Search

This study aimed to evaluate the ability of lymphoscintigraphy (LSG) to direct sentinel node biopsy (SNB) in the identification of occult metastases in the clinically N0 neck for patients with head and neck squamous cell carcinoma (HNSCC). 57 clinically N0 neck sides in 48 patients were assessed using the triple diagnostic approach of pre-operative LSG, intra-operative use of a gamma probe and blue dye. SNB was performed after radiocolloid and blue dye injection. Pre-operative LSG and the intra-operative use of a gamma probe identified radioactive sentinel nodes, and visualization of blue stained lymphatics identified blue sentinel nodes. 104 sentinel nodes were harvested from 43 patients. The identification rate was 90% (43 of 48). Of the 104 nodes harvested, 17 of 62 (27%) nodes identified as both radioactive and blue were positive for occult metastases compared with 5 of 42 (12%) nodes identified as hot or blue only (p<0.05). Sentinel nodes were identified in 39 of 48 (81%) patients using LSG. Of 39 patients in whom sentinel nodes were identified using LSG, 37 of 39 (95%) had radioactive sentinel nodes harvested intra-operatively. In patients who had no sentinel nodes identified on LSG, 4 of 9 (44%) had radioactive sentinel nodes harvested intra-operatively. This difference was statistically significant using the t-test (p<0.05). LSG directs SNB and is essential in the identification of occult metastases within the clinically N0 neck for patients with HNSCC.

Objective: To investigate the possible role of sentinel node biopsy (SNB) alone to upstage the clinically N0 neck in patients with oral and oropharyngeal squamous cell carcinoma., Design: Prospective clinical study., Setting: Head and neck referral center., Patients: Patients with primary untreated oral and/or oropharyngeal squamous cell carcinoma accessible to injection and with clinically N0 necks were enrolled in the study., Intervention: An SNB was performed after radiocolloid and blue dye injection. Preoperative lymphoscintigraphy and the perioperative use of a gamma probe identified radioactive sentinel nodes and visualization of blue-stained lymphatics identified blue sentinel nodes. If the sentinel node was found negative, there was no further treatment to the neck. If the sentinel node tested positive, a therapeutic neck dissection was performed. All patients underwent regular follow-up at the outpatient clinic to identify possible recurrence., Main Outcome Measures: Upstaging of the clinically N0 neck by SNB and development of subsequent disease in SNB-negative necks., Results: An SNB was performed on 57 clinically N0 necks in 48 patients. Sentinel nodes were harvested in 43 (90%) of 48 patients. Fifteen (35%) of 43 patients were upstaged by SNB and 28 (65%) of 43 were staged SNB negative. There was a mean follow-up of 18 months. One patient developed subsequent disease after having been staged negative with SNB. The overall sensitivity of the procedure using the full pathologic protocol was 94% (15/16)., Conclusions: Sentinel node biopsy can be used to upstage the N0 neck in patients with early subclinical nodal disease. However, before it becomes the standard of care in head and neck squamous cell carcinoma, longer follow-up observational trials are needed.

Background: Sentinel lymph node (SLN) biopsy originally was described as a means of identifying lymph node metastases in malignant melanoma and breast carcinoma. The use of SLN biopsy in patients with oral and oropharyngeal squamous cell carcinoma and clinically N0 necks was investigated to determine whether the pathology of the SLN reflected that of the neck., Methods: Patients undergoing elective neck dissections for head and neck squamous cell carcinoma accessible to injection were enrolled into our study. Sentinel lymph node biopsy was performed after blue dye and radiocolloid injection. Preoperative lymphoscintigraphy and the perioperative use of a gamma probe identified radioactive SLNs; visualization of blue stained lymphatics identified blue SLNs. A neck dissection completed the surgical procedure, and the pathology of the SLN was compared with that of the remaining neck dissection., Results: Sentinel lymph node biopsy was performed on 40 cases with clinically N0 necks. Twenty were pathologically clear of tumor and 20 contained subclinical metastases. SLNs were found in 17 necks with pathologic disease and contained metastases in 16. The sentinel lymph node was the only lymph node containing tumor in 12 of 16., Conclusions: The SLN, in head and neck carcinomas accessible to injection without anesthesia, is an accurate reflector of the status of the regional lymph nodes, when found in patients with early tumors. Sentinel lymph nodes may be found in clinically unpredictable sites, and SLN biopsy may aid in identifying the clinically N0 patient with early lymph node disease. If SLNs cannot be located in the neck, an elective lymph node dissection should be considered., (Copyright 2001 American Cancer Society.)

