Frank G. Moody

Estimation of the Functional Reserve of Human Liver

Functional hepatic reserve was determined in 32 patients with known liver or biliary tract disease employing kinetic analysis of hepatic removal of indocyanine green (ICG). The initial removal rates of incremental doses of ICG (0.5, 1.0 and 5.0 mg/kg body weight) were plotted as a reciprocal against the inverse of dose (Lineweaver-Burk plot) to provide a means of determining maximal removal rate from submaximal doses (Rmax). This function equalled 3.40 mg/kg/min in ten patients with normal livers, but was only .24 mg/kg/min in eight patients with alcoholic cirrhosis. Portasystemic shunting did not further influence Rmax. Infiltrative liver disease had only a mild depressive effect on this function. The results show that hepatic function can be precisely quantitated by classical enzyme kinetics (Michaelis-Menten). If Rmax is an estimate of protein receptor mass for organic anions, then the technique may allow an indirect means for quantitating hepatocytes even in the presence of changes in blood flow or hepatic function. The profound depression in R(max) observed in patients with alcoholic cirrhosis is consistent with the progressive loss in hepatic mass associated with this disease.

Transduodenal sphincteroplasty and transampullary septectomy for postcholecystectomy pain.

Ninety-two patients underwent a transduodenal sphincteroplasty and transampullary septectomy (extended papilloplasty) for chronic, incapacitating upper abdominal pain over an 11-year period. Seventy-nine had a prior cholecystectomy; 42 of 56 patients with reported pathology had documented gallstone disease. Serious morbidity included two moderately severe cases of postoperative pancreatitis and a pulmonary embolus. There were no deaths. Operative findings revealed stenosing papillitis (n = 45), transampullary septitis (n = 40), and papillary dysfunction (n = 7). Histologic examination of septa) biopsy specimens revealed inflammation in 34 cases and fibrosis in 19 cases. There were no microscopic abnormalities in 39 biopsy specimens. The results at 1 to 10 years in 83 patients is as follows: good in 36 patients (no pain—43%), fair in 27 patients (occasional pain—33%), and poor in 20 patients (unrelieved by the procedure—24%). Patients with prior sphincteroplasty (12 of 15 with a fair to good result) benefitted the most from the procedure. Those who underwent concomitant cholecystectomy responded poorly. Risk factors for failure include alcoholism, drug addiction, mental illness, and duodenal ulcer disease. The finding of papillary cholesterolosis at operation also was accompanied by a less than optimal result. Transduodenal sphincteroplasty with transampullary septectomy provides long-term benefit to carefully selected patients with chronic abdominal pain after cholecystectomy.

Stress and the acute gastric mucosal lesion

Gastric erosions which occur in the clinical setting of physical or thermal trauma, shock, sepsis, or head injury have through common usage been called stress ulcers (1). While this terminology serves to dramatize the clinical environment in which such lesions occur, it has done little to identify factors which lead to their occurrence. Four important facts have emerged from a wealth of clinical and laboratory investigation of the problem: (1) Only a small number of patients at risk demonstrate clinical evidence of stress erosions, (2) hydrochloric acid is a critical requisite for their formation, (3) disruption of the mucosal barrier (as evidenced by increased back-diffusion of hydrogen ions) is not an essential component of the pathologic process, and (4) disturbance in gastric mucosal perfusion probably plays an important etiologic role. The numerous physiologic and biochemical events which accompany injury have obscured definition of the precise role of stress. It is clear, however, that the occurrence of gastric erosions under the conditions enumerated above is more than a chance association. The following remarks will attempt to sort out those factors which relate to the mechanism of erosion formation, with emphasis on variables which are unique to the stressed subject.

