Capecitabine as second-line treatment for metastatic cholangiocarcinoma: A report of two cases

Background: The management of recurrent, metastatic cholangiocarcinoma still remains a problem since this tumor entity is classified as chemotherapy-resistant. When advanced or metastatic disease is diagnosed, the therapeutic efforts are essentially directed toward palliation. Patients and Methods: We report on 2 patients suffering from metastatic cholangiocarcinoma. Both had received previous chemotherapy for metastatic disease, including hepatic artery infusion {[}5-fluorouracil (5-FU)/folinic acid (FA) and oxaliplatin] and a combination therapy consisting of 5-FU/FA and gemcitabine. Since a progression of the disease was diagnosed, both patients were started on oral capecitabine at a daily dose of 2,500 mg/m(2) in 2 divided doses for 2 weeks, followed by 1 week rest. Results: Capecitabine was tolerated well and severe side effects were not observed. A stop of progression, documented by imaging procedures and tumor marker kinetics, was achieved in both patients. Conclusion: Capecitabine could potentially be used for second-line treatment in patients with progressive metastatic cholangiocarcinoma

Automated optimization of a reduced layer 5 pyramidal cell model based on experimental data.

The construction of compartmental models of neurons involves tuning a set of parameters to make the model neuron behave as realistically as possible. While the parameter space of single-compartment models or other simple models can be exhaustively searched, the introduction of dendritic geometry causes the number of parameters to balloon. As parameter tuning is a daunting and time-consuming task when performed manually, reliable methods for automatically optimizing compartmental models are desperately needed, as only optimized models can capture the behavior of real neurons. Here we present a three-step strategy to automatically build reduced models of layer 5 pyramidal neurons that closely reproduce experimental data. First, we reduce the pattern of dendritic branches of a detailed model to a set of equivalent primary dendrites. Second, the ion channel densities are estimated using a multi-objective optimization strategy to fit the voltage trace recorded under two conditions - with and without the apical dendrite occluded by pinching. Finally, we tune dendritic calcium channel parameters to model the initiation of dendritic calcium spikes and the coupling between soma and dendrite. More generally, this new method can be applied to construct families of models of different neuron types, with applications ranging from the study of information processing in single neurons to realistic simulations of large-scale network dynamics

Weekly irinotecan in a patient with metastatic colorectal cancer on hemodialysis due to chronic renal failure

Background: The cytotoxic treatment of patients suffering from advanced or metastatic cancer undergoing hemodialysis due to chronic renal failure still remains a problem, since for those patients pharmacokinetic and pharmacodynamic data on most cytotoxic agents are lacking. Case Report: We report a 45-year-old male who suffered from chronic renal failure and was diagnosed with stage-3 colorectal cancer (CRC) in February 2000. After surgical removal of the tumor an adjuvant chemotherapy of dose-reduced i.v. bolus 5-fluorouracil and folinic acid was begun (Mayo protocol). Due to excessive gastrointestinal toxicity, therapy was discontinued after the first cycle. In April 2000 liver metastases were diagnosed. The patient was then put on a weekly schedule of dose-reduced CPT-11 (50 mg/m(2), 80 mg total). No hematological or non-hematological toxicity grade 3/4 was observed. Due to excellent tolerability and lack of severe side effects the dose was increased up to 80 mg/m2 (140 mg total) weekly. A dose escalation to 100 mg/m(2) (180 mg total) resulted in severe diarrhea (grade 4). Within 2 months of treatment the patient achieved a lasting partial remission until April 2001 (12 months). A significant progression of hepatic metastases required an alternative treatment regimen beginning in July 2001 (HAI, hepatic artery infusion). Conclusion: This case report demonstrates the feasibility and efficacy of a weekly treatment with dose-reduced CPT-11 in a patient with metastatic CRC on hemodialysis due to chronic renal failure

Section 355\u27s Active Business Rule--An Outdated Inefficacy

In order to delineate the problems inherent in the active business rule, this Note first will examine the legislative history of tax-free separations, isolating the primary purpose and policy of section 355. Regulatory and judicial interpretations of section 355 will also be analyzed to determine their propriety in light of the statute\u27s purpose and to illustrate the confusion that exists in the area. This, in turn, will lead to a suggested approach for dealing with section 355 transactions in the future

The effect of fatty acid surfactants on the uptake of nitric acid to deliquesced NaCl aerosol

Surface active organic compounds have been observed in marine boundary layer aerosol. Here, we investigate the effect such surfactants have on the uptake of nitric acid (HNO<sub>3</sub>), an important removal reaction of nitrogen oxides in the marine boundary layer. The uptake of gaseous HNO<sub>3</sub> on deliquesced NaCl aerosol was measured in a flow reactor using HNO<sub>3</sub> labelled with the short-lived radioactive isotope <sup>13</sup>N. The uptake coefficient γ on pure deliquesced NaCl aerosol was γ=0.5±0.2 at 60% relative humidity and 30 ppb HNO<sub>3</sub>(g). The uptake coefficient was reduced by a factor of 5–50 when the aerosol was coated with saturated linear fatty acids with carbon chain lengths of 18 and 15 atoms in monolayer quantities. In contrast, neither shorter saturated linear fatty acids with 12 and 9 carbon atoms, nor coatings with the unsaturated oleic acid (C18, cis-double bond) had a detectable effect on the rate of HNO<sub>3</sub> uptake. It is concluded that it is the structure of the monolayers formed, which determines their resistance towards HNO<sub>3</sub> uptake. Fatty acids (C18 and C15), which form a highly ordered film in the so-called liquid condensed state, represent a significant barrier towards HNO<sub>3</sub> uptake, while monolayers of shorter-chain fatty acids (C9, C12) and of the unsaturated oleic acid form a less ordered film in the liquid expanded state and do not hinder the uptake. Similarly, high contents of humic acids in the aerosol, a structurally inhomogeneous, quite water soluble mixture of oxidised high molecular weight organic compounds did not affect HNO<sub>3</sub> uptake. As surfactant films on naturally occurring aerosol are expected to be less structured due to their chemical inhomogeneity, it is likely that their inhibitory effect on HNO<sub>3</sub> uptake is smaller than that observed here for the C15 and C18 fatty acid monolayers

