Expression of p53 in adenocarcinoma of the gallbladder and bile ducts

Abstract: Point mutation of the p53 tumor suppressor gene appears to be an important event in tumor development and progression, and overexpression of the p53 gene product has been widely studied in a variety of neoplasms. Some point mutations of the p53 gene lead to an increase in half-life in the gene product, which accumulates in the nucleus and can be detected by immunohistochemical means. We studied overexpression of p53 protein in specimens from 12 patients with adenocarcinoma of the gallbladder, two gallbladders with epithelial dysplasia without carcinoma, eight carcinomas of the common bile duct, 13 hilar cholangiocarcinomas, and six peripheral cholangiocarcinomas. The monoclonal antibody Ab-2 (Oncogene Science) was used in conjunction with citrate microwave antigen retrieval. Nuclear staining was scored as positive (graded 1 to 3, depending on number of positive nuclei) or negative. Overexpression of p53 protein was present in 7/12 (58%) gallbladder carcinomas, and was seen more often in moderately or poorly differentiated tumors. Intramucosal carcinoma adjacent to invasive carcinoma was positive in three cases, although fewer cells stained than in the carcinoma. Two cases of low-grade dysplasia not associated with carcinoma were negative. Expression of p53 was not an independent prognostic factor when survival was related to grade and stage of tumor. Three of eight (38%) common bile duct carcinomas and 5/13 (38%) hilar cholangiocarcinomas were positive for p53. Slightly fewer (2/6, 33%) peripheral cholangiocarcinomas were positive. No difference in survival relative to p53 expression was demonstrated.     

Ventilatory muscle support in respiratory failure with nasal positive pressure ventilation

Long-term intermittent mechanical ventilation results in improvements in ventilatory performance and clinical status between ventilation sessions in patients with chronic respiratory failure. The application of intermittent positive pressure ventilation through a nasal mask (NPPV) is a simple, noninvasive method for the provision of chronic intermittent ventilatory support. We investigated the effects of NPPV on inspiratory muscle activity in three normal subjects and nine patients with acute or chronic ventilatory failure due to restrictive (four subjects) or obstructive (five subjects) respiratory disorders. NPPV resulted in reductions of phasic diaphragm electromyogram amplitude to 6.7 +/- 0.7 percent (mean +/- SEM) of values obtained during spontaneous breathing in the normal subjects, 6.4 +/- 3.2 percent in the restrictive group, and 8.3 +/- 5.1 percent in the obstructive group. Simultaneous decreases in activity of accessory respiratory muscles were observed. The reductions in inspiratory muscle activity were confirmed by the finding of positive intrathoracic pressure swings on inspiration in all subjects. With NPPV, oxygen saturation and PCO2 remained stable or improved as compared with values obtained during spontaneous breathing. These results indicate that NPPV can noninvasively provide ventilatory support while reducing inspiratory muscle energy expenditure in acute and chronic respiratory failure of diverse etiology. Long-term assisted ventilation with NPPV may be useful in improving ventilatory performance by resting the inspiratory muscles.     

Impact of age, height, and body mass index on arterial diameters in infants and children: a model for predicting femoral artery diameters prior to cardiovascular procedures.

PURPOSE: To measure common femoral artery (CFA) diameters in infants and children referred for cardiac catheterization and investigate if CFA diameters can be predicted upon the basis of age, body mass index (BMI), and height. METHODS: CFA diameters were measured in 84 infants and children (50 boys; age range 1- 220 months) referred for diagnostic or therapeutic cardiac interventions. Sonographic measurements were made in a supine position utilizing a 7.5-MHz linear transducer; diameters were defined as the intima to intima distance. Age was described in months and height in centimeters. The Spearman correlation coefficient (rho) was used to test the similarity of diameters between sides; the Pearson correlation coefficient (r) was used to analyze the influence of age, height, and BMI on CFA diameter. RESULTS: Diameters of the right and left CFA were similar (rho=0.951). Age and height were highly correlated (rho=0.956), but not BMI and height (rho=0.279). The best model was CFA diameter = -0.838 + 0.031 height + 0.046 BMI. Height was the most relevant determinant for CFA diameter (p<0.0001, 90% CI 0.027 to 0.036; BMI: p=0.093, 90% CI 0.001 to 0.090, and the intercept: p=0.032, 90% CI-1.475 to-0.200). CONCLUSIONS: Common femoral artery diameter can be sufficiently predicted from height and BMI of infants and children prior to femoral catheterization or surgical reconstruction.     

Pain on common bile duct injection during ERCP: does it indicate sphincter of Oddi dysfunction?

