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Biomedical subjects

T Karrison

Publications and source records attributed to T Karrison.

At least 19 recordsLinked to original sources

UGT1A1*28 polymorphism as a determinant of irinotecan disposition and toxicity.

The metabolism of irinotecan (CPT-11) involves sequential activation to SN-38 and detoxification to the pharmacologically inactive SN-38 glucuronide (SN-38G). We have previously demonstrated the role of UGT1A1 enzyme in the glucuronidation of SN-38 and a significant correlation between in vitro glucuronidation of SN-38 and UGT1A1 gene promoter polymorphism. This polymorphism (UGT1A1*28) is characterized by the presence of an additional TA repeat in the TATA sequence of the UGT1A1 promoter, ((TA)7TAA, instead of (TA)6TAA). Here we report the results from a prospective clinical pharmacogenetic study to determine the significance of UGT1A1*28 polymorphism on irinotecan disposition and toxicity in patients with cancer. Twenty patients with solid tumors were treated with a 90 min i.v. infusion of irinotecan (300 mg m(-2)) once every 3 weeks. The frequency of UGT1A1 genotypes was as follows: 6/6--45%, 6/7--35% and 7/7--20%, with allele frequencies of 0.375 and 0.625 for (TA)7TAA and (TA)6TAA, respectively. Patients with the (TA)7TAA polymorphism had significantly lower SN-38 glucuronidation rates than those with the normal allele (6/6>6/7>7/7, P = 0.001). More severe grades of diarrhea and neutropenia were observed only in patients heterozygous (grade 4 diarrhea, n = 1) or homozygous (grade 3 diarrhea/grade 4 neutropenia, n = 1 and grade 3 neutropenia, n = 1) for the (TA)7TAA sequence. The results suggest that screening for UGT1A1*28 polymorphism may identify patients with lower SN-38 glucuronidation rates and greater susceptibility to irinotecan induced gastrointestinal and bone marrow toxicity.

Adult↗

Mitogen-activated protein kinase kinase 4 metastasis suppressor gene expression is inversely related to histological pattern in advancing human prostatic cancers.

We have shown recently (B. A. Yoshida et al., Cancer Res., 59: 5483-5487) that mitogen-activated protein kinase kinase 4 (MKK4) can suppress AT6.1 rat prostate cancer metastases in vivo. Evaluation of the expression of components of the MKK4 signaling cascade showed a loss or down-regulation of expression of MKK4 or c-Jun, a downstream mediator of MKK4, in six of eight human prostate cancer cell lines. Given these findings, we next assessed whether MKK4 dysregulation occurs during the development of clinical prostate cancer. Immunohistochemical studies showed high levels of MKK4 expression in the epithelial but not the stromal compartment of normal prostatic tissues. In neoplastic tissues, a statistically significant, direct, inverse relationship between Gleason pattern and MKK4 was established. These results demonstrate that MKK4 protein is consistently down-regulated during prostate cancer progression and support a role for dysregulation of its signaling cascade in clinical disease. To test the possibility that down-regulation of MKK4 protein is the result of allelic loss, metastatic prostate cancer lesions were examined for loss of heterozygosity (LOH) within the MKK4 locus (D17S969). These studies showed a 31% (5 of 16) LOH of MKK4 that is not associated with coding region mutations, which suggests that the nucleotide sequence of the gene in the remaining allele is infrequently mutated.

Enzyme Activation↗

Failed vaginal birth after a cesarean section: how risky is it? I. Maternal morbidity.

