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Biomedical subjects

R G Bessent

Publications and source records attributed to R G Bessent.

At least 37 records · Page 2Linked to original sources

The use of angiotensin II as a potential method of targeting cytotoxic microspheres in patients with intrahepatic tumour.

Cytotoxic microspheres have been developed for intra-arterial use in patients with liver metastases. Following injection, the distribution of microspheres reflects the pattern of hepatic arterial blood-flow. Vasoactive agents, such as angiotensin II, by producing vasoconstriction in normal liver, might divert arterial blood toward tumour and thereby enhance the delivery of drug-loaded particles. Using a double isotope technique, the distribution of radiolabelled microspheres to tumour and normal liver tissue was measured before and after angiotensin II infusion in nine patients with multiple liver metastases. The median increase in tumour: normal ratio following angiotensin II infusion was by a factor of 2.8 (range 0.8-11.7, P less than 0.05). This novel approach to regional chemotherapy, using a combination of angiotensin II infusion and cytotoxic microspheres, increases the exposure of tumour to cytotoxic agents and may, therefore, enhance tumour response rates.

Adult↗

Investigation of tubal infertility by radionuclide migration.

Investigation of the tubal factor in infertility is limited to an assessment of anatomical structure and tubal patency. No test of ascendant tubal function is currently available. The migration of radionuclide (99mTc-labelled human albumin microspheres) through the genital tract in 96 infertile women was compared with pelvic findings at laparoscopy and chromopertubation. The radionuclide test correlated with laparoscopy in the diagnosis of patency or blockage in 83 cases (86%). In nine patients, where 'blockage' was diagnosed on the radionuclide test but patency found at laparoscopy, a higher prevalence of pelvic abnormality was found, compared to the 78 patients where both tests demonstrated patency (P less than 0.02). The radionuclide test may facilitate detection of diseased but patent tubes and, as an adjunct to laparoscopy and chromopertubation, may provide useful information about tubal function.

Endometriosis↗

The biodegradation of albumin microspheres used for regional chemotherapy in patients with colorectal liver metastases.

The poor results of systemic chemotherapy for colorectal liver metastases have focussed attention on the use of regional chemotherapy. Embolizing, biodegradable particles can be coadministered with anticancer drugs to slow temporarily the arterial blood flow and increase drug uptake within the tumour-bearing liver. Alternatively, such microspheres can be loaded with cytotoxic agents and act as slow-release mechanisms following embolization. In both instances, size and rate of degradation are important. The aim of this study was to evaluate the biological degradation of albumin microspheres in the liver of patients with colorectal liver metastases. Seven patients with advanced liver metastases had a 200-250 mg bolus dose of customized albumin microspheres (diameter range: 20-40 microns), labelled throughout with covalently bound 131I, injected into the hepatic artery. The abdomen was imaged immediately before injection to give an estimation of background count rate, and daily after injection for five days. Activity-time curves were constructed for the liver region. The median biological half-time of the particles within the whole liver was 2.4 days (range: 1.5-11.7 days), but was longer in tumours than in normal liver in some patients. The rate of microsphere degradation within tumours may be an important factor in the efficacy of microsphere-based regional therapy, and can be studied accurately by the technique we have employed.

Biodegradation, Environmental↗

Dynamic hepatic scintigraphy: the effect of using high administered activity on reproducibility of hepatic perfusion index value.

The hepatic perfusion index (HPI) may be of value in the detection of both overt and occult hepatic metastases in patients with colorectal carcinoma. Using the standard technique, the low counts obtained in each region of interest can produce statistical unreliability in the curve generation and render many studies unsuitable for analysis. In this study the effects of a high administered activity (400 MBq) on the inter- and intra-observer reproducibility of dynamic hepatic scintigraphy was investigated in 18 consecutive patients with colorectal cancer. All 18 patient studies were suitable for analysis by two observers. The correlation coefficient of measurements between observers was 0.98 (P less than 0.000 01 linear regression analysis), with a root mean square difference of replicate HPI measurements between observers of 0.045. The median range of HPI for four reprocessings by one observer was 0.035, with a maximum range of 0.11. Although high administered activity improves count statistics, for the individual patient study the activity used is not the major source of uncertainty in the derived HPI value.

Colorectal Neoplasms↗

Lung scanning for pulmonary embolism: clinical and pulmonary angiographic correlations.

