Constantine Arvanitakis

Giardiasis: Clinical Spectrum and Functional-Structural Abnormalities of the Small Intestinal Mucosa

We studied 17 adult and 11 pediatric patients with giardiasis in order to examine the clinical spectrum and the functional-structural changes of the small intestinal mucosa. The most common clinical manifestations were diarrhea, weight loss, abdominal cramps, and, in children, failure to thrive. Giardiasis was frequently associated with hypogammaglobulinemia (HGG) and intestinal nodular lymphoid hyperplasia (47% and 41% of adults, respectively). Malabsorption of D-xylose and vitamin B12 occurred in 55% and 60% of patients, respectively, steatorrhea in 64%, and hypocarotinemia and low serum folate in 36%. No or only slight mucosal abnormalities were present in pretreatment jejunal biopsies of 75% of those adults on whom biopsies were performed, whereas 25% (all with HGG) had marked inflammation and changes of the villus-crypt architecture. Marked structural changes were seen in 43% of subjects with HGG. Estimates of brush border enzymes showed a significant reduction in lactase, sucrose, and leucyl-naphthylamidase specific activity in about 80% of patients assayed, whereas maltase, isomaltase, and alkaline phosphatase were not affected. Five patients were studied prospectively and absorption tests and jejunal mucosal biopsies were repeated after treatment with metronidazole or quinacrine. Resolution of symptoms with restoration of the morphologic and functional abnormalities of the small intestinal mucosa occurred after treatment in all but 1 patient. These observations indicate that Giardia cause brush border damage, which, is usually reversible with eradication of the parasite. Other factors, alone or in combination with Giardia, may be responsible for the cell damage beyond brush border injury found in some patients.

Diagnosis of pancreatic disease by a synthetic peptide. A new test of exocrine pancreatic function.

Abstract N-benzoyl-L-tyrosyl- p -aminobenzoic acid, a synthetic peptide, is specifically cleaved by the pancreatic endopeptidase chymotrypsin; the released p -aminobenzoic acid (P.A.B.A.) is absorbed and excreted in the urine. To evaluate its diagnostic value, the urinary excretion of P.A.B.A. after oral administration of this peptide was examined in patients with pancreatic disease (chronic pancreatitis with pancreatic insufficiency and pancreatic carcinoma). Recovery of P.A.B.A. in the urine was significantly lower in patients with pancreatitis (40%) and pancreatic carcinoma (56%) than in the control group (75%) (P

Diagnosis of exocrine pancreatic insufficiency in cystic fibrosis by the synthetic peptide N-benzoyl-l-tyrosyl-p-aminobenzoic acid*

The synthetic peptide N-benzoyl-L-tyrosyl-p-aminobenzoic acid is specifically cleaved by chymotrypsin to Bz-Ty and PABA. The liberated PABA is absorbed and excreted in the urine. Accordingly, PABA recovery reflects intraluminal chymotrypsin activity and is an index of exocrine pancreatic function. This test was evaluated in 24 patients with cystic fibrosis to determine its role in the diagnosis of exocrine pancreatic insufficiency. Cumulative percent PABA recovery in six hours was significantly lower in CF patients compared with the control group. No overlap was noted between the two groups. There was good correlation between PABA recovery, fecal chymotrypsin activity, and coefficient of fat absorption. These findings indicate that PABA recovery is significantly reduced in patients with CF and steatorrhea and may prove a practical and reliable test of pancreatic insufficiency.

Abnormalities of Jejunal Mucosal Enzymes in Ulcerative Colitis and Crohn’s Disease

Jejunal mucosal function and structure was examined in 31 patients with ulcerative colitis and 29 patients with Crohns disease with ileal, ileocolonic or colonic involvement; A significant reduction of the specific activity of disaccharidases (lactase, sucrase and trehalase) in jejunal mucosal homogenate occurred in patients with inflammatory bowel disease. Similarly, alkaline phosphatase was reduced in ulcerative colitis. Several dipeptidases such as glycyl-leucine, leucyl-glycine, glycyl-glycine and valyl-proline hydrolase activities were lower in patients with inflammatory bowel disease than in controls. Histological changes in jejunal mucosal biopsies occurred in 71% of patients with ulcerative colitis and 61% with Crohns disease. These changes ranged from mild abnormalities of villus architecture to marked reduction of villus height. Most patients with a reduction in mucosal enzymes had concommitant morphological changes in jejunal mucosal biopsy. The results of this study indicate that functional and structural abnormalities of the jejunal mucosa frequently occur in patients with inflammatory bowel disease without radiologic evidence of proximal small bowel involvement.

Effect of aspirin on intestinal absorption of glucose, sodium, and water in man.

The effect of aspirin on small intestinal function in six healthy volunteers was examined using a segmental perfusion technique, with a test solution of 40 mM D-glucose, 140 mM NaCl, and 0-5% polyethylene glycol. Jejunal glucose, sodium, and water absorption rates were inhibited by 50% after oral administration of 2-6 g aspirin. Adenosine triphosphate (ATP) concentration was assayed in jejunal mucosal biopsies before and after aspirin. There was an almost 50% decrease in mucosal ATP levels after aspirin. This effect may be mediated through cellular injury and impairment of mitochondrial energy metabolism. These data suggest that aspirin may significantly alter small intestinal function. It appears possible that the inhibitory effect of aspirin on glucose absorption may account, at least in part, for the lower blood sugar levels observed with the use of the drug.