OBJECTIVE: Our purpose was to determine the maternal risks associated with failed attempt at vaginal birth after cesarean compared with elective repeat cesarean delivery or successful vaginal birth after cesarean. STUDY DESIGN: From 1989 to 1998 all patients attempting vaginal birth after cesarean and all patients undergoing repeat cesarean deliveries were reviewed. Data were extracted from a computerized obstetric database and from medical charts. The following three groups were defined: women who had successful vaginal birth after cesarean, women who had failed vaginal birth after cesarean, and women who underwent elective repeat cesarean. Criteria for the elective repeat cesarean group included no more than two previous low transverse or vertical incisions, fetus in cephalic or breech presentation, no previous uterine surgery, no active herpes, and adequate pelvis. Predictor variables included age, parity, type and number of previous incisions, reasons for repeat cesarean delivery, gestational age, and infant weight. Outcome variables included uterine rupture or dehiscence, hemorrhage >1000 mL, hemorrhage >2000 mL, need for transfusion, chorioamnionitis, endometritis, and length of hospital stay. The Student t test and the chi(2) test were used to compare categoric variables and means; maternal complications and factors associated with successful vaginal birth after cesarean were analyzed with multivariate logistic regression, allowing odds ratios, adjusted odds ratios, 95% confidence intervals, and P values to be calculated. RESULTS: A total of 29,255 patients were delivered during the study period, with 2450 having previously had cesarean delivery. Repeat cesarean deliveries were performed in 1461 women (5.0%), and 989 successful vaginal births after cesarean delivery occurred (3.4%). Charts were reviewed for 97.6% of all women who underwent repeat cesarean delivery and for 93% of all women who had vaginal birth after cesarean. Vaginal birth after cesarean was attempted by 1344 patients or 75% of all appropriate candidates. Vaginal birth after cesarean was successful in 921 women (69%) and unsuccessful in 424 women. Four hundred fifty-one patients undergoing cesarean delivery were deemed appropriate for vaginal birth after cesarean. Multiple gestations were excluded from analysis. Final groups included 431 repeat cesarean deliveries and 1324 attempted vaginal births after cesarean; in the latter group 908 were successful and 416 failed. The overall rate of uterine disruption was 1.1% of all women attempting labor; the rate of true rupture was 0.8%; and the rate of hysterectomy was 0.5%. Blood loss was lower (odds ratio, 0.5%; 95% confidence interval, 0.3-0.9) and chorioamnionitis was higher (odds ratio, 3.8%; 95% confidence interval, 2.3-6.4) in women who attempted vaginal births after cesarean. Compared with women who had successful vaginal births after cesarean, women who experienced failed vaginal births after cesarean had a rate of uterine rupture that was 8.9% (95% confidence interval, 1.9-42) higher, a rate of transfusion that was 3.9% (95% confidence interval, 1.1-13.3) higher, a rate of chorioamnionitis that was 1.5% (95% confidence interval, 1.1-2.1) higher, and a rate of endometritis that was 6.4% (95% confidence interval, 4.1-9.8) higher. CONCLUSION: Patients who experience failed vaginal birth after cesarean have higher risks of uterine disruption and infectious morbidity compared with patients who have successful vaginal birth after cesarean or elective repeat cesarean delivery. Because actual numbers of morbid events are small, caution should be exercised in interpreting results and counseling patients. More accurate prediction for safe, successful vaginal birth after cesarean delivery is needed.

Adult↗

The effects of antidepressants on obstructed and unobstructed gait in healthy elderly people.

BACKGROUND: Elderly patients treated with antidepressants for depression are at high risk for injury due to falling. The primary purpose of this study was to determine the effects of amitriptyline, desipramine, and paroxetine on the gait of healthy elderly subjects during unobstructed and obstructed (i.e., stepping over obstacles) gait. Psychomotor and mood tests were also performed. METHODS: A randomized, crossover, four-period, double-blind, placebo-controlled laboratory trial was performed. Twelve healthy elderly subjects (average age, 67 years; range, 65-72 years) were tested. Subjects were assigned the three antidepressant drugs or a placebo in a random order. Single doses of amitriptyline 50 mg, desipramine 50 mg, paroxetine 20 mg, or placebo were given 4 hours prior to gait testing. Temporal-distance measures and kinematics of the lower trailing limb (i.e., limb going over obstacle last) were obtained. RESULTS: Compared with placebo, amitriptyline significantly reduced gait velocity by as much as 8.0% (p = .028), cadence by as much as 4.9% (p = .012), angular velocity of hip flexion by as much as 10.0% (p = .004), and angular velocity of knee flexion by as much as 8.3% (p = 018) during the crossing strides when stepping over obstacles. Except for knee flexion angle, unobstructed gait was not affected. Amitriptyline affected integrative capacity of the central nervous system (CNS) and ability to concentrate as measured by psychomotor and mood tests. CONCLUSIONS: The results for amitriptyline suggest that the subjects slowed their obstacle crossing speeds as a result of reduced CNS integrative capacities. Neither paroxetine nor desipramine significantly affected gait, psychomotor function, or mood.

Affect↗

HLA-G genotypes and pregnancy outcome in couples with unexplained recurrent miscarriage.

