Brief Clinical Report: Serum Tumor Necrosis Factor for Monitoring Response of Hepatic Veno-occlusive Disease to Pentoxiphyllin-A Case Report

Hepatic veno-occlusive disease (VOD) is the second most common cause of death after autologous bone marrow transplantation (ABMT). A patient with multiple myeloma undergoing ABMT developed classic features of hepatic VOD. He responded to treatment with pentoxiphyllin. Serum tumor necrosis factor (TNF) levels showed remarkable correlation with the severity of VOD and response to therapy.     

Radical aortic replacement employing simultaneous modified Bentall and elephant trunk procedure in Takayasu's arteritis

A case of Takayasu's arteritis resulting in extensive fusiform aneurysmal dilatation of the entire aorta extending from the aortic root to the abdominal bifurcation associated with aortic regurgitation is described. She underwent successful radical replacement of the aortic root, ascending, transverse arch and proximal part of the descending aorta employing simultaneous modified Bentall and Elephant trunk techniques. During aortic arch replacement the brain was protected by selective antegrade innominate perfusion under moderate hypothermia. A pattern to the best of our knowledge, has not been reported earlier.     

Improved exposure of isolated perimembranous ventricular septal defects

We describe an alternative step in the transatrial approach to the repair of ventricular septal defects. We temporarily detach the chorda of the obscuring tricuspid valve from its attachment to the septum to expose the ventricular septal defect.     

Adjuvant chemo-radiotherapy in ampullary cancers.

PURPOSE: Patterns of failure following surgical treatment of ampullary cancers indicate that up to 45% of patients develop loco-regional recurrence. The effect of adjuvant chemo-radiotherapy on survival and loco-regional control is not yet established in this malignancy. PATIENTS AND METHODS: From January 1989 to December 2000, 113 patients underwent pancreatico-duodenectomy for ampullary cancer. One hundred and four patients who survived the operation were available for analysis to study the effect of adjuvant chemo-radiotherapy on survival and loco-regional control. Forty-nine patients received adjuvant chemo-radiotherapy (median dose 50.4 Gy with concurrent 5-Flurouracil) and long-term outcome in these patients was compared with those 55 who did not receive adjuvant therapy. RESULTS: The overall median survival was 30.1 (range 1.6-140.0) months with actuarial 1, 3 and 5-year survival rates of 79, 43 and 33%, respectively. No significant difference in median survival (34.6 vs 24.5 months; P=0.3) and actuarial 5-year survival rates (38 vs 28%) was seen between those who received and those who did not receive adjuvant therapy. Adjuvant chemo-radiotherapy did not influence the survival in high-risk patients (P=0.84), in various T and N stages and had no impact on loco-regional recurrence (P=0.6). CONCLUSIONS: Adjuvant chemo-radiotherapy did not improve the long-term survival or decrease recurrence rates in patients with ampullary cancers who had undergone pancreatico-duodenectomy.     

MUC 1 core protein as a marker of gallbladder malignancy.

AIM: The significance of MUC 1 expression in the gallbladder tissues in relation to cancer and non-cancer disease is not well understood. The aim of this study was to clarify the significance of MUC 1 expression. MATERIALS AND METHODS: A monoclonal antibody (CA 15--3; DF 3) was applied to stain MUC 1 core protein in surgical specimens. RESULTS: MUC 1 expression is significantly higher (p<0.0001) in gallbladder cancer (69/88) compare to non-cancerous tissue, while, very trace in normal and inflammatory tissues. The expression rate was significantly lower (p<0.0001) when the cancer did not penetrate the mucosal layer than when cancers did penetrate this layer. The MUC 1 expression rate was (4/14) in T1 tumours, (11/14) in T4, (40/45) in T3, and (14/15) in T2, respectively. Every cell of normal and inflammatory mucosa, and T1 cancers had the polarized pattern. The depolarized pattern was dominant in cancer cells from the advanced tumours of T2, T3 and T4. That is, (45/74) of cancer cells from the mucosal layer and (58/74) of penetrating cancer cells in submucosal layer had the depolarized pattern. There was no significant correlation of MUC 1 expression rate and staining pattern with cancer differentiation and microscopic venous invasion. On the other hand, lymphatic vessel invasion was significantly correlated with the staining pattern but not with expression rate. CONCLUSION: MUC 1 core protein expression rate and pattern are suggesting that MUC 1 core protein would be a marker of malignant transformation of gallbladder epithelium and its depolarized expression would also be a marker of invasion of gallbladder cancer.     

Gemcitabine selectively eliminates splenic Gr-1+/CD11b+ myeloid suppressor cells in tumor-bearing animals and enhances antitumor immune activity.

