Chromosome 2 (2p16) abnormalities in Carney complex tumours

Carney complex (CNC) is an autosomal dominant multiple endocrine neoplasia and lentiginosis syndrome characterised by spotty skin pigmentation, cardiac, skin, and breast myxomas, and a variety of endocrine and other tumours. The disease is genetically heterogeneous; two loci have been mapped to chromosomes 17q22–24 (the CNC1 locus) and 2p16 (CNC2). Mutations in the PRKAR1A tumour suppressor gene were recently found in CNC1 mapping kindreds, while the CNC2 and perhaps other genes remain unidentified. Analysis of tumour chromosome rearrangements is a useful tool for uncovering genes with a role in tumorigenesis and/or tumour progression. CGH analysis showed a low level 2p amplification recurrently in four of eight CNC tumours; one tumour showed specific amplification of the 2p16-p23 region only. To define more precisely the 2p amplicon in these and other tumours, we completed the genomic mapping of the CNC2 region, and analysed 46 tumour samples from CNC patients with and without PRKAR1A mutations by fluorescence in situ hybridisation (FISH) using bacterial artificial chromosomes (BACs). Consistent cytogenetic changes of the region were detected in 40 (87%) of the samples analysed. Twenty-four samples (60%) showed amplification of the region represented as homogeneously stained regions (HSRs). The size of the amplicon varied from case to case, and frequently from cell to cell in the same tumour. Three tumours (8%) showed both amplification and deletion of the region in their cells. Thirteen tumours (32%) showed deletions only. These molecular cytogenetic changes included the region that is covered by BACs 400-P-14 and 514-O-11 and, in the genetic map, corresponds to an area flanked by polymorphic markers D2S2251 and D2S2292; other BACs on the centromeric and telomeric end of this region were included in varying degrees. We conclude that cytogenetic changes of the 2p16 chromosomal region that harbours the CNC2 locus are frequently observed in tumours from CNC patients, including those with germline, inactivating PRKAR1A mutations. These changes are mostly amplifications of the 2p16 region, that overlap with a previously identified amplicon in sporadic thyroid cancer, and an area often deleted in sporadic adrenal tumours. Both thyroid and adrenal tumours constitute part of CNC indicating that the responsible gene(s) in this area may indeed be involved in both inherited and sporadic endocrine tumour pathogenesis and/or progression.     

Therapeutic LMP1 polyepitope vaccine for EBV-associated Hodgkin disease and nasopharyngeal carcinoma

Development of an epitope-based vaccination strategy designed to enhance Epstein-Barr virus (EBV)-specific CD8(+) cytotoxic T lymphocytes (CTLs) is increasingly being considered as a preferred approach for the treatment of EBV-associated relapsed Hodgkin disease (HD) and nasopharyngeal carcinoma (NPC). EBV-encoded latent membrane proteins, LMP1 and LMP2, are the only target antigens available for therapeutic augmentation of CTL responses in patients with HD and NPC. Here, we describe preclinical studies using a recombinant poxvirus vaccine that encodes a polyepitope protein comprising 6 HLA A2-restricted epitopes derived from LMP1. Human cells infected with this recombinant polyepitope construct were efficiently recognized by LMP1-specific CTL lines from HLA A2 healthy individuals. Furthermore, immunization of HLA A2/K(b) mice with this polyepitope vaccine consistently generated strong LMP1-specific CTL responses to 5 of the 6 epitopes, which were readily detected by both ex vivo and in vitro assays. More important, this polyepitope vaccine successfully reversed the outgrowth of LMP1-expressing tumors in HLA A2/K(b) mice. These studies provide an important platform for the development of an LMP-based polyepitope vaccine as an immunotherapeutic tool for the treatment of EBV-associated HD and NPC.     

Microsurgical anatomy of the superior and recurrent laryngeal nerves

OBJECTIVE: To study the microsurgical anatomy of the superior laryngeal nerve (SLN) and recurrent laryngeal nerve (RLN) with respect to anatomic landmarks, and to identify their vascular supplies. METHODS: The microsurgical anatomy of the anterior neck, the course of the right and left SLN and RLN and their variations were studied in 21 cadavers. Fresh cadavers were perfused with colored silicon dye to investigate the microvasculature in detail. RESULTS: SLN originates from the inferior vagal ganglion at the C2 level and descends medially toward the thyrohyoid membrane. It branches into an external and an internal branch deep to the internal carotid artery at the C3 level. The external branch, along with the cricothyroid artery, descends deep to the superior thyroid artery toward the cricothyroid muscle. Accompanied by the superior laryngeal artery, the internal branch passes deep to the loop of the superior thyroid artery and pierces the thyrohyoid membrane. Both nerves reside in the fascia covering longus colli muscles and are supplied by their accompanying arteries. The loop of RLN is found at the T1-T3 level on the right, and more caudally at the T3-T6 level on the left, entering the larynx between C5-C7 levels on both sides. RLN receives arterial supply from the esophageal and tracheal branches of the inferior thyroid artery proximally, and by the inferior laryngeal artery distally. CONCLUSION: Incidental intraoperative injury to the SLN and RLN potentially could be avoided by understanding the detailed course of each nerve with respect to the surrounding anatomic landmarks and by recognizing their blood supplies.     

Spontaneous displacement of olecranon fracture through geode salvaged by elbow replacement

We present a case of pathological fracture of olecranon through a giant geode. Fracture was initially undisplaced and was treated conservatively. It later progressed to a transolecranon dislocation as a result of a pseudarthrosis at the fracture site. The patient presented 4 years later when she developed symptoms of ulnar nerve palsy. She was treated by a total elbow arthroplasty with ulnar nerve transposition. The current report highlights this unusual case and reviews the relevant literature.     

Aminophylline for the treatment of symptomatic bradycardia and asystole secondary to cervical spine injury

Introduction  

Bradycardia is a common complication of cervical spine damage in the weeks following injury, occurring in up to 100% of patients in some studies. Cardiac arrest and asystole have been reported in as many as 15% of these patients and cardiac events are the main cause of death within the first year. We describe the case of a 25-year-old African-American male involved in a motor vehicle collision who suffered C6–C7 subluxation.