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Mallory-Weiss syndrome (MW) has been know since 1929. Only few studies exist which focus on the prognosis of the lesion. No Danish MW data are available. The purpose of the study was to describe the demographics of patients admitted with an MW to a Danish surgical unit during a 5-year period and to investigate the prognosis of these patients.Data from the patient records of 49 patients with endoscopically verified MW admitted through a five-year period were analysed. At follow-up, 35 patients were alive and contacted. A total of 29 responded. The mean time to follow-up from admittance was 42.7 months (range: 10.1-77.1).Haemostasis was achieved in all 49 patients. Sixteen received active therapy during the endoscopic procedure. Haemoglobin at admittance was lower (p = 0.008), the presence of bleeding stigmata higher (p0.0001) and the number of patients receiving blood transfusion higher (p = 0.01) among those receiving active therapy than among the group receiving no therapy at the time of their endoscopy. At follow-up, 50% of those receiving active therapy were dead (eight of 16) compared with 18% (six of 33) in the no-therapy group (p = 0.02). In the follow-up period, 10% of the patients admitted with an MW were re-admitted for a new gastrointestinal bleeding.Our data suggests that an attitude change is needed toward MW with bleeding stigmata. The course of the disease may not be as benign as generally believed. Further prospective studies designed to resolve this matter are needed.

The present report concerns a young woman previously diagnosed as having childhood asthma who presented with a secondary spontaneous pneumothorax during the third trimester of pregnancy; at term a caesarean section was recommended for safety reasons. Post partum a severe fixed ventilatory defect unresponsive to inhaled bronchodilator and a short oral course of steroids ruled out asthma. Diffuse bronchiectasis was found on her chest CT scan, although this was not evident clinically. Known aetiologies for diffuse bronchiectasis (cystic fibrosis, anti-α1 antitrypsin deficiency, rheumatic diseases, mycobacterial infections, childhood infections and immune deficiencies) were ruled out. Therefore it is believed her bronchiectasis was idiopathic or congenital. No recommendations from recent guidelines on how to manage labour in a woman after a spontaneous pneumothorax could be found. However, a literature search revealed that pregnant women usually experience primary pneumothorax and may continue in natural labour; however, it is unknown how best to manage a woman with secondary spontaneous pneumothorax.

The most common and most serious complication of varicella (chickenpox) in adults is pneumonia, which can lead to severe respiratory failure. Varicella pneumonia is associated with considerable morbidity and even death.To summarize our experience with varicella pneumonia in terms of clinical, laboratory and radiological characteristics as well as risk factors, management and outcome.We conducted a retrospective cohort survey in our facility from 1995 to 2008.Our cohort comprised 21 patients with varicella pneumonia, of whom 19 (90%) were men; their mean age was 35 +/- 10.5 years. Nineteen patients (90%) were Bedouins and 18 (86%) were smokers. Eleven (52%) were admitted to the Medical Intensive Care Unit; 3 of them required mechanical ventilation and the remaining 10 (48%) were admitted to the general medical ward. Median length of stay was 6 +/- 7.7 days. Hypoxemia and elevated lactate dehydrogenase on admission were associated with respiratory failure. Radiological manifestations were variable and nine patients exhibited characteristic findings. All but one patient were treated with acyclovir. All patients fully recovered.In southern Israel varicella pneumonia is primarily a disease ofyoung male Bedouins who are smokers. Severity ranges from mild disease to severe, resulting at times in respiratory failure requiring mechanical ventilation. Prognosis is favorable with complete recovery.

