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Biomedical subjects

R J Hicks

Publications and source records attributed to R J Hicks.

At least 19 recordsLinked to original sources

Nuclear medicine techniques provide unique physiologic characterization of suspected and known soft tissue and bone sarcomas.

Primary bone and soft tissue tumors have a range of physiologic, biochemical and genetic characteristics which differentiate them from benign tumors and normal tissues. These "fingerprints" are amenable to noninvasive detection and quantification using nuclear medicine techniques. Functional characterization using radiotracers imaged using a gamma camera or positron emission tomography (PET) can provide unique but complementary information to that provided by anatomically-based imaging modalities such as plain radiography, computed tomography (CT) and magnetic resonance imaging (MRI). This is particularly important following therapy when residual mass lesions may cause a dilemma regarding the need for further treatment. Lack of understanding of the role of functional imaging has impeded more rational use of nuclear medicine in this field. This review addresses the role of nuclear medicine techniques in the primary evaluation, staging, and therapeutic monitoring of soft tissue and bone sarcomas. The potential of delivering targeted radiotherapy to these tumors with radiopharmaceuticals which exploit the unique pathophysiology of each individual malignant lesion is also addressed.

Bone Neoplasms

Prediction of outcome after revascularization in patients with poor left ventricular function.

BACKGROUND: In patients with poor left ventricular function, the determinants of outcome after revascularization are unknown. METHODS: We studied prospectively 57 patients with stable coronary artery disease and poor left ventricular function (left ventricular ejection fraction, 0.28 +/- 0.04) who underwent coronary artery bypass grafting. Clinical variables were assessed as predictors of outcome in all patients, and preoperative stress thallium-201 scintigraphic data were analysed in 37 patients. RESULTS: The operative mortality was 1.7%. At 12 months after operation, 46 of the 49 survivors were angina-free and 35 had fewer heart failure symptoms, but postoperative left ventricular ejection fraction (0.30 +/- 0.09) did not change significantly. Eighteen survivors had left ventricular ejection fraction improved by 0.05 or more (0.30 +/- 0.03 preoperatively, 0.40 +/- 0.05 postoperatively; p = 0.0001). The adjusted odds ratio of large reversible thallium-201 defects in predicting such outcome was 15 (95% confidence interval, 1.6 to 140), whereas other clinical variables had no predictive value. The transplantation-free 5-year survival was 73%. CONCLUSIONS: In patients with poor left ventricular function, surgical revascularization can be performed safely, with good symptomatic relief and long-term survival. One-year survival and improvement in left ventricular function is better in patients with large reversible defects on preoperative stress thallium-201 scintigraphy.

Aged

Radiosynthesis of [123I]N-methyl-4-iododexetimide and [123I]N-methyl-4-iodolevetimide: in vitro and in vivo characterisation of binding to muscarinic receptors in the rat heart.

[123I]N-methyl-4-iododexetimide, [123I]MIDEX, and its pharmacologically inactive enantiomer [123I]N-methyl-4-iodolevetimide, [123I]MILEV were prepared via electrophilic iododesilylation using Chloramine-T as oxidising agent followed by N-methylation using methyl iodide. The radiotracers were purified with semi-preparative HPLC with radiochemical yields of 80 +/- 11% (n = 6). The average time of synthesis was 100 min with specific activity > 2000 Ci/mmol. In vitro, the binding of [123I]MIDEX, after addition of carrier, measured on homogenates of rat atrium was Bmax = 4.5 +/- 0.4 pmol/mg protein, Kd = 3.3 +/- 0.2 nM while in the ventricle Bmax = 2.3 +/- 0.2 pmol/mg protein, Kd = 4.0 +/- 1.4 nM. In vitro, the binding of [123I]MILEV was non-specific. The in vivo biodistribution of [123I]MIDEX showed high uptake in the atrium (3.2% ID/g) and left and right ventricles (2.2, 2.5% ID/g respectively) at 5 min followed by clearance. High heart-to-lung and moderate liver-to-lung ratios were obtained during 60 min. Radioactivity in the atrium and ventricles was reduced by pre-administration of the m-AChR antagonist MQNB (1 mg/kg). Pretreatment of rats with other m-AChR ligands, pirenzapine (M1), methoctramine (M2) and 4-DAMP (M3) also resulted in reduction of [123I]MIDEX uptake with methoctramine being the most potent. [123I]MIDEX distribution in the rat heart was not significantly inhibited by pre-administration of selective adrenergic drugs. The uptake was highly stereoselective since the inactive enantiomer, [123I]MILEV, demonstrated very low myocardial retention. The stability of [123I]MIDEX was evaluated by performing a metabolite study on atrium samples which revealed unchanged radiotracer 60 min postinjection. These results suggest that [123I]MIDEX may be a useful single photon agent for in vivo imaging of myocardial m-AChR in humans with [123I]MILEV offering the potential of assessing non-specific binding of the active tracer.

