Search PubMed⌕ Search

Biomedical subjects

Henry P Parkman

Publications and source records attributed to Henry P Parkman.

At least 19 recordsLinked to original sources
PubMed2006

Abnormal ghrelin and pancreatic polypeptide responses in gastroparesis.

Vagal nerve dysfunction has been implicated in the pathogenesis of diabetic gastroparesis, but its role in idiopathic gastroparesis remains uncertain. The increase in pancreatic polypeptide with sham feeding is often used as a measure of vagal integrity. Ghrelin has been suggested to function as an appetite-stimulating hormone from the gut to the brain acting through vagal afferent pathways. Systemic ghrelin also rises in part due to vagal efferent pathways. Alterations in ghrelin and its effects on appetite could play a role in gastroparesis. In this study we aimed [1] to investigate the presence of vagal nerve dysfunction in patients with idiopathic and diabetic gastroparesis and [2] to determine if alterations in ghrelin concentrations occur in gastroparesis. Normal subjects and patients with diabetic, idiopathic, or postsurgical gastroparesis underwent a sham feeding protocol. Serial blood samples were obtained for plasma ghrelin and pancreatic polypeptide. Sham feeding was characterized by an increase in pancreatic polypeptide and ghrelin in normal controls and patients with idiopathic gastroparesis. The changes in pancreatic polypeptide and ghrelin levels in diabetic and postsurgical gastroparesis were significantly less than those in normal subjects. Vagal nerve dysfunction, as evidenced by an impaired pancreatic polypeptide response with sham feeding, is present in diabetic gastroparesis but not idiopathic gastroparesis. Systemic ghrelin concentrations increased with sham feeding in normal subjects and patients with idiopathic gastroparesis but not in diabetic or postsurgical gastroparesis. Vagal function and regulation of ghrelin levels are impaired in diabetic gastroparesis.

Adult↗
PubMed2006

Delayed gastric emptying: whom to test, how to test, and what to do.

Gastroparesis, or delayed gastric emptying, is a common cause of chronic nausea and vomiting as seen in a gastroenterology practice. Diabetic, postsurgical, and idiopathic causes remain the three most common forms of gastroparesis. In addition to nausea and vomiting, symptoms of gastroparesis may include early satiety, postprandial fullness, and abdominal pain. Physiologic changes that may explain symptoms in patients with gastroparesis, in addition to delayed gastric emptying, include impaired fundic accommodation, antral hypomotility, gastric dysrhythmias, pylorospasm, and perhaps visceral hypersensitivity. Diagnosis of gastroparesis is best determined using a radioisotope-labeled solid meal with scintigraphic imaging for at least 2 hours, and preferably 4 hours, postprandially. Most commonly, a 99mTc sulfur colloid-labeled egg sandwich with imaging at 0, 1, 2, and 4 hours is used. Extension of the gastric emptying test to 4 hours improves the accuracy of the test, but unfortunately, this is not commonly performed at many centers. Emptying of liquids remains normal until the late stages of gastroparesis and is less useful. The aims of treatment should be to control symptoms and maintain adequate nutrition and hydration. Patients should be advised to eat small meals and to limit their intake of fat and fiber. Additional dietary recommendations may include increasing caloric intake in the form of liquids. For diabetic patients, control of blood glucose levels is important, as symptom exacerbation is frequently associated with poor glycemic control. Specific treatment often begins with metoclopramide, 10 mg, up to four times daily, after a discussion of possible side effects with the patient. An antiemetic agent, such as prochlorperazine, 5 to 10 mg orally or 25 mg by suppository, can be added on an as-needed basis every 4 to 6 hours to control nausea. If these antiemetic medications are not effective, or if side effects develop, orally dissolving ondansetron, 8 mg every 8 to 12 hours, can be tried on an as-needed basis. If this regimen is unsuccessful, then alternative prokinetic agents--erythromycin, 125 mg, or tegaserod, 6 mg, prior to meals--can be tried. For cases refractory to these treatments, referral to a center with US Food and Drug Administration permission to use domperidone should be considered. Alternatively, symptom modulators such as low-dose tricyclic antidepressants can be tried to reduce symptoms, but these do not improve gastric emptying. In patients for whom all medical therapy fails, other options that are tried at experienced centers include the injection of botulinum toxin into the pylorus, placement of a feeding jejunostomy, and/or placement of a gastric electrical stimulator.

Journal Article↗
PubMed2006

Update on gastrointestinal scintigraphy.

