Further delineation of interstitial chromosome 6 deletion syndrome and review of the literature

Interstitial deletions of chromosome 6q are a relatively rare finding. Deletions have ranged from the loss of a single band to larger deletions spanning multiple bands. The clinical phenotype varies, but some features commonly seen include cardiac anomalies, hypotonia, facial dysmorphism and mental retardation. To further delineate the syndrome, we report an infant with facial dysmorphism, ectrodactyly and tetralogy of Fallot owing to interstitial deletion 6q16.1-6q22.32. On array comparative genomic hybridization analysis, the deletion spanned from the 93 377 323rd base to the 127 650 582nd base on chromosome 6 [coordinates are based on Human Mar. 2006 (hg18) assembly of International Human Genome Sequencing Consortium]. A literature review identified 16 additional cases with overlapping interstitial deletions of chromosome 6q between q13 and q23.1. Genotype-phenotype correlations are considered.     

Local Anaesthesia in Dentistry: A Review

Over the past century, there is perhaps no greater contribution to the practice of clinical dentistry than the development and application of local anaesthesia. What were once considered painful procedures have now been made routine by the deposition and action of local anaesthetics. This article will serve as a review of basic pharmacological principles of local anaesthesia, subsequent sequelae that can arise from their use, considerations when using local anaesthetics, and recent advances in the delivery of local anaesthetics.     

Embolisation of spinal dural arteriovenous fistulae with Onyx

Surgery is currently the standard treatment for spinal dural arteriovenous fistulae (DAVF). Endovascular embolisation of these lesions using N-butyl cyanoacrylate (NBCA) has a high success rate. Onyx is a new liquid embolic agent whose viscosity makes it suitable for treatment of spinal DAVF where penetration into the proximal radicular vein is required. It is delivered with greater control than NBCA without the necessity for rapid withdrawal of the catheter and may therefore overcome some of the drawbacks of NBCA. We report two patients who underwent Onyx embolisation of spinal DAVF; to our knowledge this is the first such report.     

The superior trapezius myocutaneous flap in head and neck reconstruction.

The superior trapezius myocutaneous flap, based on the paraspinous perforating branches of the intercostal vessels, is generally not a first-line choice for reconstruction of head and neck defects. However, after wound breakdown following radical neck dissection and radiation therapy, the superior trapezius flap is extremely reliable for coverage of exposed major neck vessels. The flap was used in 30 patients undergoing lateral neck reconstruction. All 30 patients had undergone prior neck dissection and all but two had undergone prior radiation therapy. There were no flap failures. The superior trapezius flap is unique among other regional myocutaneous flaps presently in use in that it has a superiorly based pedicle, which reduces the problem of gravitational pull on the suture lines of severely unfavorable recipient beds. Another advantage of using the denervated muscle of this flap is that it imposes no additional functional loss. The deficiencies of this flap are primarily related to its limited arc of rotation, thereby precluding its use when resurfacing defects that extend beyond the midline of the neck. The reliability of the superior trapezius flap after neck dissection can be explained by the angiosome concept. Based on that concept, previous ligation of the transverse cervical vessels during a neck dissection serves to simultaneously stage this flap, thereby improving its reliability and potential surface area available.     

The kinase inhibitor PP1 blocks tumorigenesis induced by RET oncogenes

Oncogenic activation of the RET receptor tyrosine kinase is common in different human cancers. We found that the pyrazolo-pyrimidine PP1 inhibited RET-derived oncoproteins with a half maximal inhibitor concentration of 80 nM. Furthermore, RET/PTC3-transformed cells treated with 5 microM of PP1 lost proliferative autonomy and showed morphological reversion. PP1 prevented the growth of two human papillary thyroid carcinoma cell lines that carry spontaneous RET/PTC1 rearrangements and blocked anchorage-independent growth and tumorigenicity in nude mice of NIH3T3 fibroblasts expressing the RET/PTC3 oncogene. These findings suggest targeting RET oncogenes with PP1 or related compounds as a novel treatment strategy for RET-associated neoplasms.     

Elevated platelet vesicular monoamine transporter density in untreated patients diagnosed with major depression

The intraneuronal uptake of monoamines into brain synaptic vesicles is mediated by the vesicular monoamine transporter (VMAT2). This transporter plays a major role in monoamine storage and quantal release. Recently we demonstrated a high degree of similarity between the pharmacodynamic characteristics of platelet and brain VMAT2. In the present study we measured the VMAT2 density, using [3H]dihydrotetrabenazine ([3H]TBZOH) as a ligand, in platelets of untreated patients diagnosed with major depressive disorder (MDD) (n=10; three with recurrent depression and seven with first episode depression) compared to sex- and age-matched healthy control subjects (n=23). A significant elevation in the VMAT2 density (B(max)) was observed in the platelets of untreated MDD patients (+24%) compared to healthy control subjects. No significant change was found in the affinity constant (K(d)). The increased platelet VMAT2 density may reflect depression-related enhancement of the capacity to accumulate monoamines in the vesicles in the presence of lower monoamine turnover.     

Genomic association/linkage of sodium lithium countertransport in CEPH pedigrees

Little is known about genetic determinants explaining variation in the erythrocyte sodium-lithium countertransport (SLC), an intermediate phenotype of essential hypertension. We characterized the SLC in immortalized lymphoblasts and showed that its behavior is similar to that of erythrocyte SLC. We then performed association and linkage analyses of the SLC in immortalized lymphoblasts from 5 large pedigrees from the Center d'Etude du Polymorphisme Humain (CEPH) genomics repository. The results of these analyses showed that a number of genomic regions harboring genes involved in glutathione metabolism might explain variations in SLC activity. These findings support evidence that thiol groups play a central role in SLC activity.     

Evaluation of immunological methods for detection of bovine growth hormone (BGH) produced in E. coli

The use of several immunological methods for studies on synthesis of bovine growth hormone (BGH) by E. coli is described here. The ELISA procedure was shown to be the least sensitive and unfit for assaying BGH in E. coli extracts. The solid-phase radioimmunoassay (RIA) proved to be highly sensitive, but since E. coli extract itself (not containing BGH) interfered with the immunological reaction, its use for measuring BGH was practically limited. The best adequate procedure proved to be radioimmunoassay in solution, which was not adversely affected by the E. coli extract and was sufficiently sensitive to detect nanogram quantities of BGH. The size of the BGH produced by normal bacterial cells was investigated by protein fractionation, transfer to nitrocellulose paper and detection by anti-BGH serum. This method was also served for semi-quantitative determination of BGH in the bacterial extract.     

Orbital imaging: Part 1. Normal anatomy

Advanced imaging techniques enable the radiologist to detect an increasing number of structures within the orbit not previously identifiable. We describe the imaging techniques and orbital anatomy with an emphasis on radiologically identifiable structures. In a second review of orbital pathology we present pathological processes that may involve these structures.