The effect of normalization of plasma amino acids on hepatic encephalopathy in man.

Previous work from this laboratory has suggested that the plasma amino acid pattern, known to be deranged in hepatic encephalopathy, may be related causally. In order to test this hypothesis, 23% dextrose and a special amino acid solution whose components were calculated to normalize the plasma amino acid pattern were infused in 11 patients, eight with chronic cirrhosis and acute exacerbation (Group 1) and three patients with fulminant hepatitis (Group 2), in amounts of up to 120 Gm. of protein equivalent per 24 hours. Plasma amino acids were abnormal but different in both groups. In Group 1 (cirrhosis) changes in plasma amino acid pattern including elevated phenylalanine, tyrosine, glutamate, aspartate, and methionine and decreased valine, leucine, and isoleucine. In Group 2 all amino acids were elevated, with the exception of the branched chains which were normal. Hepatic encephalopathy improved in all patients in Group 1 and in one of three patients in Group 2 following the infusion. The ratio (see article) showed an excellent correlation with a grade of encephalopathy. When this ratio, previously 1.0 in the presence of encephalopathy, returned to the normal value near 3.0 to 3.5, encephalopathy improved. An excellent correlation was obtained between the ratio and the grade of encephalopathy and was dose related as well. The results suggest that different amino acid patterns in hepatic encephalopathy of differing etiologies require treatment modalities which may differ for the two types of encephalopathy. Whereas amino acid infusion appears to be a valuable, efficacious way of providing nutrition in treating hepatic encephalopathy in patients with cirrhosis and acute deterioration and coma, other means of therapy such as plasms "laundering" appear to be necessary in patients with fulminant hepatitis.

Vasoactive intestinal peptide inhibition of stimulated gastric secretion. I. Inhibition of meat-stimulated gastric secretion.

In an effort to demonstrate a physiologic role of vasoactive intestinal peptide, awake dogs with either Heidenhain pouches or Thiry-Vella loops and duodenal cannulas with duodenoduodenostomies to prevent obstruction were stimulated with meat meals given by mouth and infusions of various substances given intraduodenally, including hypertonic saline solution or 0.16 normal hydrochloric acid. Stimulated Heidenhain pouch secretion was significantly inhibited by concomitant intraduodenal administration of hydrochloric acid. Plasma vasoactive intestinal polypeptide was highest in the animals who received hydrochloric acid intraduodenally among all the intraduodenal stimuli. These findings support a role for vasoactive intestinal polypeptide as a physiologic inhibitor of gastric secretion, at least in dogs.

Vasoactive intestinal peptide-associated inhibition of stimulated gastric secretion. II. Inhibition of pentagastrin-stimulated gastric secretion.

The possible role of vasoactive intestinal peptide as an inhibitor of stimulated gastric secretion was investigated. Awake dogs with Heidenhain pouches were stimulated with pentagastrin alone and in combination with intraduodenal instillation of various potential inhibitors of gastrointestinal secretion including isotonic phenylalanine, 3 percent hypertonic saline solution and 0.16 normal hydrochloric acid. Plasma vasoactive intestinal peptide is significantly increased by pentagastrin, and this release is enhanced by intraduodenal hydrochloric acid. Simultaneously, there is significant inhibition of pentagastrin-stimulated Heidenhain pouch secretion. These findings provide evidence for a possible physiologic role of vasoactive intestinal peptide as an inhibitor of gastric secretion, at least in dogs.

Release of VIP by calcium stimulation.

Calcium has been shown to be a reliable releaser of VIP, as has been observed with most peptide hormones. VIP is released throughthe gastrointestinal tract. The challenge of VIP release by calcium could reveal different "potentials" in the production of the hormone, that are not appreciated in the basal state. Calcium stimulation thus showed a slightly greater level of VIP release from the pancreaticoduodenal vein than from the portal radicals. But although the significance of this finding remains to be defined, calcium release could have a clinical applicability in the challenge of equivocal VIPomas.

Release of vasoactive intestinal peptide in the central nervous system in man.

Recent work has shown that vasoactive intestinal peptide (VIP), one of the many candidate hormones of the gut, also occurs widely in neurones. To determine whether the neuronal peptide may have a neurotransmitter function, we studied changes in immunoreactive VIP in dog plasma and human cerebrospinal fluid after the infusion of choline esterase inhibitors (neostigmine and physostigmine, respectively). Immunoreactive VIP was released in both situations. The systemic changes (in VIP levels) were enhanced five weeks after portacaval shunting in dogs. Our results demonstrate that the immunoreactive VIP level increases as a result of choline esterase inhibitors. The plasma "release" may originate either from peripheral peptidinergic nerve terminals or from APUD cells of the gastroenteropancreatic system. The increase in immunoreactive cerebrospinal fluid VIP may very well originate from central neurons, since the peptide does not apparently cross the blood-brain barrier.

In vitro release of gastrin from isolated perfused antrum.