Nuclear medicine offers a variety of studies for evaluating motility throughout the gastrointestinal tract. Gastric emptying remains the "gold standard" for studying gastric motor function, but its application in most centers remains limited to measuring only total gastric emptying in spite of data that show assessment of both fundal and antal function is of clinical value for evaluating patients with dyspepsia. Similarly, newer methods to study small bowel and colon transit have not gained widespread use. This review summarizes the state-of-the-art of prior established and newer scintigraphic studies with an emphasis on their clinical applications.

Gastric Emptying↗
PubMed2006

Training in gastrointestinal motility.

Gastrointestinal (GI) motility and functional GI disorders are common reasons for patients to see gastroenterologists. Knowledge of the evaluation and treatment of these disorders is important to appropriately care for these patients in clinical practice. Training in GI motility is important to GI fellows and their subsequent role as gastroenterologists. The aim of this paper is to discuss the importance of GI motility disorders for trainees in gastroenterology, provide some suggestions for training activities for GI fellows in GI motility, and discuss ways to address the unmet clinical need for caring for patients with GI motility disorders that gastroenterologists routinely see in their clinical practice.

Gastroenterology↗
PubMed2005

Detection of JC virus DNA sequences and expression of viral T antigen and agnoprotein in esophageal carcinoma.

BACKGROUND: The human polyomavirus JC virus (JCV) causes progressive multifocal leukoencephalopathy. Subclinical infection with JCV occurs in 85-90% of the population worldwide. The virus usually remains latent but can reactivate under immunosuppressive conditions, resulting in progressive multifocal leukoencephalopathy. JCV is oncogenic in experimental animals and is associated with human brain tumors. JCV is found in normal mucosa of the gastrointestinal tract, and some colon carcinomas express the oncogenic JCV T-antigen protein. The objective of this study was to examine the presence of JCV DNA sequences and JCV protein expression in normal and malignant human esophageal tissues. METHODS: The authors examined the presence of JCV DNA sequences and protein expression in normal and malignant human esophageal tissues. Seventy well characterized biopsy specimens from patients with a spectrum of esophageal disorders were studied by immunohistochemistry, and 18 specimens were analyzed further by polymerase chain reaction amplification. RESULTS: JC viral DNA was isolated from 11 of 13 normal esophageal biopsy specimens (85%) and from 5 of 5 esophageal carcinomas (100%). Using immunohistochemistry, JCV T antigen was detected in 10 of 19 carcinomas (53%), agnoprotein was detected in 8 carcinomas (42%), p53 tumor suppressor was detected in 11 carcinomas (58%), and beta-catenin was detected in 4 carcinomas (21%). Zero of 51 normal, benign, and premalignant esophageal samples expressed viral proteins. Laser-capture microdissection verified the presence and specificity of JCV DNA sequences. beta-Catenin and p53 were colocalized with JCV T-antigen in the nuclei of neoplastic cells. CONCLUSIONS: The results provide evidence for infection of gastrointestinal tract cells by JCV and suggest a potential role of JCV in the development of upper digestive tract carcinomas.

Adult↗
PubMed2005

Increased Barrett's esophagus for the decade between 1991 and 2000 at a single university medical center.

Barrett's esophagus is being diagnosed increasingly in the United States. The aim of this study was to determine whether the increased diagnosis of Barrett's esophagus is due to endoscopic reporting and/or a truly increasing rate. This retrospective study reviewed 18,183 endoscopy reports at Temple University Hospital from January 1991 through December 2000. Annual rates of new cases of endoscopically suspected Barrett's esophagus were determined. Biopsy results were reviewed for the diagnosis of Barrett's esophagus (i.e., specialized intestinal metaplasia). Rates of Barrett's esophagus increased from 3.22 to 8.28 per 100 endoscopies (257%; P < 0.01) on endoscopy and from 0.67 to 2.76 per 100 endoscopies (412%; P < 0.01) on histology from 1991 to 2000. Twenty-four and seven-tenths percent (252/1020) of patients suspected at endoscopy to have Barrett's esophagus were confirmed by histology. This study demonstrates an increasing rate of new cases of suspected Barrett's esophagus on endoscopy and confirmed Barrett's esophagus on histology over the last decade. The endoscopic impression of Barrett's esophagus was about four times higher than the confirmed diagnosis of Barrett's esophagus (intestinal metaplasia) on histology.

Academic Medical Centers↗
PubMed2005

Regional postprandial differences in pH within the stomach and gastroesophageal junction.

