Influence of fructooligosaccharides on Peyer's patch lymphocyte numbers in healthy and endotoxemic mice

OBJECTIVE: The purpose of this study was to determine whether fructooligosaccharides (FOS) exert an immunomodulating effect on Peyer's patches (PP), the main inductive site of the intestinal immune system. We investigated the effects of FOS in healthy and endotoxemic animals. METHODS: Six-week-old female Balb/c mice were fed a control diet or a diet supplemented with 10% FOS over a period of 16 d. To induce endotoxemia, mice were challenged intraperitoneally with lipopolysaccharide (LPS) on day 15. PP were excised from mice, and lymphocyte subpopulations (B lymphocytes, T lymphocytes, CD4(+) cells, and CD8(+) cells) were determined by flow cytometry. RESULTS: The FOS-enriched diet increased the total cell yield in healthy and endotoxemic mice (P < 0.001). Similarly, B lymphocytes were increased in both groups (P < 0.001). In contrast, T lymphocytes were unaltered in healthy mice but increased in LPS-challenged mice after FOS enrichment (P < 0.001). In endotoxemic mice but not in control animals, the increase of CD4(+) cells (P < 0.001) was more pronounced than that of CD8(+) cells (P < 0.001), thus increasing the CD4:CD8 ratio (P < 0.01). CONCLUSION: FOS showed an immunostimulating effect on PP lymphocytes under healthy and endotoxemic conditions. Thus it can be concluded that FOS administration affects not only the large intestine but also the main inductive part of the mucosal immune system in the small intestine.     

Salvinorin A: the "magic mint" hallucinogen finds a molecular target in the kappa opioid receptor

Salvinorin A, a neoclerodane diterpene, is the most potent naturally occurring hallucinogen known and rivals the synthetic hallucinogen lysergic acid diethylamide in potency. Recently, the molecular target of salvinorin A was identified as the kappa opioid receptor (KOR). Salvinorin A represents the only known non-nitrogenous KOR selective agonist. Based on the selectivity of salvinorin A for the KOR, this receptor represents a potential molecular target for the development of drugs to treat disorders characterized by alterations in perception, including schizophrenia, Alzheimer's disease and bipolar disorder.     

Liver inflammation during monocrotaline hepatotoxicity

Monocrotaline (MCT) is a pyrrolizidine alkaloid (PA) plant toxin that causes hepatotoxicity in humans and animals. Human exposure occurs from consumption of contaminated grains and herbal teas and medicines. Intraperitoneal injection (i.p.) of 300 mg/kg MCT in rats produced time-dependent hepatic parenchymal cell (HPC) injury beginning at 12 h. At this time, an inflammatory infiltrate consisting of neutrophils (PMNs) appeared in areas of hepatocellular injury, and activation of the coagulation system occurred. PMN accumulation was preceded by up-regulation of the PMN chemokines cytokine-induced neutrophil chemoattractant-1 (CINC-1) and macrophage inflammatory protein-2 (MIP-2) in the liver. The monocyte chemokine, monocyte chemoattractant protein-1 (MCP-1), was also upregulated. Inhibition of Kupffer cell function with gadolinium chloride (GdCl₃) significantly reduced CINC-1 protein in plasma after MCT treatment but had no effect on hepatic PMN accumulation. Since inflammation can contribute to either pathogenesis or resolution of tissue injury, we explored inflammatory factors as a contributor to MCT hepatotoxicity. To test the hypothesis that PMNs contribute to MCT-induced HPC injury, rats were depleted of PMNs with a rabbit anti-PMN serum prior to MCT treatment. Anti-PMN treatment reduced hepatic PMN accumulation by 80% but had no effect on MCT-induced HPC injury or activation of the coagulation system. To test the hypothesis that Kupffer cells and/or tumor necrosis factor- (TNF-) are required for MCT-induced HPC injury, rats were treated with either GdCl₃ to inhibit Kupffer cell function or pentoxifylline (PTX) to prevent synthesis of TNF-. Neither treatment prevented MCT-induced HPC injury. Results from these studies suggest that PMNs, Kupffer cells and TNF- are not critical mediators of MCT hepatotoxicity. Accordingly, although inflammation occurs in the liver after MCT treatment, it is not required for HPC injury and possibly occurs secondary to hepatocellular injury.     

