Ellen Kahn

Increased oxidative stress and decreased antioxidant defenses in mucosa of inflammatory bowel disease.

Inflammatory bowel disease (IBD) is characterized by chronic intestinal inflammation whose cellular components are capable of oxidative respiratory bursts that may result in tissue injury. Mucosal biopsies were analyzed for protein carbonyl content (POPs), DNA oxidation products [8-hydroxy-2′-deoxyguanosine (8-OHdG)], reactive oxygen intermediates (ROIs), trace metals (copper, zinc, and iron) and superoxide dismutase (Cu-Zn SOD). In Crohns disease biopsies, there was an increase in ROIs, POPs, 8-OHdG, and iron, while decreased copper and Cu-Zn SOD activity were found in inflamed tissues compared to controls. For ulcerative colitis, there was an increase in ROIs, POPs, and iron in inflamed tissue compared to controls, while decreased zinc and copper were observed. An imbalance in the formation of reactive oxygen species and antioxidant micronutrients may be important in the pathogenesis and/or perpetuation of the tissue injury in IBD and may provide a rationale for therapeutic modulation with antioxidants.

Endoscopically removed malignant colorectal polyps: Clinicopathologic correlations

BACKGROUND/AIMS Treatment options for patients with endoscopically removed malignant colorectal polyps are polypectomy alone vs. polypectomy followed by surgery. The aim of this study was to define histopathologic parameters that can be used for clinically relevant treatment decisions. METHODS Five pathologists evaluated 140 polyps for the presence or absence of unfavorable histology. Unfavorable histology was tumor at or near (< or = 1.0 mm) the margin and/or grade III and/or lymphatic and/or venous invasion. Adverse outcome was recurrent and/or local cancer and/or lymph node metastasis. RESULTS Adverse outcome was 19.7% (14 of 71), 8.6% (2 of 23), and 0% (0 of 46) when unfavorable histology was present, indefinite (lack of agreement), and absent, respectively (P < 0.0005, present vs. absent). Four patients with cancer > 1.0 mm from the margin had an adverse outcome (2 with lymphatic invasion and 2 indefinite for lymphatic invasion). Four patients with negative resections later developed distant metastases. Eight patients (6.3%) died of disease, and 2 of 69 without unfavorable histology (both indefinite for lymphatic invasion) had an adverse outcome. Interobserver strength of agreement was substantial to almost perfect for margin, grade, and venous invasion and fair to substantial for lymphatic invasion. CONCLUSIONS This system is usable clinically. Patients with unfavorable histology are probably best managed by resection postpolypectomy, whereas in the absence of unfavorable histology, they probably can be treated by polypectomy only.

Sclerosing cholangitis, chronic pancreatitis, and sjogren's syndrome: A syndrome complex

The disease complex of chronic pancreatitis, sclerosing cholangitis, and Sjogrens syndrome seems to be a well-defined entity with an autoimmune cause similar to that which occurs in primary biliary cirrhosis. Treatment depends on the component of primary sclerosing cholangitis and, more particularly, on the degree of extrahepatic involvement.

Hypertension secondary to renin-secreting juxtaglomerular cell tumor: case report and review of 38 cases.

A 15-year-old girl with severe high renin hypertension caused by a juxtaglomerular cell tumor (JCT) was successfully treated with the calcium channel blocker nifedipine until surgical removal effected a permanent cure. This case was incorporated into a review of the 37 cases previously published. Comparison of the children and adolescents with the adult population showed that the features of JCT were similar in the two groups except for the average duration of symptoms prior to diagnosis (pediatric group 2.6 years vs. 6.0 years for the adult group). Analysis of all 38 cases demonstrated the following:1.Teenagers constituted the largest single population with JCT (39%) and approximately two-thirds of the entire population were female.2.Many patients failed to show persistent hypokalemia despite high plasma renin activity and secondary hyperaldosteronism.3.Renal angiography was initially negative in more than half the cases.4.Renal vein renin failed to show lateralization to the affected kidney in 52% of the cases.5.Computerized tomography demonstrated a renal mass in all of the cases in which it was performed, even when other imaging studies were negative.6.Calcium channel blockers may evolve as the preferred treatment for the high renin hypertension of JCT.

Multiple ischemic infarcts in a child with AIDS, varicella zoster infection, and cerebral vasculitis

A 4 1/2-year-old girl with acquired immunodeficiency syndrome and prolonged varicella zoster virus skin infection developed multiple ischemic strokes and radiologic and histopathologic evidence of central nervous system vasculitis. Typical features of acquired immunodeficiency syndrome encephalitis were not present and there was no evidence of vasculitis outside the nervous system. Central nervous system vasculitis probably resulted from varicella zoster virus infection that persisted because of immunodeficiency. This acquired immunodeficiency syndrome complication has only rarely been described in adults and to our knowledge has not been described in children.

