Pulmonary retention of primed neutrophils: a novel protective host response, which is impaired in the acute respiratory distress syndrome.

RATIONALE: Acute respiratory distress syndrome (ARDS) affects over 200000 people annually in the USA. Despite causing severe, and often refractory, hypoxaemia, the high mortality and long-term morbidity of ARDS results mainly from extra-pulmonary organ failure; however the mechanism for this organ crosstalk has not been determined. METHODS: Using autologous radiolabelled neutrophils we investigated the pulmonary transit of primed and unprimed neutrophils in humans. Flow cytometry of whole blood samples was used to assess transpulmonary neutrophil priming gradients in patients with ARDS, sepsis and perioperative controls. MAIN RESULTS: Unprimed neutrophils passed through the lungs with a transit time of 14.2 s, only 2.3 s slower than erythrocytes, and with <5% first-pass retention. Over 97% of neutrophils primed ex vivo with granulocyte macrophage colony-stimulating factor were retained on first pass, with 48% still remaining in the lungs at 40 min. Neutrophils exposed to platelet-activating factor were initially retained but subsequently released such that only 14% remained in the lungs at 40 min. Significant transpulmonary gradients of neutrophil CD62L cell surface expression were observed in ARDS compared with perioperative controls and patients with sepsis. CONCLUSIONS: We demonstrated minimal delay and retention of unprimed neutrophils transiting the healthy human pulmonary vasculature, but marked retention of primed neutrophils; these latter cells then 'deprime' and are re-released into the systemic circulation. Further, we show that this physiological depriming mechanism may fail in patients with ARDS, resulting in increased numbers of primed neutrophils within the systemic circulation. This identifies a potential mechanism for the remote organ damage observed in patients with ARDS.

F18-FDG-PET evaluation of patients for resection of colorectal liver metastases.

BACKGROUND/AIMS: Liver resection is the only treatment which offers long-term survival for patients with colorectal liver metastases. However, the significant mortality and morbidity associated with hepatectomy makes accurate patient selection paramount. Current staging by CT and MRI has limitations, with these modalities delivering a sensitivity and specificity of only 70-80%. Thus some patients may be deprived of long-term survival, and others subjected to futile surgery. METHODOLOGY: We report our experience of the influence of F18-FDG-PET scanning in the management of 31 consecutive patients with colorectal liver metastases referred for liver resection. RESULTS: F18-FDG-PET scanning detected liver and pulmonary metastases with a sensitivity of 96% and 100% respectively, in comparison to corresponding figures of 70% and 83% for CT. Furthermore, the sensitivity of F18-FDG-PET scanning in identifying extra-hepatic and extra-pulmonary disease was 100% in comparison to 20% for CT. Overall, F18-FDG-PET scanning resulted in a significant alteration of management in 29% of patients. CONCLUSIONS: F18-FDG-PET scanning has an important clinical impact on the management of patients being considered for resection of colorectal liver metastases.

P-glycoprotein expression is associated with sestamibi washout in primary hyperparathyroidism.

BACKGROUND: The detection of parathyroid adenomas by (99m)Tc-labelled hexakis 2-methoxyisobutyl isonitrile (sestamibi) scintigraphy is influenced by several factors, including tumour size and serum level of parathyroid hormone (PTH). This study examined the relationship between sestamibi accumulation and multidrug resistance (MDR)-related P-glycoprotein (P-gp) expression in a large series of surgically excised parathyroid tumours. METHODS: Seventy-eight patients underwent dual-phase sestamibi imaging before parathyroidectomy. Expression of P-gp within tumour cells was assessed by immunohistochemistry. Tumour size was measured and the ellipsoid volume calculated. Scan results were analysed in relation to preoperative serum levels of calcium and PTH, P-gp expression and tumour volume. RESULTS: Sixty-four of the 78 sestamibi scans were positive and 14 negative. Smaller adenomas (less than 0.5 cm(3)) were more likely to be sestamibi negative than larger lesions (P = 0.006). Ten of 14 adenomas with negative imaging showed strong P-gp membrane positivity and 45 of 64 lesions with a positive scan did not show P-gp membrane expression, indicating a significant association between high P-gp membrane immunoreactivity and negative sestamibi result (P = 0.006). CONCLUSION: These data suggest an association between P-gp membrane expression and false-negative sestamibi scan result. Inhibition of the P-gp transmembrane pump using MDR modulators may therefore improve the sensitivity of sestamibi scintigraphy.

