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Biomedical subjects

S Shirazi

Publications and source records attributed to S Shirazi.

At least 19 recordsLinked to original sources
PubMed1996

Role of altered responsiveness of hypertrophic smooth muscle in manometric abnormalities of the obstructed opossum oesophagus.

The movements of the obstructed oesophagus are abnormal, but whether this relates to the disease causing the obstruction, to the altered load conditions or to abnormal neuromuscular functions in hypertrophic smooth muscle is unclear. In an opossum model of chronic oesophageal obstruction, we compared the mechanical responsiveness of hypertrophic smooth muscle in vitro to in vivo manometric function. Related to their greater thickness, strips of hypertrophic muscle generated greater force in response to electrical stimulation and to stretch than control strips. Hypertrophic muscle often generated repetitive contractions; spread of contractions orad from the stimulus site was common in hypertrophic oesophageal bands. On manometry, the obstructed oesophagus generated abnormally high pressures proximally, and highly variable pressure amplitudes in the middle and distally; pressure waves often occurred simultaneously throughout the oesophagus, were repetitive or multi-peaked and led to a lasting rise of oesophageal pressure. Alterations in the intrinsic neuromuscular functions of hypertrophic smooth muscle including generation of greater force, repetitive or spontaneous contractions, and retrograde spread of contractions explain many, but not all, of the manometric abnormalities seen in the chronically obstructed oesophagus.

Animals↗
PubMed1996

Volume shifts, unfolding and rolling of haustra in the isolated guinea pig caecum.

The large intestine extracts water from chyme and compacts chyme into faecal conglomerates; it is unclear what role the special pockets known as colonic haustra have in these events. Here we monitored the movements of haustra in isolated preparations of guinea pig caecum using videocamera and ultrasound and related them to contractions of muscle flaps and movements of glass beads in haustral pockets. We found that in partially filled caecal loops localized contractions of taeniae shift volume back and forth between adjacent haustra; volume unfolds haustral walls in a characteristic sweep with sequential intrahaustral folds popping out; cyclic contractions and relaxations of the fold then produce the caterpillar-like movement known as haustral rolling; ultrasound showed that haustral rolling made the haustral flow channel narrower and longer as haustral folds increase their height from 7.5 +/- 1.5 mm to 16 +/- 4 mm and their distance from 4.1 +/- 0.2 mm to 7.9 +/- 0.3 mm; luminal contents were alternatively shaken off the haustral wall, whirled around the lumen or left to settle. We also suspended the row of haustra between two taeniae inside a frame and attached flaps of taeniae and haustral folds to strain gauges to record their mechanical activity; both taeniae and haustral folds produced an undulating baseline tension; during rolling, folds produced phasic contractions at 17 +/- 2 cycles min-1 which propagated distally across haustral septa; rolling constantly shuffled around glass beads placed inside the haustra. When we stimulated the intramural nerves to the caecum through bipolar electrodes, all contractile activity was temporarily inhibited and haustral septa flattened; a rebound contraction then propagated aborally from the caecal pole and swept the glass beads ahead of it. Thus, tonic contractions of taeniae shift caecal contents back and forth across haustral septa; expansion of haustra triggers haustral rolling which shuffles contents; both these movements produce local flow within and between haustra which might enhance the separation of solid and liquid colonic contents.

Animals↗
PubMed1995

Cecum of guinea pig is a reservoir and sigmoid is a high-resistance conduit.

