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Biomedical subjects

G J Bautovich

Publications and source records attributed to G J Bautovich.

At least 19 recordsLinked to original sources
PubMed1998

Optimized acquisition time and image sampling for dynamic SPECT of Tl-201.

With the recent development in scatter and attenuation correction algorithms, dynamic single photon emission computerized tomography (SPECT) can potentially yield physiological parameters, with tracers exhibiting suitable kinetics such as thallium-201 (Tl-201). A systematic way is proposed to investigate the minimum data acquisition times and sampling requirements for estimating physiological parameters with quantitative dynamic SPECT. Two different sampling schemes were investigated with Monte Carlo simulations: 1) Continuous data collection for total study duration ranging from 30-240 min. 2) Continuous data collection for first 10-45 min followed by a delayed study at approximately 3 h. Tissue time activity curves with realistic noise were generated from a mean plasma time activity curve and rate constants (K1 - k4) derived from Tl-201 kinetic studies in 16 dogs. Full dynamic sampling schedules (DynSS) were compared to optimum sampling schedules (OSS). We found that OSS can reliably estimate the blood flow related K1 and Vd comparable to DynSS. A 30-min continuous collection was sufficient if only K1 was of interest. A split session schedule of a 30-min dynamic followed by a static study at 3 h allowed reliable estimation of both K1 and Vd avoiding the need for a prolonged (>60-min) continuous dynamic acquisition. The methodology developed should also be applicable to optimizing sampling schedules for other SPECT tracers.

Animals↗
PubMed1997

Effect of increasing doses of hypertonic saline on mucociliary clearance in patients with cystic fibrosis.

BACKGROUND: Patients with cystic fibrosis are known to have decreased mucociliary clearance. It has previously been shown that inhalation of a 7.0% solution of hypertonic saline significantly improved mucociliary clearance in a group of adult patients with cystic fibrosis. The aim of this study was to measure the response to increasing concentrations of inhaled hypertonic saline. METHODS: Ten patients (seven men) of mean (SE) age 22 (4) years and mean forced expiratory volume in one second (FEV1) 52.0 (6.7)% predicted completed the study. Mucociliary clearance was measured using a radioaerosol technique for 90 minutes after the interventions which comprised 0.9% NaCl + voluntary cough (control), 3.0% NaCl, 7.0% NaCl, and 12% NaCl. RESULTS: There was a significant increase in the amount of activity cleared from the right lung with all concentrations of hypertonic saline (HS) compared with control. The amount cleared at 90 minutes on the control day was 12.7% (95% confidence interval (CI) 9.8 to 17.2) compared with 19.7% (95% CI 13.6 to 29.5) for 3% HS, 23.8% (95% CI 15.9 to 36.7) for 7% HS and 26.0% (95% CI 19.8 to 35.9) for 12% HS. The improvement in mucociliary clearance was not solely due to coughing as the number of coughs recorded on the control day exceeded that recorded on any other day. The hypertonic saline did not induce a clinically significant change in FEV1. CONCLUSIONS: Within the range of concentrations examined in this study, the effect of hypertonic saline appears to be dose dependent. Inhalation of hypertonic saline remains a potentially useful treatment for patients with cystic fibrosis.

Administration, Inhalation↗
PubMed1996

Detection of malignant tumors using Tc-99m labeled Fab' fragments from a monoclonal antibody with specificity for D-dimer of cross-linked fibrin.

The authors present the case studies of two patients whose malignant tumors were detected with a Tc-99m labeled antifibrin monoclonal antibody (DD-3B6/22), which is specific for cross-linked fibrin. The first case was a malignant fibrous histiocytoma involving the proximal aspect of the left thigh, whereas in the second case, the patient was receiving treatment for a squamous cell carcinoma of the right mainstem bronchus. The results highlight the potential of this anti-D-dimer radiopharmaceutical for noninvasive detection of malignant tumors.

Aged↗
PubMed1996

Effect of hypertonic saline, amiloride, and cough on mucociliary clearance in patients with cystic fibrosis.

In patients with cystic fibrosis (CF), dehydration of airway secretions leads to a decrease in mucociliary clearance (MCC). We examined the acute effect of MCC of a single administration by aerosolization of hypertonic saline (7%) (HS), amiloride (0.3% in 0.12% NaCl) (AML) and a combination of AML and HS (AML + HS) in 12 patients with CF using a radioaerosol technique. Isotonic saline [0.9%] (IS) was used as a control solution. As both the AML and HS solutions induced cough in some patients, the last nine patients studied also underwent a cough clearance day. This was to eliminate the possible confounding effect of cough on MCC measurement. Patients ranged from 18 to 28 yr (mean +/- SD, 22 +/- 3) with an FEV1 of 27 to 112% predicted (61 +/- 30%). Following deposition of the radioaerosol, baseline clearance was assessed for 30 min. This was followed by a 30-min intervention period. Assessment of post-intervention clearance for a further 30 min was then performed. Comparison of the amount of radioaerosol cleared from the right lung was made at 60 min (%C60) and 90 min (%C90) using repeated measures ANOVA. The percent cleared at 60 and 90 min was significantly increased with HS (%C60 = 26.5%, %C90 = 29.4%) and the combination of AML + HS (%C60 = 23.1%, %C90 = 27.4%) compared with both IS (%C60 = 14.7%, %C90 = 17.5%) and COUGH (%C60 = 18.0%, %C90 = 19.5%), p < 0.01. Inhalation of hypertonic saline is a potentially useful treatment in patients with cystic fibrosis.