Stress Ulcers: Their Pathogenesis, Diagnosis, and Treatment

Stress ulcers are multiple, superficial erosions which occur mainly in the fundus and body of the stomach. They develop after shock, sepsis, and trauma and are ofter found in patients with peritonitis and other chronic medical illness. Stress ulcers should be differentiated from reactivation of chronic duodenal or gastric ulcers. Cushings ulcer following head injury, or drug-induced gastritis. Digestive symptoms are usually absent, hemorrhage is the most common manifestation, and perforation and obstruction are rare. The presence of luminal acid and ischemia are necessary for the production of stress ulcer, while disruption of the gastric mucosal barrier by refluxed duodenal content may contribute to the pathogenesis. Endoscopy is the mainstay of the diagnostic procedure, and angiography should be used if endoscopy fails to identify the bleeding lesions. Medical management should include volume replacement, nasogastric aspiration, and the use of antacid. Selective intraarterial infusion of pitressin has shown encouraging preliminary results. Surgical treatment is reserved only for those patients who continue to bleed despite all medical management. The operation of choice is open to question. We prefer vagotomy, pyloroplasty, and oversewing the ulcers as an initial operation. Since the result of all forms of therapy has been poor, it seems resonable to try to prevent ulcer development. The use of vitamin A, hyperalimentation, and growth hormones is still in an experimental stage. Large clinical studies with case control are necessary before recommendations can be made. The use of potent and frequent antacid to buffer the gastric content has shown promising results; however, these observations need to be confirmed in a properly controlled and randomized study.

The cytoprotective effects of (±)-15-deoxy-16-α,β-hydroxy-16-methyl PGE1 methyl ester (SC-29333) versus aspirin-shock gastric ulcerogenesis in the dog

Abstract SC-29333 (SC) has been reported to protect the gastric mucosa from the effects of topical aspirin. We compared SC and 16,16-dimethyl PGE2 (16-dm) in 20 chambered canine stomachs (6 controls and 7 of each PG). Prostaglandin was added to an acid solution (100 mM HCl; 54 mM NaCl) at 0, .001, .01, 0.1, and 1.0 ug/ml (two periods each). Then aspirin (20 mM) and PG (1.0 ug/ml) (two periods) were followed by hemorrhagic shock (near 60 mm Hg mean arterial pressure). 16-dm caused a significant efflux of fluid (−6.5 ± 5.3 to 17.3 ± 6.7 ul/min), Na+ (2.1 ± 0.5 to 6.8 ± 1.6 uEq/min), and Cl− (−0.9 ± 2.4 to 5.3 ± 1.3 uEq/min), but did not affect K+ or H+. 16-dm also caused a slight drop in potential difference (PD) (67.6 ± 1.7 to 60.3 ± 2.0 mV). 16-dm did not significantly affect total blood flow. Percent lesion formation was more severe than controls (20.2 ± 3.5 vs 11.6 ± 1.7 percent) but not statistically significant. SC had no significant effect on fluid, H+, Na+, K+, or Cl−. It caused an increase in blood flow (6.85 ± 1.46 to 26.20 ± 2.74 ml/min, p

Transampullary septectomy for post-cholecystectomy pain

Twenty-eight patients with chronic, incapacitating upper abdominal pain after cholecystectomy had excision of the common wall between the terminal bile duct and duct of Wirsung (ampullary septum). Twenty-two also had a sphincteroplasty; six had had this procedure previously. Pancreatic function studies, scintiscans, ultrasound and pancreatograms were non-diagnositc. Hyperamylasemia was an uncommon finding. Eight patients were found to have evidence of mild pancreatitis at exploration. There was gross scarring of the ampullary septum in 22 cases. Histologic examination revealed inflammation in 12 septa; the degree of fibrosis could not be assessed since 14 control septa from autopsy material free from biliary tract disease revealed a comparable degree of collagen and smooth muscle. There were no deaths, and minimal morbidity. In follow-up from seven to 59 months (mean = 26), 16 patients are relatively free of pain, five have occasional episodes which require non-narcotic analgesics, and seven have gained no relief from the operative procedure. A randomized controlled trial is recommended.

Direct effects of endotoxin on canine gastric mucosal permeability and morphology.

Abstract The effects of endotoxin on gastric mucosal permeability and morphology were studied by intra-arterial infusion of sublethal doses of endotoxin into a single artery perfusing an exteriorized segment of canine stomach. Endotoxin infusion produced a profound change in mucosal appearance from bright, uniform red to mottled, palewhite discoloration when exposed to acid or mannitol. Gross erosions occurred in four of 13 mucosae bathed with 0.15 N HCl within 1 hr of infusion of endotoxin in the absence of arterial hypotension. Histological changes seen in most experiments include release of mucus from surface epithelial cells and elevation of the epithelium from the basement membrane. In more advanced lesions, severe injury extended into the gastric glands and surrounding connective tissue with cellular necrosis. In spite of gross and microscopic gastric mucosal injury, no significant change was seen in hydrogen ion back diffusion or sodium efflux. These observations suggest that gastric mucosal injuries can occur in endotoxemia without systemic arterial hypotension and that anatomical mucosal injuries are not associated with the destruction of the hydrogen-sodium permeability barrier.

