Effects of Antidepressants on Gastric Function in Patients with Functional Dyspepsia.

BACKGROUND: Functional dyspepsia (FD) is a highly prevalent functional bowel disorder. The effects of antidepressant therapy (ADTx) on gastric sensorimotor function in FD patients are poorly understood. AIMS: Determine whether FD and subtypes with abnormalities in gastric function respond differently to ADTx compared to those with normal physiology. METHODS: This multicenter, prospective trial randomized FD patients to 12 weeks of amitriptyline (AMI; 50 mg), escitalopram (ESC; 10 mg), or matching placebo. Demographics, symptoms, psychological distress, gastric emptying, and satiation were measured. Gastric accommodation (GA) using single-photon emission computed tomography imaging was performed in a subset of patients. An intent to treat analysis included all randomized subjects. The effect of treatment on gastric emptying was assessed using ANCOVA. A post hoc appraisal of the data was performed categorizing patients according to the Rome III subgrouping (PDS and EPS). RESULTS: In total, 292 subjects were randomized; mean age=44 yrs. 21% had delayed gastric emptying. Neither antidepressant altered gastric emptying, even in those with baseline delayed gastric emptying. GA increased with ADTx (P=0.02). Neither antidepressant affected the maximal-tolerated volume (MTV) of the nutrient drink test although aggregate symptom scores improved compared to placebo (P=0.04). Patients with the combined EPS-PDS subtype (48%) had a lower MTV on the nutrient drink test compared to the EPS group at baseline (P=0.02). Postprandial bloating improved with both AMI (P=0.03) and ESC (P=0.02). CONCLUSIONS: Amitriptyline (50 mg) improves FD symptoms but does not delay gastric emptying, even in patients with baseline delayed gastric emptying. GA improved with low-dose ADTx; the precise mechanism of action is unknown warranting further study.

Utilization of wireless pH monitoring technologies: a summary of the proceedings from the esophageal diagnostic working group.

Gastroesophageal reflux disease (GERD) can be difficult to diagnose - symptoms alone are often not enough, and thus, objective testing is often required. GERD is a manifestation of pathologic levels of reflux into the esophagus of acidic, nonacidic, and/or bilious gastric content. However, in our current evidence-based knowledge approach, we only have reasonable outcome data in regards to acid reflux, as this particular type of refluxate predictably causes symptoms and mucosal damage, which improves with medical or surgical therapy. While there are data suggesting that nonacid reflux may be responsible for ongoing symptoms despite acid suppression in some patients, outcome data about this issue are limited. Therefore, this working group believes that it is essential to confirm the presence of acid reflux in patients with 'refractory' GERD symptoms or extraesophageal symptoms thought to be caused by gastroesophageal reflux before an escalation of antireflux therapy is considered. If patients do not have pathologic acid reflux off antisecretory therapy, they are unlikely to have clinically significant nonacid or bile reflux. Patients who do not have pathologic acid gastroesophageal reflux parameters on ambulatory pH monitoring then: (i) could attempt to discontinue antisecretory medications like proton pump inhibitors and H2-receptor antagonists (which are expensive and which carry risks - i.e. C. diff, etc.); (ii) may undergo further evaluation for other causes of their esophageal symptoms (e.g. functional heartburn or chest pain, eosinophilic esophagitis, gastroparesis, achalasia, other esophageal motor disorders); and (iii) can be referred to an ear, nose, and throat/pulmonary/allergy physician for assessment of non-GERD causes of their extraesophageal symptoms.

The hyaluronate receptor is associated with actin filaments.