A high incidence of abnormal pulmonary function tests has been reported in cross-sectional studies among patients with rheumatoid arthritis. Few patients have been enrolled in longitudinal studies.To perform PFT in rheumatoid arthritic patients without pulmonary involvement and to identify variables related to changes in PFT over 5 years of follow-up.Consecutive RA patients underwent PFT according to recommendations of the American Thoracic Society. All surviving patients were advised to repeat the examination 5 years later.PFT was performed in 82 patients (21 men, 61 women). Their mean age was 55.7 (15.9) years and the mean RA duration was 11.1 (10) years. Five years later 15 patients (18.3%) had died. Among the 67 surviving patients, 38 (56.7%) agreed to participate in a follow-up study. The initial PFT revealed normal PFT in only 30 patients (36.6%); an obstructive ventilatory defect in 2 (2.4%), a small airway defect in 12 (17%), a restrictive ventilatory defect in 21 (25.6%), and reduced DLco in 17 (20.7%). Among the 38 patients participating in the 5 year follow-up study, 8 developed respiratory symptoms, one patient had a new obstructive ventilatory defect, one patient developed a restrictive ventilatory defect, and 5 patients had a newly developed small airway defect. The DLco had improved in 7 of the 8 patients who initially had reduced DLco, reaching normal values in 5 patients. Over the study period a new reduction in DLco was observed in 7 patients. Linear regression analyses failed to identify any patient or disease-specific characteristics that could predict a worsening in PFT. The absolute yearly decline in forced expiratory volume in 1 sec among our RA patients was 47 ml/year, a decline similar to that seen among current smokers.Serial PFT among patients with RA is indicated and allows for earlier identification of various ventilatory defects. Small airways disturbance was a common finding in our RA patients.

We evaluated the organisation, management and outcome for patients undergoing elective liver resection in Denmark in the period 2002-2007.Nationwide data based on the National Patient Registry and discharge information from hospital departments in the period 1 January 2002 to 31 December 2007 were analysed.Twenty-three departments performed 818 resections with five departments performing 96% and 18 departments performing 4% of the operations. The amount of non-anatomical resections constituted 30% (248 of 818) of the resections. The median postoperative stay was nine days, and the hospital mortality rate was 3.9%, distributed between 2.4% for non-anatomical resections, 2.9% for segmental resections and 5.2% for right-sided hepatectomy.The number of treated patients was too small as was the number referred to highly specialised liver surgery units. Moreover, the amount of non-anatomical resections was too high as was the average postoperative stay and the hospital mortality rate. In future, we propose that liver resections be centralised in 2-3 hospitals each capable of providing all the following services: surgery, hepatology, oncology and interventional radiology.

Monocytes/macrophages are known to represent a potential reservoir of human immunodeficiency virus type 1 (HIV-1), which ensures continuous replication of the virus in patients on highly active antiretroviral therapy (HAART). Infected macrophages are a highly productive source of HIV-1 during infections with common opportunistic pathogens. Previous studies report that toll like receptors (TLR)s play a role in HIV-1 replication in macrophages. Here, we investigate the three main pathways activated through TLR4 and the interactions with the HIV-1 long terminal repeat (LTR), using human embryonic kidney (HEK) 293 cells expressing TLR4 and transfected with a luciferase reporter under the control of the HIV-1 LTR. Here, we demonstrate, that TLR4-mediated activation of HIV-LTR is largely governed by the nuclear factor-kappaB pathway. Neither of the mitogen-activated protein kinases ERK1/2, JNK, or p38 nor the transcription factor interferon regulatory factor 3 were involved in the direct transactivation of HIV-LTR through stimulation of TLR4.

Acute interstitial pneumonia is a rapidly progressive disease frequently leading to respiratory failure and mechanical ventilation. The prognosis is usually poor despite aggressive diagnostic and treatment efforts.In this retrospective cohort survey, we enrolled patients with hypoxemic respiratory failure who met predefined criteria of acute idiopathic interstitial pneumonia. Patients' records, radiologic studies, and pathologic specimens were reviewed. All data were recorded in each patient's study file and subsequently analyzed.Our cohort consisted of 5 men and 4 women with a mean age of 69.4 yr (55-80 yr). The chest radiograph in all patients progressed to diffuse bilateral infiltrates over a 12-day course. All nine patients had histological proof of diffuse alveolar damage consistent with acute interstitial pneumonia, obtained by either transbronchial biopsy or open lung biopsy. All patients required admission to the medical intensive care unit and mechanical ventilation. The mortality rate was 100%, and patients died within 5-26 days of their admission to the unit.Acute interstitial pneumonia (Hamman-Rich syndrome) is an idiopathic, rapidly progressive and, at times, fatal form of interstitial lung disease. A transbronchial biopsy is a logical first diagnostic step, to be followed by an open lung biopsy, if necessary. Response to corticosteroids in our series was minimal. In patients who fail to respond to conventional therapy and are otherwise appropriate candidates, lung transplantation may be considered as an additional alternative.