Our objective was to determine regional differences in intragastric pH after different types of meals. Ten normal subjects underwent 27-hr esophagogastric pH monitoring using a four-probe pH catheter. Meals were a spicy lunch, a high-fat dinner, and a typical bland breakfast. The fatty dinner had the highest postprandial buffering effect, elevating proximal and mid/distal gastric pH to 4.9 +/- 0.4 and 4.0 +/- 0.4, respectively, significantly (P < 0.05) higher compared to 4.2 +/- 0.3 and 3.0 +/- 0.4 for the spicy lunch and 3.0 +/- 0.3 and 2.5 +/- 0.8 for the breakfast. The buffering effect of the high-volume fatty meal to pH > 4 was also longer (150 min) compared to that of the spicy lunch (45 min) and the bland breakfast, which did not increase gastric pH to > 4 at any time. Proximal gastric acid pockets were seen between 15 and 90 min postprandially. These were located 3.4 +/- 0.8 cm below the proximal LES border, extending for a length of 2.3 +/- 0.8 cm, with a drop in mean pH from 4.7 +/- 0.4 to 1.5 +/- 0.9. Acid pockets were seen equally after the spicy lunch and fatty dinner but less frequently after the bland breakfast. We conclude that a high-volume fatty meal has the highest buffering effect on gastric pH compared to a spicy lunch or a bland breakfast. Buffering effects of meals are significantly higher in the proximal than in the mid/distal stomach. Despite the intragastric buffering effect of meals, focal areas of acidity were observed in the region of the cardia-gastroesophageal junction during the postprandial period.

Adult↗
PubMed2005

Chronic Intestinal Pseudo-Obstruction.

Chronic intestinal pseudo-obstruction (CIP) is a gastrointestinal motility disorder characterized by chronic symptoms and signs of bowel obstruction in the absence of a fixed, lumen-occluding lesion. Radiographic findings consist of dilated bowel with air-fluid levels. Pseudo-obstruction is an uncommon condition and can result from primary or secondary causes. The management is primarily focused on symptom control and nutritional support to prevent weight loss and malnutrition. The principles of management of patients with CIP involve 1) establishing a correct clinical diagnosis and excluding mechanical obstruction; 2) differentiating between idiopathic and secondary forms; 3) performing a symptomatic and physiologic assessment of the parts of the gastrointestinal (GI) tract involved by manometric and whole gut transit scintigraphic studies; 4) careful assessment of nutritional status of the patient; and 5) developing a therapeutic plan addressing the patient's symptoms and nutritional status. Treatment of CIP includes frequent small meals with a low-fat, low-fiber diet, liquid nutritional supplements may be needed; prokinetic agents such as metoclopramide may help to reduce upper GI symptoms. Trials of drugs such as erythromycin, domperidone, cisapride, and tegaserod may be considered if there is no response. Subcutaneous octreotide may be helpful to improve small bowel dysmotility especially in patients with scleroderma. In patients with symptoms suggestive of bacterial overgrowth, courses of antibiotics such as metronidazole, ciprofloxacin, and doxycycline may be needed. Nutritional assessment and support is an important aspect of management. Enteral nutrition is usually preferred. In carefully selected patients, feeding jejunostomy with or without decompression gastrostomy may be tried. Long term parenteral nutrition should be reserved for patients who can not tolerate enteral nutrition. Complications associated with total parenteral nutrition include infections, sepsis, and cholestatic hepatic dysfunction.

Journal Article↗
PubMed2005

Cholecystokinin (CCK) down regulates PGE2 and PGI2 release in inflamed Guinea pig gallbladder smooth muscle cell cultures.

This study examines the hypothesis that cholecystitis down-regulates Guinea pig gallbladder (GPGB) smooth muscle cholecystokinin (CCK)-stimulated prostaglandin (PG) release. Guinea pig gallbladder from Control and 48 h bile duct ligated (BDL) animals were placed in cell culture and grown to confluence. The cultures underwent Western Blot analysis for smooth muscle cell content of COX-1, COX-2, Prostacyclin Synthase (PS), or were incubated with CCK at 10(-8)M or 10(-6)M with and without indomethacin for 1h and analyzed for release of 6-keto-PGF1alpha, PGE2 and TxB2 by EIA. BDL increased Guinea pig gallbladder cell culture basal PGE2 and PGI2 release which was in part due to increased COX-2 content. CCK incubation down-regulated BDL Guinea pig gallbladder cell culture release of 6-keto-PGF1alpha and PGE2 and down-regulated COX-2 content but did not alter the Control group. The decrease in CCK-mediated BDL cell Guinea pig gallbladder release may be an endogenous mechanism to limit physiologic derangements induced by increased endogenous gallbladder PG synthesis during early acute cholecystitis.

