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Abstract Background The existence of large pores in the blood-tumor barrier (BTB) of malignant solid tumor microvasculature makes the blood-tumor barrier more permeable to macromolecules than the endothelial barrier of most normal tissue microvasculature. The BTB of malignant solid tumors growing outside the brain, in peripheral tissues, is more permeable than that of similar tumors growing inside the brain. This has been previously attributed to the larger anatomic sizes of the pores within the BTB of peripheral tumors. Since in the physiological state in vivo a fibrous glycocalyx layer coats the pores of the BTB, it is possible that the effective physiologic pore size in the BTB of brain tumors and peripheral tumors is similar. If this were the case, then the higher permeability of the BTB of peripheral tumor would be attributable to the presence of a greater number of pores in the BTB of peripheral tumors. In this study, we probed in vivo the upper limit of pore size in the BTB of rodent malignant gliomas grown inside the brain, the orthotopic site, as well as outside the brain in temporalis skeletal muscle, the ectopic site. Methods Generation 5 (G5) through generation 8 (G8) polyamidoamine dendrimers were labeled with gadolinium (Gd)-diethyltriaminepentaacetic acid, an anionic MRI contrast agent. The respective Gd-dendrimer generations were visualized in vitro by scanning transmission electron microscopy. Following intravenous infusion of the respective Gd-dendrimer generations (Gd-G5, N = 6; Gd-G6, N = 6; Gd-G7, N = 5; Gd-G8, N = 5) the blood and tumor tissue pharmacokinetics of the Gd-dendrimer generations were visualized in vivo over 600 to 700 minutes by dynamic contrast-enhanced MRI. One additional animal was imaged in each Gd-dendrimer generation group for 175 minutes under continuous anesthesia for the creation of voxel-by-voxel Gd concentration maps. Results The estimated diameters of Gd-G7 dendrimers were 11 ± 1 nm and those of Gd-G8 dendrimers were 13 ± 1 nm. The BTB of ectopic RG-2 gliomas was more permeable than the BTB of orthotopic RG-2 gliomas to all Gd-dendrimer generations except for Gd-G8. The BTB of both ectopic RG-2 gliomas and orthotopic RG-2 gliomas was not permeable to Gd-G8 dendrimers. Conclusion The physiologic upper limit of pore size in the BTB of malignant solid tumor microvasculature is approximately 12 nanometers. In the physiologic state in vivo the luminal fibrous glycocalyx of the BTB of malignant brain tumor and peripheral tumors is the primary impediment to the effective transvascular transport of particles across the BTB of malignant solid tumor microvasculature independent of tumor host site. The higher permeability of malignant peripheral tumor microvasculature to macromolecules smaller than approximately 12 nm in diameter is attributable to the presence of a greater number of pores underlying the glycocalyx of the BTB of malignant peripheral tumor microvasculature.

Abstract Background Effective transvascular delivery of nanoparticle-based chemotherapeutics across the blood-brain tumor barrier of malignant gliomas remains a challenge. This is due to our limited understanding of nanoparticle properties in relation to the physiologic size of pores within the blood-brain tumor barrier. Polyamidoamine dendrimers are particularly small multigenerational nanoparticles with uniform sizes within each generation. Dendrimer sizes increase by only 1 to 2 nm with each successive generation. Using functionalized polyamidoamine dendrimer generations 1 through 8, we investigated how nanoparticle size influences particle accumulation within malignant glioma cells. Methods Magnetic resonance and fluorescence imaging probes were conjugated to the dendrimer terminal amines. Functionalized dendrimers were administered intravenously to rodents with orthotopically grown malignant gliomas. Transvascular transport and accumulation of the nanoparticles in brain tumor tissue was measured in vivo with dynamic contrast-enhanced magnetic resonance imaging. Localization of the nanoparticles within glioma cells was confirmed ex vivo with fluorescence imaging. Results We found that the intravenously administered functionalized dendrimers less than approximately 11.7 to 11.9 nm in diameter were able to traverse pores of the blood-brain tumor barrier of RG-2 malignant gliomas, while larger ones could not. Of the permeable functionalized dendrimer generations, those that possessed long blood half-lives could accumulate within glioma cells. Conclusion The therapeutically relevant upper limit of blood-brain tumor barrier pore size is approximately 11.7 to 11.9 nm. Therefore, effective transvascular drug delivery into malignant glioma cells can be accomplished by using nanoparticles that are smaller than 11.7 to 11.9 nm in diameter and possess long blood half-lives.

