Citations

Childhood sexual abuse (CSA) is common and is associated with both mental and physical health problems in adulthood. Using data from an age- and sex-stratified population survey of 600 Olmsted County, Minnesota, residents, a Sexual Abuse Severity Score was developed. The abuse characteristics of 156 CSA respondents were associated with self-reported trauma, somatization, and alcohol use. Characteristics included age of first sexual abuse, more than one perpetrator, degree of coercion, severity of abuse (i.e., attempted intercourse is more severe than fondling), and the number of occurrences. This is one of the few reports to develop a risk summary that quantifies the severity of CSA.

AbstractThe assessment of the influence of many rare BRCA2 missense mutations on cancer risk has proved difficult. A multifactorial likelihood model that predicts the odds of cancer causality for missense variants is effective, but is limited by the availability of family data. As an alternative, we developed functional assays that measure the influence of missense mutations on the ability of BRCA2 to repair DNA damage by homologous recombination and to control centriole amplification. We evaluated 22 missense mutations from the BRCA2 DNA binding domain (DBD) that were identified in multiple breast cancer families using these assays and compared the results with those from the likelihood model. Thirteen variants inactivated BRCA2 function in at least one assay; two others truncated BRCA2 by aberrant splicing; and seven had no effect on BRCA2 function. Of 10 variants with odds in favor of causality in the likelihood model of 50:1 or more and a posterior probability of pathogenicity of 0.99, eight inactivated BRCA2 function and the other two caused splicing defects. Four variants and four controls displaying odds in favor of neutrality of 50:1 and posterior probabilities of pathogenicity of at least 1 × 10−3 had no effect on function in either assay. The strong correlation between the functional assays and likelihood model data suggests that these functional assays are an excellent method for identifying inactivating missense mutations in the BRCA2 DBD and that the assays may be a useful addition to models that predict the likelihood of cancer in carriers of missense mutations. [Cancer Res 2008;68(9):3523–31]

OBJECTIVES. Mumps outbreaks continue to occur throughout the world, including in highly vaccinated populations. Vaccination against mumps has been successful; however, humoral and cellular immune responses to mumps vaccines vary significantly from person to person. We set out to assess whether HLA and cytokine gene polymorphisms are associated with variations in the immune response to mumps viral vaccine.METHODS. To identify genetic factors that might contribute to variations in mumps vaccine–induced immune responses, we performed HLA genotyping in a group of 346 healthy schoolchildren (12–18 years of age) who previously received 2 doses of live mumps vaccine. Single-nucleotide polymorphisms (minor allele frequency of >5%) in cytokine and cytokine receptor genes were genotyped for a subset of 118 children.RESULTS. Median values for mumps-specific antibody titers and lymphoproliferative stimulation indices were 729 IU/mL and 4.8, respectively. Girls demonstrated significantly higher mumps antibody titers than boys, indicating gender-linked genetic differences in humoral immune response. Significant associations were found between the HLA-DQB1*0303 alleles and lower mumps-specific antibody titers. An interesting finding was the association of several HLA class II alleles with mumps-specific lymphoproliferation. Alleles of the DRB1 (*0101, *0301, *0801, *1001, *1201, and *1302), DQA1 (*0101, *0105, *0401, and *0501), and DQB1 (*0201, *0402, and *0501) loci were associated with significant variations in lymphoproliferative immune responses to mumps vaccine. Additional associations were observed with single-nucleotide polymorphisms in the interleukin-10RA, interleukin-12RB1, and interleukin-12RB2 cytokine receptor genes. Minor alleles for 4 single-nucleotide polymorphisms within interleukin-10RA and interleukin-12RB genes were associated with variations in humoral and cellular immune responses to mumps vaccination.CONCLUSIONS. These data suggest the important role of HLA and immunoregulatory cytokine receptor gene polymorphisms in explaining variations in mumps vaccine–induced immune responses.

Background— Multiple factors create discrepancies between electroanatomic maps and merged, preacquired computed tomographic images used in guiding atrial fibrillation ablation. Therefore, a Carto-based 3D ultrasound image system (Biosense Webster Inc) was validated in an animal model and tested in 15 atrial fibrillation patients. Methods and Results— Twelve dogs underwent evaluation using a newly developed Carto-based 3D ultrasound system. After fiducial clip markers were percutaneously implanted at critical locations in each cardiac chamber, 3D ultrasound geometries, derived from a family of 2D intracardiac echocardiographic images, were constructed. Point-source error of 3D ultrasound-derived geometries, assessed by actual real-time 2D intracardiac echocardiographic clip sites, was 2.1�1.1 mm for atrial and 2.4�1.2 mm for ventricular sites. These errors were significantly less than the variance on CartoMerge computed tomographic images (atria: 3.3�1.6 mm; ventricles: 4.8�2.0 mm; P< 0.001 for both). Target ablation at each clip, guided only by 3D ultrasound-derived geometry, resulted in lesions within 1.1�1.1 mm of the actual clips. Pulmonary vein ablation guided by 3D ultrasound-derived geometry resulted in circumferential ablative lesions. Mapping in 15 patients produced modestly smaller 3D ultrasound versus electroanatomic map left atrial volumes (98�24 cm 3 versus 109�25 cm 3 , P< 0.05). Three-dimensional ultrasound-guided pulmonary vein isolation and linear ablation in these patients were successfully performed with confirmation of pulmonary vein entrance/exit block. Conclusions— These data demonstrate that 3D ultrasound images seamlessly yield anatomically accurate chamber geometries. Image volumes from the ultrasound system are more accurate than possible with CartoMerge computed tomographic imaging. This clinical study also demonstrates the initial feasibility of this guidance system for ablation in patients with atrial fibrillation.

