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Biomedical subjects

J W Harmon

Publications and source records attributed to J W Harmon.

At least 19 recordsLinked to original sources
PubMed1991

Advantages of handsewn over stapled bowel anastomosis.

Bowel anastomoses are conventionally performed using a handsewn technique or a stapling device. Each has potential benefits and disadvantages. The most clinically significant complications of the bowel anastomosis are anastomotic leakage and stricture formation. The indices of healing and tissue cohesion were compared dynamically over time in 24 dogs randomized to undergo either a standard two-layer handsewn anastomosis or a stapled anastomosis with the Premium CEEA (United States Surgical Corporation, Norwalk, CT). Animals were sacrificed at 1, 4, 7, and 28 days postoperatively. Each anastomosis was evaluated for anastomotic index, burst pressure, collagen content, and histologic appearance. The anastomotic index was similar on postoperative day (POD) 1, 4, and 7; but on day 28 all handsewn anastomoses had larger diameters than the widest CEEA anastomosis. Burst pressure was higher in handsewn anastomoses at all intervals. Collagen content tended to be higher on POD 7 in the CEEA anastomoses. Histological evaluation showed more complete epithelialization and less inflammation in handsewn anastomoses on POD 28. The higher level of collagen in the CEEA anastomoses on POD 7 may be implicated in the tendency toward stricture formation found with this type of anastomosis. This study demonstrates that the greater speed and ease of the stapled anastomosis is offset by the greater strength, reduced tendency to stricture, and more complete healing of the handsewn anastomosis.

Anastomosis, Surgical↗
PubMed1991

Somatostatin analogue treatment inhibits post-resectional adaptation of the small bowel in rats.

Post-resectional hyperplasia is the phenomenon in which residual small bowel increases in size and absorptive capacity after segmental enterectomy. This experiment studied the effect of somatostatin analogue therapy on the development of two structural parameters of post-resectional hyperplasia in rats subjected to 40% proximal small bowel resection. Octreotide acetate-treated rats failed to develop increased villus height (902 +/- 50 microns) relative to saline-treated rats (1,103 +/- 98 microns). Augmentation of residual intestinal weight was also significantly impaired in analogue-treated rats (92 +/- 3 versus 118 +/- 5 mg/cm). We conclude that somatostatin analogue treatment during the early postoperative period does impair the growth of residual bowel in rats. These findings raise concern regarding the use of this drug for postoperative patients who have undergone massive small bowel resection in whom the process of post-resectional adaptation may be critical to allow sustenance with enteral nutrition.

Adaptation, Physiological↗
PubMed1991

Excitation of neurons in the medullary raphe increases gastric acid and pepsin production in cats.

The nucleus raphe obscurus (NRO) has recently emerged as an important nucleus for excitation of gastric motor activity through projections to the dorsal motor nucleus of the vagus (DMV) [P. J. Hornby, C. D. Rossiter, R. L. White, W. P. Norman, D. H. Kuhn, and R. A. Gillis. Am. J. Physiol. 258 (Gastrointest. Liver Physiol. 21): G91-G96, 1990; and M. J. McCann, G. E. Herman, and R. C. Rogers. Brain Res. 486: 181-184, 1989]. A neurotransmitter thought to be involved in this NRO-DMV pathway is thyrotropin-releasing hormone (TRH), a peptide that excites gastric activity when microinjected into the DMV. The purpose of the present study was to determine whether gastric acid and pepsin secretion were altered by 1) activation of neurons in the NRO by microinjection of kainic cid and 2) microinjection of TRH into the DMV in chloralose-anesthetized cats. Microinjection of kainic acid into the NRO increased gastric acid secretion [baseline was 6 +/- 2 (mu eq) H+/15 min (n = 7) and increased to 8 +/- 2, 26 +/- 11 (P less than 0.05), and 21 +/- 7 mu eq/15 min (P less than 0.05) during the first, second, and third 15-min periods after microinjection, respectively]. Pepsin output also increased from a baseline of 287 +/- 67 pepsin units (PU) (n = 4) to 507 +/- 126 PU 15 min postinjection, 541 +/- 118 PU 30 min after injection (P less than 0.05), 608 +/- 92 PU 45 min after injection (P less than 0.05), and 700 +/- 156 PU 60 min postinjection (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Bile acid accumulation in gastric mucosal cells.