Gastrin is released from isolated perfused rat antra in a regular fashion by a variety of stimuli, including acetylcholine, glycine, and calcium. Two peaks are seen with the physiologic stimulus, acetylcholine, suggesting perhaps two different antral gastrin populations.

A maneuver to improve the shutter mechanism in inguinal hernias.

A technique for improving the shutter mechanism in the treatment of inguinal hernias is presented. The lateral leaf of the external oblique is fashioned to accommodate the emerging spermatic cord and is brought to a more posterior plane by suturing it to the inguinal ligament. This supporting flap is anchored to the internal oblique aponeurosis and anterior rectus sheath, keeping the sutures deep to the internal oblique, but superficial to the transverse plane.

Vasoative intestinal peptide and the watery diarrhea syndrome.

A sensitive and specific radioimmunoassay for the detection of vasoactive intestinal peptide has been used to study patients with the watery diarrhea syndrome. In eleven patients the syndrome was associated with tumors, and plasma levels of vasoactive intestinal peptide were elevated. VIP levels returned towards normal in five treated patients coincident with amelioration of symptoms. Normal values were obtained in patinets with chronic pancreatitis, sprue, medullary carcinoma, Zollinger-Ellison Syndrome and laxative abuse. In six other patients with indistinguishable syndrome and no findings of tumor at laparotomy and autopsy, vasoactive intestinal peptide levels were normal. The results suggest that VIP may be the causative agent in patients with the watery diarrhea syndrome and tumors, but that an indistinguishable syndrome exists for which VIP is not the cause.

An increase in vasoactive intestinal peptide levels in canine endotoxin shock.

Some of the many metabolic and cardiovascular activities and effects of vasoactive intestinal peptide are quite similar to the changes observed in endotoxin shock. The changes occurring in plasma vasoactive intestinal peptide levels during canine endotoxin shock were studied. Vasoactive intestinal peptide levels were markedly and significantly elevated following the administration of endotoxin, corresponding well with the drop in systemic blood pressure. In the dogs surviving the experiment, plasma vasoactive intestinal peptide levels returned to normal levels after 24 hours, corresponding well with the restoration of normal hemodynamic values. Surviving dogs exhibited significantly lower vasoactive intestinal peptide levels than did nonsurvivors. Many of the biologic activities of vasoactive intestinal peptide make it suitable for counteracting endotoxemia, thus acting as the defense of the body against endotoxin. However, the lower vasoactive intestinal peptide levels in the surviving dogs rather points to vasoactive intestinal peptide as a causative factor in canine endotoxemia.

Review of 404 patients with gastrointestinal fistulas. Impact of parenteral nutrition.

This paper represents an extensive review, spanning 30 years of experience with 404 patients with gastrointestinal fistulas. It includes the first period (1945-1960) during the introduction of antibiotics, the second period (1960-1970) which saw rapid improvements in parasurgical care including, respiratory support, perfection of antibiotics, some introduction of nutritional support and improved monitoring, and the third period which saw the introduction of parenteral nutrition specifically central venous hyperalimentation using hypertonic glucose and amino acids (1970-1975) in the treatment of patients with fistulas. The principal causes for mortality in the historical sense were malnutrition, sepsis and electrolyte imbalance. Mortality among patients with gastrointestinal cutaneous fistulas decreased between the first and second periods from approximately 48 to 15%. Surprisingly, mortality did not decrease further in the "hyperalimentation period" although spontaneous closure of gastrointestinal fistulase increased. The results suggest that the improvement in mortality in patients with gastrointestinal cutaneous fistulas is mostly due to the introduction of improved parasurgical care. It is acknowledged that nutritional support was practiced in the 1960's although this was generally not in the form of hyperalimentation. The addition of hyperalimentation in large scale to the treatment of gastrointestinal cutaneous fistulas has improved spontaneous closure and is a valuable part of the armamentarium. The decrease in mortality however, cannot be attributed to parenteral nutrition.

Hepatic inactivation of vasoactive intestinal peptide in man and dog.

IN AN EFFORT TO DOCUMENT THE ROLE OF THE LIVER IN THE CATABOLISM OF VASOACTIVE INTESTINAL PEPTIDE, SEVERAL DIFFERENT TYPES OF EXPERIMENTS WERE CARRIED OUT, INCLUDING: 1) simultaneous measurement of portal and systemic immunoreactive vasoactive intestinal peptide, both in the basal state and following calcium stimulation; 2) by measuring plasma concentrations of immunoreactive vasoactive intestinal peptide before and after portacaval shunt; 3) by measuring plasma VIP before and after portacaval shunt following calcium, prostigmine and pentagastrin stimulation; 4) by determining plasma VIP levels in patients with liver disease and in hepatic failure, and in patients with variceal hemorrhage before and serially after portal systemic shunt; 5) by measuring CSF vasoactive intestinal peptide in dogs before and after portacaval shunt and when the animals finally succumb to hepatic failure. The results consistently suggest that the shunting of portal blood away from the liver does not result in significant elevation of basal peripheral plasma levels of vasoactive intestinal peptide. Following stimulation however, increased amounts of peripheral plasma VIP are detected, following calcium, pentagastrin and prostigmine release of VIP. Portal vein levels are always significantly higher than peripheral plasma VIP again, confirming a catabolic role for the liver. In patients, elevation of peripheral plasma VIP is seen in hepatic failure, but not after portacaval shunt. Finally, cerebrospinal fluid VIP is elevated in dogs following hepatic failure, confirming the presence of a neural-gut axis and suggesting an influence of hepatic catabolism of VIP not only in the periphery, but also within the central nervous system.

