Botulinum toxin: An effective treatment for prosthesis-related hyperhidrosis in patients with traumatic amputations.

Hyperhidrosis-related to prosthesis use in patients who have suffered a traumatic limb amputation presents itself as a barrier to comfort, prosthesis use and overall quality of life. This review intends to encourage dermatologists to consider the use of botulinum toxin A or B for the treatment of hyperhidrosis in the residual limb and may serve as a stimulus for a modern, in-depth, and more comprehensive study. A review of the literature was conducted using the PubMed database, focusing on hyperhidrosis treatment after traumatic limb amputation. Articles discussing hyperhidrosis treatment for amputations secondary to chronic medical conditions were excluded. Seven case studies published over the last 12 years have demonstrated positive outcomes of this treatment strategy. Overall, there is little data examining this topic and current publications focus primarily on small case series. A larger, double-blind, placebo-controlled study would likely benefit veterans, service members, and civilians.

PET/CT imaging of squamoid eccrine ductal carcinoma.

Squamoid eccrine ductal carcinoma is an extremely uncommon type of eccrine carcinoma (EC). An important distinguishing feature of EC is potential for metastasis. Eccrine carcinoma has been reported to metastasize in up to 50% of cases. Despite tumor aggressivity, no recommendations for staging exist. We present the case of a 91-year-old woman with a lesion involving the left index finger confirmed to be squamoid eccrine ductal carcinoma by dermatopathologic evaluation. 18F-FDG PET/CT images revealed widespread multifocal FDG-avid metastatic disease. Although rare, staging of EC with 18F-FDG PET/CT imaging of the entire body is indicated.

Verruca plana as a complication of CO2 laser treatment: a case report.

Carbon dioxide (CO2) laser treatment is a common therapeutic modality for many dermatologic conditions. It uses a high energy, infrared beam of light, which selectively targets water-containing tissue resulting in controlled ablative resurfacing. This modality, however, can manifest significant cosmetic side effects. Here we report a case of verruca plana manifesting as a response to CO2 laser treatment. A 74-year-old female with recent Mohs surgery for a basal cell carcinoma, presented for full-face-fractionated CO2 treatment to address her surgical scars in addition to treating her mild diffuse actinic damage. Six weeks post treatment, the patient developed erythematous thin plaques over the areas that had been treated. Histology was consistent with verruca plana. Lesions showed mild improvement with topical tretinoin. Verruca plana are benign and typically self-limited; however, they can present a significant cosmetic burden to patients and are an important complication to consider when performing elective cosmetic procedures.

Cutaneous squamous cell carcinoma with perineural invasion: a case report and review of the literature.

Perineural invasion (PNI) is an uncommon manifestation of cutaneous squamous cell carcinoma (SCC). We report a case of recurrent cutaneous SCC with PNI diagnosed both clinically and histologically. We also provide a review the literature. Clinicians should be aware of this uncommon finding, as PNI has been associated with increased local recurrence, local and distant metastasis, and poor prognosis. Patients with clinical findings associated with perineural involvement have a poorer prognosis than those incidentally discovered on histologic examination, which emphasizes the importance of a thorough history and neurologic examination in patients with cutaneous SCC to identify those who will require more aggressive therapy.

Management considerations for giant congenital melanocytic nevi in adults.

Giant congenital melanocytic nevi (GCMN) are a rare type of melanocytic nevus that covers a large body surface, often with satellite nevi scattered on the rest of the skin. There are several complications associated with GCMN, including malignant melanoma and neurocutaneous melanosis. The management of GCMN is very complex because of the cosmetic appearance and the associated psychological distress, the risk of severe complications, and the need for long-term follow-up. We report a case of a 43-year-old active-duty female with a GCMN reporting new and symptomatic satellite lesions with atypical features on dermoscopy.

Genome-wide Profiling of RNA splicing in prostate tumor from RNA-seq data using virtual microarrays.

BACKGROUND: Second generation RNA sequencing technology (RNA-seq) offers the potential to interrogate genome-wide differential RNA splicing in cancer. However, since short RNA reads spanning spliced junctions cannot be mapped contiguously onto to the chromosomes, there is a need for methods to profile splicing from RNA-seq data. Before the invent of RNA-seq technologies, microarrays containing probe sequences representing exon-exon junctions of known genes have been used to hybridize cellular RNAs for measuring context-specific differential splicing. Here, we extend this approach to detect tumor-specific splicing in prostate cancer from a RNA-seq dataset. METHOD: A database, SPEventH, representing probe sequences of under a million non-redundant splice events in human is created with exon-exon junctions of optimized length for use as virtual microarray. SPEventH is used to map tens of millions of reads from matched tumor-normal samples from ten individuals with prostate cancer. Differential counts of reads mapped to each event from tumor and matched normal is used to identify statistically significant tumor-specific splice events in prostate. RESULTS: We find sixty-one (61) splice events that are differentially expressed with a p-value of less than 0.0001 and a fold change of greater than 1.5 in prostate tumor compared to the respective matched normal samples. Interestingly, the only evidence, EST (BF372485), in the public database for one of the tumor-specific splice event joining one of the intron in KLK3 gene to an intron in KLK2, is also derived from prostate tumor-tissue. Also, the 765 events with a p-value of less than 0.001 is shown to cluster all twenty samples in a context-specific fashion with few exceptions stemming from low coverage of samples. CONCLUSIONS: We demonstrate that virtual microarray experiments using a non-redundant database of splice events in human is both efficient and sensitive way to profile genome-wide splicing in biological samples and to detect tumor-specific splicing signatures in datasets from RNA-seq technologies. The signature from the large number of splice events that could cluster tumor and matched-normal samples into two tight separate clusters, suggests that differential splicing is yet another RNA phenotype, alongside gene expression and SNPs, that can be exploited for tumor stratification.

