Citations

AbstractPrurigo pigmentosa (PP) is a rare inflammatory dermatosis of unknown cause characterized by a predominantly truncal eruption of pruritic erythematous papules in a reticular pattern, resolving with hyperpigmentation. PP is twice as common in girls and women, and the mean age at onset is 25 years. Diagnosis of PP is challenging and is aided by characteristic histopathologic findings. We report a case of PP in a 17‐year‐old white boy. The eruption arose during strict adherence to a ketogenic diet.

AbstractIntrathecal drug delivery systems (IDDSs) are used to treat resistant pain states as well as intractable spasticity via medication delivery into the spinal fluid. Risks associated with implantation of these devices include infection, bleeding, intrathecal granuloma formation, and neurologic sequelae similar to other neuraxial procedures. Intrathecal catheter placement creates the additional risk of persistent spinal fluid leak, which can lead to postdural puncture headaches as well as seroma formation and may require subsequent surgical exploration or explantation. This retrospective case series examines 3 patients at a single institution with persistent spinal fluid leak after IDDS placement (and explantation in one case) resulting in headache and/or seroma formation that were treated with epidural fibrin glue.Three patients underwent IDDS implantation with baclofen for spasticity. In 1 patient, a cerebral spinal fluid leak developed at 1‐week postoperatively. After several unsuccessful epidural blood patches and surgical exploration with a catheter revision, she was ultimately treated successfully with a fibrin glue patch. The second patient received an IDDS and did well until a seroma developed 1 year later. He was likewise treated with an epidural fibrin glue patch after 2 failed blood patches. In a third patient, a spinal fluid leak developed after explantation of an IDDS and was treated with an epidural fibrin glue patch as initial therapy.

Abstract Ovarian cancer is a clinically and molecularly heterogeneous disease. The driving forces behind this variability are unknown. Here, we report wide variation in the expression of the DNA cytosine deaminase APOBEC3B, with elevated expression in the majority of ovarian cancer cell lines (three SDs above the mean of normal ovarian surface epithelial cells) and high-grade primary ovarian cancers. APOBEC3B is active in the nucleus of several ovarian cancer cell lines and elicits a biochemical preference for deamination of cytosines in 5′-TC dinucleotides. Importantly, examination of whole-genome sequence from 16 ovarian cancers reveals that APOBEC3B expression correlates with total mutation load as well as elevated levels of transversion mutations. In particular, high APOBEC3B expression correlates with C-to-A and C-to-G transversion mutations within 5′-TC dinucleotide motifs in early-stage high-grade serous ovarian cancer genomes, suggesting that APOBEC3B-catalyzed genomic uracil lesions are further processed by downstream DNA "repair" enzymes including error-prone translesion polymerases. These data identify a potential role for APOBEC3B in serous ovarian cancer genomic instability. Cancer Res; 73(24); 7222–31. ©2013 AACR.

Study ObjectiveTo assess the relationship of the 33 single nucleotide polymorphisms (SNPs) previously associated with fasting glucose in Caucasians in genome‐wide association studies (GWAS) with glucose response to antihypertensive drugs shown to increase risk for hyperglycemia and diabetes.DesignRandomized, multicenter clinical trial.PatientsA total of 456 Caucasian men and women with uncomplicated hypertension.Measurements and Main ResultsThe Pharmacogenomic Evaluation of Antihypertensives Responses study evaluated blood pressure and glucose response in uncomplicated hypertensive patients randomized to either atenolol or hydrochlorothiazide (HCTZ) monotherapy, followed by combination therapy with both agents. Association of these SNPs with atenolol‐ or HCTZ‐induced glucose response was evaluated in 456 Caucasian patients using linear regression adjusting for age, sex, body mass index, baseline glucose, baseline insulin, and principal component for ancestry.The SNP rs340874 in the 5′ region of PROX1 gene was significantly associated with atenolol‐induced glucose change (p=0.0013). Participants harboring the C allele of this SNP had greater glucose elevation after approximately 9 weeks of atenolol monotherapy (β = +2.39 mg/dl per C allele), consistent with the direction of effect in fasting glucose GWAS, that showed the C allele is associated with higher fasting glucose.ConclusionThese data suggest that PROX1 SNP rs340874, discovered in fasting glucose GWAS, may also be a pharmacogenetic risk factor for antihypertensive‐induced hyperglycemia. β‐blockers and thiazides may interact with genetic risk factors to increase risk for dysglycemia and diabetes.

Shotgun proteomics technology has matured in the research laboratories and is poised to enter clinical laboratories. However, the road to this transition is sprinkled with major technical unknowns such as long‐term stability of the platform, reproducibility of the technology and clinical utility over traditional antibody‐based platforms. Further, regulatory bodies that oversee the clinical laboratory operations are unfamiliar with this new technology. As a result, diagnostic laboratories have avoided using shotgun proteomics for routine diagnostics. In this perspectives article, we describe the clinical implementation of a shotgun proteomics assay for amyloid subtyping, with a special emphasis on standardizing the platform for better quality control and earning clinical acceptance. This assay is the first shotgun proteomics assay to receive regulatory approval for patient diagnosis. The blueprint of this assay can be utilized to develop novel proteomics assays for detecting numerous other disease pathologies. Copyright © 2013 John Wiley & Sons, Ltd.

