Ultraviolet A1 phototherapy: a British Photodermatology Group workshop report.

Whole-body ultraviolet (UV)A1 (340-400 nm) phototherapy was first introduced 30 years ago, but is currently available in the UK in only three dermatology departments. A workshop to discuss UVA1 was held by the British Photodermatology Group in May 2009, the aim of which was to provide an overview of UVA1 phototherapy and its role in practice, and to identify areas in which further studies are required. The conclusions were that UVA1 phototherapy is an effective treatment in several inflammatory skin diseases, including localized scleroderma and atopic eczema (AE); however, deficiencies and limitations exist in the published evidence base. For most diseases, such as AE, other treatments also exist, which are generally more effective than UVA1. However, for some diseases, particularly morphoea, the evidence of efficacy is stronger for UVA1 than for other treatments. Acute adverse effects of UVA1 are minimal. The risk of long-term adverse effects, particularly skin cancer, is unknown. Medium to high doses of UVA1 are needed for efficacy in most situations, but the equipment to deliver such doses is large, expensive and difficult to install. UVA1 is currently underprovided, and the recommendation of the workshop is that more tertiary centres should have access to UVA1 phototherapy in the UK.

A model of the UV skin dose distribution in paediatric whole-body phototherapy.

The radiance equation is applied in this study to model the ultraviolet (UV) radiation dose distribution over the skin in paediatric and adult patients treated in a whole-body phototherapy cabin. This approach extends a previously published model of UV radiation dose based on thermal radiation exchange between surfaces (Colemanet al2020Biomed. Phys. Eng. Express6055023). The new model makes it feasible to predict the distribution of UV irradiance over the head, trunk and legs in patients of varying height. The modelled irradiance distributions to directly lamp-facing skin surfaces agree to within 10% of those measured in simulated clinical paediatric treatments in a modern narrowband UVB treatment cabin. For a 10 year old (of height 1.36 m), for example, the model and the clinical measurements both show a UV radiation dose to the face that is around 25% more than that in an adult (of height 1.8 m). The dose to the crown of the head of a 10 year old is both predicted and measured to be more than double that of an adult. The automated dosimetry system, incorporated within the treatment cabin, is also predicted to overestimate irradiance to the body by between 10% and 25% in patients aged between 10 and 4 years (height 1.36-1.0 m). The value of the model and its implications for paediatric whole-body UV treatment in adult-size whole-body treatment cabins are considered.

A thermal radiation exchange model of whole-body UV phototherapy.

A novel model of the skin dose in whole-body UV phototherapy treatment cabins is presented. The model is based on an analysis of the thermal radiation exchange between two surfaces, in this case the UV source and the patient. It is shown to allow analytical treatment of the multiple internal reflections in a treatment cabin that account for around 40% of the skin irradiance. The model provides predictions of the absolute irradiance at the skin and shielding factors in seven different UVA and NB-UVB cabins that are within 6% of those measured using a calibrated radiometer and within 12% for all nine cabins. The model predicts reducing skin irradiances with increasingly patient size, a trend demonstrated in clinical measurements. The exact sensitivity to patient size in automated cabin dosimetry systems, however, varies with in-built sensor positioning. The potential to extend the use of the model to investigate improved design of automated dosimetry systems is discussed.

Interprofessional education in dentistry.

A collaborative health workforce is required to respond to the increasing demands on healthcare resources. Various national and international bodies are promoting interprofessional education (IPE) as a method to provide this collaborative health workforce. IPE is therefore becoming increasingly prominent within healthcare training and will be an essential aspect of dental education. A literature search was completed to provide this narrative review which will introduce IPE, discuss the rationale for IPE within dentistry and the challenges faced. Based on current literature, it will provide practical advice on how to implement an effective IPE learning activity within dentistry.

Acoustic streaming in lithotripsy fields: preliminary observation using a particle image velocimetry method.

