Pancreatitis caused by common bile duct stones in a 3-year-old boy with prior surgery for a choledochal cyst.

Pancreatitis in children is uncommon. Compared to adults, pancreatitis in children is usually related to trauma, anatomic anomalies, infections, hereditary, and systemic disease, but not gallstones or alcohol. Most cases do not require endoscopic intervention. We report an unusual case of recurrent pancreatitis in a child related to common bile duct stones requiring endoscopic treatments after surgical treatment for choledochal cyst.

Therapeutic ERCP in the management of pancreatitis in children.

BACKGROUND: The use of diagnostic and therapeutic endoscopic retrograde cholangiopancreatography (ERCP) is increasing in the management of pancreatobiliary diseases in children. METHODS: Over a 32-month period, we performed 34 ERCP procedures for the treatment of pancreatitis in 22 children at two university hospitals. Demographics and clinical data and ERCP findings were documented. Clinical status was assessed 6 months before the first ERCP and 6 months after the last ERCP, according to general condition, severity and frequency of pain, and health care encounters (emergency department visits, clinic visits, and hospital admissions related to the pancreatitis). RESULTS: Mean age of the patients was 10.7 years (range 1.5 to 17 years). Abdominal pain was the main presenting symptoms with hyperamylasemia and hyperlipasemia. Clinical diagnoses included acute pancreatitis (6), recurrent pancreatitis (5), and chronic pancreatitis (11). The mean follow-up was 16.4 months. Nine patients had sphincter manometry, with abnormal results leading to biliary sphincterotomy in 4. Fifteen patients underwent a total of 23 therapeutic ERCP procedures unrelated to sphincter dysfunction. There were 2 complications of 34 procedures (6%), both being mild pancreatitis after sphincter manometry. There were no deaths. There was a significant reduction in frequency (p < 0.01) and severity of pain (p < 0.01) after intervention. Patients without pancreatographic changes of chronic pancreatitis had the most marked clinical improvement (p < 0.05). In those with ductal changes of chronic pancreatitis, clinical improvement was not predicted by the extent of ductal changes. There was a significant decrease in health care encounters (p < 0.05) and improvement in general condition (p < 0.01) after endoscopic therapy, especially in those with a normal pancreatogram. CONCLUSIONS: Therapeutic ERCP is safe in pediatric patients with pancreatitis. Significant clinical improvement is achieved in patients with biliary or pancreatic stone disease. Prospective studies with long-term follow-up are needed to determine the impact of endoscopic therapy in patients with chronic pancreatitis and sphincter of Oddi dysfunction.

Crohn's disease in the Chinese population. An experience from Hong Kong.

PURPOSE: Crohn's disease was extremely rare among Chinese. We reviewed all cases diagnosed as having Crohn's disease during a five-year period. METHODS: A diagnosis of Crohn's disease was made only if all of the following criteria were fulfilled: 1) clinical symptom(s) and sign(s) compatible with chronic inflammatory bowel disease; 2) exclusion of intestinal infection by repeated stool cultures; 3) macroscopic features of small and/or large intestinal inflammation with skip lesion, stricture, and fistula formation; 4) histologic features of Crohn's disease, i.e., focal lymphoid aggregate, focal cryptitis, and granuloma formation; 5) clinical response to conventional therapy for inflammatory bowel disease. RESULTS: Fifteen ethnic Chinese patients were diagnosed as having Crohn's disease in this period. All patients had colitis, whereas small intestine inflammation was documented in only 47 percent of patients. Extraintestinal manifestations were uncommon except for arthropathy: ankylosing spondylitis (2), sacroiliitis (1), juvenile rheumatoid arthritis (1), and colitic arthritis (1). The majority of our patients responded to medical therapy. Surgery was undertaken in 33 percent of patients. CONCLUSION: Although there is a general increased incidence of Crohn's disease in the Western world, we too are beginning to see more cases in the Far East. Nevertheless, gastrointestinal infection with bacteria and/or parasites should still be carefully excluded in these countries.

A humanized antibody specific for the platelet integrin gpIIb/IIIa.

C4G1, a murine mAb reactive with the platelet gpIIb/IIIa integrin, was humanized for potential treatment of thrombosis-related disorders. The variable regions of light- and heavy-chain cDNAs from the C4G1 hybridoma were first cloned and sequenced. Humanized C4G1 Ab of the IgG1 isotype was constructed by combining the complementarity-determining regions of C4G1 with human framework and constant regions. The human framework was chosen to maximize homology with the C4G1 variable region sequence, and a computer model of C4G1 was used to aid design of the final framework sequence. Genetic constructs were also developed to produce Fab and F(ab')2 fragments of the humanized C4G1 Ab. The humanized IgG1 Ab as well as the Fab and F(ab')2 fragments showed equivalent binding affinities to their murine counterparts, indicating no loss in binding affinity during the humanization process. The humanized Ab and its fragments were also shown to inhibit platelet aggregation and to inhibit binding of fibrinogen to gpIIb/IIIa in vitro.

The RRE of human immunodeficiency virus type 1 contributes to cell-type-specific viral tropism.

As part of a general program investigating the mechanism of the Rev axis of human immunodeficiency virus type 1 (HIV-1) autoregulation, a series of proviral HIV-1 mutants which differ from the parental HXB2 strain at selected positions within the RRE were constructed. All of the mutations were designed to perturb the RRE by introducing local helix disruptions without altering the coding potential of the overlapping envelope open reading frame. Viral replication in various cell types was monitored by a cell supernatant reverse transcriptase assay and Northern (RNA blot) analysis. All proviral RRE mutants displayed at least some impairment in replication. However, the relative impairment varied drastically among the various cell types tested. This suggests that the RRE may contribute to cell-type-specific viral tropism.

Genomic heterogeneity of DNA repair. Role in aging?

The introduction and repair of DNA lesions are generally heterogeneous with respect to different genomic domains. In particular, the repair of helix-distorting damage, such as the cyclobutane pyrimidine dimers (CPD) induced by ultraviolet light occurs selectively in expressed genes. This is due in large part to the preferential repair of transcribed DNA strands, which is then reflected in a bias toward mutagenesis from persisting lesions in nontranscribed strands. Consequently, determination of overall genomic repair efficiencies may not be a good indicator of cellular sensitivity to agents that damage DNA. Although some studies suggest an age-related accumulation of altered nucleotides in DNA, we do not know the intragenomic distribution of those changes and whether they are relevant to the physiological aspects of aging. Subtle changes in the pattern of preferential repair during maturation could have profound effects on cell and tissue function. DNA repair has been analyzed in differentiating cell systems as possible models for aging. We have observed attenuated overall repair of CPD in differentiated rat myoblasts or PC12 neuron-like cells. In both model systems, several expressed genes have been shown to be repaired relatively efficiently but without strand specificity. In another model system of human HT1080 fibroblasts differentiating in the presence of dexamethasone, we demonstrated enhanced repair in the gene for plasminogen activator inhibitor I whose transcription is induced and, correspondingly, a reduced repair rate in the urokinase plasminogen activator gene whose transcription is suppressed. We conclude that any attempted correlation of the phenomena of aging with DNA repair should focus on the relevant genes in the tissue of interest.