The use of 18-fluoro-dihydroxyphenylalanine and 18-fluorodeoxyglucose positron emission tomography scanning in the assessment of metaiodobenzylguanidine-negative phaeochromocytoma.

123I-metaiodobenzylguanidine (123I-MIBG) scintigraphy scanning is commonly used in the imaging of phaeochromocytoma (and paraganglioma) to confirm the site of disease and whether any spread has occurred. However, 123I-MIBG imaging is negative in 15% of cases of benign phaeochromocytoma and around 50% of cases of malignant phaeochromocytoma. In recent years, positron emission tomography (PET) scanning using various different radiotracers has been shown to be a good alternative or supplementary investigation in phaeochromocytoma. We present the cases of four patients with symptoms and signs suggestive of phaeochromocytoma, but who had negative 123I-MIBG scans, and illustrate the usefulness of 18-fluoro-dihydroxyphenylalanine PET scanning in their assessment. In one of the patients, we illustrate how fluorodeoxyglucose PETscanning can provide useful information about the extent of malignant disease. These illustrative cases lend further support for the use of PET scanning in the assessment of phaeochromocytoma and suggest that it may have a particularly important role in the investigation of patients in whom 123I-MIBG scanning is negative.

16-Detector multislice CT in the detection of stress fractures: a comparison with skeletal scintigraphy.

AIMS: To test the hypothesis that the improved resolution afforded by 16-detector computed tomography (CT) would translate to better stress fracture detection when compared with skeletal scintigraphy. MATERIALS AND METHODS: Thirty-three cases of suspected stress fractures in 26 patients were investigated using skeletal scintigraphy and 16-detector CT performed on the same day. Planar images of the lower limbs were taken 3h post-injection of 400MBq (99m)Tc-methylene diphosphonate ((99m)Tc-MDP). (99m)Tc-MDP uptake was quantified at suspected fracture sites. CT was performed using a 16-detector multisection machine employing 0.75mm detectors and images reconstructed in 0.5mm increments. Examinations were reported independently and discordant results were compared at follow-up. RESULTS: At initial reporting scintigraphy identified fractures in 13 of the 33 cases and CT identified four of the 33. In one case, on review of the CT images, a fracture was present in the distal fibula that was not initially identified. This resulted in eight scintigraphic-positive CT-negative discordant cases. The (99m)Tc-MDP uptake was significantly lower in the discordant fracture group compared with the concordant group (p<0.01). CONCLUSIONS: Despite technological advances in CT, scintigraphy appeared to detect more stress fractures. As such, multidetector CT should not be used as a routine initial investigation in stress fracture detection. The potential use of (99m)Tc-MDP quantification at fracture sites is of interest and may be worth further investigation.

16 detector multislice CT versus skeletal scintigraphy in the diagnosis of wrist fractures: value of quantification of 99Tcm-MDP uptake.

To compare the measured uptake of 99Tcm-methylene diphosphonate (99Tcm-MDP) in those scaphoid fractures seen on both 16 detector multislice CT and scintigraphy, with those seen only on scintigraphy. Over a 12 month period a total of 51 patients with suspected fracture underwent both conventional 99Tcm-MDP scintigraphy and 16 detector multislice CT on the same day. The 99Tcm-MDP uptake was then quantified in patients with identified fracture. This was measured by placing a region of interest (ROI) over the fracture site and the mean and maximum number of counts were compared with those in a similar size ROI placed over background bone activity. A total of 23 fractures were identified on scintigraphy of which 16 were also detected on CT (concordant). In seven cases the fracture was not seen on CT, even in retrospect (discordant). In the discordant cases, follow-up radiographs and MRI (where available) also failed to demonstrate a fracture. The mean fracture count to background bone activity ratio averaged 7.7 (range 3.2-18.5) for concordant fractures and 3.8 (range 1.7-5.3) for discordant fractures (t-test p=0.04). The maximum fracture count to background bone activity ratio averaged 12.7 (range 4.3-27.7) for concordant fractures and 6.3 (range 2.6-9.5) for discordant fractures (t-test p=0.03). It is speculated whether these discordant fractures with less 99Tcm-MDP uptake may represent a less severe injury such as bone bruise.

