Co-existent Paget's Disease of the Bone, Prostate Carcinoma Skeletal Metastases and Fracture on Skeletal Scintigraphy-Lessons to be Learned.

UNLABELLED: Bone scintigraphy, despite being non-specific, is a very sensitive and simple investigation for patients with active Paget's disease of the bone. Skeletal metastases and Paget's disease may co-exist in the elderly patients as both conditions are commonly seen in this age group. Clinical and radiological correlation may help to improve the diagnostic specificity of a bone scintigram. We report a patient in whom concurrent Paget's disease and a rib fracture became evident only on repeat scintigraphy following successful treatment of prostate carcinoma skeletal metastases. CONFLICT OF INTEREST: None declared.

Recombinant HPA-1a antibody therapy for treatment of fetomaternal alloimmune thrombocytopenia: proof of principle in human volunteers.

Fetomaternal alloimmune thrombocytopenia, caused by the maternal generation of antibodies against fetal human platelet antigen-1a (HPA-1a), can result in intracranial hemorrhage and intrauterine death. We have developed a therapeutic human recombinant high-affinity HPA-1a antibody (B2G1Δnab) that competes for binding to the HPA-1a epitope but carries a modified constant region that does not bind to Fcγ receptors. In vitro studies with a range of clinical anti-HPA-1a sera have shown that B2G1Δnab blocks monocyte chemiluminescence by >75%. In this first-in-man study, we demonstrate that HPA-1a1b autologous platelets (matching fetal phenotype) sensitized with B2G1Δnab have the same intravascular survival as unsensitized platelets (190 hours), while platelets sensitized with a destructive immunoglobulin G1 version of the antibody (B2G1) are cleared from the circulation in 2 hours. Mimicking the situation in fetuses receiving B2G1Δnab as therapy, we show that platelets sensitized with a combination of B2G1 (representing destructive HPA-1a antibody) and B2G1Δnab survive 3 times as long in circulation compared with platelets sensitized with B2G1 alone. This confirms the therapeutic potential of B2G1Δnab. The efficient clearance of platelets sensitized with B2G1 also opens up the opportunity to carry out studies of prophylaxis to prevent alloimmunization in HPA-1a-negative mothers.

Oesophageal conduit - a cause of diffuse mediastinal uptake on thyroid scintigraphy.

UNLABELLED: 99mTc-pertechnetate scintigraphy plays an essential role in the management of a variety of thyroid and parathyroid disorders. The authors report an unusual case of mediastinal tracer distribution of 99mTc-pertechnetate and 99mTc-MIBI in relation to an oesophageal conduit following oesophago-gastrectomy and reconstructive surgery on thyroid scintigraphy. This is a rare but important cause of diffuse mediastinal uptake on thyroid scintigraphy. An awareness of abnormal anatomy as well as altered physiological tracer uptake would help to avoid any diagnostic pitfall. CONFLICT OF INTEREST: None declared.

Use of 111-Indium-labeled autologous eosinophils to establish the in vivo kinetics of human eosinophils in healthy subjects.

Eosinophils are the major cellular effectors of allergic inflammation and represent an important therapeutic target. Although the genesis and activation of eosinophils have been extensively explored, little is known about their intravascular kinetics or physiological fate. This study was designed to determine the intravascular life span of eosinophils, their partitioning between circulating and marginated pools, and sites of disposal in healthy persons. Using autologous, minimally manipulated 111-Indium-labeled leukocytes with blood sampling, we measured the eosinophil intravascular residence time as 25.2 hours (compared with 10.3 hours for neutrophils) and demonstrated a substantial marginated eosinophil pool. γ camera imaging studies using purified eosinophils demonstrated initial retention in the lungs, with early redistribution to the liver and spleen, and evidence of recirculation from a hepatic pool. This work provides the first in vivo measurements of eosinophil kinetics in healthy volunteers and shows that 111-Indium-labeled eosinophils can be used to monitor the fate of eosinophils noninvasively.