Bile acids are one of the components of the gastric contents capable of disrupting the mucosal barrier to diffusion. The mechanism by which bile acids can damage the gastric epithelium is not completely understood. Several studies have emphasized mucosal lipid solubilization by bile acids in the pathogenesis of mucosal injury. Bile acid entry into gastric mucosal cells may be a critical and early step in the genesis of mucosal injury, but this possibility has not yet been investigated. The present study was designed to explore the interaction of bile acids with dispersed gastric mucosal cells isolated from the rabbit and guinea pig stomach. Results showed that both glycocholic and deoxycholic acid rapidly associated with the gastric cells and reached a steady state concentration by 30 min. Glycocholic acid accumulated in the cells to a concentration approximately eight times greater than that in the surrounding medium. The amount of bile acid associated with the cells was greater at an acidic than at a neutral pH, and was a function of the concentration of both the cells and the bile acid. The process did not require cellular energy, was nonsaturable, and was not species specific. Experiments with 86Rb, a cytoplasmic marker, revealed that approximately one half of the cellular glycocholic acid was associated with the cytoplasmic compartment and the rest with the membranes. These findings are consistent with a combination of intracellular entrapment of the bile acids due to intracellular ionization and bile acid binding to cellular membrane components being the mechanisms by which bile acids accumulate in cells. Acid-driven bile acid accumulation may explain how relatively low luminal concentrations of bile acid can be damaging to the gastrointestinal mucosa.

Animals↗
PubMed1991

Capsaicin-sensitive nerves mediate esophageal mucosal protection.

The esophageal mucosa is exposed to damaging agents both by ingestion and reflux. Using our in vivo rabbit model of esophagitis, we have observed that acute luminal exposure (within 1 to 5 minutes) to potentially harmful agents, such as acid, bile, or ethanol, induces a rapid increase in mucosal blood flow; whereas prolonged exposure (10 to 60 minutes) results in mucosal injury and ablation of blood flow. We have also shown that capsaicin-sensitive mucosal afferent nerves can modulate esophageal blood flow. These findings led us to hypothesize that the reactive increase in blood flow induced by luminal agents represents a mechanism of protection mediated by capsaicin-sensitive nerves. The objective of these experiments was to determine if luminal capsaicin, a specific probe for visceral afferent nerves, could both preserve mucosal blood flow and protect against ethanol injury. Rabbits were subjected to luminal instillation of 50% ethanol with or without 1% capsaicin. Blood flow was measured with microspheres at baseline and after 2 and 10 minutes. Rabbits exposed only to ethanol developed severe mucosal injury coincident with near ablation of mucosal blood flow. In contrast, rabbits exposed to ethanol with capsaicin showed protection of the epithelium with a sixfold increase in mucosal blood flow. We conclude that capsaicin-sensitive nerves in the esophagus are local effectors of mucosal protection by virtue of preserving blood flow.

Animals↗
PubMed1990

Anastomotic compression button: a new mechanical device for sutureless bowel anastomosis.

The anastomotic compression button is a new mechanical device that uses three interlocking polypropylene buttons to produce a sutureless bowel anastomosis. The device is unique in that it allows application of the buttons via a device similar to the popular intraluminal stapler, but it leaves no staples or foreign body of any kind in the bowel wall. The authors compared the 25-mm anastomotic compression button with the 25-mm intraluminal stapler in the colon of dogs. After 28 days, the mucosal blood flow, burst pressure, and anastomotic indices were found to be identical between the anastomotic compression button and the stapler. The anastomotic compression button was easier to use, and microscopic examination showed less ulceration, fibrosis, and inflammation, and better re-epithelialization at the anastomotic compression button site. The anastomotic compression button appears to have the potential to be a superior method compared with stapled anastomoses in the colon.

Anastomosis, Surgical↗
PubMed1990

Bismuth subsalicylate reduces peptic injury of the oesophagus in rabbits.

