Mutations in SOX2 cause anophthalmia-esophageal-genital (AEG) syndrome

Table 1     

Reduced blood clearance and increased urinary excretion of N-nitrosodimethylamine in patas monkeys exposed to ethanol or isopropyl alcohol.

Low concentrations of N-nitrosodimethylamine are metabolized in rodent and human liver by cytochrome P450IIE1, an activity competitively inhibitable by ethanol. In rodents coadministration of ethanol with N-nitrosodimethylamine results in increased tumorigenicity in extrahepatic organs, probably as a result of reduced hepatic clearance. To test this concept in a primate, the effects of ethanol cotreatment on the pharmacokinetics of N-nitrosodimethylamine were measured in male patas monkeys. Ethanol, 1.2 g/kg given p.o. before i.v. N-nitrosodimethylamine (1 mg/kg) or concurrently with an intragastric dose resulted in a 10-50-fold increase in the area under the blood concentration versus time curves and a 4-13-fold increase in mean residence times for N-nitrosodimethylamine. Isopropyl alcohol, 3.2 g/kg 24 h before N-nitrosodimethylamine, also increased these parameters 7-10-fold; this effect was associated with persistence of isopropyl alcohol and its metabolic product acetone, both IIE1 inhibitors, in the blood. While no N-nitrosodimethylamine was detected in expired air, trace amounts were found in urine. Ethanol and isopropyl alcohol pretreatment increased the maximum urinary N-nitrosodimethylamine concentration 15-50-fold and the percentage of the dose excreted in the urine by 100-800-fold. Thus ethanol and isopropyl alcohol greatly increase systemic exposure of extrahepatic organs to N-nitrosodimethylamine in a primate.     

Recovery and Utilization of Deceased Donor Kidneys from Small Pediatric Donors

The optimal use of kidneys from small pediatric deceased donors remains undetermined. Using data from the Scientific Registry of Transplant Recipients, 2886 small (< 21 kg) pediatric donors between 1993 and 2002 were identified. Donor factors predictive of kidney recovery and transplantation (1343 en bloc; 1600 single) were identified by logistic regression. Multivariable Cox regression was used to assess the risk of graft loss. The rate of kidney recovery from small pediatric donors was significantly higher with increasing age, weight and height. The odds of transplant of recovered small donor kidneys were significantly higher with increasing age, weight, height and en bloc recovery (adjusted odds ratio = 65.8 vs. single; p < 0.0001), and significantly lower with increasing creatinine. Compared to en bloc, solitary transplants had a 78% higher risk of graft loss (p < 0.0001). En bloc transplants had a similar graft survival to ideal donors (p = 0.45) while solitary transplants had an increased risk of graft loss (p < 0.0001). En bloc recovery of kidneys from small pediatric donors may result in the highest probability of transplantation. Although limited by the retrospective nature of the study, kidneys transplanted en bloc had a similar graft survival to ideal donors but may not maximize the number of successfully transplanted recipients.     

Video-assisted thoracic surgery: basic technical concepts and intercostal approach strategies.

Video-assisted thoracic surgery is emerging as a viable approach to a number of intrathoracic disorders. Technical difficulties related to improper instrument selection and suboptimal intercostal operative access can reduce the utility of, and the enthusiasm for, the video-assisted thoracic surgical approach. This report describes the intercostal access strategy and the instrument positioning that we now prescribe for many video-assisted thoracic surgical procedures. These approaches have become refined during the course of our experience with 467 patients undergoing video-assisted thoracic operations over the last 18 months.     

Symptom profile and asthma control in school-aged children.

BACKGROUND: Children with poorly controlled asthma are at high risk of airway remodeling, sleep disruption, school absenteeism, and limited participation in activities. OBJECTIVE: To determine asthma prevalence and characterize disease severity and burden in school-aged children. METHOD: A case-finding study was conducted via a multiple-choice questionnaire and asthma algorithm. Items used for analysis include physician diagnosis of asthma, symptom severity, and health care utilization. The chi2 test was used to determine the significance of differences among cases. Logistic regression was used to evaluate the association of patient factors and asthma indicators. RESULTS: Of the 5,417 children surveyed, 1,341 (25%) were classified as being at risk of asthma. Of these asthma cases, 55% were positive by diagnosis and algorithm (active), 10% were positive per algorithm alone (suspected), and 35% were positive per diagnosis alone (nonactive). Only 14% of all asthma cases reported experiencing no respiratory symptoms (< 1% active, 2% suspected, and 40% nonactive) compared with 75% of noncases. Also, 75% of noncases reported never missing school compared with 19%, 33%, and 54% of active, suspected, and nonactive asthma cases. African American race, Medicaid enrollment, and male sex were independent predictors of asthma risk. Similarly, African American race, Medicaid enrollment, age, and persistent asthma were independent predictors of emergency department use among asthma cases. DISCUSSION: Prevalence of active symptoms suggestive of poor asthma control was extremely high among urban, minority children enrolled in Arkansas' largest public school district. Poor asthma control greatly affects quality of life, including school attendance and performance. Interventions should raise expectations and emphasize the importance of achieving asthma control.     