Idiopathic accelerated gastric emptying presenting in adults with post-prandial diarrhea and reactive hypoglycemia: a case series.

INTRODUCTION: We have previously reported the association of gastrointestinal and hypoglycemic symptoms, with idiopathic accelerated gastric emptying. We now report the first series of six similar cases. CASE PRESENTATIONS: Patient 1: A 24-year-old Caucasian man presented to our facility with a six-month history of post-prandial nausea, flatulence, bloating, abdominal discomfort and associated diarrhea. He had associated episodes of fatigue, sweating, anxiety, confusion and craving for sweet foods. Patient 2: A 52-year-old Caucasian woman presented to our facility with a 15-year history of post-prandial bloating, abdominal pain and diarrhea, often associated with nausea, severe sweating, and fatigue. Patient 3: An 18-year-old Caucasian woman presented to our facility with a nine-year history of post-prandial diarrhea, abdominal bloating and pain. There was associated nausea, tremor, lethargy, and craving for sweet foods. Patient 4: A 77-year-old Caucasian woman presented to our facility with a four-month history of epigastric distension, pain after eating and a change in bowel habit. She experienced intermittent severe diarrhea and marked fatigue, nausea and sweating. Patient 5: A 23-year-old Caucasian woman presented to our facility with a two-year history of early satiety, and diarrhea after eating. She also complained of feeling faint and weak between meals, when she became cold and clammy, and on several occasions lost consciousness during these episodes. Patient 6: A 64-year-old Caucasian woman presented to our facility with a 10-year history of nausea, early satiety and profound bloating followed by diarrhea. All symptoms predominantly occurred in the first three hours after eating, when she felt faint, lethargic, and had a craving for sweet foods. In all cases, symptoms were alleviated or resolved by taking sweet food or drink and response to treatment was 90% or greater in all cases. CONCLUSIONS: This series extends our description of this new clinical syndrome. All patients responded well to treatment for accelerated gastric emptying. Clinicians in the disciplines of endocrinology, gastroenterology, neurology and general practice are likely to find this information useful as they will consult patients with some or all of these symptoms and in a proportion of these patients idiopathic accelerated gastric emptying may be present and provide a useful avenue for therapeutic intervention.

Evaluation of the sensitivity and specificity of (11)C-metomidate positron emission tomography (PET)-CT for lateralizing aldosterone secretion by Conn's adenomas.

CONTEXT: Identification of unilateral aldosterone-producing (Conn's) adenomas has traditionally required lateralization by the invasive and technically difficult procedure of adrenal vein sampling (AVS). (11)C-metomidate, a potent inhibitor of adrenal steroidogenic enzymes, is a positron emission tomography (PET) radiotracer that is selectively accumulated by Conn's adenomas. OBJECTIVE: The objective of the study was to compare the sensitivity and specificity of (11)C-metomidate PET-computed tomography (CT) against the current gold standard of AVS. DESIGN: The design of the study was within-patient comparison of diagnostic techniques. SETTING: The study was conducted at a single center-university teaching hospital. PATIENTS: Thirty-nine patients with primary hyperaldosteronism (PHA) and five with nonfunctioning adenomas (incidentalomas) participated in the study. INTERVENTION(S): The first six PHA patients were studied on three occasions to determine whether steroid pretreatment reduced (11)C-metomidate uptake by normal adrenal. Subsequent patients received dexamethasone for 3 d prior to injection of (11)C-metomidate 150-500 MBq. MAIN OUTCOME MEASURE(S): Maximum standardized uptake values (SUV(max)) over regions of interest determined from 35-45 min after injection were measured. RESULTS: Dexamethasone increased tumor to normal adrenal SUV(max) ratio by 25.6 ± 5.0% (P < 0.01). PET-CT visualized subcentimeter adenomas and distinguished hot from cold adenomas within a gland. In 25 patients with PHA and AVS lateralization to the side of an adenoma, SUV(max) over tumor (mean ± sem) of 21.7 ± 1.6 was greater than over normal adrenal, 13.8 ± 0.6 (P = 0.00003); this difference was absent in 10 patients without lateralization on AVS (P = 0.28) and in four of five incidentalomas. On receiver-operator characteristics analysis, an SUV(max) ratio of 1.25:1 provided a specificity of 87% [95% confidence interval (69, 104)] and sensitivity of 76% (59, 93); in tumors with SUV(max) greater than 17, the specificity rose to 100%. CONCLUSIONS: (11)C-metomidate PET-CT is a sensitive and specific noninvasive alternative to AVS in the management of PHA.

