Pancreatic metastasis of malignant melanoma diagnosed by EUS-guided fine needle aspiration (EUS-FNA)]

Pancreatic metastasis of malignant melanoma is rarely diagnosed while the patient is alive. We report a case of metastatic melanoma of the pancreas in a 35-year-old woman presenting with a solid mass of the pancreas. Her past medical history included a radical hysterectomy 2 years previously for malignant melanoma of the vagina. Twelve months later, lung metastasis was also resected. EUS-guided fine needle aspiration (EUS-FNA) identified that the pancreatic tumor was histologically and immunohistochemically identical to the surgical specimen of her lung neoplasm. Imaging studies including US, CT, and MRI have limited value to distinguish the tumors from primary ductal adenocarcinoma. EUS-FNA can provide tissue diagnosis from pancreatic masses, specifically when other modalities have failed.     

Effects of chronic treatment with haloperidol and methamphetamine on hippocampal kindled seizures in the cat

We assessed the effects of chronic treatment with haloperidol (0.5-2 mg/kg/day, p.o., 17 days) and methamphetamine (1-2 mg/kg/day, p.o., 17 days; 4 mg/kg/day, p.o. 9 days) on hippocampal kindled seizures using a kindling procedure with low-frequency (about 3 Hz) electrical stimulation in cats. The number of stimulating pulses required to trigger epileptic afterdischarge (pulse-number threshold, PNT) was considered an indicator of seizure threshold. Haloperidol, 0.5 and 1.0 mg/kg, reduced the duration of epileptic afterdischarge (afterdischarge duration, ADD) without affecting PNT, and 2.0 mg/kg strongly reduced PNT and ADD. Methamphetamine, 2.0 mg/kg, reduced PNT and ADD, and 4.0 mg/kg preferentially reduced PNT. The effects of the two drugs on hippocampal kindled seizures were found to be partially opposite to those on amygdala kindled seizures, suggesting the different response of these limbic structures to dopamine receptor manipulation.     

Priming effect of RANTES on eosinophil oxidative metabolism

Background RANTES has been shown to possess chemotactic activity for eosinophils, which have also been considered to play a role in allergic inflammation through reactive oxygen species. Thus, in this study, we examined the effect of RANTES on radical oxygen products from eosinophils.
Methods Purified eosinophils by CD16-negative selection or an eosinophilic cell line (EoL-1) were incubated with or without RANTES (2.5 x 10⁻⁶). To the mixture of eosinophils and luminol, calcium ionophore (A23187) or opsonized zymosan (OZ) was added, and radical oxygen products were determined by luminol-dependent chemiluminescence for 600 s.
Results Eosinophil-mediated radical oxygen products of untreated eosinophils produced with A23187 gave a peak value of 14.09 + 2.40 (mean±SE, n = 12) relative light units (RLU) and an integrated value of 3232.20 + 513.09 RLU. However, with treatment with RANTES, a peak value of 18.66 + 2.40 RLU and an integrated value of 5301.05 ±561.02 RLU were obtained. Eosinophil oxidative metabolism-induced A23187 or OZ was apparently augmented by the preincubation with RANTES. In addition, the radical oxygen products of EoL-1 showed similar results.
Conclusions Thus, we concluded that RANTES may play an important role the pathogenesis of allergic inflammation through its involvement in eosinophil activation, as evidenced by oxygen products, as well as in selective eosinophil infiltration as selective eosinophil chemoattractant.     

Lamivudine and IFN-beta sequential therapy in HBe antigen-positive patients with chronic hepatitis B virus genotype C infection.

Sequential treatment with lamivudine and interferon (IFN) has induced sustained biochemical and virologic responses in the majority of patients with chronic hepatitis B in France. However, the efficacy of sequential treatment in patients with chronic hepatitis B virus (HBV) genotype C infection has not been evaluated. Twenty-four HBe antigen-positive patients were treated with 100 mg lamivudine alone for 16-32 weeks, then with both 6 MU IFN-beta and lamivudine for 4 weeks, and lastly with IFN-beta alone for 20 weeks. Sustained response was achieved in 7 (29%) patients 24 weeks after the end of therapy. No lamivudine-resistant variants emerged in any patient. Hepatitis flare occurred in 3 patients after the withdrawal of lamivudine, but none had decompensation. The patients with sustained response were significantly younger at baseline (p = 0.033) and had a significantly lower HBV DNA level at the start of IFN (p = 0.020) than those without sustained response. In conclusion, the rate of response to sequential therapy with lamivudine and IFN in HBe antigen-positive patients with HBV genotype C infection was lower than the rate reported previously. Patients who were young or who had a favorable virologic response to lamivudine were more likely to have a sustained response.     

The combination of IFN-alpha2 and IFN-alpha8 exhibits synergistic antiproliferative activity on renal cell carcinoma (RCC) cell lines through increased binding affinity for IFNAR-2.

