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Biomedical subjects

C E Pope

Publications and source records attributed to C E Pope.

At least 37 records · Page 2Linked to original sources

The gastroesophageal flap valve: in vitro and in vivo observations.

BACKGROUND: This study was performed to confirm the presence and significance of a gastroesophageal flap valve. METHODS: The pressure gradient needed to induce reflux across the gastroesophageal junction and the level of a high-pressure zone were determined in 13 cadavers. On inspection in the cadavers, a mucosal flap valve at the entrance of the esophagus into the stomach was seen through a gastrostomy. This valve was deficient or absent in cadavers with a hiatal hernia. The valve was inspected in controls and in patients with reflux with a retroflexed endoscope. RESULTS: In cadavers with no hiatal hernia, a gradient across the gastroesophageal junction was present in nearly all cadavers. The gradient could be increased by surgically accentuating the valve without a concomitant rise in pressure in the high-pressure zone. Reduction of the hiatal hernia in the cadaver and anchoring of the gastroesophageal junction to the normal attachment to the preaortic fascia restored the valve and the gradient as seen through a gastrostomy. Control subjects had a prominent fold of tissue that extended 3 to 4 cm along the lesser curve of the stomach and tightly grasped the shaft of the endoscope. This was diminished or absent in reflux patients. Inspection of the valve in control subjects and subjects with reflux allowed for a grading system with Grades I through IV. This grading system was applied to a cohort of patients with and without reflux. The appearance of the flap valve was a better predictor of the presence or absence of reflux than was lower esophageal sphincter pressure. Endoscopic viewing of the valve during surgery can confirm that a competent valve has been reconstructed. CONCLUSIONS: Grading of the gastroesophageal valve is simple, reproducible, and offers useful information in the evaluation of patients with suspected reflux undergoing endoscopy.

Esophagogastric Junction↗

Successful in vitro and in vivo development of in vitro fertilized two- to four-cell cat embryos following cryopreservation, culture and transfer.

In vitro and in vivo survival of in vitro-derived 2- to 4-cell cat embryos following cryopreservation was examined. Prefreeze 1- vs 2-step cryoprotectant exposure (Experiment 1) and warming method (Experiment 2) on zona pellucida damage and development in vitro were compared. To determine viability in vivo, frozen/thawed embryos were cultured in vitro to the morula/early blastocyst stage and transferred to synchronous recipients (Experiment 3). At 24 to 26 h after IVF, embryos were cryopreserved in 1.4 M propanediol (Pr)+0.125 M sucrose (Su) by cooling at 0.3 degrees C/min from -6 degrees C to -30 degrees C and storing in liquid nitrogen. Autologous embryos were cultured in vitro for 7 d. After warming for 5 sec in air and 10 sec at 37 degrees C in water (Experiments 1 to 3), or at room temperature air (22 degrees C; Experiment 2), the cryoprotectant was removed and embryos were cultured in vitro for 6 d (Experiments 1 and 2). Development was assessed after staining by counting cell numbers/embryo and determining the percentages at the 2- to 4-cell (nonsurvivor), pre (5 to 15), early (16 to 32), mid (33 to 50), late (>50) morula or blastocyst stages. Post-thaw development to late morula/blastocyst after 1-step exposure (68%, 15 min Pr+Su) was higher (P<0.05) than that after 2-step exposure (36%, 15 min Pr and 15 min Pr+Su). Both warming methods produced similar percentages of embryos with damaged zonae (13 to 15%) and equivalent development to morula/blastocyst (64 to 69%). Development in vitro to early morula/blastocyst of frozen embryos with intact zonae was similar to that of nonfrozen embryos. Following cryopreservation, most 2- to 4-cell cat embryos retained their capability for in vitro development to morula/blastocyst, and in vivo viability was demonstrated by the birth of 3 live kittens to 2 of 4 recipients following the transfer of 58 embryos.