Clinical significance of scintigraphic rapid gastric emptying.

OBJECTIVES: To analyse our results of gastric-emptying scintigraphy in relation to presenting symptoms, and examine in detail the clinical significance of rapid gastric emptying (RGE). MATERIALS AND METHODS: Results of 642 consecutive patients who underwent a solid gastric-emptying scintigraphy in our department over an 11-year period were retrospectively reviewed with particular emphasis to the presenting symptoms and the clinical profile of patients, especially of those who showed an accelerated pattern of emptying. RESULTS: Seventy (11%) patients were clinically suspected to have a RGE and 572 (89%) patients had presumed gastroparesis. Gastric emptying was found to be normal in 290 (45%), rapid in 182 (28%) and delayed in 170 (27%) patients. Normal, rapid and delayed gastric emptying were seen, respectively, in 17 (24%), 48 (69%) and five (7%) patients with the clinical suspicion of dumping and 273 (48%), 134 (23%) and 165 (29%) patients with suspected gastroparesis. The positive predictive value of clinical suspicion for RGE was 62%, whereas the positive predictive value of delayed gastric emptying was 29%. Of the 182 patients with RGE, 144 (79%) were found to have no obvious explanation for this result; reactive hypoglycaemia was present in a quarter of these patients, but diarrhoea was seen only in 3%. CONCLUSION: Upper gastrointestinal symptoms have a poor clinical specificity to the actual rate of gastric emptying on scintigraphy. Diarrhoea as a symptom does not appear to be associated frequently with RGE, but our results confirm its relationship with hypoglycaemia. The majority of patients with a rapid emptying on gastric-emptying scintigraphy have no identifiable cause for an accelerated motility. Scintigraphic gastric-emptying studies provide a reliable and noninvasive method of investigation in patients where conventional investigations have failed to establish the cause of upper gastrointestinal dysfunction.

Post-prandial reactive hypoglycaemia and diarrhea caused by idiopathic accelerated gastric emptying: a case report.

INTRODUCTION: The majority of cases of post-prandial reactive hypoglycemia are considered idiopathic. Abnormalities of B-cell function and glucose regulation by insulin and glucagon have been postulated as causes but associated gastrointestinal dysfunction has not been reported. We report the first case of accelerated gastric emptying associated with post-prandial reactive hypoglycemia, abdominal bloating and diarrhea. We consider that gastric dysmotility is an important cause of this condition as treatment of the underlying abnormal gastric emptying allows effective control of symptoms. CASE PRESENTATION: A 20-year-old Caucasian woman presented with post-prandial fatigue, sweating, nausea, faintness and intermittent confusion, which had led to pre-syncope and syncope on occasions. She also experienced marked abdominal bloating and diarrhea over the same period. These episodes responded to oral administration of sweet drinks. Her symptoms were ameliorated by modification of her diet. CONCLUSION: This is an original case report of the association of idiopathic accelerated gastric emptying with post-prandial reactive hypoglycemia and diarrhea. Family physicians, endocrinologists and gastroenterologists often consult patients with a constellation of post-prandial symptoms, which are considered to be idiopathic in most cases. This case indicates that gastric dysmotility might be the primary cause of these symptoms in some patients and, if found, offers a therapeutic target which in our case was successful.

Quantification of neutrophil migration into the lungs of patients with chronic obstructive pulmonary disease.