This study considers the acoustic streaming in water produced by a lithotripsy pulse. Particle image velocimetry (PIV) method was employed to visualize the acoustic streaming produced by an electromagnetic shock wave generator using video images of the light scattering particles suspended in water. Visualized streaming features including several local peaks and vortexes around or at the beam focus were easily seen with naked eyes over all settings of the lithotripter from 10 to 18 kV. Magnitudes of the peak streaming velocity measured vary in the range of 10-40 mm s(-1) with charging voltage settings. Since the streaming velocity was estimated on the basis of a series of the video images of particles averaged over 1/60s, the time resolution limited by the video frame rate which is 1-2 orders of magnitude larger than driving acoustic activities, measured velocities are expected to be underestimated and were shown a similar order of magnitude lower than those calculated from a simple theoretical consideration. Despite such an underestimation, it was shown that, as predicted by theory, the magnitude of the streaming velocity measured by the present PIV method was proportional to acoustic intensity. In particular it has almost a linear correlation with peak negative pressures (r=0.98683, p=0.0018).

Toward dissecting the etiology of schizophrenia: HDAC1 and DAXX regulate GAD67 expression in an in vitro hippocampal GABA neuron model.

Schizophrenia (SZ) is associated with GABA neuron dysfunction in the hippocampus, particularly the stratum oriens of sector CA3/2. A gene expression profile analysis of human postmortem hippocampal tissue followed by a network association analysis had shown a number of genes differentially regulated in SZ, including the epigenetic factors HDAC1 and DAXX. To characterize the contribution of these factors to the developmental perturbation hypothesized to underlie SZ, lentiviral vectors carrying short hairpin RNA interference (shRNAi) for HDAC1 and DAXX were used. In the hippocampal GABA neuron culture model, HiB5, transduction with HDAC1 shRNAi showed a 40% inhibition of HDAC1 mRNA and a 60% inhibition of HDAC1 protein. GAD67, a enzyme associated with GABA synthesis, was increased twofold (mRNA); the protein showed a 35% increase. The expression of DAXX, a co-repressor of HDAC1, was not influenced by HDAC1 inhibition. Transduction of HiB5 cells with DAXX shRNAi resulted in a 30% inhibition of DAXX mRNA that translated into a 90% inhibition of DAXX protein. GAD1 mRNA was upregulated fourfold, while its protein increased by ~30%. HDAC1 expression was not altered by inhibition of DAXX. However, a physical interaction between HDAC1 and DAXX was demonstrated by co-immunoprecipitation. Inhibition of HDAC1 or DAXX increased expression of egr-1, transcription factor that had previously been shown to regulate the GAD67 promoter. Our in vitro results point to a key role of both HDAC1 and DAXX in the regulation of GAD67 in GABAergic HiB5 cells, strongly suggesting that these epigenetic/transcription factors contribute to mechanisms underlying GABA cell dysfunction in SZ.

Metabolism and kinetics of oxaprozin in normal subjects.

Absorption, biotransformation, excretion, and kinetics of oxaprozin (4,5-diphenyl-2-oxazolepropionic acid) were examined in subjects after an oral dose of 14C-oxaprozin alone as well as before, during, and after long-term administration of unlabeled drug. A single dose of 14C-oxaprozin was rapidly absorbed and the unchanged drug was essentially the only labeled substance in plasma. Recovery of radioactivity in excreta, mostly in urine, exceeded 90%. Major biotransformation routes were glucuronidation of the carboxyl group and hydroxylation of the phenyl rings followed by glucuronidation. Administration of unlabeled oxaprozin did not affect the absorption, qualitative, or quantitative metabolite profile, or recovery of 14C-oxaprozin. Following a single dose, the kinetic parameters for 14C and unchanged drug in plasma were nearly the same. A2-compartment model with first-order elimination adequately describes kinetic disposition. The slow clearance (Clp), 0.08 to 0.12 1/hr, was almost entirely due to biotransformation and the plasma half-lifes, which ranged from 49 to 69 hr, reflected the small Clp. The small volume of distribution (VD beta = 8 to 9 1) indicates limited extravascular distribution. Multiple doses of unlabeled drug, especially when given concurrently, increased the Clp of 14C-oxaprozin. This effect is apparently related to decreased binding of high concentrations of oxaprozin to plasma protein. As a result of increased Clp, steady-state levels are only 40% of levels predicted from the single-dose study.

