Outcomes of external and endonasal dacryocystorhinostomy according to a modified Lacrimal Symptom Questionnaire (Lac-Q).

Background: Nasolacrimal duct obstruction is usually treated using endoscopic or external dacryocystorhinostomy (DCR). The anatomic outcomes of both the endoscopic and external approaches are considered excellent. However, anatomic success does not translate into patient satisfaction. The current study assessed pre- and postoperative lacrimal problems using the symptom-based Lacrimal Symptom Questionnaire (Lac-Q) and investigated patient satisfaction depending on the choice of surgical technique. Methods: A total of 112 eligible patients with lacrimal problems treated using external or endonasal DCR at the ophthalmology and ear, nose, and throat clinics at Skane University Hospital, Scania, Sweden, over a four-year period, were enrolled in this retrospective study. Patients were considered eligible if they experienced preoperative epiphora and had lacrimal duct stenosis. They were offered treatment using either external or endonasal DCR and were allowed to freely choose the technique. Exclusion criteria consisted of previous ipsilateral DCR, congenital NLDO, age < 18 years, presence of cancer, previous orbital trauma, or noncompliance with postoperative follow-up. After surgery, the patients were sent the Lac-Q to evaluate their lacrimal symptoms pre- and postoperatively. Complementary questions were added pertaining to the operative scar and the patients' overall satisfaction with the operation. Results: In total, 67 (60%) patients with ages ranging from 18 to 88 years completed the questionnaire, 33 (49%) of whom underwent external DCR and 34 (51%) endonasal DCR. Of the 67 respondents, 51 (76%) were women and 16 (24%) were men. Patients scored preoperative lacrimal problems highly on the Lac-Q, reporting both symptomatic and social problems due to epiphora. Following surgery, the group that underwent external DCR remained home from work for 2 - 14 days (median, 3.5 days). However, 17 (52%) were retired. After the endonasal DCR, the patients remained home for 0 - 7 days (median, 2 days). Most patients were satisfied after DCR surgery, with both techniques significantly improving total, lacrimal symptom, and social impact scores (all P < 0.001). No differences in postoperative satisfaction were observed between the external DCR and endonasal DCR groups (P > 0.05). A small number of patients expressed scar-related concerns after external DCR. Conclusions: The patients perceived lacrimal problems as a significant symptomatic and social burden. Postoperative satisfaction and symptom relief were good regardless of the surgical approach. Further prospective studies assessing patient satisfaction and its correlation with anatomical and functional success rates after external and endonasal DCR could provide robust, practical, real-world implications.

Helicobacter pylori overcomes natural immunity in repeated infections.

Repeated experimental reinfection of two subjects indicates that Helicobacter pylori infection does not promote an immune response protective against future reinfection. Our results highlight the importance of preventing reinfection after eradication, through public health initiatives, and possibly treatment of family members. They indicate difficulties for vaccine development, especially therapeutic vaccines.

Gastrectomy alters emotional reactivity in rats: neurobiological mechanisms.

Gastrectomy (Gsx) is associated with altered emotional function and a predisposition to depression/anxiety disorders. Here we investigated the effects of Gsx on emotional reactivity in rats and explored the underlying neurobiological mechanisms. Gsx- and sham-operated rats were exposed to behavioural tests that explore anxiety- and depression-like behaviour (open field, black and white box, elevated plus maze, social interaction, forced swim) as well as memory (object recognition). The potential neurobiological mechanisms underlying these differences were explored by measuring (i) turnover of candidate neurotransmitter systems in the nucleus accumbens, (ii) hippocampal neurogenesis by BrdU labelling or by analysis of candidate genes involved in neuronal growth and (iii) changes in mRNA expression of candidate genes in dissected hippocampal and amygdala tissue. Data from individual behavioural tests as well as from multivariate analysis revealed differing emotional reactivity between Gsx- and sham-operated rats. Gsx rats showed reduced emotional reactivity in a new environment and decreased depression-like behaviour. Accumbal serotonin and dopamine turnover were both reduced in Gsx rats. Gsx also led to a memory deficit, although hippocampal neurogenesis was unaffected. Of the many candidate genes studied by real-time RT-PCR, we highlight a Gsx-associated decrease in expression of Egr-1, a transcription factor linked to neural plasticity and cognition, in the hippocampus and amygdala. Thus, Gsx induces an alteration of emotional reactivity and a memory/cognitive deficit that is associated with reduced turnover of serotonin and dopamine in the nucleus accumbens and decreased expression of Egr-1 in the hippocampus and amygdala.

