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Biomedical subjects

T N Pappas

Publications and source records attributed to T N Pappas.

At least 37 records · Page 2Linked to original sources

Conversion factors for laparoscopic splenectomy for immune thrombocytopenic purpura.

BACKGROUND: Since 1994, 27 patients at our institution have undergone laparoscopic splenectomy for immune thrombocytopenic purpura (ITP). Laparoscopic splenectomy was completed in 22 of these patients. We sought to identify factors that precluded successful laparoscopic splenectomy in the remaining 5 patients. METHODS: Retrospective review of 27 patients with ITP undergoing laparoscopic splenectomy was performed at Duke University Medical Center from August, 1994 to September, 1997. RESULTS: Laparoscopic splenectomy was performed in 16 women and 11 men with a mean age of 47.2 years. Five (18%) of these procedures were converted to open splenectomy. There was no significant difference in age, ASA score, gender, weight, height, or splenic size between the converted and laparoscopic groups. However, preoperative and postoperative platelet counts were significantly higher in the laparoscopic group than in the converted group (p < 0.001). Operative times also were significantly longer for the laparoscopic group than for the converted group (p < 0.001). Adherent adjacent structures, associated comorbidities, and technical errors prohibited laparoscopic completion in five patients. Technical errors with subsequent bleeding required conversion in two patients. A thickened greater omentum blanketing the splenic capsule and a densely adherent pancreatic tail extending well into the splenic hilum prevented laparoscopic completion in two patients. Increased peak airway pressures greater than 60 mmHg after pneumoperitoneum necessitated conversion in the remaining patient, who had a previous history of pulmonary insufficiency. Regardless of surgical approach, all patients achieved a therapeutic response after splenectomy. Splenectomies completed laparoscopically resulted in a significantly shorter length of hospital stay (p < 0.01). CONCLUSIONS: Densely adherent adjacent structures, technical errors, and cardiopulmonary instability may preclude successful completion of laparoscopic splenectomies. Thorough preoperative evaluation with an emphasis on the cardiopulmonary system may elicit a cohort of individuals with ITP who are unlikely to undergo laparoscopic splenectomy successfully. This cohort also may include individuals with preoperative platelet counts less than 35,000 mm(-3).

Female↗

Central modulation of rectal distension-induced blood pressure changes by alosetron, a 5-HT3 receptor antagonist.

Irritable bowel syndrome (IBS) represents one of the most common gastrointestinal-related diagnoses. Although the precise etiologic basis of IBS is not known, a common presenting symptom is abdominal pain or discomfort that is thought to develop, at least in part, from a heightened awareness of visceral nociceptive input. Agents capable of reducing this heightened visceral nociception would, therefore, have utility in the treatment of IBS. In this study we evaluated the effects of intravenous and intracerebroventricular administration of a 5-HT3 receptor antagonist, alosetron, on blood pressure changes associated with rectal distension in anesthetized and awake dogs. This vasoactive reflex serves as a model for visceral nociception. For intracerebroventricular studies, the cerebroventricular guides were placed over the lateral ventricle. In anesthetized studies, blood pressure was measured by femoral artery cannulation. In awake studies, blood pressure was monitored by noninvasive measurement. A rectal balloon was placed in the rectum of each dog and maintained throughout the experiments. Each dose of alosetron was given to the dogs as an intravenous or intracerebroventricular bolus, and every 30 min the rectal balloon was inflated and blood pressure responses observed. In both anesthetized and awake dogs alosetron produced a significant inhibition of the vasoactive reflex. In particular, alosetron showed high potency when administered intracerebroventricularly. Alosetron, administered either centrally or peripherally, appears to modulate the visceral nociceptive effect of rectal distension in dogs.

Animals↗

Review article: evaluation of drugs in experimental gut distension models.

Distension of the gastrointestinal tract elicits abdominal pain, as well as sensations such as discomfort or fullness. Many patients with irritable bowel syndrome have been reported to show a reduced threshold to the pain or discomfort due to experimental rectal distension. This hypersensitivity of the gut may be characteristics of the irritable bowel, as well as other functional gastrointestinal disorders. Intestinal distension in animals induces a range of responses which have been used as indexes of visceral nociception. This paper reviews a recently introduced canine model used to assess the antinociceptive properties of a novel 5-HT3 receptor antagonist, alosetron.

