Mucosal adaptation is an essential process in gut homeostasis. The intestinal mucosa adapts to a range of pathological conditions including starvation, short-gut syndrome, obesity, and bariatric surgery. Broadly, these adaptive functions can be grouped into proliferation and differentiation. These are influenced by diverse interactions with hormonal, immune, dietary, nervous, and mechanical stimuli. It seems likely that clinical outcomes can be improved by manipulating the physiology of adaptation. This review will summarize current understanding of the basic science surrounding adaptation, delineate the wide range of potential targets for therapeutic intervention, and discuss how these might be incorporated into an overall treatment plan. Deeper insight into the physiologic basis of adaptation will identify further targets for intervention to improve clinical outcomes.

Phenobarbital (PB) therapy is frequently associated with elevated serum alanine aminotransferase (ALT) and alkaline phosphatase (AP) activities in dogs without clinical signs of liver disease. The goal of this study was to determine if increased serum ALT and AP activities in clinically healthy PB-treated epileptic dogs are due to hepatic enzyme induction or to subclinical liver injury. Liver biopsies were obtained from 12 PB-treated dogs without clinical signs of liver disease but with elevated serum ALT and/or AP activities or both. Liver biopsies were obtained from eight healthy control dogs not receiving PB. Biopsies were evaluated histopathologically (all dogs) and liver homogenates were assayed for ALT (all dogs) and AP (six treated dogs, all controls) activities. As a positive control, liver cytochrome P4502B, an enzyme known to be induced by PB, was measured by benzyloxyresorufin-O-dealkylase activity and immunoblotting (five treated dogs, all controls). Serum AP isoenzyme analyses were performed. Results showed that ALT and AP activities in liver homogenates were not increased in treated dogs compared with controls, whereas the positive control for induction, CYP2B, was dramatically increased in treated dogs. Histopathological examination of liver biopsies revealed more severe and frequent abnormalities in treated dogs compared to controls, but similar types of abnormalities were found in both groups. Serum AP isoenzyme analyses in treated dogs demonstrated increased corticosteroid-induced and liver isoenzyme activities compared to controls. Results do not support induction of ALT or AP in the liver as the cause of elevated serum activities of these enzymes due to PB.

A study was conducted to determine if supplement withdrawal (omission of dietary vitamin and trace mineral premixes and a two-thirds reduction in dietary inorganic phosphorus) for 28 d preslaughter and the feeding of wheat middlings (dietary concentrations of 5, 15, and 30% from weaning to 16, 16 to 28, and 28 kg to slaughter, respectively) affect growth performance, carcass characteristics, and fecal mineral concentrations ofthe pig, as well as the nutrient content and oxidative stability of the longissimus dorsi muscle. Crossbred pigs (n = 64) were blocked by weight and assigned to one of four dietary treatments in a 2 x 2 factorial design (with or without supplement withdrawal, and with or without wheat middlings). Supplement withdrawal and wheat middling inclusion did not influence average daily gain (ADG), average daily feed intake, gain/feed, or carcass traits, except for a decrease (P < 0.01) in the ADG of pigs from 28 to 65 kg when fed wheat middlings. Supplement withdrawal decreased (P < 0.01) fecal Ca, P, Cu, Fe, Mn, and Zn concentrations. In diets containing full vitamin and mineral supplementation, wheat middling inclusion decreased (P < 0.01) fecal Ca, Cu, Fe, and Zn concentrations and increased (P < 0.01) fecal Mn. Supplement withdrawal decreased (P < 0.05) concentrations of riboflavin, niacin, and P in the longissimus dorsi muscle, but did not affect longissimus dorsi thiamin, vitamin E, Fe, Cu, Zn, and Ca concentrations. Inclusion of wheat middlings increased (P < 0.04) longissimus dorsi thiamin, niacin, riboflavin, and vitamin E concentrations and decreased (P < 0.04) Cu concentrations. However, wheat middling inclusion did not affect (P > 0.05) longissimus dorsi Ca, P, Fe, and Zn concentrations. Dietary treatment did not affect either Cu/Zn superoxide dismutase or glutathione peroxidase activity in the longissimus dorsi. The results from this study indicate that supplement withdrawal and dietary wheat middling inclusion alter pork nutrient content and fecal mineral concentration, but not the oxidative stability of pork.