The selective action of beta-adrenoceptor blocking drugs and the nature of beta1 and beta2 adrenoceptors.

1 Purified membranes retaining a catecholamine responsive adenylate cyclase have prepared from rabbit heart, lung and (pseudo-pregnant) uterus. 2 These preparations have the characteristics of plasma membranes and both heart and lung respond to beta-adrenoceptor agonists in the order: (+/-)-isoprenaline greater than (-)-noradrenaline greater than (-)-adrenaline greater than (+)-isoprenaline greater than salbutamol. The sensitivity of the adenylate cyclase to beta-adrenoceptor stimulation is improved by pre-treatment of the animals with reserpine and syrosingopine. 3 Dose-ratios for several concentrations of propranolol (non-selective beta-adrenoceptor blocker), practolol and atenolol (cardio-selective beta-adrenoceptor blockers) have been measured on all three membrane preparations. Schild plots of log (dose ratio -1) vs. log dose were virtually coincident for heart and lung with a dissociation constant (Kb) for propranolol very close to the pharmacological value. The ratio of Kb values was 0.65 for practolol and 1.23 for atenolol compared with pharmacological cardio-selectivity ratios (measured on isolated atria and tracheal chain) of 67.6 and 110 respectively. The uterus/heart Kb ratio was 51.5 for atenolol. Inhibition of the uterus by practolol gave a Schild plot with slope significantly less than 1, indicating a different mechanism of action from the heart. 4 Kb values obtained by measuring adenylate cyclase stimulation in chopped tissue (including preparations of bronchial tree and alveolar tissue as well as whole lung) resembled the membrane values rather than those found in whole organs. 5 The results show that the pharmacological selectivity of practolol and atenolol is maintained at the receptor-adenylate cyclase level, at least as far as heart and uterus are concerned, though the smaller selectivity ratios in the biochemical system suggest that receptor differences is not the only factor and that phase distribution of the drug may also be important. Membranes prepared from whole lung show that phase distribution of the drug may also be important. Membranes prepared from whole lung show an overall beta1 response which may simply reflect the predominance of beta1 cell types containing beta1-adrenoceptors over bronchial smooth muscle.

Physical characteristics of Dornier extracorporeal shock-wave lithotriptor.

Measurements of the pressure, noise, and radiation dose levels from a Dornier lithotriptor are reported. The distribution of the peak pressure around the treatment focus was investigated, and the highest pressures were found to occur within an elongated volume. Within the treatment room, noise levels of 80-90 dB were produced during each shock wave, rising to 95 dB by the patient's head. Ear protection for the staff and patient is recommended, and careful room design is necessary to minimize the sound disturbance to adjacent quarters. Measurements of the radiation skin dose received by patients from the x-ray localization system were relatively high and ranged from 2-55 cGy (rad), with a mean of 12 cGy. The operator needs to be aware of these high doses and should take precautions to minimize them.

Traceable calibration of ultraviolet meters used with broadband, extended sources.

A calibration system has been developed to provide increased accuracy in the measurement of the irradiance responsivity appropriate for UV meters used with broadband, extended sources of the type employed in phototherapy. The single wavelength responsivity of the test meter is obtained in the wavelength range 250-400 nm by intercomparison with a transfer standard meter in a narrow, monochromatic beam. Traceability to primary standard irradiance scales is provided via the National Measurement System with a best uncertainty of 7% (at 95% confidence). The effective responsivity of the test meter, when used with broadband extended sources, is calculated using the measured spectral and angular response of the meter and tabulated data on the spectral and spatial characteristics of the source radiance. The uncertainty in the effective responsivity, independent of the source variability, is estimated to be 10% (at 95% confidence). The advantages of this calibration system over existing approaches are discussed.