✓The aim of this study is to evaluate the presentation of unusual dementias in 4 patients and correlate these presentations with the histopathological findings after brain biopsy sampling to define a diagnostic entity. The authors detail the cases of 4 patients (2 women, 46 and 56 years of age; and 2 men, 67 and 74 years of age) who presented with acute and subsequently subacute encephalopathies. Their bizarre presenting symptom complexes and the results of neurological examinations, radiographic studies, electroencephalography (EEG) recordings, and serological marker tests are reviewed. The diagnostic surgical procedures and successful treatments in these patients are discussed. All 4 patients underwent craniotomy and excisional brain biopsy sampling as part of a comprehensive evaluation. Histopathological confirmation of nonvasculitic autoimmune inflammatory meningoencephalitis (NAIM) by a neuropathologist was present in all 4 patients. All patients were successfully treated with a course of corticosteroid medication. Nonvasculitic autoimmune inflammatory meningoencephalitis is a potentially treatable form of dementia whose salient features include a younger average age at onset, rapid progression with significant cognitive and behavioral features, absence of family history, abnormal EEG findings, and elevated levels of inflammatory markers. Although it is an invasive procedure, brain biopsy sampling is safe and can offer histological confirmation of this condition. This procedure is important because NAIM can be treated successfully if it is distinguished from the nontreatable dementias that mimic it.

Object Patients with trigeminal neuralgia (TN) and persistent or recurrent facial pain after microvascular decompression (MVD) typically undergo less invasive procedures in the hope of providing pain relief. The outcomes and risks of repeat posterior fossa exploration (PFE) for these patients are not clearly understood. Methods From September 2000 to November 2006, 29 patients (14 men, 15 women) underwent repeat PFE. The mean number of surgeries per patient at the time of repeat PFE was 3.2 (range 1–6). The mean follow-up duration after surgery was 33.7 months. Results Compression of the trigeminal nerve was noted in 24 patients (83%) by an artery (13 patients, 45%), vein (4 patients, 14%), or Teflon (7 patients, 24%). Four patients (14%) who underwent operations elsewhere had incorrect cranial nerves decompressed at their first surgery. Only MVD was performed in 18 patients (62%) and a partial nerve section (PNS) was performed in 11 patients (38%). An excellent facial pain outcome (no pain, no medications required) was achieved and maintained for 80% and 75% of patients at 1 and 3 years after surgery, respectively. Patients with Burchiel Type 1 TN were pain free without medications (91% at 1 year and 85% at 3 years) more frequently than patients with Burchiel Type 2 TN (27% at both 1 and 3 years; hazard ratio = 5.4, 95% confidence interval 1.4–21.1, p = 0.02). Fifteen patients (52%) had new or increased facial numbness. Two patients (7%) developed anesthesia dolorosa; both had undergone PNS. Two patients (7%) had hearing loss after surgery. Conclusions Repeat PFE for patients with idiopathic TN has facial pain outcomes that are comparable with both percutaneous needle-based techniques and stereotactic radiosurgery. Patients with persistent or recurrent TN should be considered for repeat PFE, especially if other less invasive surgeries have not relieved their facial pain.

Abstract There is a great need for a screening test that results in the detection of asymptomatic lung cancer, at a time when there is a substantially better chance for curative treatment. Based on the significant limitations in the results reported to date from nonrandomized, observational screening trials, the authors do not recommend computed tomography screening for lung cancer at this time. Results of two major randomized controlled trials will soon be available.

The aim of this study was to define the outcome and complications following open reduction and internal fixed-angle plating of distal radius fractures for patients on chronic immunosuppression medications. A retrospective study identified 11 patients with distal radius fractures that had been on chronic immunosuppressive medication. The mean patient age was 59.9 years (40–82 years). According to the Orthopedic Trauma Association classification, there was one 23A3, one 23B3, and nine 23C type fractures. There were two open fractures. All patients received preoperative antibiotics and underwent reduction and fixation with a volar, fixed-angle plate. Postoperative measurements included postoperative and final radiographic indices, wrist flexion and extension, forearm rotation, and grip strength. Clinical follow-up averaged 13 months, and radiographic follow-up averaged 14.9 months. Statistical analysis was performed comparing means of various parameters with a two-sided t test with an alpha value ≤0.05. All fractures healed, and there were no infections. The final mean ulnar variance, volar tilt, and radial inclination were –0.1 mm (ulnar negative; –2.0 to +2.5 mm), 13° (5–23°), and 21° (15–27°), respectively. The mean articular gap or step was 0.4 mm. There was a small but significant decrease between the final and postoperative mean ulnar variance ( p=0.03). Mean wrist flexion was 47°, extension 47°, pronation 77°, and supination was 76°. Grip strength averaged 16.3 kg versus 25.1 kg for the opposite extremity. The one major complication included a postoperative carpal tunnel syndrome. Fixed-angle volar plate fixation for distal radius fractures in patients with chronic immunosuppression was associated with union (with acceptable radiographic alignment), no wound-healing problems or infections, and with functional wrist and forearm motion and grip strength.