Transepithelial migration of polymorphonuclear neutrophils (PMN) plays a crucial role in inflammatory conditions of the intestine, such as inflammatory bowel diseases. Hypertonic saline (HS) exerts various inhibitory effects on PMN function. We hypothesized that HS could inhibit transepithelial migration of PMN and thereby prevent inflammatory events in experimental colitis. Isolated human PMN were treated with HS (40 mM), and their transmigration across a monolayer of T84epithelial cells was induced by N-formyl-methionyl-leucyl-phenylalanine. Monolayer disruption was assessed by monitoring changes in transepithelial conductance in an Ussing chamber. Colitis in mice was induced by oral administration of dextran sulfate sodium (DSS). Animals were treated with 4 or 8 ml/kg of 7.5% saline intraperitoneally two times daily for 7 days. Controls received equivalent volumes of normal saline (NS, n = 6) or no intraperitoneal treatment (DSS, n = 12). The severity of inflammation was evaluated based on disease activity index and histology score. HS treatment of PMN in vitro significantly reduced cell migration and the disruption of T84monolayers compared with untreated control cells ( n = 5, P < 0.05). This effect of HS was dose dependent. HS treatment in vivo also reduced colitis-induced gut tissue damage, as indicated by an improved histology score compared with the NS and DSS groups. We conclude that HS inhibits transepithelial migration of PMN in vitro and gut tissue damage in vivo in a mouse model of colitis. Thus HS may have clinical value to reduce PMN-mediated intestinal damage.

This study investigated the long-term survival rate of 589 patients enrolled in a trial in 1992-1995 who underwent colorectal surgery. The patients were randomised to receive leucocyte-depleted or buffy-coat-poor blood when transfusion was indicated. Significantly more of the non-transfused patients (59%) were alive seven years later compared to patients transfused with leucocyte-depleted blood (41%) and to patients transfused with buffy-coat-poor blood (45%).

The Salmonella effector protein SigD is an inositol phosphate phosphatase that inhibits phosphatidylinositol 3-kinase-dependent signaling. Because epidermal growth factor (EGF) inhibits chloride secretion via phosphatidylinositol 3-kinase, we explored whether Salmonella infection might modify the inhibitory effect of EGF. As expected, EGF inhibited chloride secretion induced by carbachol in T84epithelial cells. Infection with wild-type (WT) but not sigD−mutant S. typhimurium SL1344 decreased CCh-stimulated chloride secretion. Moreover, WT but not sigD−Salmonella reduced the inhibitory effect of EGF on carbachol-stimulated chloride secretion. Complementation of sigD restored the ability of mutant Salmonella to reverse the inhibitory effect of EGF. EGF-induced EGF receptor phosphorylation was similar in cells infected with either WT or mutant Salmonella, and neither WT nor sigD−Salmonella altered recruitment of the p85 subunit of phosphatidylinositol 3-kinase to EGF receptor, implying that SigD acts downstream of these signaling events. Furthermore, transepithelial resistance fell more rapidly in cells infected with WT vs. sigD−Salmonella, indicating an early role for SigD in reducing barrier function, perhaps via activation of protein kinase C. We conclude that the Salmonella bacterial effector protein SigD may play critical roles in the pathogenesis of disease caused by this microorganism.

