Biomedical subjects

R E Coleman

Publications and source records attributed to R E Coleman.

At least 19 recordsLinked to original sources

PubMed1992

Glucocorticoids in cancer therapy.

Glucocorticoids are often included with other agents in cancer treatment although the mode of action is not clear. They are useful in the primary combination chemotherapy of both acute and chronic lymphocytic leukaemias, Hodgkin's and non-Hodgkin's lymphomas, multiple myeloma and breast cancer. Other uses for glucocorticoids in cancer patients include an anti-inflammatory action for the oedema of cranial and spinal metastases, a weak antihypercalcaemic effect and the ability to suppress tumour-related fever.

Breast Neoplasms↗

PubMed1992

The future of positron emission tomography in clinical medicine and the impact of drug regulation.

Positron emission tomography (PET) was initially developed as a research tool for evaluating normal and abnormal physiology. Subsequently, the potential clinical utility of PET was recognized, and several specific clinical indications have been defined. PET has been demonstrated to be clinically useful in evaluating certain disorders of the brain and heart. PET holds significant promise for use in the evaluation of psychiatric illness and in multiple aspects of evaluation of malignancy. A major limiting factor for the growth of clinical PET is the absence of policies for reimbursement by third-party payers. Although rubidium-82 chloride is approved by the Food and Drug Administration (FDA), the lack of FDA approval of fluorine-18 2-fluoro-2-deoxyglucose (FDG) is hampering reimbursement for PET studies. The jurisdiction of the FDA over cyclotron-produced PET radiopharmaceuticals synthesized and used on site is a matter of debate because these drugs are not introduced into interstate commerce and because these activities appear to be permissible under certain exemptions in the Federal Food, Drug, and Cosmetic Act relating to the practices of medicine and pharmacy. The jurisdictional authority of the FDA in regulating these radiopharmaceuticals would be established with certainty only through litigation, but no individual or organization has elected to challenge the FDA at this time. The Institute for Clinical PET (ICP) is developing a Drug Master File that can be used in support of site-specific New Drug Applications (NDAs) for cyclotron-produced radiopharmaceuticals by any organization desiring an NDA. The ICP is optimistic that this method of obtaining FDA-approval of FDG and other cyclotron-produced PET radiopharmaceuticals will be successful and beneficial to sites using PET clinically.

Forecasting↗

PubMed1992

Clinical PET scanning. A "short-lived" orphan.

Positron emission tomography (PET) is a method of nuclear medicine imaging that uses short-lived radiopharmaceuticals to detect and quantify the metabolic abnormalities of disease processes. PET initially was developed in a research environment as a research tool; data from these research studies resulted in the gradual recognition that PET studies would be useful for various routine clinical applications. The diffusion of PET into clinical practice has been slow in comparison with other new imaging methods (e.g., magnetic resonance imaging). This slow diffusion is attributable to several factors, including the complexity and high cost of PET, the uncertain role of the U.S. Food and Drug Administration in regulating the radiopharmaceuticals that are produced and used on-site for PET studies, and the apparent slow pace at which the Health Care Financing Administration and other third-party payers are developing policies for reimbursing for PET.

Centers for Medicare and Medicaid Services, U.S.↗

PubMed1992

Preliminary results of the use of urinary excretion of pyridinium crosslinks for monitoring metastatic bone disease.

The collagen crosslinks, pyridinoline and deoxypyridinoline, are recently described markers of the rate of bone resorption. The urinary excretion of these compounds, expressed as a ratio to urinary creatinine, has been measured using ion-pair reversed phase high-performance liquid chromatography in 20 patients receiving oral pamidronate for bone metastases from breast cancer. Before treatment the ratio of pyridinoline and deoxypyridinoline to creatinine in urine (UPCR and UdPCR respectively) were each above normal in 16/20 (80%) patients. Urinary calcium excretion (UCCR) was elevated in 15/20 (75%). There was a strong correlation between UPCR and UdPCR, but neither of the crosslink measurements correlated well with UCCR. Urinary excretion of all three indices of bone resorption fell significantly during pamidronate treatment. The median values after 4 weeks treatment were 63% of baseline for UPCR, 45% for UdPCR and 26% for UCCR. From this preliminary study urinary pyridinoline and deoxypyridinoline excretion appear to be promising markers of bone resorption in advanced malignancy. Their role in response assessment and the advantages over UCCR measurements merit further study.

Administration, Oral↗

PubMed1992

Three-dimensional SPECT reconstruction of combined cone beam and parallel beam data.