Although certain drugs of abuse are known to disrupt brain glucose metabolism ( BGluM), the effects of opiates on BGluM are not well characterized. Moreover, preclinical positron emission tomography ( PET) studies anesthetize animals during the scan, which limits clinical applications. We investigated the effects of (i) isoflurane anesthesia and (ii) intravenous morphine self-administration ( MSA) on BGluM in rats. Jugular vein cannulated adult male Sprague-Dawley rats self-administered either saline ( SSA) or morphine (0.5 mg/kg/infusion, 4 h/day for 12 days). All animals were scanned twice with [18F]-fluoro-deoxy-glucose ( FDG)- PET/ CT at a baseline and at 2-day withdrawal from self-administration. After the IV injection of FDG, one batch of animals ( n = 14) was anesthetized with isoflurane and the other batch ( n = 16) was kept awake during the FDG uptake (45 min). After FDG uptake, all animals were anesthetized in order to perform a PET/ CT scan (30 min). Isoflurane anesthesia, as compared to the awake condition, reduced BGluM in the olfactory, cortex, thalamus, and basal ganglia, while increasing BGluM in the midbrain, hypothalamus, hippocampus, and cerebellum. Morphine self-administered animals exhibited withdrawal signs (piloerection and increased defecation), drug seeking, and locomotor stimulation to morphine (0.5 mg/kg) during the 2 day withdrawal. The BGluM in the striatum was increased in the MSA group as compared to the SSA group; this effect was observed only in the isoflurane anesthesia, not the awake condition. These findings suggest that the choice of the FDG uptake condition may be important in preclinical PET studies and increased BGluM in the striatum may be associated with opiate seeking in withdrawal. [ABSTRACT FROM AUTHOR]

Non-invasive measurements of brain metabolism using 18F-fluorodeoxyglucose (FDG) with positron emission tomography (PET) may provide important information about injury severity following traumatic brain injury (TBI). There is growing interest in the potential of combining functional PET imaging with anatomical and functional magnetic resonance imaging (MRI). This study aimed to investigate the effectiveness of combining clinically available FDG-PET with T2 and diffusion MR imaging, with a particular focus on inflammation and the influence of glial alterations after injury. Adult male Sprague Dawley rats underwent a moderate controlled cortical impact (CCI) injury followed by FDG-PET, MRI, and histological evaluation. FDG uptake showed significant alterations in the corpus callosum, hippocampus, and amygdala after TBI, demonstrating that a relatively 'focal' CCI injury can result in global alterations. Analysis of MRI T2 intensity and apparent diffusion coefficient (ADC) also showed significant alterations in these regions to include cytotoxic and vasogenic edema. Histology showed increased glial activation in the corpus callosum and hippocampus that was associated with increased FDG uptake at sub-acute time-points. Glial activation was not detected in the amygdala but neuronal damage was evident, as the amygdala was the only region to show a reduction in both FDG uptake and ADC at sub-acute time-points. Overall, FDG-PET detected glial activation but was confounded by the presence of cell damage, whereas MRI consistently detected cell damage but was confounded by glial activation. These results demonstrate that FDG-PET and MRI can be used together to improve our understanding of the complex alterations in the brain after TBI. [ABSTRACT FROM AUTHOR]

Global climate change is expected to alter the Arctic bioregion markedly in coming decades. As a result, monitoring of the expected and actual changes has assumed high scientific significance. Many marine science objectives are best supported with the use of scientific diving techniques. Some important keystone environments are located in extremely remote locations where land-based expeditions offer high flexibility and cost-effectiveness over ship-based operations. However, the extreme remoteness of some of these locations, coupled with complex and unreliable land, sea and air communications, means that there is rarely quick access (< 48 h) to any specialized diving medical intervention or recompression. In 2009, a landbased expedition to the north end of Baffin Island was undertaken with the specific aim of establishing an inventory of the diversity of seaweeds and their pathogens that was broadly representative of a high Arctic marine environment. This account highlights some of the logistical considerations taken on that expedition; specifically it outlines the non-recompression treatment pathway that would have been adopted in the event of a diver suffering decompression illness. [ABSTRACT FROM AUTHOR]

The article presents a study which probed the transfer modality in three distinct groups of presenting divers with decompression illness on the west coast of Scotland. The study used the procedures of implied consent run by the National Health Service in Great Britain for clinical audit. The subject population was examined for basic demographics and the amount of recreational divers. Overall time from symptom onset to therapy was found to be shorter for intense cases compared with mild and moderate ones.

The article discusses saturation treatment in shore-based chambers for divers with deteriorating cerebro-spinal decompression sickness (DCS). Two cases are presented that include air saturation treatment and helium saturation treatment. The article also outlined the basic principles and delivery protocols of saturation treatment.

The article presents a study which analyzed two sets of divers with actual or suspected decompression illness (DCI), a group of 300 divers treated for DCI by the Dunstaffnage Hyperbaric Unit (Oban) between 1972 and 2007 and a group of 536 divers treated by the Scottish recompression chamber network between 1991 and 2003 with some divers common to both groups. It concludes that shorter and shallower treatment may result in poorer outcomes compared with RN 62/USN 6 treatment.