HLA-G is a non-classical human leukocyte antigen expressed primarily in fetal tissues at the maternal-fetal interface. This expression pattern is unique among HLA genes and suggests that HLA-G may be involved in interactions that are critical in establishing and/or maintaining pregnancy. To evaluate the role of polymorphisms at this locus in maternal-fetal interactions, 113 couples with unexplained recurrent miscarriage were genotyped for seven polymorphisms that define 12 HLA-G alleles. Logistic regression analysis was used to assess whether HLA-G genotypes were associated with an increased risk for a subsequent miscarriage. The presence of an HLA-G*0104 or HLA-G*0105N allele in either partner was significantly associated with an increased risk for miscarriage, after adjustment for maternal age, number of previous miscarriages, history of a previous liveborn, and treatment with paternal mononuclear cells. The *0104 and *0105N alleles are defined by polymorphisms in the alpha-2 domain and encode protein variants that are present only in the full-length HLA-G1 protein. The significant genotype-specific risk in this population suggests that allelic variation in the alpha-2 domain of the HLA-G1 isoforms contributes to recurrent miscarriage.

Abortion, Habitual↗

Methylnaltrexone for reversal of constipation due to chronic methadone use: a randomized controlled trial.

CONTEXT: Constipation is the most common chronic adverse effect of opioid pain medications in patients who require long-term opioid administration, such as patients with advanced cancer, but conventional measures for ameliorating constipation often are insufficient. OBJECTIVE: To evaluate the efficacy of methylnaltrexone, the first peripheral opioid receptor antagonist, in treating chronic methadone-induced constipation. DESIGN: Double-blind, randomized, placebo-controlled trial conducted between May 1997 and December 1998. SETTING: Clinical research center of a university hospital. PARTICIPANTS: Twenty-two subjects (9 men and 13 women; mean [SD] age, 43.2 [5.5] years) enrolled in a methadone maintenance program and having methadone-induced constipation. MAIN OUTCOME MEASURES: Laxation response, oral-cecal transit time, and central opioid withdrawal symptoms were compared between the 2 groups. RESULTS: The 11 subjects in the placebo group showed no laxation response, and all 11 subjects in the intervention group had laxation response after intravenous methylnaltrexone administration (P<.001). The oral-cecal transit times at baseline for subjects in the methylnaltrexone and placebo groups averaged 132.3 and 126.8 minutes, respectively. The average (SD) change in the methylnaltrexone-treated group was -77.7 (37.2) minutes, significantly greater than the average change in the placebo group (-1.4 [12.0] minutes; P<.001). No opioid withdrawal was observed in any subject, and no significant adverse effects were reported by the subjects during the study. CONCLUSIONS: Our data demonstrate that intravenous methylnaltrexone can induce laxation and reverse slowing of oral cecal-transit time in subjects taking high opioid dosages. Low-dosage methylnaltrexone may have clinical utility in managing opioid-induced constipation.

Adult↗

Does pneumonectomy for lung cancer adversely influence long-term survival?

OBJECTIVE: The increased operative mortality associated with pneumonectomy has stimulated the use of lung-sparing operations such as sleeve lobectomy. Whether pneumonectomy adversely affects long-term outcome after lung resection is unknown. METHODS: We reviewed the cases of patients who underwent lobectomy/bilobectomy or pneumonectomy because of non-small cell lung cancer between January 1980 and June 1998. Survival curves were compared by the log-rank test. Covariates were determined for operative mortality and survival using logistic regression analysis and Cox proportional hazards estimation, respectively. RESULTS: There were 259 men and 183 women who underwent lobectomy/bilobectomy (340) or pneumonectomy (102). Operative mortality was 36 (8.1%) patients overall, 24 (7.0%) for lobectomy/bilobectomy and 12 (12%) for pneumonectomy. Mean follow-up was 41 months (range 0-222 months). Median survival was worse for pneumonectomy (stage II: 17.9 vs 36.3 months, log-rank P =. 05; stage III: 11.7 vs 21.3 months, log-rank P =.07). However, important covariates for survival were age, primary tumor status, regional nodal status, and forced expiratory volume in 1 second. After adjusting for these covariates, survival did not differ significantly between the types of operations (hazard ratio for pneumonectomy 1.21; 95% CI 0.88-1.68). CONCLUSIONS: We did not detect a significant long-term adverse influence of pneumonectomy on survival after adjusting for other prognostic factors, but randomized clinical trials would be needed to definitively address this issue.

