Health Status and Lifestyle Habits of US Medical Students: A Longitudinal Study.

BACKGROUND: Evidence shows that physicians and medical students who engage in healthy lifestyle habits are more likely to counsel patients about such behaviors. Yet medical school is a challenging time that may bring about undesired changes to health and lifestyle habits. AIMS: This study assessed changes in students' health and lifestyle behaviors during medical school. SUBJECTS AND METHODS: In a longitudinal study, students were assessed at both the beginning and end of medical school. Anthropometric, metabolic, and lifestyle variables were measured at a clinical research center. Data were collected from 2006 to 2011, and analyzed in 2013-2014 with SAS version 9.3. Pearson's correlations were used to assess associations between variables and a generalized linear model was used to measure change over time. RESULTS: Seventy-eight percent (97/125) of participants completed both visits. At baseline, mean anthropometric and clinical measures were at or near healthy values and did not change over time, with the exception of increased diastolic blood pressure (P = 0.01), high-density lipoprotein-cholesterol (P < 0.001), and insulin (P < 0.001). Self-reported diet and physical activity habits were congruent with national goals, except for Vitamin D and sodium. Dietary intake did not change over time, with the exceptions of decreased carbohydrate (percent of total energy) (P < 0.001) and sodium (P = 0.04) and increased fat (percent of total energy) and Vitamin D (both P < 0.01). Cardiovascular fitness showed a trend toward declining, while self-reported physical activity increased (P < 0.001). CONCLUSIONS: Students' clinical measures and lifestyle behaviors remain generally healthy throughout medical school; yet some students exhibit cardiometabolic risk and diet and activity habits not aligned with national recommendations. Curricula that include personal health and lifestyle assessment may motivate students to adopt healthier practices and serve as role models for patients.

A PEX10 defect in a patient with no detectable defect in peroxisome assembly or metabolism in cultured fibroblasts.

Zellweger spectrum disorders (ZSD) are diagnosed by biochemical assay in blood, urine and cultured fibroblasts and PEX gene mutation identification. In most cases studies in fibroblasts corroborate results obtained in body fluids. In 1996 Clayton and colleagues described a 10-year old girl with evidence of a peroxisome disorder, based on elevated bile acid metabolites and phytanate. At the time it was not possible to distinguish whether she had a ZSD or a single peroxisomal protein defect. Studies in our laboratory showed that she also had elevated plasma pipecolate, supporting the former diagnosis. Despite the abnormal metabolites detected in blood (phytanate, bile acid intermediates and pipecolate), analysis of multiple peroxisomal pathways in fibroblasts yielded normal results. In addition, she had a milder clinical phenotype than usually associated with ZSD. Since complementation analysis to determine the gene defect was not possible, we screened this patient following the PEX Gene Screen algorithm (PGS). The PGS provides a template for sequencing PEX gene exons independent of complementation analysis. Two mutations in PEX10 were identified, a frameshift mutation inherited from her father and a de novo missense mutation in a conserved functional domain on the other allele. This case highlights that molecular analysis may be essential to the diagnosis of patients at the milder end of the ZSD spectrum. Furthermore, it supports the concept that some tissues are less affected by certain PEX gene defects than brain and liver.

Micellar solubilisation of cholesterol is essential for absorption in humans.

