Esophageal involvement in eosinophilic gastroenteritis

The radiologic appearance of esophageal involvement due to eosinophilic gastroenteritis in a 15-year-old boy is presented. The lower two thirds of the esophagus was narrowed and the peristalsis diminished. The mucosa appeared smooth. This is the fourth reported case of esophageal involvement in eosinophilic gastroenteritis.     

The role of long chain fatty acids in regulating food intake and cholecystokinin release in humans

BACKGROUND AND AIMS: The mechanism of intraduodenal fat induced inhibition of food intake is still unclear. Therefore, we tested the ability of duodenal fatty acids to suppress food intake at a lunchtime meal; in addition, we were interested to test if these effects were mediated by cholecystokinin (CCK) A receptors. SUBJECTS AND METHODS: Three sequential double blind, three period crossover studies were performed in 12 healthy males each: (1) subjects received intraduodenal fat with or without 120 mg of tetrahydrolipstatin, an inhibitor of gastrointestinal lipases, or saline; (2) volunteers received intraduodenal long chain fatty acids, medium chain fatty acids, or saline; (3) subjects received long chain fatty acids or saline together with concomitant intravenous infusions of saline or loxiglumide, a specific CCK-A receptor antagonist. The effect of these treatments on food intake and feelings of hunger was quantified. RESULTS: Intraduodenal fat perfusion significantly (p<0.05) reduced calorie intake. Inhibition of fat hydrolysis abolished this effect. Only long chain fatty acids significantly (p<0.05) decreased calorie intake, whereas medium chain fatty acids were ineffective. Infusion of loxiglumide abolished the effect of long chain fatty acids. CONCLUSIONS: Generation of long chain fatty acids through hydrolysis of fat is a critical step for fat induced inhibition of food intake; the signal is mediated via CCK-A receptors.     

In a fully H-2 incompatible chimera, T cells of donor origin can respond to minor histocompatibility antigens in association with either donor or host H-2 type

Fully H-2 incompatible radiation chimeras were prepared using BALB congenic mice. Such chimeric mice were immunized in vivo against histocompatibility antigens of the C57BL/10Sn (B10) background in association with either of the parental H-2 haplotypes, and their spleen cells subsequently boosted in vitro with the same minor antigens. Strong H-2-restricted cytotoxic activity against minor antigens was detected, and the specificity of the restriction could be to the H-2 haplotype of the donor or the host depending on the cells used for priming or boosting. Cross priming could also be demonstrated in these mice. The results show that fully allogenic radiation chimeras can produce H-2-restricted T-cell responses to minor histocompatibility (H) antigens, and are discussed in relation to contrasting results recently obtained against viral antigens.     

Friendly and dangerous signals: is the tissue in control?

In their own defense, tissues send a panoply of signals that initiate immunity and guide the choice of effector class. T(H)1-T(H)2 and T(reg) is far too simple a representation of the breathtaking variety of the resulting responses.     

Danger signals: SOS to the immune system

The activation of dendritic cells, necessary for the initiation of primary and secondary immune responses, can be induced by endogenous danger signals - released by tissues undergoing stress, damage or abnormal death - and also by exogenous danger signals elaborated by pathogens. Some endogenous danger signals that recently have been discovered are heat-shock proteins, nucleotides, reactive oxygen intermediates, extracellular-matrix breakdown products, neuromediators and cytokines like the IFNs. We propose that allergy may be initiated by the direct damage of dendritic or other cells by toxic chemicals and allergenic proteases, and suggest that the triggering of danger signal receptors by exogenous pathogen-derived molecules may be more to the advantage of the pathogen than to the host.     

CD4 cells can be more efficient at tumor rejection than CD8 cells

Researchers designing antitumor treatments have long focused on eliciting tumor-specific CD8 cytotoxic T lymphocytes (CTL) because of their potent killing activity and their ability to reject transplanted organs. The resulting treatments, however, have generally been surprisingly poor at inducing complete tumor rejection, both in experimental models and in the clinic. Although a few scattered studies suggested that CD4 T "helper" cells might also serve as antitumor effectors, they have generally been studied mostly for their ability to enhance the activity of CTL. In this mouse study, we compared monoclonal populations of tumor-specific CD4 and CD8 T cells as effectors against several different tumors, and found that CD4 T cells eliminated tumors that were resistant to CD8-mediated rejection, even in cases where the tumors expressed major histocompatibility complex (MHC) class I molecules but not MHC class II. MHC class II expression on host tissues was critical, suggesting that the CD4 T cells act indirectly. Indeed, the CD4 T cells partnered with NK cells to obtain the maximal antitumor effect. These findings suggest that CD4 T cells can be powerful antitumor effector cells that can, in some cases, outperform CD8 T cells, which are the current "gold standard" effector cell in tumor immunotherapy.     

