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1.
Diabetologia ; 57(9): 1820-9, 2014 Sep.
Article in English | MEDLINE | ID: mdl-24891020

ABSTRACT

AIMS/HYPOTHESIS: Although obesity is a major risk factor for diabetes, little is known about weight gain trajectories across adulthood, and whether they are differentially associated with metabolic markers of diabetes. METHODS: We used fasting blood samples and longitudinal weight data for 5,436 adults (5,734 observations, aged 18-66 years) from the China Health and Nutrition Survey (1991-2009). Using latent class trajectory analysis, we identified different weight gain trajectories in six age and sex strata, and used multivariable general linear mixed effects models to assess elevated metabolic markers of diabetes (fasting glucose, HbA1c, HOMA-IR, insulin) across weight trajectory classes. Models were fitted within age and sex strata, and controlled for baseline weight (or baseline weight by weight trajectory interaction terms), height, and smoking habit, with random intercepts to control for community-level correlations. RESULTS: Compared with weight gain, classes with weight maintenance, weight loss, or a switch from weight gain to loss had lower values for metabolic markers of diabetes. These associations were stronger among younger women (aged 18-29 and 30-39 years) and men (18-29 years) than in older (40-66 years) men and women. An exception was HOMA-IR, which showed class differences across all ages (at least p < 0.004). CONCLUSION: Trajectory analysis identified heterogeneity in adult weight gain associated with diabetes-related metabolic markers, independent of baseline weight. Our findings suggest that variation in metabolic markers of diabetes across patterns of weight gain is masked by a homogeneous classification of weight gain.


Subject(s)
Body Weight/physiology , Adolescent , Adult , Age Distribution , Aged , China , Fasting/blood , Female , Humans , Insulin Resistance/physiology , Male , Middle Aged , Obesity/metabolism , Obesity/physiopathology , Young Adult
2.
J Low Genit Tract Dis ; 18(1): 46-9, 2014 Jan.
Article in English | MEDLINE | ID: mdl-23959297

ABSTRACT

OBJECTIVE: Recommendations regarding treatment of cervical intraepithelial neoplasia (CIN) 2 in women have evolved over the years: young women with CIN 2 may be offered observation with Pap smears and colposcopy every 6 months instead of immediate excision or ablation of disease. The purpose of this study was to observe patient follow-up during the initiation of this management protocol for young women with CIN 2. MATERIALS AND METHODS: This was a retrospective review of clinical outcomes of women younger than 30 years with CIN 2 on index biopsy and planned follow-up at UNC between July 2009 and August 2010. A chart review for clinical variables, follow-up visits, and progression of disease was conducted. Primary analysis determined the rate of follow-up and pathology at 6 months. Secondary analysis investigated risk factors for incomplete follow-up. RESULTS: Seventy women met inclusion criteria; 46 were managed with observation. Twenty-eight (60.8%; 28/46) women completed a follow-up visit. Demographic and clinical variables did not reach statistical significance in predicting the likelihood of completion of a follow-up visit, although there was a trend toward greater follow-up in employed patients (odds ratio = 5.25, 95% confidence interval = 0.84-34.78). Approximately half (52.4%; 11/21) of women with a completed cervical biopsy demonstrated regression of disease during the study period. CONCLUSIONS: On the basis of these data, follow-up in this population was unpredictable based on basic demographic or clinical factors that we often use to judge likelihood of compliance with medical recommendations. The percentage of patients with regression at follow-up was as expected from the natural history of CIN 2.


Subject(s)
Health Services Research , Observation/methods , Uterine Cervical Dysplasia/diagnosis , Uterine Cervical Dysplasia/pathology , Adolescent , Adult , Biopsy , Female , Histocytochemistry , Humans , Retrospective Studies , Young Adult
3.
J Hand Surg Am ; 38(1): 40-8, 2013 Jan.
Article in English | MEDLINE | ID: mdl-23218558