We compared the filling responses of the cecum and the sigmoid of the guinea pig using volumes up to 60 ml and 2.5 ml, respectively. In the isolated cecum, each 1-cm increment of hydrostatic pressure above zero led to accommodation of 10 ml volume; in the sigmoid, the yield pressure (at which accommodation first occurred) was 6 cm H2O, and pressure increments up to 20 cm H2O produced volume increments of less than 0.5 ml. Resting pressure at half-maximal filling was 5.0 +/- 0.7 cm H2O for the sigmoid and 1.7 +/- 0.6 cm H2O for the cecum. K+ depolarization led to a significant upward shift in the pressure curves of both segments. Ca2+ withdrawal decreased sigmoid and cecal pressures at some volumes. Distension of the cecum triggered intermittent contractions, which began with the shortening of the teniae and were associated with low-amplitude pressures and expulsion of a 5- to 10-ml volume. Distension of the sigmoid produced propagating contractions that were associated with high-amplitude pressures and lengthening; compartmentalization in the sigmoid prevented efflux from it, and volume inflow was not affected by pressure waves. Our observations indicate that its large capacity and great distensibility make the cecum suitable for reservoir functions, whereas its narrowness and lack of distensibility make the sigmoid a high-resistance conduit.

Animals↗
PubMed1995

Preservation of peristaltic reflex in hypertrophied ileum of guinea pig.

Chronic obstruction of the guinea pig ileum leads to distension and muscular hypertrophy, but how this affects passive biomechanical and nerve-mediated contractions and clearance known as peristaltic reflex is unclear. Ileum of controls had a diameter of 3.0 +/- 1.1 mm and a circular muscle thickness of 37.2 +/- 11.2 microns; 4 wk after placement of a nonconstricting Gore-Tex band, the ileum was distended to 10.0 +/- 0.19 mm, and its muscle had hypertrophied to 195.0 +/- 61.2 microns. Hypertrophied segments exceeded controls in capacity (e.g., 5.1 +/- 1.1 vs. 1.1 +/0 0.2 ml at 6 cm), compliance, and hysteresis. Threshold volumes and pressures that triggered the reflex were 3.3 +/- 1.3 ml and 3.1 +/- 0.01 mmHg in hypertrophied vs. 0.7 +/- 0.2 ml and 1.5 +/- 0.2 mmHg in controls. The diameter increase that triggered the reflex was 1.4 +/- 0.1 mm in hypertrophied segments and 0.6 +/- 0.1 mm in controls. Hypertrophied segments generated fewer contractions of virtually double the amplitude and failed to generate a pressure differential between up- and downstream sites as controls did. Hypertrophied segments generated larger stroke volumes and cumulative clearance than controls. The ratio of antegrade to retrograde clearance was similar in hypertrophied and control segments. The length of the occluding segment in hypertrophied preparations exceeded that of controls. Control contractions indented the antimesenteric border and propagated antegrade from their site of origin; bizarre writhing movements of hypertrophied segments made their contractions difficult to monitor. Thus distension and muscular hypertrophy do not interfere with the ability of the chronically obstructed guinea pig ileum to generate a peristaltic reflex at least as readily and as powerful and as effective in clearing the lumen as controls.

Animals↗
PubMed1994

Dynamic imaging of obstructed opossum esophagus. From altered load to altered contractility.

We studied by barium contrast the dynamics of experimental obstruction in the opossum esophagus. Immediately after banding the gastroesophageal junction, entrapment of the bolus between the band and the peristaltic contraction led to esophageal bulging, forceful retropulsion of the bolus at the band, and the repeated triggering of peristaltic contractions by the retropelled bolus. In ensuing weeks, triggering of contractions became more difficult and contractions led to bizarre "corkscrew" movements of the increasingly distended and tortuous esophagus. A tight contraction ring that moved very slowly retrograde was occasionally observed in the chronically distended esophagus. Computer-assisted analysis showed that the area and perimeter of the bolus were abnormally large in chronic obstruction and that during its passage through the esophagus the compactness of the bolus increased no longer. Configurational analysis of the cone that the peristaltic contraction shapes at the tail of the barium column showed this to narrow progressively on passage through the normal esophagus and, paradoxically, to widen in both acute and chronic obstruction.

Animals↗
PubMed1993

Morphological changes of myenteric neurons in the partially obstructed opossum esophagus.