Animals

Impact of complementary parathyroid scintigraphy and ultrasonography on the surgical management of hyperparathyroidism.

BACKGROUND: An ongoing debate exists regarding the relative merits of full versus limited neck exploration in the surgical management of parathyroid adenomata. The aim of this study was to assess the impact of localization studies on the subsequent surgical management of hyperparathyroidism. METHODS: The accuracy of complementary ultrasonography and 201TI/99mTc parathyroid subtraction scintigraphy in hyperparathyroidism was evaluated retrospectively during a 10-year period in patients referred for localization studies. Surgical and pathologic confirmation of the diagnosis was possible in 121 patients, and these data formed the basis of this study. Operative procedure, times, outcome, and complications were recorded. RESULTS: The sensitivity, specificity, and accuracy for combined scintigraphy and ultrasonography were 86%, 98%, and 96%, respectively. Limited neck exploration was performed in 61 of 121 patients, and 60 patients underwent full neck exploration. In primary hyperparathyroidism 59 of 105 patients underwent limited and 46 underwent full neck exploration with average operative times of 70 and 109 minutes, respectively. (p < 0.0001). Complications developed in five patients who underwent full neck exploration. CONCLUSIONS: Confident localization of parathyroid adenomata facilitated successful limited neck exploration in most of the patients, questioning the need for full neck exploration in all patients with primary hyperparathyroidism.

Adenoma

Antibiotics and respiratory infections: are patients more satisfied when expectations are met?

BACKGROUND: Antibiotics are frequently prescribed for respiratory infections, even though most of these infections are viral. To understand why physicians do so, we studied patients' and physicians' expectations for antibiotics and the effects of the patient-physician interaction on patient satisfaction. METHODS: Patients with a respiratory infection were asked to complete a questionnaire before and after visiting with physicians at three family medicine centers. Physicians completed a questionnaire following the visit. RESULTS: Sixty-five percent of the 113 patients with respiratory infection expected antibiotics. Physicians had some ability to perceive this expectation and frequently prescribed antibiotics for patients who expected them. Antibiotics were prescribed to over 75% of patients with sinusitis or bronchitis and to 18% of those diagnosed with only viral infections. No association was found between a prescription for antibiotics and patient satisfaction; however, patient satisfaction did correlate with the patients' report that they understood the illness and that the physician spent enough time with them. CONCLUSIONS: Physicians frequently prescribe antibiotics for upper respiratory infections when they believe patients expect it, but receiving a prescription for antibiotics is not in and of itself associated with increased patient satisfaction.

Adolescent

Antibiotics and respiratory infections: do antibiotic prescriptions improve outcomes?

