Citations

AbstractAlthough useful palliation can often be achieved when external beam irradiation and chemotherapy are used to treat locally advanced gastrointestinal malignancies, local control and long‐term survival are infrequent in view of the limited tolerance of surrounding organs and tissues. In view of dose limitations of external beam irradiation, intraoperative irradiation (IORT) with electrons has been used as a supplement to external treatment in an attempt to improve the therapeutic ratio of local control versus complications. An IORT dose of 10 to 20 Gy has been combined with fractionated external beam doses of 45 to 55 Gy in 1.8 Gy fractions in studies performed in the United States, Japan, Europe, and Scandinavian countries. In this paper the indications for and the results of aggressive combined techniques that include IORT are discussed. Results obtained with external beam techniques alone or with chemotherapy and resection are presented by site to demonstrate the need for higher doses of irradiation. When results from IORT series are compared to standard treatment with regard to disease control and survival, local control appears better with locally advanced colorectal, gastric, and pancreatic cancer; and survival appears better with colorectal ± biliary cancers. With pancreatic cancer, improvements in local control do not translate into increased survival in view of the high incidence of subsequent liver and peritoneal failures. Implications for future strategies in all sites are discussed.

ABSTRACT A collection of 99 staphylococcal isolates associated with prosthetic joint infection and 23 coagulase-negative staphylococci isolated from noninfected arthroplasty-associated specimens were screened in order to determine whether the presence of icaA could be used to distinguish between pathogens and nonpathogens. All Staphylococcus aureus prosthetic joint infection isolates ( n = 55) were icaA positive. A total of 46% (20 out of 44) of coagulase-negative staphylococcal prosthetic joint infection isolates were icaA positive, and 30% (7 out of 23) of arthroplasty-associated non-prosthetic joint infection-associated coagulase-negative staphylococcal isolates were icaA positive ( P = 0.23). Certain coagulase-negative Staphylococcus species appeared more likely to be isolated as either arthroplasty-associated non-prosthetic joint infection-associated isolates (e.g., Staphylococcus warneri and Staphylococcus hominis ) or pathogens (e.g., Staphylococcus lugdunensis ). The presence of icaA in a coagulase-negative staphylococcal isolate associated with an arthroplasty is not a useful diagnostic indicator of pathogenicity.

Hepatic steatosis predisposes the liver to cold ischemia-warm reperfusion (CI/WR) injury by unclear mechanisms. Because hepatic steatosis has recently been associated with a lysosomal pathway of apoptosis, our aim was to determine whether this cell-death pathway contributes to CI/WR injury of steatotic livers. Wild-type and cathepsin B-knockout ( Ctsb −/−) mice were fed the methionine/choline-deficient (MCD) diet for 2 wk to induce hepatic steatosis. Mouse livers were stored in the University of Wisconsin solution for 24 h at 4°C and reperfused for 1 h at 37°C in vitro. Immunofluorescence analysis of the lysosomal enzymes cathepsin B and D showed a punctated intracellular pattern consistent with lysosomal localization in wild-type mice fed a standard diet after CI/WR injury. In contrast, cathepsin B and D fluorescence became diffuse in livers from wild-type mice fed MCD diet after CI/WR, indicating that lysosomal permeabilization had occurred. Hepatocyte apoptosis was rare in both normal and steatotic livers in the absence of CI/WR injury but increased in wild-type mice fed an MCD diet and subjected to CI/WR injury. In contrast, hepatocyte apoptosis and liver damage were reduced in Ctsb −/− and cathepsin B inhibitor-treated mice fed the MCD diet following CI/WR injury. In conclusion, these findings support a prominent role for the lysosomal pathway of apoptosis in steatotic livers following CI/WR injury.

AbstractA number of surgical methods, including use of the long intestinal tube, have been designed to decrease the incidence of recurrent small bowel obstruction. The aim of the present study was to review the indications, morbidity, and long‐term results of the long intestinal tube at the Mayo Clinic. During the 12‐year period 1981–1992, 47 patients had such tubes placed. The patients formed a complex surgical group: 46 patients had previously undergone at least one laparotomy (median 4, range 1–10); 41 patients had been hospitalized at least once for small bowel obstruction (median 3, range 1–15); and all 41 of these patients had undergone at least one previous laparotomy for obstruction (median 2, range 1–7). Eleven patients had a history of inflammatory bowel disease, and eight had a history of irradiation. In addition to dense adhesions in 46 patients, operative findings included large bowel tumors in six patients, intraperitoneal carcinomatosis in four, intraabdominal abscess in four, and small bowel stricture in three. Twenty patients required either a small bowel or large bowel resection, and three had a stoma fashioned. Only one case of morbidity (tube retraction) was related to tube placement. Among the 36 patients with complete follow‐up, nine patients developed episodes of recurrent adhesional small bowel obstruction after a mean follow‐up of 48 months, although only one required laparotomy. Of the remaining 11 patients it is known that two developed small bowel obstruction, one of whom required laparotomy. Use of the long intestinal tube has generally been reserved for surgically complex cases. In light of the diverse and complicated nature of the patients in this series, the long‐term reoperation rate for adhesional small bowel obstruction appears to be low.