BACKGROUND AND AIMS: Intralumenal bile acid (BA) concentrations have a profound effect on cholesterol absorption. We performed studies to assess the effects of markedly reduced lumenal BA on cholesterol absorption in children with inborn errors in BA synthesis and the role of micellar solubilisation of cholesterol on its absorption in an animal model using human intestinal contents. METHODS: We studied five subjects: two with 3beta hydroxy-C27 steroid dehydrogenase isomerase deficiency (3-HSD), two with Delta(4)-3-oxosteroid 5beta reductase deficiency (5beta reductase), and one with 2-methylacyl CoA racemase deficiency (racemase). Subjects were studied on supplemental BA therapy and three weeks after withdrawal of supplements. During each treatment period a liquid meal was consumed. Duodenal samples were collected and analysed, and cholesterol absorption and cholesterol fractional synthetic rates were measured. Human intralumenal contents were infused in a bile diverted rat lymph fistula model to assess micellar versus vesicular absorption of cholesterol. RESULTS: Without BA supplementation, intralumenal BA concentrations were below the critical micellar concentration (CMC) whereas intralumenal BAs increased to above the CMC in all subjects on BA supplementation. Lumenal cholesterol was carried primarily as vesicles in untreated subjects whereas it was carried as both micelles and vesicles in treated subjects. Cholesterol absorption increased approximately 55% in treated compared with untreated subjects (p=0.041), with a simultaneous 70% decrease in synthesis rates (p=0.029). In the rat lymph fistula model, minimal vesicular cholesterol was absorbed whereas vesicular and micellar fatty acid and phospholipid were comparably absorbed. CONCLUSIONS: Increasing micellar cholesterol solubilisation by supplemental BA in subjects with inborn errors of BA synthesis leads to an improvement in cholesterol absorption and reduction in cholesterol synthesis due to improved micellar solubilisation of cholesterol.

Hepatocyte glycogen accumulation in patients undergoing dietary management of urea cycle defects mimics storage disease.

OBJECTIVES: Anecdotal reports have described excess hepatocyte glycogen in patients with urea cycle enzyme defects. Retrospectively, the authors evaluated the prevalence and possible cause of liver glycogen accumulation in such patients. METHODS: The authors searched the files of the Division of Pathology at Cincinnati Children's Hospital from 1975 and 2004 for cases of urea cycle enzyme defects and identified 11 patients who had had liver biopsy performed and/or liver transplantation. All patients were on diets containing essential amino acids as the protein source before liver biopsy and/or transplantation. RESULTS: All but one patient had focal or diffuse glycogen accumulation in hepatocytes in at least one specimen by light microscopic examination. Two young infants also had cholestasis. Electron microscopy performed on six patients showed diffuse or focal glycogen excess in the cytoplasm of individual hepatocytes. Biochemical studies of three patients revealed two with hepatic glycogen content in the upper normal range and one that was abnormally high. Glycolytic enzyme activities were normal in two patients, and one patient had low phosphorylase activity. CONCLUSIONS: Hepatocyte glycogen accumulation in urea cycle enzyme defects resembles that seen in glycogen storage disease but can be distinguished in most cases by non-uniformity of distribution and/or the absence of sinusoidal compression by expanded hepatocytes. We speculate that therapeutic modification of dietary protein content by restriction to essential amino acids, including leucine, may promote glycogen accumulation by increasing insulin secretion.

Enteral metronidazole for the prevention of graft versus host disease in pediatric marrow transplant recipients: results of a pilot study.

The use of enteral antibiotics to prevent acute graft versus host disease (GvHD) has not been studied prospectively in children. We hypothesized the risk of GvHD in pediatric bone marrow transplant (BMT) recipients would be decreased with enteral metronidazole. Eligible subjects included pediatric patients referred to one center for first allogeneic BMT. Enteral metronidazole 20 mg/kg/day divided thrice daily (maximum 750 mg/day) was administered from day -14 to day +35. The risk of GvHD grade II or more severe among subjects treated with metronidazole was compared to historical controls. There were no significant differences between treated (n=19) and historical controls (n=83) with respect to age, gender, prophylaxis, or conditioning regimens, proportion receiving unrelated donor marrow, proportion receiving umbilical cord blood, or transplantation indication. The probability of remaining free of GvHD at day +100 was lower in the treated group (P=0.047). The adjusted relative risk of developing GvHD among subjects treated with metronidazole was 0.36 (95% CI: 0.13-0.997; P=0.05). Five patients were unable to complete the study; two were likely related to study medication. We conclude that enteral metronidazole appears effective in the prevention of GvHD. These results suggest that a randomized trial is justifiable in children, especially recipients of alternative donor BMT.

Bioavailability of pure isoflavones in healthy humans and analysis of commercial soy isoflavone supplements.