Single photon emission computed tomography (SPECT) using cone beam (CB) collimation exhibits increased sensitivity compared with acquisition geometries using parallel (P) hole collimation. However, CB collimation has a smaller field-of-view which may result in truncated projections and image artifacts. A primary objective of this work is to investigate maximum likelihood-expectation maximization (ML-EM) methods to reconstruct simultaneously acquired parallel and cone beam (P&CB) SPECT data. Simultaneous P&CB acquisition can be performed with commercially available triple camera systems by using two cone-beam collimators and a single parallel-hole collimator. The loss in overall sensitivity (relative to the use of three CB collimators) is about 15 to 20%. We have developed three methods to combine P&CB data using modified ML-EM algorithms. The first method consists of using both data sets to reconstruct a single intermediate image after each iteration using the ML-EM algorithm. The other two iterative algorithms combine intermediate parallel beam (PB) and CB source estimates to enhance image quality. For these methods, a PB estimate and a CB estimate are obtained for the first iteration. The second method consists of summing the PB and CB estimates for each subsequent iteration to obtain new PB and CB estimates. The third method is similar to the second method, with the exception that the new PB estimate simply is set equal to the PB estimate after each iteration. The combined source estimate is used in each subsequent iteration step of the EM algorithm. These algorithms are evaluated using projection data simulated using a Monte Carlo SPECT model. The P&CB SPECT images demonstrate marked improvement as compared with the CB-only reconstruction, particularly when the projections are truncated.

Algorithms↗

PubMed1992

Simultaneous compensation for attenuation, scatter and detector response for SPECT reconstruction in three dimensions.

A three-dimensional reconstruction method for simultaneous compensation of attenuation, scatter and distance-dependent detector response for single photon emission computed tomography is described and tested by experimental studies. The method determines the attenuation factors recursively along each projection ray starting at the intersected source voxel closest to the detector. The method substracts the scatter energy window data from the primary energy window data for scatter compensation. The detector response is modelled to be spatially invariant at a constant distance from the detector. The method convolves source distribution with the modelled response function to compensate for the smoothed by use of a non-uniform entropy prior to searching for the maximum a posteriori probability solution. The method was tested using projections acquired from a chest phantom by a three-headed detector system with parallel hole collimators. An improvement was shown in image noise, recognition of object sizes and shapes, and quantification of concentration ratios.

Image Processing, Computer-Assisted↗

PubMed1992

Three-dimensional photon detection kernels and their application to SPECT reconstruction.

In single photon emission computed tomography (SPECT), three-dimensional photon detection kernels characterize the probabilities that photons emitted by radio-isotopes in different parts of the source region will be detected at particular projection pixels of the projection images. Monte Carlo modelling is used to study these kernels for the case of parallel hole collimators. The use of vectorized Monte Carlo computer code speeds the modelling computations. The contributions of direct and scattered photons to projection data in a transverse plane from neighbouring planes are significant for the case of uniform activity within a water-filled cylinder. A reconstruction method using the 3D kernels is proposed in which projection measurements in three adjacent planes are used simultaneously to estimate the source activity of the center plane. This multiple slice method accounts for the fact that photons detected in a given transverse plane may have originated in other transverse planes with different activity distributions. The matrix equations for image reconstruction are solved using generalized matrix inverses. The new method shows compensation for 3D photon detection effects when applied to projection data from a numerical simulation and a cardiac phantom experiment. Quantitation for the numerical study is improved compared with results from a single slice reconstruction method.

Heart↗

PubMed1992

Laboratory and field evaluation of five repellents against the black flies Prosimulium mixtum and P. fuscum (Diptera: Simuliidae).

Deet (N,N-diethyl-3-methyl-benzamide), the lactone CIC-4 ([2-hydroxy-methyl-cyclohexyl] acetic acid lactone), the USDA Proprietary Chemicals AI3-37220 (1- [3-cyclohexen-1-ylcarbonyl]-2-methylpiperidine) and ++[3-35765 (1-[3-cyclohexen-1-ylcarbonyl] piperidine), and the U.S. military extended duration repellent formulation (EDRF) of deet were evaluated for repellency in the laboratory and field against the black flies Prosimulium mixtum and P. fuscum. CIC-4, AI3-37220, and AI3-35765 were as effective as deet at repelling P. mixtum and P. fuscum in laboratory and field experiments. Only the EDRF provided significantly longer protection than the deet standard against these black flies in the field.

Animals↗

PubMed1992

Perfusion quantitation using positron emission tomography.