We have previously described a model of partial esophageal obstruction which leads to hypertrophic and degenerative changes in the smooth muscle cells. In the present communication we describe changes occurring in the myenteric plexus including increased thickness, varicosities and irregular angulations of nerve fiber bundles. The perikarya of myenteric neurons in the obstructed esophagus showed elongated mitochondria, dilated cisternae of the endoplasmic reticulum and increased numbers of secondary lysosomes and multimembranous dense bodies. In myenteric axons, there was infiltration of Schwann cell subunit by collagen fibrils.

Animals↗
PubMed1993

Infiltration of hypertrophic esophageal smooth muscle by mast cells and basophils.

Partial obstruction leads to chronic distension and muscular hypertrophy of the opossum esophagus. The smooth muscle cells of the circular muscle layer enlarge, become pleomorphic and are surrounded by an amorphous ground substance in the extracellular space. Here we describe the histological and ultrastructural features of a peculiar cellular infiltrate in the hypertrophic smooth muscle. The infiltrate consisted uniquely of mast cells and basophils. In per unit area, the number of mast cells increased from 0.9 +/- 0.1 cells in controls to 3.7 +/- 0.2 in hypertrophic smooth muscle; the corresponding numbers for basophils were 2.5 +/- 0.2 and 7.2 +/- 0.3 cells. Cells were seen primarily in the septal spaces of the circular muscle layer and at the interface of the circular and longitudinal muscle layer. The cytoplasm of basophils is normally packed with round and oval granules. The granules stain metachromatically and with varying intensity on Wright-Giemsa stains. On transmission electronmicroscopy, granules display a membrane and a great diversity in the structure of their luminal contents. In hypertrophic muscle, most granules were discharging their contents into the cytoplasm or extracellular space. The membranes of adjacent empty granules then fused to form a chain of vacuoles. Similar changes occurred also in the mast cells which differed from the basophil by their lack of nuclear lobulation and by the greater homogeneity of their cytoplasmic granules. It is possible that these inflammatory cells are involved in the reconstruction of the smooth muscle and its connective tissue which occur during esophageal distension and hypertrophy.

Animals↗
PubMed1991

Hypertrophic smooth muscle in the partially obstructed opossum esophagus. The model: histological and ultrastructural observations.

Obstruction is a complication of many esophageal diseases, but the morphological changes occurring in the obstructed esophagus are poorly understood. We developed a model of esophageal obstruction in the American opossum, Didelphis virginiana. A nonconstricting band around the gastroesophageal junction led to esophageal distention and tortuosity in the weeks following its placement. Despite a marked increase of the esophageal circumference, the esophageal wall was not thinned, and the circular muscle layer had actually increased its thickness. This was due to an increase in the size of individual smooth muscle cells with proportional increases in the cell surface area and volume. The electron density of hypertrophic smooth muscle cells varied much more than that of normal esophageal smooth muscle cells. As cell size increased, the tissue became more compact and the size of the extracellular space decreased. Also, the extracellular space was filled by an amorphous electron-dense material. Additional changes in the structure of hypertrophic smooth muscle cells included prominent intermediate filaments in the vicinity of thick filaments. There was no difference in the structure of the hypertrophic smooth muscle at 4 weeks and at 8 weeks after placement of the band. The morphological features described here resemble those seen in human esophageal spasm and achalasia of humans and could affect esophageal smooth muscle function.

Animals↗
PubMed1991

Hypertrophic smooth muscle in the partially obstructed opossum esophagus. Excitability and electrophysiological properties.