The cell-surface receptor for hyaluronate is an integral membrane glycoprotein of Mr 85,000 (Underhill, C. B., A. L. Thurn, and B. E. Lacy, 1985, J. Biol. Chem., 260:8128-8133) that is thought to mediate many of the effects that hyaluronate has on cell behavior, such as migration, angiogenesis, and phagocytosis. To determine if the receptor is associated with the underlying cytoskeleton, Swiss 3T3 cells were extracted with a solution of Triton X-100, which solubilized most of the cellular components, but which left behind an insoluble residue containing the cytoskeleton. This detergent-insoluble residue was found to contain the bulk of the hyaluronate-binding activity, suggesting that the receptor might indeed be associated with the cytoskeleton. To further define the cytoskeletal element with which the receptor interacts, 3T3 cells were extracted with Triton X-100 under a variety of different ionic conditions. In each case, the amount of hyaluronate-binding activity in the detergent-insoluble residue was related to the amount of actin present, but not to either tubulin or vimentin. In addition, the recovery of hyaluronate-binding activity was dramatically enhanced (to 100% in most cases) if the cells were extracted in the presence of phalloidin, a drug that stabilizes actin filaments. However, the recovery of binding activity was dramatically decreased when whole cells were treated with cytochalasin B before extraction, and when extracted cells were treated with DNase I, which promotes the depolymerization of actin filaments. In addition, preincubating an extract of SV-40-transformed Swiss 3T3 cell membranes with DNase I caused a change in the elution profile of the receptor as judged by molecular-sieve chromatography. Presumably this decrease in the size of the receptor is due to the loss of associated actin filaments. The results of these experiments strongly suggest that the receptor for hyaluronate is associated either directly or indirectly with cytosolic actin filaments.

Irritable bowel syndrome: patients' attitudes, concerns and level of knowledge.

BACKGROUND: Irritable bowel syndrome (IBS) is a common, chronic disorder that reduces patients' quality-of-life. Although highly prevalent, little is known about patients' understanding of this disorder. AIM: To evaluate the knowledge, fears and concerns of IBS patients. METHODS: Seven hundred thirty-six IBS patients (Rome II criteria) were eligible for inclusion in this prospective study. Each patient received a validated questionnaire to evaluate knowledge, attitudes and fears regarding IBS. RESULTS: A total of 261 of 664 potential respondents completed the questionnaire (39.3%). 83% of respondents were women, with a mean age of 53.7 years, and mean duration of symptoms of 14.2 years. Patients frequently believed that IBS develops because of anxiety (80.5%), dietary factors (75.1%) and depression (63.2%). Few respondents (28.7%) recognized that abdominal pain is the cardinal symptom of IBS, and 40.6% stated that colonoscopy can diagnose IBS. One in seven patients stated that IBS turns into cancer, and 29.9% noted that IBS increases the risk of inflammatory bowel disease. CONCLUSIONS: Many IBS patients have significant misconceptions regarding the nature of their disease and its prognosis. An overwhelming majority of IBS patients believe that anxiety, dietary factors and depression cause IBS. These findings are discordant with physicians' views and practices and highlight the need for patient-oriented educational programs.

Emerging treatments in neurogastroenterology: eluxadoline - a new therapeutic option for diarrhea-predominant IBS.

BACKGROUND: Irritable bowel syndrome (IBS) is the most common functional gastrointestinal disorder worldwide. The global prevalence of IBS is estimated to be as high as 15%. For many patients, IBS is a chronic disorder which can significantly reduce quality of life. Just as important as the effects on any one individual, IBS also places a significant impact on the population as a whole with its negative effects on the health care system. Irritable bowel syndrome is categorized into one of three main categories: IBS with diarrhea, IBS with constipation, and IBS with mixed bowel habits. Patients with diarrhea-predominant IBS (IBS-D) comprise a substantial proportion of the overall IBS population. A number of therapeutic options exist to treat the symptoms of abdominal pain, bloating, diarrhea, and fecal urgency, including non-pharmacologic therapies such as dietary changes and probiotics, or pharmacologic therapies such as loperamide and alosetron. However, many patients have persistent symptoms despite these therapies. This unmet need led to the development of eluxadoline, a mu-opioid receptor agonist/delta-opioid receptor antagonist/kappa-receptor agonist. Approved by the FDA in May 2015, this medication shows promise in the treatment of diarrhea-predominant IBS for both men and women. PURPOSE: This monograph will briefly review the impact of IBS, discuss current treatments for IBS-D, and then focus on the pharmacology, clinical efficacy and safety of eluxadoline. Potential mechanisms related to rare events of acute pancreatitis or elevated liver tests will be discussed.