The pharmacokinetic behavior of naturally occurring isoflavones has been determined for the first time in healthy adults. We compared plasma kinetics of pure daidzein, genistein and their beta-glycosides administered as a single-bolus dose to 19 healthy women. This study demonstrates differences in the pharmacokinetics of isoflavone glycosides compared with their respective beta-glycosides. Although all isoflavones are efficiently absorbed from the intestinal tract, there are striking differences in the fate of aglycones and beta-glycosides. Mean time to attain peak plasma concentrations (t(max)) for the aglycones genistein and daidzein was 5.2 and 6.6 h, respectively, whereas for the corresponding beta-glycosides, the t(max) was delayed to 9.3 and 9.0 h, respectively, consistent with the residence time needed for hydrolytic cleavage of the glycoside moiety for bioavailability. The apparent volume of distribution of isoflavones confirms extensive tissue distribution after absorption. Plasma genistein concentrations are consistently higher than daidzein when equal amounts of the two isoflavones are administered, and this is accounted for by the more extensive distribution of daidzein (236 L) compared with genistein (161 L). The systemic bioavailability of genistein [mean AUC = 4.54 microg/(mL x h)] is much greater than that of daidzein [mean AUC = 2.94 microg/(mL x h)], and bioavailability of these isoflavones is greater when ingested as beta-glycosides rather than aglycones as measured from the area under the curve of the plasma appearance and disappearance concentrations. The pharmacokinetics of methoxylated isoflavones show distinct differences depending on the position of the methoxyl group in the molecule. Glycitin, found in two phytoestrogen supplements, underwent hydrolysis of the beta-glycoside moiety and little further biotransformation, leading to high plasma glycitein concentrations. Biochanin A and formononetin, two isoflavones found in one phytoestrogen supplement, were rapidly and efficiently demethylated, resulting in high plasma genistein and daidzein concentrations typically observed after the ingestion of soy-containing foods. These differences in pharmacokinetics and metabolism have implications for clinical studies because it cannot be assumed that all isoflavones are comparable in their pharmacokinetics and bioavailability. An analysis of 33 phytoestrogen supplements and extracts revealed considerable differences in the isoflavone content from that claimed by the manufacturers. Plasma concentrations of isoflavones show marked qualitative and quantitative differences depending on the type of supplement ingested. These studies indicate a need for improvement in quality assurance and standardization of such products.

Liver involvement in childhood histiocytic syndromes.

The histiocytic syndromes of childhood are disorders of the reticuloendothelial system with variable clinical manifestations. Included among them are Langerhans cell histiocytosis and hemophagocytic lymphohistiocytosis. This discussion will be restricted to these two disorders. Liver disease in these conditions is common. Langerhans cell histiocytosis is characterized by the abnormal clonal proliferation of the macrophage-derived Langerhans cell. Liver involvement at diagnosis has management and prognostic significance. In a subgroup of patients, sclerosing cholangitis develops, which may lead to end-stage liver disease requiring liver transplantation. Hemophagocytic lymphohistiocytosis is a disease of abnormally activated macrophages that can involve multiple organ systems, including the liver. Differentiation between this disorder and other causes of pediatric liver disease is critical, because treatment strategies include chemotherapy, immunosuppression, and frequently bone marrow transplantation.

Pharmacokinetics, tolerability, and clinical effectiveness of quetiapine fumarate: an open-label trial in adolescents with psychotic disorders.