Human Barrett's adenocarcinoma of the esophagus, associated myofibroblasts, and endothelium can arise from bone marrow-derived cells after allogeneic stem cell transplant.

This study characterizes the contribution of bone marrow-derived cells (BMDCs) to Barrett's adenocarcinoma of the esophagus using a mouse surgical model of disease and human specimens. Transplantation of bone marrow expressing beta galactosidase into a wild-type mouse, followed by surgical esophagojejunostomy, allowed tracking of BMDCs into the surgical anastomosis and resulting Barrett's metaplasia. Human tissue from a male patient who had been transplanted with female bone marrow and later developed esophageal adenocarcinoma allowed us to tract donor-derived cells into the tumor. Using a combination of antibodies directed against beta-galactosidase (animal studies) and X/Y fluorescent in situ hybridization (FISH) (human studies), combined with specific lineage staining directed against epithelial, fibroblast, endothelial, and leukocyte markers, we show that bone marrow cells contribute to both the epithelial and stromal component of esophageal adenocarcinoma. These findings demonstrate that BMDCs can generate cancer-associated fibroblasts as well as contribute directly to epithelial cells in cancer of the esophagus.

Helicobacter pylori--the latest in diagnosis and treatment.

BACKGROUND: European and North American guidelines on the management of Helicobacter pylori infection were updated in 2007. New diagnostic methods have been introduced and in Australia, the recommended therapy choices in cases of penicillin allergy and for second line treatment are only accessible through the Therapeutic Goods Administration Special Access Scheme. OBJECTIVE: The article aims to update general practitioners on recommendations for testing and treating H. pylori infection, practical aspects of diagnostic methods, proof of cure testing to prove eradication, and the management of eradication failure and recurrent infection. DISCUSSION: Urea breath tests are the best way to diagnose current H. pylori infection. Serology should primarily be used when UBTs may be false negative, eg. current bleeding ulcer or H. pylori suppressing drugs. For children who cannot use UBTs, stool antigen tests may be useful. In case of eradication failure with standard clarithromycin based therapy, bismuth based quadruple therapy is the favoured second line therapy. Preparing the patient for possible side effects is important as poor compliance and antibiotic resistance are the main reasons for eradication failure.

Ischemia mobilizes histamine but not pancreastatin from ECL cells of rat stomach: evidence for a cytosolic histamine compartment.

Histamine in the rat stomach resides in enterochromaffin-like (ECL) cells and mast cells. The ECL cells are peptide-hormone-producing endocrine cells known to release histamine and chromogranin-A-derived peptides (such as pancreastatin) in response to gastrin. Ischemia (induced by clamping of the celiac artery or by gastric submucosal microinfusion of the vasoconstrictor endothelin) mobilizes large amounts of ECL-cell histamine in a burst-like manner. This report examines the ECL-cell response to ischemia and compares it with that induced by gastrin in rats. Arterial clamping (30 min) and gastric submucosal microinfusion (3 h) of endothelin, vasopressin, or adrenaline caused ischemia, manifested as a raised lactate/pyruvate ratio and mucosal damage. Whereas microinfusion of gastrin released both histamine and pancreastatin, ischemia mobilized histamine only. The mucosal concentrations of histamine and pancreastatin, the number and immunostaining intensity of the ECL cells, and the ultrastructure of the ECL cells were unchanged following ischemia. The long-term effects of ischemia and reperfusion (60-90 min) on gastric mucosa were examined in rats treated with the proton pump inhibitor omeprazole for 4 days. The activity of the ECL cells was suppressed (reflected in low histamine-forming capacity) but returned to normal within 1 week, illustrating the ability of the ECL cells to recover. We suggest that ischemia mobilizes cytosolic ECL-cell histamine without affecting the storage of histamine (and pancreastatin) in the secretory organelles and without causing lasting ECL-cell impairment.

Characterization of obestatin- and ghrelin-producing cells in the gastrointestinal tract and pancreas of rats: an immunohistochemical and electron-microscopic study.