ABSTRACT

PURPOSE: To assess the ability of volar locked plating to achieve and maintain normal radiographic parameters for articular stepoff, volar tilt, radial inclination, ulnar variance, and radial height in distal radius fractures. METHODS: We performed a retrospective review of 185 distal radius fractures that underwent volar locked plating with a single plate design over a 5-year period. We reviewed radiographs and recorded measurements for volar tilt, radial inclination, ulnar variance, radial height, and articular stepoff. We used logistic regression to determine the association between return to radiographic standard norms and fracture type. RESULTS: At the first and final postoperative follow-up visits, we observed articular congruence less than 2 mm in 92% of fractures at both times. Normal volar tilt (11°) was restored in 46% at the first follow-up and 48% at the final one. Radial inclination (22°) was achieved in 44% at the first follow-up and 43% at the final one, and ulnar variance (01 ± 2 mm) was achieved in 53% at the first follow-up and 53% at the final one. In addition, radial height (14 ± 1mm) was restored in 14% at the first follow-up and 12% at the final one. More complex, intra-articular fractures (AO class B and C and Frykman types 3, 4, 7, and 8) were less likely to be restored to normal radiographic parameters. However, because of the small sample size for some fracture types, it was difficult to discover significant associations between fracture type and radiographic outcome. CONCLUSIONS: Volar locked plating for distal radius fractures achieved articular stepoff less than 2 mm in most fractures but only restored and maintained normal radiographic measurements for volar tilt, radial inclination, and ulnar variance in 50% of fractures. The ability of volar locked plating to restore and maintain ulnar variance and volar tilt decreased with more complex intra-articular fracture types. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.


Subject(s)
Bone Plates , Radius Fractures/diagnostic imaging , Radius Fractures/surgery , Adolescent , Adult , Aged , Female , Fracture Fixation, Internal , Humans , Intra-Articular Fractures/diagnostic imaging , Intra-Articular Fractures/surgery , Logistic Models , Male , Middle Aged , Radiography , Retrospective Studies , Treatment Outcome , Wrist Joint/diagnostic imaging , Young Adult
4.
Pediatr Blood Cancer ; 58(4): 616-20, 2012 Apr.
Article in English | MEDLINE | ID: mdl-21721114

ABSTRACT

BACKGROUND: Pneumatosis Intestinalis (PI) is a rare complication following hematopoietic stem cell transplant (HSCT). We sought to assess the incidence, risk factors, and outcome associated with PI. PROCEDURE: We retrospectively reviewed the incidence of PI among 178 patients who underwent allogeneic HSCT between September 1999 and February 2010. RESULTS: Eighteen of 178 children (10.1%) who received allogeneic HSCT developed PI at a median of 94 days (range, 11-1169) after transplant. All patients presented with either abdominal pain or distention, and half of the patients had free air on radiographs. Patients who developed PI had a significantly higher proportion of acute (83% vs. 44%, P = 0.002) and chronic graft versus host disease (GVHD; 56% vs. 18%, P < 0.001). Only 39% of patients with PI had GVHD involving the gasterointestinal track. All patients were managed conservatively without surgery. Transplant related mortality (TRM) was significantly higher in patients who developed PI compared to those who did not (OR 4.3, 95% CI: 1.3-13.1; P = 0.007), but no deaths were attributable to PI. CONCLUSIONS: We conclude that PI is a common complication associated with treatment of GVHD after HSCT, and patients who develop PI experience higher TRM. Patients who develop PI should be managed medically.


Subject(s)
Graft vs Host Disease/mortality , Graft vs Host Disease/therapy , Pneumatosis Cystoides Intestinalis , Stem Cell Transplantation , Acute Disease , Child , Child, Preschool , Chronic Disease , Female , Humans , Incidence , Male , Pneumatosis Cystoides Intestinalis/etiology , Pneumatosis Cystoides Intestinalis/mortality , Pneumatosis Cystoides Intestinalis/therapy , Retrospective Studies , Risk Factors , Time Factors , Transplantation, Homologous
5.
Crit Care Med ; 39(6): 1343-50, 2011 Jun.
Article in English | MEDLINE | ID: mdl-21336116

ABSTRACT

OBJECTIVES: To determine whether prehospital statin use is associated with a lower risk of sepsis, acute lung injury/acute respiratory distress syndrome, and mortality in critically ill patients. We also investigated the effect of combined prehospital use of both statins and aspirin. DESIGN: Cross-sectional analysis of a prospective cohort. PATIENTS: A total of 575 critically ill patients admitted to the medical or surgical intensive care unit of an academic tertiary-care hospital. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 575 patients, 149 (26%) were on statin therapy before hospitalization. A multivariable analysis including age, gender, current tobacco use, prehospital aspirin use, race, and Acute Physiology and Chronic Health Evaluation II score revealed that patients on statin therapy before hospitalization were less likely to have or develop severe sepsis (odds ratio 0.62, 95% confidence interval 0.40-0.96) or acute lung injury/acute respiratory distress syndrome (odds ratio 0.60, 95% confidence interval 0.36-0.99) during the first four intensive care unit days. In-hospital mortalities for patients with and without prehospital statin use (odds ratio 1.06, 95% confidence interval 0.62-1.83) were similar. Patients who had prehospital use of both statins and aspirin had the lowest rates of severe sepsis, acute lung injury/acute respiratory distress syndrome, and mortality. CONCLUSIONS: Prehospital use of statins may be protective against sepsis and acute lung injury. This effect may be potentiated by prehospital aspirin use.