BACKGROUND AND OBJECTIVES: Antibiotics are frequently prescribed for respiratory infections though most of these infections are viral. To determine whether this practice contributes to patient health and patient satisfaction, we studied the effect of antibiotic prescriptions on outcomes at 7 to 10 days. We also studied the effect of antibiotic prescriptions upon the accuracy of patients' beliefs about viruses. METHODS: One hundred thirteen patients with a respiratory infection completed questionnaires before and after their visit with their primary care doctor. A phone interview was completed 7 to 10 days later. Questions elicited their expectations for antibiotics, their beliefs about the efficacy of antibiotics, and satisfaction with the doctor. The phone interview asked whether they felt better, whether they had returned to the doctor about the same illness, satisfaction, and whether they would expect antibiotics for the same disease in the future. The doctors provided information about their diagnosis and treatment. RESULTS: No correlation was found between prescription of antibiotics and patient satisfaction, feeling better, return physician visits, or phone calls. Receiving antibiotics increased the likelihood the patients would expect antibiotics the next time they had an upper respiratory infection and made them more likely to have an inaccurate belief, that antibiotics kill viruses. CONCLUSIONS: The study found no evidence that antibiotics improve patient outcome in upper respiratory infections by making patients feel better at 7 to 10 days. Nor did it find evidence that antibiotics help physicians by reducing return visits or increasing patient satisfaction. Doctors are invited to reconsider their policies for prescribing antibiotics for upper respiratory infection.

Adolescent

Prostate cancer screening. What family physicians believe is best.

OBJECTIVE: To determine current family physician beliefs concerning prostate cancer screening. DESIGN: Two hundred eighty-six Oklahoma family physicians were surveyed by mail. Fifty-three percent of physicians returned the questionnaire. Physicians were questioned on what tests they order for prostate screening, the reasons for ordering a serum prostate-specific antigen (PSA) test, what test results would cause a urologic referral for further evaluation of prostate cancer, and whether prostate cancer screening would decrease the patient's mortality or improve quality of life. RESULTS: Most physicians (74%) believed that both a digital rectal examination and a serum PSA determination are appropriate for prostate cancer screening. Physicians' primary reasons for ordering a PSA test were to decrease patient mortality and morbidity. Sixty-two percent of physicians believed that prostate cancer screening would decrease mortality and 69% agreed that screening would improve quality of life. Approximately 90% of physicians would refer patients with a PSA level greater than 12 micrograms/L or a PSA level of 5 micrograms/L and an indurated prostate. Significant variation was found between groups of physicians in their beliefs about prostate cancer screening. CONCLUSION: Although the literature has been inconclusive on the benefit of prostate cancer screening, the majority of Oklahoma family physicians would choose to screen their patients and believe that patients' mortality and morbidity are decreased by early identification of prostate cancer.

Adult

Iodine-123 N-methyl-4-iododexetimide: a new radioligand for single-photon emission tomographic imaging of myocardial muscarinic receptors.

Cardiac muscarinic receptor ligands suitable for positron emission tomography have previously been characterised. Attempts to develop radioligands of these receptors suitable for single-photon emission tomographic (SPET) imaging have not been successful due to high lung retention and high non-specific binding of previously investigated potential tracers. The purpose of this study was to evaluate the biodistribution and in vivo imaging characteristics of a new radiopharmaceutical, [123I]N-methyl-4-iododexetimide. Biodistribution studies performed in rats showed high cardiac uptake (2.4% ID/g) 10 min after injection with a heart to lung activity ratio of 5:1. Specificity and stereoselectivity of cardiac binding were demonstrated using blocking experiments in rats. Dynamic imaging studies in anaesthetised greyhounds demonstrated rapid and high myocardial uptake and low lung binding with stable heart to lung activity ratios of > 2.5:1 between 10 and 30 min, making SPECT imaging feasible. Administration of an excess of an unlabelled muscarinic antagonist, methyl-quinuclidinyl benzylate rapidly displaced myocardial activity to background levels and the pharmacologically inactive enantiomer, [123I]N-methyl-4-iodolevetimide, had no detectable cardiac uptake, indicating specific and stereoselective muscarinic receptor binding. SPET revealed higher activity in the inferior than in the anterior wall, this being consistent with previously described regional variation of cardiac parasympathetic innervation. [123I]N-methyl-4-iododexetimide shows promise as an imaging agent for muscarinic receptor distribution in the heart and may be helpful in evaluating diverse cardiac diseases associated with altered muscarinic receptor function, including heart failure and diabetic heart disease.

