Medullary carcinoma of the large intestine: a population based analysis.

Medullary carcinoma (MC) of the colorectum is a relatively new histological type of adenocarcinoma characterized by poor glandular differentiation and intraepithelial lymphocytic infiltrate. To date, there has been no epidemiological study of this rare tumor type, which has now been incorporated as a separate entity in the World Health Organization (WHO) classification of colorectal cancers. We used the population-based registries of the Surveillance, Epidemiology and End Results (SEER) database to identify all cases of colorectal MC between 1973 and 2006 and compared them to poorly and undifferentiated colonic adenocarcinomas (PDA and UDA, respectively). We observed that MCs were rare tumors, constituting approximately 5-8 cases for every 10,000 colon cancers diagnosed, with a mean annual incidence of 3.47 (+/-0.75) per 10 million population. Mean age at diagnosis was 69.3 (+/-12.5) years, with incidence increasing with age. MCs were twice as common in females, who presented at a later age, with a lower stage and a trend towards favorable prognosis. MCs were extremely rare among African-Americans. MCs were most common in the proximal colon (74%), where they present at a later age than the sigmoid colon. There were no cases reliably identified in the rectum or appendix. Serum carcinoembryonic antigen levels (CEA) were elevated prior to first course of treatment in 40% of the patients. MCs were more commonly poorly differentiated (72%), with 22% being undifferentiated. MCs commonly presented with Stage II disease, with 10% presenting with metastases. Only one patient presented with N2b disease (>7 positive nodes). Early outcome analyses showed that MCs have 1- and 2-year relative survival rates of 92.7 and 73.8% respectively. Although MCs showed a trend towards better early overall survival, undifferentiated MCs present more commonly with Stage III, with comparatively worse early outcomes.

Proteomic assessment of sympathetic ganglia from adult mice that possess null mutations of ExonIII or ExonIV in the p75 neurotrophin receptor gene.

Neurotrophins, such as nerve growth factor (NGF), are capable of binding to the transmembrane p75 neurotrophin receptor (p75NTR), which regulates a variety of cellular responses including apoptosis and axonal elongation. While the development of mutant mouse strains that lack functional p75NTR expression has provided further insight into the importance of this neurotrophin receptor, there remains a paucity of information concerning how the loss of p75NTR expression may alter neural phenotypes. To address this issue, we assessed the proteome of the cervical sympathetic ganglia from two mutant lines of mice, which were compared to the ganglionic proteome of age-matched wild type mice. The ganglionic proteome of mice possessing two mutant alleles of either exonIII or exonIV for the p75NTR gene displayed detectable alterations in levels of Lamin A, tyrosine hydroxylase, and Annexin V, as compared to ganglionic proteome of wild type mice. Decreased expression of the basic isoform of tyrosine hydroxylase may be linked to perturbed NGF signaling in the absence of p75NTR in mutant mice. Stereological measurement showed significant increases in the number of sympathetic neurons in both lines of p75NTR-deficient mice, relative to wild type mice. This enhanced survival of sympathetic neurons coincides with shifts toward the more basic isoforms of Annexin V in mutant mice. This study, in addition to providing the first comparative proteomic assessment of sympathetic ganglia, sheds new light onto the phenotypic changes that occur as a consequence of a loss of p75NTR expression in adult mice.

Thermal inkjet application in the preparation of oral dosage forms: dispensing of prednisolone solutions and polymorphic characterization by solid-state spectroscopic techniques.

The utility of thermal inkjet (TIJ) technology for preparing solid dosage forms of drugs was examined. Solutions of prednisolone in a solvent mixture of ethanol, water, and glycerol (80/17/3 by volume) were dispensed onto poly(tetrafluoroethylene)-coated fiberglass films using TIJ cartridges and a personal printer and using a micropipette for comparison. The post-dried, TIJ-dispensed samples were shown to contain a mixture of prednisolone Forms I and III based on PXRD analyses that were confirmed by Raman analyses. The starting commercial material was determined to be Form I. Samples prepared by dispensing the solution from a micropipette initially showed only Form I; subsequent Raman mapping of these samples revealed the presence of two polymorphs. Raman mapping of the TIJ-dispensed samples also showed both polymorphs. The results indicate that the solvent mixture used in the dispensing solution combined with the thermal treatment of the samples after dispensing were likely the primary reason for the generation of the two polymorphs. The advantages of using a multidisciplinary approach to characterize drug delivery systems are demonstrated using solid state mapping techniques. Both PXRD and Raman spectroscopy were needed to fully characterize the samples. Finally, this report clarifies prednisolone's polymorphic nomenclature existent in the scientific literature.

trans-Difluorosilicon(IV) Complexes of Tetra-p-tolylporphyrin and Tetrakis(p-(trifluoromethyl)phenyl)porphyrin: Crystal Structures and Unprecedented Reactivity in Hexacoordinate Difluorosilanes(1).

Single-crystal X-ray structures have been determined for the difluoro(porphyrinato)silicon(IV) complexes trans-(Por)SiF(2) (Por = the dianions of tetra-p-tolylporphyrin (TTP) and tetrakis(p-(trifluoromethyl)phenyl)porphyrin). Crystallographic data for (TTP)SiF(2).Et(2)O: monoclinic, space group C2/c, a = 30.228(4) Å, b = 9.913(4) Å, c = 15.474(5) Å, alpha = gamma = 90 degrees, beta = 114.58(3) degrees, V = 4217(2) Å(3), Z = 4, R1 = 0.0588. Crystallographic data for (TTFP)SiF(2): monoclinic, space group C2/c, a = 31.557(2) Å, b = 9.546(1) Å, c = 15.941(1) Å, alpha = gamma = 90 degrees, beta = 115.83(1) degrees, V = 4322.4(8) Å(3), Z = 4, R1 = 0.0489. In both structures, the silicon lies in a slightly distorted octahedral geometry (average distances: Si-F 1.642 Å and Si-N 1.919 Å) with the fluorides in a trans configuration, and the porphyrin is in a ruf nonplanar form. The trans-(Por)SiF(2) structures were compared to the structures of related hexacoordinate cis-difluorosilanes and other group 14 metalloporphyrins. (TTP)SiF(2) readily reacts with excess MeMgBr or LiPh to give (TTP)SiMe(2) or (TTP)SiPh(2), respectively, in contrast to related hexacoordinate cis-difluorosilanes which do not react with strong nucleophiles. The enhanced reactivity of (TTP)SiF(2) may be a combination of a trans-effect, even though the structural parameters for cis and trans Si-F bonds and Si-N bonds are essentially the same, and a single-electron transfer process involving the porphyrin ligand.