Subject(s)
Acute Lung Injury/epidemiology , Aspirin/therapeutic use , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Platelet Aggregation Inhibitors/therapeutic use , Respiratory Distress Syndrome/epidemiology , Sepsis/epidemiology , Aged , Cohort Studies , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Prevalence
6.
Pediatr Blood Cancer ; 56(7): 1114-9, 2011 Jul 01.
Article in English | MEDLINE | ID: mdl-21488156

ABSTRACT

BACKGROUND: 25-hydroxyvitamin D insufficiency is common in healthy children and adolescents. There have been limited studies of the 25-hydroxyvitamin D status of survivors of pediatric and adolescent acute lymphoblastic leukemia (ALL). PROCEDURE: In a cohort of 78 ALL survivors (52 chemotherapy-treated and 26 HCT-treated), we determined the prevalence of, and host, treatment and environmental risk factors for 25-hydroxyvitamin D insufficiency and deficiency. RESULTS: There were no differences in serum 25-hydroxyvitamin D levels between ALL survivors treated with conventional chemotherapy and those treated with HCT (median 26.0 vs 25.5 ng/ml). Fifty-three percent of pediatric ALL survivors were 25-hydroxyvitamin D insufficient (15-29 ng/dl), and 12% were deficient (<15 ng/dl). Younger age, higher reported dietary vitamin D intake, use of vitamin D supplementation, and increased ambient ultraviolet light were associated with higher serum 25-hydroxyvitamin D levels. There was not enough evidence to suggest treatment type, gender, race, years since diagnosis or BMI were associated with serum 25-hydroxyvitamin D levels. Only 27% of conventional chemotherapy-treated ALL survivors and 8% of HCT-treated ALL survivors met RDA for dietary vitamin D intake. CONCLUSIONS: The prevalence of vitamin D deficiency and insufficiency in ALL survivors is similar to that of the general pediatric population in the United States, and there is no difference in serum 25-hydroxyvitamin D status between chemotherapy-treated and HCT-treated ALL survivors. ALL survivors rarely meet the RDA requirements for vitamin D. Further studies are needed to determine whether dietary and behavioral interventions can improve the vitamin D status of ALL survivors.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/adverse effects , Neoplasm Recurrence, Local/therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy , Stem Cell Transplantation/adverse effects , Vitamin D Deficiency/etiology , Adolescent , Adult , Child , Combined Modality Therapy , Cross-Sectional Studies , Cyclophosphamide/administration & dosage , Female , Humans , Male , Neoplasm Recurrence, Local/mortality , Precursor Cell Lymphoblastic Leukemia-Lymphoma/mortality , Prednisone/administration & dosage , Prospective Studies , Radiotherapy Dosage , Salvage Therapy , Survival Rate , Survivors , Transplantation, Homologous , Treatment Outcome , Vitamin D/analogs & derivatives , Vitamin D/blood , Vitamin D Deficiency/blood , Young Adult
7.
Pediatr Blood Cancer ; 56(3): 372-8, 2011 Mar.
Article in English | MEDLINE | ID: mdl-20860019

ABSTRACT

BACKGROUND: Obesity and hypertension are reported among survivors of pediatric acute lymphoblastic leukemia (ALL). However, little is known about the trajectory of body mass index (BMI) and blood pressure over the course of ALL therapy. PROCEDURE: In a retrospective cohort of 183 pediatric ALL patients diagnosed from 2000 to 2008, prevalence, severity, and risk factors for obesity and hypertension were assessed during treatment. RESULTS: At diagnosis, 36% of patients were overweight and 19% were obese. Median BMI increased during induction therapy with a return to baseline soon after, but increased again over the first 22 months of maintenance therapy. At the end of therapy, 49% were overweight and 21% were obese. Increased BMI z-score at diagnosis was associated with increased z-score during maintenance (P < 0.001). Elevated parental BMI was associated with elevated BMI at diagnosis. Median BMI z-score increased over the first 22 months of maintenance (P < 0.001). Patients with high risk disease had lower BMI z-scores regardless of cranial radiotherapy exposure (P < 0.001). Pre-hypertension was prevalent over the course of therapy (31.1% with systolic pre-hypertension and 18.6% with diastolic pre-hypertension). Hypertension was also highly prevalent with 41.5% meeting systolic criteria and 24.0% meeting diastolic criteria. CONCLUSIONS: During ALL therapy, patients are at risk for early development of elevated BMI and blood pressure, which places them at potentially increased risk for future adverse health conditions. Future studies are needed to develop strategies to mitigate these risks, such as potential reduction of corticosteroid pulses or a family-based diet and exercise intervention during maintenance therapy.