Positron emission tomography (PET) is assuming increasing importance as a clinical and investigative functional imaging modality. Cerebral blood flow determination with PET is now more easily performed due to improvement in tomography design, increased speed and ease of data analysis, and improvement in radiopharmaceutical synthesis and delivery. This article reviews the historic development of the PET, the evolution of cerebral blood flow measurement techniques with PET, technical considerations in PET imaging, radiopharmaceuticals for cerebral blood flow determination, and tracer kinetic models used for cerebral blood flow determination. Representative examples of PET cerebral blood flow imaging are shown and the evolving applications to brain mapping are discussed.

Animals↗

PubMed1992

Gametocytocidal and sporontocidal activity of antimalarials against Plasmodium berghei ANKA in ICR Mice and Anopheles stephensi mosquitoes.

The gametocytocidal and sporontocidal activity of three 8-aminoquinolines (primaquine, WR-238605, and WR-242511), three dihydroacridine-diones (floxacrine, WR-250547, and WR-250548), a 1,4-naphthoquinone (menoctone), a synthetic aminoalcohol (halofantrine), and a guanide (WR-182393) was determined against a cloned line of Plasmodium berghei ANKA. Gametocytocidal activity was assessed by treating mice with a single intraperitoneal inoculation of a given compound (25 mg base drug/kg mouse body weight) four days after the mice were infected with P. berghei. Thin blood smears were made every other day, and the percent parasitemia and macrogametocyte and microgametocyte rates were determined. Floxacrine, menoctone, WR-242511, WR-250547, and WR-250548 effectively cleared sexual and asexual parasites from the peripheral circulation within six days of drug administration. Halofantrine, primaquine, WR-182393, and WR-238605 were ineffective at clearing P. berghei ANKA from circulating erythrocytes at the doses tested; however, mice survival time increased markedly with these compounds when compared with the controls. Significant numbers of macrogametocytes and microgametocytes were present throughout the duration of the infection in mice treated with halofantrine, primaquine, WR-182393, and WR-238605. Sporontocidal activity was evaluated by allowing Anopheles stephensi mosquitoes to feed on P. berghei-infected mice 90 min after treatment with a particular drug. Halofantrine and WR-182393 exhibited no sporontocidal activity, while floxacrine, menoctone, primaquine, WR-238605, WR-242511, WR-250547, and WR-250548 exhibited significant activity. Minimum effective doses (mg base drug/kg of mouse body weight) that prevented mosquitoes from developing sporozoite-infected salivary glands were 0.1563 mg/kg for WR-250547, 0.625 mg/kg for menoctone, 1.25 mg/kg for primaquine, 10 mg/kg for floxacrine, 10 mg/kg for WR-242511, 10 mg/kg for WR-250548, and 25 mg/kg for WR-238605.

Acridines↗

PubMed1992

Studies of primary central nervous system lymphoma with fluorine-18-fluorodeoxyglucose positron emission tomography.

Primary CNS lymphoma is a rare and highly malignant primary brain tumor. Ten patients with biopsy-proven primary CNS lymphoma were studied with 18F-2-fluoro-2-deoxy-D-glucose (FDG) and positron emission tomography (PET) to demonstrate the findings in patients with this tumor. The accumulation of FDG in primary CNS lymphoma is similar to that seen in anaplastic gliomas and is significantly more prominent than in low grade astrocytomas (p = 0.001). Steroid therapy substantially reduced the amount of FDG uptake in the one case studied both before and after its administration. The difference in FDG uptake between steroid-treated and untreated cases of primary CNS lymphoma, however, did not reach statistical significance (p = 0.40). Primary CNS lymphoma, like gliomas, suppresses the metabolism of both contiguous and distant but functionally linked areas of the brain. This study thus shows that the metabolic behavior of primary CNS lymphoma, as monitored by FDG-PET, resembles that of malignant glial tumors.

Adult↗

PubMed1992

Fluorine-18-antimyosin monoclonal antibody fragments: preliminary investigations in a canine myocardial infarct model.

