Proliferative and anti-apoptotic activity of esophageal mucosa in gastroesophageal reflux disease is not affected by fundoplication: a 4-year follow-up study.

BACKGROUND: The role of fundoplication in the prevention of esophageal adenocarcinoma is controversial. Development of cancer is associated with proliferation and anti-apoptosis, for which little data exist regarding their response to fundoplication. METHODS: Ki-67 and Bcl-2 expression was assessed in the esophagogastric junction (EGJ) and the distal and proximal esophagus of 20 patients with gastroesophageal reflux disease (GERD) treated by fundoplication and in 7 controls. Endoscopy was performed preoperatively and 6 (20 patients) and 48 months (16 patients) postoperatively. RESULTS: There were positive correlations between Ki-67 and Bcl-2 levels in the EGJ (p > 0.001) and in the distal (p = 0.001) and proximal esophagus (p = 0.013). Compared to the preoperative level, Ki-67 expression was elevated in the distal (p = 0.012) and proximal (p = 0.007) esophagus at 48 months. In addition, compared to control values, Ki-67 expression was lower at the 6-month follow-up in the EGJ (p = 0.037) and the proximal esophagus (p = 0.003), and higher at the 48-month follow-up in the distal esophagus (p = 0.002). Compared to control values, Bcl-2 was lower at 6 months in the EGJ (p = 0.038). CONCLUSIONS: Proliferative activity after fundoplication increased in the long term in the distal esophagus despite a normal fundic wrap and healing of GERD.

Paricalcitol aggravates perivascular fibrosis in rats with renal insufficiency and low calcitriol.

Cardiovascular complications are a major problem in chronic renal failure. We examined the effects of plasma calcium, phosphate, parathyroid hormone (PTH), and calcitriol on cardiac morphology in 5/6 nephrectomized rats. Fifteen weeks after nephrectomy rats were given a control diet, high-calcium or -phosphorus diet, or given paricalcitol treatment for 12 weeks. Sham-operated rats were on a control diet. Blood pressure, plasma phosphate, and PTH were increased, while the creatinine clearance was reduced in remnant kidney rats. Phosphate and PTH were further elevated by the high-phosphate diet but suppressed by the high-calcium diet, while paricalcitol reduced PTH without influencing phosphate or calcium. The high-calcium diet increased, while the high-phosphate diet reduced plasma calcium. Plasma calcitriol was significantly reduced in other remnant kidney groups, but further decreased after paricalcitol. Cardiac perivascular fibrosis and connective tissue growth factor were significantly increased in the remnant kidney groups, and further increased in paricalcitol-treated rats. Hence, regardless of the calcium, phosphate, or PTH levels, cardiac perivascular fibrosis and connective tissue growth factor increase in rats with renal insufficiency in association with low calcitriol. Possible explanations are that aggravated perivascular fibrosis after paricalcitol in renal insufficiency may be due to further suppression of calcitriol, or to a direct effect of the vitamin D analog.

Severity of tubulointerstitial inflammation and prognosis in immunoglobulin A nephropathy.

Many risk factors for progression in immunoglobulin A nephropathy (IgAN) have been found. We focused on renal leukocyte infiltrations and cytokines in IgAN. The subjects were 204 IgAN patients. Renal histopathological changes were semiquantitatively graded. Expression of tubulointerstitial Leukocyte common antigen (LCA), CD3, CD68, interleukin (IL)-1beta, and IL-10 was evaluated by immunohistochemistry. These parameters were correlated with progression of IgAN. The significance of these correlations was tested by a multivariate analysis. Glomerulosclerosis, tubular atrophy, interstitial inflammation, and hyaline arteriolosclerosis correlated with progression in all patients and also in patients with initially normal serum creatinine. Tubulointerstitial LCA, CD3, CD68, and IL-1beta expression correlated with progression. CD3 had the strongest correlation. In the multivariate analysis, tubulointerstitial CD3, hypertriglyceridemia, elevated serum creatinine concentration, and interstitial fibrosis were independently associated with progressive disease in all patients, and tubulointerstitial CD3 expression and hyaline arteriolosclerosis in patients with initially normal serum creatinine. We found parameters reflecting tubulointerstitial inflammation to predict deterioration of renal function in IgAN. This was also seen in patients whose serum creatinine was normal at the time of renal biopsy. Our findings show that, an immunohistochemical evaluation of tubulointerstitial inflammation seems to be a useful tool in determining the prognosis in IgAN.

Thrombus imaging with 99mTc-HMPAO-labeled platelets and 111In-labeled monoclonal antifibrin antibodies.

Eighteen patients with suspicion of deep venous thrombosis (DVT) in the lower extremities were imaged both with autologous 99mTc-HMPAO-labeled platelets (Tc-PLT) and 111In-labeled monoclonal antifibrin antibodies (In-MoAbs) on the same day. Presence or absence of thrombosis was verified by venography. Tc-PLT was given i.v. followed after 30 min by In-MoAbs. Anterior and posterior projections of the lower extremities were obtained with a large field-of-view gamma camera at 5 to 25 min, 2 h, 4 to 6 h, and 20 h after administration of the marker. Both Tc-PLT and In-MoAbs detected DVT well but less frequently than venography. Thrombi were visualized at 2 to 4 h after injection. The quality of images was better with Tc-PLT than with In-MoAbs. In the patients treated during the study, heparin significantly (p < 0.01) inhibited the uptake of Tc-PLT but not of In-MoAbs. We conclude that both Tc-PLT and In-MoAbs are suitable agents for the detection of DVT especially in patients without anticoagulation.