Adolescent↗
PubMed1992

Evaluation of thrombus detection in a rabbit model using a technetium-99m-labelled anti-fibrin monoclonal antibody.

Technetium-99 m (99mTc)-labelled conjugates of an anti-fibrin monoclonal antibody, DD-3B6/22, have been assessed for their detection of vascular thrombi in a rabbit model. DD-3B6/22 binds to a D-dimer epitope present on cross-linked fibrin but absent from the fibrin monomer or fibrinogen. Injection of a 99mTc-labelled Fab' fragment of DD-3B6/22 allowed delineation of model thrombi as early as 30 min postinjection (p.i.) with optimal localization at 4-5 h. Thrombus label uptake at 4 h p.i. was 0.304 +/- 0.106% injected dose/g (% ID/g) compared with 0.022 +/- 0.001% ID/g after the injection of a control Fab' fragment. These results suggest that the 99mTc-labelled Fab' fragment of DD-3B6/22 has excellent potential for scintigraphic detection of vascular thrombi in humans.

Animals↗
PubMed1991

Preclinical evaluation of 99m technetium-labeled DD-3B6/22 Fab' for thrombus detection.

Injection of 99mTc-labeled Fab' fragments of the anti-fibrin antibody DD-3B6/22, in the baboon, resulted in clear visualisation of both fresh and aged autologous thrombi by gamma scintigraphy. Whole body scintigraphy, pharmacokinetics and urine analysis showed rapid renal excretion of the conjugate with little accumulation of label in other organs. 99mTc-DD-3B6/22 Fab' appears a suitable candidate for further investigation as a radioimaging agent for thrombi in humans.

Animals↗
PubMed1990

Detection of experimental thrombi in rabbits with an 131I-labelled fibrin-specific monoclonal antibody.

The detection of thrombi in rabbits has been investigated with 131I-labelled DD-3B6/22, a monoclonal antibody (Mab) reactive at high affinity (Kd = 2.68 x 10(-10) M) with human D Dimer (DD). DD-3B6/22 bound well to both "fresh" and "aged" human clots in an in vitro assay but showed poor binding to rabbit clots. However, reactivity was restored to rabbit blood if it was seeded, before clotting, with human DD covalently coupled to Sepharose beads. Thus, a rabbit model was developed in which blood was allowed to clot around DD-Sepharose beads introduced into the jugular vein. Gamma camera imaging showed that intact 131I-labelled DD-3B6/22 localised to these clots within 24 h. Uptake at this time was 0.202 +/- 0.012% injected dose per gram (%ID/g) compared with 0.086 +/- 0.018%ID/g after injection of control antibody. 131I-labelled F(ab')2 fragments of DD-3B6/22 allowed earlier scintigraphic detection of the clot which was evident 4 h after injection. Uptake in the clot at 24 h was 0.154 +/- 0.038 %ID/g compared with 0.109 +/- 0.027 %ID/g for a control F(ab')2. As antigen levels in the clot are estimated to be less than 300 micrograms DD, thus representing a very small human clot, the DD-3B6/22 Mab would appear to have a good potential for the sensitive detection of thrombi in a clinical setting.

Animals↗
PubMed1990

Current role of gallium scanning in the management of lymphoma.

Gallium 67 scanning in the malignant lymphomas has been done, with variable success, for over 20 years. After initial enthusiasm, the technique fell into disrepute and it was not until the early 1980s that it enjoyed a revival. There have been many major contributions to the literature, both favourable and unfavourable. The reasons for the latter include: poor instrumentation (only single-pulse height analysis), low gallium 67 doses, impatient and careless scanning techniques, timing of the study after treatment (chemotherapy, radiation) and insensitive methods of confirmation of the presence or absence of disease ("truth"). Anatomical diagnostic techniques (computed tomography, plain X-radiography, magnetic resonance imaging and others) are incapable of distinguishing viable tumour in normal-size lymph nodes or necrotic/fibrotic residual masses. With improvements in instrumentation (triple-pulse height analysis, gamma camera resolution and tomographic techniques) gallium 67 can detect active tumour in residual masses and in normal-size nodes. This is due to gallium 67's unique ability to localize in viable tumour cells. It has greater than 90% sensitivity, specificity, accuracy and positive predictive value in patients with lymphoma. Its major contributions are in: staging (changing management of mediastinal disease, obviating the need for a laparotomy and clearly identifying stage IV disease); detecting relapse or residual, progressive disease (it establishes true complete remission and is often the first and only evidence of relapse before clinical evidence); predicting response to therapy (failure to convert to a negative scan post-treatment signals a poor prognosis and alternative therapy is required); and predicting outcome--prognosis (it is the only diagnostic modality to predict outcome accurately).