Feasibility and Efficacy of Accelerated Weekly Concomitant Boost Postoperative Radiation Therapy Combined with Concomitant Chemotherapy in Patients with Locally Advanced Head and Neck Cancer

Background  The aim of this study was to assess feasibility and efficacy of weekly concomitant boost accelerated postoperative radiation therapy (PORT) with concomitant chemotherapy (CT) in patients with locally advanced head and neck cancer (LAHNC). Methods and Materials  Conformal or intensity-modulated 66-Gy RT was performed in 5.5 weeks in 40 patients. Cisplatin was given at days 1, 22, and 43. Median follow-up was 36 months. Results and Discussion  Grade 3 mucositis, dysphagia, and erythema was observed in ten (25%), nine (23%), and six (13%) patients, respectively. Grade 3 or more anemia was observed in two (6%) patients, and leukopenia in five (13%) patients. No grade 3 or 4 thrombocytopenia was observed. Grade 3 nephrotoxicity was observed in one patient (3%). No treatment-related mortality was observed. Grade 2 or more xerostomia and edema were observed in ten (25%) and one (3%) patient, respectively. Locoregional relapse occurred in eight patients, and seven patients developed distant metastases. Median time to locoregional relapse was 6 months. Three-year overall, disease-free survival, and locoregional control rates were 63%, 62%, and 81%, respectively. Multivariate analysis revealed that the only prognostic factor was nodal status. Conclusion  Reducing overall treatment time using accelerated PORT/CT by weekly concomitant boost (six fractions per week) combined with concomitant cisplatin CT is easily feasible with acceptable morbidity. Abderrahim Zouhair and Mahmut Ozsahin contributed equally as senior author. Presented in part at the 14th European Cancer Organisation (ECCO), Barcelona, Spain, 23–27 September 2007; and at the 49th Annual Meeting of the American Society for Therapeutic Radiology and Oncology (ASTRO), Los Angeles, CA, USA, 28 October–1 November 2007.     

Decrease in Hemoglobin Levels Following Surgery Influences the Outcome in Head and Neck Cancer Patients Treated with Accelerated Postoperative Radiotherapy

Aim  To assess the influence of hemoglobin (Hb) levels in locally advanced head and neck cancer (LAHNC) patients treated with surgery and postoperative radiotherapy (PORT). Material and Methods  Pre- and postoperative Hb levels were collected in 79 patients treated with surgery followed by accelerated PORT for LAHNC. Median follow-up was 52 months (range 12–95 months). Results and Discussion  Four-year overall survival (OS) rate was 51%. Neither pre- nor postoperative Hb level (<120 or 130 g/l in women or men, respectively) influenced the outcome. However, when Hb decrease between pre- and postoperative Hb values was taken into account, 4-year OS was significantly higher in patients with Hb difference less than 38 g/l (quartile value) compared with those with Hb decrease 38 g/l or more (61% versus 16%, P = 0.008). Conclusion  Decrease in Hb level by more than 38 g/l after surgery secondary to blood loss influences the outcome when postoperative RT is indicated. Berrin Pehlivan and Abderrahim Zouhair contributed equally to this work. Presented in part at the 6th International Conference on Head and Neck Cancer, August 7-11, 2004, Washington, DC.     

Role of free fatty acids in regulating gastric emptying and gallbladder contraction

The limited effectiveness of orlistat, an inhibitor of gastrointestinal lipases, in inhibiting fat digestion is not completely understood. Therefore we studied the effect of orally and duodenally administered orlistat on gastric emptying, cholecystokinin (CCK) secretion, and gallbladder contraction. In healthy males, gastric emptying of solids and fat were quantified scintigraphically, gallbladder contraction by ultrasound and CCK release by radioimmunoassay. Three studies were performed: (1) oral and (2) duodenal orlistat with a fat-containing meal, and (3) duodenal orlistat with a fat-free meal. Gastric emptying rates of solids and fat (T50% accelerated by 16 and by 22%, p < 0.05, respectively) were significantly faster after duodenal perfusion of orlistat; gallbladder contraction and CCK release were reduced under these conditions (p < 0.005, respectively). With oral orlistat no significant effect was documented on these parameters. We conclude that fat hydrolysis is essential in the regulation of fat-induced gastric emptying and gallbladder contraction.