Sexual dimorphism in trauma? A retrospective evaluation of outcome

PURPOSE: Multiple studies have demonstrated a heightened immune response in female animals subjected to trauma-hemorrhage models and have implied a subsequent survival advantage. PROCEDURES: A retrospective review of outcome in 15,170 trauma admissions over a 5-year-period (1993-1997) at a level 1-trauma center was performed. A comparison of outcome by gender, age, injury severity score (ISS), mechanism of injury, location of injury (AIS), and length of hospitalization (intensive care unit and total hospitalization) was performed. FINDINGS: There were 12,456 male and 2714 female patients included in the study. Overall survival rates (male = 90.2%, female = 90.8%) and survival of serious (ISS > or = 15) trauma (male = 63.5%, female = 60.5%) were not statistically different. Logistic regression analysis identified age, mechanism and ISS as factors associated with survival. CONCLUSION: Retrospective evaluation of our trauma population failed to show a difference in outcome between male and female trauma patients. Age, mechanism and severity of injury-but not gender-were identified as factors influencing survival.     

Sacral pseudotumor complicating iliac bone harvest: radiographic, CT and MRI appearances

We present the imaging appearances of a lytic pseudotumor in the right sacral ala presenting with referred pain to the right thigh. Subsequent imaging revealed the presence of a cystic lesion arising at the site of previous bone graft harvest; CT-guided aspiration yielded synovial fluid presumed to arise from the contiguous sacroiliac joint.     

Microsatellite alterations in esophageal dysplasia and squamous cell carcinoma from laser capture microdissected endoscopic biopsies

Esophageal squamous cell carcinoma (ESCC), with a 5 year survival below 15%, is one of the most common fatal cancers worldwide. Significant reduction in mortality may be achieved by detecting and treating asymptomatic precursor lesions and curable early cancers. To explore this possibility and look for potential early detection markers, we examined alterations in 16 microsatellite markers in laser capture microdissected (LCM) endoscopic biopsies from the esophagus, including 15 dysplasias and 22 ESCCs, in patients from Shanxi Province, a region in north-central China. We found a significant increase in the total frequency of allelic loss with increasing disease severity. Allelic loss was seen in 2% of the markers in patients with low grade dysplasia (LGD), 15% of the markers in patients with high grade dysplasia (HGD), and 35% of the markers in patients with ESCC. Ten different markers (D3S4513, D5S2501, D8S1106, D9S118, D9S910, D13S1493, D13S894, D13S796, D15S655, and D17S1303) showed allelic loss in one or more of the premalignant lesions tested. The frequency of microsatellite instability (MSI) also increased with histological severity, from 22% in LGD to 33% in HGD and 59% in ESCC. These results indicate that the development of ESCC is associated with genetic instability, that this instability can be detected in endoscopic biopsies of recognized precursor lesions in patients without invasive cancer, and that these markers may be useful as predictive markers in the early detection of ESCC. Finally, we also report methodologic/technical modifications that enhance the use of LCM for screening endoscopic biopsies.     

Long-term outcome of phase II trial evaluating chemotherapy,chemoradiotherapy, and surgery for locoregionally advanced esophageal cancer