The spatial distribution of cavitation induced acoustic emission, sonoluminescence and cell lysis in the field of a shock wave lithotripter.

This study examines the spatial distribution of various properties attributed to the cavitation field generated by a shock wave lithotripter. These properties include acoustic emission and sonoluminescence, which result from violent bubble collapse, and the degree of cell lysis in vitro, which appears to be related to cavitation. The acoustic emission detected with a 1 MHz, 12 cm diameter focused hydrophone occurs in two distinct bursts. The immediate signal is emitted from a small region contained within the 4 MPa peak negative pressure contour. A second, delayed, burst is emitted from a region extending further along the beam axis. The delay between these two bursts has also been mapped, and the longest delay occurs at positions close to the regions of maximum peak negative pressure. Sonoluminescence from both single and multiple shocks occurs in a broader region than the acoustic emission but the measurement technique does not allow time resolution of the signal. Cell lysis occurs in a relatively small region that correlates closely with the immediate acoustic emission for a shock propagating in a gelatine solution.

The influence of fluid properties and pulse amplitude on bubble dynamics in the field of a shock wave lithotripter.

This study concerns the radial dynamics of a bubble driven by pulsed ultrasound of the type generated during extracorporeal shock wave lithotripsy. In particular, a numerical model has been used to examine the sensitivity of the bubble oscillations to changes in both the amplitude of the driving field and the physical conditions of the fluid surrounding the bubble: viscosity, surface tension, temperature and gas content. It is shown that, at high negative pressures (p- = 10 MPa) as in lithotripsy, the timing and amplitude of bubble collapses have a considerably reduced sensitivity to the initial bubble size and all fluid parameters, except gas content, compared with those expected in lower-amplitude fields (p- = 0.2 MPa). This study indicates that, in the lithotripsy fields, the differences in the viscosity, surface tension and temperature of body fluids and the initial bubble size will have little effect on bubble dynamics compared with those expected in water.

An experimental shock wave generator for lithotripsy studies.

An electrohydraulic shock wave generator has been constructed to facilitate investigation of the acoustic field generated during extracorporeal shock wave lithotripsy (ESWL). Pressure waveforms at the generator aperture and the beam focus, measured using a PVDF needle hydrophone, are compared with those from a commercial lithotripter, the Dornier HM3.

A survey of the acoustic output of commercial extracorporeal shock wave lithotripters.

A survey of the pressures and intensities generated by different commercial extracorporeal shock wave (ESWL) lithotripters is reported. The lithotripters included in the survey are the Dornier HM3, Wolf Piezolith 2200 and 2300, Siemens Lithostar, Technomed Sonolith 2000 and 3000, and EDAP LT-01. Measurements were made using a polyvinylidene difluoride (PVdF) membrane hydrophone in water. The zero crossing frequency of one complete cycle of the focused pulse from ESWL equipment is in the range 0.1 to 1 MHz. Spatial-peak temporal-peak positive and negative pressures up to 114 MPa and 10 MPa, respectively, have been measured and the rise times of the positive pressure half cycle at maximum output settings are 30 ns or less. The mean spatial-peak temporal-average intensity of the lithotripters is 5.0 x 10(2) W m-2 when operated at a pulse repetition frequency of 1 Hz. The spatial-peak pulse-average intensity ranges from 6.6 x 10(7) to 1.24 x 10(9) W m-2. The estimated acoustic energy in a single pulse (at the focus) at the maximum output setting of the lithotripters varies from 2.0 x 10(-3) J to about 9.0 x 10(-2) J. The beam area in the focal plane varies by a factor of 100 on different lithotripters and the temporal-peak pressure at the position of the skin at the entry point of the beam by a factor of 30. Measurement problems associated with hydrophone damage and the uncertainties in the hydrophone calibration at high pressures are discussed and an estimate of the total uncertainty in the absolute measurements of the spatial-peak temporal-peak positive pressure is given as +/- 36%.