The effects of tegaserod, a 5-HT receptor agonist, on gastric emptying in a murine model of diabetes mellitus.

UNLABELLED: The C57BLKS/J db/db transgenic mouse is a model of diabetes mellitus that has been shown to have delayed gastric emptying. We assessed gastric emptying rates in C57BLKS/J mice, and determined the effects of tegaserod, a new selective 5-HT(4) receptor partial agonist, on gastric emptying. METHODS: Gastric emptying rates of a 20% glucose test meal were determined in 12-20-week-old female db/db mice and control littermates. The effects of tegaserod (0.1-2.0 mg kg(-1), i.p.) on gastric transit were tested in a second group of db/db mice. Pretreatment with GR11308, a specific 5-HT(4)antagonist, was used to confirm the mechanism of action of tegaserod on gastric emptying. RESULTS: Gastric emptying of glucose was significantly slower in db/db mice than in control littermates. Tegaserod (0.1 mg kg(-1)) significantly accelerated the gastric emptying rate of glucose in db/db mice, reducing the fraction of the meal remaining in the stomach at 30 min by 80%. GR11308 blocked the gastrokinetic effects of tegaserod. CONCLUSIONS: Gastric emptying was impaired in db/db mice. Low dose tegaserod improved gastric emptying rates in this model of gastroparesis through the activation of 5-HT(4) receptors. These findings suggest that 5-HT(4) receptor agonists may prove useful for improving delayed gastric emptying in gastroparesis.

The impact of obesity on oesophageal acid exposure time on and off proton pump inhibitor therapy.

BACKGROUND: Obesity is associated with increased oesophageal acid exposure time (AET) in patients with gastro-oesophageal reflux (GER), and may decrease the effects of proton pump inhibitors (PPIs). AIM: To evaluate the effects of increased body mass on the ability of PPI therapy to decrease AET in patients with reflux symptoms. METHODS: Acid exposure time profiles collected from adult patients using wireless pH-metry while on or off PPI therapy was retrospectively reviewed. Patients were separated into five body mass index (BMI) categories as defined by the World Health Organization. A multivariable logistic regression evaluated the association between abnormal AET and BMI groups while controlling for age, gender and pH capsule placement methods. RESULTS: The study group comprised 968 patients with 336 (34.7%) studied on a PPI and 632 (65.3%) studied off PPI therapy. AET (total greater than 5.3%) was found more frequently in the overweight (67%) and obese classes (74-80%) compared to those who were normal weight (40%) while off acid-suppressing medications (P < 0.001). No significant differences were found between these groups when studied on acid-suppressing medications, and the proportion of patients with abnormal AET across BMI classes was similar regardless of taking a PPI either once or twice daily. CONCLUSIONS: This is the largest study to report on the relationship between BMI and oesophageal acid exposure time in patients with GER on and off PPI therapy. We conclude that obesity is related to increased acid exposure time, but with no significant difference in acid exposure time among different weight-based groups when taking a once or twice-daily PPI.

The effects of an inhaled beta(2)-adrenergic agonist on lower esophageal function: a dose-response study.