We have previously shown that Gq protein-coupled receptor (GqPCR) agonists stimulate epidermal growth factor receptor (EGFr) transactivation and activation of mitogen-activated protein kinases (MAPK) in colonic epithelial cells. This constitutes a mechanism by which Cl- secretory responses to GqPCR agonists are limited. In the present study we examined a possible role for the EGFr in regulating Cl- secretion stimulated by agonists that act through GsPCRs. All experiments were performed using monolayers of T84 colonic epithelial cells grown on permeable supports. Protein phosphorylation and protein-protein interactions were analyzed by immunoprecipitation and Western blotting. Cl- secretion was measured as changes in short-circuit current (DeltaIsc) across voltage-clamped T84 cells. The GsPCR agonist, vasoactive intestinal polypeptide (VIP; 100 nM), rapidly stimulated EGFr phosphorylation in T84 cells. This effect was mimicked by a cell-permeant analog of cAMP, Bt2cAMP/AM (3 microM), and was attenuated by the protein kinase A (PKA) inhibitor, H-89 (20 microM). The EGFr inhibitor, tyrphostin AG1478 (1 microM), inhibited both Bt2cAMP/AM-stimulated EGFr phosphorylation and Isc responses. VIP and Bt2cAMP/AM both stimulated ERK MAPK phosphorylation and recruitment of the p85 subunit of phosphatidylinositol 3-kinase (PI3K) to the EGFr in a tyrphostin AG1478-sensitive manner. The PI3K inhibitor, wortmannin (50 nM), but not the ERK inhibitor, PD 98059 (20 microM), attenuated Bt2cAMP/AM-stimulated secretory responses. We conclude that GsPCR agonists rapidly transactivate the EGFr in T84 cells by a signaling pathway involving cAMP and PKA. Through a mechanism that likely involves PI3K, transactivation of the EGFr is required for the full expression of cAMP-dependent Cl- secretory responses.

Specific effects of the cytotoxic secondary lipid oxidation product, 4-hydroxynonenal (10(-8)-10(-4) M), on intact sheets of rat jejunum were measured as changes in short circuit current (delta(I)sc) following cumulative addition to either the mucosal or serosal side, using the analogous aldehyde, nonenal, as reference. 4-Hydroxynonenal stimulated I(sc) from the serosal side (maximal delta(I)sc = 27.2 +/- 3.5 microA/cm2, mean +/- SEM, N = 32) while nonenal stimulated I(sc) primarily from the mucosal side (maximal delta(I)sc = 16.2 +/- 3.4 microA/cm2, N = 20). Inhibition by 100 microM bumetanide (4-hydroxynonenal: 88.9 +/- 3.0%, N = 6, p0.05, nonenal: 69.3 +/- 2.9%, N = 6, P0.05) indicated chloride secretion. Nonenal-induced delta(I)sc was inhibited (72.5 +/- 1.2%, N = 8, P0.05) by a combination of nordihydroguaiaretic acid (100 microM) and piroxicam (10 microM), while 4-hydroxynonenal-induced delta(I)sc, was abolished by piroxicam (N = 8, P0.001) and inhibited by 1 microM tetrodotoxin (69.8 +/- 9.7%, N = 6, P0.001). These data indicate that 4-hydroxynonenal stimulates chloride secretion mediated by prostaglandins and the enteric nervous system. The site of action (serosal) being opposite to the reference aldehyde.