A group of 78 patients with suspected pulmonary embolism was studied by both ventilation perfusion lung scanning and pulmonary angiography. Symptoms and clinical signs were analysed using Bayesian techniques to produce pre-test odds for pulmonary embolism in individual patients. While, as a group, those with embolism could be discriminated from those without on this basis, major overlap existed between the groups, invalidating the use of this approach for individual patients. Strict diagnostic criteria for interpretation of lung scans were accurate using pulmonary angiography as the 'gold standard', but at the expense of a significant number of patients (38 per cent) in the indeterminate (non-diagnostic) group. In the 48 patients in whom the test yielded a diagnostic result, there was a sensitivity of 100 per cent (15/15) and a specificity of 97 per cent (32/33). In the series as a whole, the likelihood of lung scanning correctly diagnosing pulmonary embolism was 55 per cent (15/27) and of correctly excluding embolism, 63 per cent (32/51). By the use of strict criteria for interpretation of lung scanning, reliable information can be obtained on the presence or absence of pulmonary embolism in a large proportion of patients suspected of having the condition. Such information is more discriminating than clinical signs and symptoms.

Adult↗

Gallbladder emptying following cholecystokinin and fatty meal in normal subjects.

A quantitative study of gallbladder emptying using 99mTc-HIDA as a bile tracer was performed with either CCK or a fatty meal as gallbladder stimulant. Its aims were to establish; (1) the reproducibility of CCK- and fatty-meal-induced gallbladder contraction, and (2) temporal patterns of gallbladder emptying following a physiological meal. Nineteen healthy, fasted volunteers were selected for 3-minute CCK administration (IV Boots Pancreozymin 2CHR units/kg) or a 40 g fatty meal. Each underwent repeat scans not less than 14 days after the first. Quantitative activity/time curves were drawn with computer analysis establishing gallbladder ejection fractions (GBEF) for each stimulus. Our results demonstrated: (1) poor reproducibility of CCK-induced gallbladder contraction precluding its diagnostic use, (2) improved but still variable meal-induced gallbladder contraction, and (3) evidence for a neurocephalic emptying response with a fatty meal stimulus.

Adult↗

Clinical evaluation of angiotensin II enhanced perfusion scintigraphy in metastatic liver disease.

The hepatic perfusion index (HPI) may be of value in the diagnosis of liver micro-metastases. However, raised values of HPI also occur in some benign liver conditions (e.g. cirrhosis), thereby weakening the diagnostic power of this test. It has been suggested that infusion of the vaso-active agent angiotensin II might improve the predictive value of dynamic scintigraphy because it has been shown to alter liver perfusion in patients with metastatic liver disease. Basal HPI values were not significantly different in a group of patients with metastases (n = 10) and a group with cirrhosis (n = 9). A significant rise in HPI occurred in the metastatic group using angiotensin II enhancement (p less than 0.01, Wilcoxon test). In the cirrhotic group there was no significant increase in the HPI with angiotensin II enhancement. Within the groups, there was considerable variation in response, with eight of ten metastatic and five of nine cirrhotic patients showing a rise in HPI during an angiotensin II infusion. As a result, there was complete overlap in the angiotensin II enhanced HPI for the two groups. Angiotensin II enhancement of HPI is therefore unlikely to improve the diagnostic power of dynamic scintigraphy in individual patients with established hepatic disease.

Angiotensin II↗

99mTc-nanocolloid bone marrow scintigraphy in prostatic cancer.

Bone marrow scintigraphy was performed in 23 patients with histologically proven carcinoma of the prostate, using a new radiopharmaceutical, Technetium-99m nanocolloid. The results suggest that although bone marrow scintigraphy is less sensitive than conventional bone scintigraphy in the detection of skeletal metastases from prostatic carcinoma, the technique may have a place in the management of patients with advanced metastatic disease, especially those who are anaemic, by identifying those patients at risk from myelosuppressive therapy.

Adult↗

Imaging for infection: caution required with the Charcot joint.

Scintigraphic techniques for detecting bone infection can be misleading in neuroarthropathy (Charcot joint). Three patients showed strongly positive three phase bone and 67Ga imaging despite absence of osteitis. Indium labelled white cell imaging provided the correct information on each patient. The findings have important implications for the investigation of diabetic patients with suspected bone infection.

Adult↗

Single photon emission computed tomographic studies (SPECT) of hepatic arterial perfusion scintigraphy (HAPS) in patients with colorectal liver metastases: improved tumour targetting by microspheres with angiotensin II.

As intra-arterial chemotherapy for liver metastases of colorectal origin becomes accepted, methods of further improving drug delivery to the tumour have been devised. Degradable microspheres have been shown to reduce regional blood flow by transient arteriolar capillary block, thereby improving uptake of a co-administered drug, when injected into the hepatic artery. In our study of five patients, we combined hepatic arterial perfusion scintigraphy (HAPS) and SPECT to assess the localization of approximately 1 X 10(5) labelled microspheres of human serum albumin (99Tcm MSA) in tumour. In addition, in three patients, we assessed the effect of an intra-arterial infusion of the vasoactive agent angiotension II during HAPS. Results were interpreted by comparing transaxial slices with corresponding slices of a tin colloid liver-spleen scan. Two of five patients showed good localization of 99Tcm MSA in tumour without an angiotensin II infusion. Of the three patients receiving angiotensin II, all showed good tumour targetting with the vasoconstrictor compared with only one of these three before its use. Thus, hepatic arterial infusion of angiotensin II greatly improves microsphere localization in tumour in some patients with colorectal liver metastases. This technique may be useful in the assessment of tumour targetting before and during locoregional therapy.