Subject(s)
Blood Pressure , Hypertension/etiology , Obesity/etiology , Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy , Adolescent , Adult , Body Mass Index , Child , Child, Preschool , Cohort Studies , Female , Humans , Infant , Male , Overweight/etiology , Precursor Cell Lymphoblastic Leukemia-Lymphoma/physiopathology , Prognosis , Retrospective Studies , Risk Factors , Young Adult
9.
Biol Blood Marrow Transplant ; 15(12): 1620-7, 2009 Dec.
Article in English | MEDLINE | ID: mdl-19896086

ABSTRACT

Total body irradiation (TBI)-based conditioning regimens for pediatric patients with acute myelogenous leukemia (AML) beyond first complete remission (CR1) are controversial. Because the long-term morbidity of busulfan (Bu)-based regimens appears to be lower, determining efficacy is critical. We retrospectively evaluated 151 pediatric patients with AML beyond CR1, comparing outcomes in 90 patients who received a TBI-based conditioning regimen and 61 patients who received a Bu-based conditioning regimen. There were no differences between the 2 groups with respect to age, sex, duration of CR1, time from most recent remission to transplantation, or donor source. The probability of relapse at 2 years also did not differ between the 2 groups (26% and 27%, respectively; P=.93). No significant difference in event-free survival (EFS) (P=.29) or overall survival (OS) (P=.11) was noted between the 2 groups. These findings were supported by a multivariate analysis in which TBI was not associated with improved EFS (hazard ratio [HR]=1.17; 95% confidence interval [CI]=0.66-2.10; P=.58) or OS (HR=1.42; 95% CI=0.76-2.64; P=.27). Shorter CR1 and receiving an HLA-mismatched transplant adversely affected EFS and OS in this cohort. Our study provides no evidence of an advantage to using TBI in children with AML beyond CR1. A prospective, randomized study is needed to confirm these results.


Subject(s)
Antineoplastic Agents, Alkylating/therapeutic use , Busulfan/therapeutic use , Hematopoietic Stem Cell Transplantation/methods , Leukemia, Myeloid, Acute/therapy , Transplantation Conditioning/methods , Adolescent , Adult , Bone Marrow Transplantation/methods , Bone Marrow Transplantation/mortality , Child , Child, Preschool , Cohort Studies , Cord Blood Stem Cell Transplantation/adverse effects , Cord Blood Stem Cell Transplantation/methods , Disease-Free Survival , Female , Hematopoietic Stem Cell Transplantation/adverse effects , Humans , Infant , Leukemia, Myeloid, Acute/drug therapy , Leukemia, Myeloid, Acute/surgery , Male , Multivariate Analysis , Remission Induction , Retrospective Studies , Survival Rate , Transplantation Conditioning/adverse effects , Treatment Outcome , Whole-Body Irradiation , Young Adult
10.
Autism ; 13(4): 375-87, 2009 Jul.
Article in English | MEDLINE | ID: mdl-19535467

ABSTRACT

Parents of children with developmental disabilities, particularly autism spectrum disorders (ASDs), are at risk for high levels of distress. The factors contributing to this are unclear. This study investigated how child characteristics influence maternal parenting stress and psychological distress. Participants consisted of mothers and developmental-age matched preschool-aged children with ASD (N = 51) and developmental delay without autism (DD) ( N = 22). Evidence for higher levels of parenting stress and psychological distress was found in mothers in the ASD group compared to the DD group. Children's problem behavior was associated with increased parenting stress and psychological distress in mothers in the ASD and DD groups. This relationship was stronger in the DD group. Daily living skills were not related to parenting stress or psychological distress. Results suggest clinical services aiming to support parents should include a focus on reducing problem behaviors in children with developmental disabilities.


Subject(s)
Autistic Disorder/diagnosis , Child Behavior Disorders/prevention & control , Developmental Disabilities/diagnosis , Mothers/psychology , Parenting/psychology , Stress, Psychological/diagnosis , Activities of Daily Living/psychology , Adaptation, Psychological , Adult , Autistic Disorder/epidemiology , Autistic Disorder/psychology , Child Behavior Disorders/psychology , Child, Preschool , Comorbidity , Developmental Disabilities/epidemiology , Developmental Disabilities/psychology , Female , Humans , Male , Parent-Child Relations , Personality Inventory , Stress, Psychological/psychology , Surveys and Questionnaires
11.
Cancer Epidemiol Biomarkers Prev ; 17(11): 3076-80, 2008 Nov.
Article in English | MEDLINE | ID: mdl-18957524