Journal Article↗

In vitro fertilization in domestic and non-domestic cats including sequences of early nuclear events, development in vitro, cryopreservation and successful intra- and interspecies embryo transfer.

The domestic cat may be used as a model for developing assisted reproduction techniques including in vitro fertilization (IVF), embryo culture, cryopreservation and embryo transfer (ET) for application to threatened and endangered species of non-domestic cats. Interoestrous domestic cats were injected with a total of 1.0-6.0 mg follicle-stimulating hormone (FSH) daily for 4 days and with 100 iu human chorionic gonadotrophin (hCG) on day 5. Follicular oocytes recovered at 26 +/- 1 h after hCG were co-incubated for 4-6 h at 38 degrees C in 5% CO2 with spermatozoa (1-2 x 10(5) motile spermatozoa ml-1) collected by artificial vagina. To determine the timing of sperm penetration and early fertilization events in vitro, oocytes were fixed and examined at intervals from 0.5 to 10 h after sperm exposure. The penetration rate of metaphase II (MII) oocytes at 0.5-3 h was equivalent to that at 3-6 h (95 versus 96%). Second polar body extrusion, pronuclear formation and apposition were observed at 2, 6-8 and 10 h, respectively. Simple (Tyrode's) and complex (F-10, M-199 and CMRL-1066) culture media with 10% fetal calf serum were compared for their ability to support development to the morula or blastocyst stage during culture periods of 96-168 h after IVF. The average number of cells per embryo was similar (P > 0.05) in the various media at each interval except that CMRL-1066 reduced (P < 0.05) development at 96 h if it was used before the two-cell stage. In F-10, neither the presence of intact cumulus cells nor changing to fresh F-10 medium at 48 h affected development at 96 h. Blastocyst development at 168 h was similar in both F-10 (18%) and Tyrode's (26%). To determine developmental ability in vivo, IVF-derived embryos (n = 586) were transferred at 96 or 120 h to recipients (n = 49) that had undergone synchronous oocyte recovery as donors. The percentage of recipients producing kittens after transfer of embryos cultured for 96 or 120 h in F-10 was 31 and 25, respectively, compared with 55% of 120 h recipients receiving embryos cultured in M-199 or Tyrode's. Overall, more pregnancies occurred following transfer of > or = 12 embryos (11/26) than if < 12 embryos were transferred (6/23).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Medical and surgical treatment of nonallergic asthma associated with gastroesophageal reflux.

Patients presenting to a chest clinic because of adult-onset wheezing with no history of allergy had a 90 percent prevalence of gastroesophageal reflux, even though reflux symptoms were mild or absent. Ninety patients were randomly assigned to receive cimetidine or an identical placebo or to undergo antireflux surgery. During a six-month period, all groups improved clinically; the cimetidine and surgical groups improved more than the placebo group. The intake of pulmonary medication decreased significantly in both cimetidine and surgical groups. Pulmonary function test results improved in the cimetidine- and surgically treated patients; improvement was not statistically significant. At long-term follow-up, the surgical group maintained clinical improvement and decreased pulmonary medication intake, whereas the placebo group worsened. We conclude that gastroesophageal reflux can play a significant role in some patients with nonallergic pulmonary disease and that its treatment can improve pulmonary symptoms and objective measurements of pulmonary function.

Adult↗

A baboon model for pregnancy-associated antigens (PAPP-A, PP5, PP14).

