Intraoperative ultrasonography in pancreatic cancer.

Intraoperative ultrasonography (I.US) has been introduced in order to overcome the limits of the preoperative imaging modalities (notably, ultrasonography and computed tomography), both in pancreatic cancer diagnosis and staging. The authors' experience encompasses 32 cases, selected according to the following criteria: lesions that could not be detected both preoperatively and at surgical exploration; lesions detected but not properly characterized, requiring differential diagnosis between cancer and pancreatitis; tumoral lesions with a perspective of radical surgery, in which the preoperative judgment of resectability had to be verified. In the only case of the first group, I.US allowed the identification of a small cancer in a jaundiced patient. In the 11 cases of the second group, I.US-guided fine-needle aspiration biopsy showed three cancers; however, among the other 8 lesions classified as pancreatitis there was one false negative diagnosis (a tumoral mass with liver metastases was demonstrated by computed tomography 6 mo later). Regarding the intraoperative staging of the proven cancers (20 cases of the third group; 4 cases of the first and second groups), I.US changed the planned surgical approach in 9 cases (showing vascular involvement or detecting liver metastases and enlarged lymph nodes not seen preoperatively); in 12 cases it confirmed the possibility of radical surgery. Finally, in the remaining 3 cases, I.US provided dubious information: only vascular dissection during surgery could achieve a correct evaluation, ruling out vascular involvement and thus allowing tumor resection.     

Identification and conditions for selective expression of megakaryocytic markers in Friend erythroleukemia cells

Friend murine erythroleukemia cells (MELCs) have been reevaluated in terms of their nature and potential pathways of differentiation. MELC induced with 5 mmol/L hexamethylene bisacetamide (HMBA), in addition to expression of known markers of the erythroid phenotype, were also found to exhibit traits of the megakaryocytic lineage. Erythroid differentiation was shown by the typical synthesis and accumulation of hemoglobin (Hb); megakaryoblastoid differentiation of MELCs upon induction was shown by increased specific activity of acetylcholinesterase (AChE). Incubation of MELCs with 5 mmol/L HMBA in RPMI supplemented with 1% fetal calf serum (FCS) (instead of the usual 5%), induced cells to selectively express high levels of AChE (up to approximately 170 mU/mg protein) with little activation of Hb synthesis (less than 5% B+ cells). The increase in AChE levels was a general phenomenon affecting the whole cell population and approached its maximum within 3 days of incubation with the inducer. Subsequently, MELCs become committed to terminal division, undergoing growth arrest and expression of the megakaryocytic phenotype even after the removal of HMBA. There were no appreciable changes of basal AChE levels in MELCs that were either made resistant to HMBA or treated with 0.1 mmol/L hemin that activated differentiated erythroid function without commitment. Phorbol 12-myristate 13-acetate (PMA), known to repress induced Hb synthesis in these cells, did not prevent the full increase in AChE when incubated with MELCs 2 days before HMBA addition. HMBA- induced MELCs always underwent AChE increase that was more or less pronounced depending on the low or high serum content in culture, respectively. Conversely, Hb expression was permitted only when MELCs were transferred in the late phase or at the end of commitment from low to high serum media. Variations of FCS content in culture media proved to be a simple and reliable approach to change the MELC response to inducers and to modulate expression of either megakaryocytic or mixed erythromegakaryocytic phenotype. These findings suggested that MELC might be considered, at least, as a bipotential model of differentiation to be used for studies on regulation of either megakaryocytic or erythroid markers and on competition between the two hematopoietic lineages. In this regard, it was intriguing that AChE levels attained under selective induction (low serum) were always higher than under conditions allowing coexpression of both AChE and Hb (high serum). Moreover, MELCs were also found to bind the specific rat- antimouse platelet monoclonal antibody 4A5.(ABSTRACT TRUNCATED AT 400 WORDS)     

The effects of (±)-idazoxan and its stereoisomers on mouse vas deferens motility in vitro. A comparison with yohimbine

The effects of idazoxan (IDZ) and its stereoisomers were compared to that of a classical alpha 2-antagonist, yohimbine (YOH), on para-aminoclonidine (PAC)- and norepinephrine (NE)-mediated inhibition of the twitch response evoked in the mouse vas deferens by low-frequency (0.1 Hz) field stimulation. (+/-)-IDZ and (+)-IDZ antagonized the inhibitory effects of PAC, (+)-IDZ being twice as potent as (+/-)-IDZ; in contrast, antagonism by (-)-IDZ failed to meet Schild criteria for a competitive mechanism. YOH completely reversed the inhibition of twitch response induced by NE, but not that induced by PAC; in the latter case, residual inhibition was almost fully reversed by (+)-IDZ and to a lesser extent by (+/-)-IDZ, while (-)-IDZ proved ineffective. These results provide pharmacological evidence of alpha 2-receptor heterogeneity at the vas deferens level. A possible additional mechanism involving imidazoline binding sites is discussed.     

Quantitative computed tomographic study in schizophrenia: cerebral density and ventricle measures

Twenty-seven chronic schizophrenics and nineteen controls, all male, were evaluated by computed tomography (CT) scans. Lateral, third and fourth ventricles and cerebral density numbers were measured. In the schizophrenic patients there was a significant increase in third ventricle width, Ventricular Brain Ratio (VBR) and there were significantly higher densities of white matter in the right frontal and parietal region.     

