John W. Birk

Flavor-flavor associations induce hedonic shifts in taste preference

Two experiments allowed rats to drink freely two neutral flavors (almond and vanilla) in simultaneous compound with two hedonically valued flavors (quinine and saccharin). The neutral flavor previously paired with saccharin was subsequently preferred. The neutral flavor that had been paired with quinine was subsequently avoided. Experiment 3 found similar results when the animals were hand-fed a preset amount of the solution. Preference shifts were not obtained when differential amounts of the neutral flavors were consumed in isolation. The data indicate that flavor-flavor associations can shift taste preferences.

Naloxone antagonism of diazepam-induced feeding in the Syrian hamster

Abstract Three experiments investigated the effects of the intragastric administration of the benzodiazepine diazepam on feeding in non-deprived Syrian hamsters ( mesocricetus auratus ). In the first experiment diazepam (0, 0.5, 1.0, 2.0, and 4.0 mg/kg) produced dose dependant increases in feeding. 4.0 mg/kg of diazepam produced significantly more feeding than the other doses tested and the lowest dose tested (0.5 mg/kg) produced a significant increase in feeding. In the second experiment naloxone (10 mg/kg) partially antagonized the effect of 4 mg/kg of diazepam on feeding. In the third experiment the ability of naloxone (0.1, 1.0, 5.0, 10.0 or 20 mg/kg) to reduce feeding produced by either 4 mg/kg or 2 mg/kg of diazepam was tested. Naloxone partially antagonized the effects of 4 mg/kg of diazepam on feeding in a dose dependant manner. While 2 mg/kg of diazepam produced significantly less feeding than 4 mg/kg, naloxone did not antagonize the effect of 2 mg/kg on feeding. The results suggest that two mechanisms are involved in diazepam-induced feeding in hamsters. The high dose of diazepam may produce increased feeding by activating the endorphin system while the low dose of diazepam produces increased feeding via a naloxone insensitive mechanism.

Risk factors for sessile serrated adenomas.

Background Although sessile serrated adenomas (SSAs) may represent a separate and important pathway for colorectal cancer (CRC), little is known about the risk factors for these lesions. Molecular abnormalities such as BRAF have been observed in SSA and smokers. Our hypothesis is that smoking may be associated with these lesions. Methods All patients diagnosed with an SSA from January 2007 to September 2010 were identified retrospectively based on a pathology database query. There were 2 sets of controls. One group had no adenomas, whereas another group had tubular adenomas. These groups were randomly identified from 2007 to 2010. Data collected included age, sex, ethnicity, height, weight, family history of CRC, diabetes mellitus, use of aspirin, statins, and calcium, and serum trigylcerides and cholesterol. We defined smokers as those patients who smoked at least 20 pack-years. Results We identified 90 patients with an SSA of any size, 90 patients with tubular adenomas, and 200 controls with no adenomas. Of the 90 SSAs, 42 were 6 mm or larger and 19 of them were ≥1 cm. Most of the SSAs was flat (76/90; 84.4%). After multivariate analyses, smokers with at least 20 pack-year exposure were found to have an increased risk [adjusted odds ratio (OR)=7.31; 95% confidence interval (CI), 3.92-13.63] of having any SSAs, SSAs ≥6 mm (adjusted OR=7.77; 95% CI, 3.48-17.35), and large SSAs (adjusted OR=10.20; 95% CI, 3.31-31.41) compared with nonsmokers. We also observed this relationship when comparing patients with SSAs to those with tubular adenomas. Conclusions Our data suggest that smoking at least 20 pack-years is strongly associated with any and large SSAs. In addition, diabetes mellitus and obesity seem to be associated with SSAs as well. Our data has implications for CRC screening.

A prospective randomized placebo-controlled double-blinded pilot study of misoprostol rectal suppositories in the prevention of acute and chronic radiation proctitis symptoms in prostate cancer patients

OBJECTIVE:Radiation proctitis is a known complication of radiation therapy for prostate cancer. Available medical treatment is usually ineffective and has focused on relieving symptoms after damage has occurred. Our study aimed at evaluating the use of misoprostol rectal suppositories in the prevention of acute as well as chronic radiation proctitis symptoms.METHODS:A prospective, randomized, placebo-controlled, double-blinded trial was conducted in patients with recently diagnosed stages B and C prostate cancer who underwent external beam irradiation. Patients received either a misoprostol or a placebo suppository 1 h before each radiation session. Misoprostol suppositories were made from two 200-μg tablets (Cytotec, Searle Pharmaceuticals, Skokie, IL), whereas the placebo was made from cocoa butter. A 12-point radiation proctitis symptom score was obtained from each patient at 4, 8, 12, and 36 wk after radiation therapy.RESULTS:A total of 16 patients were enrolled. Seven patients received placebo, and nine patients received misoprostol. Mean radiation proctitis symptom scores in the placebo group were 4.86, 5.86, 5.71, and 3.83 at 4, 8, 12, and 36 wk, respectively. The mean scores in the misoprostol group were 0.78, 0.67, 0.33, and 0.37 at 4, 8, 12, and 36 wk, respectively. The difference between the two groups was statistically significant (p < 0.05) at 4, 8, 12, and 36 wk.CONCLUSIONS:Misoprostol rectal suppositories significantly reduce acute and chronic radiation proctitis symptoms in patients receiving radiation therapy for prostate cancer.