Bismuth subsalicylate was tested in an in vivo perfused rabbit model of oesophagitis for its ability to prevent the mucosal injury caused by pepsin. Treatment efficacy was assessed under both a treatment-before-injury protocol and a treatment-after-injury protocol. Oesophageal mucosal barrier function was evaluated by measuring flux rates of H+, K+, and glucose. The degree of oesophagitis was determined by gross and microscopic examination of the mucosa by several independent observers. Results showed that under both treatment protocols, bismuth subsalicylate significantly reduced the pepsin induced disruption of the mucosal barrier, as well as the morphologic changes. Bismuth subsalicylate when given after exposure to pepsin was also found to protect against the morphologic injury in a dose dependent manner. Experiments in vitro suggested that bismuth subsalicylate inhibits the proteolytic action of pepsin by interacting with pepsin, rather than with the pepsin substrate. We conclude that bismuth subsalicylate can protect the oesophageal mucosa against peptic injury, probably through inactivation of pepsin.

Animals↗
PubMed1990

Alterations in serum creatine kinase and lactate dehydrogenase. Association with abdominal aortic surgery, myocardial infarction and bowel necrosis.

Experimental studies have shown that peripheral serum creatine kinase and lactate dehydrogenase change with bowel infarction. Some clinical reports have suggested that similar changes occur in patients. This prospective study documents the changes in these enzymes associated with acute myocardial infarction, acute bowel necrosis (MES INF), and uncomplicated abdominal aortic reconstruction. Analysis of 15 patients with AMI, 13 patients undergoing major AAS, and eight patients with MES INF has shown that these conditions may be differentiated by analysis of serum CK and LD isoenzymes. The study suggests that in the absence of electrocardiographic changes, a patient with epigastric distress with elevated levels of serum CK and either CK-MB or CK-BB bands present may well have a mesenteric rather than a myocardial infarction. Acute myocardial infarction can be ruled out further through analysis of serum LD1/LD2 ratios.

Aged↗
PubMed1990

Insulin-like growth factor I receptors in the arteries of the rabbit: autoradiographic mapping and receptor characterization.

Insulin-like growth factor I (IGF-I) is a polypeptide hormone structurally related to insulin with insulin-like metabolic effects. It is a potent mitogen, eliciting cell multiplication in tissue culture by increasing deoxyribonucleic acid and protein synthesis. IGF-I was found to promote the growth of cultured arterial smooth muscle cells. We studied the in situ distribution of IGF-I receptors in different arteries of the rabbit by autoradiography and examined their binding characteristics in the wall of the thoracic aorta. The thoracic and abdominal aortas and carotid, superior mesenteric, renal, and iliac arteries of three adult New Zealand rabbits were harvested and stored at -70 degrees C. Autoradiographic analysis of 125I-labeled IGF-I binding to frozen arterial sections showed that silver-grain density was consistently located in the arterial wall. Binding studies in the thoracic aorta demonstrated high-affinity IGF-I receptors with a dissociation constant of 2 nmol/L and maximum IGF-I binding capacity of 4.17 pmol/mg protein. Inhibition studies with insulin, IGF-I, and IGF-II showed that these binding sites were more specific for IGF-I than for IGF-II or insulin, with a concentration of peptide that inhibits 50% of maximum binding of 1.75 nmol/L, 5 nmol/L, and greater than 100 mumol/L, respectively. The presence of high-affinity, specific IGF-I receptor binding in rabbit arteries suggests that IGF-I plays an important role in regulating the multiplication of arterial smooth muscle cells; a role that may prove important in different pathologic processes.

Animals↗
PubMed1989

Epidural anesthesia in patients undergoing thoracic surgery.

Epidural anesthesia has been reported to exert beneficial effects in surgical procedures. Over the past 3 years at the Veterans Administration Medical Center in Washington, DC, thoracic surgical procedures have been done using a combined technique of epidural anesthesia with light general anesthesia. A retrospective review of this experience from January 1984 to November 1987 was done in 90 consecutive patients. Postoperative extubation of patients was accomplished immediately in 32%, within 1 hour in 34%, within 3 hours in 28%, within 18 hours in 4%, and was prolonged in only 1% of patients. Mortality was 2% and morbidity was 3%. This analysis indicates that the technique of epidural anesthesia with light general anesthesia provided satisfactory anesthesia with low mortality and morbidity in a high-risk group of patients undergoing surgery.

Adult↗
PubMed1989

Distribution of vasoactive intestinal polypeptide and substance P receptors in human colon and small intestine.