Hepatocellular carcinoma tumour thrombus in a re-canalised para-umbilical vein: detection by 18-fluoro-2-deoxyglucose positron emission tomography imaging.

This case report describes an unusual site of tumour thrombus in a re-canalised para-umbilical vein, in a patient with hepatocellular carcinoma (HCC) and cirrhosis. The tumour thrombus was suspected on conventional radiography and confirmed using PET imaging, illustrating the complimentary value of structural and functional imaging in achieving the correct diagnosis.

Case report: False negative 16 detector multislice CT for scaphoid fracture.

We discuss a case of a 19-year-old man with scaphoid trauma. We describe the imaging findings on three sets of radiographs, bone scintigraphy, CT and MRI. CT failed to identify a scaphoid fracture, which was present on 6 week radiographs, MRI and scintigraphy. The case illustrates that despite multidetector technology, CT still relies upon cortical and or trabecular displacement to demonstrate fractures.

Large renal cell carcinoma isometabolic with normal liver on F-18 FDG PET scan.

Positron emission tomography (PET) using F-18 fluorodeoxyglucose (FDG) is a very effective imaging modality in the diagnosis, staging, and monitoring of a variety of malignant conditions. The principle of imaging is based on the enhanced utilization of glucose by cancer. In this report, we describe a patient with renal cell carcinoma who showed FDG uptake isometabolic to normal liver.

Cerebral neutrophil recruitment, histology, and outcome in acute ischemic stroke: an imaging-based study.

BACKGROUND AND PURPOSE: Evidence now exists for a pathogenic role for neutrophils in acute cerebral ischemia. We have studied the patterns and temporal profile of cerebral neutrophil recruitment to areas of acute ischemic stroke (IS) and have attempted to correlate this with neurological status and outcome. METHODS: Patients with cortical middle cerebral artery (MCA) IS were recruited within 24 hours of clinical onset. Neutrophil recruitment was studied using indium-111 (111In) troponolate-labeled neutrophils, planar imaging, and single-photon emission computed tomography (SPECT). Volume of brain infarction was calculated from concurrent computed tomography (CT). Hematoxylin and eosin sections were obtained postmortem (n=2). Outcome was measured using Barthel, Rankin, and National Institute of Health Stroke (NIHSS) scales. RESULTS: Fifteen patients were studied. Significant 111In-neutrophil recruitment to ipsilateral hemisphere, as measured by asymmetry index (AI), was demonstrated within 24 hours of onset in 9 patients; this response was heterogenous between patients and on repeated measurement attenuated over time. Histologically, recruitment was confirmed within intravascular, intramural, and intraparenchymal compartments. Interindividual heterogeneity in neutrophil response did not correlate with infarct volume or outcome. In an exploratory analysis, neutrophil accumulation appeared to correlate significantly with infarct expansion (Spearman rho=0.66; P=0.03, n=12). CONCLUSIONS: Neutrophils recruit to areas of ischemic brain within 24 hours of symptom onset. This recruitment attenuates over time and is confirmed histologically. While neutrophil accumulation may be associated with either the magnitude or the rate of infarct growth, these results require confirmation in future studies.

Focused parathyroid surgery with intraoperative parathyroid hormone measurement as a day-case procedure.