Angiotensin II↗

Arteriovenous shunting of microspheres in patients with colorectal liver metastases: errors in assessment due to free pertechnetate, and the effect of angiotensin II.

In patients receiving locoregional therapy for liver metastases degradable microspheres are being increasingly used in an attempt to improve cytotoxic delivery to the tumour. However, counterproductive arteriovenous shunting through the liver following intrahepatic arterial injection can occur, leading to deposition in the lung. Measurement of the degree of shunting is important in the monitoring of this kind of therapy. In this study we describe the use of technetium-labelled microspheres of serum albumin (99Tcm MSA) to measure baseline shunting during hepatic arterial perfusion scintigraphy in five patients with liver metastases of colorectal origin, and assess the significance of the values obtained for relative lung uptake (RLU) which we define as: RLU = Activity in lung field/Activity in liver + lung fields X 100%. We found that shunting was less than 5% in all cases, zero shunting occurring in 14 of the 16 patients studied. The sources of error in this technique have been assessed, the most important being the presence of free pertechnetate in the injectate. The use of Boots 10 ml vials and glass syringes respectively to dispense and administer this radiopharmaceutical reduces this error to a small predictable level. In our small group of patients, we found no evidence to suggest that use of the vasoactive agent angiotensin II significantly increases baseline shunting in patients with colorectal liver tumour.

Angiotensin II↗

Reporting of ventilation perfusion images for pulmonary embolism: accuracy and precision.

Thirty-four hospital patients with suspected pulmonary embolism (PE) had ventilation perfusion (VP) imaging after pulmonary angiography to assess the performance of highly specific criteria for diagnosis of PE and to evaluate the precision of image reporting. A diagnostic result was obtained from VP imaging in 21 of 34 patients giving a sensitivity for PE of 80% and a specificity of 100% in this subgroup. Six of 11 patients with PE had an indeterminate study which reduced the overall sensitivity of the technique for PE in the whole group. A critical analysis of image reporting by two readers gave an 85% inter-observer agreement on ranking as diagnostic or indeterminate for PE (k 0.69) and 91%-94% agreement for consensus reproducibility (k 0.82). We conclude that the degree of accuracy and precision of reporting that can be obtained using specific criteria will provide a reliable diagnosis in a significant number of patients suspected of having PE. Consensus reporting by two readers is shown to be more reliable than individual reporting.

Angiography↗

Successful localisation of parathyroid adenomata by thallium-201 and technetium-99m subtraction scintigraphy: description of an improved technique.

An improved method for parathyroid scanning using thallium-201 and technetium-99m subtraction imaging is described. The technique successfully localised ten of eleven parathyroid adenomas confirmed at neck exploration. Two false-positive studies were encountered in patients with no adenoma at operation, probably due to thyroid nodules. The technique was less successful in identifying diffusely hyperplastic parathyroid glands and was negative in a single patient with recurrent, functional parathyroid carcinoma.

Adenoma↗

A study of zinc metabolism in alcoholic cirrhosis.

1. Zinc metabolism was studied in 11 patients with alcoholic cirrhosis and 13 healthy volunteers using the isotope tracer 65Zn. 2. Intestinal absorption, whole-body content and total daily elimination of zinc were all increased in alcoholic cirrhosis, but the biological half-life of zinc did not differ from controls. 3. Hepatic zinc concentration was reduced in alcoholic cirrhosis and correlated with changes in hepatic alcohol dehydrogenase activity. 4. Patients with alcoholic cirrhosis in this study were not demonstrated to be zinc-deficient.

Adult↗

Relative distribution of diphosphonate between bone and soft tissue at 4 and 24 hours: concise communication.

Digital bone scintigrams were obtained in 19 patients using Tc-99m hydroxyethylidene diphosphonate (HEDP). These were quantitated for skeletal, soft-tissue and renal uptake of tracer using a contrast-enhancement technique to define the regions of interest. Twenty-four hr whole-body retention (WBR) of HEDP was also measured. It was found that approximately 70% of retained diphosphonate was localized in the skeleton at 24 hr, with 26% in soft tissue and 4% in kidneys. However, we have shown that over a wide spectrum of whole-body retention measurements (18 to 70%) the 24-hr soft-tissue component, as a percentage of administered dose, remained relatively constant whereas skeletal tracer accumulation mirrored WBR (r = 0.98, p less than 0.001). The present study indicates that, despite a significant but essentially stable soft-tissue component, measurement of 24-hr WBR of HEDP accurately reflects skeletal metabolism.

Bone and Bones↗