Electrophoretic isolation of extrachromosomal DNA from tumor cells

Gene amplification allows transformed cells to overexpress specific genes and gain a survival advantage. For this reason, cloning and characterization of amplified genes can improve our understanding of the biology of transformed cells. The techniques of in-gel renaturation and chromosome microdissection can enrich for amplified DNA sequences, but both are labor intensive and have other drawbacks. We have developed an alternative strategy of enriching for amplified DNA sequences that involves two-directional agarose gel electrophoresis of extrachromosomal circular DNA. Extrachromosomal circles can be detected with repetitive DNA probes and can be used to produce DNA probes suitable for fluorescence in situ hybridization for location of genomic origin. The ability to enrich for amplified DNA without specialized equipment or transformed cell metaphases should prove useful in the search for new genes which are important in tumor cell progression.     

Ischemic necrosis of the entire femoral head and rapidly destructive hip disease: potential causative relationship

 Objective. Rapidly destructive hip disease (RDHD) is an uncommon disorder of the hip that has been considered a disease of unknown cause and distinct from ischemic necrosis of the femoral head. The objective of this study was to investigate ischemic necrosis of the femoral head as one potential cause of RDHD. Design and patients. In 600 patients who underwent MR imaging of the hip, 20 cases of ischemic necrosis involving the entire femoral head in 18 patients (3%) were retrospectively studied with routine radiography and MR imaging. All patients had surgically confirmed ischemic necrosis of the femoral head. Results and conclusions. All patients showed rapid destruction of the femoral head on routine radiography and MR imaging as compared with the gradual onset of clinical symptoms. Plain radiographs showed several bone fragments at the inferomedial aspect of the femoral head (75%), acetabular erosions (55%), eccentric depression at the lateral articular surface of the femoral head conforming to the adjacent acetabulum (35%), and mild osteoarthritis (15%). Bone sclerosis was often present at sites of impaction between the femoral head and the acetabulum. MR imaging showed marked distention of the joint capsule in all cases. In 14 of 20 cases, the contents of the joint space showed predominantly low or intermediate signal intensity on T1- and T2-weighted images. Ischemic necrosis involving the entire femoral head may represent one of the causes of RDHD.     

Distribution of normal and abnormal fluid collections in the glenohumeral joint: Implications for MR arthrography

Although magnetic resonance (MR) images of the glenohumeral joint frequently demonstrate intraarticular fluid, no specific criteria have, to the authors' knowledge, been published that allow accurate assessment of the amount of fluid present. Also, despite the increasing use of MR arthrography of the shoulder, the optimal amount of intra-articular fluid that should be used with this technique has not been determined. The authors progressively distended the glenohumeral joint in six cadaveric shoulder specimens with a dilute gadopentetate dimeglumine solution and obtained MR images after injection of 2, 5, 10, 15, and 20 mL of the solution. The pattern of fluid distribution was evaluated, and these results were then used to estimate the amount of fluid that was present in the glenohumeral joint on MR images of 20 shoulders obtained in 12 asymptomatic volunteers. In 14 of these shoulders, intraarticular fluid was present; however, in none was more than 2 mL evident. Results of the cadaveric study also indicated that 15 mL of intraarticular fluid appears to be the optimal amount for MR arthrography.     

Rapidly enhancing hepatic hemangiomas at MRI: Distinction from malignancies with T2-weighted images

The purpose of this study is to describe a subset of atypical hepatic hemangiomas that enhance rapidly and diffusely and to determine whether heavily T2-weighted images could distinguish between atypically enhancing liver hemangiomas and hypervascular malignancies. A retrospective search of MR records identified seven patients with liver hemangiomas that demonstrated diffuse early enhancement and 23 patients with biopsy-proven malignant liver lesions that were hypervascular on dynamic gadolinium-enhanced MR images. Quantitative analysis of signal intensity measurements was performed on the T2-weighted images, heavily T2-weighted (TE < 140), and dynamic gadolinium-enhanced images. Blinded reader comparison of the T2-weighted images and gadolinium-enhanced images was performed. Hypervascular hemangiomas enhanced to a greater degree than hypervascular malignant liver lesions on the early phase gadolinium-enhanced images. Perilesional parenchymal enhancement was demonstrated in five cases of rapidly enhancing hemangiomas. Signal intensity and contrast-to-noise ratios on the heavily T2-weighted images of the hemangiomas were significantly greater than that of the hypervascular malignant lesions (P < .05). Hemangiomas were differentiated from the hypervascular malignant liver lesions with high accuracy (97–100%) by three blinded readers based on the T2-weighted images. A subset of hemangiomas have atypical rapid diffuse enhancement on dynamic gadolinium-enhanced images. These atypical hemangiomas can be distinguished from hypervascular malignant liver lesions on T2-weighted MR images.     