AbstractOur aim was to examine the long‐term success of cholecystoenterostomy performed for the relief of benign extrahepatic biliary obstruction. Concern about the ability of cholecystoenterostomy to provide reliable long‐term biliary decompression has led many to abandon its use for benign biliary obstruction. Thirty‐four patients who underwent cholecystoenterostomy for benign biliary obstruction over a 17‐year period were reviewed. Patients were followed until cholecystoenterostomy failure, death, or to date. Failure was defined as recurrent biliary obstruction or cholangitis requiring therapeutic intervention. Mean follow‐up was 8.0 years. Early postoperative morbidity occurred in 11 patients (32%), but only one early complication (cholangitis) was related directly to the cholecystoenteric anastomosis. Five patients (15%) experienced late biliary tract complications related directly to the cholecystoenterostomy including recurrent biliary stones with biliary obstruction in four and anastomotic stricture in one. All required reoperation and conversion to choledochoenterostomy at a mean of 112 months. Cholecystoenterostomy can provide reasonably effective long‐term biliary decompression in selected patients with benign biliary obstruction.

Background— Swimming is a relatively genotype-specific arrhythmogenic trigger for type 1 long-QT syndrome (LQT1). We hypothesize that mimickers of concealed LQT1, namely catecholaminergic polymorphic ventricular tachycardia (CPVT), may also underlie swimming-triggered cardiac events. Methods and Results— Between August 1997 and May 2003, 388 consecutive, unrelated patients were referred specifically for LQTS genetic testing. The presence of a personal and/or family history of a near-drowning or drowning was determined by review of the medical records and/or phone interviews and was blinded to genetic test results. Comprehensive mutational analysis of the 5 LQTS-causing channel genes, KCNQ1 (LQT1), KCNH2 (LQT2), SCN5A (LQT3), KCNE1 (LQT5), and KCNE2 (LQT6), along with KCNJ2 (Andersen-Tawil syndrome) and targeted analysis of 18 CPVT1-associated exons in RyR2 , was performed with the use of denaturing high-performance liquid chromatography and direct DNA sequencing. Approximately 11% (43 of 388) of the index cases had a positive swimming phenotype. Thirty-three of these 43 index cases had a “Schwartz” score (≥4) suggesting high clinical probability of LQTS. Among this subset, 28 patients (85%) were LQT1, 2 patients (6%) were LQT2, and 3 were genotype negative. Among the 10 cases with low clinical probability for LQTS, 9 had novel, putative CPVT1-causing RyR2 mutations. Conclusions— In contrast to previous studies that suggested universal LQT1 specificity, genetic heterogeneity underlies channelopathies that are suspected chiefly because of a near-drowning or drowning. CPVT1 and strategic genotyping of RyR2 should be considered when LQT1 is excluded in the pathogenesis of a swimming-triggered arrhythmia syndrome.

Background— Patients with heart failure have high levels of central sympathetic outflow and also have a high prevalence of sleep-related breathing disorders, predominantly central sleep apnea. The options for treating central sleep apnea in heart failure are limited and include theophylline. Whether theophylline alters sympathetic activity in heart failure patients is not known. Methods and Results— Using a single-blinded, randomized, placebo-controlled study design, we investigated the sympathetic, hemodynamic, neurohumoral, and ventilatory effects of theophylline in patients with congestive heart failure compared with healthy control subjects closely matched for age, sex, and body mass index. Theophylline increased muscle sympathetic nerve activity and lowered transcutaneous CO 2 in the control subjects but only lowered transcutaneous CO 2 in the heart failure patients. Theophylline nearly doubled plasma renin concentration in both the healthy subjects ( P <0.01) and the heart failure patients ( P <0.02). Conclusions— Our study shows that in heart failure patients, there are differential effects of theophylline: in contrast to healthy subjects, theophylline does not increase sympathetic activity in heart failure, whereas increases in plasma renin and ventilation are still evident. These novel findings may have important implications for understanding the potential harmful and beneficial effects of theophylline and related substances in heart failure patients.