Partial obstruction of the opossum esophagus leads to thickening of the circular muscle, hypertrophy of smooth muscle cells, and diminution of the extracellular space. The pharmacological and electrophysiological properties of this hypertrophied muscle were studied. Carbachol produced phasic and tonic contractions of the circular muscle. The EC50 for tonic contractions was greater for hypertrophied than for normal muscle (21.1 +/- 3.9 mumol/L vs. 4.8 +/- 2.2 mumol/L; P less than 0.05). The resting membrane potential difference of hypertrophied muscle (-50.8 +/- 0.2 mV) was similar to that of normal muscle (-50.0 +/- 0.2 mV). Electrical stimulation of intrinsic nerves in the normal muscle produced a hyperpolarization followed by a depolarization of smooth muscle membrane potential. Hypertrophied muscle responded either with an attenuated hyperpolarization or no hyperpolarization, both of which were followed by a depolarization. The space constant in the long axes of the hypertrophied circular muscle cells was greater than normal (4.4 +/- 0.2 mm vs. 3.4 +/- 0.1 mm; P less than 0.001). The threshold potential for initiation of action potentials was more negative for hypertrophied (-43.2 +/- 0.4 mV) than for normal circular muscle (-41.6 +/- 0.2 mV; P less than 0.005). These data indicate that alterations in neuromuscular function accompany the hypertrophy of esophageal smooth muscle.

Animals↗
PubMed1989

Motility changes in opossum esophagus from experimental esophagitis.

We assessed how acute inflammation affects the contractile activity of the esophageal body. Two models of esophagitis were used: nine opossums had an esophageal perfusion of 100 meq hydrochloric acid for 2 hr and were studied at 24 hr. Ten had the perfusion for 4 h and their esophagitis were studied in vitro after 72 hr. Comparisons were made in all instances to animals who had esophageal saline perfusion for identical periods. All acid-perfused animals developed gross and histologic evidence of mucosal inflammation; in three animals, inflammatory changes extended into the submucosa and the muscularis propria. Manometric recordings in the acid-perfused animals revealed esophageal shortening, frequent failure of primary peristalsis and frequent occurrence of spontaneous contractions. Recordings of isometric tension of muscle in vitro revealed spontaneous contractions in strips from the mucosa and from the circular and from the longitudinal muscle. The amplitude of contractions in response to electrical stimulation was decreased, but the duration of contractions was increased largely because of a prolonged recovery phase. These changes in mechanical response occurred with stimulus parameters directed at both the muscle and the intrinsic nerves. We conclude that esophageal inflammation can lead to an increased irritability and decreased stimulus response of the smooth muscle of the esophagus even where it is not directly involved in an inflammatory response. These changes correspond to the functional abnormalities of the esophagus seen in patients with reflux esophagitis.

Animals↗
PubMed1989

Anorectal manometry in active and quiescent ulcerative colitis.

Anorectal function was measured in 11 patients with active medically intractable ulcerative colitis, seven patients with quiescent ulcerative colitis, and 18 healthy subjects. The anal resting pressure, squeeze pressure, and ability to defecate a balloon were similar in all groups. Significantly lower rectal distention volumes were required for rectal sensation, critical volume, and to induce rectal contractility in patients with active disease compared to controls or patients with quiescent disease. Rectal compliance was significantly reduced in patients with active and quiescent disease. The increased rectal sensitivity and contractility in patients with active colitis appear to be related to active mucosal inflammation and ulceration. Episodes of mucosal inflammation may be responsible for chronic changes in the rectal wall resulting in fibrosis and decreased compliance in patients with quiescent disease. The frequency and urgency of defecation and the fecal incontinence may be due to a hypersensitive, hyperactive, and poorly compliant rectum.

Adult↗
PubMed1989

Rectosigmoid motility in patients with quiescent and active ulcerative colitis.

We studied the pathophysiology of diarrhea in ulcerative colitis by evaluating and comparing rectosigmoid motility before, during, and after a 900-cal meal in healthy subjects, patients with quiescent ulcerative colitis, and patients with active ulcerative colitis. Three intraluminal pressure transducers were used for recording of rectosigmoid motility. Motility during fasting, eating, and after eating a meal was similar in patients with quiescent disease and controls. Motility increased significantly during eating in controls, but not in patients with quiescent disease. In patients with active colitis, motility was significantly reduced during fasting, eating, and after eating, compared with controls. Motility increased significantly during eating in patients with active disease. Propagated activity was similar in the three study groups; therefore, the decreased motility was due to decrease in segmental contractions. These findings suggest that diarrhea in patients with active colitis may be related to the loss of normal segmental contractions which delay distal stool transport.

