Jean Perrault

EPIDEMIOLOGIC AND CLINICAL CHARACTERISTICS OF CHILDREN WITH NEWLY DIAGNOSED INFLAMMATORY BOWEL DISEASE IN WISCONSIN: A STATEWIDE POPULATION-BASED STUDY

OBJECTIVE To define epidemiologic and clinical characteristics of newly diagnosed pediatric inflammatory bowel disease (IBD) in a large population-based model. STUDY DESIGN All pediatric gastroenterologists providing care for Wisconsin children voluntarily identified all new cases of IBD during a 2-year period. Demographic and clinical data were sent to a central registry prospectively for analysis. RESULTS The incidence of IBD in Wisconsin children was 7.05 per 100,000, whereas the incidence for Crohns disease was 4.56, more than twice the rate of ulcerative colitis (2.14). An equal IBD incidence occurred among all ethnic groups, and children from sparsely and densely populated counties were equally affected. The majority (89%) of new IBD diagnoses were nonfamilial. CONCLUSIONS This study provides novel, prospective, and comprehensive information on pediatric IBD incidence within the United States. The surprisingly high incidence of pediatric IBD, the predominance of Crohns disease over ulcerative colitis, the low frequency of patients with a family history, the equal distribution of IBD among all racial and ethnic groups, and the lack of a modulatory effect of urbanization on IBD incidence collectively suggest that the clinical spectrum of IBD is still evolving and point to environmental factors contributing to the pathogenesis.

Protein-losing enteropathy after the Fontan operation

Patients were observed after the Fontan operation to determine the frequency and severity of protein-losing enteropathy. A total of 427 patients who survived for 30 days after the Fontan operation, performed between 1973 and January 1987, were analyzed and, thus far, protein-losing enteropathy has developed in 47 of 427. The cumulative risk for the development of protein-losing enteropathy by 10 years was 13.4% among 30-day survivors, and 5-year survival after the diagnosis was 46%. Hemodynamic studies done coincident with the diagnosis of protein-losing enteropathy have shown increased systemic venous pressure, decreased cardiac index, increased pulmonary vascular resistance, and increased ventricular end-diastolic pressure. Medical management of protein-losing enteropathy was only partially successful. Statistical analysis has shown that factors related to protein-losing enteropathy were ventricular anatomy, increased preoperative ventricular end-diastolic pressure, longer operative bypass time, increased length of hospital stay, and postoperative renal failure. This study suggests that scrupulous selection of cases for the Fontan operation is mandatory and that certain perioperative factors may predispose to this serious complication of the Fontan procedure.

Fate of the rectal mucosa after rectal mucosectomy and ileoanal anastomosis

The aim of our study was to determine if the rectal mucosa regenerates after rectal mucosectomy and endorectal ileoanal anastomosis for chronic ulcerative colitis. Such regenerated rectal mucosa could be the site of recurrent disease, leading to complications of the operation, and potential malignant degeneration. Pathologic specimens of the ileoanal anastomosis, surrounded by rectal muscular cuff, were obtained from eight patients who required takedown of their ileoanal anastomosis between one and 18 months after construction. Reepithelialization of the rectal cuff was not observed. In two patients, small islets of rectal mucosa and anal glands were identified. In all patients, the rectal muscularis propria was adherent to the serosa of the ileum by fibrous reaction. Three patients were diagnosed, both clinically and pathologically, as having chronic ulcerative colitis at the original ileoanal operation, but features suggestive of Crohns disease were noted in the subsequently resected neo-rectum. Our observations suggest that, although isolated rectal mucosal cells may remain after mucosectomy, extensive rectal mucosal regeneration does not occur, thus minimizing the risk of recurrent disease and potential malignant change. Failure of an ileoanal anastomosis is therefore most likely related either to technical factors or to the presence of unsuspected Crohns disease.

Physiologie Aspects of Continence After Colectomy, Mucosal Proctectomy, and Endorectal lleo-anal Anastomosis

We examined the physiology of continence in 12 patients at least four months after colectomy, mucosal proctectomy, and endorectal ileo-anal anastomosis for ulcerative colitis and familial polyposis. The mean fecal output (+/-SEM) was 598 +/- 60 gm, passed as 12 +/- 4 movements/24 hr, of which 4 +/- 1 were passed at night. The patients were generally continent during the day and could distinguish gas from stool, but 11 of 12 leaked stools at night. Anal sphincter resting pressures (71 +/- 8 cm H2O) and squeeze pressures (171 +/- 15 cm H2O) of patients were similar to those of ten healthy controls (P greater than 0.05), although the rectal inhibitory reflex was absent in the patients. After operation, the distal bowel had a pressure-volume curve of greater slope (0.15 +/- 0.05 ml/cm H2O) than it had in controls (0.07 +/- 0.01 ml/cm H2O, P less than 0.05) and a lesser maximum capacity (patients, 248 +/- 31 ml; controls, 406 +/- 26 ml; P less than 0.05). The greater the capacity of the neorectum, the fewer was the number of bowel movements/day (r = 0.91, P less than 0.001). We concluded that the operation preserved the anal sphincter, although it decreased the capacity and compliance of the distal bowel and impaired continence.