The pyloric neural circuit of the herbivorous crab Pugettia producta shows limited sensitivity to several neuromodulators that elicit robust effects in more opportunistically feeding decapods

Modulation of neural circuits in the crustacean stomatogastric nervous system (STNS) allows flexibility in the movements of the foregut musculature. The extensive repertoire of such resulting motor patterns in dietary generalists is hypothesized to permit these animals to process varied foods. The foregut and STNS of Pugettia producta are similar to those of other decapods, but its diet is more uniform, consisting primarily of kelp. We investigated the distribution of highly conserved neuromodulators in the stomatogastric ganglion (STG) and neuroendocrine organs of Pugettia, and documented their effects on its pyloric rhythm. Using immunohistochemistry, we found that the distributions of Cancer borealis tachykinin-related peptide I (CabTRP I), crustacean cardioactive peptide (CCAP), proctolin, red pigment concentrating hormone (RPCH) and tyrosine hydroxylase (dopamine) were similar to those of other decapods. For all peptides except proctolin, the isoforms responsible for the immunoreactivity were confirmed by mass spectrometry to be the authentic peptides. Only two modulators had physiological effects on the pyloric circuit similar to those seen in other species. In non-rhythmic preparations, proctolin and the muscarinic acetylcholine agonist oxotremorine consistently initiated a full pyloric rhythm. Dopamine usually activated a pyloric rhythm, but this pattern was highly variable. In only about 25% of preparations, RPCH activated a pyloric rhythm similar to that seen in other species. CCAP and CabTRP I had no effect on the pyloric rhythm. Thus, whereas Pugettia possesses all the neuromodulators investigated, its pyloric rhythm, when compared with other decapods, appears less sensitive to many of them, perhaps because of its limited diet

Are serial CA 19-9 kinetics helpful in predicting survival in patients with advanced or metastatic pancreatic cancer treated with gemcitabine and cisplatin?

Background: Serial kinetics of serum CA 19-9 levels have been reported to reflect response and survival in patients with pancreatic cancer undergoing surgery, radiotherapy, and chemotherapy. We prospectively studied serial kinetics of serum CA 19-9 levels of patients with locally advanced or metastatic disease treated with gemcitabine and cisplatin. Patients and Methods: Enrolled in the study were 87 patients (female/male = 26/61; stage III/IV disease = 24/63). Patients received gemcitabine 1,000 mg/m(2) on days 1, 8, and 15 plus cisplatin 50 mg/m(2) on days 1 and 15, every 4 weeks. Serum samples were collected at the onset of chemotherapy and before the start of a new treatment cycle (day 28). Results: 77 of 87 patients (88.5%) with initially elevated CA 19-9 levels were included for evaluation. According to imaging criteria, 4 (5.2%) achieved a complete remission and 11 (14.3%) achieved partial remission, yielding an overall response rate of 19.5%. 43 (55.8%) patients were CA 19-9 responders, defined by greater than or equal to50% decrease in CA 19-9 serum levels within 2 months after treatment initiation. Except for one, all patients who had responded by imaging criteria (n = 14) fulfilled the criterion of a CA 19-9 responder. Despite being characterized as non-responders by CT-imaging criteria (stable/progressive disease), 29 patients were classified as CA 19-9 responders (positive predictive value 32.5%). Independent of the response evaluation by CT, CA 19-9 responders survived significantly longer than CA 19-9 non-responders (295 d; 95% CI: 285-445 vs. 174 d; 95% CI: 134-198; p = 0.022). Conclusion: CA 19-9 kinetics in serum serve as an early and reliable indicator of response and help to predict survival in patients with advanced pancreatic cancer receiving effective treatment with gemcitabine and cisplatin

Stability and Hermitian-Einstein metrics for vector bundles on framed manifolds

We adapt the notions of stability of holomorphic vector bundles in the sense of Mumford-Takemoto and Hermitian-Einstein metrics in holomorphic vector bundles for canonically polarized framed manifolds, i.e. compact complex manifolds X together with a smooth divisor D such that K_X \otimes [D] is ample. It turns out that the degree of a torsion-free coherent sheaf on X with respect to the polarization K_X \otimes [D] coincides with the degree with respect to the complete K\"ahler-Einstein metric g_{X \setminus D} on X \setminus D. For stable holomorphic vector bundles, we prove the existence of a Hermitian-Einstein metric with respect to g_{X \setminus D} and also the uniqueness in an adapted sense.Comment: 21 pages, International Journal of Mathematics (to appear