OBJECTIVE: To quantify neutrophil migration into the lungs of patients with chronic pulmonary obstructive disease (COPD). METHODS: Neutrophil loss via airways was assessed by dedicated whole-body counting 45 min, 24 h and 2, 4, 7 and 10 days after injection of very small activities of (111)In-labelled neutrophils in 12 healthy nonsmokers, 5 healthy smokers, 16 patients with COPD (of whom 7 were ex-smokers) and 10 patients with bronchiectasis. Lung accumulation of (99m)Tc-labelled neutrophils was assessed by sequential SPECT and Patlak analysis in six COPD patients and three healthy nonsmoking subjects. RESULTS: Whole body (111)In counts, expressed as percentages of 24 h counts, decreased in all subjects. Losses at 7 days (mean ± SD) were similar in healthy nonsmoking subjects (5.5 ± 1.5%), smoking subjects (6.5 ± 4.4%) and ex-smoking COPD patients (5.8 ± 1.5%). In contrast, currently smoking COPD patients showed higher losses (8.0 ± 3.0%) than healthy nonsmokers (p = 0.03). Two bronchiectatic patients lost 25% and 26%, indicating active disease; mean loss in the remaining eight was 6.9 ± 2.5%. The rate of accumulation of (99m)Tc-neutrophils in the lungs, determined by sequential SPECT, was increased in COPD patients (0.030-0.073 min(-1)) compared with healthy nonsmokers (0-0.002 min(-1); p = 0.02). CONCLUSION: In patients with COPD, sequential SPECT showed increased lung accumulation of (99m)Tc-labelled neutrophils, while whole-body counting demonstrated subsequent higher losses of (111)In-labelled neutrophils in patients who continued to smoke. Sequential SPECT as a means of quantifying neutrophil migration deserves further evaluation.

Detection of extensive melorheostosis on bone scintigram performed for suspected metastases.

Melorheostosis is a rare but benign disorder characterized by asymmetric osteosclerotic dysplasia. Radiographic appearances are characteristic and described as "melting wax flowing down a candle." This disorder may involve more than one bone contiguously across the joints following a sclerotomal distribution. It is often asymptomatic but occasionally presents with pain and contractures. The authors report accidental detection of bilateral upper and lower limb melorheostosis in an elderly woman with the history of breast cancer and recent onset of low back pain, which was referred for a bone scintigram for suspected metastases. The images showed bilateral femoral and tibial melorheostosis, which was subsequently confirmed on plain radiograph and by clinical follow-up.

Solitary phalangeal metastasis of renal cell carcinoma on bone scintigram.

Renal cell carcinoma is known to cause lytic metastasis at various sites including axial and appendicular skeleton. However, it is unusual to find an isolated metastasis of renal cell carcinoma in the distal extremity on bone scintigraphy. A 70-year-old woman with renal cell carcinoma was referred to the Nuclear Medicine Department for a bone scintigram to exclude metastasis. The whole-body planar images were unremarkable, but the local views of the hands demonstrated a solitary metastasis in the middle phalanx of the finger. This rare experience illustrates the need for including local views of extremities in a standard whole-body study.

Measuring whole-body neutrophil redistribution using a dedicated whole-body counter and ultra-low doses of 111Indium.

BACKGROUND: There is increasing interest in the 'homing' of neutrophils to bone marrow. The aim of this study was to measure the whole-body redistribution of (111) In using a whole-body counter following the administration of ultra-small activities of (111) In-labelled neutrophils. METHODS: The detectors of a dedicated whole-body counter were fitted with lead collimators. Whole-body (111) In distribution was recorded at 45 min, 24 h, and 2, 4, 7 and 10 days after administration of (111) In-labelled neutrophils (0·29-0·74 MBq) in eight healthy non-smokers, five healthy smokers, eight patients with inactive bronchiectasis, three with asthma and nine with chronic obstructive pulmonary disease (COPD). RESULTS: Intravascular 45-min (111) In-labelled neutrophil recovery was not significantly different between groups, ranging from 33 (SD 8%) in healthy smokers to 45 (14%) in healthy non-smokers (P > 0·05). Peaks were identified on the whole body count profile corresponding to the chest, upper abdomen (liver/spleen) and pelvis (bone marrow). (111) In distribution changed between 45 min and 24 h and then remained stable thereafter. Peak chest counts increased ∼ 1·5-fold between 45 min and 24 h, whereas upper abdominal peak counts decreased by ∼ 25% with no significant inter-group differences. The increment in pelvic counts (∼ 2·7-fold) was similar between groups, except COPD patients, in whom it was 2·04 (0·35; P < 0·02 vs. healthy participants). CONCLUSIONS: Assuming neutrophils are distributed only between blood, liver, spleen and bone marrow, the data suggest that marrow pools 25% and destroys 67% of circulating neutrophils, rising in COPD to 40% and 80%, respectively, possibly as a result of the effects on marrow of chronic hypoxaemia.