The hallmark of a range of intestinal infectious diseases is diarrhea. With the exception of intestinal pathogens that elaborate enterotoxins, the mechanisms underlying intestinal dysfunction during infections with many bacteria remain largely unestablished. The intestinal epithelium is the initial site of contact between enteric microorganisms and the gastrointestinal mucosa and is a continuous layer of cells lining the entire gastrointestinal tract. It acts as a physical barrier, preventing the entry of harmful substances from the intestine into the body, and transports water to and from the intestinal contents. Water transport is a passive process, which is driven by the active transport of ions and nutrients. Normally, there is a net absorption of ions and water but in conditions of disease, such as intestinal bacterial infection, the epithelium can rapidly convert from its absorptive to a net secretory phenotype. Salmonellae are gram-negative bacteria that can cause gastroenteritis and enteric fever and represent a major public health problem worldwide. All Salmonella serotypes share the ability to invade their host by inducing their own uptake into nonphagocytic cells of the intestinal epithelium. They facilitate this uptake through proteins secreted by a type III protein secretion system encoded within the Salmonella pathogenicity island 1 that also encodes the effector proteins required for invasion (13). This system is abundant in several bacteria and, in addition to being responsible for invasion, functions to secrete virulence proteins into host cells. Thus, through secreted virulence proteins, through invasion, or both, Salmonella can induce changes in the epithelium, altering the function of the intestinal lining and presumably converting it to a hypersecretory state. However, the underlying mechanism(s) by which Salmonella induces diarrhea are not fully understood. The understanding of diarrheal disease requires the application of model systems. Animal tissues are commonly used but have a number of shortcomings due to significant species differences between experimental animals and human hosts. Moreover, studies with isolated epithelial cell lines lack relevant cell-cell interactions. Thus, new models for studying intestinal bacterial infections are being sought. In this regard, we have previously described a human-derived tissue model for the study of ion transport mechanisms (4). This model employs fetal intestinal tissues grown as xenografts in severe combined immunodeficient (SCID) mice (22). The main advantage of intestinal xenografts is that they provide a model consistent with intact human intestinal tissue, which allows for prolonged infection with bacteria and enables studies of the interactions of different cell types, in both human small and large intestine, during bacterial infection. Infection studies with epithelial cell lines have shown that Salmonella induces host cell responses, including chemokine and cytokine secretion (8, 9), and upregulation of expression of cyclooxygenase 2 (Cox-2) (8, 21). Coculture studies also show transepithelial migration of polymorphonuclear leukocytes early after Salmonella-epithelial cell contact (17) and that epithelial invasion by Salmonella is not necessary for polymorphonuclear leukocyte movement (11). However, changes in the secretory phenotype of intestinal epithelial cell lines show a considerable latency after Salmonella infection and are difficult to dissociate from frankly injurious effects of the infectious process (21). These various observations suggest that interactions between intestinal epithelial cells and Salmonella play a key role in orchestrating the inflammatory response (9, 17, 18) and underscore the limitations inherent in cell line models to understand the full picture of Salmonella infection in human tissue. It is therefore relevant to the elucidation of Salmonella pathogenesis to utilize the intestinal xenograft model to extend findings obtained with cell lines to a more physiological setting, in which cell-cell interactions may amplify responses to the pathogen. Thus, we sought to examine here whether Salmonella infection of xenografts had any consequences in terms of transport function and the characteristics and mechanisms of any responses seen. (This work was presented in part at the 2001 meeting of the American Gastroenterological Association and has been published in abstract form [Gastroenterology 120:A3812, 2001].)

We evaluated the changes in Denmark since the 1980s in the incidence, management and outcome of oesophageal resections.The national patient hospital register and discharge information from the hospitals were examined for the number of oesophageal resections performed, the length of the postoperative stay, readmission, postoperative complications, and hospital mortality in the period 1/1-1997 to 30/6-2000.Twenty-six departments in 18 hospitals performed 476 resections. Five hospitals accounted for 92% of all the resections performed. In three hospitals, the resections were carried out in three different departments and 18 departments performed fewer than four resections per year. The postoperative stay was 19.2 days. The frequency of surgical complications was 19% and hospital mortality was 10.7%.The small number of oesophageal resections performed in many departments in Denmark is not in accordance with international recommendations, which say that the operation should be performed in high volume centres by experienced oesophageal surgeons, including thoracic surgeons, surgical gastroenterologists, and thoracic anaesthesiologists. On these results, it is recommended that the operation is performed in few centres and by few surgeons in multidisciplinary teams.

We report a hemodialysis patient with acute hypercapnic respiratory failure managed on noninvasive intermittent positive pressure ventilation and progressive metabolic acidosis. Dialysate bicarbonate concentration of 25 mEq/l was associated with exacerbation of metabolic acidosis, while higher dialysate bicarbonate concentration of 30 mEq/l induced a dangerous increase in PCO2 level. Excessive bicarbonate buffering and CO2 production induced by severe metabolic acidosis, malnourishment and tissue hypoxia, could explain inadequate correction of metabolic acidosis and worsening of hypercapnia in this patient. Our findings suggest the need for close monitoring of blood gases and cautious modulation of dialysate bicarbonate concentration in the presence of progressive metabolic acidosis in hypercapnic hemodialysis patients.

A case of acute intoxication presented as toxic pneumonitis after exposure to Roundup (glyphosate) (Solaris Group, Monsanto; San Ramon, CA) herbicide in an agriculture worker. The correct etiologic factor causing this specific clinical picture was identified only 2 weeks later, after a thorough occupational history was taken and meticulous delineation of the working conditions and exposures of the involved worker were made. As a rule, occupational related diseases are not readily elucidated by nonoccupational physicians. However, most acute intoxication events are first encountered by such physicians. In these situations, rapid and comprehensive evaluation is necessary in order to clearly identify the causative agent(s) and to initiate the appropriate treatment. Consulting occupational physicians at this early stage may facilitate early and accurate diagnosis.