Abdominal Pain↗

The laparoscopic management of gastroesophageal reflux disease.

Laparoscopic fundoplication has replaced open fundoplication as the gold standard for the surgical management of patients with GERD. The improvements in technique that have led to the excellent results on long-term follow-up have broadened the indications for surgical involvement along the continuum of severity in GERD. Therefore, the importance of accurate preoperative testing for appropriate patient classification must be emphasized to all who care for these patients.

Fundoplication↗

Growing use of laparoscopic cholecystectomy in the national Veterans Affairs Surgical Risk Study: effects on volume, patient selection, and selected outcomes.

OBJECTIVE: To study the introduction of laparoscopic cholecystectomy to the 43 tertiary-care university-affiliated Veterans Administration medical centers (VAMCs) participating in the National Veterans Affairs Surgical Risk Study from October 1991 through December 1993. SUMMARY BACKGROUND DATA: Previous studies in the private sector have documented growth in the number of cholecystectomies and falling clinical thresholds for cholecystectomy with the introduction of laparoscopic cholecystectomy. METHODS: The following were analyzed for changes over time: measures of patient preoperative risk, complexity of surgery, severity of biliary disease, numbers of procedures, postoperative length of stay, and 30-day postoperative mortality and general complication rates. RESULTS: The number of cholecystectomies performed laparoscopically increased, but the total number of cholecystectomies performed remained stable over time. The proportion of patients with acute cholecystitis, emergent cholecystectomies, and technically complex cholecystectomies did not change or increased slightly over time. Adjusted odds for postoperative general complications were lower for laparoscopic than for open cholecystectomy, but 30-day postoperative mortality and general complication rates for all cholecystectomies remained constant over time. Postoperative length of stay for all cholecystectomies fell significantly. Implementation rates of laparoscopic cholecystectomy varied widely between hospitals. Laparoscopic cholecystectomy was adopted more slowly and used in a lower percentage of cholecystectomies than in non-VA settings. CONCLUSIONS: In contrast to non-VA studies showing increases in overall cholecystectomy volume since the introduction of laparoscopic cholecystectomy, these VAMCs implemented laparoscopic cholecystectomy without growth in cholecystectomies or a change in the clinical threshold for cholecystectomy. Laparoscopic cholecystectomy was associated with better outcomes, but its introduction in the setting of stable cholecystectomy volume and biliary disease case mix did not change postoperative mortality and complication rates. The stable cholecystectomy volume and biliary disease case mix, slower adoption, and lower use of laparoscopic cholecystectomy contrast with previous reports and may result from differences in patients and organization and financing of VA versus non-VA settings.

Aged↗

Laparoscopic ventral and incisional hernioplasty.

BACKGROUND: While the first laparoscopic ventral hernia repair was reported in 1992, there have been no studies comparing laparoscopic to conventional ventral herniorrhaphy. METHODS: Twenty-one ventral hernias repaired laparoscopically are compared to a similar group of 16 patients undergoing traditional open repair during a 2-year period. Operative and hospital courses along with outcomes and cost analysis are analyzed. RESULTS: There was no statistical difference between groups in number of previous abdominal operations, prior hernia repairs, and comorbidities. Patients undergoing open repair were older with larger fascial defects. Open repairs had a shorter operative time as compared to the laparoscopic group, but statistically longer postoperative stays and costs. Postoperative complications occurred in 31% of the open group and 23% of the laparoscopic group. There were two recurrences in each group. CONCLUSIONS: Laparoscopic herniorrhaphy is as safe and effective as the traditional open technique with shorter length of stay and decreased hospital costs.

Adult↗

The effect of caloric load and nutrient composition on induction of small intestinal satiety in dogs.