The purpose of this study was to determine in a canine model whether selective myocardial infarct uptake of 18F-labeled antimyosin monoclonal antibody fragments could be achieved in a time frame compatible with the short half-life of this nuclide. Antimyosin monoclonal antibody fragments were labeled with 18F using a succinimidyl [18F]fluorobenzylamine ester acylation agent. Six dogs had myocardial infarction induced by coronary artery occlusion and were reperfused prior to the intravenous administration of 0.6-4.7 mCi of 18F-labeled F(ab')2 (two dogs) or Fab (four dogs). Analysis of tissues obtained 2-4 hr after antibody administration revealed infarct:normal myocardium uptake ratios as high as 14-21:1 for F(ab')2 and 9-12:1 for Fab. Even with Fab, however, prolonged 18F activity in the blood pool interfered with delineation of infarcts by PET imaging. In one dog, perfusion imaging with [13N]ammonia before antimyosin administration was performed, and regions of normal and ischemic myocardium were determined. With these regions of interest, infarct:normal myocardium uptake ratios calculated from the 18F-labeled Fab images increased from 1.5:1 at 1 hr to 4.0:1 at 5 hr. We conclude that 18F-labeled antimyosin fragments may be of value for hot-spot imaging of damaged myocardium with PET; however, blood-pool subtraction techniques will probably be required.

Animals↗

PubMed1992

Advanced breast cancer in Egyptian women: clinical features and response to endocrine therapy. The Anglo-Egyptian Health Agreement Collaborative Study.

Response to endocrine therapy and its relationship to the clinical features of the disease were studied in 84 Egyptian patients with inoperable, locally advanced or metastatic breast cancer. Twenty-four premenopausal patients were treated by oophorectomy with or without concurrent prednisolone. Only one of 20 evaluable patients achieved an objective response. Median time to progression for premenopausal patients was 3 months. Sixty postmenopausal patients received tamoxifen 10 mg twice daily either alone or with prednisolone. Fourteen of 57 (25%) evaluable patients achieved an objective response (four complete remission, 10 partial remission). Median duration of response was 13 months and median time to progression for all postmenopausal patients was 5 months (range 1-30 months). The outcome for postmenopausal patients was similar to that found in a parallel study at Guy's Hospital, London. The response rate for premenopausal Egyptian patients was, however, disappointing and lends support to the claim that breast cancer in Egyptian women is particularly aggressive.

Adult↗

PubMed1991

Does dexamethasone enhance control of acute cisplatin induced emesis by ondansetron?

OBJECTIVE: To determine the contribution of dexamethasone to the efficacy of the 5-hydroxytryptamine antagonist ondansetron in control of cisplatin induced nausea and vomiting. DESIGN: Randomised double blind crossover study. SETTING: Two cancer centres in teaching hospitals, one in the United Kingdom and the other in Germany. SUBJECTS: 100 patients (53 men and 47 women) new to cisplatin chemotherapy, 84 of whom completed two consecutive courses of chemotherapy. INTERVENTIONS: Patients were given intravenous dexamethasone (20 mg) or physiological saline with intravenous ondansetron 8 mg before cisplatin, then ondansetron 1 mg/h for 24 hours. Oral ondansetron 8 mg was taken three times daily on days 2-6. MAIN OUTCOME MEASURES: Incidence of complete or major control of emesis (0-2 episodes in the 24 hours after chemotherapy). RESULTS: Complete or major control was obtained in 49 out of 71 (69%) of patients after receiving ondansetron plus dexamethasone compared with 40 out of 71 (56%) when they were given ondansetron alone (p = 0.012). This effect was most pronounced in the first 12 hours after chemotherapy. Patients receiving the combination also had significantly less nausea. Of the 53 patients who expressed a preference, 38 (72%) preferred the combination treatment (p = 0.002) to ondansetron alone. The effect of ondansetron on delayed emesis was less pronounced. CONCLUSIONS: Dexamethasone makes a significant contribution to the efficacy of ondansetron in the control of acute platinum induced emesis.

Acute Disease↗

PubMed1991

Effects of exercise training on cardiorespiratory function in men and women older than 60 years of age.

This study reports the physiologic effects of up to 14 months of aerobic exercise in 101 older (greater than 60 years) men and women. After an extensive baseline physiologic assessment (Time 1), in which aerobic capacity and blood lipids were measured, subjects were randomized to an aerobic exercise condition (cycle ergometry, 3 times per week for 1 hour), nonaerobic yoga (2 times per week for 1 hour), or a waiting list nonexercise control group for 4 months, and then underwent a second (Time 2) assessment. At the completion of the second assessment, all remaining subjects completed 4 months of aerobic exercise and were reevaluated (Time 3). Subjects were given the option of participating in 6 additional months of supervised aerobic exercise, and all available subjects completed a fourth assessment (Time 4) 14 months after their initial baseline evaluation. Results indicated that subjects generally exhibited a 10 to 15% improvement in peak oxygen consumption after 4 months of aerobic exercise training, and a 1 to 6% improvement in aerobic power with additional aerobic exercise training. On the other hand, subjects, especially men, continued to have improvements in submaximal exercise performance (i.e., anaerobic threshold). In addition, aerobic exercise was associated with an improved lipid profile; subjects participating in aerobic exercise for up to 14 months exhibited increased levels of high-density lipoprotein cholesterol. Maintenance of regular aerobic exercise for an extended time interval is associated with greater cardiovascular benefits among older adults than has been reported previously.