Gallium Radioisotopes↗
PubMed1990

Tc-99m white cell scintigraphy in suspected acute infection.

The usefulness of In-111 labeled white cells in acute infection is well documented but the role of Tc-99m labeled white cell scintigraphy (WCS) has not been as clearly established. Using stannous fluoride colloid and a simple labelling procedure with 20 ml of autologous whole blood, three cases are presented in which Tc-99m WCS established unexpected diagnoses in patients who had remained undiagnosed despite extensive investigation.

Acute Disease↗
PubMed1989

Comparison of doxazosin and atenolol in mild hypertension, and effects on exercise capacity, hemodynamics and left ventricular function.

The effects of once-daily therapy with doxazosin (1 to 8 mg/day) on exercise capacity, left ventricular performance and hemodynamics (radionuclide ventriculography) were compared with those of atenolol (50 to 100 mg/day) and placebo in a randomized, double-blind crossover trial in 16 patients (9 men) with mild hypertension. Both medications controlled blood pressure (BP) to a similar degree (mean BP was 150 +/- 12, 137 +/- 17 and 141 +/- 14 mm Hg for placebo, atenolol and doxazosin, respectively) but by different mechanisms. Changes during maximal semierect bicycle exercise were similar to those seen at rest. Doxazosin decreased total peripheral resistance and maintained cardiac output, whereas atenolol decreased cardiac output. Exercise capacity (136 +/- 56 watts with placebo) was maintained by doxazosin (135 +/- 56 watts) but decreased with atenolol (122 +/- 55 watts). Compared with atenolol, doxazosin slightly increased the left ventricular ejection fraction at rest and during exercise. The significance of this study is in the choice of a first-line antihypertensive agent. Both are once-a-day medications that control BP. However, doxazosin does so by improving the abnormal physiology of essential hypertension and, consequently, does not adversely affect exercise performance.

Antihypertensive Agents↗
PubMed1989

Normalised radionuclide measures of left ventricular diastolic function.

Abnormal left ventricular diastolic function is being increasingly recognised in patients with clinical heart failure and normal systolic function. A simple routine radionuclide measure of diastolic function would therefore be useful. To establish this, the relationship of peak diastolic filling rate (normalized for either end diastolic volume, stroke volume, or peak systolic emptying rate), and heart rate, age, and left ventricular ejection fraction was studied in 64 subjects with normal cardiovascular systems using routine gated heart pool studies. The peak filling rate, when normalized to end diastolic volume, correlated significantly with heart rate, age and left ventricular ejection fraction, whereas normalization to stroke volume correlated significantly to heart rate and age but not to left ventricular ejection fraction. Peak filling rate normalized for peak systolic emptying rate correlated with age only. Multiple regression equations were determined for each of the normalized peak filling rates in order to establish normal ranges for each parameter. When using peak filling rate normalized for end diastolic volume or stroke volume, appropriate allowance must be made for heart rate, age and ejection fraction. Peak filling rate normalized to peak ejection rate is a heart rate independent parameter which allows the performance of the patient's ventricle in diastole to be compared with its systolic function. It may be used in patients with normal systolic function to serially follow diastolic function or if age corrected, to screen for diastolic dysfunction.

Adolescent↗
PubMed1989

The effect of circulating antigen on radioimmunodetection and monoclonal antibody localisation: studies in a normal rat model.

The effect of circulating antigen (human kappa light chains (LC] on radioimmunoscintigraphy was examined in a normal rat model. Rats were implanted subcutaneously with kappa (test) and lambda (control) LC coupled to sepharose beads (500 micrograms LC/ml swollen gel). When 131I-labelled monoclonal antibody, K-1-21 was injected, clear images of specific antibody localisation to the kappa implant were seen 6 days later. The kappa implant: blood ratio (K:B) was 7.69 +/- 0.45, which represented an implant uptake of 2.52 +/- 0.20 percent injected dose per gram (%ID/g). When 131I-K-1-21 was preincubated with 125I-kappa LC at ratios of up to 1:10 antibody: antigen, (w/w) before injection; or if antigen was given daily by bolus injection or continuously infused via an osmotic pump, very clear specific images of antibody localisation to the kappa implant were still obtained. There was, however, a decline in the absolute uptake of label by the kappa implant. The greatest change was observed following continuous antigen infusion, when kappa implant uptake fell to 1.26 +/- 0.1 %ID/g. Nevertheless, the K:B ratio was still maintained at 6.8 +/- 0.2, due to increased clearance of antibody from the blood. Thus, in this case, where antigen and antibody might be expected to form small, soluble immune complexes, there was no major deleterious effect on radioimmunoscintigraphy.