ABSTRACT

OBJECTIVE: To evaluate the association between lipid-lowering agents, antihypertensive medications, and colorectal cancer risk. We hypothesized a reduction in colorectal cancer risk with 3-hydroxy-3-methylglutaryl coA reductase inhibitors (statins) and angiotensin-converting enzyme inhibitors. METHODS: We conducted a case-control study at Group Health Cooperative, an integrated delivery system in Washington State. Incident colorectal cancer cases diagnosed between January 1, 2000, and December 31, 2003, were identified from the western Washington Surveillance, Epidemiology, and End Results cancer registry. Controls were matched by age, sex, and duration of enrollment. Data on medication use and potential confounders were obtained from health plan records. We estimated odds ratios and 95% confidence intervals (95% CI) using multivariate conditional logistic regression. RESULTS: Risk for colorectal cancer was not associated with use of statins (odds ratio, 1.02; 95% CI, 0.65-1.59), other lipid-lowering agents (odds ratio, 1.31; 95% CI, 0.70-2.47), angiotensin-converting enzyme inhibitors (odds ratio, 0.98; 95% CI, 0.67-1.43), calcium channel blockers (odds ratio, 1.06; 95% CI, 0.72-1.55), or diuretics (odds ratio, 1.00; 95% CI, 0.70-1.44). Risk did not differ by duration of medication use, including long-term use. CONCLUSIONS: Risk for colorectal cancer was not reduced by use of statins or angiotensin-converting enzyme inhibitors. Other lipid-lowering and antihypertensive medications were also not associated with colorectal cancer risk.


Subject(s)
Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Antihypertensive Agents/therapeutic use , Calcium Channel Blockers/therapeutic use , Cardiovascular Diseases/drug therapy , Colorectal Neoplasms/epidemiology , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Aged , Case-Control Studies , Colorectal Neoplasms/prevention & control , Female , Humans , Incidence , Logistic Models , Male , Risk , SEER Program , Washington/epidemiology
12.
J Am Heart Assoc ; 5(9)2016 09 16.
Article in English | MEDLINE | ID: mdl-27638785

ABSTRACT

BACKGROUND: Recent longitudinal work suggests that weight change is an important risk factor for inflammation across the full range of BMI. However, few studies have examined whether the risk of inflammation differs by patterns of weight gain over time. Using latent class trajectory analysis, we test whether patterns of weight gain are associated with elevated high-sensitivity C-reactive protein (hs-CRP 2-10 mg/L). METHODS AND RESULTS: Data come from China Health and Nutrition Survey (CHNS) participants (n=5536), aged 18 at baseline to 66 years in 2009, with measured weight over 18 years. Latent class trajectory analysis was used to identify weight-change trajectories in 6 age and sex strata. Multivariable general linear mixed-effects models fit with a logit link were used to assess the risk of elevated hs-CRP across weight trajectory classes. Models were fit within age and sex strata, controlling for baseline weight, adult height, and smoking, and included random intercepts to account for community-level correlation. Steeper weight-gain trajectories were associated with greater risk of elevated hs-CRP compared to more moderate weight-gain trajectories in men and women. Initially high weight gain followed by weight loss was associated with lower risk of elevated hs-CRP in women aged 18 to 40. CONCLUSIONS: Latent class trajectory analysis identified heterogeneity in adult weight change associated with differential risk of inflammation independently of baseline weight and smoking. These results suggest that trajectories of weight gain are an important clinical concern and may identify those at risk for inflammation and the development of cardiometabolic disease.


Subject(s)
Asian People , C-Reactive Protein/immunology , Obesity/immunology , Weight Gain/immunology , Adolescent , Adult , Age Factors , Aged , China , Disease Progression , Female , Humans , Linear Models , Longitudinal Studies , Male , Middle Aged , Multivariate Analysis , Nutrition Surveys , Overweight/immunology , Sex Factors , Young Adult
13.
Am J Med ; 129(8): 792-5, 2016 08.
Article in English | MEDLINE | ID: mdl-26972793

ABSTRACT

In today's hospital and clinic environment, the obstacles to bedside teaching for both faculty and trainees are considerable. As electronic health record systems become increasingly prevalent, trainees are spending more time performing patient care tasks from computer workstations, limiting opportunities to learn at the bedside. Physical examination skills rarely are emphasized, and low confidence levels, especially in junior faculty, pose additional barriers to teaching the bedside examination.


