Axillary lymph-node metabolic activity assessment on 18F-FDG-PET/CT in rheumatoid arthritis patients treated with biologic therapies.

Objective: Recent studies have provided new insights into the role of lymph nodes (LNs) in rheumatoid arthritis (RA). The aim of this study was to evaluate the metabolic activity of the axillary LNs in relation to that of the upper limb joints and the clinical assessment of disease activity in RA patients treated with biologic therapies.Method: 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (18F-FDG-PET/CT) scans were acquired for 64 patients with RA at baseline and after 6 months of biologic therapy, and the patients' clinical status was evaluated. The maximum standardized uptake value (SUVmax), metabolic active volume, and total lesion glycolysis (TLG) were used to assess glucose metabolism in the LNs and 12 joints. Clinical evaluations included serum markers and the Disease Activity Score based on 28-joint count-erythrocyte sedimentation rate (DAS28-ESR).Results: Changes in the SUVmax and TLG for the axillary LNs correlated significantly with those of the ipsilateral wrist joints. There was a positive correlation between the changes in the three metabolic parameters of the axillary LNs and the changes in disease activity after treatment. After 6 months of biologic therapy, all metabolic parameters for the axillary LNs in patients with a DAS28-ESR < 3.2 were significantly lower than those of patients with a DAS28-ESR ≥ 3.2.Conclusion: A relationship between the glucose metabolism of the axillary LNs and the ipsilateral wrist joints was demonstrated by the 18F-FDG-PET/CT parameters. The metabolic activity and active volume of axillary LNs may reflect the therapeutic response to the biologic treatment of RA.

Diffusion-weighed MR imaging of pancreatic carcinoma.

PURPOSE: The aim of this study was to demonstrate the feasibility of body diffusion-weighted (DW) MR imaging in the evaluation of a pancreatic carcinoma. MATERIAL AND METHODS: In nine normal volunteers and in eight patients with pancreatic carcinoma, DW images were obtained on the axial plane scanning with a multisection spin-echo-type single-shot echo planar sequence with a body coil. Moreover, we measured the apparent diffusion coefficient (ADC) value in a circular region of interest (ROI) within the normal pancreas, pancreatic carcinoma, and tumor-associated chronic pancreatitis. RESULTS: On the DW images, all eight carcinomas were clearly shown as high signal intensity relative to the surrounding tissue. The ADC value (x10(-3) mm(2)/s) in the carcinoma was 1.44 +/- 0.20, which was significantly lower compared to that of normal pancreas (1.90 +/- 0.06) and tumor-associated chronic pancreatitis (2.31 +/- 0.18). CONCLUSION: Diffusion-weighted (DW) images can be helpful in detecting the pancreatic carcinoma and accessing the extent of the tumor.

Overexpression of a DEAD box/RNA helicase protein, rck/p54, in human hepatocytes from patients with hepatitis C virus-related chronic hepatitis and its implication in hepatocellular carcinogenesis.

Hepatitis C virus (HCV) infection is the most common cause of chronic hepatitis, which frequently progresses to hepatocellular carcinoma. The pathogenesis of its persistent infection and tumour progression has not been fully characterized yet. The RCK gene was previously cloned at the breakpoint of the t(11;14)(q23;q32) chromosome translocation observed in human B-cell lymphoma cell line RC-K8. The RCK protein, rck/p54, which is a 54-kDa cytoplasmic protein belonging to the DEAD box/RNA helicase family, is considered to facilitate the translation of mRNA(s) of genes for cell proliferation and malignant transformation not only in B-cell lymphomas having the t(11;14) translocation but also in other solid tumours. The aim of this work was to examine the involvement of rck/p54 in carcinogenesis of hepatocellular carcinoma from HCV-related chronic hepatitis. We examined the expression of rck/p54 in 29 cases of HCV-related chronic hepatitis and eight cases of hepatocellular carcinoma by immunohistochemistry and Western blot analysis. Twenty-six of 29 cases with HCV-related chronic hepatitis and all cases with hepatocellular carcinoma tested overexpressed rck/p54 protein. The expression of rck/p54 was lowered by treatment with IFN-alpha in two cases who showed the decrease in HCV RNA levels. These findings suggest that rck/p54 protein is possibly involved in the replication of HCV genomes in hepatocytes and in tumourigenesis of hepatocellular carcinomas.

