Clogging of biliary endoprostheses: a new perspective.

Endoscopic palliation with biliary endoprostheses is now an established treatment for benign and malignant strictures of the biliary tree. These endoprostheses, however, tend to clog with time. We investigated this problem by undertaking in vitro studies on stents of different designs made of different polymer materials. The stent that performed best was then tested in an in vivo trial. There was a direct relation in vitro between the frictional coefficient of a polymer and the amount of encrusted material. Catheters perfused in bacterially contaminated bile, irrespective of material and design, accrued significantly more sludge than catheters perfused with sterilised bile. The presence of side holes significantly increased the amount of sludge in the stents, but eliminated any differences between the various materials. We therefore investigated the effect of omitting side holes in a clinical trial which consisted of two groups of 20 patients each. The group treated with conventional stents accrued significantly more sludge in the stents than the group treated with experimental stents without side holes (p less than 0.05). The absence of side holes did not cause incomplete drainage or increase morbidity. Side holes are detrimental to stent patency, which is adversely affected by other factors including bacteria and proteins.     

Impaired drinking capacity in patients with functional dyspepsia: relationship with proximal stomach function.

BACKGROUND & AIMS: Impaired fundic accommodation to a meal and hypersensitivity to distention are increasingly recognized as important mechanisms underlying functional dyspepsia (FD). In the present study, we evaluated whether a drink test can predict such abnormalities and thus represent a noninvasive tool to study proximal stomach motor function. METHODS: Healthy volunteers (HV), nonconsulters with mild dyspeptic symptoms (MS), and patients with FD filled out a disease-specific questionnaire and underwent a drink test with either water or with a high calorie fluid. The maximal ingested volume and the subsequent symptoms were meticulously recorded. In addition, all subjects underwent a gastric barostat study assessing meal-induced relaxation and sensation to distention. RESULTS: Drinking capacity was not significantly related to any particular dyspeptic symptom. FD were able to consume less water (893 +/- 70 mL) and caloric liquid (767 +/- 50 mL) compared with HV (water, 1764 +/- 120 mL; caloric liquid, 1308 +/- 96 mL) or MS (water, 1645 +/- 120 mL; caloric liquid, 973 +/- 45 mL). Approximately half of the FD had an abnormal water or Nutridrink test compared with 9% of MS and 4% of HV. Furthermore, FD developed significantly more symptoms than MS or HV after both drink tests. The drinking capacity did not predict impaired fundic accommodation or visceral hypersensitivity. CONCLUSIONS: FD, but not MS, have an impaired drinking capacity to both water and a nutrient liquid. The drinking capacity is not related to a specific dyspeptic symptom and does not predict proximal stomach motor function.     

Carcinoma of the ampulla of vater

Summary Endoscopically placed biliary endoprostheses were used to treat obstructive jaundice in 71 patients with ampullary carcinoma. Successful placement of an endoprosthesis was achieved in 68 patients (95.8%). Bilirubin declined in 67 patients (98.5%). There was no procedure-related mortality. Twenty-two patients (31%) received further surgical therapy, and 47 received an endoprosthesis as their only therapeutic intervention. In the latter group, bilirubin normalized in 44 of 46 patients surviving longer than 30 days (95.7%). Mean survival was 466 days (median 410, range 23-1515), which compares favorably with surgical palliation. Complications mainly involved clogging of the endoprosthesis, which was easily treated endoscopically and, more significantly, duodenal stenoses secondary to continued tumor growth in almost 25% of the patients. Although endoscopic drainage is a safe and effective method of relieving biliary obstruction in patients with ampullary carcinoma, we feel it should be reserved for poor surgical candidates and for those patients with a limited life expectancy due to metastatic disease.     

Colloidal bismuth subcitrate in peptic ulcer disease

The pharmacological mechanism of ulcer coating and cytoprotection associated with colloidal bismuth have important therapeutic implications for the management of peptic ulcer disease. While the short-term healing rate is similar to that obtained by the H2 antagonists, the relapse rate appears lower.     

Laser photocoagulation in the palliation of colorectal malignancies

Besides surgical intervention, there are virtually no palliative treatment modalities available for bleeding and/or obstructing colorectal malignancy. The usefulness and safety of laser photocoagulation was prospectively investigated in 63 patients with colorectal cancer. The merits were evaluated in the treatment of obstruction (16 patients), bleeding (32 patients), and combined hemorrhage and obstruction (15 patients). Luminal patency could be restored in 15 (94%), hemostasis was achieved in 28 (88%), and treatment was effective in 13 (87%) patients with bleeding and obstructing tumors. In the 56 evaluable and initially responding patients, no beneficial long-term results were achieved in six patients, as major complications of (re)stenosis, necessitating colostomy, occurred in three, posttreatment hemorrhage with need for blood transfusion in two, and a pararectal abscess formation was seen in one patient. Except probably for this pararectal abscess, there was no treatment-related death. Transient stenosis and laser-induced bleeding, as minor complications present in 12 (19%), responded favorably upon reinstitution of laser photocoagulation. The beneficial effect of laser photocoagulation was, in general, evident after 2 to 3 sessions. Forty-six patients could be discharged from the hospital and their treatment could be continued in the outpatient clinic. Further hospital admission could be avoided in 39. Laser treatment for palliation of obstructing and/or bleeding colorectal cancer proved to be an efficacious, safe, and rapidly effective therapy. Laser photocoagulation can be considered as a valuable alternative to aggressive surgical intervention in the absence of other conservative treatment modalities in palliation.     

Morphine-6beta-glucuronide and morphine-3-glucuronide, opioid receptor agonists with different potencies.

Using heterologous expression in Xenopus laevis oocytes, we compared the potencies of morphine, morphine-6beta-glucuronide (M6G), and morphine-3-glucuronide (M3G) for cloned human mu- (hMOR), kappa- (hKOR), and delta-opioid receptors (hDOR). Each receptor subtype was individually co-expressed with heteromultimeric G-protein coupled inwardly rectifying K(+) (GIRK) channels, consisting of GIRK1 and GIRK2 subunits, and RGS4, a regulator of G-protein signaling. The two-microelectrode voltage clamp technique was used to measure the opioid receptor-activated GIRK1/GIRK2 channel responses. Compared with morphine, M6G had higher potency at the hMOR, lower potency at the hKOR, and similar potency at the hDOR, while M3G showed a 1000-fold lower and non-selective potency via opioid receptors. In contrast to naloxone, M3G did not antagonize the effects of morphine at the hMOR. We also investigated whether Trp318 and His319 provide the molecular basis for mu/delta selectivity and mu/kappa selectivity of morphinan alkaloids by mutating these residues to their corresponding residues in kappa- and delta-opioid receptors. A single-point mutation (W318L) on hMOR completely conferred delta-like potency for morphine and M6G on the mutant mu-receptor. Double mutation at Trp318 and His319 positions (Trp318Y/His319Y) only partially conferred kappa-like potency for morphine and M6G; the decrease in potency for M6G was significantly larger than for morphine. The results of our study show that both M6G and M3G are opioid receptor agonists with different potencies and that the potency of morphinan receptor ligands can be changed by selective mutations of hMOR at the Trp318 and His319 positions.