Diagnostic criteria for testing for BRCA1 and BRCA2: the experience of the Department of Defense Familial Breast/Ovarian Cancer Research Project

The Department of Defense Familial Breast/Ovarian Cancer Research Project has offered genetic counseling and testing for BRCA1 and BRCA2 on a research basis to patients meeting specific diagnostic criteria, with risk for BRCA1 and BRCA2 mutations calculated based on the Couch model. In 2.5 years, 250 patients were evaluated and 101 patients met criteria requirements, including 33 who met criteria in more than one category. Ninety patients elected to undergo DNA testing. In this group of 90 patients, 14 mutations (15.5%) and 16 unclassified variants (17.7%) were identified. The most common inclusion criteria were onset of breast/ovarian cancer before age 45 years (n = 32) and onset of breast/ovarian cancer before age 45 years with strong family history (n = 21). However, when number of mutations and unclassified variants found were compared separately across all diagnostic criteria (including those of more than one capacity) using the chi 2 statistic, no significant differences were seen among the categories to suggest that one criterion was more predictive of mutations or variants than another. Couch risk values for patients with mutations showed a mean of 14% and ranged from 3.2 to 43.5% (range for all patients, 1.2-69.7%). These findings emphasize the importance of using multiple diagnostic criteria and suggest that a Couch risk value of > 3% may be useful in selecting patients for testing. The data also underscore the necessity of genetic counseling in the testing process, particularly given the large number of unclassified variants diagnosed and their uncertain status for disease predisposition.     

Nausea and vomiting after outpatient ACL reconstruction with regional anesthesia: are lumbar plexus blocks a risk factor?

STUDY OBJECTIVE: To track the incidence of in-hospital postoperative nausea and vomiting (PONV) requiring postoperative parenteral nursing interventions after outpatient reconstruction of the anterior cruciate ligament (ACL) with one of two types of regional anesthesia to determine the extent to which various anesthetic techniques, preemptive antiemetics, and other factors were associated with the lowest probability of PONV. DESIGN: Retrospective chart (database) review of all ACL procedures at the University of Pittsburgh Medical Center from August 1997 through June 1999. SETTING: University medical center. MEASUREMENTS: We reviewed our institutional database of 347 consecutive patients undergoing ACL reconstruction with either spinal with femoral nerve block (SPI-FNB) or lumbar plexus and sciatic nerve block (LUM-SCI). Recorded variables and outcomes included gender, history of PONV, intravenous (i.v.) fentanyl before and during surgery, preemptive antiemetics given, and parenteral nursing interventions for PONV performed. Chi-square tests and logistic regression were used to determine factors associated with PONV. MAIN RESULTS: For SPI-FNB, PONV incidence was 13% (26/208), but it was higher for LUM-SCI [25%, 34/139, p = 0.002; odds ratio (OR) = 2.2]. Regression modeling demonstrated that women (OR = 2.8, p = 0.003) and LUM-SCI patients (OR = 3.0, p = 0.005) were at greater risk for PONV. The combination of dexamethasone (4 to 10 mg i.v.) and perphenazine (1.2 to 2.0 mg i.v.) was associated with less PONV (OR = 0.3, p = 0.005). Type of local anesthetic used for lumbar plexus block was not associated with PONV incidence. CONCLUSIONS: For ACL reconstruction with regional anesthesia, use of LUM-SCI was associated with a higher rate of PONV, whereas combination antiemetic prophylaxis with perphenazine and dexamethasone was associated with less PONV.     

