N-(p-amylcinnamoyl) anthranilic acid attenuates remedial effects of memantine on memory deficits following intracerebroventricular streptozotocin administration in rats.

N-(p-amylcinnamoyl) anthranilic acid (ACA) is a blocker of transient receptor potential melastatin-2 (TRPM2) which is a non-selective, Ca2+-permeable and oxidative stress sensor cation channel. Intracerebroventricular (ICV) streptozotocin (STZ) induction successfully generates spatial memory deficits in rats. The purpose of this study was to investigate effects of ACA on a rat model of STZ-induced learning and memory deficits. A total of 60 Wistar rats randomly divided into six groups; (1) control, (2) sham-operated, (3) ICV-STZ administered, (4) ICV-STZ + memantine (5 mg/kg i.p.), (5) ICV-STZ + ACA (25 mg/kg i.p.) and (6) a combination therapy group, ICV-STZ + ACA (25 mg/kg) + memantine (5 mg/kg). Effects of the drugs on spatial memory deficits were appraised in Morris water maze (MWM) apparatus. Anxiety-like behavior of the rats were also assessed by using both the elevated plus maze (EPM) and open field maze (OFM) apparatuses. Western blot analysis of hippocampal tissues revealed TRPM2-L channel protein expression levels. Serum levels of tumor necrosis factor alpha (TNF-α) and malondialdehyde (MDA) were detected by enzyme-linked immunosorbent assay (ELISA) kits. Memantine treatment ameliorated the spatial memory deficits induced, as evidenced by the MWM tests. However, ACA treatment did not provide any improvement, instead positive effects of memantine were attenuated by ACA treatment. Western blot analysis in hippocampal tissues showed that TRPM2-L protein expression was markedly suppressed in ICV-STZ administered group. The ACA treatment reversed that suppression. Surprisingly, the memantine treatment resulted in overexpression of TRPM2-L, to a certain extent. Examination of the rats in EPM and OFM apparatuses, as a display of anxiety-like behavior, did not reveal any marked difference among groups. Serum levels of TNF-α and MDA also did not vary significantly among groups, as well. Conclusively, our findings showed for the first time that TRPM2-L protein expression was significantly suppressed in the ICV-STZ induced memory deficit model. Even though ACA reversed this suppression, no improvement in spatial memory was observed following ACA treatment.

Effects of low-level laser therapy on osteoblastic bone formation and relapse in an experimental rapid maxillary expansion model.

AIMS AND OBJECTIVES: The aim of this study was to investigate the effects of low-level laser therapy (LLLT) on osteoblastic bone formation and relapse during expansion of rat palatal sutures. MATERIALS AND METHODS: Thirty-two Wistar rats were randomly allocated into two groups of 16 rats each. In the first group, LLLT was applied 4 days after expansion commenced. Seven days after expansion, retainers were applied for 10 days. The second group was similarly treated, with the exception of laser therapy. All rats were sacrificed on day 7 (n = 1) (the end of the expansion period; laser group (LG) 1 [LLLT 1] and control group (CG) 1 [control 1]) and day 17 (n = 8) (the end of the retention period; LG 2 [LLLT 2] and CG 2 [control 2]) for histological assessment. RESULTS: The LLLT 1 group had significantly higher numbers of osteoclasts than did the control 1 group (P = 0.036). No significant between-group difference in osteoblast cell or capillary numbers was evident when day 7 and 17 data were compared. CONCLUSION: Histologically, LLLT stimulated bone formation, as revealed by analysis after the retention period. LLLT during expansion may accelerate bone healing.

Effect of cellulose acetate materials on the oxidative burst of human neutrophils.

Following adverse clinical events involving seven patients undergoing renal dialysis using 12-year-old cellulose acetate hemodialyzers, this in vitro study was proposed in an effort to characterize the inflammatory response to the constituent cellulose acetate (CA) fiber materials. Chemiluminescence (CL) and apoptosis assays were used to determine whether human neutrophils were activated by CA fiber materials and/or are sensitive to degradation/alteration of these fibers over time. Furthermore, the study examined in vitro assays with human neutrophils using a CA film, the solvents used in the film preparation and CA resin. The film could be cut to identical sized pieces in an effort to compare hemodialysis material effects in standardized amounts. For the CL assays, 60-min exposure was followed by secondary stimulation with n-formyl-met-leu-phe (fMLP) or phorbol-12-myristate-13-acetate (PMA). Short-term exposure (60-min postintroduction to CA materials) increased the inflammatory response as measured by the respiratory burst of neutrophils (p < or =.05), with CA fiber exposure significantly compared with cells alone. There was a trend toward an increased response with exposure to older fibers with secondary PMA stimulation. Apoptosis was increased 12% with exposure to the more aged fibers versus 2% with the new fibers. The fiber storage component, glycerol, significantly inhibited the oxidative response (p < or =.001; > or =80% suppression with concentrations of 5-20%). The solvents used in film preparation, N,N-dimethylacetamide and tetrahydrofuran, produced greater than a 70% and 60% suppression, respectively, of CL activity for all concentrations > or =1%. More work is needed to determine the specific nature of the interaction of inflammatory cells with CA materials, but early evidence suggests that neutrophils are activated by CA and display an altered response to more aged fibers.