BACKGROUND: This is the first investigation of the pharmacokinetics, tolerability, and efficacy of quetiapine fumarate in adolescents with chronic or intermittent psychotic disorders. METHOD: Ten patients with DSM-IV chronic or intermittent psychotic disorders (ages 12.3 through 15.9 years) participated in an open-label, rising-dose trial and received oral doses of quetiapine twice daily (b.i.d.), starting at 25 mg b.i.d. and reaching 400 mg b.i.d. by day 20. The trial ended on day 23. Key assessments were pharmacokinetic analysis of plasma quetiapine concentrations and neurologic, safety, and efficacy evaluations. RESULTS: No statistically significant differences were observed between 100-mg b.i.d. and 400-mg b.i.d. quetiapine regimens for total body clearance, dose-normalized area under the plasma concentration-time curve, or dose-normalized premorning- or postmorning-dose trough plasma values obtained under steady-state conditions after multiple-dose regimens. No unexpected side effects occurred with quetiapine therapy, and no statistically significant changes from baseline were observed for the UKU Side Effect Rating Scale items that were rated. No serious adverse events or clinically important changes in hematology or clinical chemistry variables were reported. The most common adverse events were postural tachycardia and insomnia. Extrapyramidal side effects improved, as evidenced by significant (p < .05) decreases from baseline to endpoint in the mean Simpson-Angus Scale total scores and Barnes Akathisia Scale scores. Quetiapine improved positive and negative symptoms, as shown by significant (p < .05) decreases from baseline to endpoint in the mean Brief Psychiatric Rating Scale total score, the Clinical Global Impressions-Severity of Illness scale, and the Modified Scale for the Assessment of Negative Symptoms summary score. CONCLUSION: Quetiapine pharmacokinetics were dose proportional in adolescents and were similar to those previously reported for adults. Quetiapine was well tolerated and effective in the small number of adolescents studied.

Correlation of serum cholylglycine level with hepatic dysfunction in children with sickle cell anemia.

Hepatic dysfunction occurs commonly in children with sickle cell disease (SCD). Although the etiology is multifactorial, cholestasis is a prominent feature. Serum cholylglycine (CG) has been found to be a very sensitive indicator of cholestasis. Our objective was to determine whether CG levels are elevated in children with SCD and whether they are predictive of hepatic dysfunction. Blood samples were obtained from 97 children with SCD. Liver function tests were done and serum CG concentrations were measured. Patients were followed up for 2 years. Thirty-eight percent of the patients had an elevated CG level. During the 2 years of follow-up, 16% of the children with a previously elevated CG level developed abnormal liver function test results or required a cholecystectomy as compared with 13% with a previously normal CG level (p = 0.92). We conclude that although CG level was elevated in 38% of the patients with SCD, it did not appear to predict liver dysfunction during the ensuring 2 years.

Isoflavone content of infant formulas and the metabolic fate of these phytoestrogens in early life.

Soy-based infant formulas have been in use for >30 y. These formulas are manufactured from soy protein isolates and contain significant amounts of phytoestrogens of the isoflavone class. As determined by HPLC, the isoflavone compositions of commercially available formulas are similar qualitatively and quantitatively and are consistent with the isoflavone composition of soy protein isolates. Genistein, found predominantly in the form of glycosidic conjugates, accounts for >65% of the isoflavones in soy-based formulas. Total isoflavone concentrations of soy-based formulas prepared for infant feeding range from 32 to 47 mg/L, whereas isoflavone concentrations in human breast milk are only 5.6 +/- 4.4 microg/L (mean +/- SD, n = 9). Infants fed soy-based formulas are therefore exposed to 22-45 mg isoflavones/d (6-11 mg x kg body wt(-1) x d(-1)), whereas the intake of these phytoestrogens from human milk is negligible (<0.01 mg/d). The metabolic fate of isoflavones from soy-based infant formula is described. Plasma isoflavone concentrations reported previously for 4-mo-old infants fed soy-based formula were 654-1775 microg/L (mean: 979.7 microg/L: Lancet 1997:350;23-7), significantly higher than plasma concentrations of infants fed either cow-milk formula (mean +/- SD: 9.4 +/- 1.2 microg/L) or human breast milk (4.7 +/- 1.3 microg/L). The high steady state plasma concentration of isoflavones in infants fed soy-based formula is explained by reduced intestinal biotransformation, as evidenced by low or undetectable concentrations of equol and other metabolites, and is maintained by constant daily exposure from frequent feeding. Isoflavones circulate at concentrations that are 13,000-22,000-fold higher than plasma estradiol concentrations in early life. Exposure to these phytoestrogens early in life may have long-term health benefits for hormone-dependent diseases.

Bone mineral content in children with short bowel syndrome after discontinuation of parental nutrition.