The influence of caloric load and nutrient composition on small intestinal satiety was investigated in six dogs with chronic esophageal fistulas. Dogs received small bowel infusion of a mixed nutrient liquid meal, a fat, carbohydrate, and a protein solution over two hours. Each infusion was given over a range of caloric densities which represented between 0 to 20% of the total 24 h caloric requirement for each animal. Satiety was measured by sham feeding at the end of the infusion. Infusion of 0.25 cal/ml (equivalent to 5% of the 24 h caloric requirement) of a liquid mixed nutrient meal (Isocal) significantly suppressed sham feeding (volume sham fed: control 265 +/- 28 ml/min; Isocal 0.25 cal/ml 218 +/- 52 ml/min, p < 0.05). Oleate and dextrose polymer also significantly reduced sham feeding at a caloric concentration of 0.25 cal/ml (volume sham fed: control 265 +/- 28 ml/min; oleate 112 +/- 28 ml/min; oleate 112 +/- 9 ml/min; dextrose polymer 190 +/- 11 ml/min), whereas peptone did not significantly suppress sham feeding until a solution with 0.5 cal/ml was given. These studies demonstrate that caloric load of intestinal nutrients must reach a threshold to produce satiety in sham feeding dogs. The threshold caloric load is different for the three nutrient groups, with fats requiring the lowest caloric load to produce satiety. These provide insight into the mechanisms by which small intestinal signals might contribute to regulation of the inter-meal interval.

Animals↗

Total parenteral nutrition alters NPY/PYY receptor levels in the rat brain.

The regulation of appetite and satiety is complex and may involve peptide mediators such as cholecystokinin (CCK) and neuropeptide Y (NPY). Studies have indicated that calories administered enterally and parenterally impact on feeding, and possibly via the release of such mediators. Recent data from our laboratory have shown that total parenteral nutrition (TPN) reduces sham feeding in dogs by 50%. We hypothesized that TPN may alter feeding via an NPY-mediated mechanism. To test our hypothesis, we examined the effect of continuous administration of TPN on NPY receptor levels in the rat brain. Rats were surgically prepared with intravenous catheters. After 72 h of TPN infusion, the rats were anesthesized with sodium pentobarbital and their brains were removed. Neuropeptide Y receptor density was assessed by autoradiography in the paraventricular nucleus, olfactory cortex, dentate gyrus, and thalamus. These results were compared to the control group receiving intravenous saline. A third group receiving enteral nutrition was examined as well. Neuropeptide Y receptor numbers were significantly increased in the paraventricular nucleus of rats receiving TPN compared to the groups receiving intravenous saline or enteral nutrition. We conclude that continuous parenteral nutrition significantly increases NPY receptor density in the rat brain suggesting that TPN may impact feeding via the regulation of NPY receptor-mediated effects.

Animals↗

Clinical uses of gut peptides.

OBJECTIVE: The authors review clinical applications of gut-derived peptides as diagnostic and therapeutic agents. SUMMARY BACKGROUND DATA: An increasing number of gut peptides have been evaluated for clinical use. Earlier uses as diagnostic agents have been complemented more recently by increasing application of gut peptides as therapeutic agents. METHOD: The authors conducted a literature review. RESULTS: Current experience with clinical use of gut peptides is described. Initial clinical applications focused on using secretomotor effects of gut peptides in diagnostic tests, many of which have now fallen into disuse. More recently, attention has been directed toward harnessing these secretomotor effects for therapeutic use in a variety of disorders, and also using the trophic effects of gut peptides to modulate gut mucosal growth in benign and malignant disease. Gut peptides have been evaluated in a variety of other clinical situations including use as adjuncts to imaging techniques, and modification of behaviors such as feeding and panic disorder. CONCLUSIONS: Gut peptides have been used successfully in an increasing variety of clinical conditions. Further refinements in analogue and antagonist design are likely to lead to even more selective agents that may have important clinical applications. Further studies are needed to identity and evaluate these new agents.

Adenoma, Islet Cell↗

Abdomen after a Puestow procedure: postoperative CT appearance, complications, and potential pitfalls.