Financial Implications of Pancreas Transplant Complications: A Business Case for Quality Improvement

We quantified the financial implications of surgical complications following pancreas transplantation. We reviewed medical and financial records of 49 pancreas transplant recipients at the University of Michigan Health System (UMHS) between 1/6/2002 and 11/22/2004. The association of donor, transplant recipient and financial variables was assessed. The median costs to UMHS of procedures and follow-up were $92,917 for recipients without surgical complications versus $108,431 when a surgical complication occurred, a difference of $15,514 (p = 0.03). Median reimbursement by the payer was $17,363 higher in patients with a surgical complication (p = 0.001). Similar trends (higher insurer costs) were noted when stratifying by payer (public and private) and specific procedure (SPK and PAK). All parties (patient, physician, payer and medical center) should benefit from quality improvement, with payers having a financial interest in pancreas transplant surgical quality initiatives.     

Psychological Functioning, Nonadherence and Health Outcomes After Pediatric Liver Transplantation

The present study empirically assessed the relationships between adherence behaviors and HRQOL, parent and child psychological functioning and family functioning, and investigated the relationship between adherence behaviors and health outcomes in children who were within 5 years of their liver transplantation. Participants included 38 children (mean = 8.5 years, range 28 months to 16 years) and their parent/guardian(s). HRQOL and psychological functioning were examined using well-validated assessment measures. Measures of adherence included the rate of clinic attendance and standard deviations (SDs) of consecutive tacrolimus blood levels, which were collected and evaluated retrospectively. Measures of child health status included the frequency of hospital admissions, liver biopsies, episodes of rejection and graft function for the year prior to study participation. Results indicated that nonadherence was related to lower physical HRQOL, more limitations in social and school activities related to emotional and behavioral problems, parental emotional distress and decreased family cohesion. Nonadherence was also related to frequency and duration of hospitalizations, liver biopsies and rejection episodes. These results suggest that empirically based assessment of HRQOL, parenting stress and family functioning may help identify patients at risk for nonadherence, and may allow for the need-based delivery of appropriate clinical interventions.     

Do commonly used oral antihypertensives alter fetal or neonatal heart rate characteristics? A systematic review.

OBJECTIVE: To examine fetal (FHR) and neonatal heart rate patterns following use of common oral antihypertensives in pregnancy. METHODS: A systematic review of randomized controlled trials (RCTs), observational studies (N >/= 6 women), and animal studies. Data were abstracted (two reviewers) to determine relative risk (RR) (or risk difference (RD) for low event rates) and 95% CI. RESULTS: Eighteen RCTs (1858 women), one controlled observational study (N = 22), and seven case series (N = 117) were reviewed. Most hypertension was pregnancy-induced (N = 14 studies). The FHR was assessed by cardiotocogram (CTG) (N = 17 studies (visual interpretation); 1 study (computerized CTG), or umbilical artery velocimetry (N = 4). Four studies examined neonatal heart rate. In placebo-controlled RCTs (N = 192 women), adverse FHR effects did not differ between groups [9/101 (drugs) vs. 7/91 (placebo); RD 0.02, 95% CI (- 0.06, 0.11); chi2 = 1.02]. In six drug vs. drug RCTs (295 women), adverse FHR effects did not differ between groups [29/144 (methyldopa) vs. 42/151 (other drugs); RR 0.72, 95% CI (0.49, 1.07); chi2 = 0.69]. In one labetalol vs. placebo trial, neonatal bradycardia did not differ between groups [4/70 (labetalol) vs. 4/74 (placebo); OR 1.06, 95% CI (0.26, 4.39)], while in three drug vs. drug RCTs, neonatal bradycardia was not observed (0/24 vs. 0/26). CONCLUSIONS: Available data are inadequate to conclude whether oral methyldopa, labetalol, nifedipine, or hydralazine adversely affect fetal or neonatal heart rate and pattern. Until definitive data are available, FHR changes cannot be reliably attributed to drug effect, but may be due to progression of the underlying maternal or placental disease.