To determine whether children with short bowel syndrome had evidence of metabolic bone disease, total body bone mineral content was measured by dual-energy x-ray absorptiometry in 18 patients and 36 age-, sex-, and race-matched control subjects. Children with short bowel syndrome had decreased bone mineral content compared with control subjects; however, it was not significant when adjusted for differences in weight and height. Whether these children will have normal bone accretion throughout puberty is not known.

Therapeutic misadventures with acetaminophen: hepatoxicity after multiple doses in children.

We compiled reports of acetaminophen hepatotoxicity after multiple overdoses from published cases, cases reported to the Food and Drug Administration, and cases from Children's Hospital Medical Center, Cincinnati, Ohio. Forty-seven children (age range, 5 weeks to 10 years) received 60 to 420 mg/kg/day for 1 to 42 days; 52% had received adult preparations of acetaminophen. The mean peak serum aspartate aminotransferase level was 10,225 IU/L (n = 45), and the mean serum alanine aminotransferase level was 7355 IU/L (n = 31), which were significantly higher (both p < 0.001) than the mean serum aspartate aminotransferase level of 3500 IU/L and alanine aminotransferase level of 3098 IU/L found in children (n = 12) with non-acetaminophen-associated hepatic failure. Serum acetaminophen levels for which an estimate of time from last dose could be calculated were available for 30 patients, of which 22 levels were greater than the toxic range described for acute ingestion. Twenty-four of 43 patients (55%) died, with an additional three surviving after orthotopic liver transplantation. Parents should be advised about the potential hepatotoxicity of acetaminophen when given to ill children in doses exceeding weight-based recommendations.

The role of magnesium in the pathogenesis of bone disease in childhood cholestatic liver disease: a preliminary report.

BACKGROUND: Magnesium deficiency may contribute to the metabolic bone disease that complicates chronic cholestatic liver disease. We hypothesized that magnesium deficiency alters vitamin D metabolism by decreasing parathyroid hormone (PTH) response, resulting in decreased serum osteocalcin and decreased bone accretion. METHODS: Nine subjects, age 3-22 years, with cholestatic liver disease were evaluated with the magnesium retention test. The response of PTH, 1,25(OH)2 vitamin D, and osteocalcin to provocative stimuli and dual x-ray absorptiometry measurement of bone mineral density (BMD) of the lumbar spine were assessed. Thereafter, subjects were treated with oral magnesium supplements. RESULTS: All nine subjects were magnesium depleted. Repletion with magnesium was successful in seven subjects, and required 4 to 31 (median 14) months with doses of 6 to 34 (median 11) mg/kg/day. Baseline serum PTH was significantly reduced in the cholestatic subjects compared to 15 age-matched controls. Comparison of baseline to repleted provocative testing was performed in six Mg-repleted subjects. Osteocalcin response increased significantly (p = 0.048) with repletion, while PTH response increased (p = 0.061). Lumbar spine BMD increased modestly with repletion (p = 0.093). CONCLUSIONS: This preliminary report suggests that magnesium depletion is extremely common in children with chronic cholestasis. We speculate that magnesium supplementation may be warranted to forestall the progression of metabolic bone disease in chronic cholestasis.

The 13C-xylose breath test for the diagnosis of small bowel bacterial overgrowth in children.