Both ghrelin and obestatin are derived from preproghrelin by post-translational processing. We have morphologically characterized the cells that produce obestatin and ghrelin in new-born and adult Sprague-Dawley rats that were freely fed, fasted, or subjected to gastric bypass surgery or reserpine treatment. Tissue samples collected from the gastrointestinal tract and pancreas were examined by double-immunofluorescence staining, immunoelectron microscopy, and conventional electron microscopy. Obestatin was present in the stomach, duodenum, jejunum, colon, and pancreas. In the stomach, differences were noted in the development of obestatin- and preproghrelin-immunreactive (IR) cells on the one hand and ghrelin-IR cells on the other, particularly 2 weeks after birth. Preproghrelin- and obestatin-IR cells were more numerous than ghrelin-IR cells in the stomach, suggesting the lack of ghrelin in some A-like cells. Most obestatin-producing cells in the stomach were distributed in the basal part of the oxyntic mucosa; these cells co-localized with chromogranin A (pancreastatin) and vesicle monoamine transporters type 1 and 2, but not with serotonin or histidine decarboxylase. Immunoelectron microscopy revealed the obestatin- and ghrelin-producing cells to be A-like cells, characterized by numerous highly electron-dense granules containing ghrelin and obestatin. Some granules exhibited an even electron density with thin electron-lucent halos, suggestive of monoamines. Feeding status, gastric bypass surgery, and reserpine treatment had no obvious effect on the A-like cells. In the pancreas, obestatin was present in the peripheral part of the islets, with a distribution distinct from that of glucagon-producing A cells, insulin-producing beta cells, and cells producing pancreatic polypeptide Y. Thus, obestatin and ghrelin co-localize with an anticipated monoamine in A-like cells in the stomach, and obestatin is found in pancreatic islets.

Hypothalamic gene expression following ghrelin therapy to gastrectomized rodents.

We investigated whether ghrelin depletion (by gastrectomy surgery) and/or treatment/replacement with the gastric hormone ghrelin alters the expression of key hypothalamic genes involved in energy balance, in a manner consistent with ghrelin's pro-obesity effects. At 2 weeks after surgery mice were treated with ghrelin (12 nmol/mouse/day, sc) or vehicle for 8 weeks. Gastrectomy had little effect on the expression of these genes, with the exception of NPY mRNA in the arcuate nucleus that was increased. Ghrelin treatment (to gastrectomized and sham mice) increased the mRNA expression of orexigenic peptides NPY and AgRP while decreasing mRNA expression of the anorexigenic peptide POMC. Two weeks gavage treatment with the ghrelin mimetic, MK-0677, to rats increased NPY and POMC mRNA in the arcuate nucleus and MCH mRNA in the lateral hypothalamus. Thus, while predicted pro-obesity ghrelin signalling pathways were activated by ghrelin and ghrelin mimetics, these were largely unaffected by gastrectomy.

Does Helicobacter pylori infection per se cause gastric cancer or duodenal ulcer? Inadequate evidence in Mongolian gerbils and inbred mice.

A role for Helicobacter pylori infection in the development of gastric cancer in humans is well established; however, evidence for its carcinogenicity in animals remains inadequate. Mongolian gerbils and mice are commonly used to investigate the carcinogenicity of H. pylori, yet it is unclear whether H. pylori infection per se causes gastric cancer or duodenal ulcers in these animal models. Gastric adenocarcinoma in the gerbils was reported over 10 years ago, but this species has proved an unreliable model for studying H. pylori infection-associated gastric cancer. Helicobacter pylori infection alone appears insufficient to induce gastric cancer in these animals; additional carcinogenic insult is required. The development of invasive adenocarcinoma in inbred mice is rare regardless of the mouse or bacterial strain, and many long-term studies have failed to induce gastric cancer in these animals. Helicobacter pylori infection is also an established causative factor for duodenal ulcer in humans. However, few studies have attempted to develop animal models of H. pylori infection-induced duodenal ulcer. We therefore conclude that both Mongolian gerbils and inbred mice may be inadequate models for studying H. pylori infection-associated gastric cancer and that there is no animal model of H. pylori infection-induced duodenal ulcer.

Swedish moist snuff accelerates gastric cancer development in Helicobacter pylori-infected wild-type and gastrin transgenic mice.

The Swedish variant of moist oral smokeless tobacco (snus) is popular in Sweden and Norway, banned from sale within the European Union and is currently being introduced in USA. The aim of the present study was to determine if snus is carcinogenic to the stomach, particularly in Helicobacter pylori (H.P.)-infected hosts at increased risk for gastric cancer development. Snus (Generaltrade mark; Swedish Match, Sweden) was mixed with powdered standard mouse chow at a concentration of 5-9% (wt/wt) and given to wild-type (WT, FVB) and gastrin transgenic (INS-GAS, FVB) mice for 6 months with or without H.P. (strain 67:21, CagA+, VacA+) infection. At necropsy, pathological evaluation of stomachs from uninfected snus-treated WT mice showed mild morphological changes, whereas 50% snus-treated INS-GAS mice developed carcinoma in situ (CIS), compared with 25% not exposed to snus. When snus was given to H.P.-infected mice, 9 of 17 WT mice developed CIS with intramucosal invasion, and the remaining 8 of 17 WT mice developed high-grade dysplasia (score >1.5) that was associated with increased gastritis, epithelial defects, oxyntic atrophy, hyperplasia and intestinal metaplasia. Twelve of 12 H.P.-infected INS-GAS mice developed CIS with intramucosal invasion and submucosal herniation. We suggest that snus is a potential gastric carcinogen in mice. The development of CIS was associated with increased rates of the epithelial cell proliferation and apoptosis, common features of gastric carcinogenesis.