Multicenter trial of d-α-tocopheryl polyethylene glycol 1000 succinate for treatment of vitamin E deficiency in children with chronic cholestasis

BACKGROUND Malabsorption and deficiency of vitamin E causing neurological degeneration are common consequences of chronic childhood cholestatic liver disease. The objective of this study was to determine the long-term efficacy and safety of d-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS) in correcting vitamin E deficiency in children with chronic cholestasis who were unresponsive to other forms of oral vitamin E. METHODS Sixty vitamin E-deficient children with chronic cholestasis unresponsive to 70-212 IU.kg-1.day-1 of oral vitamin E were entered into a trial at eight centers in the United States. After initial evaluation, treatment was started with 25 IU.kg-1.day-1 of TPGS. Vitamin E status, neurological function quantitated by a specific scoring system, and clinical and biochemical parameters were monitored during therapy. RESULTS All children responded to TPGS with normalization of vitamin E status. Neurological function, which had deteriorated before entry in the trial, improved in 25 patients, stabilized in 27, and worsened in only 2 after a mean of 2.5 years of therapy. No adverse effects were observed. CONCLUSIONS TPGS (20-25 IU.kg-1.day-1) appears to be a safe and effective form of vitamin E for reversing or preventing vitamin E deficiency during chronic childhood cholestasis.

Pediatric “psc-ibd”: A Descriptive Report of Associated Inflammatory Bowel Disease Among Pediatric Patients With Psc

Background Inflammatory bowel disease (IBD) in adults with primary sclerosing cholangitis (PSC) is characterized by pancolonic involvement, a high frequency of rectal sparing, and an increased risk of pouchitis and colorectal neoplasia. The clinical features of IBD in pediatric patients with PSC have not been well described. The aim of this study was to characterize the frequency, clinical features, and natural history of IBD in pediatric patients diagnosed with PSC. Methods A retrospective chart review was performed for all patients 18 years of age or younger diagnosed with PSC seen at the Mayo Clinic between 1975 and 1999. Endoscopic and histologic features and surgical and postsurgical outcomes were recorded. Results Fifty-two children with PSC were identified. Forty-three patients (84%) were also diagnosed with IBD. In 36 of 43 cases, there was a sufficient diagnostic evaluation to allow a detailed review. Thirty-two of 36 patients (89%) had ulcerative colitis and 4 of 36 patients (11%) had Crohn’s disease. In 4 of 36 patients (11%), IBD was asymptomatic. Although the most frequent endoscopic presentation of IBD was universal colitis, endoscopic rectal sparing was frequently noted (27% of colonoscopic studies). Of the four patients diagnosed with Crohn disease, in none did perianal, fistulizing, or stricturing disease develop. Proctocolectomy was performed in six patients (17%); three operations were performed for dysplasia. Pouchitis complicated four of the five ileal pouch–anal anastomoses procedures. Conclusions Among pediatric patients (1) PSC without IBD is uncommon; (2) asymptomatic IBD may be associated with PSC; (3) because the time to dysplasia may be accelerated, once the diagnosis of IBD is made in the setting of PSC, heightened endoscopic surveillance may be indicated; (4) pouchitis occurs frequently in these patients.

Measurement of heparin concentration in whole blood with the Hepcon/HMS device does not agree with laboratory determination of plasma heparin concentration using a chromogenic substrate for activated factor X.

UNLABELLED Measurement of circulating heparin concentration has been suggested to optimize anticoagulation during cardiopulmonary bypass. The Hepcon/HMS device (Medtronic HemoTec, Inc., Parker, Colo.) uses heparin/protamine titration to quantitatively determine heparin concentration. Extensive validation of this instrument is still lacking. METHODS Agreement between heparin concentrations measured by the Hepcon/HMS system and by laboratory determination was evaluated in 16 patients undergoing cardiac operations. For laboratory determinations, plasma heparin concentration was derived from the measure of anti-Xa activity by means of chromogenic substrate technique. The Hepcon/HMS instrument and cartridges measured whole blood heparin concentration. Samples were analyzed 5 minutes after administration of heparin, 15 and 30 minutes after the start of cardiopulmonary bypass, 5 minutes after aortic unclamping, at the end of cardiopulmonary bypass, and after administration of protamine. Data were plotted and interpreted according to the method of Bland and Altman: First, a difference less than 1.4 U/ml (i.e., +/- 0.7 U/ml) was chosen as acceptable, because it would not cause major difficulties in clinical interpretation; second, the difference between the two measurement techniques was plotted against the mean of the two measures. RESULTS The mean difference (bias) between heparin concentrations derived by the Hepcon/HMS device and those obtained by laboratory determination was as expected for measures performed on whole blood versus plasma (1.45 U/ml). Nevertheless, heparin concentrations derived by the Hepcon/HMS device may be as much as 2.76 U/ml above or 6.17 U/ml below the concentrations measured in the laboratory, differences well outside the predetermined limits of agreement and clearly unacceptable for clinical purposes. CONCLUSION We conclude that heparin concentrations determined with the Hepcon/HMS instrument do not agree with laboratory determination of heparin concentration. Monitoring of heparin concentrations during bypass with the Hepcon/HMS device cannot be recommended.