BACKGROUND: This study assessed the feasibility, efficacy and safety of focused parathyroidectomy combined with intraoperative parathyroid hormone (IOPTH) measurement in a day-case setting. METHODS: Over 28 months 50 consecutive patients (mean age 63 (range 33-92) years) with clear evidence of unifocal disease on sestamibi scanning or ultrasonography underwent unilateral neck exploration via a small lateral incision. Blood samples for measurement of IOPTH were taken at induction of anaesthesia, before adenoma excision and after adenoma excision (at 5, 10 and 20 min). Ten patients were discharged within 23 h and 40 patients on the day of surgery. RESULTS: A solitary adenoma was identified in all but one patient, with a mean operating time of 30 (range 16-57) min. After parathyroidectomy, IOPTH levels fell appropriately except in one patient with multiglandular hyperplasia. No patient developed symptomatic hypocalcaemia during the 2 weeks after operation, enabling cessation of oral supplements. All patients remained normocalcaemic on follow-up (mean 26 (range 8-84) weeks) and histological examination confirmed parathyroid adenoma (48 patients), hyperplasia (one) or carcinoma (one). CONCLUSION: After accurate preoperative localization of uniglandular disease, patients with primary hyperparathyroidism may be managed successfully and safely by focused parathyroidectomy with IOPTH measurement as a day-case procedure.

Minimally invasive parathyroid surgery for recurrent intrathyroid multiple endocrine neoplasia (MEN).

A case of recurrent multiple endocrine neoplasia-related hyperparathyroidism treated by minimally invasive parathyroid surgery is discussed.

Sentinel lymph node biopsy in breast cancer--is lymphoscintigraphy really necessary?

The role of lymphoscintigraphy in sentinel node biopsy in breast cancer remains debatable. This study assesses the value of lymphoscintigraphy in axillary sentinel node biopsy in women undergoing surgery for breast cancer. Sixty-two patients underwent sentinel node biopsy using a combination of technetium-labelled nanocolloid, lympho-scintigraphy and patent blue dye. Lymphoscintigraphy was successful in 84% of patients. Axillary sentinel nodes were identified intraoperatively in all these patients. Internal mammary nodes were identified on lymphoscintigraphy in 19%. Despite lymphoscintigraphy being unsuccessful in 10 patients, axillary sentinel nodes were found intraoperatively in eight of these patients. Lymphoscintigraphy did not increase the detection rate of axillary sentinel nodes and a negative scan did not preclude identification of an axillary sentinel node intraoperatively. This study questions the contribution of lymphoscintigraphy in axillary sentinel node biopsy, however its value may lie in the detection of extra-axillary nodes.

The use of nuclear medicine techniques in the emergency department.

Nuclear medicine techniques have received little attention in the practice of emergency medicine, yet radionuclide imaging can provide valuable and unique information in the management of acutely ill patients. In this review, emphasis is placed on the role of these techniques in patients with bone injuries, non-traumatic bone pain and in those with pleuritic chest pain. New developments such as single photon emission computed tomography (SPECT) in myocardial infarction are outlined and older techniques such as scrotal scintigraphy are reviewed. Radionuclide techniques are discussed in a clinical context and in relation to alternative imaging modalities or strategies that may be available to the emergency medicine physician. Aspects of a 24 hour nuclear medicine service are considered.

Memory lost, memory regained: neuropsychological findings and neuroimaging in two cases of paraneoplastic limbic encephalitis with radically different outcomes.

OBJECTIVE: To report two cases of paraneoplastic limbic encephalitis (PNLE) with similar clinical presentation, but dramatically different outcome and to highlight the role of neuropsychological and radiological evaluation in PNLE. METHODS: Both patients underwent an extensive battery of neuropsychological tests designed to document general intellectual function, anterograde verbal and visual memory, naming, knowledge and executive ability. In addition, structural (CT and MRI) and functional (HMPAO-SPECT) brain scans were performed. RESULTS: Both patients presented with fairly sudden onset of profound and persistent memory loss in the absence of other neurological symptoms. Their subsequently diagnosed small cell lung cancer was treated with a combination of radiotherapy and chemotherapy, leading to remission of the tumour. The memory of patient 1 recovered fully and he died from an unrelated cause 1 year later; neuropsychological testing showed a severe, but isolated, anterograde amnesia, brain MRI was normal and HMPAO-SPECT showed left medial temporal hypoperfusion. Patient 2 remained densely amnesic despite regression of her lung tumour; neuropsychological testing disclosed both anterograde and extensive retrograde amnesia together with more generalised cognitive deficits including anomia and executive impairments, MRI showed gross atrophy of the hippocampus and amygdala bilaterally, and HMPAO-SPECT showed pronounced frontal and temporal hypoperfusion. CONCLUSION: Complete remission from PNLE may occur and seems to be associated with pure anterograde amnesia without evidence of structural hippocampal damage in MRI. By contrast, cognitive deficits beyond severe anterograde amnesia and evidence of destructive medial temporal lobe pathology on MRI seem to be poor prognostic features.