Subject(s)
Clinical Competence , Clinical Medicine/education , Education, Medical/methods , Physical Examination , Teaching , Electronic Health Records , Humans , Physician-Patient Relations , Point-of-Care Systems
14.
PLoS One ; 10(2): e0116190, 2015.
Article in English | MEDLINE | ID: mdl-25699674

ABSTRACT

BACKGROUND: Over the past three decades, obesity-related diseases have increased tremendously in China, and are now the leading causes of morbidity and mortality. Patterns of weight change can be used to predict risk of obesity-related diseases, increase understanding of etiology of disease risk, identify groups at particularly high risk, and shape prevention strategies. METHODS: Latent class trajectory modeling was used to compute weight change trajectories for adults aged 18 to 66 using the China Health and Nutrition Survey (CHNS) data (n = 12,611). Weight change trajectories were computed separately for males and females by age group at baseline due to differential age-related patterns of weight gain in China with urbanization. Generalized linear mixed effects models examined the association between weight change trajectories and baseline characteristics including urbanicity, BMI category, age, and year of study entry. RESULTS: Trajectory classes were identified for each of six age-sex subgroups corresponding to various degrees of weight loss, maintenance and weight gain. Baseline BMI status was a significant predictor of trajectory membership for all age-sex subgroups. Baseline overweight/obesity increased odds of following 'initial loss with maintenance' trajectories. We found no significant association between baseline urbanization and trajectory membership after controlling for other covariates. CONCLUSION: Trajectory analysis identified patterns of weight change for age by gender groups. Lack of association between baseline urbanization status and trajectory membership suggests that living in a rural environment at baseline was not protective. Analyses identified age-specific nuances in weight change patterns, pointing to the importance of subgroup analyses in future research.


Subject(s)
Obesity/epidemiology , Weight Gain , Adolescent , Adult , Age Distribution , Aged , China/epidemiology , Female , Humans , Longitudinal Studies , Male , Middle Aged , Nutrition Surveys , Risk Factors , Urban Population , Urbanization , Young Adult
15.
Clin Colorectal Cancer ; 12(3): 168-78, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23773459

ABSTRACT

BACKGROUND: Molecular analysis has become important in colorectal carcinoma (CRC) evaluation. Alterations in KRAS, BRAF, or mismatch repair (MMR) genes may determine therapeutic response or define a hereditary cancer syndrome. Correlation of DNA studies with clinical findings will further clarify the clinical utility of these markers. PATIENTS AND METHODS: A retrospective study was performed on 111 paraffin-embedded tumor specimens submitted for microsatellite instability (MSI) testing based on clinical history or histologic examination, or both. DNA samples were screened for 7 KRAS mutations and the BRAF p.V600E mutation using fluorescent allele-specific polymerase-chain reaction (PCR) and capillary electrophoresis. Clinical data were collected through chart review. RESULTS: Fifty-eight male and 53 female patients were studied. The incidence of KRAS and BRAF mutations was 49.5% and 7.2%, respectively. Dideoxy sequencing verified KRAS mutation status in 46 of 49 specimens tested. There was a trend toward significance of individual KRAS mutations on survival (P = .003). Dually positive KRAS and MSI tumors exclusively demonstrated p.G12D and p.G13D mutations (G>A transitions). BRAF-mutated tumors were predominantly right-sided and associated with a borderline worse prognosis. Forty-eight percent of tumors with MSI were present in the left colon or rectum. CONCLUSION: Allele-specific PCR is an accurate and convenient method to assess KRAS and BRAF mutations and may detect mutations not identified by dideoxy sequencing. KRAS mutation status, in conjunction with morphologic or clinical parameters, may be useful in determining whether a tumor should be tested for MSI. MSI testing should not be considered exclusively in right-sided lesions. BRAF analysis may not be useful in rectal adenocarcinomas and should be evaluated in larger studies.


Subject(s)
Biomarkers, Tumor/genetics , Colorectal Neoplasms/genetics , Microsatellite Instability , Mutation/genetics , Proto-Oncogene Proteins B-raf/genetics , Proto-Oncogene Proteins/genetics , ras Proteins/genetics , Adult , Colorectal Neoplasms/mortality , Colorectal Neoplasms/pathology , Female , Follow-Up Studies , Humans , Male , Middle Aged , Neoplasm Staging , Prognosis , Proto-Oncogene Proteins p21(ras) , Retrospective Studies , Survival Rate
16.
J Pediatr Surg ; 47(6): 1272-9, 2012 Jun.
Article in English | MEDLINE | ID: mdl-22703805