STUDY OBJECTIVES: Albuterol, a beta(2)-adrenergic agonist that is commonly used to treat asthma, reduces bronchial smooth muscle tone. The pharmacodynamics of inhaled albuterol on esophageal function were studied in healthy volunteers. DESIGN: A prospective, randomized, placebo-controlled, double-blind crossover design. SETTING: An academic medical center. PATIENTS: Nine healthy volunteers (five men, four women; age, 22 to 30 years). INTERVENTIONS: Albuterol (2.5 to 10 mg) or placebo was given via nebulizer. Volunteers were studied at two sessions, 1 week apart, using a 6-cm manometry assembly and a low-compliance pneumohydraulic pump. The percentage of lower esophageal sphincter (LES) relaxation, the frequency of transient LES relaxations (TLESRs), and the amplitude, duration, and propagation velocity of esophageal contractions were measured at 5 and 10 cm above the LES. Dependent measures were evaluated using two-way, repeated-measures analysis of variance. MEASUREMENTS AND RESULTS: Albuterol therapy reduced LES basal tone in a dose-dependent manner (baseline, 17.0 +/- 2.6 mm Hg; at 10 mg, 8.9 +/- 2.1 mm Hg; p = 0.01). The frequency of TLESRs was not different from placebo (not significant). Albuterol reduced the amplitude of esophageal contractions at 5 cm above the LES (baseline, 72.5 +/- 18.6 mm Hg; at 10 mg, 48.8 +/- 10.0 mm Hg; p<0.05). A significant reduction in esophageal body contractile amplitudes was noted at 10 cm (F[1,6] = 7.05; p<0.05). CONCLUSIONS: Inhaled albuterol reduced LES basal tone and contractile amplitudes in the smooth muscle esophageal body in a dose-dependent manner. Inhaled beta(2)-agonists may increase the likelihood of acid reflux in a subset of patients who receive cumulative dosing.

Treatment for constipation: new and old pharmacological strategies.

BACKGROUND: Constipation is a very common entity. Despite the high prevalence, treatment of constipation remains problematic. PURPOSE: Review the current literature on new and existing constipation treatment modalities.

Responders vs clinical response: a critical analysis of data from linaclotide phase 3 clinical trials in IBS-C.

BACKGROUND: US Food and Drug Administration (FDA) set a rigorous standard for defining patient responders in irritable bowel syndrome-C (IBS-C; i.e., FDA's Responder Endpoint) for regulatory approval. However, this endpoint's utility for health-care practitioners to assess clinical response has not been determined. We analyzed pooled IBS-C linaclotide trial data to evaluate clinically significant responses in linaclotide-treated patients who did not meet the FDA responder definition. METHODS: Percentages of FDA non-responders reporting improvement in abdominal pain, bowel function and/or global relief measures were determined using pooled data from two linaclotide Phase 3 IBS-C trials. KEY RESULTS: 1602 IBS-C patients enrolled; 34% of linaclotide-treated and 17% of placebo-treated patients met the FDA Responder Endpoint (p < 0.0001). Among FDA non-responders at week 12, 63% of linaclotide-treated patients reported their abdominal pain was at least somewhat relieved, compared with 48% of placebo-treated patients. For stool frequency, 62% of linaclotide-treated patients reported that they were at least somewhat improved at week 12, compared with 46% of placebo-treated patients. For global IBS symptoms, 65% of linaclotide-treated patients reported at least some IBS-symptom relief, 43% reported adequate relief of IBS symptoms, and 57% reported being satisfied with linaclotide treatment, vs placebo rates of 48%, 34%, and 41% respectively. CONCLUSIONS & INFERENCES: Most linaclotide-treated IBS-C patients who were FDA non-responders reported some improvement in abdominal pain and stool frequency, and global relief/satisfaction. In addition to the FDA Responder Endpoint, differing response thresholds and symptom-specific change from baseline should be considered by clinicians for a complete understanding of clinical response to linaclotide and other IBS-C therapies.

Functional dyspepsia: the economic impact to patients.