Expandable metal stents in achalasia--is there a role?

OBJECTIVE: Achalasia is treated with pneumatic dilation or myotomy, and botulinum toxin injections are occasionally used. We review our community's experience with expandable metal stents in six patients who failed medical treatment or were poor surgical candidates. METHODS: Eight stents were placed in six patients between July 1995 and November 1997. Four patients had achalasia and two pseudoachalasia. Four patients underwent successive botulinum toxin injections. One patient only agreed to periodic Maloney dilatations or a stent. Pneumatic dilation was performed in one patient and considered high risk in the rest. All were poor surgical candidates. Three different stents were used: Gianturco Rosch Z stent, Wallstent I, and Wallstent II. RESULTS: One-month mortality and morbidity were 33% and 50%, respectively. Two patients were asymptomatic on a liquid diet for > or =6 months but required repeat endoscopy for recurrent dysphagia because of food bolus impaction and proximal stent migration in each. CONCLUSIONS: Expandable metal stents in achalasia or pseudoachalasia do not provide sustained symptom relief, and their use is associated with unacceptably high morbidity and mortality. We do not recommend the use of these devices in patients who have failed medical therapy or who are poor surgical candidates.

Irritable bowel syndrome (IBS) and alcohol abuse or dependence.

Irritable bowel syndrome (IBS) has been reported in 10-22% of adults. Using a semistructured clinical interview to study the prevalence of IBS, we compared 31 patients seeking treatment for alcohol abuse or dependence in an outpatient setting with an age- and sex-matched control group of 40 patients who were seeking treatment in a general physician's office for other medical illnesses. The control group did not have any Axis I disorders. IBS was diagnosed according to the criteria of Drossman et al. Thirteen (41.9%) patients with alcohol abuse or dependence met the criteria for IBS, in contrast to 1 (2.5%) patient in the control group. We conclude that IBS is common and frequently underdiagnosed in patients with alcohol abuse or dependence.

Effect of transjugular intrahepatic portosystemic shunt on secondary hypersplenism.

BACKGROUND: Portal hypertension is frequently associated with secondary hypersplenism, two common clinical manifestations of which are leukopenia and thrombocytopenia. Surgical portosystemic shunts alleviate portal hypertension but their effect on hypersplenism remains unpredictable. Transjugular intrahepatic portosystemic shunt (TIPS) is a minimally invasive procedure for portal decompression. From current reports it is not clear if TIPS improves hypersplenism in patients with portal hypertension. We present a retrospective review of our experience with TIPS to determine the effect on hypersplenism. PATIENTS AND METHODS: Sixty-five patients who had a TIPS procedure between December 1991 and June 1994 were evaluated retrospectively. The records were specifically reviewed for platelet and white blood cell counts performed before the procedure, within a week after the procedure, and then again within the subsequent 3 weeks. Hypersplenism was defined as thrombocytopenia (platelet count of <100,000/mm3), leukopenia (white blood cell count of <5,000/mm3), or both. RESULTS: Thrombocytopenia alone was present in 33 patients and leukopenia alone in 4 patients before TIPS was performed. Both leukopenia and thrombocytopenia were present in 12 individuals. At least one of these indices of hypersplenism was present in 49 patients. Leukocyte count improved in 11 of 16 patients (69%) whereas platelet count improved in 34 of 45 patients (75%) within a week of the procedure. In the subsequent 3 weeks, leukopenia was relieved in 5 of 10 patients (50%) and thrombocytopenia in 21 of 28 patients (75%), respectively. Of the 12 patients who had both leukopenia and thrombocytopenia before TIPS, the indices improved in 4 patients (33%) within a week of the procedure. Thrombocytopenia was more consistently corrected as opposed to leukopenia, albeit in the short term. CONCLUSION: The TIPS procedure is a promising, minimally invasive method of portal decompression that is effective in the treatment of complications of portal hypertension including secondary hypersplenism.

