of 15 KS patients compared to three of 12 controls. Chamber size was normal for both ventricles in only 14 patients (67%) with right ventricular dilatation seen in seven patients (33%). Wall motion abnormalities were also seen in nine patients (42.9%), with the right ventricle affected in eight patients (38.1%), chiefly involving the apex. No chamber size or wall motion abnormalities were seen in the control patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗

PubMed1990

Validation of left ventricular function parameters acquired with the non-imaging nuclear probe: comparison with tantalum marker cine-fluoroscopy.

We evaluated the accuracy of the non-imaging nuclear probe for measuring various parameters of left ventricular function by comparing these with simultaneous measurements acquired via tantalum marker cine-fluoroscopy. Eight patients with surgically implanted mid-myocardial tantalum markers were studied during cardiac catheterization. High temporal resolution tantalum marker-derived volume/time curves were generated and calibrated to absolute endocardial volumes by comparison with contrast left ventricular angiography. Left ventricular function parameters were acquired at baseline and during atrial pacing, nitroprusside infusion and volume loading. Simultaneous measurements obtained with the nuclear probe and via tantalum marker cine-fluoroscopy were compared. The following correlation coefficients were obtained: ejection fraction, r = 0.49, P less than 0.001; peak ejection rate, r = 0.41, P less than 0.01; mean ejection rate, r = 0.62, P less than 0.001; time to peak ejection, r = 0.73, P less than 0.001; peak filling rate, r = 0.73, P less than 0.001; time to peak filling, r = 0.58, P less than 0.001. Relative changes in end-diastolic volume were accurately tracked by the nuclear probe in six of seven patients (r values 0.77-0.93). These results suggest that measurements of certain left ventricular volume parameters with the nuclear probe may not accurately reflect true volume changes as measured by tantalum marker cine-fluoroscopy. Although, the probe may be useful in tracking relative changes in end-diastolic volume, we would advise caution in using this instrument for studies requiring accurate measurements of ejection and filling parameters.

Cardiac Catheterization↗

PubMed1990

Quantitation of skeletal muscle necrosis using 99Tcm-pyrophosphate with SPECT in a canine model.

Patients with acute arterial occlusion may suffer from significant muscle necrosis. It is important to determine the amount of regional muscle necrosis for prognostic purposes and evaluation of therapy. We have used technetium-99m-pyrophosphate (PPi) with single photon emission computed tomography (SPECT) to quantitate muscle necrosis. A canine gracilis muscle ischaemia model was used. PPi was injected 1.5 h before the muscle preparation was removed from the dog. SPECT was performed on the muscle preparations. An automatic edge detection program using the threshold technique determined the number of pixels with significant PPi activity in each transaxial section. Volume was calculated by summing the number of pixels with significant PPi activity and multiplying by the voxel size. The results were compared with quantitation using computerized planimetry with nitroblue tetrazolium staining (correlation coefficient = 0.93). PPi with SPECT is an accurate method for quantiating muscle necrosis.

Animals↗

PubMed1990

Effect of intracoronary nifedipine on coronary bloodflow and myocardial metabolism during pacing-induced ischemia.

The effects of intracoronary nifedipine on coronary bloodflow, its regional distribution, myocardial oxygen consumption and lactate metabolism during pacing-induced angina were evaluated in 15 subjects. These responses were directly compared to 10 subjects who received an alcohol-based control solvent. Myocardial bloodflow was measured by thermodilution, with changes in regional coronary flow assessed using a dual radiolabelled (technetium-99m and indium-111) intracoronary microsphere technique and single photon emission tomography. Neither intracoronary nifedipine (100 micrograms) or the control solvent produced changes in systemic arterial pressure (nifedipine -2 mmHg and control +2 mmHg, both not significant). Intracoronary nifedipine markedly increased left ventricular end diastolic pressure (pre-nifedipine 13.0 mmHg versus post nifedipine 20.1, P less than 0.05), while increasing total coronary sinus bloodflow (pre-nifedipine 134 mL/min versus post nifedipine 189, P less than 0.05): Regional coronary bloodflow increased in all myocardial segments, regardless of the severity of coronary stenosis (64 to 132% baseline, all P less than 0.05). In addition, intracoronary nifedipine increased myocardial oxygen consumption (pre-nifedipine 12.3 mL/min versus post nifedipine 15.7, P less than 0.05), with a trend towards improved lactate extraction (pre-nifedipine 0.24 mg/mL versus post nifedipine 0.12, not significant). Although decreased ventricular afterload (left ventricular systolic wall stress) may contribute to nifedipine's antianginal properties, a primary increase in regional coronary bloodflow also appears to be an important factor in the alleviation of myocardial ischemia.