By radioimmunoassays established on human derived antigens, PAPP-A, PP5 and PP14 immunoreactivity was detected in placental extracts and blood of pregnant baboons. None of the serial dilution curves suggested parallelism between respective human and baboon samples. Based on slopes of regressed logit-log transformed binding data, PAPP-A demonstrated the greatest degree of interspecies immunological crossreactivity. PP14 showed the least conservation of antigenic determinants. Physicochemical characterization on heparin, zinc chelate and bovine thrombin affinity matrices could not distinguish human from baboon-derived antigens. As in the human, baboon PAPP-A and PP5 were not detected in blood of male or non-pregnant animals. PP14 was detected in baboon follicular fluid, and only PP5 immunoreactivity was measured in culture media of baboon embryos. Of the three antigens, PAPP-A was detected in pregnant baboons at about 61 days gestation, that is, 4 weeks before PP5 and PP14. With the exception of PP14 which attained peak concentration at 118 days of pregnancy, PAPP-A and PP5 concentrations were greatest at term. In conjunction with physicochemical and immunological criteria, these physiological kinetics clearly support a role for developing a baboon model to serve for further studies into feto-maternal signals, particularly antigens such as PAPP-A and PP5.

Animals↗

Extended esophageal pH monitoring. An analysis of the literature and assessment of its role in the diagnosis and management of gastroesophageal reflux.

In this review article we examine several facets of extended pH monitoring of the esophagus. The different types of instrumentation and the technical difficulties of obtaining and interpreting tests are discussed. The wide variations among different laboratories in the duration and timing of pH monitoring sessions are summarized. We outline the problems in interpretation and reproducibility such as normal control values, criteria for separation of abnormal from normal subjects, correlation of pH events with symptoms and with esophageal injury. Comparison of extended with short-term monitoring of esophageal pH are drawn, as well as comparisons between results of extended monitoring and other tests of reflux. Cost considerations are listed. Finally, we present a proposed scheme for the use of extended pH monitoring as well as a cautious note about accepting extended pH monitoring as a routine clinical test at present.

Costs and Cost Analysis↗

Respiratory complications of gastro-oesophageal reflux.

The association between pulmonary symptoms and gastro-oesophageal reflux has been well documented. However, it is still unclear whether abnormal pulmonary function causes increased reflux or reflux causes pulmonary symptoms. Available data suggest that both theories may be accurate. Clinical features of patients with reflux-induced pulmonary complications have been identified, although there are no specific methods for confirming this diagnosis. An algorithm that defines a series of diagnostic tests is presented. From the results of the small number of published clinical trials, it appears that antireflux surgery is the most effective and longest-lasting treatment for the correction of pulmonary symptoms.

Algorithms↗

Effect of stress on oesophageal motor function in normal subjects and in patients with the irritable bowel syndrome.

Stress can modulate the motor function of the stomach, small bowel, and colon in healthy subjects, and of the small bowel and colon in patients with the irritable bowel syndrome (IBS). The effect of stress on oesophageal motility in eight healthy subjects and in eight IBS patients was studied, using two pressure transducers positioned just above the lower oesophageal sphincter and 5 cm proximally. Stressors were: a video arcade game, delayed audio feedback, and hand immersion in cold water. Each stress period was followed by five swallows of water. Frequency and amplitude of oesophageal contractions and the number of simultaneous and multipeaked contractions were manually counted for each stress period and compared to the preceding rest period. Frequency of contractions (per minute) tended to decrease during stress periods, but achieved significance only with the video arcade game in the control group (2.0 (0.6) v 1.2 (0.4); p less than 0.01). No other trend was evident in either control or IBS patients. No abnormalities of oesophageal body function were recorded in IBS patients either in basal conditions, or under stress. Unlike the more complex motor programmes elsewhere in the gut, the preprogrammed nature of oesophageal peristalsis is not modulated by stress.

Adult↗

Cryopreservation and transfer of baboon embryos.

The feasibility of modifying bovine cryopreservation methods for use with baboon embryos was evaluated. Twenty-six baboon embryos at the eight-cell to blastocyst stage of development were transferred after being frozen using glycerol as cryoprotectant. Either a two-step fast of a controlled linear temperature depression was achieved to -40 degrees C, followed by plunging into liquid nitrogen. After thawing, embryos were rehydrated in medium containing sucrose (0.5 to 1.0 M) using various methods of glycerol dilution. Embryos were transferred nonsurgically to anesthetized recipient baboons. Two term pregnancies resulted from six embryos frozen using the controlled linear cooling method and rehydrated by dropwise dilution of the sucrose (0.8 M) medium. Later cell stages had a greater morphological integrity postthaw than did earlier developmental stages, and embryos frozen by the linear cooling-rate method had less cell damage than those frozen by the fast method.