Aspirated foreign bodies in the tracheobronchial tree: report of 250 cases.

During the last 14 years, 250 patients with aspirated foreign bodies in the tracheobronchial tree were admitted to Kuwait Chest Diseases Hospital. Ninety-six per cent of the cases were under 10 years of age and 38% gave a clear history of foreign body inhalation. The rest were diagnosed either clinically, from the chest radiograph findings or because of unexplained pulmonary symptoms. In 247 cases, bronchoscopy under general anaesthesia was successful in removing the foreign bodies. In only three cases was bronchotomy needed. Seventy per cent of the foreign bodies were melon seeds. Asphyxia and cardiac arrest occurred in four cases during bronchoscopy but the patients were successfully resuscitated. In 10 cases a tracheostomy was done before bronchoscopy and the removal of the foreign body, while in five it was needed after bronchoscopy. Fifteen patients developed late complications such as recurrent pneumonia or atelectasis of the lung. Early diagnosis and adequate treatment are essential to prevent pulmonary and cardiac complications and to avoid radical lung surgery.

Maternal fetal and placental gastrin concentrations.

The radioimmunoassay technique was used to measure maternal, placental and fetal serum gastrin levels. A progressive increase in gastrin levels occurred with the advance of pregnancy reaching mean peak levels of 62 (SEM 12) pg/ml during labour. Umbilical artery (74 pg/ml: SEM 7) or vein (73 pg/ml: SEM 7) gastrin concentration was higher than maternal gastrin levels. Placental gastrin concentration was 840 pg/g (SEM 96) and amniotic fluid contained 22 pg/ml (SEM 2). This study implies that one of the reasons for increased maternal gastric residue seen during pregnancy is due to an increased serum gastrin concentration. Also the advanced stage of development of gastrointestinal system of the newborn is in accord with high fetal gastrin concentration.

Hepatic and pulmonary clearance of exogenous vasoactive intestinal peptide in the rat.

1125-labeled vasoactive intestinal peptide (VIP) has been injected into the portal and systemic circulations of rats in an attempt to identify the distribution and fate of the circulating peptide. When VIP I125 was introduced into the portal circulation radioactivity was concentrated in the liver (415.5% +/- 57.2 at 10 min--counts per minute (cpm) per gram of tissue as percentage cpm per milliliter of plasma). Radioactivity in kidney and lung was 346.6% +/- 37.4 and 136.4% +/- 11.4, respectively. In contrast, if the liver was bypassed by performing a portacaval shunt or by injecting into the inferior vena cava, radioactivity was maximal in the lung (2,454.3% +/- 302.3 10 min after IVC injection) with activity in the liver of only 89.3% +/- 10.6. Analysis of the pattern of radioactivity in plasma and tissue extracts by gel filtration chromatography showed the presence of a number of fragments of smaller molecular weight than VIP with a progressive diminution of the amount of VIP-like radioactivity. Both liver and lung have the capacity to concentrate VIP from the circulation. Vasoactive intestinal peptide released into the portal circulation is probably taken up initially by the liver, and this may prevent subsequent uptake by pulmonary tissue. There is some evidence to suggest that the liver and the lung may handle VIP in different ways. If this is so, the enhanced pulmonary extraction of VIP when the liver is bypassed may have some significance for the cardiovascular complications of fulminant liver failure.

"Somatostatinoma": a somatostatin-containing tumor of the endocrine pancreas.

We studied the pancreatic and enteric hormone profile of a 46-year-old woman who had hyperglycemia and a pancreatic tumor. Before operation, there was no evidence of overproduction of glucagon or insulin. The tumor's ultrastructure had a distinctive endocrine morphology, resembling D cells. Prompted by the recent demonstration of somatostatin in D cells of pancreatic islets, we analyzed the tumor and found a large quantity of immunoreactive somatostatin (301 ng per milligram of tissue). Insulin, glucagon, gastrin, vasoactive intestinal polypeptide and human pancreatic polypeptide were present in only trace quantities. The tumor cells were cultured in monolayers, which remained viable up to 51 days and released somatostatin into the culture medium. In seven insulinomas and two glucagonomas, we found the somatostatin content either much lower (less than 0.6 ng per milligram of tissue) or undetectable. After complete resection of the tumor, our patient became euglycemic and has remained so for the past 20 months.