Kottekkattu Balan

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 200 000 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.

Use of 111-Indium-labelled 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.

Utility of 111In-labelled leucocyte scintigraphy in patients with fever of unknown origin in an era of changing disease spectrum and investigational techniques.

Background111In-labelled leucocyte, imaging is often used to investigate patients with fever of unknown origin (FUO). Its diagnostic performance, however, has been variable and a broad range of sensitivities and specificities have been reported. The purpose of this investigation was to evaluate the usefulness of 111In-labelled leucocytes scintigraphy in the detection of a cause of FUO in the light of a changing spectrum of diseases causing it and advances in investigational techniques. Materials and methodsSixty-one patients with a clinical diagnosis of FUO underwent whole-body 111In-troponolate-labelled leucocyte scintigraphy in our department over a 2 year period between February 2004 and February 2006. Of these, 54 patients were retrospectively reviewed to identify a cause of FUO. Other parameters such as C-reactive protein (CRP), leucocyte count and radiological findings were also evaluated. ResultsLeucocyte scintigraphy was found to be true positive in 12 patients, true negative in 24 patients, false positive in 10 patients and false negative in eight patients. The overall sensitivity of scintigraphy was 60%, specificity 71%, positive predictive value 55%, and negative predictive value 75%. There was no difference in the scintigraphic sensitivity between patients with spontaneous FUO and those with post-operative FUO although the latter showed a higher specificity and PPV. CRP and leucocyte count did not differ significantly between patients with true positive and true negative scintigrams. Overall, 83% of patients with abnormal radiological examinations had positive findings on scintigraphy and 87% of patients with negative findings on radiology had normal scintigraphy. ConclusionDespite changes in disease spectrum and advances in investigational techniques, our results suggest that 111In-leucocyte scintigraphy is still a useful technique in establishing the cause of FUO. A higher PPV of this test in post-operative situations makes it especially applicable in this category of patients. Equally, the higher NPV in patients with spontaneous FUO virtually excludes infection/inflammation. Finally, a higher pre-test probability based on the radiological tests seems to be important in the optimal use of leucocyte imaging.

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

Eur J Clin Invest 2010; 41 (1): 77–83

Clinical significance of scintigraphic rapid gastric emptying.

ObjectivesTo 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 methodsResults 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. ResultsSeventy (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 in170 (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%. ConclusionUpper 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.

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

BackgroundTo review our experience of doing whole gut transit scintigraphy in patients presenting with functional gastrointestinal problems and to determine its clinical usefulness. MethodAll whole gut transit studies using a liquid meal over a 5-year-period were reviewed and clinical outcome assessed. ResultsFifty-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. ConclusionLiquid-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.

Bilateral adrenal metastases from malignant melanoma: concordant findings on 18F-FDG and 18F-FDOPA PET

Adrenal masses often pose a diagnostic challenge. The majority represent functional adrenal adenomas, but primary or secondary malignancy must be considered. Therefore functional characterisation of the lesion is important in determining the type of treatment. The adrenal gland is the fourth most common site of metastasis after the lungs, liver and bone [1]. Malignant melanoma is one of the most common primary tumours that metastasise to the adrenal gland apart from lung, breast, kidney, thyroid and colon cancers [1]. In the literature the incidence of adrenal metastases from malignant melanoma is about 50%. The prognosis and treatment are linked to the early detection of metastatic disease in malignant melanoma [2, 3]. Ffluorodeoxyglucose positron emission tomography (FFDG PET) is a well-accepted method for the detection of metastatic disease in malignant melanoma [4]. However, some benign lesions may be classified as malignant

I-123 Mibg Uptake in a Gastrointestinal Stromal Tumor (gist)

Abstract: I-123 metaiodobenzylguanidine (MIBG) scintigraphy is the examination of choice for visualizing tumor sites of pheochromocytoma. We report a middle-aged woman with incomplete Carneys Triad (association of pheochromocytoma/paraganglioma, gastrointestinal stromal tumor [GIST], and pulmonary chondromas) in whom a GIST was identified on the basis of its MIBG uptake. She had undergone surgical resection of a pheochromocytoma and postoperatively developed a mass in the epigastrium, which was thought to be recurrence. The lesion was MIBG-positive. However, following surgery, histologic examination of the specimen revealed findings suggestive of GIST.

Chilaiditi sign appearing as a liver lesion on FDG PET.

Abstract: A clear understanding of normal physiological distribution of the radiopharmaceutical, commonly encountered normal variants, and benign pathologic uptake is important to avoid mistaken diagnosis on an F-18 FDG PET scan. The distribution of FDG in the bowel is variable and may occasionally lead to diagnostic pitfalls. Chilaiditi sign is a well-known anatomic variant and describes the interposition of bowel between the liver and diaphragm. The authors present a case where an apparent abnormality in the liver on an FDG PET only study was proven to be due to bowel activity related to Chilaiditi sign on CT correlation.

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.