Animals↗
PubMed2005

Endoscopic pyloric injection of botulinum toxin A for the treatment of refractory gastroparesis.

BACKGROUND: Botulinum toxin A injected into the pyloric sphincter has been reported in small case series to treat gastroparesis. This study reviews the use of this treatment in a large number of patients with gastroparesis. METHODS: Patients who underwent pyloric botulinum injection for treatment of gastroparesis were identified. Response was defined as improvement or resolution of the patient's major symptom and/or two minor symptoms for 4 weeks. RESULTS: Of 115 patients treated, 63 patients met the study criteria. There were 53 women, 10 men, mean age 42 years. Most patients (56%) had idiopathic gastroparesis. Twenty-seven of 63 (43%) patients experienced a symptomatic response to treatment. By stepwise logistic regression, male gender was associated with response to treatment (OR 3.27: 95% CI[1.31, 8.13], p = 0.01). Vomiting as a major symptom was associated with a lack of response (OR 0.16: 95% CI[0.04, 0.67], p = 0.01). Despite the association of male gender with response, the mean duration of response for those patients responding, with a minimum of 3 months' follow-up was 4.9 months (+/-2.7 months) for women and 3.5 months (+/-0.71 months) for men (p = 0.59). The corresponding medians and interquartile ranges (IQR) were 5 (IQR 3-6) for females and 3.5 (IQR 3-4) for males. CONCLUSIONS: Of the patients, 43% had a response to botulinum toxin treatment that lasted a mean of approximately 5 months. Male gender was associated with a response to this therapy; however, durability of response was unrelated to gender. Vomiting as a major symptom predicted no response.

Abdominal Pain↗
PubMed2004

Regional gastric contractility alterations in a diabetic gastroparesis mouse model: effects of cholinergic and serotoninergic stimulation.

The C57BLKS/J db/db mouse develops hyperglycemia and has delayed gastric emptying that is improved with tegaserod, a partial 5-HT4 agonist. Our aims here were to determine regional gastric contractility alterations in C57BLKS/J db/db mice and to determine the effects of serotonin and tegaserod. The contractile effects of bethanechol, serotonin, and tegaserod in fundic, antral, and pyloric circular muscle were compared in C57BLKS/J db/db mice and normal littermates. The effects of tetrodotoxin, atropine, and 5-HT receptor antagonists were studied. Contractions in response to bethanechol were decreased in the fundus, similar in the antrum, but increased in the pylorus in diabetic mice compared with controls. Serotonin and, to a lesser extent, tegaserod caused contractions that were more pronounced in the fundus than in the antrum and pylorus in both diabetic and normal mice. Serotonin-induced contractions were partially inhibited by atropine, the 5-HT4 antagonist GR113808, and the 5-HT2 antagonist cinanseron but not tetrodotoxin. Regional gastric contractility alterations are present in this diabetic gastroparesis mouse model. Fundic contractility was decreased, but pyloric contractility was increased in the pylorus to cholinergic stimulation in diabetic mice. Serotonin's contractile effect is mediated, in part, through muscarinic, 5-HT2, and 5-HT4 receptors. This study suggests that fundic hypomotility and pyloric hypercontractility, rather than antral hypomotility, play important roles for the gastric dysmotility that occurs in diabetes.

Animals↗
PubMed2004

The use of botulinum toxin for the treatment of gastrointestinal motility disorders.

Botulinum toxin type A is used extensively for the management of gastrointestinal smooth muscle disorders. This review is a comprehensive summary of the current status of this therapy. It includes English-language research from 1966 to 2003 and relevant abstracts from subspecialty meetings from the past 3 years. Botulinum toxin appears to be beneficial for achalasia, gastroparesis, sphincter of Oddi dysfunction, anal fissure and anismus. Very few placebo-controlled trials have been performed despite widespread use of toxin for the past 10 years. Botulinum toxin appears to be safe and side effects are uncommon. Despite uncontrolled data, botulinum toxin is now used for a variety of spastic disorders of GI smooth muscle. In some instances this therapy may preclude the need for more invasive treatments. Controlled trials are needed.

Anti-Dyskinesia Agents↗
PubMed2004

Esophageal bacteria and Barrett's esophagus: a preliminary report.