Although there are at least 13 interferon-alpha (IFN-alpha) subtypes in humans, interactions between the subtypes remain unknown. To understand IFN-alpha interactions, we examined the antiproliferative activities and the receptor binding affinities of different combinations of IFN-alpha2 and IFN-alpha8 using six renal cell carcinoma (RCC) cell lines. Although IFN-alpha8 was the more potent subtype, synergistic and antagonistic antiproliferative effects were also observed in certain combinations of IFN-alpha2 and IFN-alpha8. To analyze the interactions between IFN-alpha2 and IFN-alpha8, the receptor-binding kinetics of different combinations of IFN-alpha2 and IFN- alpha8 to the IFN-alpha receptors, IFNAR-1 or IFNAR-2, were measured using a surface plasmon resonance-based biosensor. Unexpectedly, the receptor binding kinetics to IFNAR-2 but not to IFNAR-1 were mutually related to antiproliferative activity and increase in the binding speed (K(a)) for IFNAR-2. Moreover, we observed the increased fluorescence intensity (FI) of biotin-labeled IFN-alpha8 to IFNAR-2 by receptor binding inhibition assay with unlabeled IFN-alpha2 but not the other combinations. These findings indicate that the binding manner of IFN-alpha8 for IFNAR-2 is different from that of IFN-alpha2, suggesting that binding of IFN-alpha8 rather than binding of IFN-alpha2 to IFNAR-2 leads to activation and subsequent antiproliferative activity despite the same antiviral activity in RCC.     

Fetal intraventricular bleeding possibly due to maternal vitamin K deficiency

We report a rare case of fetal intraventricular bleeding possibly due to maternal vitamin K deficiency. A 20-year-old woman was admitted to our hospital due to impending premature delivery and loss of dietary intake at 28 weeks of gestation. Her blood examination showed metabolic alkalosis, prolonged prothrombin time, and extremely high level of plasma des-gamma-carboxyprothrombin (protein induced by vitamin K absence, PIVKA-II). Intraventricular hemorrhage was demonstrated by ultrasonography 6 days after admission. She delivered a 2,288-gram girl infant at 40 weeks of gestation. Cranial computerized tomography and magnetic resonance images obtained postnatally demonstrated a reduced cerebral parenchyma adjacent to the interior side of the right lateral ventricle and the deficit of left cerebellum. The infant's head control was insufficient and central impaired hearing was noted at 6 months of life.     

Changes in epidermal growth factor concentrations of submandibular gland, plasma and urine of normal and sialoadenectomized female mice during various reproductive stages

The concentrations of epidermal growth factor (EGF) were measured by radioimmunoassay in the submandibular gland, plasma and urine of adult female C3H/HeN mice whilst virgin and during pregnancy, lactation and after lactation. During gestation there was a significant increase in the submandibular EGF concentration which was five to seven times higher than that found in virgin mice. The level of EGF in the gland remained high during the period of lactation and even several weeks after lactation. Plasma EGF levels were also increased during the periods of pregnancy, lactation and after lactation when compared with those of virgin mice. These increases were, however, apparent only between 24.00 and 08.00 h, because of circadian variations in circulating EGF. The level of plasma EGF was significantly (P less than 0.05) higher during the 24.00-08.00 h period than during the 12.00-20.00 h period in all stages examined. Concentrations of EGF in the urine of virgin, pregnant, lactating and primiparous mice remained relatively constant, and the levels were much higher than those in the plasma. Similar studies using sialoadenectomized pregnant and lactating mice indicated that the plasma levels of EGF were below the level of sensitivity of the assay (less than 16.5 pmol/l (less than 0.1 ng/ml] even during the 24.00-08.00 h period, whereas urinary EGF remained at high levels which were similar to those of normal pregnant and lactating mice. These results suggest that submandibular EGF contributes to the increase in plasma EGF which occurs after gestation, but is not the major source of the urinary EGF.     

Monitoring the content of reticulocyte hemoglobin (CHr) as the progression of anemia in nondialysis chronic renal failure (CRF) patients

BACKGROUND: We previously showed that the content of reticulocyte hemoglobin (CHr) is a reliable measure of iron status in chronic dialysis patients with erythrocytopoiesis. The CHr was significantly correlated with conventional parameters of iron deficiency in dialysis patients. We attempted to utilize the measurement of CHr levels to monitor iron status and clarify the changes in iron levels that occur as renal anemia progresses in patients with chronic renal failure (CRF). METHODS: We measured CHr, iron parameters, and the intrinsic erythropoietin (EPO) concentration in nondialysis CRF patients who visited our outpatient clinic (n=211). Iron deficiency was defined according to the transferrin saturation (TSAT) and ferritin levels. Conventional red blood cell parameters and CHr levels were measured using an ADVIA120 autoanalyzer (Bayer Medical, USA). RESULTS: The mean CHr value of the nondialysis CRF patients (creatinine clearance less than 70 mL/min) was 32.3 pg, which was not significantly different from that of the dialysis patients. Significant correlations were found between CHr and ferritin levels (r=0.042, p<0.0403) and CHr and TSAT levels (r=0.040, p<0.0157). A positive correlation was observed between the CHr and serum creatinine levels. Nondialysis CRF patients treated with recombinant human EPO (rHuEPO) at a dose of 24,000 U/month exhibited lower CHr levels, compared with those of other patients who received less than 24,000 U/month. CONCLUSION: CHr is an easily measurable and trustworthy marker of iron status in nondialysis CRF patients. Moreover, the CHr level was also sensitive to iron alterations in nondialysis CRF patients receiving rHuEPO treatment, and thus, the CHr value could likely provide useful information regarding the need for iron supplementation.