In vivo confocal microscopy findings of cornea and tongue mucosa in patients with Sjögren's syndrome.

INTRODUCTION AND OBJECTIVES: We aimed to investigate whether Sjögren's syndrome (SS) had distinctive findings in tongue confocal microscopy in a non-invasive manner. MATERIALS AND METHODS: This retrospective case-control study evaluated corneal and tongue confocal microscopy findings of the right eyes of 25 patients with aqueous deficient dry eye and 12 healthy volunteers without dry eye findings. There were a total of 14 patients diagnosed with SS-associated dry eye (SSDE), while 11 cases were evaluated as non-Sjögren dry eye (NSDE). RESULTS: A significant difference was observed in the dendritic cell count at the corneal subbasal nerve level between the SSDE and NSDE groups (P=.018). In SSDE group, the confocal microscopy images of dendritiform hyperreflective inflammatory cells in the tongue mucosa were in favor of inflammation. However, these findings were not found in patients with NSDE or in controls. CONCLUSIONS: This study showed that confocal microscopy provided a non-invasive evaluation of the inflammatory cells in the tongue of SS patients.

Pleiotropic effects of pitavastatin: a pilot study using the saphenous vein endothelial cell model of endothelial injury and prevention of atherosclerosis.

OBJECTIVE: Cardiovascular diseases are responsible for the majority of deaths on a global scale. Atherosclerosis is the main risk factor for cardiovascular disorders and represents a complex phenomenon associated with endothelial dysfunction and inflammation. Statins, especially atorvastatin (ATV) and pitavastatin (PTV), are common agents used to control ongoing atherosclerotic events in the body to minimize cardiovascular disease-based deaths. MATERIALS AND METHODS: The present study aimed at comparing the efficacy of ATV and PTV in a cell line model of inflammation. Human saphenous vein cells were treated with TNF-alpha to mimic atherosclerotic conditions, and the cells were divided into 7 groups, including control, DMSO, TNF-alpha (10 ng/mL-6 hours), ATV (50 µM/24 hours), PTV (2 µM/24 hours), ATV (50 µM/24 hours)+TNF-alpha (10 ng/mL-6 hours) and PTV (2 µM/24 hours)+TNF-alpha (10 ng/mL-6 hours). The expression levels of 20 proinflammatory cytokines and chemokines were investigated in these groups using a human atherosclerosis antibody array. RESULTS: Possible pathway interactions were determined by STRING and PANTHER analyses. Comparison with the effect of ATV indicated that PTV reduced the levels of 4 proinflammatory cytokines: CCL11, CSF2, CCL20, and TGFB1 (p<0.05). CONCLUSIONS: Pleiotropic effects of pitavastatin against cardiovascular diseases appeared to be better; however, additional studies are required to compare statins and to identify new drugs that maintain broader protection from the risks of cardiovascular diseases.

[125/123I] 5-Iodo-3-pyridyl ethers. syntheses and binding to neuronal nicotinic acetylcholine receptors.

Three 3-pyridyl ether nicotinic ligands-(S)-5-Iodo-3-[(2-pyrrolidinyl)-methoxy]pyridine (5-iodo-A-85865), (S)-5-Iodo-3-[1-(methyl)-2-pyrrolidinyl-methoxy]pyridine (5-Iodo-A-84543), and (S)-5-iodo-3-[1-methyl-(2-azetidinyl)-methoxy]pyridine (5-iodo-N-Me-A-85380) were labeled with I-125/I-123, and their ability to label high-affinity brain nicotinic acetylcholine receptors (nAChRs) was evaluated. The most promising ligand, [123/125I] 5-iodo-A-85865, showed approximately 65% inhibition of radioactivity uptake in thalamus in mice pretreated with cytisine. Preliminary SPECT imaging studies with [123I] 5-iodo-A-85865 revealed a distribution profile consistent with nAChRs (thalamus > frontal cortex > cerebellum) and a more rapid pharmacokinetic profile relative to azetidinyl 3-pyridyl ether based ligands.