Animals

Hyperthyroidism after radiographic contrast in a patient with separate cervical and intrathoracic multinodular goiters.

The authors report a case of multinodular goiter in both cervical thyroid and aberrant intrathoracic thyroid tissue which was associated with thyrotoxicosis after the use of radiographic contrast material. The role of correlative imaging in assessment of cervical and anterior mediastinal masses and the phenomenon of iodine-induced thyrotoxicosis are also discussed.

Aged

Managing patients with benign prostatic hyperplasia.

Benign prostatic hyperplasia is the usual cause of prostatism--irritative and obstructive urinary symptoms. Steps in making the diagnosis include a focused neurologic examination, urinalysis, serum creatinine determination and, possibly, catheterization to detect urinary retention. It is difficult to predict the likelihood of future complications, such as complete urinary obstruction, even for patients with severe symptoms. The natural course of prostatism is a waxing and waning of symptoms. Treatment options are watchful waiting, medication, transurethral prostatectomy, and newer surgical treatments such as microwave thermopathy and laser ablation. The family physician can counsel patients about the potential side effects of these treatments as well as the problems incurred by simply adjusting to the disabilities associated with benign prostatic hyperplasia.

Aged

Comparison of ultrasound and blood pool scintigraphy in the diagnosis of lower limb deep venous thrombosis.

We report a prospective, blinded comparison of compression ultrasound (US) and Tc-99m erythrocyte-labelled venous blood pool scintigraphy (BPS) in patients presenting with symptoms of deep venous thrombosis (DVT). Contrast venography (CV) was used as the gold standard. Ninety-eight lower limbs of 76 patients were examined. DVT was present at CV in 38 of 98 limbs and was isolated to the calf veins in eight. Sensitivity and specificity of ultrasound for femoropopliteal thrombus were 81.5% and 96% and of venous blood pool scintigraphy were 55% and 96%. For deep venous thrombosis in the whole limb sensitivity and specificity of ultrasound were 74% and 90% and of venous blood pool scintigraphy were 61% and 88%. In the calf sensitivity and specificity of US were 61% and 94% and of venous blood pool scintigraphy were 61% and 89%. Excluding equivocal venous blood pool scintigraphy results, the predictive values of a positive and negative venous blood pool scintigraphy study for the whole limb were 84% and 86%. The predictive values of a positive and negative ultrasound where the examination was adequate were 82% and 86%. US is a more sensitive alternative to CV than BPS for femoropopliteal DVT. When neither US nor CV can be performed, BPS remains a useful initial test for DVT, provided it is unequivocally positive or negative.

Adolescent

Relation of regional function, perfusion, and metabolism in patients with advanced coronary artery disease undergoing surgical revascularization.