The objective of this experiment was to compare the effects of dietary mannan oligosaccharide (MOS) and a feed-grade antimicrobial (AM) on growth performance of nursery pigs reared on three different farms (A and B were large-scale commercial farms, and C was located at Michigan State University). On all farms, production was continuous flow by building, but all-in/all-out by room. Within each nursery facility, all pigs on the experiment were in one room. Pigs (Farm A, n = 771, weaning age = 18.4 d; Farm B, n = 576, weaning age = 19.0 d; Farm C, n = 96, weaning age = 20.6 d) were blocked (within farm) by BW and sex and allotted randomly to dietary treatments arranged in a 2 x 2 factorial. The two factors were 1) with and without MOS (0.3% in Phase I, 0.2% in Phases II, III, and IV; as-fed basis) and 2) with and without AM (110 mg of tylosin and 110 mg of sulfamethazine/kg of diet in all phases; as-fed basis). The four nursery phases were 4, 7, 14, and 17 d, respectively. With 35, 20, and 4 pigs per pen on Farms A, B, and C, respectively, space allowances per pig were 0.29, 0.26, and 0.56 m2. Across all farms, the addition of AM and MOS plus AM increased (P < 0.05) ADG (368, 406, and 410 g/d for control, AM, and MOS plus AM, respectively and increased ADFI (661, 703, and 710 g/d for control, AM, and MOS plus AM, respectively) for the entire 42-d experiment. The addition of MOS also increased ADG (P < 0.05) from d 0 to 42 of the experiment (394 g/d). Performance differed depending on farm (P < 0.01). Antimicrobial did not affect growth performance on Farm B, but it increased (P < 0.05) ADG on Farms A and C, ADFI on Farm A, and G:F on Farm C. Growth improvements with MOS on Farms A and B were not significant; however, pigs on Farm C fed MOS had greater (P < 0.05) ADG, ADFI, and G:F than controls. The results of this study suggest that MOS may be an alternative to tylosin and sulfa-methazine as a growth promotant in nursery diets.

Stress has been cited as an important precipitator of smoking relapse. Dysregulation of neurobiological pathways related to stress might mediate effects of stress on smoking relapse. This study assessed the extent to which beta endorphin response to stress is associated with early smoking relapse. Forty-five smokers interested in smoking cessation were recruited and attended a laboratory session 24 h following the beginning of their abstinence period. During this session beta endorphin samples were collected before and after performing two acute stressors (public speaking and cognitive tasks). Participants also attended four weekly follow-up sessions to assess their smoking status. Results were compared between smokers who relapsed within the 4-week follow-up period and those who maintained abstinence over the same period. The acute stressors were associated with significant increases in measures of craving and withdrawal symptoms (ps<0.01). While baseline measures of beta endorphin did not differ between relapsers and successful abstainers (F<1), results demonstrated that smokers who relapsed exhibited attenuated beta endorphin response to the two stressors relative to those who maintained abstinence over the same period (ps<05). These results support recent evidence indicating that a dysregulated stress response is a key component in predicting smoking relapse.