BACKGROUND: Although highly prevalent, little is known about the economic impact of functional dyspepsia (FD). AIMS: To quantify FD patients' health care utilisation patterns and to estimate direct and indirect costs of FD to patients. METHODS: ICD-9 codes identified adult patients with dyspepsia. A validated questionnaire was mailed to patients who met Rome III criteria for FD. RESULTS: Three hundred and fifty-five patients met all inclusion criteria. The response rate was 63%. The respondents' mean age was 50 (14) years; 75% were women; 52% of respondents rated their FD as moderate. Patients reported 3 visits (mean) to their PCP over 12 months; 75% reported having blood work, 92% an EGD, 59% an ultrasound and 40% a CT scan. The direct cost of testing using Medicare reimbursement rates per patient was $582. To treat FD symptoms, 89% tried dietary changes, 89% over-the-counter medications, 87% prescription medications and 25% alternative therapies. Mean patient expenditure over the last year was $246 for OTC medications (range $0-12,000), $290 for co-payments (range $0-9,000) and $110 for alternative treatments (range $0-3,741). Total mean direct cost yearly to patients was $699. In the 7 days prior to completing the questionnaire, respondents reported a mean of 1.4 h absence from work. Extrapolating the results to the US population, we conservatively calculate the costs of FD were $18.4 billion in 2009. CONCLUSIONS: Functional dyspepsia patients incur significant direct and indirect costs and work productivity is impaired by dyspeptic symptoms.

Linaclotide in the management of gastrointestinal tract disorders.

Chronic constipation is a highly prevalent, heterogeneous disorder that significantly affects patients' lives. Nearly 15% of the U.S. population meets diagnostic criteria for chronic constipation (1). Chronic constipation reduces patients' quality of life and imposes a significant economic burden to the healthcare system (2, 3). A number of therapeutic options are currently available to treat symptoms of chronic constipation, although they are not universally successful (4, 5). Irritable bowel syndrome (IBS) is another common functional gastrointestinal disorder, with a prevalence rate estimated at up to 12% in the U.S. (6). Similar to chronic constipation, IBS imposes a significant impact on both the healthcare system and the individual patient (7-12). Currently, only one medication (lubiprostone) is approved by the U.S. Food and Drug Administration for the treatment of IBS with constipation (IBS-C), and is approved only for women (13). Although effective in many patients, it is not universally effective for the treatment of constipation symptoms in all patients with IBS-C. Other treatment options are therefore needed for those patients with chronic constipation and IBS-C who fail currently available therapies. This article will present information on the pharmacology and pharmacokinetics of linaclotide, a new agent designed to treat symptoms of both chronic constipation and IBS-C. Preclinical data, clinical studies and safety data will also be reviewed.

Review article: current treatment options and management of functional dyspepsia.

BACKGROUND: Functional dyspepsia (FD), a common functional gastrointestinal disorder, is defined by the Rome III criteria as symptoms of epigastric pain or discomfort (prevalence in FD of 89-90%), postprandial fullness (75-88%), and early satiety (50-82%) within the last 3 months with symptom onset at least 6 months earlier. Patients cannot have any evidence of structural disease to explain symptoms and predominant symptoms of gastroesophageal reflux are exclusionary. Symptoms of FD are non-specific and the pathophysiology is diverse, which explains in part why a universally effective treatment for FD remains elusive. AIM: To present current management options for the treatment of FD (therapeutic gain/response rate noted when available). RESULTS: The utility of Helicobacter pylori eradication for the treatment of FD is modest (6-14% therapeutic gain), while the therapeutic efficacy of proton pump inhibitors (PPI) (7-10% therapeutic gain), histamine-type-2-receptor antagonists (8-35% therapeutic gain), prokinetic agents (18-45%), tricyclic antidepressants (TCA) (response rates of 64-70%), serotonin reuptake inhibitors (no better than placebo) is limited and hampered by inadequate data. This review discusses dietary interventions and analyses studies involving complementary and alternative medications, and psychological therapies. CONCLUSIONS: A reasonable treatment approach based on current evidence is to initiate therapy with a daily PPI in H. pylori-negative FD patients. If symptoms persist, a therapeutic trial with a tricyclic antidepressant may be initiated. If symptoms continue, the clinician can possibly initiate therapy with an anti-nociceptive agent, a prokinetic agent, or some form of complementary and alternative medications, although evidence from prospective studies to support this approach is limited.