Characterization of alternative spliceoforms and the RNA splicing machinery in pancreatic cancer.

OBJECTIVES AND METHODS: Alternative splicing provides proteomic diversity that can have profound effects. The extent, pattern, and roles of alternative splicing in pancreatic cancer have not been systematically investigated. We have utilized a spliceoform-specific microarray and polymerase chain reaction to evaluate all known splice variants in human pancreatic cancer cell lines representing a spectrum of differentiation, from near-normal HPDE6 to Capan-1 and poorly differentiated MiaPaCa2 cells. Validation of altered spliceoforms was verified in primary cancer specimens and normal pancreatic ductal cells. In addition, expression of 92 spliceosomal genes was examined to better understand the mechanism for observed differences in mRNA splicing. RESULTS: A statistically significant reduction in alternative splicing was found in the pancreatic cancer cell lines compared with HPDE6 cells. Many splice variants identified in Capan-1 and MiaPaCa2 cells were observed in grades 3 and 4 tumors. Analysis of genes encoding spliceosomal proteins revealed that 28 of 92 genes had significantly decreased expression in cancer compared with normal pancreas. CONCLUSIONS: Pancreatic cancer has reduced alternative splicing diversity compared with normal pancreas. This is demonstrated in both cell lines and primary tumors, with the loss in splicing diversity correlated with relative reduction in expression of spliceosomal genes.

The ABCs of human alternative splicing: a review of ATP-binding cassette transporter splicing.

Human ATP-binding cassette (ABC) transporters are proteins that translocate solutes across cellular membranes. They are highly expressed in tissues that represent significant barriers of pharmacologic and toxicologic significance, such as the gastrointestinal tract, liver, kidney and brain, and therefore play a pivotal role in the absorption, distribution and excretion of xenobiotics and in host detoxification processes. This review explores the extent of alternative splicing of ABC transporters, based on studies of individual genes, genetic variation and sequence databases. Large-scale informatics studies have found multiple coding and non-coding splice isoforms for each transporter. While the importance of splicing in individual variation of drug response is not fully known, recent studies demonstrate that genetic mutations often induce alternative splicing of ABC transporters which may make certain individuals more susceptible to altered pharmacological and toxicological responses. Newer technologies such as exon/junction microarrays, multiplexed PCR assays and next generation sequencing may further clarify the relevance of ABC transporter splicing in drug development and disease management.

Extent and diversity of human alternative splicing established by complementary database annotation and microarray analysis.

Alternative splicing generates functional diversity in higher organisms through alternative first and last exons, skipped and included exons, intron retentions and alternative donor, and acceptor sites. In large-scale microarray studies in humans and the mouse, emphasis so far has been placed on exon-skip events, leaving the prevalence and importance of other splice types largely unexplored. Using a new human splice variant database and a genome-wide microarray to probes thousands of splice events of each type, we measured differential expression of splice types across six pair of diverse cell lines and validated the database annotation process. Results suggest that splicing in humans is more complex than simple exon-skip events, which account for a minority of splicing differences. The relative frequency of differential expression of the splice types correlates with what is found by our annotation efforts. In conclusion, alternative splicing in human cells is considerably more complex than the canonical example of the exon skip. The complementary approaches of genome-wide annotation of alternative splicing in human and design of genome-wide splicing microarrays to measure differential splicing in biological samples provide a powerful high-throughput tool to study the role of alternative splicing in human biology.

Cases from the aerospace medicine residents' teaching file. Penetrating chest trauma from a home accident: rapid response saves a pilot.

Penetrating cardiac chest trauma can be associated with a high degree of mortality. Prognostic factors that favor a high survival rate include OR thoracotomy vs. ER thoracotomy, prompt resuscitation, fast transport, urgent diagnostic study, and immediate surgery. Cardiac tamponade, in some cases, may lessen the amount of hemorrhage. Reported is a case of penetrating cardiac trauma in an aviator. With a high degree of suspicion and rapid transport, early intervention was possible resulting in a favorable outcome. The patient, a United State Marine Corps Harrier pilot, returned to flight status with a waiver.