Apoptosis, inflammatory bowel disease and carcinogenesis: overview of international and Greek experiences.

Apoptosis is critical for organ development, tissue homeostasis, the elimination of abnormal cells and the maintenance of immune homeostasis by variable regulatory mechanisms. The death of T lymphocytes following their activation involves a series of proteases (caspases), which comprise the central executioners of apoptosis. Abnormal regulation of apoptosis results in disease. T-cell resistance against apoptosis contributes to inappropriate T-cell accumulation and the perpetuation of the chronic inflammatory process in inflammatory bowel disease with potential tumourigenic effect. The use of antitumour necrosis factor-alpha, anti-interleukin-6R and anti-interleukin-12 antibodies suppresses colitis activity by induction of T-cell apoptosis, thereby having important implications for the design of effective therapeutic strategies in inflammatory bowel diseases. Contrary to international data, the incidence of cancer in Greek patients with inflammatory bowel disease appears to be low. A balance between cell proliferation (Ki-67 overexpression) and apoptosis (Bax protein overexpression) may partly explain the low incidence of cancer development in Greek inflammatory bowel disease patients.     

Ampullary carcinoma: Demonstration by current MR techniques

The objective of this study was to demonstrate the appearance of ampullary carcinoma using current MR techniques, including fat suppression, gadolinium enhancement, and MR cholangiography. Nine patients with ampullary carcinoma were examined by MRI at 1.5 T. MR examinations included T1-weighted spoiled gradient echo, T1-weighted fat-suppressed, and immediate postgadolinium spoiled gradient echo images for all patients and MR cholangiography for three patients. The imaging features of ampullary carcinomas, including tumor size and morphology, signal intensity, and enhancement characteristics, were determined. Ampullary carcinomas shown on MR images ranged in size from 1.5 to 5.5 cm. Tumors were low in signal intensity on precontrast T1-weighted spoiled gradient echo and T1-weighted fat-suppressed images relative to normal pancreatic tissue and enhanced less than normal pancreas on immediate postgadolinium spoiled gradient echo images. Tumor conspicuity was greatest on immediate postgadolinium spoiled gradient echo images. MR cholangiography demonstrated high grade obstruction of the common bile duct and mild dilatation of the pancreatic duct at the level of the ampulla with abrupt termination of the ducts in two untreated patients and moderate dilatation of the common bile duct in one patient who had a biliary stent. Ampullary carcinomas can be demonstrated on MR images as small masses arising at the ampulla. Tumors are well defined on immediate postgadolinium spoiled gradient echo images.     

Perfusion imaging by a flow-sensitive alternating inversion recovery (Fair) technique: Application to functional brain imaging

Perfusion is a crucial physiological parameter for tissue function. To obtain perfusion-weighted images and consequently to measure cerebral blood flow (CBF), a newly developed flow-sensitive alternating inversion recovery (FAIR) technique was used. Dependency of FAIR signal on inversion times (TI) was examined; signal is predominantly located in large vessels at short TI, whereas it is diffused into gray matter areas at longer TI. CBF of gray matter areas in the human brain is 71 ± 15 SD ml/100 g/min (n = 6). In fMRI studies, micro- and macrovessel inflow contributions can be obtained by adjusting TIs. Signal changes in large vessel areas including the scalp were seen during finger opposition at a TI of 0.4 s; however, these were not observed at a longer TI of 1.4 s. To compare with commonly used BOLD and slice selective inversion recovery techniques, FAIR and BOLD images were acquired at the same time during unilateral finger opposition. Generally, activation sites determined by three techniques are consistent. However, activation of some areas can be detected only by FAIR, not by BOLD, suggesting that the oxygen consumption increase couples with the CBF change completely. Relative and absolute CBF changes in the contralateral motor cortex are 53 ± 17% SD (n = 9) and 27 ± 11 SD ml/100 g/min (n = 9), respectively.     

Immediate postgadolinium spoiled gradient-echo MRI for evaluating the abdominal aorta in the setting of abdominal MR examination

To assess the reproducibility and image quality of immediate postgadolinium chelate spoiled gradient-echo MRI in demonstrating disease of the abdominal aorta. All patients (27 patients: 21 men, 6 women) with substantial disease of the abdominal aorta, who underwent abdominal MR examinations at 1.5 T between 1991 and 1995, were entered in the study. Patients were referred for evaluation of suspected aortic disease (14 patients) or other abdominal diseases (13 patients). Three experienced investigators manually measured luminal and external aortic wall diameters and rated image quality, definition of inner and outer walls, extent of disease, and presence of other abdominal abnormalities, in an independent fashion. A cardiovascular surgeon then rated all studies to determine whether clinical management could be based on the MR findings alone. There was 98 to 99% agreement in measurements of luminal and external wall diameter between the three investigators. Overall image quality was rated as good in 77.8 to 88.9% of patients. A total of 31 additional nonaortic abdominal abnormalities were detected by all observers. The cardiovascular surgeon rated 25 of 27 studies as adequate to determine clinical management based on MR findings alone. Immediate postgadolinium spoiled gradient-echo MRI is a reproducible technique for the demonstration of abdominal aortic disease and possesses good image quality. Advantages of this technique include simultaneous evaluation of other nonvascular diseases of the abdomen, short examination time, and easy implementation as part of routine abdominal MRI scanning protocol.     