Adult↗

Effects of enteric-coated methylnaltrexone in preventing opioid-induced delay in oral-cecal transit time.

BACKGROUND: Methylnaltrexone is the first peripheral opioid receptor antagonist. It has the potential to prevent or reverse the peripherally mediated gastrointestinal effects of opioids. In previous human volunteer trials, we demonstrated that oral uncoated methylnaltrexone prevented morphine-induced delay in gastrointestinal transit time. METHODS: This trial consisted of two studies: a pilot study and a controlled study. The lactulose hydrogen breath test was used to measure the oral-cecal transit time. RESULTS: In the pilot study with three subjects, an oral dose of 6.4 mg/kg enteric-coated methylnaltrexone effectively reversed the effects of morphine, producing transit times shorter than baseline levels. Subsequently, in the controlled study with another nine subjects, the transit time increased after intravenous morphine administration in all nine subjects, and the lower dose (3.2 mg/kg) of enteric-coated methylnaltrexone completely prevented the morphine-induced change in oral-cecal transit time in all nine subjects. Morphine significantly increased oral-cecal transit time from baseline level of 96.7 +/- 54.1 minutes (mean +/- SD) to 155.0 +/- 53.6 minutes (P = .014). After enteric-coated methylnaltrexone and morphine, the transit time returned to the baseline level (93.3 +/- 56.0 minutes; P = .55 compared with placebo). Plasma concentrations after 6.4 mg/kg and 3.2 mg/kg enteric-coated methylnaltrexone were substantially lower compared with those after 6.4 mg/kg of the uncoated formulation. CONCLUSION: Our results suggest that there is a prevailing direct and local luminal effect of enteric-coated methylnaltrexone and that the enteric-coated formulation exerts its gut pharmacologic actions more efficiently than the uncoated formulation.

Administration, Oral↗

Peripartum hysterectomy.

OBJECTIVES: To review the cases receiving peripartum hysterectomies treated in this hospital during the period 1967-1995. Clinical characteristics, indications, and results were more closely analyzed. STUDY DESIGN: A chart review of all cases operated since January 1967 to December 1995 was done. Demographic and clinical data were extracted, coded, and entered into a computer file for analysis. Indications, type of operation, pre-op planning or emergency decision, blood loss, transfusion, complications, were compared and cross-tabulated. Statistical analysis included: chi-square and Fisher exact tests, where appropriate, and two-sample t test. RESULTS: In 58% of 217 cases the operation was planned, and total hysterectomy was done in 94%. Indications changed through the years, from predominantly elective to almost exclusively emergencies. These were mostly bleeding complications, in particular placenta previa and/or accreta. The presence of a uterine scar or submucous fibroid was associated with 79% (26/33) of accretas, and 51% (19/37) of previas. Among the 126 planned, 57% did not receive a transfusion and 84% of 91 emergencies did have one. The average amount of blood received by the latter was 3009 ml compared to 1262 ml for the former (p < 0.0001). There was a direct relationship between amount of blood loss and volume transfused. There were 26% intraoperatory bleeding complications and 5% urinary tract injuries. Postoperatory morbidity such as bleeding, infections, wound dehiscence, and others was observed in 17% of planned, and 23% of emergencies. Twelve patients needed another operation to treat some of these complications. There were no deaths recorded. CONCLUSIONS: Peripartum hysterectomy is a major operation, and in current times almost always an emergency with high risk for significant blood loss. The obstetrician should be ready to do it, and an early decision should save blood and prevent complications. Postoperative complications, mostly bleeding and infections may be severe. Early intervention and proper technique facilitate good outcomes.

Blood Transfusion↗

Human breast cancer susceptibility to paclitaxel therapy is independent of Bcl-2 expression.