Long-term histological prognosis and serum fibrosis markers in chronic hepatitis C patients treated with interferon.

BACKGROUND: Interferon (IFN) therapy is effective in 20-40% of patients with chronic hepatitis C, but the relationship between histological changes and the response to interferon is still unclear. We investigated the long-term histological prognosis and the changes of serum fibrosis markers after interferon therapy relation to the response. METHODS AND RESULTS: One hundred and eighteen patients with chronic hepatitis C who received interferon therapy were divided into four groups based on the detection of viremia and the serum alanine aminotransferase (ALT) level after treatment. A histological examination was performed by using the histological activity index and the criteria of the METAVIR score. Serum fibrosis markers were used to measure the levels of hyaluronic acid and type IV collagen 7s. Responders, whose serum ALT levels became normal after treatment, demonstrated histological improvement. Histological improvement was more rapid in sustained virological responders with hepatitis C virus (HCV) RNA seronegativity than in biochemical responders with HCV-RNA seropositivity. Only sustained virological responders exhibited histological cure. In partial responders, whose serum ALT levels decreased to less than twice the upper of normal, and non-responders whose serum ALT levels were not reduced, liver fibrosis was unchanged or showed progression. Serum fibrosis markers increased with progression of the histological stage and varied depending on the response to interferon. CONCLUSION: Normalization of serum ALT levels after interferon therapy led to a histological improvement, and that with viral clearance achieved histological cure. Serum fibrosis markers were useful indicators for long-term according to the response of IFN therapy.

FDG PET measurement of the proliferative potential of non-small cell lung cancer.

UNLABELLED: The goals of this study were to correlate FDG uptake with cell proliferation and cellular density in non-small cell lung cancer. METHODS: Thirty-one patients with 32 non-small cell lung cancers were examined with FDG PET. For semiquantitative analysis, standardized uptake values (SUVs) were calculated. All patients underwent thoracotomy within 4 wk after the FDG PET study. Cell proliferation was immunohistochemically assessed as the relative number of cells expressing the proliferating cell nuclear antigen ([PCNA] labeling index). Cellular density was also evaluated using light microscopy. RESULTS: SUVs correlated significantly with PCNA labeling index (r = 0.740; P < 0.0001) but only weakly with cellular density (r = 0.392; P = 0.0266). High FDG uptake correlated with high PCNA expression. The PCNA labeling index and SUVs were significantly lower in bronchioloalveolar carcinomas (n = 8) (12.3 +/- 9.45% and 1.45 +/- 0.76, respectively) than in nonbronchioloalveolar carcinomas (n = 19) (33.5 +/- 21.8%, P = 0.015, and 3.75 +/- 1.93, P = 0.003, respectively). However, no significant differences in cellular density were seen between bronchioloalveolar carcinomas and nonbronchioloalveolar carcinomas. CONCLUSION: FDG uptake is related to cell proliferation rather than to the cellular density of non-small cell lung cancer.

Balloon-occluded retrograde transvenous obliteration of high risk gastric fundal varices.