Adult↗

PubMed1989

Labelling of monoclonal antibodies 10B, 8C, and M2A with indium-111.

Monoclonal antibodies 10B, 8C and M2A were conjugated with cyclic DTPA anhydride to a substitution level of 1-2 mol DTPA/mol antibody. The DTPA-conjugated antibodies were purified by size-exclusion mini-column chromatography and labelled with [111In]In acetate to a specific activity of 37-74 kBq/micrograms (1-2 microCi/micrograms). The radiochemical purity of the antibody preparation was 76-81%. The immunoreactive fraction of the radiolabelled antibodies ranged from 0.17 to 0.31, significantly lower than that of their radioiodinated analogs.

Antibodies, Monoclonal↗

PubMed1989

Scintigraphic findings in congenital lipodystrophy.

The scintigraphic findings of a patient with characteristic clinical, laboratory, and radiographic features of congenital lipodystrophy were studied. Bone scan showed uniform increased bone uptake of Tc-99m MDP with markedly enhanced peri-articular activity and very prominent renal activity. Liver-spleen scan showed marked hepatosplenomegaly. This combination of scintigraphic abnormalities is unique in congenital lipodystrophy and constitutes a very interesting constellation of findings. Observed scintigraphic findings are compatible with previously described radiographic findings.

Adult↗

PubMed1989

Gallium scan finding in a patient with suppurative lymphangitis secondary to sporotrichosis.

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Female↗

PubMed1989

A comparison of three methods to determine the radiochemical purity of 99Tcm-hexamethylpropylene amine oxime (99Tcm-HMPAO).

Determining the radiochemical purity of 99Tcm-HMPAO using the standard method suggested by the manufacturer of the HMPAO kit is slow, consuming much of the 30 min useful shelf-life of the radiopharmaceutical. We have compared two new methods (a solvent extraction technique and a method involving a disposable, pre-packed reverse phase chromatography cartridge) with the standard method for determining the radiochemical purity of 99Tcm-HMPAO. There were no significant differences (F test, p less than 0.05) in the results obtained by all three methods. However, the reversed phase chromatography method gave better agreement (correlation coefficient of 0.877) with results obtained using the standard method than did the solvent extraction technique (correlation coefficient of 0.693). The solvent extraction technique took about 10 min to perform whereas the reversed phase chromatography method took only 5 min. Both of the new methods did not achieve complete separation of the secondary, less lipophilic 99Tcm-HMPAO complex from the primary, lipophilic 99Tcm-HMPAO complex but the error introduced was small (typically only 3-5%). The new methods offer the capability of determining the radiochemical purity of 99Tcm-HMPAO quickly, reliably and accurately, prior to administration of the radiopharmaceutical to the patient.

Organotechnetium Compounds↗

PubMed1989

Hepatocellular carcinoma: pilot trial of treatment with Y-90 microspheres.

The potential use of yttrium-90 glass microspheres in the treatment of hepatocellular carcinoma was assessed in a pilot study of seven patients. The Y-90 microspheres were injected via a hepatic artery catheter. In this group of patients, no toxicity was observed for absorbed doses of between 5,000 and 10,000 cGy to the liver and up to 32,000 cGy to the tumor itself. Tumor response was seen only at the higher absorbed doses. The new Y-90 glass microspheres can safely deliver large doses of internal radiation to hepatic tumors as long as extrahepatic shunting can be excluded. Extrahepatic shunting will be the main limitation to this form of radiation therapy.

Brachytherapy↗

PubMed1988

Quantitation of postischemic skeletal muscle necrosis: histochemical and radioisotope techniques.

Skeletal muscle necrosis will result from prolonged periods of ischemia. The purpose of this study was to develop a method to estimate the extent of necrosis using nitroblue tetrazolium staining and technetium scanning. The bilateral canine gracilis muscle preparation with total vascular isolation was exposed to 4 hr of complete normothermic ischemia followed by reperfusion. After 45 hr of reperfusion 99mTc pyrophosphate (PYP) was injected and 3 hr later the muscles were harvested, cut into six slices, and stained with nitroblue tetrazolium. Biopsies were taken from tetrazolium-positive and -negative areas for electron microscopy to confirm the ability of the stain to distinguish viable from necrotic muscle. Computerized planimetry of the staining pattern was used to estimate the extent of necrosis as a percentage of the total muscle. Electron microscopy confirmed the validity of nitroblue tetrazolium to discriminate between viable and necrotic skeletal muscle in this experimental model. After 4 hr of ischemia the percentage necrosis was 30.2 +/- 6.1% (mean +/- SEM, n = 12), there was no difference in the extent of necrosis in left vs right paired muscles, using tetrazolium staining or technetium PYP uptake. There was a statistically significant correlation between the percentage necrosis and the density of 99mTc PYP uptake per muscle (r = 0.83, P less than 0.001) and per slice (r = 0.94, P less than 0.001). This study demonstrates the ability of tetrazolium staining to accurately differentiate between viable and necrotic skeletal muscle and provides a reproducible method for estimating the extent of necrosis in the gracilis muscle model.