Is the dyspnea during adenosine cardiac stress test caused by bronchospasm?

BACKGROUND: Adenosine cardiac stress is widely used as an alternative to exercise testing during myocardial perfusion imaging (MPI). Dyspnea often accompanies the adenosine stress test. Although known asthmatic patients are excluded from this test because of the danger of bronchospasm, there is incomplete information regarding the role of factors such as chronic obstructive pulmonary disease (COPD) and tobacco smoking in adenosine-induced dyspnea. PATIENTS AND METHODS: A total of 122 consecutive patients (75 male, 47 female; mean age 59 years, SD 10 years) undergoing pharmacologic stress testing with an intravenous infusion of adenosine also had volume-flow spirometry (Vitalograph Compact, Vitalograph Ltd) before, during, and after the test. The indices assessed were forced expiratory volume in one second, its ratio to the forced vital capacity, and peak expiratory flow rate. RESULTS: Mild to severe symptoms were experienced by 81% of patients during adenosine infusion. More than half the patients had dyspnea, but there was no associated bronchospasm. Although the patients with COPD showed parameters indicative of bronchial resistance compared with those without this problem, there was no further deterioration after adenosine infusion. Similarly, patients with a history of tobacco abuse, despite showing a tendency toward increasing airways resistance, had no bronchospasm during the administration of adenosine. CONCLUSIONS: (1) Although dyspnea is a common problem during adenosine stress MPI, it is not associated with any appreciable bronchospasm. (2) COPD and tobacco abuse do not appear to be contraindications to adenosine stress MPI studies. However, it is probably safe to exclude patients with severe COPD from adenosine stress MPI until after further evaluation with larger numbers of patients.

Sentinel lymph node biopsy in impalpable breast cancer.

Sentinel lymph node biopsy has been investigated using combined radioactive colloid and supra vital blue dye in 27 patients with impalpable breast cancers. Sentinel nodes were identified in 25 cases (93%). Seven patients had involved nodes of whom all had a positive sentinel node. Sentinel node biopsy is ideally suited for use in impalpable breast cancers.

Radiolabeled leucocyte imaging in diffuse granulomatous involvement of the meninges in Wegener's granulomatosis: scintigraphic findings and their role in monitoring treatment response to specific immunotherapy (humanized monoclonal antilymphocyte antibodies).

BACKGROUND AND PURPOSE: Diffuse involvement of the meninges by remote granulomas in Wegener's granulomatosis is rare. This study reports the radiolabeled leucocyte imaging findings in five such patients. The diagnosis was made by MR imaging in five patients and confirmed in four by findings at meningeal biopsy. The potential role of serial radiolabeled leucocyte examinations in assessing treatment response is discussed. METHODS: Three of the five patients underwent whole-body planar 111In-labeled leucocyte imaging. Two of these patients had serial imaging and one had, in addition, a 99mTc-HMPAO-labeled leucocyte single-photon emission CT brain examination. Two of the five patients had whole-body planar 99mTc-HMPAO-labeled leucocyte imaging. Of these, one patient had serial imaging. The radiolabeled leucocyte imaging findings were correlated with MR findings and with the patients' clinical course. RESULTS: In four patients there was a midline linear area of increased tracer uptake in the brain, and in one of these, tracer uptake also extended laterally over the brain convexity. In two patients linear tracer uptake extended in an inferolateral direction from the midline. These abnormalities correlated with meningeal thickening in the falx, over the brain convexity, and in the tentorium cerebelli on MR images. Serial imaging in three patients revealed a reduction or disappearance in tracer uptake after treatment with anti-CD52, which correlated with clinical improvement. CONCLUSION: In patients with Wegener's granulomatosis, abnormal uptake corresponding to meningeal thickening can be seen on planar radiolabeled leucocyte images. Leucocyte imaging may be useful for monitoring treatment response.