Percutaneous transluminal angioplasty: delayed response in neurofibromatosis

Percutaneous transluminal angioplasty (PTA) was eventually successful in a patient with renal artery stenosis due to neurofibromatosis. Although the immediate postangioplasty appearance showed little improvement, the residual stenosis has completely resolved at 5 months. Delayed response to PTA has been previously documented in other types of vascular disease. Its occurrence in renal artery stenosis due to neurofibromatosis emphasizes the importance of long-term follow-up and may be a factor in the poor short-term results that some have reported for PTA in patients with this condition.     

Oral contraceptives, reproductive factors and p53 gene expression in colorectal cancer

Protective effects of oral contraceptives and high parity on the development of colorectal cancer have been hypothesized. However, the epidemiological data are inconsistent. This inconsistency may be due in part to the biological heterogeneity of colorectal tumors. A recent investigation of hepatocellular carcinoma demonstrated an association between lack of p53 expression and oral contraceptive use. We investigated the relationship between oral contraceptive use and other reproductive factors with p53 over-expression in 64 post-menopausal women, 45-86 years of age, with non-familial colorectal adenocarcinoma. Fifty per cent (32/64) of colorectal tumors displayed nuclear over- expression of p53 protein. Women with a history of oral contraceptive use were significantly less likely to have p53 positive (+) tumors than women who never used oral contraceptives (P = 0.02). In contrast, tumors from women who had never been pregnant were more likely to be p53 + compared to tumors from parous women (P = 0.10). These data suggest that oral contraceptive use and pregnancy are associated with a p53 independent pathway in the development of colorectal cancer.      

Thrombopoietic effects and toxicity of interleukin-6 in patients with ovarian cancer before and after chemotherapy: a multicentric placebo- controlled, randomized phase Ib study

Recombinant human interleukin-6 (IL-6) has previously been shown to increase platelet counts in normal and sublethally irradiated mice, dogs, and primates. To assess its tolerance and efficacy in clinical use, we performed a randomized phase Ib study in patients with ovarian carcinoma. IL-6 was administered during an initial 7-day cycle before any chemotherapy. Beginning 7 days later, six cycles of chemotherapy containing carboplatin were administered every 3 weeks. During chemotherapy cycles 2 to 6, IL-6 was administered from day 4 through day 17 at escalating dose levels from 0.5 to 10 micrograms/kg/d. At each level, three patients received IL-6 and one patient received a placebo. During the prechemotherapy cycle of IL-6, a dose-dependent increase in platelet count was observed from day 12 to 15 and was maximal on day 15 (r = .77; P < .01). The median ploidy of bone marrow megakaryocytes shifted from 16 N to 32 N after 7 days of the initial prechemotherapy IL-6 administration. Dose-dependent increases in C- reactive protein (CRP) and fibrinogen levels were observed on day 8 (P < .0001 for both). A significant decrease in hemoglobin level occured rapidly after initiation of IL-6 therapy and was maximal on day 8 (P < .001). When given after chemotherapy, IL-6 accelerated platelet recovery after chemotherapy cycles 2 to 6. Postponements of scheduled chemotherapy due to thrombocytopenia were less frequent in patients treated with IL-6. No difference in either neutrophils or peripheral blood progenitor assays was observed during or after IL-6 treatment. Toxicity of IL-6 appeared mild and was not dose-limiting up to 10 micrograms/kg/d. Systemic symptoms such as fever, headache, and myalgia were the main side effects and were easily relieved by acetaminophen administration. No biologic toxicity was observed. The data indicate that IL-6 is a well-tolerated cytokine and capable of accelerating platelet recovery in patients receiving chemotherapy.     

Endothelial interactions of hairy cells: the importance of alpha 4 beta 1 in the unusual tissue distribution of the disorder

The tissue-homing of all lymphocytes involves their interactions with endothelial cells (ECs) and with various tissue accessory cells. However, in hairy cell leukemia (HCL), these processes are particularly prominent and result in diagnostic appearances in the spleen, liver, and bone marrow. The present study explores the mechanisms that underlie these tissue reactions. Using a human umbilical vein EC (HUVEC) model, various possible receptor-ligand interactions between hairy cells (HCs) and ECs were examined and a central importance for alpha 4 beta 1/vascular cell adhesion molecule-1 (VCAM-1) was established. This receptor-ligand pair was shown to be important both for strong adhesion and for HC motility/transmigration. A similar importance for alpha 4 beta 1/VCAM-1 was established for the interaction between HCs and relevant tissue accessory cells. The in vitro relevance of these findings was confirmed by the demonstration of VCAM-1 in HCL spleen and by the fact that, in frozen sections, HCs adhered (via VCAM-1) to the red pulp, but not to other areas of normal spleen. These results indicate that alpha 4 beta 1/VCAM-1 is central to the interaction between HCs and endothelium/accessory cells. Such interactions, together with the intrinsic cell activation characteristic of HCL and the HC's consequent ability to interact with matrix, are responsible for many of the characteristic features of the disease.