Animals↗

PubMed1987

Right ventricular function: a comparison between blood and crystalloid cardioplegia.

Blood cardioplegia resulted in better left ventricular (LV) function than crystalloid cardioplegia after elective coronary artery bypass operations. However, most methods of cardioplegic delivery may not adequately cool and protect the right ventricle, and right ventricular (RV) dysfunction may limit hemodynamic recovery. Therefore, RV and LV temperatures were measured intraoperatively and RV and LV function were evaluated postoperatively in 80 patients with double-vessel or triple-vessel coronary artery disease who were randomized to receive either blood cardioplegia or crystalloid cardioplegia. Myocardial performance, systolic function, and diastolic function were assessed with nuclear ventriculography by evaluating the response to volume loading. Preoperatively the groups were similar. Intraoperatively, blood cardioplegia resulted in significantly warmer LV and RV temperatures (left ventricle: 15.5 degrees +/- 0.2 degrees C with blood cardioplegia and 12.6 degrees +/- 0.3 degrees C with crystalloid cardioplegia [p less than .0001]; right ventricle: 18.3 degrees +/- 0.3 degrees C with blood cardioplegia and 15.1 degrees +/- 0.3 degrees C with crystalloid cardioplegia [p less than .0001]). Postoperatively, blood cardioplegia resulted in better LV performance (higher LV stroke work index at a similar LV end-diastolic volume index [EDVI]) (p = .01), better LV systolic function (similar systolic blood pressures at smaller LV end-systolic volume indexes [ESVI]), (p = .04), and improved LV diastolic function (lower left atrial pressures at similar LVEDVIs) (p = .03).(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure↗

PubMed1987

Transient biventricular dysfunction following coronary bypass surgery with potassium cardioplegia.

Although myocardial revascularization relieves anginal symptoms, the effect on ventricular function remains controversial. Sixty-six patients undergoing elective coronary bypass surgery with normal right and left ventricular function were studied 1 month preoperatively (PRE), 3-5 hours perioperatively (PERI) and 3-5 months postoperatively (POST). Nuclear ventriculograms were employed to calculate right and left ventricular ejection fractions (RVEF, LVEF), end diastolic volume indices (RVEDVI, LVEDVI) and end systolic volume indices (RVESVI, LVESVI). Cardiac index (CI), stroke index (SI) and an approximation of left ventricular stroke work index (LVSWI) were also calculated from the scintigraphic data. Right and left ventricular ejection fractions were lower perioperatively (PRE:RVEF 37 +/- 2.5, LVEF 61 +/- 3; PERI:RVEF 32 +/- 3, LVEF 51 +/- 4; POST:RVEF 35 +/- 3, LVEF 56 +/- 4%, p less than 0.01 by analysis of variance, ANOVA) despite lower end diastolic volume indices perioperatively, (p less than 0.05 by ANOVA). The ratio of systolic blood pressure to LVESVI was significantly lower PERI than PRE or POST, (p less than 0.01 by ANOVA). SI, LVSWI, LVEF and RVEF were lower perioperatively at any level of LVEDVI or RVEDVI (p less than 0.01 by paired analyses of covariance), suggesting transient depression of right and left ventricular performance perioperatively. Right ventricular recovery was incomplete 4 months postoperatively. The patients were able to exercise longer at higher workloads postoperatively (p less than 0.01 by ANOVA). Chest pain resulted in discontinuation of exercise in 57% of patients PRE but only 5% POST (p less than 0.01), even though all patients were receiving full medical therapy preoperatively and no therapy postoperatively. Myocardial revascularization provided symptomatic relief and increased work capacity. However, right and left ventricular function were transiently depressed in the early perioperative period.

Coronary Artery Bypass↗

PubMed1986

Persistent ventricular adaptations in postoperative coarctation of the aorta.