AbstractBackgroundBortezomib, a proteasome inhibitor used to treat multiple myeloma, has been administered (± plasma exchange ± intravenous immunoglobulin [IVIg]) in attempts to reduce antibodies against human leukocyte antigens (HLA) in sensitized patients undergoing organ transplantation. To our knowledge, bortezomib has not been investigated for its effect on natural anti‐pig antibodies. If bortezomib could reduce the production of anti‐pig antibodies, this would likely be beneficial to the outcome of pig organ grafts in primates.MethodsNine patients received bortezomib either to reduce anti‐HLA antibody levels before organ allotransplantation or to treat antibody‐mediated rejection. Patients at the Mayo Clinic (Group 1; n = 4) received bortezomib alone, whereas at the UPMC (Group 2; n = 5), this was combined with plasmaphereses ± IVIg in some cases. Anti‐pig IgM and IgG levels against wild‐type (WT) and α1,3‐galactosyltransferase gene knockout (GTKO) pig aortic endothelial cells (flow cytometry—relative mean fluorescence intensity) and anti‐Gal IgM and IgG (ELISA–OD480 nm) were measured pre‐ and post‐bortezomib therapy.ResultsMean anti‐pig IgM levels were 11.2 (WT) and 1.9 (GTKO) pre‐bortezomib treatment and 9.4 (WT: P = 0.02) and 1.7 (GTKO: P = 0.33) post‐bortezomib treatment, respectively. Mean anti‐pig IgG levels were 4.3 (WT) and 1.5 (GTKO) pre‐bortezomib treatment and 3.6 (WT: P = 0.21) and 1.4 (GTKO: P = 0.20) post‐bortezomib treatment, respectively. Mean anti‐Gal IgM and IgG levels were 0.7 and 1.1, respectively, pre‐treatment, and 0.6 (P = 0.03) and 1.1 (NS), respectively, post‐treatment. When the data were analyzed in Groups 1 and 2 separately, there were no significant differences between the pre‐ and post‐bortezomib levels of anti‐pig, anti‐non‐Gal, or anti‐Gal IgM or IgG.ConclusionsFrom this limited study, we conclude that bortezomib might reduce anti‐Gal IgM levels in primates, but, in this respect alone, is unlikely to have any significant effect on the outcome of GTKO pig organ transplantation.

ObjectivesTo 1) describe and validate an ultrasound‐guided ischial bursa injection technique in an unembalmed cadaveric model and 2) to compare the distance between the ischial tuberosity and the sciatic nerve in a hip neutral versus 90° flexed hip position in asymptomatic volunteers.DesignThe first part was a single‐blind prospective study. The second part was a prospective cohort study.SettingAn academic institution procedural skills laboratory and outpatient clinic.ParticipantsThe first part of the study involved 1 cadaveric specimen. The second part of the study involved 20 asymptomatic subjects. The mean age of the subjects was 28 years, and the mean (standard deviation) body mass index was 23.2 ± 2.8 kg/m2 (minimum, 18.3 kg/m2; maximum, 29.5 kg/m2).MethodsIn the first part of the study, a single operator completed bilateral ultrasound‐guided ischial bursa injections in an unembalmed cadaveric specimen by using diluted colored latex. In the second part of the study, ultrasound was used in 20 asymptomatic volunteer subjects (10 men and 10 women) to measure the distance from the lateral edge of the ischial tuberosity to the sciatic nerve.Main Outcome MeasurementsThe injections were graded for accuracy as follows: accurate (all injectate contained within the ischial bursa), accurate with overflow (injectate within the ischial bursa but also located in adjacent structures other than the needle track), or inaccurate (injectate not within the ischial bursa). The second part of the study measured the distance from the ischial tuberosity to the sciatic nerve with subjects in 2 different positions (prone and side lying with the tested hip flexed to 90°).ResultsPostinjection cadaveric dissections revealed that both ultrasound‐guided injections accurately placed liquid latex within the ischial bursae. There was no evidence of injury to surrounding neurovascular structures. Among asymptomatic volunteers, the average distance between the ischial tuberosity and the sciatic nerve increased from 28.4 mm (range, 20.5‐38.9 mm) in the neutral position to 41.9 mm (range, 30.9‐66.0 mm) with the hip flexed to 90° (average change, 13.5 mm away from the ischial tuberosity; P = .0001).ConclusionsUltrasound‐guided ischial bursa injections are technically feasible. Flexing the hip to 90° increases the distance between the ischial tuberosity and the sciatic nerve in asymptomatic volunteers, thus potentially resulting in a safer needle trajectory when ischial bursa injections are clinically indicated. Further investigation in clinical settings is warranted to validate these findings.

Introduction. Accessory breast tissue is a rare finding in the general population with an incidence of 1-2%. An even rarer occurrence is accessory breast tissue afflicted with breast carcinoma. We present a brief report discussing diagnosis and management of a patient who presented with primary breast adenocarcinoma in vulval supranumerary tissue.Brief Report. A 60-year-old Caucasian female presented with a lesion in her left vulva that she first identified during adolescence. The lesion began to grow and ulcerate prompting her to receive treatment. Biopsy was inconclusive, and metastatic workup was negative, so her lesion was treated as an isolated breast lump and removed via wide local excision.Conclusion. Primary breast adenocarcinoma of the vulva is exceedingly rare. A paucity of the literature on this topic unfortunately means that strong evidence does not exist detailing the best management of this patient cohort. However, given that histological data confirms these cancers are virtually the same as breast cancers, it logically follows that the best treatment practices for breast cancer may be applied to treat these patients presenting with primary vulva cancers of ectopic breast tissue.