Technetium-99m hexamethylpropylene amine oxime (99mTc-HMPAO) white cell scintigraphy is invaluable for assessing the presence and extent of disease activity in patients with inflammatory bowel disease. Interpretation of images can be compromised by physiological excretion of tracer into the bowel via the biliary tree. This study assesses the effect of intravenous pethidine administered with the labelled white cells in an attempt to reduce the enterohepatic circulation of the tracer. Ninety-one subjects with proven or suspected inflammatory bowel disease were included in this study, all of whom underwent 99mTc-HMPAO white cell scintigraphy. The control group of 50 subjects underwent the standard protocol for this study performed in our department. The other 41 subjects received an intravenous injection of 0.3 mg/kg of pethidine at the same time as re-injection of the labelled white cells. Images were graded using a five-point scale at both 1 and 2.5 h and categorised as positive, negative or non-diagnostic. Each scan was also assessed for the presence of a visible gall-bladder. The pethidine group had significantly fewer non-diagnostic scans than the control group (P=0.003), and significantly (P=0.001) more studies in which the gall-bladder was visualised. It is concluded that the use of pethidine appears to reduce biliary excretion of tracer during 99mTc-HMPAO white cell scintigraphy. This may allow the delayed images, and early images with low-grade tracer uptake in the bowel, to be interpreted with greater confidence and thereby reduce the number of scans classified as non-diagnostic.

Background: This prospective study was designed to test the hypothesis that abnormal liver blood flow is related to poor prognosis in patients with colorectal cancer., Methods: The hepatic perfusion index (HPI), measured by dynamic hepatic scintigraphy, was assessed in 202 patients with colorectal cancer. Assessment for overt hepatic metastasis included liver palpation at laparotomy and perioperative computed tomography (CT). Follow-up at a dedicated clinic included regular abdominal ultrasonography and CT., Results: The HPI was abnormal (greater than 0.37) in 92 (88 per cent) of 105 patients with overt liver metastases. Of 89 patients with no evidence of overt metastases or residual tumour after primary resection, 52 had an abnormal and 37 a normal HPI. At a median follow-up of 39 (range 13-76) months, 25 of 38 patients with recurrence had an abnormal HPI. Some 31 of 45 patients who died had an abnormal HPI. The HPI predicted overall recurrence (P=0.04, log rank test). Multivariate analysis showed the HPI was independent of Dukes stage for predicting disease-free survival (P=0.04, relative risk 1.94 (95 per cent confidence interval (c.i.) 1.03-3.67)) but this just failed to attain significance for overall survival (P=0.055, relative hazard 1.88 (95 per cent c.i. 1.00-3.58))., Conclusion: The HPI predicts a poor outcome in patients with colorectal cancer and may be useful in patient selection for adjuvant chemotherapy.

A recent trend among physicians is the categorisation of lung scans as normal [excludes pulmonary embolism (PE)], high probability (confirms PE) and non-diagnostic (no judgement on PE risk). The low probability scan is therefore being eliminated as a functional category. This occasional survey contends that such an approach is misguided. Correction of the original PIOPED data with certain assumptions provides a more reproducible, albeit restricted, low probability scan category which excludes PE in 97% of cases in the low pre-test clinical category. Patients with a low probability scan with risk factors for PE (i.e. medium clinical risk) will require further investigation. More important, the very low probability scan category excludes PE in 98% of patients with low and more than 92% of patients with medium pre-test clinical likelihood. The demise of "low probability" is premature.

Reporting of lung scans for pulmonary embolism (PE) using a descriptive probability notation is tried and tested. Subjectivity in interpretation of this jargon can be a problem for internists. Parallel descriptive and numerical probability reporting has been recommended, but the numerical probability scale is less precise than likelihood ratios expressed as odds. We therefore assessed internists' intuitive understanding of lung scan reports in the odds format compared to the descriptive probability notation. A questionnaire was sent to Scotland's 217 internists to assess their intuitive understanding of odds reporting and to compare their management strategies when confronted by lung scan reports in both an odds and a descriptive probability notation. There was a broad understanding of numerical odds. Internists used 'normal' and '100:1 against PE' identically; similarly, 'low probability' and '10:1 against PE'. There was a statistically significant preference for the diagnosis of PE when internists were given the '1:1 evens' report compared with the 'indeterminate' report. There does appear to be a greater awareness of the risk of PE when non-diagnostic lung scans are reported in numerical odds as compared with the descriptive probability format.