PURPOSE: To evaluate the postoperative computed tomographic (CT) appearance, complications, and potential pitfalls after a Puestow procedure (lateral side-to-side pancreaticojejunostomy). MATERIALS AND METHODS: Forty CT examinations were performed after the Puestow procedure in 20 patients. Images were retrospectively reviewed by three radiologists. RESULTS: The pancreaticojejunal anastomosis was identified at 30 examinations and was immediately anterior to the pancreatic body or tail. The anastomosis contained fluid or gas on 11 scans and oral contrast material on four scans. On 15 scans, the anastomosis appeared as collapsed bowel without gas, fluid, or oral contrast material. The Roux-en-Y loop was identified on 28 (70%) scans and contained fluid or gas on 16 scans and oral contrast material on six scans. The Roux-en-Y loop appeared as collapsed bowel on six scans. When the anastomosis or Roux-en-Y loop contained fluid and gas, the appearance mimicked that of a pancreatic or parapancreatic abscess. Peripancreatic stranding was present on 28 scans and was due to either ongoing pancreatitis or postoperative change. Complications included 15 transient fluid collections, three abscesses, four pseudocysts, one hematoma, and one small-bowel and Roux-en-Y obstruction. CONCLUSION: Knowledge of the anatomy after a Puestow procedure is essential for accurate interpretation of CT scans.

Abscess↗

Inhibition of sham feeding-stimulated acid secretion in dogs by immunoneutralization of gastrin.

A monoclonal antibody to gastrin was used to study the role of circulating gastrin in mediating acid secretion stimulated by sham feeding in dogs. On separate days, four conscious, fasted, adult mongrel dogs with esophageal and gastric fistulae were pretreated intravenously with either 7 mg of gastrin monoclonal antibody (MAb 28.2), 7 mg of keyhole limpet hemocyanin monoclonal antibody as control, or 12.5 micrograms/kg atropine sulfate. Thirty minutes later, acid secretion was stimulated first by sham feeding for 5 min, then, 60 min later, by an intravenous infusion of a maximum stimulatory dose of histamine (40 micrograms/kg) for 60 min, and after returning to basal, by intravenous infusion of a submaximal stimulatory dose of gastrin (200 pmol.kg-1.h-1) for 60 min. Acid output from secretions collected every 15 min by gravity drainage was determined by titration to pH 7.0 with 0.2 N NaOH. Sham feeding-stimulated acid output (17.7 +/- 5.5 mmol/h) was significantly inhibited by administration of either MAb 28.2 (0 mmol/h) or atropine (1.7 +/- 1.1 mmol/h). Histamine-stimulated acid output (19.6 +/- 3.4 mmol/h) was not reduced by either pretreatment. Gastrin-stimulated acid output (3.9 +/- 0.6 mmol/h) was significantly reduced only by pretreatment with MAb 28.2 (0.1 +/- 0.1 mmol/h) and not by atropine (2.2 +/- 1.4 mmol/h). A background intravenous infusion of pentagastrin (0.5 microgram.kg-1.h-1) restored sham feeding-stimulated acid output blocked by administration of MAb 28.2, although the intrinsic acid response to sham feeding could not be seen with the background pentagastrin infusion. Furthermore, the plasma gastrin response to sham feeding was not blocked by atropine pretreatment. Because immunoneutralization of both gastrin and cholinergic blockade significantly inhibited acid output during sham feeding, circulating gastrin and cholinergic pathways are involved in mediating the cephalic phase of gastric acid secretion in dogs.

Animals↗

Increased substance P receptor expression by blood vessels and lymphoid aggregates in Clostridium difficile-induced pseudomembranous colitis.

Pseudomembranous colitis is most often caused by toxins secreted by Clostridium difficile following bowel flora overgrowth after antibiotic use. The secretory and inflammatory effects observed in C. difficile toxin A-induced enterocolitis in the rat ileum are inhibited by CP-96,345, a substance P (SP) receptor antagonist. To determine if SP plays a role in the pathogenesis of human pseudomembranous colitis, SP receptor distribution was examined in a toxin A-positive specimen of bowel. Quantitative receptor autoradiography was used to examine SP receptors in tissue from a patient who tested positive for C. Difficile toxin. SP receptors were massively increased in small blood vessels and lymphoid aggregates in the pseudomembranous colitis bowel in comparison to control specimens. The SP binding was saturable and exhibited similar affinities for SP and CP-96,345. SP may contribute to the inflammatory response in pseudomembranous colitis via a massive increase in SP receptor antagonists may offer a novel therapeutic intervention for pseudomembranous colitis.