In laboratory studies, ectopic overexpression of the antiapoptotic protein Bcl-2 has been shown to result in resistance to the cytotoxic effects of many chemotherapeutic drugs. Furthermore, posttranslational modification of moderately expressed endogenous Bcl-2 has been correlated with susceptibility to paclitaxel treatment in vitro. To determine whether tumor expression of Bcl-2 protein correlates with response and ultimate outcome in vivo, we quantified Bcl-2 expression by immunohistochemical analysis of archived biopsy specimens from metastatic breast cancer patients treated with single-agent paclitaxel. The statistical association between the degree of Bcl-2 expression, objective tumor response, and clinical outcome was then determined. In patients (n = 39) whose tumors had low (< or = 10% cells positive) Bcl-2 levels by immunohistochemical analysis, the overall response (complete response + partial response) rate was 21% versus an overall response rate of 22% in patients (n = 36) with high (>10% cells positive) Bcl-2 expression (P = 0.92). In patients with low Bcl-2 expression, the median time to progression was 126 days [95% confidence interval (CI), 63-160 days]. This was not significantly different than the 105 days for patients with high tumor Bcl-2 expression (95% CI, 84-214 days). The median survival time from initiation of paclitaxel therapy for patients with low Bcl-2 expression was 663 days (95% CI, 456-1119 days) and was not significantly different than the 450 days (95% CI, 239-1058 days) observed for patients with high Bcl-2 expression. In conclusion, we found that in metastatic breast cancer, there is no significant association between tumor Bcl-2 expression and response to paclitaxel, median time to progression, or survival, suggesting that the main mechanism of paclitaxelinduced cytotoxicity in breast tumors is independent of Bcl-2 expression.

Adult↗

Mononuclear-cell immunisation in prevention of recurrent miscarriages: a randomised trial.

BACKGROUND: Couples with unexplained recurrent miscarriage may have an alloimmune abnormality that prevents the mother from developing immune responses essential for the survival of the genetically foreign conceptus. Immunisation with paternal mononuclear cells is used as a treatment for such alloimmune-mediated pregnancy losses. However, the published results on this treatment are conflicting. In this study (the Recurrent Miscarriage [REMIS] Study), we investigated whether paternal mononuclear cell immunisation improves the rate of successful pregnancies. METHODS: Women who had had three or more spontaneous abortions of unknown cause were enrolled in a double-blind, multicentre, randomised clinical trial. 91 were assigned immunisation with paternal mononuclear cells (treatment) and 92 immunisation with sterile saline (control). The primary outcomes were the inability to achieve pregnancy within 12 months of randomisation, or a pregnancy which terminated before 28 weeks of gestation (failure); and pregnancy of 28 or more weeks of gestation (success). Two analyses were done: one included all women (intention to treat), and the other included only those who became pregnant. FINDINGS: Two women in each group received no treatment, and eight (three treatment, five control) were censored after an interim analysis. In the analysis of all randomised women who completed the trial, the success rate was 31/86 (36%) in the treatment group and 41/85 (48%) in the control group (odds ratio 0.60 [95% CI 0.33-1.12], p=0.108). In the analysis of pregnant women only, the corresponding success rates were 31/68 (46%) and 41/63 (65%; odds ratio 0.45 [0.22-0.91], p=0.026). The results were unchanged after adjustment for maternal age, number of previous miscarriages, and whether or not the couple had had a previous viable pregnancy. Similar results were obtained in a subgroup analysis of 133 couples with no previous livebirth. INTERPRETATION: Immunisation with paternal mononuclear cells does not improve pregnancy outcome in women with unexplained recurrent miscarriage. This therapy should not be offered as a treatment for pregnancy loss.

Abortion, Habitual↗

The effect of alcohol abuse on the health status of older adults seen in the emergency department.

OBJECTIVE: To examine the effect of alcohol abuse on the subsequent health status of elderly patients seen in an emergency department (ED). PATIENTS AND METHODS: A sample of 966 patients aged 65 or older who presented to one urban academic ED between the hours of 8 A.M. and 12 midnight was followed for 1 year. A personal interview was administered during the ED visit. Current problem drinkers had a score of 1 or greater on the CAGE questionnaire at ED presentation and drank within the prior 6 months; former problem drinkers had a score of 1 or greater on the CAGE questionnaire at ED presentation and a last drink more than 6 months previously. We used 13 items from the Medical Outcomes Study short form adapted to the ED setting and 6 items from the Index of Activities of Daily Living (ADL) to measure health status. RESULTS: In multivariate models for repeated-measures controlling for potential confounding factors, current problem drinkers had worse overall health (parameter estimate beta -3.6; 95% CI -7.1 to -0.04), and former problem drinkers had worse mental health (beta -3.6; CI -6.9 to -0.24) on follow-up. We could find no effect of problem drinking on physical health or social function. CONCLUSIONS: Current problem drinking is associated with worse self-perceived health among elderly patients in the year following presentation to an ED. The magnitude of decline in health perception may approximate the effect of having back pain, sciatica, or other musculoskeletal complaints. Elderly former problem drinkers suffer from more severe mental health problems over that same period.