Background: Idiopathic slow transit constipation (ISTC) is considered to be a heterogeneous condition in which patients have varying sites and degrees of delayed gastrointestinal transit. The majority of patients have pancolonic disease, and colectomy with ileocolorectal anastomosis has been the mainstay of surgical treatment. Severe constipation following traumatic childbirth is now being recognized and this subgroup of patients may have delayed transit confined to the rectosigmoid colon. In theory, proximal transit in these patients should be normal., Methods: Gastric emptying was studied in patients with constipation following childbirth or ISTC and in controls. After an overnight fast, both patients and controls received breakfast, which consisted of cornflakes, sugar and milk. The liquid marker 111In-labelled di-ethylene tri-amine penta-acetic acid (DTPA) was added to the milk. A solid marker, 99mTc-labelled colloid, was impregnated on to paper and sealed with cellulose. The t1/2 for gastric emptying was calculated., Results: Liquid phase emptying was normal in both constipation following childbirth and ISTC. Solid phase emptying was delayed significantly in ISTC compared with that in patients with constipation following childbirth and controls. In addition, half the patients with ISTC had delayed transit through the small bowel and proximal colon. Small bowel and colonic transit were normal in patients with constipation following childbirth., Conclusion: Patients with constipation following childbirth represent a distinct subgroup with normal proximal gastrointestinal function. Gastric emptying studies may be helpful in selecting patients for surgical management of severe constipation.

The clinical usefulness of the hepatic perfusion index (HPI) at the time of presentation has been evaluated in patients with colorectal cancer. In 83 consecutive patients, the HPI was abnormally elevated in 34 of 37 (93%) patients with overt metastases. This study confirms that the HPI is elevated in most patients with overt hepatic metastases. Long-term follow-up of patients with abnormal HPI and no obvious liver metastases is continuing.

The aim of this study was to analyse the understanding of the verbal probability language used for communicating lung scan findings. A questionnaire providing a series of expressions of probability in lung scan reporting was sent to 211 consultant nuclear medicine providers in the UK. Respondents were asked to estimate the probability of pulmonary embolism (PE) communicated by each reporting expression on a visual linear probability scale. Analysis of 135 replies revealed a wide variation in the interpretation of the probability language. We suggest that different training, the nature of the probability scale itself and the difficulties of expressing a verbal report on a numerical scale are major reasons for this finding. We conclude that use of verbal probability language complicates the communication of PE risk and that likelihood ratios provide a logical alternative.

A questionnaire was sent to 217 consultant physicians in Scotland who were likely to encounter pulmonary embolism (PE) in their daily practice. Replies were received from 194 (89%). Only 34% of physicians understood that a normal lung scan made PE highly unlikely, while 65% considered a low probability scan equivalent to an uncertain diagnosis. This pattern of interpretation of lung scan reports was confirmed by a question on post-test management. After a normal lung scan report, 31% of physicians were uncertain about the diagnosis and this uncertainty increased to 37% for a low probability scan report. This survey has shown misunderstanding by a significant number of physicians of the risk of PE indicated by normal and low probability lung scan reports. It underlines the need for individuals reporting the test to provide informed guidance for clinical staff following ventilation/perfusion (V/Q) imaging. It may point in addition to a need for a more easily understood style of reporting of lung scans.

The migration of radionuclide through the genital tract was observed, comparing 20 patients with endometriosis and infertility with a control group of 23 infertile patients who had a normal pelvis. All patients had patent tubes at laparoscopy and chromopertubation, performed in both groups for the investigation of infertility and to diagnose the presence and extent of endometriosis. A radionuclide tubal test, using human albumin microspheres labelled with 99m-technetium (99mTc) was subsequently undertaken to observe the extent of genital tract migration of radionuclide to uterus, Fallopian tube and peritoneal cavity. The results show that radionuclide migration to the peritoneal cavity was impaired in patients with endometriosis, compared with the control group (30 versus 83%, respectively; P < 0.001). There was no relationship between migration and the severity of endometriosis. We conclude that impaired tubal function may be a cause of infertility in some patients with endometriosis.

Total calculated uniform liver doses of up to 150 Gy were achieved using glass yttrium-90 microspheres administered via the hepatic artery and targeted to tumour using angiotensin II in seven patients with colorectal liver metastases. No toxicity was observed. Hepatic metastatic progression was delayed in six patients. Median survival was 11 months (range 5-25 + months).

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.

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.