Animals↗

Electromyography of human oesophageal smooth muscle.

The aim was to study whether electromyography (EMG) activity is synchronous with oesophageal motor activity as assessed by manometry from the same oesophageal site. Patients with different motor disorders of the oesophagus and control subjects were investigated. EMG recordings were made by means of a suction capsule with silver/silver chloride spike electrodes. Slow EMG waves synchronous with respiration were recorded from the lower oesophageal sphincter and intermittently from the body of the oesophagus. Edrophonium increased spike discharges; atropine diminished or abolished spike discharges after swallowing. Swallowing caused a burst of spiking activity which began immediately after deglutition. Continuous sips of water produced constant EMG activity but no peristaltic contractions as seen by manometry. In a patient with scleroderma and aperistalsis, swallowing elicited vigorous electrical activity. The different EMG findings without simultaneous contractions at manometry are interpreted as a response to a swallow by the longitudinal muscle of the oesophagus.

Animals↗

Severe idiopathic constipation is associated with a distinctive abnormality of the colonic myenteric plexus.

We analyzed the clinical, radiographic, esophageal manometric, and pathologic features of 26 women with severe, idiopathic constipation. Twenty-four patients were between 19 and 39 yr of age. Stool frequency was once every 5-28 days. On barium enema examination, 9 of 24 patients had colons of increased length and 4 of these 9 patients had colons of increased width (greater than 10 cm). Radionuclide solid-meal gastric-emptying studies were normal in 23 patients tested. Esophageal manometry demonstrated high-amplitude waves in 10 of 22 patients and long-duration waves in 3 of these 10 patients. Rectal biopsy specimens showed normal submucosal neurons in all patients and melanosis coli in 6. Twelve patients underwent subtotal colectomies for constipation. Conventional light microscopy using hematoxylin and eosin serial sections showed (a) melanosis coli in 4 patients; (b) normal smooth muscle in 11; (c) thinning of the circular muscle in 1; and (d) no apparent abnormalities of the myenteric plexus in any. In contrast, silver stains of the myenteric plexus showed (a) quantitatively reduced numbers of argyrophilic neurons in 10 patients; (b) morphologically abnormal argyrophilic neurons in 11; (c) decreased numbers of axons in 11; and (d) increased numbers of variably sized nuclei within ganglia in all 12. A coded analysis of the silver stains of colons from 8 patients with constipation and 19 control cases demonstrated that the pathologic abnormalities of severe idiopathic constipation could be differentiated from controls. Thus, severe idiopathic constipation is associated with a pathologically identifiable abnormality of the myenteric plexus. This abnormality appears different from anything previously described in intestinal pseudoobstruction.

Adult↗

Measurement of esophageal reflux by scintigraphy.

Gastroesophageal reflux and clearance of the refluxed material can be measured by plotting a time-activity curve from an esophageal area of interest after 1 mCi of 99mTc sulfur colloid is placed in the stomach. Control subjects do not have peaks exceeding a value twice that of the baseline count levels. Reflux patients exceed this value, either spontaneously or after Valsalva maneuvers. This technique has a sensitivity which is greater than that of barium and equal to the sensitivity of a pH probe in patients with both moderate and severe reflux. Scintigraphic reflux was shown in 62% of moderate refluxes and 85% of those with severe reflux as defined clinically. Clearing of the refluxed material occurs rapidly in most patients if measured by this scintigraphic technique. This test can be performed rapidly with minimal radiation exposure and is noninvasive.

Adult↗