Irritable bowel syndrome and dysthymia. Is there a relationship?

Irritable bowel syndrome (IBS) has been reported in 10% to 22% of adults. The authors compared patients seeking treatment for dysthymia (N = 59) in an outpatient setting to an age- and sex-matched comparison group of patients (N = 54) seeking treatment in a general physician's office for other medical illnesses. The comparison group did not have any Axis I disorders. IBS was diagnosed by using the criteria established by Drossman and colleagues. Of the patients screened, 59.32% of the patients with dysthymia met criteria for IBS in contrast to 1.85% of the comparison group (P < 0.000005). IBS is extremely prevalent in patients seeking treatment for dysthymia and is often undiagnosed and untreated.

Colonic tattooing with India ink: benefits, risks, and alternatives.

OBJECTIVE: To provide comprehensive information on key issues concerning colonic tattooing with India ink in reported literature. METHODS: A total of 735 citations on India ink alone were present in the English literature (1966-1995), including 16 on India ink and colonic tattooing. Nine major studies were identified and reviewed for 1) preparation before tattooing (type of ink used, sterilization process, colonic preparation, and antibiotic prophylaxis), 2) the tattooing process (technique and volume injected), 3) success in localization, and 4) complications. RESULTS: A'total of 447 cases of colonic tattooing with India ink have been reported. Major indication was preoperative marking of tumor site. Various India ink preparations were used. Ink was unsterilized in 57% (255/447), autoclaved in 42% (187/447), and gas sterilized in 1% (5/447) of cases. Colonic preparation varied similarly. Prophylactic antibiotics were used in 1% (5/447) of cases. Dilution of India ink varied from undiluted to 1:100 (with 0.9% saline). The volume injected ranged from 0.1 to 2 ml per site injected, commonly with tangential needle insertion and delivery of ink into the submucosa in the majority of the cases. Intraoperative localization was easier with multiple tattoo injections. Five reports of complications have been made. In only one instance did overt clinical complications develop. Risk of a clinical complication with colonic tattooing with India ink is 0.22%. CONCLUSION: Marked variability in technique, as well as potential for reporting bias, limit the quantitative conclusions. In general, colonic tattooing with India ink is a safe, accurate, and inexpensive method for preoperative marking and prospective study of colonic lesions.

The relationship of irritable bowel syndrome (IBS) and panic disorder.

Irritable bowel syndrome (IBS) has been reported in 10 to 22% of adults. Using a semi-structured clinical interview to study the prevalence of irritable bowel syndrome, we compared 41 patients seeking treatment for panic disorder in an outpatient setting to an age- and sex-matched control group of 40 patients who were seeking treatment in a general physician's office for other medical illnesses. The control group did not have any Axis I disorders. IBS was diagnosed according to the criteria of Drossman et al. Nineteen (46.3%) patients with panic disorder met the criteria for IBS, in contrast to one (2.5%) patient in the control group (p < 0.000005). Patients with panic disorder and IBS were more likely to report symptoms of back pain as well as a personal history of bowel disease compared to patients with panic disorder but without IBS. IBS is fairly common in patients seeking treatment for panic disorder. Prospective studies should address the question whether treatment of panic disorder leads to an improvement or resolution of the symptoms of IBS.

Major depression and irritable bowel syndrome: is there a relationship?

BACKGROUND: Irritable bowel syndrome (IBS) has been reported in 10% to 22% of adults. Seventy percent to 90% of patients with IBS who seek medical attention have psychiatric comorbidity, most commonly major depression. In contrast, few studies have looked at the prevalence of IBS among psychiatric patients. METHOD: Using a semistructured clinical interview to study the prevalence of IBS, we compared 56 patients seeking treatment for major depression in an outpatient setting to an age- and sex-matched control group of patients (N = 40) who were seeking treatment in a general physician's office for other medical illnesses. The control group had no Axis I disorders. IBS was diagnosed according to the criteria of Drossman et al. RESULTS: Twenty-seven percent (N = 15) of patients with major depression met criteria for IBS in contrast to 2.5% (N = 1) of the control group (p = .0005). Patients with major depression and IBS were more likely to report symptoms of back pain, weakness, heartburn, and nocturnal bowel movements as well as a personal or family history of bowel disease compared with patients with major depression but without IBS. CONCLUSION: IBS is fairly common in patients seeking treatment for major depression. Prospective studies should address the question whether treatment of major depression leads to an improvement or resolution of the symptoms of IBS.