Analysis of screw pullout strength: A function of screw orientation in subtalar joint arthrodesis

The purpose of this cadaveric study was to compare the pullout strength and failure load of 2 different screw orientations for subtalar arthrodesis. Twenty-six specimens from 13 cadaver donors (1 left and 1 right each) were used. A 7.3- x 65-mm long-thread profile (32-mm length) cannulated screw inserted into the calcaneus from dorsal to plantar (calcaneal specimens) was compared with a 7.3- x 65-mm short-thread profile (16-mm length) cannulated screw inserted into the talus from plantar to dorsal (talar specimens). A torque screwdriver with a calibrated electronic vernier scale measured the torque of screw insertion. Screw pullout strength and load failure were measured by using a servohydraulic materials testing machine. Distraction was applied along the axis of the screw at a displacement rate of 25 mm/min. The peak torque of insertion in all calcaneal specimens was reached on initial insertion through the dorsal subchondral bone plate of the calcaneus; in talar specimens, it was reached as the screw threads were completely buried into the talus. A significant difference (P = .00647) was found between the mean torque of insertion for the calcaneal (1.50 Nm) and talar specimens (1.30 Nm). A comparison of pullout forces showed a significantly stronger mean failure load for calcaneal specimens (P = .000085). The mean failure load for paired calcaneal specimens was 1782 N compared with a mean 1245 N for talar specimens. Although the pullout force was clearly greater in the dorsal-to-plantar screw application, the pullout force in the plantar-to-dorsal orientation was also considerable.     

Local visual perception bias in children with high-functioning autism spectrum disorders; do we have the whole picture?

Objective: While local bias in visual processing in children with autism spectrum disorders (ASD) has been reported to result in difficulties in recognizing faces and facially expressed emotions, but superior ability in disembedding figures, associations between these abilities within a group of children with and without ASD have not been explored. Methods: Possible associations in performance on the Visual Perception Skills Figure–Ground test, a face recognition test and an emotion recognition test were investigated within 25 8–12-years-old children with high-functioning autism/Asperger syndrome, and in comparison to 33 typically developing children. Results: Analyses indicated a weak positive correlation between accuracy in Figure–Ground recognition and emotion recognition. No other correlation estimates were significant. Conclusion: These findings challenge both the enhanced perceptual function hypothesis and the weak central coherence hypothesis, and accentuate the importance of further scrutinizing the existance and nature of local visual bias in ASD.     

Treatment of delayed and nonunited fractures and osteotomies with pulsed electromagnetic field in children and adolescents

Nonunion of fractures or osteotomies in the pediatric population is rare. The gold standard for the treatment of nonunions involves harvesting autologous iliac crest bone graft and sometimes internal fixation, which are invasive procedures. The purpose of this study was to evaluate the effectiveness of pulsed electromagnetic field on a non-united fracture or osteotomy in the pediatric population. A retrospective study was performed on all patients at the authors' institution who used pulsed electromagnetic field as part of their treatment for nonunion or delayed union. Success of the initial nonunion treatment was defined as complete union of the fracture or osteotomy site. Two types of treatment were administered once delayed bone healing was identified: pulsed electromagnetic field alone or pulsed electromagnetic field plus an adjunct treatment. Twenty-one patients were included; 8 osteotomies and 14 fractures developed a nonunion. Average patient age was 11.7 years. Average age for patients who healed with the initial treatment was 10.7 years, whereas nonhealers had an average age of 14 years. Eighty-nine percent of osteotomy nonunions healed with their first management. Fifty-seven percent of fracture nonunions healed at the first attempt. The use of pulsed electromagnetic field is a good option for the initial treatment of pediatric nonunions, especially for patients who develop nonunions secondary to osteotomies. Adding bone marrow aspiration improves the outcomes and is minimally invasive compared with autologous iliac crest bone graft, with no complications.     

