p27kip1 Expression Is Associated With Tumor Response to Preoperative Chemoradiotherapy in Rectal Cancer

BACKGROUND: Our aim was to ascertain whether or not the response to preoperative chemoradiotherapy for rectal cancer is associated with p27kip1 and p53 protein expression. METHODS: Thirty-eight patients (27 male, 11 female) with a mean age of 59 years (age range 33-87) and stage II-III rectal cancer received preoperative chemoradiotherapy (45-50.4 Gy; 5-FU 350 mg/m2/day and leucovorin 10 mg/m2/day). Thirty-one underwent low anterior resection; seven underwent abdominoperineal excision. Endoscopic tumor biopsies, performed before adjuvant therapy, were evaluated for: histologic type, tumor differentiation, mitotic index, and p27kip1 and p53 protein expression which were immunohistochemically determined. p53 expression was graded as: a) absent or present in < or =10% of tumor cells; b) present in 11-25%; c) present in 26-75%; and d) present in >75% of tumor cells. p27kip1 expression was assessed using both light microscopy (percent of stained cells x10 HPF) and cytometry with an image analysis workstation. Tumor response, ascertained with histology, was classified using a scale from 0 (no response) to 6 (complete pathologic response). RESULTS: The mitotic index for the endoscopic biopsies was low in 14 cases, moderate in 17 cases, and high in 7 cases. p53 protein expression was found in 21 (a), 3 (b), 3 (c), and 11 (d) cases. The mean percentage of cells expressing the p27kip1 protein was 34 (range 0-77.14%). A close correlation was found between cytometric and light microscopy findings for p27kip1 (r2 = 0.92, P = .0001). Tumor differentiation was good in 5 cases, poor in 2 cases, and moderate in the remaining 31 cases. While the response to adjuvant therapy was good/complete in 25 (65.78%) cases, it was absent/poor in 13 (34.21%) cases. Univariate analysis associated type of adjuvant therapy (chemoradiotherapy, P = .0428) and p27kip1 protein lower expression (P = .0148) with a poor response to adjuvant treatment. Stepwise linear regression found overexpression of p53 and p27kip1 and young age to be independent variables that were linked to a good response to adjuvant therapy. CONCLUSIONS: Lack of p27kip1 and p53 protein expression in rectal cancer is associated with a poor response to preoperative adjuvant therapy.     

Expression and Membrane Association of Hepatitis C Virus Envelope 1 Protein

The expression of hepatitis C virus (HCV) E1 protein is toxic for Escherichia coli cells. For this reason, we have cloned the E1 gene in the pET3a vector and analyzed the inducible expression of the protein in two strains of E. coli characterised by a different level of reduction of basal synthesis. The results indicated that synthesis of E1 was supported only by the BL21(DE3)pLysS strain which provides a tightest control of protein expression before the induction. The BL21(DE3)pLysS cells were then used for the expression of E1 gene, varying at its carboxy terminus in order to retain (E1, aa 192–383) or delete (E1t, aa 192–340) a C-terminal hydrophobic region that may be involved in membrane association. Following cell fractionation, E1 protein was found associated with the membrane fraction. By contrast, the truncated mutant E1t, was identified in the soluble phase suggesting a direct role for the C-terminal domain in E1 membrane association.     

A randomized validation study comparing embedded versus extracted FACT Head and Neck Symptom Index scores

Objective To evaluate the impact of administration context (embedded versus stand-alone) on the reliability and validity of the FACT Head and Neck Symptom Index (FHNSI). Methods Ninety-eight patients with head and neck cancer were randomized to one of two assessment conditions to evaluate the FHNSI’s context (items administered embedded within the FACT-H&N or as stand-alone scale) and order of administration in the battery. Results Planned comparisons on the item and scale levels revealed no systematic order or context differences. The embedded and stand-alone versions of the FHNSI showed high internal consistency (Cronbach's alpha 0.79–0.87). Correlations were high between the FHNSI versions and the physical and functional well-being scales of the FACT-H&N (0.70–0.84) and measures of pain intensity (−0.73, −0.74) and depression (−0.71, −0.74); moderate to large with the Performance Status Scale for Head and Neck subscales (PSS-HN; 0.46–0.71); and low with an anxiety measure (0.30, 0.34). Both FHNSI versions differentiated patients grouped by performance status (p < .0001, p < .0001) and global rating of change (p < .0001, p < 0.01). The FHNSI's minimally important difference range was 3–4 points. Conclusion The FHNSI is a reliable and valid symptom index, which can be administered alone or scored using items embedded within the FACT-H&N. Athanassios Argiris—Formerly of Feinberg School of Medicine, Northwestern University, Chicago, IL.     