Synthesis of an I-123 analog of A-85380 and preliminary SPECT imaging of nicotinic receptors in baboon.

A radiosynthetic method to prepare the nicotinic acetylcholine receptor radioligand (S)-5-[123I]iodo-3-(2-azetidinylmethoxy)pyridine, 5-IA, has been developed. The two-step sequence produced [123I]-5-IA in high radiochemical yield (52%), high radiochemical purity (98%), and high specific radioactivities (> 8,500 mCi/mumol). Preliminary single photon emission computed tomography studies with [123I]-5-IA in baboon demonstrated the appropriate regional localization for a high-affinity nicotinic radioprobe (thalamus > frontal cortex > cerebellum). Pretreatment with cytisine blocked [123I]-5-IA uptake in all brain regions (78-59% reduction), demonstrating the specificity of the radiotracer.

99mTc-MIBI scintigraphy in metastatic renal cell carcinoma: clinical validation of the relationship between 99mTc-MIBI uptake and P-glycoprotein expression in tumour tissue.

Technetium-99m hexakis-2-methoxyisobutylisonitrile (MIBI) and thallium-201 imaging was performed in a patient with metastatic renal cell carcinoma (RCC), which is a well-known tumour type demonstrating P1-glycoprotein (PGP) overexpression. Two scintigraphic patterns - Tl(+)/MIBI(-) in primary tumour and Tl(+)/MIBI(+) in metastatic tumour - were observed, suggesting high- and low-level PGP expression, respectively. Immunochemical study for PGP revealed strong staining of the primary tumour cells. This case clinically validates the previously suggested relationship between 99mTc-MIBI uptake and PGP expression.

Early and delayed thallium-201 scintigraphy in thyroid nodules: the relationship between early thallium-201 uptake and perfusion.

Seventy-six patients with thyroid nodules were studied. Initially, 74 MBq of thallium-201 was injected. The thyroid gland was imaged 15 min (early) and 3 h (delayed) after the injection. Thereafter, 185 MBq technetium-99m pertechnetate was injected. Immediately after the injection, a 1-min perfusion image was acquired, followed by an image at 20 min. Increased early and delayed 201Tl uptake compared with the contralateral thyroid tissue was adopted as the criterion for malignancy. Sensitivity, specificity and negative predictive values were found to be 85%, 64% and 78%, respectively, in operated patients, but these values were 86%, 87% and 95%, respectively, in the whole group, including patients followed with fine-needle aspiration biopsy. With the purpose of investigating the relationship between perfusion and early 201Tl uptake, both perfusion and early images were graded comparing nodular activity with contralateral thyroid activity. There was a poor correlation between perfusion and 201Tl uptake. The correlation was even worse in hyperactive nodules. It is concluded that early and delayed 201Tl imaging should not be used in the differential diagnosis of cold nodules and that early 201Tl uptake seems to be more closely related to factors other than perfusion.

Detection of bone lesions in Langerhans cell histiocytosis: complementary roles of scintigraphy and conventional radiography.

PURPOSE: This research was undertaken to determine the relative sensitivity of scintigraphic and radiographic bone survey examinations in detecting bone lesions in various regions of the skeleton in patients with a histopathologic diagnosis of Langerhans cell histiocytosis (LCH). PATIENTS AND METHODS: Radionuclide skeletal scintigraphy (RNSS) and x-ray skeletal surveys (XRSS) of 42 children with a histopathologic diagnosis of LCH were evaluated retrospectively. RESULTS: Of the 191 lesions detected in 42 patients, 36 (19%) were missed on RNSS and 55 (29%) were missed on XRSS. Most of the missed lesions on RNSS were in the skull (26 of 36). XRSS also missed 13 skull lesions seen on RNSS. Most of the lesions missed on XRSS were in the ribs (20 of 30 rib lesions), whereas RNSS identified 29 of them. XRSS also missed 13 of 38 lesions in the spine and pelvis, while RNSS demonstrated all of them. Both modalities showed comparable sensitivity in the extremities. CONCLUSION: RNSS has a greater value in detecting sites of bone involvement with LCH than reported previously. RNSS is more sensitive than XRSS in detecting histiocytic lesions in the ribs, spine and pelvis and less sensitive in identifying lesions in the skull.