ABSTRACT

PURPOSE: We aimed to assess the late effects of ovarian salvage or oophorectomy on gonadal function and fertility as measured by menstrual regularity. METHODS: We performed a 10-year retrospective review of females aged 20 years or younger who required surgery to treat an ovarian disorder. A mail survey was distributed to these patients to evaluate the effects of ovarian surgery on menarche, menstrual regularity, and pregnancy. RESULTS: A total of 180 females had surgery to treat an ovarian disorder. Eighty-six of these underwent unilateral oophorectomy (48%), whereas 94 (52%) had an ovary sparing procedure. Eighty-one patients (45%) returned completed surveys. Of the respondents, 44 had oophorectomy, and 37 had ovarian salvage. Ages of menarche were similar between surgical groups. Symptoms of menstrual irregularity differed most significantly according to painful menses (oophorectomy, 27.3%; salvage, 59.5%; P < .04). Interestingly, continuation of regular menses after surgery was higher in the oophorectomy group (oophorectomy, 70%; salvage, 15%; P = .013). CONCLUSIONS: Unilateral oophorectomy does not appear to impair late gonadal function when compared with ovarian salvage. Surprisingly, oophorectomy appears to maintain more normal ovarian activity as estimated by menstrual regularity. Oophorectomy may be performed without apparent adverse effect on gonadal activity.


Subject(s)
Ovariectomy/adverse effects , Ovary/physiology , Adolescent , Child , Child, Preschool , Female , Follow-Up Studies , Humans , Infant , Infant, Newborn , Infertility, Female/epidemiology , Infertility, Female/etiology , Menarche , Menstruation , Menstruation Disturbances/epidemiology , Menstruation Disturbances/etiology , Organ Sparing Treatments , Ovarian Diseases/surgery , Ovary/surgery , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Pregnancy , Retrospective Studies , Salpingectomy , Surveys and Questionnaires , Torsion Abnormality/surgery , Young Adult
17.
J Clin Oncol ; 29(29): 3932-8, 2011 Oct 10.
Article in English | MEDLINE | ID: mdl-21911716

ABSTRACT

PURPOSE: Factors that influence hematology-oncology fellows' choice of academic medicine as a career are not well defined. We undertook a survey of hematology-oncology fellows training at cancer centers designated by the National Cancer Institute (NCI) and the National Comprehensive Cancer Network (NCCN) to understand the factors fellows consider when making career decisions. METHODS: Program directors at all NCI and NCCN cancer centers were invited to participate in the study. For the purpose of analysis, fellows were grouped into three groups on the basis of interest in an academic career. Demographic data were tested with the Kruskal-Wallis test and χ² test, and nondemographic data were tested by using the multiscale bootstrap method. RESULTS: Twenty-eight of 56 eligible fellowship programs participated, and 236 fellows at participating institutions responded (62% response rate). Approximately 60% of fellows graduating from academic programs in the last 5 years chose academic career paths. Forty-nine percent of current fellows ranked an academic career as extremely important. Fellows choosing an academic career were more likely to have presented and published their research. Additional factors associated with choosing an academic career included factors related to mentorship, intellect, and practice type. Fellows selecting nonacademic careers prioritized lifestyle in their career decision. CONCLUSION: Recruitment into academic medicine is essential for continued progress in the field. Our data suggest that fewer than half the current fellows training at academic centers believe a career in academic medicine is important. Efforts to improve retention in academics should include focusing on mentorship, research, and career development during fellowship training and improving the image of academic physicians.


Subject(s)
Career Choice , Hematology/education , Medical Oncology/education , Adult , Fellowships and Scholarships , Female , Humans , Male , United States
18.
Mol Imaging Biol ; 13(5): 840-52, 2011 Oct.
Article in English | MEDLINE | ID: mdl-20809209

ABSTRACT

PURPOSE: Metabolism, and especially glucose uptake, is a key quantitative cell trait that is closely linked to cancer initiation and progression. Therefore, developing high-throughput assays for measuring glucose uptake in cancer cells would be enviable for simultaneous comparisons of multiple cell lines and microenvironmental conditions. This study was designed with two specific aims in mind: the first was to develop and validate a high-throughput screening method for quantitative assessment of glucose uptake in "normal" and tumor cells using the fluorescent 2-deoxyglucose analog 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxyglucose (2-NBDG), and the second was to develop an image-based, quantitative, single-cell assay for measuring glucose uptake using the same probe to dissect the full spectrum of metabolic variability within populations of tumor cells in vitro in higher resolution. PROCEDURE: The kinetics of population-based glucose uptake was evaluated for MCF10A mammary epithelial and CA1d breast cancer cell lines, using 2-NBDG and a fluorometric microplate reader. Glucose uptake for the same cell lines was also examined at the single-cell level using high-content automated microscopy coupled with semi-automated cell-cytometric image analysis approaches. Statistical treatments were also implemented to analyze intra-population variability. RESULTS: Our results demonstrate that the high-throughput fluorometric assay using 2-NBDG is a reliable method to assess population-level kinetics of glucose uptake in cell lines in vitro. Similarly, single-cell image-based assays and analyses of 2-NBDG fluorescence proved an effective and accurate means for assessing glucose uptake, which revealed that breast tumor cell lines display intra-population variability that is modulated by growth conditions. CONCLUSIONS: These studies indicate that 2-NBDG can be used to aid in the high-throughput analysis of the influence of chemotherapeutics on glucose uptake in cancer cells.