OBJECTIVE: Balloon-occluded retrograde transvenous obliteration is an effective new method for treating gastric fundal varices, but subsequent occurrence of esophageal varices creates a problem. The relationship between portal hemodynamics and the occurrence of esophageal varices after prophylactic balloon-occluded retrograde transvenous obliteration was investigated. METHODS: Ten cirrhotic patients considered to have high risk gastric fundal varices underwent angiography. Six patients showed a communication between blood flow in gastric wall vessels and that in the gastrorenal shunt (type I), whereas the others (type II) did not. Depending on the flow direction in the left gastric vein, the two groups were further divided into hepatopetal (a) and hepatofugal (b) subgroups. The therapeutic effect on portal hemodynamics and the relationship between pretreatment portal hemodynamics and posttreatment occurrence of esophageal varices were investigated. RESULTS: Fundal varices disappeared endoscopically in all 10 patients and the gastrorenal shunt was also occluded after the procedure. No patient showed worsening of liver function or systemic complications during follow-up. The increase in portal blood flow was more significant in type Ib patients than in the others. Esophageal varices occurred in all type I patients, and as to those in type Ib, high risk varices developed within 6 months after treatment. On the other hand, esophageal varices did not occur in type II patients. CONCLUSIONS: This procedure was effective for treating gastric fundal varices. However, type Ib patients are likely to develop high risk esophageal varices after occlusion of the gastrorenal shunt.

Effect of theophylline on hypoxic pulmonary vasoconstriction in awake rats.

Whether or not theophylline inhibits hypoxic pulmonary vasoconstriction in vivo still remains uncertain. We therefore studied the effect of theophylline on hypoxic pulmonary vasoconstriction in awake rats. Two days before hemodynamic measurement, indwelling catheters were placed. Animals were divided into three groups; Group-H (20 mg/kg of theophylline), Group-L (8 mg/kg of theophylline), Group-S (saline). At the day of hemodynamic measurement, animals breathed 21% and 10% O2 gas. [{Pulmonary vascular resistance (PVR) during 10% O2-PVR during 21% O2}/PVR during 21% O2] x 100 was termed as hypoxic pulmonary vasoconstriction (HPV). The first HPV measurement was followed without drug administration and then the second HPV measurement was performed with theophylline or saline infusion. Post-theophylline HPV was divided by pre-theophylline HPV to normalize individual variation. Ratio of post-theophylline HPV to pre-theophylline HPV was 0.49 +/- 0.10, 0.77 +/- 0.23, 1.06 +/- 0.33 in Group -H, -L, -S, respectively (means +/- S.E.M). Ratio of post-theophylline HPV to pre-theophylline HPV was significantly less in Group-H than in Group-S. This result suggests that theophylline used in the present study (18.6-26.9 micrograms/ml) attenuates hypoxic pulmonary vasoconstriction in the unanesthetized rat.

Orally administered beraprost sodium inhibits pulmonary hypertension induced by monocrotaline in rats.

Rats were fed on distilled water (DW) or DW containing beraprost sodium (BPS). BPS concentration was 1.5 or 3.0 mu/ml in DW for the low BPS groups and 6.0 or 10.0 mu/ml in DW for the high BPS group. Monocrotaline (MCT) was subcutaneously given (60 mg/kg), and saline was injected as control. Data were analyzed among the following groups; Groups (Saline + DW), (Saline + Low BPS), (MCT + DW), (MCT + Low BPS) and (MCT + High BPS). Three weeks later, pulmonary (Ppa) and systemic (Psa) arterial pressure were measured under anesthesia. MCT caused significant elevation of Ppa [18.3 +/- 0.6 cmH2O for Group (Saline + DW) vs. 27.2 +/- 1.2 cmH2O for Group (MCT + DW), p < 0.001, mean +/- S.E.] and Ppa was significantly and dose-dependently suppressed by BPS; Group (MCT + DW) vs. Groups (MCT + Low BPS), 23.4 +/- 0.7 cmH2O and (MCT + High BPS), 22.5 +/- 0.5 cmH2O, p < 0.05, mean +/- S.E.). Psa was not lowered dose-dependently by BPS. We conclude that oral beraprost sodium suppresses pulmonary hypertension produced by monocrotaline in rat.

Pulmonary haemodynamics in awake rats following treatment with endotracheal pancreatic elastase.