BACKGROUND: Imaging of myocardial glucose metabolism using [18F]fluorodeoxyglucose (FDG) with positron emission tomography (PET) has been proposed for identification of tissue viability in patients with advanced coronary artery disease. This study was designed to evaluate the predictive value of flow and metabolic imaging for functional recovery after revascularization in myocardial segments of varying degrees of dysfunction. METHODS AND RESULTS: Thirty-seven patients (mean age, 59 +/- 11 years) with coronary artery disease and impaired left ventricular function (ejection fraction, 34 +/- 10%) were studied with PET using FDG and [13N]ammonia before surgical coronary revascularization (3 +/- 1 grafts per patient). Tissue was scintigraphically characterized as normal, nonviable (concordant reduction of perfusion and FDG uptake), viable without discordance of perfusion and metabolism (mildly reduced perfusion and metabolism), or ischemically compromised (mismatch of reduced perfusion and maintained FDG uptake). Functional outcome was assessed by serial radionuclide ventriculography before and at 13 +/- 13 weeks (median interval of 8 weeks) after coronary revascularization. Preoperatively impaired regional wall motion improved significantly in ischemically compromised (mismatch) revascularized segments but not in nonviable myocardium or in viable myocardium without discordance of perfusion and metabolism. The negative predictive value of PET for functional recovery was 86%, whereas the positive predictive value in revascularized regions ranged from 48% to 86% depending on severity of baseline wall motion abnormalities. CONCLUSIONS: PET identifies metabolically active tissue, which benefits from revascularization. Although the negative predictive value of PET for recovery was high, functional improvement of viable but ischemically compromised tissue was less frequent than previously reported. The predictive value of PET was highest in left ventricular segments with severe dysfunction and a mismatch or reduced perfusion but preserved metabolism. Integration of PET, angiographic, and functional data is necessary for the optimal selection of patients with advanced coronary artery disease and impaired left ventricular function for revascularization.

Adult

Use of carbon-11 acetate and dynamic positron emission tomography to assess regional myocardial oxygen consumption in patients with acute myocardial infarction receiving thrombolysis or coronary angioplasty.

Carbon-11 (C-11) acetate has been introduced for the noninvasive measurements of myocardial oxygen consumption. This study was designed to assess regional C-11 acetate clearance in patients with acute myocardial infarction. Thirty-one patients were studied within 8 days of acute myocardial infarction. C-11 acetate washout-rate constants were significantly lower in the infarct territory than in the remote myocardium (p < 0.008). The scintigraphic measurements correlated with heart rate-blood pressure product in the remote as well as infarct areas (0.52 and 0.48, respectively). There was no significant correlation to left ventricular ejection fraction. C-11 washout rates were significantly affected by beta-receptor therapy as assessed by multiple regression analysis. Thus, C-11 acetate kinetics allow noninvasive characterization of regional myocardial oxygen demand, which may be useful in assessing the extent of myocardial injury and myocardial oxygen demand of remote myocardium.

Adult

Myocardial glucose uptake in patients with insulin-dependent diabetes mellitus assessed quantitatively by dynamic positron emission tomography.

BACKGROUND: Animal studies have demonstrated reduced myocardial glucose utilization in the diabetic heart, suggesting abnormalities in glucose transport. This study was designed to evaluate myocardial glucose uptake as assessed by 2-fluoro-(fluorine-18)2-deoxy-D-glucose (FDG) and positron emission tomography (PET) in patients with insulin-dependent diabetes mellitus (IDDM) under standardized metabolic conditions. METHODS AND RESULTS: A hyperinsulinemic-euglycemic clamp technique was used during PET data acquisition in nine healthy male volunteers and seven young male patients with a history of IDDM for less than 5 years. Oxidative metabolism was assessed with C-11 acetate, and glucose uptake was quantitatively measured with FDG using Patlak graphic analysis. Hemodynamic data and C-11 acetate kinetics were comparable. Myocardial glucose uptake averaged 0.44 +/- 0.12 mumol.g-1.min-1 in normal subjects and 0.43 +/- 0.16 mumol.g-1.min-1 in patients with IDDM (P = NS). Blood tracer clearance was also similar in both groups as determined by the ratio of peak blood tracer activity to the activity at 55 to 60 minutes after tracer injection. F-18 activity ratio between myocardium and blood pool averaged 7.2 +/- 3.4 in the normal heart and 7.5 +/- 3.0 in the diabetic heart (P = NS). CONCLUSIONS: These data indicate that metabolic standardization and supplementation with insulin in young patients with IDDM is associated with myocardial glucose uptake similar to that observed in the normal heart. Chronic therapy with insulin may prevent the metabolic abnormalities observed in diabetic animal models.

Acetates