PURPOSE: To evaluate the long-term outcome of chemotherapy, chemoradiotherapy, and surgery for patients with locoregionally advanced esophageal cancer. METHODS AND MATERIALS: Thirty-eight patients with locoregionally advanced esophageal cancer were entered into a Phase II study between November 1996 and October 1998 at the University of Texas M. D. Anderson Cancer Center. Patients initially received two cycles of chemotherapy with paclitaxel (200 mg/m(2)), 5-fluorouracil (750 mg/m(2)/d for 5 days), and cisplatin (15 mg/m(2)/d for 5 days), followed by chemoradiotherapy, consisting of radiation (45 Gy during 5 weeks) with 5-fluorouracil (300 mg/m(2)/d during radiation) and cisplatin (15 mg/m(2)/d for 5 days). Surgical resection was performed 4-6 weeks after the completion of the chemoradiotherapy. RESULTS: Most patients had adenocarcinoma (n = 32; 84%). Pretreatment endoscopic ultrasonography revealed T3 tumors in 33 patients (87%) and N1 disease in 25 patients (66%). Thirty-seven patients (97%) completed the planned chemotherapy and chemoradiotherapy, and 35 patients (92%) underwent surgery, with a 30-day mortality rate of 6% (2 of 35 patients). A pathologic complete response or microscopic residual carcinoma (<10% viable) was found in 25 (71%) of 35 patients and was associated with a disease-free survival rate of 72% at 3 years and 51% at 5 years. On the basis of an intention-to-treat analysis and a median potential follow-up of 58 months, the 3- and 5-year overall survival rate for all 38 patients was 63% and 39%, respectively. CONCLUSION: The long-term results of this study suggest that the strategy of induction chemotherapy followed by chemoradiotherapy and surgery is safe and warrants further evaluation in the treatment of patients with locoregionally advanced esophageal cancer.     

Postoperative pulmonary complications after preoperative chemoradiation for esophageal carcinoma: correlation with pulmonary dose-volume histogram parameters

PURPOSE: To clarify the relationship between the percentage of lung receiving low radiation doses with concurrent chemotherapy and the occurrence of postoperative pulmonary complications in the treatment of esophageal carcinoma. METHODS: From 117 patients who underwent preoperative chemoradiation for esophageal cancer at our institution between 1998 and 2002, we selected 61 patients for whom complete pulmonary dose-volume histogram (DVH) data were available and analyzed the incidence of pneumonia and acute respiratory distress syndrome (ARDS) in this group. All patients received concurrent chemoradiation therapy, and 39 patients also received induction chemotherapy before concurrent chemoradiation. The median age was 62 years, and the median radiotherapy dose was 45 Gy. The percentage of lung volume receiving at least 10 Gy (V10), 15 Gy (V15), and 20 Gy (V20) were recorded from each pulmonary DVH. RESULTS: Eleven (18%) of the 61 patients had pulmonary complications, 2 of whom died after progression of pneumonia. Pulmonary complications were noted more often (35% vs. 8%, p = 0.014) when the pulmonary V10 was > or =40% vs. <40% and when the V15 was > or /=30% vs. < 30% (33% vs. 10%, p = 0.036). An apparent increase in pulmonary complication rate when V20 was > or =20% vs. <20% (32% vs. 10%, p = 0.079) was not significant. None of the other factors analyzed (surgical procedure, tumor location, use of induction chemotherapy, use of concurrent taxane-based chemoradiation, or smoking history) was associated with the occurrence of pulmonary complications. The median hospital stay was 17 days for patients who had pulmonary complications vs. 12 days for patients who did not (p = 0.08). CONCLUSIONS: The use of multimodality therapy may require minimization of lung volume irradiation to levels lower than previously expected. Radiotherapy techniques that decrease the volume of lung receiving low radiation doses may significantly reduce the risk of this potentially life-threatening complication.     

State of measures of quality assurance for radiotherapy units in Switzerland

In Switzerland 57 X-ray therapy units are in operation at present. According to the Swiss Ordinance on Radiation Protection, a quality-assurance program must regularly be applied in to these units. However, as the Swiss X-ray Ordinance gives explicit control parameters only for diagnostic units, the present article issues proposals for the realization of a quality-assurance program for the therapy units. In this regard, it is distinguished between checks performed by technical personnel of the X-ray manufacturers and checks performed by a medical physicist with corresponding qualification, or under his supervision. The so-called mentor project for the performance of annual constancy checks in institutes without medical physicists is also taken into account. These proposals should be helpful for the discussion and clarification of competencies, hence contributing to standardization of control practices in Switzerland.