Subject(s)
Glucose/metabolism , Neoplasms/metabolism , Cell Line, Tumor , Fluorescence , Humans
19.
Am Surg ; 77(5): 612-20, 2011 May.
Article in English | MEDLINE | ID: mdl-21679597

ABSTRACT

Complete pancreatic transection (CPT) in children is managed commonly with distal pancreatectomy (DP). Alternatively, Roux-en-Y distal pancreaticojejunostomy (RYPJ) may be performed to preserve pancreatic tissue. The purpose of this study was to review our experience using either procedure in the management of children sustaining CPT after blunt abdominal trauma. We retrospectively reviewed the records of all children admitted to our institution during the last 15 years who were confirmed at operation to have CPT after blunt mechanisms. Summary statistics of demographic data were performed to describe children receiving either RYPJ or DP. CPT occurred in 28 children: 15 had DP, 10 had RYPJ, and three had cystogastrostomy. RYPJ children, compared with DP, were younger (7.5 vs. 12.3 years, P = 0.039) and sustained more grade IV pancreatic injuries (70% vs. 14%, P = 0.01). DP patients were 5.63 times more likely to tolerate full enteral feeds (P = 0.009). Nevertheless, when controlling for age, injury severity score, and pancreatic injury grade, procedure type did not statistically affect total and postoperative lengths of stay and postoperative complications. In the operative management algorithm of children sustaining CPT, DP may afford an earlier return to full enteral feeds. RYPJ seems otherwise equivalent to DP and preserves significant pancreatic glandular tissue and the spleen.


Subject(s)
Abdominal Injuries/surgery , Pancreas/surgery , Pancreatectomy/methods , Salvage Therapy , Wounds, Nonpenetrating/surgery , Abdominal Injuries/diagnosis , Abdominal Injuries/mortality , Adolescent , Age Factors , Analysis of Variance , Anastomosis, Surgical/methods , Child , Child, Preschool , Cohort Studies , Female , Follow-Up Studies , Humans , Infant , Injury Severity Score , Male , Minimally Invasive Surgical Procedures/methods , Pancreas/injuries , Pancreatectomy/adverse effects , Postoperative Care/methods , Postoperative Complications/mortality , Postoperative Complications/physiopathology , Proportional Hazards Models , Retrospective Studies , Risk Assessment , Statistics, Nonparametric , Survival Rate , Treatment Outcome , Wounds, Nonpenetrating/diagnosis , Wounds, Nonpenetrating/mortality
20.
World J Gastroenterol ; 16(4): 453-7, 2010 Jan 28.
Article in English | MEDLINE | ID: mdl-20101770

ABSTRACT

AIM: To assess the role of IgM and IgG immunohistochemistry (IHC) in the evaluation of autoimmune liver conditions--autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), and primary sclerosing cholangitis (PSC). METHODS: Forty one biopsies from untreated patients diagnosed with autoimmune liver disease (AIH, n = 20; PBC, n = 13; PSC, n = 8) and fourteen biopsies of patients with chronic hepatitis C were selected. IgM and IgG-positive plasma cells were counted in each sample. RESULTS: A predominance of IgG-positive plasma cells was seen in AIH (90% of cases), PSC (75% of cases), and chronic hepatitis C (100% of cases), while IgM-positive plasma cells predominated in PBC (92.8% of cases). The IgM /IgG ratio (< 1 or > or = 1) accurately distinguished PBC from AIH in 90.9% of cases (sensitivity = 92.3%, specificity = 90%), and PBC from either AIH or PSC in 87.8% of cases (sensitivity = 92.3%, specificity = 85.7%). CONCLUSION: Plasmacytic infiltrates expressing predominantly IgM are characteristic of PBC, while other forms of liver disease analyzed in this study, including AIH, typically show an IgG-predominant plasma cell infiltrate. Our data indicate that IgM and IgG IHC may be a useful tool when PBC is a diagnostic consideration.


Subject(s)
Cholangitis, Sclerosing/diagnosis , Hepatitis, Autoimmune/diagnosis , Immunoglobulin G/metabolism , Immunoglobulin M/metabolism , Liver Cirrhosis, Biliary/diagnosis , Adolescent , Adult , Aged , Biopsy , Child , Child, Preschool , Cholangitis, Sclerosing/immunology , Female , Hepatitis, Autoimmune/immunology , Humans , Immunohistochemistry , Liver/immunology , Liver/pathology , Liver Cirrhosis, Biliary/immunology , Male , Middle Aged , Plasma Cells/metabolism , Young Adult
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