Treatment of toxic megacolon a comparative review of 29 patients

A review of 29 patients with toxic megacolon complicating ulcerative colitis was undertaken to (1) compare the results of medical and surgical treatment; (2) determine the optimal timing for surgical intervention; and (3) identify possible precipitating factors. Twenty-one patients were treated medically with nasogastric suction, steroids, parental fluids, blood transfusion, and antimicrobial agents. Of the 21 patients, 11 (53%) showed improvement by subjective and objective creria and 10 (47%) failed to respond. Sixteen patients were treated surgically. This group was subdivided into 8 patients who failed to respond to medical treatment and 8 treated surgically. Total proctocolectomy with ileostomy was performed in 8, and subtotal colectomy and ileoproctostomy in 8, with subsequent proctectomy and ileostomy in 6 patients. Six of 8 patients (75%) treated primarily surgically improved, and 2 (25%) died. Seven of 8 patients (87.5%) treated surgically after failure of medical trial showed definite postoperative improvement, and 1 (12.5%) failed. Those who were operated on within the first 48–72 hr after the diagnosis of toxic megacolon was made responded uniformly well. Anticholinergics, opiates, barium enema, and colonoscopy were identified as possible precipitating factors in 70% of cases. The results of this study in this patient population indicate that early surgical therapy in toxic megacolon is associated with better results than medical therapy (P<0.025). Although intensive, optimal medical therapy plays a significant role in the management of toxic megacolon, failure to induce rapid improvement within 48–72 hr constitutes an indication for definitive surgical treatment.

Lower esophageal ring: endoscopic and therapeutic aspects.

The endoscopic and therapeutic aspects of lower esophageal ring (LER) were examined in 34 patients. Nine symptomatic patients were treated with bougienage; 7 responded satisfactorily, and 2 required pneumatic dilation. After successful disruption of the ring, symptoms recurred in only 1 patient.

Diagnostic Value of Serum Ferritin in Primary Hepatocellular Carcinoma

The diagnostic value of serum ferritin levels was evaluated in 19 patients with biopsy-proven primary hepatocellular carcinoma (PHC) and 26 patients with chronic liver disease (CLD). Serum ferritin levels were significantly elevated in PHC, as compared with CLD and controls (p less than 0.0005). Similarly, serum ferritin/SGOT ratio, an index of increased ferritin production, was significantly higher in PHC than in CLD and controls. Serum alpha-fetoprotein (alpha-FP) was higher in PHC than in CLD (p less than 0.0025). No significant correlation was noted between serum ferritin and alpha-fetoprotein or SGOT in PHC and CLD. 17 of 19 patients with PHC had serum ferritin values over 450 ng/ml (sensitivity 88%). By contrast, only 10 of 17 patients with PHC (59%) demonstrated alpha-FP levels over 25 ng/ml, compatible with the diagnosis of PHC. 9 of these 10 patients had ferritin levels over 450 ng/ml, within the distribution of values for PHC. Conversely, 7 of 17 patients with PHC (40%) had normal levels of alpha-FP (false-negative). However, 6 of these patients (86%) had ferritin levels over 450 ng/ml, consistent with values in PHC. In this study, the overall sensitivity of serum ferritin in PHC was higher than that of alpha-FP (88 versus 59%) and its specificity 85 versus 68% for alpha-FP. These data indicate that serum ferritin may be utilized as a useful diagnostic marker in the evaluation of patients with PHC.

Evaluation of [14C]aminopyrine breath test, peripheral clearance of [99mTc]EHIDA, and serum bile acid levels in liver function and disease.

The purpose of this study is to evaluate the diagnostic value of the following tests in the assessment of patients with chronic liver disease (CLD) and cholestatic syndrome (CS):(1) aminopyrine breath test, measuring14CO2 excretion in the expired air, (2) peripheral clearance of [99mTc]EHIDA, and (3) postprandial levels of glycocholic acid (GCA) and glycochenodeoxycholic acid (GCDCA). The results indicate that: (1)14CO2 2-hr excretion rate is a specific and sensitive marker of liver function, with good correlation with postprandial bile acid levels, [99mTc]EHIDA retention, and the conventional tests of serum albumin and prothrombin time. (2) Peripheral clearance and retention of [99mTc]EHIDA increased in both groups of CLD and CS vs controls, but it does not discriminate between the two. (3) Postprandial bile acids were elevated in CLD, particularly those of GCDCA, whereas GCA levels were significantly elevated in CS compared with CLD. This may be due to increased synthesis and entry into the blood. (4) The combination of [14C]aminopyrine breath test and postprandial levels of GCDCA enhance the diagnostic value, specificity, and sensitivity in the assessment of patients with CLD.

A Possible Association of Pernicious Anemia with Neoplasia

7 out of 39 patients with pernicious anemia developed 9 different neoplasms during a period of 3--20 years after the diagnosis of pernicious anemia. These primary neoplasms originated from the lymph nodes, larynx, colon, stomach, kidney, meninges, maxillary sinus and eighth nerve. Treatment with vitamin B12 did not influence the development of tumor. Statistical analysis showed that the observed incidence of 9 neoplasms in this group was significantly higher than the expected 3.3 cases during the aggregate follow-up period (p = 0.002). Although a higher incidence of neoplasms in patients with other underlying diseases does not necessarily indicate an association, a high degree of suspicion for neoplastic disease is justifiable in patients with pernicious anemia.