Cytoprotection of the gastric epithelium

The lining of the stomach of man is protected from its unique secretion, hydrochloric acid, by a variety of highly specialized characteristics. Foremost is its relative impermeability to hydrogen ions. The gastric surface epithelial cell which forms a continuous integument from the esophagus to the duodenum plays an important role in this barrier function. Disruption of the barrier by injurious agents, sepsis, or shock may lead to severe erosive gastritis when acid is present within the lumen of the stomach. This process is accelerated during periods of low mucosal blood flow. The relationship of the rate of back-diffusion of hydrogen ions to mucosal blood flow appears critical. Factors which (a) inhibit acid secretion, (b) strengthen the barrier to H+ diffusion, or (c) increase mucosal blood flow will protect the stomach from injury. Prostaglandins of the A, E, and F series offer a level of protection in experimental erosive gastritis that is out of proportion to their effect on acid secretion and mucosal perfusion. The secretion or filtration of an alkaline secretion may be an important component of the cytoprotection which follows the topical exposure of gastric mucosa to 16,16-dimethyl (PGE2). The role of mucus release in this situation requires further elucidation.RésuméLa paroi gastrique de lhomme est protégée contre sa propre sécrétion, lacide chlorhydrique par plusieurs mécanismes hautement spécialisés. Le plus important est limperméabilité relative de la muqueuse aux ions hydrogènes. Les cellules de lépithélium de surface, qui tapissent en une couche continue tout lestomac depuis loesophage jusquau duodénum, jouent un rôle important dans la fonction de cette barrière muqueuse. Toute rupture de la barrière, par des agents délétères, par une infection ou par un état de choc, peut provoquer, si le contenu gastrique est acide, lapparition dune gastrite érosive grave. Le développement des lésions est accéléré par toute réduction du débit sanguin dans la muqueuse. La relation entre rétrodiffusion des ions hydrogènes et débit sanguin muqueux semble être un facteur critique. Les facteurs qui (1) inhibent la sécrétion dacide, (2) renforcent la barrière à la diffusion des ions H+, (3) accroissent le débit sanguin dans la muqueuse, protègent lestomac contre le développement des lésions. Dans des conditions expérimentales, les prostaglandines de types A, E et F protègent contre la gastrite érosive; cette protection est sans rapport avec leurs effets sur la sécrétion dacide et la perfusion de la muqueuse. La sécrétion ou la filtration dune composante alcaline est peut-être un facteur important de la cytoprotection que donne le 16, 16-diméthyl (PGE 2) en application locale. Le rôle du mucus dans ces circonstances est encore mal connu.

Effects of Carbenoxolone on Gastric Mucosal Permeability and Blood Flow in the Dog

The effects of topical application of carbenoxolone at neutral and acidic pH were compared in exteriorized, chambered segments of canine gastric corpus. When dissolved in saline at pH 7.5 to 8.0, 0.25% carbenoxolone caused a rapid drop in gastric potential difference of 56 +/- 2 mv and greatly increased permeability to H+ ions. Blood flow, as measured by radioactive microspheres, was not changed by carbenoxolone treatment, but subsequent exposure to isotonic HC1 caused an abrupt rise in flow. Application of 0.25% carbenoxolone suspension in isotonic HC1 caused no change in potential difference, permeability, or blood flow. Neither carbenoxolone preparation had a significant effect on aspirin-induced H+ back-diffusion or injury.

Twenty-Five-Year Survival After Surgery For Complete Extrahepatic Biliary Atresia: A case report

Abstract At 12 weeks of age, the patient whom we report underwent cholangioduodenostomy for treatment of complete atresia of the common bile duct. After surgery, her course was punctuated by episodes of cholangitis and jaundice. When she was 25 years of age, a liver biopsy showed biliary cirrhosis. Percutaneous cholangiography revealed dilated and deformed intrahepatic biliary ducts containing stones. Surgical removal of the stones and revision of the cholangioduodenal anastomosis was performed. Intrahepatic cholelithiasis has not previously been reported as a complication of this disorder. Her survival is the longest reported in the world literature for this condition, and emphasizes the need to vigorously pursue potentially operable cases.