Aged↗

PubMed1991

Single photon emission computed tomography and positron emission tomography in cancer imaging.

Single photon emission computed tomography (SPECT) and positron emission tomography (PET) are now being used to improve the information available from radioisotopic imaging of patients with cancer. These nuclear medicine techniques offer the potential for studying regional function and biochemistry by using radiolabeled substrates. The chemical changes of malignancy precede anatomic changes, and PET and/or SPECT may detect these changes before anatomic changes have occurred. The superiority of SPECT compared with planar imaging has been demonstrated for cardiac and brain imaging. Radiopharmaceuticals containing technetium 99 m (99mTc) are best suited for SPECT imaging because large amounts of radioactivity are administered and the collimator-camera systems are optimized for the 140 keV photons of 99mTc. The current interest in imaging cancer with SPECT relates to the use of gallium 67 citrate and monoclonal antibodies labeled with iodine 123 or indium 111. SPECT can image these radioisotopes, but the advantages compared with planar imaging have not been clearly defined. Furthermore, the ability to quantitate the distribution of single photon emitters other than 99mTc has not been demonstrated. New SPECT systems with three heads or rings of detectors offer promise for improved, quantitative imaging. PET has the capability of imaging tracers with the biologically important elements C-11, N-13, O-15, and F-18 used for positron labeling. These radioisotopes have short half-lives and require a cyclotron close to the PET facility. The most prominently used radiopharmaceutical for PET is F-18 fluorodeoxyglucose (FDG). PET studies with FDG in patients with primary brain tumors have demonstrated the ability to determine the degree of malignancy, to differentiate necrosis from recurrent tumor after radiation therapy or chemotherapy, and to predict prognosis. Other metabolic functions of cancer have been studied, including amino acid accumulation, thymidine uptake, oxygen utilization, intermediary metabolism, and receptor status. PET has the potential to make a major impact on the characterization of a malignancy and the effect of therapy.

Fluorine Radioisotopes↗

PubMed1991

Identification of early recurrence of primary central nervous system tumors by [18F]fluorodeoxyglucose positron emission tomography.

As aggressive neurosurgery and adjuvant therapy have become standard care for most patients with primary central nervous system (CNS) tumors, limitations of posttreatment neuroimaging techniques have become more apparent. Interpretation of computed cranial tomography (CT) and magnetic resonance imaging (MRI) in patients with brain tumors is complicated by changes related to surgery, corticosteroids, radiation, and chemotherapy. We investigated the role of 18F-2-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (FDG-PET) in these difficult diagnostic situations by obtaining FDG-PET scans in 5 patients following temporal lobectomy for epilepsy, in 5 patients with recurrent anaplastic gliomas before and after corticosteroid therapy, and in 5 patients after the development of histologically confirmed radionecrosis. We also obtained postoperative FDG-PET scans in 32 consecutive patients undergoing initial resection of a primary brain tumor. Our results indicate that glucose uptake as detected by FDG-PET scanning with [18F]fluorodeoxyglucose is not increased in the postoperative period; is not affected by steroid therapy; and accurately predicts early recurrence of tumor, supplementing other predictors of tumor behavior, including extent of resection, histological diagnosis, and postoperative CT. Thus PET using [18F]fluorodeoxyglucose can contribute to the optimum management of patients with primary brain tumors.

Adult↗

PubMed1991

The clearance and bioavailability of pamidronate in patients with breast cancer and bone metastases.

The pharmacokinetics and bioavailability of pamidronate were assessed in patients with breast cancer, 6 subjects received the drug intravenously and 7 orally. The initial plasma half-life of pamidronate was short (42 +/- 27 min) and the apparent total plasma clearance was high (471 +/- 298 ml/min). The renal clearance (74 +/- 34 ml/min) was similar to the creatinine clearance (66 +/- 19 ml/min). Most of the renal elimination occurred during and immediately post a 4 h infusion of the drug (23.2 +/- 7.9% in 24 h). The non-renal clearance was ascribed to uptake by bone and deep tissue compartments. Little additional drug appeared in the urine after 24 h. The mean bioavailability was estimated using a parallel study design to be 0.3% for a 300 mg oral dose.

Administration, Oral↗