The purpose of this paper was to study pulmonary haemodynamics in an elastase-induced emphysema model in awake rats (Group-EL, n = 9) in comparison with saline-treated controls (Group-C, n = 12). Four weeks before haemodynamic study, porcine pancreatic elastase and normal saline were intratracheally instilled in Group-EL and Group-C, respectively. Indwelling pulmonary artery and abdominal aortic catheters were positioned two days before the haemodynamic study. Breathing room air, mean pulmonary artery pressure (Ppa) tended to be higher in Group-EL than in Group-C, although the difference was not statistically significant. Systemic pressure, total systemic vascular resistance and cardiac index did not differ between groups. When exposed to 10% O2, Ppa and pulmonary vascular resistance (PVR) of both groups rose significantly. The increase of Ppa, (but not PVR) in Group-EL during hypoxia was significantly higher than that in Group-C. The magnitude of hypoxic pulmonary vasoconstriction (HPV) tended to be larger in Group-EL than in Group-C. Right ventricles of Group-EL were more hypertrophic than those of Group-C, suggesting a period of higher pulmonary artery pressure than for Group-C. The present results imply that the pressor response of pulmonary vasculature to acute alveolar hypoxia is possibly enhanced in awake rats upon examination four weeks after elastase treatment.

Changes in pulmonary hemodynamics during normoxia and hypoxia in awake rats treated with intratracheal bleomycin.

Pulmonary hemodynamics of bleomycin-induced interstitial fibrosis model (group-BLM, n = 10) and saline-treated control (group-C, n = 12) were studied in awake rats. Four weeks before hemodynamic study, bleomycin sulfate and normal saline was intratracheally instilled to the group-BLM and the group-C, respectively. Pulmonary artery and abdominal aortic catheters were indwelled two days before the hemodynamic study. In room air, mean pulmonary artery pressure (Ppa) was significantly higher and systemic artery pressure was significantly lower in group-BLM than in group-C; Ppa = 21 +/- 1 cmH2O (mean +/- S.E.) for group-C and 38 +/- 4 cmH2O for group-BLM. Cardiac output did not differ among the groups. Mean pulmonary vascular resistance (PVR) of group-BLM was double that of group-C. Right ventricle was hypertrophic in group-BLM. When exposed to 10% O2, PVR of group-C significantly rose, whereas PVR of group-BLM showed very little increase, showing attenuation of the hypoxic pulmonary vasoconstriction (HPV). Magnitude of the HPV was inversely related to Ppa during air breathing. We conclude that notable pulmonary hypertension and right ventricular hypertrophy occur, and HPV is blunted four weeks after bleomycin instillation, at the most severe period of this lung fibrosis model. We speculate that the high intravascular pressure partly contributed to the blunted HPV in bleomycin-treated group.

Dose dependency of intratracheal elastase-induced changes in pressure volume curve and morphometry in rat lungs.

We studied the dose-dependency of the lung pressure-volume curve (n = 37) and morphometry (n = 30) with intratracheally administered elastase. Four weeks after elastase was instilled at dosages of 20 (EL-20), 40, 80, and 100 U/100 g wt., chord compliance between 50 and 70% of total lung capacity (TLC) (C50-70) and that between 80 and 100% TLC (C80-100) were measured. After a significant initial reduction, the weight of the EL-80 group recovered to the control level, whereas the weight curve of the EL-100 significantly decreased below that of the EL-80. Lung volumes of all the elastase-treated groups were significantly larger than those of control. Air-filled lung volumes monotonously increased when the elastase dose was increased from 20 to 80 U/100 g wt. In contrast lung volume of the EL-100 was significantly lower than that of the EL-80. On the other hand, liquid-filled lung volumes monotonously increased from 20 to 100 U/100 g wt. C80-100 was significantly smaller in the EL-100 than in the EL-80. The mean linear intercept increased and alveolar surface area decreased monotonously over the dose range tested. We conclude that there is a critical dose of elastase below which lung volume is increased and above which the increase is suppressed when elastase is administered intratracheally to Wistar rats.