The reproduction of a patient's biliary-type pain upon initial injection of contrast material into the common bile duct during diagnostic ERCP is a dramatic experience for both patient and physician. The significance of this phenomenon is not clear, but it is touted by some to be a provocative test for sphincter of Oddi dysfunction. Sphincter of Oddi manometry was performed on 224 consecutive patients referred over a 2-year period for evaluation of post-cholecystectomy syndrome and suspected sphincter of Oddi dysfunction. All patients received only intravenous diazepam as premedication for ERCP. Delayed drainage time (greater than 45 min), bile duct dilation (greater than or equal to 12 mm), and a basal sphincter of Oddi pressure of greater than 40 mm Hg (mean +/- 3 SD) were considered elevated. We observed a reproduction of pain in 15 of 224 patients (6.7%) immediately following contrast injection. There was no correlation between pain on contrast injection and elevated basal sphincter of Oddi pressure, delayed common bile duct drainage, bile duct dilation, or abnormal liver enzymes. Therefore, we feel that reproduction of the patient's biliary-type pain associated with contrast injection of ERCP is not a provocative test for sphincter of Oddi dysfunction.     

Effects of sodium cyanide and nicotine on upper airway resistance in anesthetized dogs

The purpose of this study was to determine whether pharmacologic interventions which increase respiratory drive could also reduce flow resistance in the upper airway. Studies were performed in twelve anesthetized supine dogs. In six animals breathing spontaneously through the intact upper airway, intravenous administration of respiratory stimulants (sodium cyanide and nicotine) produced a dose-related decrease in upper airway. In nine animals, upper airway resistance was measured across the isolated upper airway. The stimulants produced a dose-related decrease in upper airway resistance. In both preparations inspiratory resistance fell at lower doses than expiratory resistance. Eventually a dose could be given which resulted in comparable, minimal values of resistance during both inspiration and expiration. Mechanisms for changes in resistance were clarified using lateral radiographs of the neck and transbronchoscopic views of the upper airway. Pharmacologic challenge resulted in a change in the route of airflow (from nose only to nose-and-mouth breathing) as well as a change in caliber of the airway at the level of the naso-pharynx and hyoid apparatus. In anesthetized dogs, respiratory stimulants will decrease upper airway resistance by increasing activation of upper airway muscles which may enlarge the airway, change the route of flow, and thus overcoming collapsing forces produced by increased chest wall muscle activation.     

The Association of Remote Streptococcus bovis Bacteremia with Colonic Neoplasia

We prospectively studied five patients with a remote history of Streptococcus bovis bacteremia who had not previously been evaluated for colonic pathology. This study was prompted by several reports of concomitant neoplasia in patients with recent S. bovis bacteremia. The patients were studied at a mean of 32 months after bacteremia. Despite the absence of other signs or symptoms suggestive of bowel disease, a negative test for occult blood in stool and a negative fecal culture for S. bovis , two patients were found to have neoplastic polyps of the colon. These findings suggest that the risk of colonic neoplasia in patients with remote S. bovis septicemia is similar to that found in patients with recent bacteremia, but evaluation of a larger group of these patients will be necessary to establish this risk.     

Plasma membrane Ca2+ ATPase 1 (PMCA1) but not PMCA4 is critical for B-cell development and Ca2+ homeostasis in mice

The amplitude and duration of Ca²⁺ signaling is crucial for B-cell development and self-tolerance; however, the mechanisms for terminating Ca²⁺ signals in B cells have not been determined. In lymphocytes, plasma membrane Ca²⁺ ATPase (PMCA) isoforms 1 and 4 (PMCA1 and PMCA4, aka ATP2B1 and ATP2B4) are the main candidates for expelling Ca²⁺ from the cell through the plasma membrane. We report here that Pmca4 (Atp2b4) KO mice had normal B-cell development, while mice with a conditional KO of Pmca1 (Atp2b1) had greatly reduced numbers of B cells, particularly splenic follicular B cells, marginal zone B cells, and peritoneal B-1a cells. Mouse and naïve human B cells showed only PMCA1 expression and no PMCA4 by western blot, in contrast to T cells, which did express PMCA4. Calcium handling was normal in Pmca4^−/− B cells, but Pmca1 KO B cells had elevated basal levels of Ca²⁺, elevated levels in ER stores, and reduced Ca²⁺ clearance. These findings show that the PMCA1 isoform alone is required to ensure normal B-cell Ca²⁺ signaling and development, which may have implications for therapeutic targeting of PMCAs and Ca²⁺ in B cells.