David Branski

Dysphagia as a Primary Manifestation of Hyperthyroidism

A 69-year old woman suffered from severe dysphagia, abdominal pain, and weight loss. The dysphagia was accompanied by nasal speech, nasal regurgitation of food, weakness, and wasting of the proximal muscles of the upper and lower girdles. Laboratory data revealed T3 sephadex uptake 65.2%; T4 15.1 mcg%; and T3 250 ng%. Treatment with antithyroid medication reversed the manifestation of all the symptoms, including dysphagia. Cine-studies revealed esophageal motor dysfunction as the cause of the dysphagia. Hyperthyroidism is a rare, but treatable cause of unexplained dysphagia.

Small intestinal changes in enterocolitis complicating Hirschsprung's disease.

Hirschsprungs disease is one of the more common causes of childhood bowel obstruction. The disease can cause enterocolitis which, untreated, may result in considerable mortality. We describe our evaluation of two infants who suffered from intractable diarrhea of infancy secondary to Hirschsprungs disease. We found that mucosal damage to the small bowel and disaccharidase deficiency are among the most important mechanisms producing this complication. Therefore, management of enterocolitis including parenteral alimentation should proceed as soon as the complication is observed.

Intrahepatic cholestasis for 15 years without cirrhosis.

Whether prolonged cholestasis is followed by hepatic cirrhosis is still controversial. We have studied two unrelated children who have had cholestasis for 15 years, but neither of whom have developed cirrhosis. Both have severe growth retardation, peculiar facies, pulmonic stenosis, transitory renal tubular acidosis, and vitamin D-resistant rickets. The patients presented in infancy with hepatomegaly and direct hyperbilirubinemia; liver biopsy at that time revealed cholestasis and paucity of bile ducts. Subsequent serial liver biopsies have continued to demonstrate cholestasis, but there has been no evidence of cirrhosis. Electron microscopy has revealed swollen and blunted microvilli of the canalicular membrane of the hepatocyte. The patients have had elevated bile acids in the serum as well as a reversed ration of tri- to dihydroxy bile acids. Treatment with cholestyramine and phenobarbital has brought about symptomatic relief from severe pruritus and excoriation and has lowered the level of serum bile acids, although they are still above the normal range. These findings suggest that cholestasis accompanied by an elevated and reversed bile acid ratio does not universally cause hepatic cirrhosis.

Small Intestinal Epithelial Brush Border Enzymatic Changes in Suckling Mice Infected with Reovirus Type 3

Summary: Suckling mice infected with reovirus type 3 were examined for changes in the epithelial brush border of the small intestine. After 3 days of infection with reovirus type 3, no significant changes were found in intestinal morphology or activity of any enzymes tested. After 6 days, villi were shortened and blunted with lymphangiectatic lesions and mild mononuclear infiltration in the lamina propria. In addition, there was a significant decrease in lactase (P < 0.001) and enterokinase activity (P < 0.05). However, there were no significant changes in the activities of alkaline phosphatase. In contrast, maltase (P < 0.001) and leucine amino-peptidase (P < 0.05) activities in the infected mice were significantly increased. These data suggest that brush border enzymes are affected differently by reovirus infection.Speculation: The decrease in lactase activity and increase in maltase and leucine aminopeptidase in infant mice infected with reovirus type 3 can be a reflection of accelerated maturation subsequent to an increased turnover of the epithelial cells of the crypt and villi or to an induction of specific enzymes. In addition, it is possible that the severe decrease of lactase activity in comparison to other brush border enzyme changes is due to the fact that lactase is more vulnerable than are other enzymes to mucosal injury and the possibility that lactase is a receptor for the virus.

Reovirus type 3 infection in a suckling mouse: the effects on pancreatic structure and enzyme content.

Summary: Alterations in pancreatic function and structure were examined in suckling mice infected intraperitoneally with reovirus type 3. The results were compared to pancreatic zymogen enzyme activities and histology in adult mice infected with the same virus. No effect of the reovirus type 3 on the adult mice could be elicited.In contrast, the suckling mice infected by the reovirus type 3 revealed a definite change in pancreatic zymogen enzymes. However, the zymogen enzymes were affected in a nonparallel fashion and three groups of enzymes with different responses were noted. Amylase and lipase activities were significantly diminished (P < 0.001) at 6 days of viral infection. The endopeptidases, trypsin (P < 0.025) and chymotrypsin (P < 0.001) activities were increased significantly in the infected group. The exopeptidases, carboxypeptidase A and B in the infected animals were not changed significantly compared to the control.It seems reasonable that the reovirus type 3 infection in the suckling mouse causes diminished lipase and amylase activities that might contribute to the pathogenesis of viral enteritis.Speculation: Studies on viral enteritis in infants and young animals have primarily implicated changes in the small intestine as the cause of diarrhea. The viral invasion of the intestinal mucosa causes villous cell destruction and as a consequence, the mucosa generated is immature and incapable of handling normal salt and water absorption.In addition, changes in pancreatic function as a result of an extension of the viral infection to the pancreatic parenchyma might contribute to the pathophysiologic mechanisms operating in viral enteritis.In the infected suckling mice, only amylase and lipase activities are diminished to a large extent, while trypsin and chymotrypsin activities are elevated and carboxypeptidase A and B activities remain unaffected. The nonparallel change in pancreatic enzymes toward a viral insult can be explained by a separate effect of the virus on the biosynthesis of each of the zymogen pancreatic enzymes. It is conceivable that amylase and lipase while in a developing stage, are more affected by the virus than the other pancreatic enzymes which are already developed to a certain extent. Another explanation is that lipase and amylase activities are intrinsically more prone to be decreased in response to different disease states affecting the pancreas. Diminished lipolytic and amylolytic activities due to viral gastroenteritis is a possible contributing factor of the diarrhea in infants and children.

