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Hugh K Richards

Publications and source records attributed to Hugh K Richards.

8 recordsLinked to original sources
PubMed2006

In vitro hydrodynamic properties of the Miethke ProGAV hydrocephalus shunt.

BACKGROUND: Adjustable shunts are very popular in the management of hydrocephalus and are believed to help in minimizing the number of surgical revisions. The drawback with almost all constructions is that they may be accidentally readjusted in relatively weak magnetic fields (around 30-40 mTesla) MATERIALS AND METHODS: The ProGav Miethke shunt is composed of an adjustable balloon-spring valve unit and an integrated over-drainage compensating gravitational device (known as the shunt assistant). A mechanical 'brake' is intended to prevent changes to the valve's performance level in a strong magnetic field. We evaluated the performance and hydrodynamic properties of a sample of three valves in the UK Shunt Evaluation Laboratory. RESULTS: All the shunts showed good mechanical durability over the three-month period of testing, and good stability of hydrodynamic performance over a one-month period. The pressure-flow performance curves, operating, opening and closing pressures fell within the limits specified by the manufacturer, and changed according to the programmed performance levels. The operating pressure increased when the shunt assistant was in the vertical position, as specified. The valve has a low hydrodynamic resistance (0.53 mm mmHg ml(-1) min(-1)). External programming proved to be easy and reliable. Strong magnetic fields from a 3 Tesla MR scanner were not able to change the programming of the valve. CONCLUSION: The ProGAV shunt is an adjustable, low resistance valve that is able to limit posture-related over-drainage. Unlike other adjustable valves, the ProGAV cannot be accidentally re-adjusted by external magnetic field such as a 3T MR scanner.

Journal Article↗
PubMed2006

Imaging endothelin ET(B) receptors using [18F]-BQ3020: in vitro characterization and positron emission tomography (microPET).

The endothelin (ET) receptor system has been shown to play a role in a number of vascular diseases. We have synthesized 18F-and 11C-labeled radioligands to enable in vivo imaging of the fundamental processes involved in ET receptor pharmacology in normal and diseased tissue using positron emission tomography (PET). One aim is to elucidate the proposed role of the ET(B) subtype as clearing receptor, removing ET-1 from the circulation, and whether this is an important mechanism to limit the detrimental effects caused by upregulated ET-1 in disease. To image ET(B) receptors we have labeled the selective agonist BQ3020 with 18F. In vitro characterization verified that [18F]-BQ3020 bound with a single subnanomolar affinity (K(D) = 0.34 +/- 0.10 nM, B(max) = 9.23 +/- 3.70 fmol/mg protein) to human left ventricle. Binding of [18F]-BQ3020 to human kidney was inhibited by ET-1 and unlabeled BQ3020 but not by the ET(A) selective antagonist FR139317, confirming that selectivity for the ET(B) receptor was retained. In vitro autoradiography revealed, as expected, high levels of ET(B) receptor densities in lung and kidney medulla, whereas kidney cortex and heart showed lower levels of ET(B) receptor densities. Furthermore, a high level of [18F]-BQ3020 binding was found to colocalize to macrophages in atherosclerotic coronary arteries. MicroPET studies demonstrated high uptake of [18F]-BQ3020 in ET(B) receptor-rich tissue, including lung, liver and kidney. The in vivo biodistribution of [18F]-BQ3020 was comparable to that previously obtained for [18F]-ET-1, supporting our hypothesis that the ET(B) receptor plays a significant role in the uptake of ET-1. In conclusion, [18F]-BQ3020 has retained high affinity and selectivity, allowing imaging of ET(B) receptor distributions in vitro and in vivo in human and animal tissue. Furthermore, in vitro data suggest that [18F]-BQ3020 potentially can be used to image atherosclerotic lesions in vivo using PET.

Animals↗
PubMed2005

Positron emission tomography using 18F-labelled endothelin-1 reveals prevention of binding to cardiac receptors owing to tissue-specific clearance by ET B receptors in vivo.

Our aim was to synthesise an (18)F analogue of endothelin-1 (ET-1), to dynamically image ET receptors in vivo by positron emission tomography (PET) and to elucidate the function of the ET(B) subtype as a clearing receptor in organs expressing high densities including kidney and lung.[(18)F]-ET-1 was characterised in vitro and bound with a single subnanomolar affinity (K(D)=0.43+/-0.05 nM, B(max)=27.8+/-2.1 fmol mg(-1) protein) to human left ventricle (n=4). The in vivo distribution of [(18)F]-ET-1 in anaesthetised rats was measured using a dedicated small animal PET scanner (microPET) and ex vivo analysis. Dynamic PET data demonstrated that high levels of radioligand accumulated rapidly in the lung, kidney and liver, consistent with receptor binding. The in vivo distribution correlated with the anatomical localisation of receptors detected in vitro using [(125)I]-ET-1. However, the receptor density visualised in the heart was unexpectedly low compared with that predicted from the in vitro measurements.[(18)F]-ET-1 binding in lungs could not be displaced by the ET(B) selective antagonist BQ788, in agreement with the proposed internalisation of ET-1 by ET(B) receptors. In contrast, infusion of BQ788 prior to injecting [(18)F]-ET-1 significantly reduce the amount of radioligand visualised in the ET(B) rich lung and kidney by 85% (P< 0.05, n=3) and 55% (P<0.05, n=3), respectively. Under conditions of ET(B) receptor blockade, the heart could be visualised by microPET imaging.These results suggest that clearance by ET(B) receptors in the lung and kidney prevents binding of ET-1 to receptors in the heart.