Systematic review: cardiovascular safety profile of 5-HT(4) agonists developed for gastrointestinal disorders.

BACKGROUND: The nonselective 5-HT(4) receptor agonists, cisapride and tegaserod have been associated with cardiovascular adverse events (AEs). AIM: To perform a systematic review of the safety profile, particularly cardiovascular, of 5-HT(4) agonists developed for gastrointestinal disorders, and a nonsystematic summary of their pharmacology and clinical efficacy. METHODS: Articles reporting data on cisapride, clebopride, prucalopride, mosapride, renzapride, tegaserod, TD-5108 (velusetrag) and ATI-7505 (naronapride) were identified through a systematic search of the Cochrane Library, Medline, Embase and Toxfile. Abstracts from UEGW 2006-2008 and DDW 2008-2010 were searched for these drug names, and pharmaceutical companies approached to provide unpublished data. RESULTS: Retrieved articles on pharmacokinetics, human pharmacodynamics and clinical data with these 5-HT(4) agonists, are reviewed and summarised nonsystematically. Articles relating to cardiac safety and tolerability of these agents, including any relevant case reports, are reported systematically. Two nonselective 5-HT(4) agonists had reports of cardiovascular AEs: cisapride (QT prolongation) and tegaserod (ischaemia). Interactions with, respectively, the hERG cardiac potassium channel and 5-HT(1) receptor subtypes have been suggested to account for these effects. No cardiovascular safety concerns were reported for the newer, selective 5-HT(4) agonists prucalopride, velusetrag, naronapride, or for nonselective 5-HT(4) agonists with no hERG or 5-HT(1) affinity (renzapride, clebopride, mosapride). CONCLUSIONS: 5-HT(4) agonists for GI disorders differ in chemical structure and selectivity for 5-HT(4) receptors. Selectivity for 5-HT(4) over non-5-HT(4) receptors may influence the agent's safety and overall risk-benefit profile. Based on available evidence, highly selective 5-HT(4) agonists may offer improved safety to treat patients with impaired GI motility.

The effects of intraduodenal nutrient infusion on serum CCK, LES pressure, and gastroesophageal reflux.

BACKGROUND: Fats cause reflux symptoms in many patients and cholecystokinin (CCK) may play a role. This study was designed to evaluate the effects of intraduodenal nutrient infusion on serum CCK levels, lower esophageal sphincter (LES) pressure, and gastroesophageal reflux (GER). METHODS: Twenty-four asymptomatic volunteers were studied. A Dent sleeve catheter assessed LES function while an impedance-pH catheter measured reflux events. Participants were randomized to fat (F), carbohydrate (C) or protein (P) infusion. Serum CCK and LES pressures were measured at baseline and after nutrient infusion. KEY RESULTS: Baseline LES pressures and CCK levels were similar in all three groups. A significant linear decrease was found in LES pressure during F, but not C or P, infusion (P=0.004). A significant interaction effect was noted between the infusion groups and CCK levels (P=0.002). A significant linear increase was noted in CCK levels during F but not during C or P infusion (P=0.02). A significant inverse correlation was found between CCK levels and LES pressure (ρ=-0.43; P=0.04). Esophageal acid exposure was significantly increased in the F infusion group (median; interquartile range: 1.10%; 0.25-4.7%) compared to both the C (0.03%; 0.00-0.39%) and P infusion (0.03%; 0.00-0.39%) groups (P=0.04). CONCLUSIONS & INFERENCES: Intraduodenal F infusion was associated with an increase in CCK levels, while P and C were not. LES pressure decreased significantly after fat infusion and reflux events were more frequent. Fat-induced CCK release is another mechanism that contributes to GER.

Timely confirmation of gastro-esophageal reflux disease via pH monitoring: estimating budget impact on managed care organizations.