432 THE EFFECT OF ACQUIRED POSTNATAL MALNUTRITION ON PANCREATIC ENZYMES IN THE RAT

In order to characterize the response of the pancreas to malnutrition during the critical neonatal growth phase, acquired postnatal malnutrtion was induced in the rat by using the expanded litter. An experimental nursing litter of 16 rats and control litters of 7-8 rats were formed. At 19 days of age, pups were sacrificed, the pancreas resected, weighed and prepared. Mean pancreatic weight was decreased in malnourished rats to a greater extent (49% vs 60%) than the decrease in total body weight. Decreased organ weight was due mostly to a decrease in DNA content and in cell number, with a small but significant decrease in cell size.Enzyme activities expressed per total organ were all diminished; trypsin (T), carboxypeptidase A (CPA) and B (CPB), and amylase (A) to an intermediate extent; and chymotrypsin(CH), the least. Specific activities of the enzymes and total organ activities were decreased in a non-parallel fashion. Specific activities of lipase (L) and trypsin (T) were decreased (p<.05) lipase the most severely; the remaining enzymes were resistent to change. This can be explained by either a selective effect of malnutrition on a critical development period for lipase and trypsin, or that lipase, in general, is more vulnerable to insult.

194 THE EFFECT OF INTRAUTERINE GROWTH RETARDATION (IUGR) ON SMALL INTESTINAL ENZYMES

Fetal malnutrition and growth retardation can be related, in part, to poor placental blood supply. Experimental IUGR was induced on the 18th day of gestation in pregnant rats by ligating the uterine horn, while leaving the opposite horn intact as a control. On the 22nd day of gestation, the weight of the fetal, small intestine parallels the decrease of body weight. The weight loss is related to a significant reduction in DNA content and in cell number, and to a lesser extent, to a decrease in cell size.In contrast to maltase (M), alkaline phosphatase (AP), and enterokinase (EK), only lactase (L) activity is significantly decreased in fetuses paired from same mothers. These results suggest, that in addition to the decreases in small intestinal cell number and enzyme content in IUGR, there is a proportionally greater decrease in L activity. This can be explained by either a selective effect of IUGR on a critical developmental period for lactase, or that lactase is more vulnerable to insult.(*Units ± S.D. = μmole/gm protein/min.)

400 A NON-PARALLEL DECREASE IN PANCREATIC ENZYMES IN REO VlRUS TYPE 3 INFECTION OF SUCKLING MICE

A critical phase in the structural and functional maturation of the pancreas takes place in the neonatal period. The response to Reo Virus type 3 in suckling mice was studied after injecting 1×107 PFM into 9 day old animals intraperitoneally. Both control and test animals were sacrificed either 3 or 6 days following viral injection. Histology of the pancreas, after 3 and 6 days of viral infection, revealed a normal architecture, normal acinar cells with only a mild mononuclear infiltration observed in mice after 6 days of infection (F).In the 6 day infected mice, amylase (A), is significantly reduced (p< 0.001) as compared to the control of the same age. Lipase (L) is decreased as well, but to a lesser degree. In contrast, trypsin (T), increased significantly (p<0.02) in 3 day infected, but no difference in activity is seen in 6 day infected mice. Chymotrypsin (CT), was increased significantly (p < 0.02) over the similar control group. Carboxypeptidase A (CPA) & B (CPB) activities were not altered in either the 3 or 6 day infected animals. The enzyme activities can be divided into three groups; the amylase and lipase activities are diminished, the endopeptidases, trypsin and chymotrypsin are increased and the exopeptidases, carboxypeptidase A & B are without change. The effect of the viral infection on the enzyme activities indicate a non-parallel change on the developmental pattern of the pancreatic enzymes. (*units ± S.D. = μ moles/mg protein/min.)