Metronidazole and clarithromycin resistance amongst Helicobacter pylori isolates from a large metropolitan hospital in the United States.

Background: Metronidazole and clarithromycin-based therapies are among the most efficacious treatment regimens for H. pylori infection. Resistance to metronidazole or clarithromycin is associated with impaired therapy with these agents. We conducted a retrospective review of susceptibility data to determine the frequency of primary metronidazole and clarithromycin resistance among H. pylori isolates from a single metropolitan hospital in the United States. The database comprised 933 patients who presented at the Digestive Diseases Clinic at the Veterans Affairs Medical Center in Houston between September 1988 and January 1997 with complaints of dyspepsia, abdominal pain and peptic ulcer disease. One hundred and seventy-nine of these patients had both pharmaceutical records available for evaluation and culture and antimicrobial susceptibility data for analysis. The MICs were determined by both E-test and broth microdilution tests. The frequency of primary metronidazole resistance was 37.4% (67/179). The level of primary clarithromycin resistance was 6.1%. Dual metronidazole and clarithromycin resistance was present in approx. 3%. The high level of primary metronidazole and clarithromycin resistance in H. pylori isolates from this metropolitan hospital is such that antimicrobial susceptibility data should be available so that informed choice can be made for specific eradication therapies, especially in patients who fail treatment.     

Correlation between High Intake of Glycyrrhizin and Myolysis of the Papillary Muscles: An Experimental in vivo Study

Abstract The ingestion of large quantities of glycyrrhizin, whether as a drug or a sweetener, is known, in susceptible subjects, to induce a syndrome similar to hypermineralcorticoidism, with bouts of hypertension, hypokaliaemia and rabdomyolysis, sometimes associated with severe renal failure and hypokaliaemia-induced arrythmias. Glycyrrhizin is also known to isomerize into the glycyrrhetic (or glycyrrhetinic) acids 18α- and 18β-. In previous works, we reported that these metabolites cause bouts of hypertension and reduction in diuresis at low doses in the rat. In particular, the α isomer causes significant elimination of the calcium ion in the urine. The present findings confirm that 18α-glycyrrhetic acid is more toxic than either glycyrrhizin or the β isomer. Histopathological study of tissue samples taken from rats treated with the α isomer also reveal selective damage to the myocardium with oedema, myolysis, apoptosis and blistering of the sarcoplasm. These effects begin to appear in the course of subchronic treatment, they manifest themselves in acute treatment and correlate closely with the electrocardiographic changes recorded in rats acutely treated with 18α-glycyrrhetic acid.     

Melanotic neuroectodermal tumour of maxilla in infancy

Melanotic neruoectodermal tumour of infancy is an uncommon pigmented neural crest derivative. It is usually found affecting children aged one year or less. We present a case report of a four month old male infant with this tumour arising from the right maxilla showing extensive involovement of the surrounding bony and soft tissue structures.     

The radiographic and ultrasonographic evaluation of enteric duplication cysts

The pattern of diagnostic evaluation of seven children with duplication cysts of the gastrointestinal tract (two with bronchopulmonary foregut malformations and five with mid or hindgut duplications) is presented. Each child had plain radiographs followed by ultrasonic scans and appropriate confirmatory radiographic studies with contrast. Scans showed a well defined cystic mass in each case. Radiographs were able to identify more precisely the site of origin of the duplication cyst.