Endoscopic US of the gastrointestinal tract with endoscopic, radiographic, and pathologic correlation.

Endoscopic ultrasonography (US) makes it possible to evaluate the layers of the wall of the gastrointestinal tract, as well as surrounding structures. The authors have used endoscopic US to evaluate the gastrointestinal tract in 160 patients. In the esophagus, endoscopic US is useful in staging esophageal carcinoma, planning radiation therapy ports, and locating and characterizing esophageal masses. Endoscopic US of the esophagus is also used to identify varices and evaluate the results of therapy. Applications of endoscopic US in the stomach include staging of gastric carcinoma, localization and characterization of nonmucosal gastric masses, detection and evaluation of gastric varices, and evaluation of gastric lymphoma. In the pancreas, endoscopic US is used for detecting pancreatic masses; staging pancreatic, distal common bile duct, and ampullary carcinoma; and evaluation biliary tract obstruction. Applications of endoscopic US in the rectum include localization and characterization of nonmucosal lesions and local staging of rectal carcinoma.

Efficacy of the somatostatin analog octreotide in the treatment of two patients with refractory diabetic diarrhea.

Two patients with severe refractory diabetes-related diarrhea are described. One patient had steatorrhea. Both responded to octreotide during a mean follow-up period of 7 months. The pathophysiology of diabetic diarrhea and the potential mechanism of action of octreotide are discussed. The only adverse side effect reported was hypoglycemia in one of the patients, which required a reduction of the insulin dose. Octreotide is a safe and effective agent for the treatment of refractory diabetic diarrhea.

Use of a mouth gag instrument to facilitate bite block insertion and prevent finger and probe bites during transesophageal echocardiography.

Transesophageal echocardiography greatly enhances the examination of patients difficult to image transthoracically. While of low patient risk, a potential for harm from human bites to the echocardiography staff and to the transesophageal probe remains, particularly when dealing with uncooperative patients. This risk potential prompted implementation of additional anti-bite protection in our universal precautions policy beyond use of a standard mouth guard. A mouth gag instrument was modified by placing latex rubber tubing over the instrument blades. This instrument was inserted into the mouth and set in an open position giving the operator safe access for probe and mouth bite guard insertion. This technique improved access to the patient's mouth and visualization of probe insertion without the mouth bite guard. The mouth gag instrument provided an insertion of the transesophageal probe in impaired or otherwise uncooperative patients, which was safer for the patient, laboratory staff, and the probe itself.

Application of quantitative immunofluorescence to clinical serology: antibody levels of Treponema pallidum.

A previously reported method of quantitative immunofluorescence, employing a calibrated photometric system and chemically stabilized fluorescence intensity, was used to replace the subjective, visual method of endpoint determination with a quantitative, calibrated measurement of antibodies to Treponema pallidum in serum. The results of the quantitative immunofluorescence method showed a 90% correlation with the subjective determinations of the visual method.

Mechanisms of gastric proton pump inhibition by calcium channel antagonists.

The inhibitory effects of Ca channel antagonists on gastric acid secretion [[14C]-aminopyrine (AP) uptake ratio] have been analyzed in isolated rabbit parletal cells (PC). Secretagogue-stimulated AP uptake was inhibited by verapamil and diltiazem in a dose-dependent manner with IC50 values of 15 and 100 microM, respectively, both in the presence and absence of extracellular Ca. In contrast, nifedipine had no effect on AP accumulation. Verapamil decreased histamine-stimulated respiration with the same IC50 as observed for AP uptake. Imidazole, a weak base, by buffering the acid spaces in PC, reversed the inhibitory effect of verapamil on respiration. In the bullfrog gastric mucosa, forskolin-stimulated proton transport was inhibited by verapamil (10(-4) M) from the luminal but not the serosal side. This inhibitory effect was reversed by either elevating KCl concentration in, or removing the drug from, the secretory solution. Verapamil inhibited gastric microsomal H+,K(+)-adenosine triphosphatase (H+,K(+)-ATPase) and PC K(+)-stimulated p-nitrophenyl phosphatase activities with a higher potency than diltiazem. Inhibition of these enzymes by verapamil and diltiazem was pH dependent. The drugs competed with K+ in both H+,K(+)-ATPase and K(+)-stimulated p-nitrophenyl phosphatase reactions. Our data suggest that inhibition of the gastric proton pump by verapamil or diltiazem is not due to their Ca channel antagonism but to their interaction with the luminal high affinity K(+)-site of the H+,K(+)-ATPase under acidic conditions.