Activities of Daily Living↗

Safety of peripheral intravenous catheters in children.

OBJECTIVES: To determine the overall and per-day risk of complications of short peripheral intravenous (PIV) catheters placed for indefinite periods. DESIGN: During 5 months, general pediatric patients receiving intravenous therapy through short PIV catheters were monitored. Patient and catheter characteristics were recorded, complications were noted, and rolled semiquantitative cultures of removed catheters were performed. Major endpoints were infection and phlebitis. Per-day risk of complications and catheter colonization (>15 colony-forming units) were calculated. SETTING: University children's hospital. PATIENTS: General pediatric ward inpatients with PIV. RESULTS: We studied 642 Teflon catheters in place >24 hours (mean, 3.7 days) in 525 patients. There were no cases of catheter sepsis (0%; 95% confidence interval [CI95], 0%-0.6%), one possible insertion-site infection (0.2%; CI95, 0.004%-0.9%), and seven cases of phlebitis (1.1%; CI95, 0.4%-2.3%). Catheter colonization occurred in 92 (26%) of 348 catheters cultured. Neither the per-day risk of phlebitis nor of catheter colonization increased significantly with placement >3 days. CONCLUSION: Current guidelines recommend replacement of PIV catheters in adults within 2 to 3 days; no recommendations are made for children. Our findings and those of others indicate that the overall risk of PIV catheter complications in children is extremely low and would not be reduced substantially by routine catheter replacement.

Bacteria↗

Dose-related effects of oral acetaminophen on cold-induced pain: a double-blind, randomized, placebo-controlled trial.

The cold-pressor test is a widely used pain-induction model in humans. This method has been shown to be a sensitive measure for detecting opioid analgesia. However, nonsteroidal anti-inflammatory drugs have not produced consistent analgesic effects with use of this model. The analgesic effect of acetaminophen (INN, paracetamol) on cold pressor-induced pain has not been reported by other investigators. In this study, a double-blind, randomized, placebo-controlled design was used to evaluate the dose-related effects of oral acetaminophen on cold pressor-induced pain in 18 normal healthy human subjects. We observed dose-related analgesic activity of oral acetaminophen using the cold pressor-induced pain model in these subjects. There were statistically significant main effects of both dose and time (pain and bothersomeness ratings decreased with increasing drug dose and increased over time). In pairwise comparisons only the contrast between the highest dose of acetaminophen (1000 mg) and placebo reached statistical significance. Results from our study suggest that the cold-pressor method may have clinical value in evaluating nonopioid analgesic agents.

Acetaminophen↗

Bone mineral density assessment in children with inflammatory bowel disease.

BACKGROUND & AIMS: Children with inflammatory bowel disease (IBD) are at risk for osteoporosis because of undernutrition, delayed puberty, and prolonged corticosteroid use. The aim of this study was to compare bone mineral density (BMD) in children with IBD with that in normal children and to assess the effects of nutritional and hormonal factors and corticosteroid dosages on BMD. METHODS: One hundred sixty-two subjects (99 with IBD and 63 healthy sibling controls) were enrolled. Patients underwent anthropometric assessment, pubertal staging, bone age radiography, and BMD assessment by dual energy x-ray absorptiometry of the lumbar spine, femoral neck, and radius. Laboratory evaluations included serum calcium, phosphate, alkaline phosphatase, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, parathyroid hormone, osteocalcin, urinary N-telopeptides, albumin, insulin-like growth factor I, and testosterone or estradiol. Cumulative corticosteroid doses were calculated. RESULTS: BMD Z scores at the lumbar spine and femoral neck were lower in patients with IBD, and lower in those with Crohn's disease compared with those with ulcerative colitis. Low BMD persisted after correction for bone age in girls with Crohn's disease (lumbar spine, P = 0.004; femoral neck, P = 0.002). Cumulative corticosteroid dose was a significant predictor of reduced BMD. BMD did not correlate with measures of calcium homeostasis, except elevated serum phosphate and urine calcium levels in girls. CONCLUSIONS: Low BMD occurs in children with IBD (more in Crohn's disease than in ulcerative colitis), especially pubertal and postpubertal girls. Cumulative corticosteroid dose is a predictor of low BMD, but other factors in Crohn's disease remain undetermined.

Adolescent↗