What is the significance of solitary bony abnormalities on bone scintigrams of children with malignancy?

This investigation was undertaken to evaluate the significance of solitary bony abnormalities on bone scintigrams of children with known or suspected malignancy. A total of 215 bone scans were performed in 183 children in order to look for possible metastasis over a 10-year period. Forty-nine scans (22.8%) were found to have single lesions, of which 18 were due to uptake at the primary site and were excluded from further consideration. Of the remaining 31 lesions, 13 (41.9%) were confirmed as metastases, 17 lesions were proved to be benign, and 1 indeterminate. Solitary hot spots in children with known or suspected malignancy are common and therefore have to be taken seriously due to their higher malignant potential.

Utility of whole gut transit scintigraphy in patients with chronic gastrointestinal symptoms.

BACKGROUND: To review our experience of doing whole gut transit scintigraphy in patients presenting with functional gastrointestinal problems and to determine its clinical usefulness. METHOD: All whole gut transit studies using a liquid meal over a 5-year-period were reviewed and clinical outcome assessed. RESULTS: Fifty-five patients (44 women; mean age 43 years) underwent whole gut transit scintigraphy using indium-111 diethylene triamine penta-acetic acid in water. The main symptoms were constipation (49%), dyspepsia (25%) and diarrhoea (25%). Colonic transit was delayed in 63% of patients with constipation, which was significantly (P=0.005) higher than that in patients with dyspepsia. Delayed colonic transit was also seen in 43% of patients with diarrhoea. Only 26% of patients with constipation had a delay in liquid gastric emptying and small bowel transit. Gastric emptying, small bowel transit and colonic transit were normal in 43, 79 and 29% of patients with dyspepsia, respectively. There was no statically significant difference in gastric emptying and small bowel transit between patients with constipation, diarrhoea and dyspepsia. CONCLUSION: Liquid-phase whole gut transit scintigraphy seems to be a useful investigation in patients with chronic gastrointestinal symptoms. Rational use of this modality may help the clinician change the management or better characterize the underlying problem/diagnosis in the majority of patients with functional symptoms.

Urinary reflux from ileal neobladder into a non-functioning kidney: detection during diuretic renography.

The importance of monitoring renal function in patients undergoing cystectomy and urinary diversion is well established. Dynamic renography using Tc-99m MAG3 in combination with furosemide challenge has been widely used to determine the differential function of the kidneys, occurrence of reflux as well as the patency of the outflow tract in this context. The authors have described here a patient in whom significant urinary reflux from the neo-bladder into the nonfunctioning kidney was demonstrated during MAG3 diuretic renography.

The role of bone scan in the diagnosis of carpal fracture in children.

A retrospective study was performed to evaluate the role of bone scan in the management of wrist trauma in children with equivocal radiographic findings. Thirty-one out of the 50 children showed no fracture. Six of them were treated for a median period of 9 days on clinical grounds; the others were discharged with reassurance. Four patients with evidence of soft tissue injury received no further treatment. Six of the 12 patients with a fracture on bone scan were treated with a cast for more than 4 weeks. None of the patients developed any complications. Bone scan is helpful when the diagnosis of a carpal fracture in children is equivocal.