The article presents two cases of epileptic seizures related to probable arterial gas embolism. It says such a disease is possibly a fatal complication of scuba diving and may also occur in decompression sickness (DCS). A 41-year-old male diver had brisk reflexes in his arms and legs. A 22-year-old male scaffolder, who was learning to dive with shellfish divers on the west coast of Scotland, had not undergone any dive training course or medical assessment.

The article describes cases highlighting the consequences of misinterpreting dive computers conducted by Martin D. J. Sayer et al, published in the 2008 issue of the journal "Diving and Hyperbaric Medicine." The Suunto Vytec™ computer was bought by a diver with a view to adjusting its settings to make her decompression management more conservative. It cites diving modes being supported by the Buddy Nexus™ used by an open-water diver, including open-circuit sport. Also compared were three models of dive computer.

The article presents a case study of a 33-year old diver who was found unconscious after diving more than 50 meters of water in a marine tunnel off the west coast of Scotland. The diver received hyperbaric oxygen therapy for a cerebral arterial gas embolism. During treatment, he showed a number of neurological abnormalities including visual disturbances diagnosed as prosopagnosia or the inability to recognize faces. This was the first case reported to have resulted from a diving accident.

A 33-year-old, male professional scallop diver diving on the Outer Hebrides in Scotland rapidly developed symptoms of cerebral arterial gas embolism following a provocative dive with possibly a fast ascent. During transfer by helicopter to the mainland for treatment, his symptoms improved on surface oxygen. He was recompressed on a Royal Navy Treatment Table 62 (RN TT62) with complete resolution. Just over six weeks later, again diving on the Outer Hebrides and after adopting more conservative diving practices, he developed symptoms and signs of vestibular decompression sickness after a problem-free dive, with dizziness, poor co-ordination and gait, nausea and vomiting, and rotational vertigo. He was again transported to the mainland for recompression treatment. He received an extended RN TT62 and required five further Comex 12 (223 kPa) hyperbaric oxygen treatments over the following three days before he was symptom free. A 4 mm persistent foramen ovale (PFO) was subsequently diagnosed and he underwent successful closure of the defect with Amplatzer device and returned to commercial diving a year later. [ABSTRACT FROM AUTHOR]

The article presents a summary of the 2011 British Sub-Aqua Club (BSAC) report on diving incidents in Great Britain. Results of the analysis of the facts revealed the number of cases of a medical event underwater, separation, diving in a group, deeper diving, running out of gas, rapid ascents, and cave diving. Several cases of fatal diving and decompression illness are described.

The article presents the 2010 annual report of diving incidents by the British Sub-Aqua Club (BSAC). According to the BSAC report, 364 diving incidents were recorded in Great Britain in 2010, below the 10 year average of 400 which the BSAC claims is attributable to strong campaigning and improved training of divers. During the period, 17 diving deaths were reported due to multiple contributing factors while the 105 decompression incidents reported is the lowest recorded for 14 years

The article presents the 2008 summary report of the British Sub-Aqua Club (BSC) for diving incidents with focus on fatalities and cases of decompression illness (DCI). Records showed fewer fatalities for 2008 compared to previous years while DCI cases manifested an increase. The report is recommended to all divers, diver educators and diving physicians.

The article offers information on various diving incidents included in the British Sub-Aqua Club (BSAC) 2007 report. In 2007, 349 diving incidents were reported, with 12 fatalities. The causes of reported diver fatalities include heart attacks, using rebreathers, being trapped in wrecks and diving alone. A list of the major causal factors associated with the decompression incidents is also provided.

Introduction: We examined national and single-centre datasets in Scotland to determine any trends in the treatment of diving-related disease and to assess how the choice of first treatment may be linked to the divers' condition on referral and on discharge., Method: Two datasets were analysed: (1) 300 divers treated for actual or suspected decompression illness by the Dunstaffnage Hyperbaric Unit (Oban) between 1972 and 2007; and (2) 536 divers treated by the Scottish recompression chamber network between 1991 and 2003 (some data were common to both sets). The type and frequency of initial and any subsequent hyperbaric treatment used were examined. Any trends in demographics, reasons for diving, dive series profiles and condition on admission were examined., Results: Ninety to 92 per cent of treated divers received standard or modified Royal Navy treatment table 62 (RN 62) or US Navy table 6 (USN 6) for their primary treatment. Nearly a third of the divers (32%) were rated as having a severe condition on admission; only 4% had a severe condition on discharge. Analysis of outcome versus treatment type was complicated by divers with more severe symptoms on referral tending to have a worse outcome (concomitant with their referral condition) while receiving more prolonged and complex treatments., Conclusions: Shorter and shallower treatment tables (e.g., US Navy table 5, Royal Navy table 61), when used as first treatment, may result in poorer outcomes compared with RN 62/USN 6 treatment. Although subject to ongoing analysis, the shorter and/or shallower treatments have been discouraged as a first treatment in Scotland.