To evaluate ventricular performance and myocardial contractility after surgical correction of congenital coarctation of the aorta, we studied 25 patients (16 men and 9 women, mean age 26.1 years [range 19 to 34]), an average of 10.6 years (range 2 to 25) after repair. Radionuclide ventriculography at rest and exercise and digitized, quantitative two-dimensional echocardiography were performed. Data from derived, high resolution time-activity curves by radionuclide ventriculography, combined with noninvasive hemodynamic/ventricular volume data, were compared with values in an age- and sex-matched normal population. Despite essentially identical baseline and exercise hemodynamics, postoperative coarctation subjects demonstrated enhanced ventricular contraction, as determined by the peak ejection rate at rest (-3.79 versus -3.20 stroke volume/s, p less than 0.01) and exercise (-3.00 versus -2.90 stroke volume/s, p = NS), and overall ejection fraction at rest (56.4 versus 48.0%, p less than 0.01) and exercise (70.8 versus 59.3%, p less than 0.01). An intrinsic activation-contraction delay was observed, as illustrated by a prolonged time to peak ejection rate at rest (27.7 versus 21.5% of the RR interval, p less than 0.01) and exercise (28.4 versus 21.2% of the RR interval, p less than 0.01), and total systolic time at rest (50.2 versus 43.4% of the RR interval, p less than 0.01) and exercise (56.8 versus 50.4% of the RR interval, p less than 0.01). Although left ventricular meridinal wall stress was statistically indistinguishable (62 versus 74 mm Hg/mm2, p = NS), intrinsic myocardial contractility, as assessed by the peak systolic pressure/volume ratio, was increased in the postoperative coarctation group (1.88 versus 2.87 mm Hg/ml, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗

PubMed1986

Abnormal thallium kinetics in postoperative coarctation of the aorta: evidence for diffuse hypertension-induced vascular pathology.

After operative correction of congenital coarctation of the aorta, patients continue to have excess cardiovascular mortality, including manifestations of ischemic heart disease. Previous morphologic studies support the concept of direct hypertensive vascular injury in these patients. To determine whether abnormalities of myocardial perfusion were present in an asymptomatic group of patients with coarctation repair, 18 men and 9 women with a mean age of 26 years (range 19 to 41) were studied between 2 and 25 years after operative correction. Stress electrocardiography and quantitative thallium imaging by a circumferential profile technique were used. These patients were compared with a normal group, statistically defined as having a less than 1% prevalence of significant obstructive coronary artery disease. The postoperative coarctation group demonstrated a reduction in global thallium redistribution in each view analyzed. As compared with findings in the control subjects, thallium washout in the anterior view (41.9 versus 48.6%, p = 0.02) and left anterior oblique projection (40.5 versus 48.2%, p = 0.007) was significantly diminished. Although the postoperative coarctation group had a lower thallium redistribution rate in the lateral view (41.4 versus 46.3%, p = 0.09) this difference did not reach statistical significance because of the intrinsic variability of this projection. Plots of the median percent thallium washout revealed independence from circumferential profile angle, indicating global abnormalities in perfusion. No correlation between clinical variables and thallium kinetics could be established, suggesting marked individual variability in the development of this vascular lesion. The observation of abnormal thallium kinetics in patients with coarctation repair may have consequences for long-term follow-up and therapy.

Adult↗

PubMed1986

Late postoperative ventricular function after blood and crystalloid cardioplegia.

Although blood cardioplegia preserves perioperative ventricular function better than crystalloid cardioplegia, late results are uncertain. Nuclear ventriculograms were used to assess ventricular function in 47 patients undergoing coronary bypass surgery who were randomly assigned to receive blood (23 patients) or crystalloid cardioplegia (24 patients). Data were acquired at rest and during maximal exercise (bicycle ergometer) 1 month before surgery (PRE), 5 months after surgery (POST), and perioperatively at rest 3 to 5 hr after operation (PERI). Perioperatively, blood cardioplegia decreased ischemic injury (less elevation in creatine kinase-MB fraction and aspartate aminotransferase; p less than .05), preserved ventricular performance (lower stroke work index at higher left ventricular end-diastolic volume index after crystalloid than blood cardioplegia; p = .02 by analysis of covariance [ANOCOVA]) and preserved systolic function (higher left ventricular end-systolic volume index [LVESVI] at similar systolic blood pressure after crystalloid than blood cardioplegia; p = .02 by ANOCOVA). Postoperatively, resting ventricular performance and systolic function were not different with blood and crystalloid cardioplegia and were similar to preoperative measurements. Postoperatively, the response to exercise was similar between the two groups and was improved compared with that at PRE. Postoperative systolic function at exercise was similar between the two groups but was better than that at PRE (higher systolic blood pressure at similar LVESVI; p = .01 by ANOCOVA). The type of cardioplegic solution influenced perioperative but not late postoperative function after elective coronary artery bypass surgery.

Blood↗