BACKGROUND: We evaluated the clinical utility of the 13C-xylose breath test for the diagnosis of small bowel bacterial overgrowth in children. METHODS: To determine the optimal dose of 13C-xylose, 29 healthy children, 3 to 12 years old, were randomly assigned to receive one of three doses of 13C-xylose (10, 25, or 50 mg). After an overnight fast, the oral dose of 13C-xylose was administered, and breath samples were collected every 30 minutes for 4 hours. Samples were analyzed for 13CO2 by gas chromatography with mass spectrometry. Using the 50 mg dose, we then performed nine breath tests with concurrent duodenal bacterial cultures in 6 children, 3 to 12 years old, with short-bowel syndrome (n = 2), immunodeficiency states (n = 1), and motility disorders (n = 3). RESULTS: Excretion of 13CO2 in breath peaked at 2.5 hours in all three control groups. The 50-mg dose produced the highest median peak and the smallest range of 13CO2 excretion in breath within each time period. The time of peak 13CO2 excretion in breath varied among the diseased children; however, the six patients with small-bowel bacterial overgrowth (2 x 10(5)-3.5 x 10(5) gram negative rods) all had peak 13CO2 that exceeded the maximum breath 13CO2 level in breath of the control subjects at the corresponding time period (100% sensitivity). Of the three patients with negative cultures, two had negative breath test results and one had positive results (67% specificity). One subject had normalization of both duodenal culture and breath test results after antibiotic treatment of small-bowel bacterial overgrowth. CONCLUSIONS: Our preliminary results suggest that with a dose of 50 mg 13C-xylose, breath test results reliably predict small-bowel bacterial overgrowth in susceptible children.

Exposure of infants to phyto-oestrogens from soy-based infant formula.

BACKGROUND: The isoflavones genistein, daidzein, and their glycosides, found in high concentrations in soybeans and soy-protein foods, may have beneficial effects in the prevention or treatment of many hormone-dependent diseases. Because these bioactive phyto-oestrogens possess a wide range of hormonal and non-hormonal activities, it has been suggested that adverse effects may occur in infants fed soy-based formulas. METHODS: To evaluate the extent of infant exposure to phyto-oestrogens from soy formula, the isoflavone composition of 25 randomly selected samples from five major brands of commercially available soy-based infant formulas were analysed, and the plasma concentrations of genistein and daidzein, and the intestinally derived metabolite, equol, were compared in 4-month-old infants fed exclusively soy-based infant formula (n = 7), cow-milk formula (n = 7), or human breast-milk (n = 7). FINDINGS: All of the soy formulas contained mainly glycosides of genistein and daidzein, and the total isoflavone content was similar among the five formulas analysed and was related to the proportion of soy isolate used in their manufacture. From the concentrations of isoflavones in these formulas (means 32-47 micrograms/mL), the typical daily volume of milk consumed, and average bodyweight, a 4-month-old infant fed soy formula would be exposed to 28-47 per day, or about 4.5-8.0 mg/kg bodyweight per day, of total isoflavones. Mean (SD) plasma concentrations of genistein and daidzein in the seven infants fed soy-based formulas were 684 (443) ng/mL and 295 (60) ng/mL, respectively, which was significantly greater (p < 0.05) than in the infants fed either cow-milk formulas (3.2 [0.7] and 2.1 [0.3] ng/mL), or human breast-milk (2.8 [0.7] and 1.4 [0.1] ng/mL), and an order of magnitude higher per bodyweight than typical plasma concentrations of adults consuming soy foods. INTERPRETATION: The daily exposure of infants to isoflavones in soy infant-formulas is 6-11 fold higher on a bodyweight basis than the dose that has hormonal effects in adults consuming soy foods. Circulating concentrations of isoflavones in the seven infants fed soy-based formula were 13000-22000 times higher than plasma oestradiol concentrations in early life, and may be sufficient to exert biological effects, whereas the contribution of isoflavones from breast-milk and cow-milk is negligible.

Glucocorticoids upregulate taurocholate transport by ileal brush-border membrane.