Proton pump inhibitors: the good, the bad, and the unwanted.

Abstract Proton pump inhibitors (PPIs) are one of the most commonly prescribed classes of medications in the United States. By inhibiting gastric H+/K+ adenosine triphosphatase via covalent binding to the cysteine residues of the proton pump, they provide the most potent acid suppression available. Long-term PPI use accounts for the majority of total PPI use. Absolute indications include peptic ulcer disease, chronic nonsteroidal anti-inflammatory drugs use, treatment of Helicobacter pylori, and erosive esophagitis. Although PPIs are generally considered safe, numerous adverse effects, particularly associated with long-term use have been reported. Many patients receiving chronic PPI therapy do not have clear indications for their use, prompting consideration for reduction or discontinuation of their use. This article reviews the indications for PPI use, the adverse effects/risks involved with their use, and conditions in which their use is controversial.

Trends in esophageal cancer survival in United States adults from 1973 to 2009: a SEER database analysis

The rise in incidence of esophageal cancer (EC) in the USA over the last four decades has been well documented; however, data on trends in long‐term survival and impact on modern therapies associated with survival are lacking.

Bicuculline blocks diazepam-induced feeding in Syrian hamsters.

Bicuculline antagonizes diazepam induced feeding in Syrian hamsters in a dose dependent manner using doses which do not affect running wheel activity. These results suggest that diazepam-induced feeding can be completely and specifically blocked by antagonizing GABA.

Sessile serrated adenomas in the proximal colon are likely to be flat, large and occur in smokers.

AIM To examine the epidemiology and the morphology of the proximal sessile serrated adenomas (SSAs). METHODS We conducted a retrospective study to identify patients with SSAs using a university-based hospital pathology database query from January 2007 to April 2011. Data collected included: age, gender, ethnicity, body mass index, diabetes, smoking, family history of colorectal cancer, aspirin, and statin use. We collected data on morphology of SSAs including site (proximal or distal), size, and endoscopic appearance (flat or protuberant). We also compared proximal SSAs to proximal tubular adenomas detected during same time period. RESULTS One hundred and twenty patients with SSAs were identified: 61% were distal and 39% were proximal SSAs. Proximal SSAs were more likely to be flat than distal (100% vs 78% respectively; P = 0.0001). Proximal SSAs were more likely to occur in smokers (OR = 2.63; 95%CI: 1.17-5.90; P = 0.02) and in patients with family history of colorectal cancer (OR = 4.72; 95%CI: 1.43-15.55; P = 0.01) compared to distal. Proximal SSAs were statistically more likely to be ≥ 6 mm in size (OR = 2.94; P = 0.008), and also more likely to be large (≥ 1 cm) (OR = 4.55; P = 0.0005) compared to the distal lesions. Smokers were more likely to have proximal (P = 0.02), flat (P = 0.01) and large (P = 0.007) SSAs compared to non-smokers. Compared to proximal tubular adenomas, proximal SSAs were more likely to be large and occur in smokers. CONCLUSION Proximal SSAs which accounted for two-fifths of all SSAs were more likely to present as flat lesions, larger SSAs, and were more likely to occur in smokers and in patients with family history of colorectal cancer. Our data has implications for colorectal cancer screening.

A review of the current status of endoluminal therapy as a primary approach to obesity management

Gastroenterologists are expected to play a pivotal role in the management of the global obesity epidemic in coming years as novel endoscopic approaches become more widely available, safe, and effective. This review focuses on the recent advances in the field of endoluminal therapy as a primary approach to obesity management with the aim of providing the interventional endoscopist an overview of currently available evidence along with an insight into upcoming devices and techniques. The intragastric balloon appears to be safe and effective in the short term, especially as a bridge to bariatric surgery. Although early trials support the safety and feasibility of endoscopic gastroplasty, it is technically demanding and staple-line dehiscence continues to be a problem. Moreover, with ongoing technical innovations, most devices that have been used in published trials are no longer manufactured and results of studies using newer endoscopic suturing systems are currently awaited. The duodenojejunal bypass sleeve mimics the physiology of intestinal bypass and shares the metabolic advantages of intestinal diversion. A high rate of premature device withdrawal has been its major limiting factor. Therapeutic endoscopy may be the next paradigm of bariatric care. Combining restrictive and barrier endoscopic techniques can potentially improve efficacy and should be evaluated in the setting of appropriate clinical trials.

Pancreatic cancer: an endoscopic perspective

Pancreatic cancer continues to be a diagnostic and therapeutic challenge. The advent of endoscopic ultrasound-guided interventions have brought about a paradigm shift in the endoscopic approach to diagnosis, treatment and palliation of this common malignancy. The last decade has witnessed significant advances in techniques of endoscopic biliary drainage, endoluminal stenting, celiac plexus neurolysis and image-guided radiation therapy, which have transformed the scope of palliation in pancreatic cancer. Moreover, endoscopic ultrasound-aided intratumoral delivery of fiducials, radioisotopes and chemotherapeutic agents have shown promising results and warrant further investigation. This review summarizes the recent advances in endoscopic applications for the management of pancreatic neoplasms.