Vasoactive intestinal polypeptide (VIP) and substance P are found in neurons in the lamina propria and submucosa and muscularis propria of human small intestine and colon. VIP receptors coupled to adenylate cyclase are present on epithelial, smooth muscle, and mononuclear cells. This study analyzes the distribution of [125I]VIP binding and [125I]substance P in human colon and small intestine using autoradiographic techniques. [125I]VIP binding was present in high density in the mucosal layer of colon and small intestine. [125I]VIP binding was not significantly greater than nonspecific binding in smooth muscle layers or the lymphoid follicles. In contrast, [125I]substance P binding was present in high density over the colonic muscle but was not present over the mucosal layer. In human colon cancer, [125I]VIP grain density over the malignant tissue was only slightly higher than background. These autoradiographic studies of [125I]VIP binding indicate that the highest density of VIP receptors was found in the small intestine and superficial colonic mucosa, whereas the density of substance P receptors was highest over the smooth muscle layers. These findings suggest a mismatch between immunochemical content of the peptide and autoradiographic density of the receptor.

Autoradiography↗
PubMed1989

Distribution of vasoactive intestinal peptide and its receptors in the arteries of the rabbit.

Vasoactive intestinal peptide (VIP) is a widely distributed neurotransmitter whose dilatory effects on vascular smooth muscle are believed to be mediated via specific receptors. To determine the possible role of VIP in regulating specific vascular beds, we examined the relationship between arterial wall VIP content as determined by radioimmunoassay and VIP receptors mapped by autoradiography. Analysis of arteries from 12 adult New Zealand rabbits showed that VIP receptors were consistently located in the wall of all muscular arteries, and that the 125I-VIP grain density correlated with VIP content. 125I-VIP binding in the mesenteric, renal, and iliac arteries was abundant and their VIP content was 192 +/- 56, 51 +/- 5, and 74 +/- 23 fmole/mg protein, respectively. 125I-VIP binding to the thoracic aorta was indistinguishable from nonspecific binding, its VIP content being 15 +/- 2 fmole/mg protein. The abundance of VIP receptors and the high VIP levels associated with the mesenteric, renal, and iliac arteries suggest that VIP is a potential regulator of flow to the vascular beds supplied by these arteries. In contrast, the much lower density of receptors in the extracranial carotid, which is also a muscular artery, suggests that, in rabbits, control of carotid vasomotion may be less dependent on VIP innervation. Furthermore, these results suggest that VIP receptors and VIP-containing neurons are not uniformly distributed in the arterial vasculature and that VIP may have selective vasodilatory effects.

Animals↗
PubMed1989

VIP receptors and content after bowel transplantation.

Advances in immunosuppressive therapy have renewed interest in small bowel transplantation. Little is known, however, about the functional capacity of transplanted intestine. To clarify the potential for normal function, we investigated whether elements of the enteric nervous system are preserved after denervation in our rat model of intestinal transplantation. We investigated whether VIP, a major peptide neurotransmitter of the enteric nervous system, and its receptors are preserved in the bowel after transplantation. In our model of transplantation, avascular fetal jejunum from term Fisher rats is transplanted to the subcutaneous tissues of host syngeneic rats. This "neogut" becomes vascularized and develops characteristics of native small bowel. VIP content was measured by RIA and the in situ distribution of VIP receptors was determined by the technique of receptor autoradiography. Neogut was studied 1 and 3 weeks after transplantation and compared with age-matched rat pup jejunum. Autoradiographs showed high silver grain density, representing VIP binding sites, in the mucosal layers of all tissues studied. VIP content in the transplanted bowel was comparable to that of native gut and showed a rise with developmental age similar to that of native gut. VIP levels (pmole/mg protein, x +/- SEM) were neogut 1 week, 0.26 +/- 0.14; jejunum 1 week, 0.25 +/- 0.07; neogut 3 weeks, 0.60 +/- 0.21; and jejunum 3 weeks, 0.69 +/- 0.16. These results show that VIP receptors and content are preserved in this model of transplantation. This suggests that the enteric nervous system and receptors for peptide neurotransmitters remain intact after transplantation and may retain the potential for regulatory function.

Animals↗
PubMed1989

Esophageal blood flow in the rabbit: response to calcium channel blockers.