Adult↗

Alterations in hemodynamics and left ventricular contractility during carbon dioxide pneumoperitoneum.

BACKGROUND: Carbon dioxide (CO2) pneumoperitoneum has been shown to adversely affect hemodynamics in patients. This study specifically examines the potential contribution of altered left ventricular contractility (LVC) to hemodynamic changes observed during CO2 pneumoperitoneum. METHODS: In a canine model, LV volumes, LV pressure, and intrathoracic and central venous pressures were recorded both at basal intra-abdominal pressure (IAP) and after CO2 insufflation to produce IAPs of 5-25 mmHg. RESULTS: At IAPs greater than 15 mmHg, cardiac output and LV end-diastolic volume decreased. Mean arterial pressure and heart rate were unchanged. LVC, quantified using the linear Frank-Starling relationship, was not affected by increases in IAP. CONCLUSIONS: This study is the first to quantify LVC during CO2 pneumoperitoneum and demonstrates no changes in contractility over IAPs from 5 to 25 mmHg. In the dog model, any hemodynamic alterations induced by CO2 pneumoperitoneum are secondary to altered LV preload and not alterations in contractility or LV afterload.

Animals↗

Low insertion of hepatic segmental duct VII-VIII is an important cause of major biliary injury or misdiagnosis.

BACKGROUND: The importance of variant anatomy is only mentioned generally in most articles in this era of laparoscopic cholecystectomy. We report a series of 14 patients in whom a seemingly low insertion of hepatic segmental duct VII-VIII was clinically important. METHODS: The patients were managed at Duke University Medical Center. Two intraoperative videotapes of injury were reviewed. RESULTS: Three categories of patients were identified: 6 patients who had injury in association with another major injury to the biliary system, 7 patients who had an isolated VII-VIII system injury, and 1 patient with a Klatskin tumor in whom the unobstructed variant duct was stented. After appropriate evaluation, all patients were successfully treated. Several lawsuits resulted, even when the injury was seemingly minor. Symptoms developed in all patients who filed lawsuits, but none in those who did not. CONCLUSION: Appreciation of the VII-VIII biliary variant can lead to avoidance of injury or to a successful repair. The injury can easily occur despite "normal" cholangiography. Successful clinical outcome does not necessarily correlate with freedom from lawsuits.

Bile Duct Neoplasms↗

Substance P activation of enteric neurons in response to intraluminal Clostridium difficile toxin A in the rat ileum.

BACKGROUND & AIMS: Nerves have been suggested to mediate the effects of bacterial toxins in intestinal diseases. However, the mechanisms involved are unknown. This study examined endogenous substance P (SP) activation of the substance P receptor (SPR) on enteric neurons in the rat ileum after exposure to intraluminal Clostridium difficile toxin A. METHODS: After intraluminal injection of toxin A in ileal loops, tissue was examined for pathological changes by histology and for SPR activation by immunocytochemical analysis of SP-induced SPR endocytosis. RESULTS: After toxin A administration, > 70% of enteric neurons showed SPR endocytosis and became swollen with thickened dendrites. In contrast, SPRs in control rats were largely confined to the plasma membrane. Rats denervated of primary afferent fibers with neonatal capsaicin injection and animals pretreated with a nonpeptide SPR antagonist showed few endosomal SPRs, and the pathological inflammatory effects of toxin A were ablated. CONCLUSIONS: Intraluminal toxin A causes the release of SP from primary afferent neurons: this endogenous SP then acts on enteric neurons in the submucosal and myenteric plexuses. SP is the primary mediator of an axon reflex mediating neurogenic inflammation in the intestine. SPR blockade may prove to be a novel therapy used to prevent intestinal inflammation.

Animals↗