The regulation of the enterohepatic circulation of bile acids has not been fully elucidated. Substrate availability has been shown to have a regulatory role on the ileal uptake of taurocholate (TC) by a positive feedback mechanism. Other mechanisms are likely to be involved in regulating ileal bile acid uptake. The present study was designed to test the hypothesis that the ileal bile acid transporter (iBAT) is glucocorticoid sensitive and that changes in expression are mediated by changes in iBAT synthesis. Adult Sprague-Dawley rats (300-400 g) received intraperitoneal injections with either corticosterone (5 mg/ 100 g body weight) or an equivalent vehicle (control) daily for 3 days. On day 4, ileal brush-border membrane vesicles (BBMV) and hepatic basolateral membrane vesicles (BLMV) were prepared, and TC transport was performed using the rapid filtration technique. Initial velocity was measured at selected time points, and kinetics were calculated over a range of TC concentrations. Ileal RNA was isolated, and Northern analysis of steady-state iBAT mRNA levels was determined. Western blot analysis was performed to quantitate the level of the 48-kDa iBAT protein. The initial velocity of Na(+)-dependent TC uptake at 30 s by ileal BBMV was higher in treated animals (264.3 +/- 64.6 pmol/mg protein) compared with control animals (148.3 +/- 41.1 pmol/mg protein; P = 0.07). The maximal velocity of uptake (Vmax) was significantly higher in treated vs. control animals (1,091 +/- 62.7 vs. 689.1 +/- 55.0 pmol.min-1.mg protein-1, respectively; P = 0.002), whereas there was no significant difference in the Michaelis constant (Km) between the control and treated animals (43.3 +/- 7.2 vs. 35.3 +/- 8.7 microM, respectively; P = not significant). Steady-state iBAT mRNA levels were increased twofold in the treated vs. control groups. Western blot analysis showed that the abundance of the 48-kDa iBAT protein was eightfold higher in the treated animals compared with control. Kinetic analysis of hepatic Na(+)-dependent TC uptake revealed nearly identical Vmax and Km between the study and control animals. Therefore, we conclude that TC transport by ileal BBMV is upregulated by administration of glucocorticoids. The increase in BBMV transport Vmax corresponds to an increase in both iBAT transcript and protein.

Cutaneous Crohn's disease in children.

BACKGROUND: Although cutaneous Crohn's disease is well recognized in adults, in children it is extremely rare. OBJECTIVE: Our purpose was to describe five children with cutaneous Crohn's disease and to review the literature. METHODS: The medical records of five children with cutaneous Crohn's disease were retrospectively reviewed for clinical features and laboratory data. An extensive review of the literature was conducted. RESULTS: Five children, one boy and four girls, 6 to 12 years of age at onset, had cutaneous manifestations of Crohn's disease. Three had genital swelling, and the other 2 had buttock abscesses. Most were seen before the diagnosis of gastrointestinal Crohn's disease was made. There have been 80 cases of cutaneous Crohn's disease described, including our series. Only 14 were in children. Two thirds of children with cutaneous Crohn's disease had genital involvement compared with about half of the adult cases. Sixteen of the 80 patients had cutaneous lesions without preceding gastrointestinal Crohn's disease. Of these, approximately 70% had genital lesions. CONCLUSION: Although Crohn's disease is common in children, cutaneous manifestations are rarely a presenting sign. However, when cutaneous Crohn's disease is present in children, it commonly precedes the gastrointestinal disease.

Primary bile acid malabsorption caused by mutations in the ileal sodium-dependent bile acid transporter gene (SLC10A2).

Primary bile acid malabsorption (PBAM) is an idiopathic intestinal disorder associated with congenital diarrhea, steatorrhea, interruption of the enterohepatic circulation of bile acids, and reduced plasma cholesterol levels. The molecular basis of PBAM is unknown, and several conflicting mechanisms have been postulated. In this study, we cloned the human ileal Na+/bile acid cotransporter gene (SLC10A2) and employed single-stranded conformation polymorphism analysis to screen for PBAM-associated mutations. Four polymorphisms were identified and sequenced in a family with congenital PBAM. One allele encoded an A171S missense mutation and a mutated donor splice site for exon 3. The other allele encoded two missense mutations at conserved amino acid positions, L243P and T262M. In transfected COS cells, the L243P, T262M, and double mutant (L243P/T262M) did not affect transporter protein expression or trafficking to the plasma membrane; however, transport of taurocholate and other bile acids was abolished. In contrast, the A171S mutation had no effect on taurocholate uptake. The dysfunctional mutations were not detected in 104 unaffected control subjects, whereas the A171S was present in 28% of that population. These findings establish that SLC10A2 mutations can cause PBAM and underscore the ileal Na+/bile acid cotransporter's role in intestinal reclamation of bile acids.