Hepatobiliary scintigraphy in children with cystic fibrosis and liver disease.

UNLABELLED: Intra- and extrahepatic impairment of biliary drainage is important in the pathogenesis of liver disease in cystic fibrosis. Distal common bile duct obstruction is reported to occur in 13% to 96% of these patients. Between 1975 and 1993, 17 of 372 children (4.5%) with cystic fibrosis attending The Children's Memorial Medical Center in Chicago had liver disease based on clinical and laboratory findings. METHODS: Hepatobiliary scintigraphy (HBS) with 99mTc-DISIDA was performed on 12 of the 17 children (mean age at the time of exam was 9 yr, with a range of 1 mo to 21 yr). RESULTS: All had hepatomegaly, four had splenomegaly and two had bleeding esophageal varices. Twenty HBS exams on these 12 patients documented nonvisualization of the gallbladder in 7, dilated intrahepatic ducts in 6 (only the left lobe was involved in 3 patients), nonvisualization of bowel in two, delayed peaking time in the liver (> 10 min) in four patients, and delayed clearance from the liver parenchyma (T1/2 > 20 min) in 11. There appears to be a spectrum of abnormal HBS findings in cystic fibrosis patients with liver disease. These are delayed clearance of liver parenchyma, nonvisualization of the gallbladder and dilated intrahepatic ducts with a predilection for the left lobe of the liver. These abnormal findings fluctuate in time and may not correlate with the findings on ultrasonography. CONCLUSION: Quantitative hepatobiliary scintigraphy is a valuable tool in the evaluation and management of the liver disease in this patient population.

Hepatobiliary excretion of MAG3. Simulation of a urinary leak.

A Tc-99m MAG3 renal scintigram was performed on a patient with severe renal insufficiency and bilateral ureteral stents. The Tc-99m MAG3 study displayed typical findings for renal insufficiency but also suggested the presence of lower tract obstruction. Moreover, the delayed posterior and posterior oblique views of the abdomen revealed an extrarenal collection of tracer suggestive of a urinary leak. With the help of additional views, this extrarenal activity was proven to be tracer in the bowel and biliary system. Biliary excretion of Tc-99m MAG3 can be prominent in patients with renal insufficiency and could lead to an erroneous diagnosis of urinary leak. Finally, scintigraphic diagnosis of lower tract obstruction may be difficult in patients with renal insufficiency, but some helpful signs may lead to the correct diagnosis.

A scintigraphic sign for detection of right-to-left shunts.

We evaluated the usefulness of a new scintigraphic sign, a quantum mottling pattern, in diagnosing right-to-left shunt using 99mTc-MAA particles. The quantum mottling pattern is characterized by random distribution of discrete clumps of radioactivity that are more intense than the general body background. Forty-nine 99mTc-MAA scintigrams were analyzed retrospectively for presence of a quantum mottling pattern in extrapulmonary soft tissues and brain. This distinctive pattern was observed in every patient (18/18) in whom a right-to-left shunt was confirmed by nonscintigraphic means and was noted only in one patient in whom independent proof of a right-to-left shunt was not available. In contrast, application of conventional criteria yielded a true-positive interpretation for 15/18 patients with right-to-left shunts and a false-positive interpretation for another four patients. Presence of a quantum mottling pattern on 99mTc-MAA images appears to be a reliable aid for detecting a right-to-left shunt. Use of this sign is likely to improve accuracy of the scintigraphic test in patients with small shunts.

Incidental lymph node visualization on bone scan due to subcutaneous infiltration of Tc-99m MDP. A potential for false positive interpretation.

Soft tissue localization of radiotracer on bone scintigraphy may result in false-positive interpretations, if the activity overlies a bony structure. A case is presented in which special views and follow-up clarified the soft tissue nature of focal uptake in arm and axilla.