Summary:The treatment of established veno-occlusive disease (VOD) of the liver with tissue plasminogen activator (tPA) has been disappointing. In attempts to improve upon these results we identified a subgroup of patients with consistently elevated bilirubin levels who did not meet conventional criteria for VOD (Susp VOD) but who had a significant risk of later developing clinical VOD. In January 1994 we began to treat patients who developed Susp VOD with tPA rather than waiting until they developed clinical VOD. We now report on the results of the first 37 patients who ultimately developed clinical VOD and received tPA therapy prior to Susp VOD, or at the time they had established VOD. Significant bleeding complications occurred in 13 (35%) patients but resolved with discontinuation of therapy in all but one. We found that patients treated early in the course of hepatotoxicity prior to the development of overt VOD had a significantly higher response rate and 100 day survival than patients treated at the time of established VOD. Given the poor results seen in treating late VOD, we suggest that early treatment with tPA may improve the outcome in patients who develop signs of hepatotoxicity following marrow transplantation. Keywords: tissue plasminogen activator; hepatotoxicity; bone marrow transplant Hepatic veno-occlusive disease (VOD) is a frequent and serious complication of bone marrow transplantation (BMT). Published reports indicate an incidence of 5-50%, and a mortality as high as 15% depending on the clinical series and the definition used.1-4 Clinically, VOD has been defined as hyperbilirubinemia within the first 4 weeks following BMT, with associated findings of ascites, unexplained weight gain, hepatomegaly or right upper quadrant pain. VOD is characterized histologically, by necrosis of zone 3 hepatocytes and deposition of fibrin and factor VIII in hepatic venules. These findings suggest a role of the coagulation system in the pathophysiology of VOD. sparse, and treatment options are limited. Despite the paucity of data, early experience with tissue plasminogen activator (tPA) is encouraging. Presently, tPA represents the most promising therapy for the treatment of hepatotoxicity following BMT. [6][7][8][9] Based on the promising initial reports of Bearman et al, 9 we began to treat patients with established VOD with tPA in April 1993. Our early experience in treating patients with advanced VOD using tPA was unfavorable, as in the larger trial recently reported by Bearman and colleagues.10 Others had suggested that successful treatment required early therapy.11 Thus in January 1994 we began to treat patients when they developed persistent unexplained hyperbilirubinemia (suspected VOD) without additional clinical evidence of VOD. To investigate whether earlier treatment may influence the course of hepatotoxicity, we examined only those patients who developed clinical VOD, and compared the results for those who received tPA prior to or after developing clinical VOD. Methods Patient selection and hepato...

Colonoscopy is a widely used diagnostic and therapeutic modality with a relatively low morbidity. However, given the large volume of procedures performed, awareness of the infrequent complications is essential. Perforation is an established complication of colonoscopy, and can range from 0.2%-3% depending on the series, population and modality of colonoscopy. Acute appendicitis after colonoscopy is an extremely rare event, and a cause-effect relationship between the colonoscopy and the appendicitis is not well documented. In addition, awareness of this condition can aid in prompt diagnosis. Relatively mild symptoms and exclusion of bowel perforation by contrast studies do not exclude appendicitis from the differential diagnosis for post-colonoscopy pain. In addition to the difficult diagnosis inherent to postcolonoscopy appendicitis, treatment strategies have varied greatly. This paper reviews these approaches. We also expand upon prior articles by giving guidance for the role of nonoperative management in these patients. This case and review of the literature will help to create awareness about this complication, and guide optimal treatment of pericolonoscopy appendicitis.

A multicentric prospective study was conducted to monitor the effect of phenobarbital on serum total thyroxine (T4) and thyroid-stimulating hormone (TSH) concentrations in epileptic dogs. Serum T4 concentrations were determined for 22 epileptic dogs prior to initiation of phenobarbital therapy (time 0), and 3 weeks, 6 months, and 12 months after the start of phenobarbital. Median T4 concentration was significantly lower at 3 weeks and 6 months compared to time 0. Thirty-two percent of dogs had T4 concentrations below the reference range at 6 and 12 months. Nineteen of the 22 dogs had serum TSH concentrations determined at all sampling times. A significant upward trend in median TSH concentration was found. No associations were found between T4 concentration, dose of phenobarbital, or serum phenobarbital concentration. No signs of overt hypothyroidism were evident in dogs with low T4, with one exception. TSH stimulation tests were performed on six of seven dogs with low T4 concentrations at 12 months, and all but one had normal responses. In conclusion, phenobarbital therapy decreased serum T4 concentration but did not appear to cause clinical signs of hypothyroidism. Serum TSH concentrations and TSH stimulation tests suggest that the hypothalamic-pituitary-thyroid axis is functioning appropriately.