Biodegradable albumin microspheres have been prepared incorporating either 131I or 111In/111In. Using cDTPAA/albumin molar ratios of 1, 3 and 10, approx. 0.7, 2.1 and 7 molecules of DTPA could be coupled to an albumin molecule, labelling efficiency being constant over this range. Because 131I microspheres were more stable in plasma than the system labelled with radionuclides of indium it was selected for clinical evaluation: potential uses of this radiopharmaceutical are illustrated.

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.

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.

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.

The accuracy of preoperative assessment in determining invasion of the mandible by intraoral squamous cell carcinoma was analyzed in 48 patients who underwent mandibulectomy, and the results correlated with the histopathological reports of the resected specimens. Only 50% of the patients underwent the "ideal" surgery based primarily on clinical judgement, whereas 10 patients in the series were significantly undertreated. Clinical judgement and routine preoperative x-rays are accurate in cases where there is gross involvement of the mandible (17 of 19) but are significantly less successful in determining early bone invasion, invasion of the periosteum, or periosteal new bone formation. In such cases (26 of 48), a technetium-99m bone scan provides additional information. A grading system for reporting orthopantomographics (OPTs) and bone scans has been developed and utilized to form a reference grid to determine the optimum extent of mandibular surgery. The results show that using this protocol, unnecessary mandibular surgery may be reduced and inadequate surgical excision avoided.

Blood clearance, urinary excretion, and spinal uptake of 99mTc-HEDP have been measured in ten normal control subjects. Blood clearance from 15 min is biexponential. Approximately 70% of the administered activity was excreted in the urine within 6 hr of injection. Spine-to-background ratios rise sequentially with time. Net normal bone uptake rises little after 2 hr and improved visualization of the normal skeleton therafter is due to reduction of blood background activity. In 13 patients with bone tumors, direct measurement of diphosphonate uptake by the tumor-involved and corresponding normal bone showed a continued rise in diphosphonate levels in the tumor-involved bone due to increased metabolic activity.

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.

Seventy-five female patients with early primary cancer of the breast were studied by bone scanning with 99mTc labeled phosphate at the time of initial presentation and serially during follow-up examination. Eleven patients had an abnormal bone scan at the time of presentation. During follow-up periods, which have ranged from three to 34 months with a mean of 16 months, abnormal bone scans have developed in a further 13 patients. To date, nine of the 24 patients with an abnormal bone scan have died, while only one of the 51 with a persistently normal scan has died. It is concluded that an abnormal bone scan carries a significant risk of earlier death due to metastatic disease.

The accuracy and sensitivity of the 99Tcm-phosphate bone scan and conventional skeletal radiology have been compared in 372 patients with documented malignant disease and 75 control subjects. Results indicate that the bone scan is a more sensitive method for the detection of skeletal metastases. The incidence of false-positive results with the bone scan is acceptably low. A protocol for the investigation of patients with suspected malignant disease of bone is suggested.

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.

Accurate quantitation from the bone scan image of skeletal uptake of radiopharmaceutical would be of value in the assessment of patients with metabolic bone disease. Repeat measurements of bone to soft tissue (B/ST) ratios on the one set of images were made for 103 subjects, a) by the same observer using lumbar vertebra 2 for the area of bone; b) by the same observer using lumbar vertebra 2 then lumbar vertebra 4; c) by two observers both using lumbar vertebra 2. The median difference between repeat measurements by the same observer was well under 1% but the 5-95 percentile range was -13 to +14%. Between the two observers there was a median difference of 10.6% with a 5-95 percentile range of -11 to +44%. We also measured B/ST ratios in 150 control subjects and 139 patients with various metabolic bone disorders. While statistically significant differences for B/ST ratios were found between the osteomalacia, renal osteodystrophy, Paget's groups, and the control population (P less than 0.001 in all cases), there was appreciable overlap between individual patient results and the control range. It is concluded, therefore, that measurement of B/ST ratios for the individual is of limited value in clinical practice.

Twenty normal volunteers had measurements of 24-hr whole-body retention (WBR) of three structurally related Tc-99m-labeled phosphonate skeletal imaging agents: (1-hydroxyethylidene) diphosphonate (HEDP), methylene diphosphonate (MDP), and hydroxymethylene diphosphonate (HMDP). The average WBR values, reflecting skeletal uptake, were 18.4, 30.3, and 36.6%, respectively. These results clearly illustrate that slight alterations in diphosphonate molecular structure have a significant effect upon specificity for osseous tissue, and thus may affect skeletal image quality and the usefulness of the WBR technique in diagnosing metabolic bone disease.

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.

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.