Outcomes of bariatric surgery in patients with body mass index <35 kg/m2

BackgroundPatients who are categorized with class I obesity have a body mass index (BMI) of 30–34.99 kg/m². This population of patients has a predisposition to diabetes, hypertension, and dyslipidemia. The aim of the present study was to investigate the improvements of these co-morbidities in a class I obese population that had undergone a bariatric procedure.MethodsAfter internal review board approval and with adherence to the Health Insurance Portability and Accountability Act guidelines, a retrospective review was performed of a prospectively maintained database of 42 class I obese patients who underwent a bariatric procedure at our institution during a 10-year period, from February 2000 to May 2010. The fasting glucose level, glycosylated hemoglobin level, lipid profile, initial weight, and BMI were measured in the preoperative and postoperative periods.ResultsOur patient population consisted of 30 women and 12 men, with a preoperative mean BMI of 33.9 kg/m². Laparoscopic sleeve gastrectomy was performed in 24 patients (57%), laparoscopic Roux-en-Y gastric bypass in 8 (19%), and laparoscopic adjustable gastric banding in 10 (24%). Of these 42 patients, 25 (60%) had type 2 diabetes, 1 patient was glucose intolerant, 27 (64%) had arterial hypertension, 25 (60%) had dyslipidemia, 17 (40%) had sleep apnea, and 8 (19%) had osteoarthritis. The postoperative findings included a mean BMI of 26.5 kg/m² and a mean weight loss of 41.4 lb. Of the 25 diabetic patients, 5 (20%) gained remission and 12 (48%) improvement of their diabetic status. The single patient with glucose intolerance showed improvement. Of the 27 patients with arterial hypertension, 9 (33%) showed remission and 13 (52%) improvement. Dyslipidemia resolved in 5 patients (20%) and improved in 13 (52%). Obstructive sleep apnea resolved in 10 (59%) and improvement was seen in 1 patient (6%). Finally, osteoarthritis resolved in 1 patient (12%) and improved in 5 (63%).ConclusionBariatric surgery can significantly improve or resolve co-morbid metabolic conditions in patients with class I obesity.     

Pulmonary function in individuals who underwent liver transplantation: from the US cystic fibrosis foundation registry

Severe liver disease affects 4.5% to 10% of individuals with cystic fibrosis (CF) and is the third-leading cause of death. Liver transplantation (LT) is an accepted therapy, but the effects of liver disease and LT on pulmonary function in patients with CF are controversial. Our aim was to characterize changes in pulmonary function in LT patients with CF. Using mixed effect models, we analyzed pulmonary function before and after transplantation in 168 LT patients and 840 non-LT patients with CF who were matched by age, sex, pancreatic status, infections with US CF Foundation Patient Registry data (1989-2007). The primary outcome was the change in the forced expiratory volume in 1 second (FEV(1); percent predicted) in LT and non-LT in the 3-years periods before or after transplantation; second we compared FEV(1) changes. In the 3 years before transplantation, LT had lower initial FEV(1) values (71.5% ± 1.9%, P < 0.001) and a slower decline (+0.1% ± 0.4%/year, P < 0.001) than non-LT (79.6% ± 1.3% and -1.3% ± 0.2%/year, respectively). There was no difference in the FEV(1) decline after transplantation (-1.4% ± 0.4%/year for LT versus -2.1% ± 0.2%/year for non-LT, P = 0.14). Both the (P = 0.003) and (P = 0.001) had a slower FEV(1) decline in the period before transplantation versus after transplantation. In conclusion, pulmonary function is lower and declines more slowly in patients with CF before LT versus, but parallels the decline in non-LT after transplantation. LT is neither beneficial nor detrimental to pulmonary function in CF but returns FEV(1) decline to the same trajectory found for matched non-LT individuals with CF.     

Epigenetics and developmental programming of adult onset diseases

Maternal perturbations or sub-optimal conditions during development are now recognized as contributing to the onset of many diseases manifesting in adulthood. This “developmental programming” of disease has been explored using animal models allowing insights into the potential mechanisms involved. Impaired renal development, resulting in a low nephron number, has been identified as a common outcome that is likely to contribute to the development of hypertension in the offspring as adults. Changes in other organs and systems, including the heart and the hypothalamic–pituitary–adrenal axis, have also been found. Evidence has recently emerged suggesting that epigenetic changes may occur as a result of developmental programming and result in permanent changes in the expression patterns of particular genes. Such epigenetic modifications may be responsible not only for an increased susceptibility to disease for an individual, but indirectly for the establishment of a disease state in a subsequent generation. Further research in this field, particularly examination as to whether epigenetic changes to genes affecting kidney development do occur, are essential to understanding the underlying mechanisms of developmental programming of disease.