5-HT3 Receptor-independent Inhibition of the Depolarization-induced 86Rb Efflux from Human Neuroblastoma Cells,TE671, by Ondansetron

The 5-HT₃-receptor antagonist, ondansetron, has been shown to have positive effects in selected in-vivo models of memory impairment and anxiety. The exact mechanisms underlying such bioactivities are unknown. In the present work, an ⁸⁶Rb efflux bioassay was used to show that ondansetron has a unique ability to block voltage-gated potassium channels in TE671 human neuroblastoma cells. This intrinsic potassium-channel-blocking (KCB) property is relatively weak (IC50 20 (M), but is not shared by other 5-HT₃-receptor ligands including zatosetron, MDL 72222, LY 278, 584, zacopride, 1-phenylbiguanide, and ICS 205–930 (tropisetron). Pre-incubation of the target neuroblastoma cells with several 5-HT-receptor ligands including 5-hydroxytryptamine, 8-OH-DPAT, ketanserin, 2-methyl-5-HT, as well as a number of potent 5-HT₃ agonists and antagonists and two selective neurotoxins, failed to abolish the KCB action of ondansetron. A preliminary structure-activity relationship analysis indicates that the KCB activity of ondansetron is almost entirely attributable to its structural nucleus, 2,3-dihyro-9-methyl-4(lH)-carbazolone. It is hypothesized that the KCB action of ondansetron is mediated through receptors other than 5-HT₃ receptors. The KCB activity of ondansetron may be a significant factor in the in-vivo cognition-enhancing activities of this compound, conceivably due to depolarization of the hippocampal synaptic membranes and a consequent augmentation of neurotransmission.     

Public health medicine and drinking water in Scotland

The prevention of the spread of disease by drinking water relies on a tripartate arrangement among the supplier, the regulator and their medical advisers. This paper describes the role of Public Health Medicine in Scotland in preventing a ‘significant risk to health’ from potable water. The legislative framework is highlighted. The rationale of water monitoring is examined and the role of Consultant in Public Health Medicine. The concept of Significant Medical Risk Values is introduced and their derivation, uses, and levels presented.     

Cognitive rehabilitation in the elderly: overview and future directions.

This study provides an overview of the papers emanating from the experimental trial that evaluated a new cognitive rehabilitation program in older adults who were experiencing normal cognitive decline. The main features of the design are summarized, along with evidence that the training produced long-lasting improvement in memory performance, goal management, and psychosocial status. The benefits were attributed to several factors, including the program's emphasis on techniques that promoted efficient strategic processing. Limitations of the program and directions for future research are discussed.     

Skull base surgery for malignancy: when not to operate

The purpose of this paper is to detail the contraindications for surgery, with curative intent for those patients who suffer from a head and neck malignancy that invades the intracranial space. This is based on a 30-year experience of over 250 patients. The most important contraindications are anatomical. Surgery is not done if the following structures are invaded: brain stem, eloquent portions of the cerebrum, superior sagittal sinus, both internal carotid arteries, both cavernous sinuses and certain vital bridging veins. Certain tumor factors are absolute but are occasionally relative contraindications: such as distant metastatic disease especially if multiple and at multiple anatomic sites. Some tumors that behave in a particularly virulent fashion that defy complete resection but are often difficult to predict preoperatively. Lack of patient medical fitness or absence of patient commitment to the operative procedure is make-up two serious contraindications to surgery. Presented at the 77th Annual Meeting of the German Society for Oto-Rhino-Laryngology, Head and Neck Surgery, 24–28 May 2006, Mannheim, Germany.     

Anaesthesia for Treacher Collins and Pierre Robin syndromes: A report of three cases

We present three patients with Treacher Collins or Pierre Robin syndromes who had historical and physical evidence of airway obstruction, difficulty feeding, and sleep disturbances. These preoperative findings correlated with difficult airway management intraoperatively. Based on this experience, we recommend that children with obstructive symptoms have laryngoscopy prior to anaesthetic induction. If the glottic opening is visualized, inhalational induction can proceed. If the glottic structures cannot be visualized, then the anaesthetist must choose between awake oral or nasal intubation, elective tracheostomy, or fiberoptic intubation. In all cases, a tracheostomy tray should be ready and a surgeon experienced in paediatric tracheostomy should be in attendance. After intubation, anaesthesia is best maintained with oxygen and a potent inhalational agent. Extubation should only be done with the patient fully awake and with emergency airway equipment immediately available. Postoperatively, these patients should be transferred to an intermediate care area or intensive care unit where they can be observed closely since delayed complications of airway obstruction are common in this group of patients.