Animals↗
PubMed1989

Comparison of the effects of nifedipine and nitroglycerin on hemodynamic determinants of myocardial oxygen consumption and supply during exertional angina.

To investigate the antianginal action of nitroglycerin and nifedipine, systemic and right heart pressures, cardiac output, oxygen consumption, and radionuclide left ventricular ejection fraction and volume were measured in 14 men with stable effort angina and a positive exercise electrocardiogram. Exercise tests were performed on a semiupright bicycle ergometer on no therapy and after intravenous nitroglycerin and sublingual nifedipine, which lowered mean arterial pressure by 20 mm Hg. Exercise tolerance improved from 50 +/- 4 to 61 +/- 5 W on nifedipine and to 79 +/- 4 W on nitroglycerin (p less than 0.01, nitroglycerin vs. nifedipine). At submaximal workloads, both drugs decreased arterial pressure and ventricular volumes, but heart rate was higher on nifedipine. At peak exercise on nitroglycerin (79 W), oxygen consumption, cardiac index, heart rate, and rate-pressure product were significantly increased over peak control and nifedipine values, while systolic pressure and end-diastolic volume were unchanged. Nitroglycerin reduced pulmonary wedge pressure more and systemic diastolic pressure less than nifedipine, so the coronary perfusion gradient was reduced by nifedipine and maintained by nitroglycerin. Also, there was less angina and ST-segment depression after nitroglycerin compared to control or nifedipine, and the left ventricular diastolic pressure-volume relationship was improved only by nitroglycerin. This suggests that the action of nitroglycerin in reducing ischemia is not only due to reduced myocardial oxygen demand, but that myocardial oxygen delivery may also be increased.

Adult↗
PubMed1988

Anti-fibrin monoclonal antibodies for radioimmunodetection: preliminary assessment in a rat model system.

The D Dimer (DD) site formed by linkage of D domains from adjacent fibrin (FN) molecules is unique to cross-linked FN and its degradation products and is not found in FN monomer or fibrinogen (FB). Thus monoclonal antibodies (MAb) reactive to DD should have a very suitable specificity for in vivo thrombus detection. Two anti-DD MAbs have been labelled with 131-I and assessed as scintigraphic agents in a normal rat model system. Each rat received 3 sc implants of antigen covalently coupled to Sepharose beads: 1) Human DD 2) Human FB 3) Glycine (GL) (control). Scintigraphic images taken 7 days after injection of 131-I anti DD MAb showed clear localisation of both anti-DD MAbs to the DD implant rather than to the FB or GL implants with no localisation in normal tissues. This was confirmed in biodistribution studies. Injection of anti-DD MAbs DD-3B6/22 and DD-IC3/108 resulted in DD: blood ratios of 10.4 +/- 0.6 and 4.9 +/- 0.3 respectively. These results suggest that anti-DD MAbs will have potential for thrombus radioimmunodetection.

Animals↗
PubMed1988

The role of nuclear medicine in liver transplantation.

The role of hepatobiliary isotopic scanning after liver transplantation was assessed in the first 12 adult patients in the Pilot National Liver Transplantation Programme who underwent this procedure at the Royal Prince Alfred Hospital. Iminodiacetic-acid derivative (HIDA) studies were useful in the non-invasive assessment of hepatic function and biliary excretion. The following four clinical situations were assessed by hepatobiliary scans: early graft function; rejection episodes; vascular complications; and biliary-tract problems. Nuclear medicine has an important and valuable role in the postoperative monitoring of patients after liver transplantation. The studies are non-invasive and can be performed readily at the bedside in the intensive care unit.

Adolescent↗
PubMed1987

Antianginal effects of nitroglycerin during exercise-induced angina: hemodynamic and left ventricular function changes related to indexes of myocardial oxygen consumption.

In 14 patients during exercise, intravenous nitroglycerin improved anginal threshold and increased workload compared with control subjects. At similar workloads, the decreased left ventricular volumes suggested decreased myocardial oxygen consumption due to peripheral unloading. At maximal exercise with nitroglycerin (50 +/- 17 to 79 +/- 15 watts), rate-pressure product and end-diastolic volumes were higher with less ischemia, suggesting myocardial supply was improved by nitroglycerin.

Angina Pectoris↗