The objective of this study was to investigate if esophageal bacteria are associated with Barrett's esophagus (BE). This study was comprised of a retrospective (Part 1) and a subsequent prospective (Part 2) study. In Part 1, Gram stains were performed on esophageal biopsy specimens obtained in 47 patients. Bacteria were quantitated from 0 to 4. In Part 2, Gram stains and cultured bacterial counts of esophageal biopsies were obtained in 18 GERD patients (9 with BE and 9 without BE). Part 1 results were as follows. Bacteria were found in 37 of 47 esophageal biopsies. Quantitative bacterial stain scores for BE (2.5 +/- 0.2) were higher than for non-BE (1.5 +/- 0.3; P = 0.02). The quantitative bacterial stain scores correlated with increasing severity of dysplasia (r = 0.37, P = 0.028). In Part 2, bacteria were found in 8 of 18 esophageal biopsies by Gram stain (6 of 9 patients with BE vs. 2 of 9 non-BE). The distal esophageal bacterial stain scores in BE patients (1.6 +/- 0.5) were higher than in those without BE (0.4 +/- 0.3; P = 0.07). Patients on proton pump inhibitors tended to have higher bacterial stain scores (1.2 +/- 0.4) than patients who were not (0.7 +/- 0.3; P = 0.45). Bacterial colony counts were similar in patients with BE compared to those without BE. In conclusion, bacteria in esophageal biopsies were detected more often in BE than non-BE. Increasing bacterial stain scores were associated with metaplasia and increasing dysplasia. Esophageal bacteria, possibly related to stasis or gastric acid suppression therapy, may play a role in the pathogenesis of BE and dysplasia.

Adult↗
PubMed2004

Multichannel electrogastrography (EGG) in normal subjects: a multicenter study.

The aim of this study was to record gastric myoelectric activity using multichannel electrogastrography (EGG) and to determine if there are differences due to age, gender, body mass, and study location. In 61 normal subjects from four centers, fasting multichannel EGG was recorded for 1 h, followed by two 1-h postprandial recordings after a test meal. Variables assessed included dominant frequency (DF) and its power, percentage time in 2- to 4-cpm frequency, and percentage slow-wave coupling (%SWC). There were no significant differences in EGG parameters with respect to gender or age. Subjects with a BMI > 25 had a decrease in the absolute DF power but a similar increase in the postprandial DF power. Subjects with a BMI > 25 had a postprandial decrease in the %SWC compared to those with a BMI < 25. There was a decrease in postprandial %SWC in European/Asian centers compared to American centers. In conclusion, multichannel EGG provides assessment of electrical slow-wave coupling in addition to determining dominant frequency, power, and percentage normal rhythm. This multicenter study of normal subjects shows similar multichannel EGG values among different genders and ages. Body mass and ethnicity may impact on some of the EGG values.

Adolescent↗
PubMed2004

Multichannel electrogastrography (EGG) in symptomatic patients: a single center study.

OBJECTIVES: To determine the value of multichannel versus conventional single-channel electrogastrography (EGG) and of an additional postprandial hour recording in symptomatic patients. METHODS: Eighteen normal subjects and 47 patients with upper GI symptoms underwent multichannel EGG with four cutaneous recording electrodes placed on the antral axis. Fasting EGG was recorded for 1 h, followed by meal ingestion, followed by two 1-h postprandial EGG recordings. Variables assessed: (1) dominant frequency (DF) and its power; (2) percent time in normal (2-4) cpm frequency; (3) average percent of slow wave coupling (% SWC). RESULTS: Normal values for single-channel EGG were: (1) DF from 2.5-3.3, 2.7-3.5, and 2.6-3.5 cpm in the fasting, first, and second postprandial hours; (2) percentage of time in 2-4 cpm: >50%, >65%, and >65% in the fasting, first, and second postprandial hours. Normal values for percent SWC using multichannel EGG were >50%, >55%, >55% in the fasting, first, and second postprandial hours. In the symptomatic patients, an abnormal 2-h single-channel EGG was obtained in 16 of 47 (34%) patients. Adding an additional 1 h of postprandial recording identified another 4 abnormal patients (20/47 = 43%). With multichannel EGG, abnormal results were obtained in 24 of 47 patients (51%) with the 2-h study. An additional 1 h of postprandial recording identified another 4 patients as abnormal (28/47 = 60%). CONCLUSIONS: Multichannel EGG recording improved the detection of abnormal gastric myoelectric activity in symptomatic patients. This study also demonstrates prolonging the postprandial recording to 2 h increases the diagnostic yield for both single-channel and multichannel EGG.

Adult↗