Animals↗
PubMed2004

In vivo imaging of cardiovascular endothelin receptors using the novel radiolabelled antagonist [18F]-SB209670 and positron emission tomography (microPET).

The aim of this study was to develop an F-labelled analogue of SB209670 with subnanomolar affinity for the endothelin receptor and to test whether it would have the required pharmacokinetic properties to permit binding and imaging of endothelin receptors in rat heart in vivo using small animal positron emission tomography (PET) imaging. [18F]-SB209670 could be produced in a total radiochemical yield of 14.9 +/- 3.8% in 162 +/- 7 minutes (n = 6). The radiochemical purity of the isolated radioligand was 99% and the specific activity was 100-150 GBq/micromol. In vitro characterization using ligand-binding assays demonstrated that [18F]-SB209670 bound with a single subnanomolar affinity to human heart tissue (n = 3) with a KD = 0.67 +/- 0.14 nM and a Bmax = 168.3 +/- 29.3 fmol/mg protein. The binding was time-dependent with a half-time (t(1/2)) for association of 3.8 minutes and an association rate constant (kobs) of 0.182 +/- 0.032/min. In vivo distribution in the rat was studied using microPET. Dynamic imaging revealed a fast clearance of [F]-SB209670 from the circulation by the liver, indicative of a high degree of metabolism. However, visualization of uptake in the rat heart was achievable and dynamic PET data together with the in vitro results suggest that [F]-SB209670 binds rapidly and primarily to endothelin-A receptors in the heart.

Animals↗
PubMed2004

Relationship between flow-metabolism uncoupling and evolving axonal injury after experimental traumatic brain injury.

Blood flow-metabolism uncoupling is a well-documented phenomenon after traumatic brain injury, but little is known about the direct consequences for white matter. The aim of this study was to quantitatively assess the topographic interrelationship between local cerebral blood flow (LCBF) and glucose metabolism (LCMRglc) after controlled cortical impact injury and to determine the degree of correspondence with the evolving axonal injury. LCMRglc and LCBF measurements were obtained at 3 hours in the same rat from 18F-fluorodeoxyglucose and 14C-iodoantipyrine coregistered autoradiographic images, and compared to the density of damaged axonal profiles in adjacent sections and in an additional group at 24 hours using beta-amyloid precursor protein (beta-APP) immunohistochemistry. LCBF was significantly reduced over the ipsilateral hemisphere by 48 +/- 15% compared with sham-controls, whereas LCMRglc was unaffected, apart from foci of elevated LCMRglc in the contusion margin. Flow-metabolism was uncoupled, indicated by a significant 2-fold elevation in the LCMRglc/LCBF ratio within most ipsilateral structures. There was a significant increase in beta-APP-stained axons from 3 to 24 hours, which was negatively correlated with LCBF and positively correlated with the LCMRglc/LCBF ratio at 3 hours in the cingulum and corpus callosum. Our study indicates a possible dependence of axonal outcome on flow-metabolism in the acute injury stage.

Amyloid beta-Protein Precursor↗
PubMed2003

Hydrodynamic properties of extraventricular drainage systems.

OBJECTIVE: Extraventricular drains (EVDs) are intended to control intracranial pressure for patients with acute disorders of the cerebrospinal fluid circulation. We tested five commercially available EVDs to assess their fundamental hydrodynamic properties, which determine the quality of this control. METHODS: The five most frequently used drainage systems were tested. The pressure responses to water flow from a computer-controlled infusion pump were studied in the rig constructed in the UK Shunt Evaluation Laboratory (Cambridge, England). EVDs were studied under normal conditions and after brief (20-s) contact of the vent located in the drip chamber with the test reagent. Pure water and water with 10% rat blood content were used for testing. RESULTS: All of the tested EVDs demonstrated low hydrodynamic resistance [<3.5 mm Hg/(ml/min)], indicating their ability to control intracranial pressure. When the drip chamber vents were in brief contact with the reagent, the hydrodynamic properties of two models were unaffected. For the three other EVDs, blockage of the drip chamber was observed, leading to increases in the inlet pressure to more than 150 mm Hg. All three models that demonstrated obstruction have the same vent configuration, which allows cerebrospinal fluid to accumulate close to the filter when the drip chamber is held horizontally. This feature was confirmed to be the cause of the blockage. CONCLUSION: In clinical practice, special care should be taken to avoid contact of the drip chamber vents with cerebrospinal fluid, which causes obstruction and may lead to the development of gross intracranial hypertension. Specific configurations, as identified in this testing program, are safer than others in this respect.

Animals↗