Calcium channel blockers have recently been added to the therapeutic regimen for patients who have chest pain of esophageal origin. Although relief of symptoms has been reported, this has not always been associated with changes in esophageal contraction pressures or luminal pH. Myoischemia has been proposed as one possible mechanism for esophageal chest pain. We have investigated the effect of the calcium channel blockers verapamil, nifedipine, and diltiazem on esophageal blood flow in the rabbit model. Esophageal blood flow was measured three times in each rabbit with use of the radiolabeled microsphere technique after a 30-minute continuous infusion of (1) saline solution (baseline), (2) a low dose, and (3) a high dose of each agent. Esophageal mucosal blood flow significantly decreased with nifedipine but was unchanged with verapamil and diltiazem. Esophageal muscle blood flow significantly increased--approximately 100% after administration of each of the calcium channel blockers. Thus esophageal muscle blood flow is enhanced after administration of calcium channel blockers, and this may be one therapeutic mechanism of the calcium channel blockers in the relief of esophageal chest pain in some esophageal diseases.

Animals↗
PubMed1988

Effects of prostaglandins on esophageal blood flow.

The physiologic mediators of blood flow to the esophagus are poorly understood. We have investigated the effects of prostaglandins on esophageal blood flow as they are known to alter blood flow in other organs of the gastrointestinal tract. Esophageal mucosal and muscularis blood flow (Q) were measured in New Zealand white rabbits treated intravenously with the prostaglandin analogs misoprostol (PGE1), 16,16-dmPGE2 (PGE2), and iloprost (PGI2, prostacyclin). Esophageal blood flow was measured three times in each rabbit using the radiolabeled microsphere technique after a 30-min continuous infusion of (1) saline (baseline), (2) a low dose, and (3) a high dose of each agent. Iloprost significantly increased esophageal mucosal (fourfold) and muscularis (twofold) blood flow. The other two PG analogs, misoprostol and 16,16-dmPGE2, had no significant effect on esophageal blood flow. Iloprost also significantly increased blood flow to the other organs of the gastrointestinal tract; however, the response was not as dramatic as in the esophageal mucosa. Prostacyclin may have a physiologic role in blood flow regulation to the esophagus and may be involved in pathophysiologic processes in the esophagus, such as increasing mucosal blood flow in response to injury.

16,16-Dimethylprostaglandin E2↗
PubMed1988

Inhibition of acid secretion in guinea pigs by tricyclic antidepressants: comparison with ranitidine and omeprazole.

The antisecretory properties of imipramine on gastric secretion in guinea pig in comparison with other antisecretory agents was determined. In awake guinea pigs s.c. infusion of histamine (30 micrograms/kg/hr) increased acid and fluid secretion by 3- to 4-fold. When acid output peaked, a bolus administration of the tricyclic anti-depressant imipramine inhibited acid and fluid secretion. Imipramine and other agents, such as ranitidine and omeprazole, inhibited gastric secretion in a dose-dependent fashion. The most potent was the H2-antagonist ranitidine (IC50, 0.2-0.3 mumol/kg), followed by the gastric H-K-adenosine triphosphatase inhibitor, omeprazole (IC50, 0.5-0.6 mumol/kg). Imipramine (IC50 1-2 mumol/kg) was the least potent of the inhibitors. Both ranitidine and omeprazole could abolish acid secretion, but maximal inhibition with imipramine was 60% of initial. Promethazine (25 mumol/kg), an H1 antagonist, and atropine (12 mumol/kg), a muscarinic antagonist, inhibited gastric secretion by 40 to 50%. Imipramine and atropine also inhibited basal acid secretion. In dispersed gastric cells comparison between imipramine and omeprazole showed that imipramine was about 5-fold more potent than omeprazole in blocking histamine or dibutyryl cyclic AMP stimulation of aminopyrine accumulation. Imipramine probably acts as a protonophore by increasing the rate of proton-gradient dissipation rather than by interfering with the hydrogen-pump system because, in gastric membranes, imipramine was 20-fold less potent than omeprazole in inhibiting the gastric H-K-adenosine triphosphatase activity. These results suggest that imipramine administered s.c. in guinea pigs is a potent antisecretory drug. Its action may be due to a combination of anticholinergic and antihistamine H2 activities.

Adenosine Triphosphatases↗