Adult↗
PubMed1988

Duodenal resistance to the emptying of various solutions from the isolated cat stomach.

Experiments were conducted to determine to what extent the duodenum resists the emptying of various solutions from the isolated stomach. Cat stomachs were maintained in Krebs solution in vitro, and filled with 100 ml isotonic saline solution, isotonic glucose, hypertonic saline solution, hypertonic glucose, or dilute acid. Gastric pressure was constantly monitored; gastric output was collected constantly by a cannula in the proximal or distal duodenum. For all solutions, cumulative gastric output at all times was considerably less with the distal than the proximal cannula position. This difference was almost entirely caused by a smaller fractional gastric output during the first minute of gastric emptying, and by reduced amplitude of the gastric stroke volume with the distal cannula position. Some differences were observed in the gastric emptying rate for the various solutions; isotonic saline solution emptied particularly slowly and hydrochloric acid emptied particularly fast. In addition, the various solutions produced different gastric pressure patterns, which could not be entirely explained by differences in residual gastric volume. We concluded that the cat duodenum provides a resistance to gastric emptying over and above that generated by the pylorus, and that the duodenal resistance is caused by limitations in duodenal capacity. It is furthermore concluded that the mechanical activity of the isolated stomach and duodenum is affected by the chemical composition of their luminal contents.

Animals↗
PubMed1987

Ion transport in human cecum, transverse colon, and sigmoid colon in vitro. Baseline and response to electrical stimulation of intrinsic nerves.

In a flux chamber study of ion transport in human colon, we compared baseline rates with those measured during electrical stimulation of intrinsic nerves. In baseline studies, sodium was absorbed throughout, but maximally in transverse colon. In cecum, sodium absorption accounted for the short circuit current and chloride was not absorbed. Chloride was absorbed in transverse and sigmoid colon, however. Residual current was minimal in cecum and transverse colon, but increased in sigmoid colon. Neural stimulation caused chloride secretion in cecum, reduced chloride absorption in sigmoid colon, but caused no change in transverse colon; sodium absorption decreased in cecum. A neurotransmitter of unknown identity affects baseline short circuit current in sigmoid colon. Half of the increase in short circuit caused by neural stimulation in sigmoid colon is mediated by muscarinic receptors. The identity of the other transmitter(s) is not known. It is not substance P or histamine. The three divisions of the colon differ in relative rates of baseline ion transport and in their transport responses to intrinsic nerve stimulation.

Cecum↗
PubMed1979

Surgical treatment in familial visceral myopathy.

In a kindred with a familial visceral myopathy, seven patients had operations seeking relief of chronic abdominal pain and other symptoms of intestinal obstruction; one patient had an 80% cystectomy and a Y-V-plasty of the bladder neck for urinary retention. Five patients with megaduodenum had bypass operations; a side-to-side duodenojejunostomy was done in four and a retrocolic gastrojejunostomy in one. Two of these died of postoperative complications, and one developed symptomatic adhesions. Two other patients who had duodenojejunostomy have done well for 6 years and 1 1/2 years respectively. One patient with dilation of the distal jejunum and proximal ileum had relief of intestinal obstructive symptoms from jejunostomy to decompress the destal jejunum. One patient who had a resection of the descending and sigmoid colon for sigmoid volvulus has done well for four years. Three of these seven patients developed peritonitis postoperatively, and two had symptomatic adhesions after operations. Duodenal aspiration from a patient who developed postoperative peritonitis grew E. coli, 10(13) colonies per ml. After review of the results of operations in other families and in our kindred, we favor side-to-side duodenojejunostomy in megaduodenum. Duodenal aspirate must be cultured before operation. Evidence of bacterial overgrowth in the aspirate should prompt appropriate antibiotic treatment to reduce the likelihood of sepsis.

Abdomen↗