Prevalence and clinical significance of human herpesviruses 6 and 7 active infection in pediatric liver transplant patients

Abstract:  Recent studies in adult liver transplant patients have suggested that both human herpesvirus (HHV)‐6 and HHV‐7 infection are important causes of morbidity following liver transplantation. However, the impact of HHV‐6 and ‐7 infection in pediatric liver transplant patients remains largely unknown. The aims were to determine the prevalence of HHV‐6 and ‐7 infection in pediatric liver transplant patients and to determine whether there is an association between HHV‐6 and ‐7 infection with episodes of graft rejection and cytomegalovirus (CMV) infection. A total of 46 pediatric liver transplant patients transplanted at Mayo Clinic between January 1994 and January 2000 were evaluated. Quantitative polymerase chain reaction (PCR) assays for CMV, HHV‐6 and HHV‐7 were performed on stored sera obtained prior to transplant, weekly for 8 wk and at 4 months and 1 yr post‐transplant. Pretransplant sera were tested for HHV‐6 antibodies by indirect immunofluorescence assay. A total of 215 blood samples were tested (mean 6.5 ± 3.1, range 3–18). CMV infection occurred in 11 of 33 (33.3%) patients, while CMV disease occurred in 4 of 33 (12%) patients. Infection with HHV‐6 (variant B) was detected in three of 33 (9.1%) patients. HHV‐7 infection was not detected. Case 1 and 2 were infants (10‐ and 11‐month old, respectively). Both were seronegative for HHV‐6 pretransplant. In both cases, HHV‐6 infection was associated with concurrent episodes of moderate to severe acute graft rejection. Case 3 was a 16‐yr‐old girl who was seropositive for HHV‐6 pretransplant. No clinical events were recorded and a liver biopsy performed per protocol showed no evidence of rejection. None of the three patients had concomitant CMV infection or disease. In this study, HHV‐6 infection occurred in 9% of pediatric liver transplant patients while HHV‐7 was not detected. A potential association between primary HHV‐6 infection and allograft rejection warrants further investigation.

Long-Term Follow-Up of Young Patients With Chronic Hereditary or Idiopathic Pancreatitis

We conducted a retrospective study of patients younger than 20 years of age who had a diagnosis of chronic pancreatitis and underwent assessment at the Mayo Clinic between 1960 and 1990. Those with a known etiologic factor for the pancreatitis (such as a virus, trauma, alcohol, or hyperlipidemia) were excluded from the study. We compared the clinical course of the 42 patients who had hereditary pancreatitis (HP)--defined as at least two family members affected by the condition--with that of the 28 patients who had idiopathic pancreatitis (IP). The mean age at initial assessment was 7 years for those with HP and 12 years for those with IP. All patients in both groups had abdominal pain. Vomiting was more frequent in patients with HP than in those with IP; otherwise the initial symptoms were similar in both groups. Patients with HP, however, had more complications, including pseudocysts (seven patients), steatorrhea (four), ascites (three), portal hypertension (two), and diabetes (one), than did patients with IP (one each had diabetes, steatorrhea, and a pseudocyst). Complications or pain necessitated surgical intervention in 23 of 42 patients with HP versus 4 of 28 patients with IP. Overall in comparison with IP, HP seems to be a more severe variant of chronic pancreatitis, inasmuch as it is associated with more frequent complications and need for surgical intervention.

Postdilution Hemofiltration in the Management of Acute Hepatic Failure: A Pilot Study

We conducted a pilot study to assess the feasibility and efficacy of postdilution hemofiltration (PDHF) in the management of acute hepatic failure. From January 1984 through May 1986, we encountered seven patients with acute hepatic failure and entered these consecutive patients in the study; three had non-A, non-B hepatitis and one each had type B hepatitis, fulminant Wilsons disease (hepatolenticular degeneration), acute allograft (liver) failure, and acute fatty liver of pregnancy. Two of these seven patients were unable to undergo PDHF because of a precarious hemodynamic status. Of the five patients treated with PDHF, four had amelioration of hepatic encephalopathy; in two of these patients, a close temporal relationship was noted between the improvement and the procedure. Four patients had appreciable thrombocytopenia related to PDHF and bleeding complications. Our preliminary results support a possible role for PDHF as a temporary artificial liver support system for patients with acute hepatic failure.