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.

99Tcm-HEDP bone scans were obtained in 20 acromegalic patients. Twelve patients had active disease with elevated basal serum human growth hormone (HGH) levels. Eight patients were in clinical and biochemical remission. The bone scans, assessed independently by three observers, showed features characteristic of metabolic bone disease in patients with active acromegaly. The metabolic index derived from the scan correlated well with serum HGH levels (R = 0.71, p < 0.002). The bone scan may accurately reflect oversecretion of HGH and is of potential value in the assessment of patients with acromegaly.

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.

24-h whole-body retention (WBR) of diphosphonate (a sensitive indicator of skeletal metabolism) was measured in 37 oophorectomised women. 14 women had been prescribed oestrogen supplements and 3 of these had defaulted from therapy. For the study group there was a significant correlation between WBR and both the rate of bone loss as measured by photonabsorptiometry (r = 0.7, p ¿ 0.001) and urinary hydroxyproline (r = 0.53, p < 0.001). The oestrogen-treated group had significantly lower values for WBR and rate of bone loss than the untreated group (p < 0.01, p < 0.01 respectively) indicating suppressed skeletal metabolism. However, the highest values were found in those who had defaulted from oestrogen therapy suggesting a rebound period of accelerated skeletal metabolism and bone loss. There was a significant negative correlation between WBR and oestrogen dosage (r = 0.75, p < 0.02) suggesting that it may be possible to adjust the dosage for optimal skeletal metabolic activity. WBR of diphosphonate provides a simple and sensitive measure of skeletal metabolism which correlates well with conventional measurements of bone loss. WBR may be useful in the screening and identification of women who have increased bone turnover just after the menopause and who may subsequently be at risk of osteoporosis developing.

1. The long-term clearance of radioactive vitamin B12 from serum and from whole body was measured in control subjects and patients with treated pernicious anaemia and the data were analysed by the occupancy principle to provide estimates of dietary intake, daily requirements and whole-body mass of vitamin B12. 2. In six cases the daily requirement for vitamin B12 ranged from 0.15 to 1.9 microgram with an average of 1.0 microgram. The whole-body vitamin B12 in four cases ranged from 780 to 1350 microgram with an average of 1060 microgram. 3. Estimates of the whole-body vitamin B12 on the assumption of single-pool equilibrium gave constantly changing results, which, together with discrepant half-lives for serum radioactivity and whole-body radioactivity, constitute evidence against the concept of single-pool equilibrium.

The variation of the diagnostic value of stress Tl-201 scintigraphy with prevalence of coronary heart disease (CHD) in the population has been investigated using Bayesian reasoning. From scintigraphic and arteriographic data obtained in 100 consecutive patients presenting with chest pain, the sensitivity of stress Tl-201 scintigraphy for the detection of significant CHD was 90% and the specificity was 88%. From Bayes' Theorem, the posterior probability of having CHD for a given test result was calculated for prevalences of CHD ranging from 1% to 99%. The discriminant value of stress Tl-201 scintigraphy was best when the prevalence of CHD lay between 30% and 70% and maximum for a prevalence of 52%. Thus, stress Tl-201 scintigraphy would be an unsuitable diagnostic test where the prior probability of CHD is low, e.g., population screening programmes, and would add little where the clinical probability of having CHD is already high. However, where the prior probability of having CHD is intermediate stress Tl-201 scintigraphy may provide valuable diagnostic information.

The limited role of bone scanning in the diagnosis of metabolic bone disease might be considerably improved by accurate quantification of skeletal uptake of the radiopharmaceutical. Using a standard shadow-shield whole-body monitor, we have measured whole-body retention (WBR) of Tc-99m HEDP up to 24 hr in 11 patients with renal osteodystrophy (mean WBR 88.6% at 24 hr); in ten patients with Paget's disease (mean 56.9%); in seven patients with osteomalacia (mean 40.7%); in five patients with primary hyperparathyroidism (mean 50.7%); in four patients with osteoporosis (mean 21.2%); and in 12 normals (mean 19.2%). The osteoporotic group could not be differentiated from the normal group, but the other groups were significantly different from the normal group at 24 hr (p less than 0.002), and each individual rest for the 24-hr WBR of Tc-99m HEDP in these groups lay outside our normal range. This test may, therefore, provide a sensitive means of detecting conditions with increased bone turnover. We obtained measurements of plasma activity of Tc-99m HEDP in these patients up to 24 hr, and 4-hr bone to soft-tissue ratios from bonescan images, but little additional information resulted.