PURPOSE: Myeloid suppressor (Gr-1(+)/CD11b(+)) cells accumulate in the spleens of tumor-bearing mice where they contribute to immunosuppression by inhibiting the function of CD8(+) T cells and by promoting tumor angiogenesis. Elimination of these myeloid suppressor cells may thus significantly improve antitumor responses and enhance effects of cancer immunotherapy, although to date few practical options exist. EXPERIMENTAL DESIGN: The effect of the chemotherapy drug gemcitabine on the number of (Gr-1(+)/CD11b(+)) cells in the spleens of animals bearing large tumors derived from five cancer lines grown in both C57Bl/6 and BALB/c mice was analyzed. Suppressive activity of splenocytes from gemcitabine-treated and control animals was measured in natural killer (NK) cell lysis and Winn assays. The impact of myeloid suppressor cell activity was determined in an immunogene therapy model using an adenovirus expressing IFN-beta. RESULTS: This study shows that the chemotherapeutic drug gemcitabine, given at a dose similar to the equivalent dose used in patients, was able to dramatically and specifically reduce the number of myeloid suppressor cells found in the spleens of animals bearing large tumors with no significant reductions in CD4(+) T cells, CD8(+) T cells, NK cells, macrophages, or B cells. The loss of myeloid suppressor cells was accompanied by an increase in the antitumor activity of CD8(+) T cells and activated NK cells. Combining gemcitabine with cytokine immunogene therapy using IFN-beta markedly enhanced antitumor efficacy. CONCLUSIONS: These results suggest that gemcitabine may be a practical strategy for the reduction of myeloid suppressor cells and should be evaluated in conjunction with a variety of immunotherapy approaches.     

Synthesis and Structure-Activity Relationships of Vasicine Analogues as Bronchodilatory Agents

The series of vasicine (1) analogues, an alkaloid from Adhatoda vasica Nees., were synthesized with changes in A, B or C rings. Compounds 13-19 were evaluated for in vitro bronchodilatory activity using isolated guinea pig tracheal chain. Compounds 3-8 were also synthesized in good yields using microwave-mediated synthesis under solvent free conditions. Compounds 5 and 8 with seven-member C ring were more active than etofylline and caused 100% relaxation of both the histamine and acetycholine pre-contracted guinea pig tracheal chain. The structure-activity relationship studies showed that the quinazoline and oxo functionalities were essential for activity. The compounds without C ring and instead having aliphatic and phenyl substitutions in B ring showed relaxation against histamine pre-contracted tracheal chain only, 2-methyl substituted analogues, 12 and 13, being most active with 100% relaxation effect.     

Lower Rate of Water Absorption of an Oral Rehydration Solution with Partially Hydrolyzed Guar Gum in Conscious Rats

The purpose of the present study was to elucidate the rate of water absorption of an oral rehydration solution containing partially hydrolyzed guar gum (PHGG) in the small intestine, which is the main site of water absorption when water is drunk. Seven-week-old male SD rats were employed. We prepared four types of an aqueous solution, i.e., containing mineral and sugar, containing PHGG, containing mineral and sugar and PHGG, or containing no additives. After 24 h of food and 4 h of water deprivation, the aqueous solutions were infused into the stomach of conscious rats on their hands using a syringe with a stomach sonde. We sampled the stomach and the small intestine with contents 8 min after the infusions. Causal effects were calculated using a Bayesian network. PHGG increased the residual amount of water in the gastro-intestine, which depends negatively on the absorption of water in the small intestine/the flow rate to the small intestine. The absorption of water in the small intestine depended positively on the flow rate to the small intestine, which depended negatively on the free water in the solutions. PHGG decreased water absorption in the small intestine by decreasing the free water in the aqueous solutions.     

Effect of intravenous immune globulin on natural killer cell activity: possible association with autoimmune neutropenia and idiopathic thrombocytopenia

Natural killer cell (NK) activity was assessed in patients before and after treatment with intravenously administered immune globulin (IVIG). In eight patients with hypogammaglobulinemia or agammaglobulinemia receiving 300 mg/kg/dose IVIG every 4 weeks, NK activity was significantly lower after therapy than before. In two patients, one with idiopathic thrombocytopenic purpura and one with autoimmune neutropenia, receiving high doses (2 gm/kg) of IVIG, NK activity was unusually high before therapy. After treatment, NK activity decreased in correlation with the clinical response and elevation of peripheral cell counts. These data show that IVIG diminishes NK activity in vivo and that reduction of NK activity may be associated with clinical improvement in idiopathic thrombocytopenic purpura and autoimmune neutropenia. NK activity of lymphocytes obtained from healthy volunteers was reduced by the same concentrations of maltose or sucrose present in Gamimune or Sandoglobulin, respectively; IVIG preparations, however, were more inhibitory. The diminution of NK activity therefore may be related to two components of IVIG preparations, monomeric IgG and maltose or sucrose.