Pectoralis major musculocutaneous flaps: long-term follow-up of hypopharyngeal reconstruction.

We have reviewed our experience with 25 patients who have undergone major head and neck resections and required hypopharyngeal pectoralis major flap reconstruction. Six patients were alive 1 year following reconstruction and five patients consented to evaluation of flap function with endoscopy, with biopsy, barium swallow, and esophageal manometrics. The patients were older (61 +/- 6 years) and the flaps were large (42 +/- 9 cm2). Barium studies were the most useful method of evaluating these patients. Postoperative stricture and laryngeal aspiration were found in two patients. Biopsy of the flap demonstrated loss of keratin in the overlying epidermis, while the gross appearance was more like the surrounding mucosa. A review of dietary intake in these cases revealed that two patients weighed less than their preoperative weights, while another refused oral feedings despite a good functional result. Three of five patients preferred gastrostomy feedings to oral alimentation.

Renal transplantation. A 20-year experience in a Veterans Administration Medical Center.

Between March 1963 and December 1983, 324 renal transplants were performed in 273 veteran patients at the Veterans Administration Medical Center, Nashville, Tenn. Cadaver donors were used in 273 transplants, with an overall one-year patient survival of 72.5% and one-year functional graft survival of 50%. Twenty-four living-related transplants were performed, with an overall one-year patient survival of 89% and one-year functional graft survival of 75%. For analytical purposes the 20-year transplant experience was divided into five eras. One-year patient survival increased from 45% in era 1 to 84% in era 5, while functional graft survival increased from 45% to 70%. Death has occurred in 139 patients, with sepsis being responsible for the largest number of early deaths. Cardiovascular disease was responsible for most late deaths.

Endotoxemia of cirrhosis: an observation not substantiated.

Physiologic similarities between cirrhotic and septic patients have implicated systemic endotoxemia as a possible mediator of the hemodynamic, neurologic, and hematologic complications observed in patients with cirrhosis of the liver. The recently reported high prevalence of endotoxin in ascites, as well as in portal and systemic plasma, has further incriminated endotoxin of gut origin as the responsible agent. Limulus amebocyte lysate tests were performed upon peripheral plasma of 38 cirrhotic patients; portal plasma and ascites were assayed in 14 and 11 of these patients, respectively. No endotoxin was detectable. We believe that the ubiquity of endotoxin, with the attendant opportunities for specimen contamination, is the most likely explanation for the recently reported high prevalence of endotoxin in the plasma and ascites of cirrhotic patients.

Tyrosine metabolism in cirrhosis.

The aim of this study was to define the enzyme defect responsible for tyrosinemia in cirrhotic patients. The principal hepatic degradation pathway for tyrosine, tyrosine leads to p-hydroxyphenylpyruvic acid equilibrium homogentisic acid leads to CO2 was studied in 18 cirrhotic patients and eight controls. The classic method employed in elucidation of hereditary tyrosinosis was sued. Metabolic intermediates on the pathway were measured in the basal state, and following oral loading doses (50 mg/kg BW) of tyrosine, PHPA, and homogentisic acid. Cirrhotic patients showed a significant increase (p = 0.005) in fasting plasma tyrosine and in basal PHPA excretion and impaired tolerance to all three metabolites when compared to normals. Fifteen of the 18 cirrhotic patients showed tyrosine intolerance which was not accompanied by change in distal metabolites compared to their basal levels. Nevertheless 13 of the 18 did exhibit intolerance of either PHPA or homogentisic acid. We conclude that in contrast to the single complete defect in hereditary disorders of tyrosine metabolism, cirrhotic patients have partial defects at tyrosine transaminase, PHPA oxidase, and homogentisic acid oxidase, the initial step being rate-limiting.

Tyramine kinetics and metabolism in cirrhosis.

Hypertyraminemia is common in hepatic cirrhosis and correlates in severity with encephalopathy. The mechanism of cirrhotic hypertyraminemia has not been established. The alternative possibilities are increased production from tyrosine and impaired degradation by monoamine oxidase. This investigation determined the pharmacokinetics of tyramine after an intravenous bolus injections of [3H]-tyramine (180--200 muCi 12 Ci/mmol sp act) in 13 cirrhotics and 9 controls. In normals, [3H]tyramine levels initially declined rapidly (alpha-phase) followed by a slower decline (beta-phase) with an average t 1/2 of 20.8 min. Average normal metabolic clearance rate and production rate were 13.2 liters/min and 15.4 microgram/min, respectively. In cirrhotic patients, the plasma disappearance curve for [3H]tyramine was qualitatively similar to that of the control subjects with no apparent different in beta-t 1/2 (17.2 min). The hypertyraminemia of cirrhosis resulted primarily from overproduction of tyramine, as the production rate (32.0 microgram/min) in these patients was significantly greater (P less than 0.05) than in controls, whereas the metabolic clearance rate remained normal (average 12.2 liters/min). A difference in ratio of tyramine metabolic products was noted as well. Cirrhotics had a high ratio of plasma 4-hydroxyphenylethanol:4-hydroxyphenylacetic acid (60:40 vs. 30:70) as compared with normals. Although the tyramine clearance rates are similar in normals and cirrhotics, different mechanisms may be responsible for catabolism.

Deranged tyrosine metabolism in cirrhosis.

In normal individuals, the main route for tyrosine degradation is the hepatic pathway tyrosine→4-hydroxyphenylpyruvic acid→homogentisic acid→CO(2). Quantitatively minor pathways, in large part extrahepatic, are: tyrosine→tyramine→octopamine and tyrosine→dopa→catecholamines.In cirrhosis, the main hepatic pathway is blocked to varying degrees at the first three stages. This appears to be due to lack of activity of the enzymes tyrosine transaminase, PHPA oxidase, and HGA oxidase, the first step being rate limiting. Hypertyrosinemia and tyrosine intolerance result.With the main hepatic pathway partially blocked, an abnormally large amount of tyrosine passes into the normally minor extrahepatic pathway leading to the false neurotransmitters tyramine and octopamine. Overproduction of these amines ensues and they accumulate in the body fluid.The false neurotransmitters can displace catecholamines from their storage sites in the peripheral and central nervous system, and thereby disrupt adrenergic processes in arterioles, kidneys, and brain. Their accumulation in cirrhotic patients may play a role in the pathogenesis of hepatic encephalopathy, hepatorenal syndrome, and hyperdynamic circulation.