Biliary Atresia Revisited

Extrahepatic biliary atresia (EHBA) is an inflammatory fibrosing process affecting the extrahepatic and intrahepatic biliary tree resulting in fibrous obliteration of the extrahepatic biliary tract, ductopenia of intrahepatic bile ducts, and biliary cirrhosis. EHBA is divided into a correctable and a noncorrectable type with focal patency of the otherwise atretic biliary tree in the former and no patency of the biliary tree in the noncorrectable type. EHBA is divided in a fetal, prenatal or embryonic, and a more common, perinatal, acquired form. The symptoms of the former start shortly after birth and there is frequently an association with a variety of congenital anomalies. Children with the perinatal form become jaundiced several weeks after birth; no associated congenital anomalies are present. Morphologically, an inflammatory and fibrosing process of the extrahepatic biliary tree leads to complete lumenal obliteration. The liver is characterized by a nonspecific giant cell transformation, and portal expansion by fibrous connective tissue with marked ductular proliferation. With time, ductopenia and biliary cirrhosis develop. The diffential diagnosis with other conditions with similar microscopic patterns such as as alpha-1 antitrypsin deficiency, total parental nutrition, obstruction by a choledochal cyst, arteriohepatic dysplasia, familial progressive intrahepatic cholestasis, and alteration of the bile acid metabolism is discussed. In the fetal group, abnormalities in different genes seem to play a role; ductal plate malformation is another possibility. Different etiologies have been postulated in the perinatal form of EHBA: genetic susceptilibility, vascular factors, toxins, and infections mainly by rotavirus and reovirus. The pathogenesis is complex. EHBA is a heterogenous disease, resulting from a combination of genetic factors, insults, and activition of different genetic and immunologic pathways. The treatment of EHBA is surgical, with anastomosis between the biliary tree and the intestine in the correctable type and a hepatic portoenterostomy (HPE) for the noncorrectable group. HPE is a temporizing treatment allowing the infant to develop and grow, followed in the majority of the patients by liver transplantation.

Umbilical Cord Stricture and Overcoiling Are Common Causes of Fetal Demise

Although umbilical cord stricture and umbilical cord overcoiling have been established as causes of intrauterine fetal demise, relatively few studies addressed this issue, most of them being case reports. We reviewed a total of 268 fetal autopsies during a 3-year period from 1998 to 2001. One hundred thirty nine cases of fetal demise including spontaneous abortion were identified. Nineteen percent (26 of 139) were associated with umbilical cord stricture, overcoiling, or a combination of both. Stricture of the umbilical cord was defined as a decrease in diameter in relation of the remaining umbilical cord; overcoiling as 0.3 coil/cm or greater. Fetal demise most commonly occurred in the second trimester, with a mean gestation age of 21 weeks. The average maternal age was 33 years; 15% had a prior fetal demise. We found that 77% (20 of 26) of these cases had umbilical cord stricture only or with overcoiling, 23% (6 of 26) had umbilical cord overcoiling alone. Localized deficiency of Whartons jelly and increased collagen were found in all cases with umbilical cord stricture with or without overcoiling. In patients with umbilical cord overcoiling alone, 25% had Whartons jelly deficiency; half of them had increased collagen deposition in the umbilical cords. The placenta was reviewed for secondary thrombosis of the vessels of the chorionic plate. Thrombosis of the vessels of the chorionic plate was noted in 54% of the patients. Our study suggests that umbilical cord stricture and cord overcoiling may represent two distinct pathological entities commonly causing fetal demise. This observation reinforces the importance of a fetal autopsy with careful examination of the placenta and umbilical cord with documentation of the cord coil index.

Proliferative Defects in Ulcerative Colitis Patients

The proliferative characteristics of epithelial cells in rectal biopsies from a group of 18 patients (ages 18-72) with ulcerative colitis spanning several months to over 20 years duration were examined, using an in vitro 3HTdR labeling technique. Although the labeling indices for patients with inflammatory bowel disease did not differ significantly from that of control (8.9 +/- 3.6 vs 7.7 +/- 3.9), the number of labeled cells/individual crypt column was higher among some crypts in ulcerative colitis patients. A normal proliferative pattern was demonstrated in crypts of 5/18 patients (27.8%) with DNA synthesis confined to the lower two-thirds of the crypt and the lower third the major zone of proliferation. Thirteen patients (72.2%) showed extension of the proliferative compartment to the surface of the glands, while retaining the lower third of the gland as the predominant proliferative zone (Stage I abnormality). Of these 13, seven had an additional abnormality, namely, a shift of the major zone of proliferation to the middle third of the crypt (Stage II abnormality), a pattern first reported in the colorectal mucosa of patients with a history of colon cancer. Precancerous lesions, including incompletely differentiated epithelium and lateral crypt budding, were recognized in all of these cases, suggesting that the Stage II abnormality is a proliferative parameter forecasting neoplastic transformation.

Rapidly progressive cholestasis: An unusual reaction to amoxicillin/clavulanic acid therapy in a child.

Hepatotoxity associated with amoxicillin/clavulanic acid is usually a self-limited disease with complete recovery. We report a rapidly progressing liver disease with ductopenia and portal fibrosis in a 3-year-old boy treated with Augmentin.

Cutaneous polyarteritis nodosa associated with Crohn's disease

A 13-year-old white girl with Crohns colitis developed recurrent erythematous tender cords and nodules in the lower and upper extremities. Histologic examination of subcutaneous nodules of the right arm revealed granulomatous panarteritis of two muscular arteries in the subcutis. The patients resected colon showed granulomatous transmural colitis without vasculitis. The association between Crohns disease and cutaneous polyarteritis nodosa is reviewed and emphasis placed on histologic evaluation of suspicious subcutaneous nodules for correct diagnosis.