BACKGROUND: Current guidelines recommend the use of pH monitoring to confirm the diagnosis of acid reflux in patients with a normal endoscopy. This analysis evaluated the financial impact of pH monitoring with the wireless pH capsule on a managed care organization (MCO) in the United States. METHODS: A decision model was constructed to project total 1-year costs to manage GERD symptoms with and without the adoption of wireless pH capsules in a hypothetical MCO with 10 000 eligible adult enrollees, of whom 600 presented with GERD-like symptoms. Costs of GERD diagnosis, treatment, and symptom management for those in whom a GERD diagnosis was ruled out by pH monitoring were assessed. The incremental per-member-per-month (PMPM) and per-treated-member-per-month (PTMPM) costs were the primary outcomes. Data sources included literature, expert input, and standardized fee schedules. RESULTS: An increase of 10 percentage points in the use of pH monitoring with wireless pH capsules yielded incremental PMPM and PTMPM costs of $0.029 and $0.481, respectively. The costs of proton pump inhibitor (PPI) therapy to the plan dropped to $236,363 from $238,086, while increases were observed in pH monitoring (from $16 739 to $21 973) and non-GERD therapy costs (from $1392 to $1740). The results were sensitive to the percentage of patients requiring repeat endoscopy before wireless pH monitoring and the cost of PPIs. CONCLUSIONS: Timely and increased use of pH monitoring as recommended in published guidelines leads to less unnecessary use of PPIs with a modest budgetary impact on health plans.

A protein binding assay for hyaluronate.

A relatively quick and simple assay for hyaluronate was developed using the specific binding protein, hyaluronectin. The hyaluronection was obtained by homogenizing the brains of Sprague-Dawley rats, and then centrifuging the homogenate. The resulting supernatant was used as a source of crude hyaluronectin. In the binding assay, the hyaluronectin was mixed with [3H]hyaluronate, followed by an equal volume of saturated (NH4)2SO4, which precipitated the hyaluronectin and any [3H]hyaluronate associated with it, but left free [3H]hyaluronate in solution. The mixture was then centrifuged, and the amount of bound [3H]hyaluronate in the precipitate was determined. Using this assay, we found that hyaluronectin specifically bound hyaluronate, since other glycosaminoglycans failed to compete for the binding protein. In addition, the interaction between hyaluronectin and hyaluronate was of relatively high affinity (Kd = 5.7 X 10(-10) M), and the size of the hyaluronate did not appear to substantially alter the amount of binding. To determine the amount of hyaluronate in an unknown sample, we used a competition assay in which the binding of a set amount of [3H]hyaluronate was blocked by the addition of unlabeled hyaluronate. By comparing the degree of competition of the unknown samples with that of known amounts of hyaluronate, it was possible to determine the amount of hyaluronate in the unknowns. We have found that this method is sensitive to 1 microgram or less of hyaluronate, and is unaffected by the presence of proteins.

Helicobacter pylori: ulcers and more: the beginning of an era.

Helicobacter pylori (H. pylori) may be found in up to 50% of the world's population, making it the most common infectious disease worldwide. H. pylori is a gram-negative, microaerophilic rod with flagella and normally resides in the stomach. It can be diagnosed endoscopically, via breath tests, or through a simple blood test. H. pylori can usually be eradicated with a combination of proton pump inhibitors and antibiotics. Although most people infected with this organism never develop a complication, H. pylori infection in others may produce significant mucosal inflammation leading to ulcers in the stomach and duodenum. H. pylori has also been recognized as a risk factor for the development of both gastric carcinoma and mucosal-associated lymphoid tumor. Although not widely known, H. pylori can also affect organ systems outside of the gastrointestinal tract. It is now apparent that H. pylori can infect the skin, liver and heart and that these infections may produce a number of different disease states. In addition, H. pylori infection can adversely affect the nutritional status of both children and adults. This article discusses the epidemiology and bacteriology of H. pylori, reviews the different methods of diagnosing and treating this common infection, and then focuses on the effects that H. pylori has on different organ systems within the body, including the nutritional status of those affected.