Osteonecrosis of the jaws associated with use of risedronate: report of 2 new cases.

Use of various bisphosphonates has been associated with the development of osteonecrosis of the jaws (ONJ). At least 865 cases of ONJ attributed to these agents have been reported in the English-language literature. Approximately 96% of these published cases were seen with administration of the intravenous agents pamidronate and zoledronate, whereas only 26 cases have been associated with oral bisphosphonates, 25 of them with alendronate. Only a single case of ONJ associated with the oral bisphosphonate risedronate has been previously cited. We report 2 cases of ONJ attributed to risedronate administration. The patients developed osteonecrosis 15 and 24 months after treatment for osteopenia. A regimen of antibiotics and chlorhexidine mouthrinse resolved the osseous defect in the mandible caused by complete exfoliation of a lingual torus in 1 patient. The other patient required sequestrectomy, repeated courses of antibiotics, surgical debridement, and steroids to promote closure of an oroantral fistula and management of sinusitis after bone grafting and implant placement in the posterior maxilla. A demographic profile of reported oral bisphosphonate users affected by ONJ is also provided. With the millions of patients receiving various oral bisphosphonates for osteopenia and osteoporosis, health care practitioners should be aware of the potential for the onset of osteonecrosis and familiar with its management.     

Liver lesion detection,characterization, and effect on patient management: Comparison of single-phase spiral CT and current MR techniques

This study compares liver lesion detection, characterization, and effect on patient management between single-phase spiral CT and MRI using spoiled gradient echo (SGE), T2-weighted fat-suppressed spin echo, and serial post gadolinium SGE. All patients with suspected liver lesions who underwent spiral CT and MRI within a 1-month period between January 1993 and September 1996 were included in the study. Spiral CT and MRI were interpreted prospectively in a blinded fashion by separate individual experienced investigators, and lesion detection and characterization were determined. Confirmation was obtained by surgery (6 patients), biopsy (18 patients), imaging follow-up (36 patients), or combined reading of all imaging studies and clinical follow-up (29 patients). Effect on patient management was determined by combined chart review and interview of the patients' physicians and by retrospective clinical assessment performed by a surgical oncologist and medical oncologist separately. Eighty-nine patients were included in the study. Regarding true positive lesion detection, 295 and 519 lesions were detected on spiral CT and MR images, respectively, which was significantly different on a patient-by-patient basis (P < .001). More lesions were detected on MR than on spiral CT in 44 of 89 patients (49.4%), and 11 of these 44 patients had lesions shown on MRI in whom no lesions were apparent on CT images. No patients had true positive lesions shown on spiral CT that were not shown on MRI. Regarding lesion characterization, 129 and 466 lesions were characterized on spiral CT and MRI images, respectively, which was significantly different on a patient-by-patient basis (P < .001). More lesions were characterized on MR than CT images in 67 patients (75.3%). Regarding effect on patient management, chart review with physician interview demonstrated that findings on MRI provided information that altered patient management as compared with findings on spiral CT in 57 patients. Retrospective clinical evaluation by the surgical and medical oncologist showed that MRI was considered to have a greater effect on patient management than spiral CT in 58 and 55 patients, respectively. Comparing current MRI technique to single-phase spiral CT, MRI detected more lesions in 49.4% and characterized more lesions in 75.3% of patients investigated for focal liver disease. MRI had a greater effect on patient management in each of the three methods than singlephase spiral CT in more than 61% of patients.     

Prevalence and clinical significance of anticardiolipin antibodies in patients with type 1 autoimmune hepatitis

There are few case reports on the association between autoimmune hepatitis (AIH) and anticardiolipin antibodies (anti-CLAbs) and/or antiphospholipid syndrome (APLS). We studied the anti-CLAbs prevalence in AIH and other hepatic diseases. We also investigated whether anti-CLAbs are co-factor dependent and which is their avidity since co-factor dependency or increased resistance is associated with APLS. Fifty-nine AIH patients, 228 HCV, 50 HBV, 123 with other non-viral and non-autoimmune liver disorders (nV-nALD) and 267 healthy people were investigated for anti-CLAbs and antibodies against beta-2-glycoprotein I (anti-beta2-GPI). Resistance of IgG anti-CLAbs was evaluated using 2 M urea. IgG anti-CLAbs detected in 39% of AIH, 19.7% of HCV (p=0.006), 14% of HBV (p=0.01), 8.1% of nV-nALD (p=0.000) and 1.1% of healthy (p=0.000). IgG anti-CLAbs were associated with the presence of cirrhosis and active AIH while their resistance to urea was high. Anti-beta2-GPI was detected in two AIH patients. We demonstrated a significantly higher prevalence of anti-CLAbs in patients with AIH compared to other diseases and healthy people. Anti-CLAbs were associated with AIH stage but no association was found with APLS clinical manifestations (thrombosis, pregnancy morbidity, thrombocytopenia). However, their avidity was comparable with that of APLS indicating the need for prospective studies in order to address whether anti-CLAbs in AIH may contribute to the progression of liver disease or APLS development.