Mechanism of gastric bypass-induced body weight loss: one-year follow-up after micro-gastric bypass in rats.

Bariatric surgery (Roux-en-Y or mini-gastric bypass) is designed to limit food intake by creating a small gastric pouch and to reduce nutrient absorption by bypassing the long limb of the intestine. We report 1-year follow-up results after micro-gastric bypass in rats. Micro-gastric bypass was performed by anastomosis of the esophagus and the proximal jejunum. Body weight, body composition, bone mineral density, food intake, and serum levels of ghrelin and obestatin were measured. Growing rats had a 40% weight reduction 2 months after micro-gastric bypass surgery compared to 20% after gastrectomy and 30% after stomach bypass (anastomosis of the esophagus and duodenal bulb). Six months after micro-gastric bypass surgery, the rats stopped growing compared to controls that gained continuously due to expansion of the fat compartment. Adult rats (600 g) lost 30% of their body weight 5 months after the micro-gastric bypass, while food intake was not reduced. Serum levels of obestatin (but not ghrelin) were reduced in rats with micro-gastric bypass. The results suggest that micro-gastric bypass efficiently reduced body weight, particularly fat mass; loss of the weight after micro-gastric bypass was not due to reduced food intake; and lean tissue and bone development were impaired in growing subjects after gastric bypass.

Is gastrin partially responsible for body weight reduction after gastric bypass?

BACKGROUND: The rationale for bariatric surgery is to reduce food intake by gastric restriction and/or malabsorption by intestinal bypass. Unlike ghrelin, gastrin is released in response to food intake. Here we studied the possible role of gastrin in the reduction of body weight after gastric bypass surgery. METHODS: Rats were divided into four experimental groups and were subjected to different treatments: sham operation, gastric bypass, sham operation + gastrin infusion, and gastric bypass + gastrin infusion. The gastric bypass was done by anastomosing the esophagus to the duodenal bulb without bypassing the intestine. Gastrin-17 was infused continuously for 2 months via subcutaneously implanted osmotic minipumps. Body weights were recorded; serum gastrin and ghrelin levels were measured, and the stomachs were analyzed morphologically. RESULTS: Gastric bypass resulted in reducing the body weight, stomach weight, thickness of the oxyntic mucosa, serum gastrin concentration, and activity of the ECL cells. Gastrin infusion prevented mucosal atrophy and ECL cell inactivation, and attenuated the body weight reduction that occurred following gastric bypass. Circulating ghrelin and ghrelin-producing A-like cells in stomachs that had undergone gastric bypass were unchanged with or without gastrin infusion and are thus unlikely to be responsible for the reduced body weight. CONCLUSION: We suggest that hypogastrinemia and impaired ECL cell function in the oxyntic mucosa of the stomach might be partially responsible for the reduction in body weight that occurs after gastric bypass.

Gastric bypass surgery does not increase susceptibility to Helicobacter pylori infection in the stomach of rat or mouse.

Gastric bypass is a clinical option for obesity surgery. An increased susceptibility to Helicobacter pylori infection in the bypassed stomach has been speculated. The aim of the present study was to examine the susceptibility of the bypassed stomach to H. pylori infection in rats and mice. Adult Sprague-Dawley and Wistar rats and NMRI mice were subjected to either gastric bypass or laparotomy only as control. The animals were inoculated with the CagA- and VacA- positive H. pylori strain 67/21 (not mouse-adapted) in the first experiment and with 9 additional isolates in the second, by injection into the bypassed stomach or the control stomach during surgery. The stomach of each animal was collected for H. pylori culture 2-3 weeks later. While all the rats were H. pylori negative, 54% of gastric bypassed mice and 75% of controls were positive (P = 0.4). We conclude that susceptibility to H. pylori infection in the stomach is not increased by gastric bypass surgery.