Acoustic cavitation generated by an extracorporeal shockwave lithotripter.

Evidence is presented of acoustic cavitation generated by a Dornier extracorporeal shockwave lithotripter. Using x-ray film, thin aluminum sheets, and relatively thick metal plates as targets, evidence of liquid jet impacts associated with cavitation bubble collapse was observed. The jet impact was violent enough to puncture thin foils and deform metal plates. Furthermore, numerous jet impacts were generated over a volume of greater than 200 cm3. It is likely that such violent cavitation will also occur in tissue, and observed biological effects (e.g. renal calculus disintegration and tissue trauma) may be related to cavitation damage.

Theoretical predictions of the acoustic pressure generated by a shock wave lithotripter.

A one-dimensional frequency domain model is used to predict the temporal peak acoustic pressures developed near the beam focus during extracorporeal shock wave lithotripsy (ESWL). The model includes consideration of finite amplitude effects, attenuation, diffraction and dispersion, and results are presented for the case of an electrohydraulic source with the beam geometry of the Dornier HM3 lithotripter. Propagation in castor oil, water and tissue is examined. The model predicts that nonlinear effects enhance the peak positive pressure (p+) at the beam focus in 6 cm of tissue in a Dornier type lithotripter by a factor of about 3 above that which would be expected for linear propagation. The negative peak pressure (p-), conversely, is predicted to be depressed by a factor of about 0.7 below the linear theory prediction. The model also indicates the occurrence of excess absorption due to shock formation. This is shown, for a Dornier HM3 type lithotripter, to cause a reduction in the peak positive pressure gain and a broadening of the focal depth as the output of the source is increased. A threshold aperture pressure is identified for a source with the same beam geometry as the Dornier HM3 below which shock formation does not occur. In this region the pressure gain increases and the focal depth narrows as the source output increases. These effects are characteristic of current commercial piezoelectric and electromagnetic lithotripsy fields.

Detection of acoustic emission from cavitation in tissue during clinical extracorporeal lithotripsy.

A 1-MHz focused hydrophone has been used to search for acoustic emission expected to arise from cavitation occurring in tissue during clinical extracorporeal shock-wave lithotripsy (ESWL). The hydrophone is acoustically coupled to the patient's skin and the focus directed at depth in tissue under ultrasound guidance. The measured amplitude-time variation of the acoustic emission from tissue near the shock-wave focus of the Storz Modulith SL20 lithotripter has been examined in four patients. There is evidence of increased amplitude acoustic emission at 1 MHz from regions within tissue that also appear hyperechoic in simultaneously acquired ultrasound images. The acoustic emission from these regions decays from an initial peak to the noise level in about 500 microseconds following each shock-wave pulse. Within this period, a second peak, often of higher amplitude than the first, is typically observed about 100 microseconds after the shockwave. The time between the initial and second peaks is found to increase with increasing shock-wave amplitude. The results are similar to those previously observed from cavitation induced by shock-wave exposure in water and indicate that the 1-MHz acoustic emission arises from inertial cavitation in tissue during clinical ESWL.

Pressure waveforms generated by a Dornier extra-corporeal shock-wave lithotripter.

Pressure waveforms in the acoustic field generated by a Dornier (HM3) shock-wave lithotripter have been measured using a bilaminar shielded PVDF membrane hydrophone in water. Using these waveforms, values of the peak-positive (p+) and peak-negative pressure (p-) at various positions in the field have been estimated. At the focus, p+ is 38.6 MPa (standard deviation = 9.0 MPa) and p- is 10.1 MPa (standard deviation = 1.0 MPa) at 20 kV discharge potential and an electrode separation in the range 1.3 to 2.4 mm. The peak-positive pressure is found to fall to 50% (-6 dB level) at about 60 mm either side of the focus on the major axis of the reflector and on a 10 mm radius circle around the focus in the focal plane. A shot-to-shot variation of +/- 25% in p+ is attributed to the inherent variability of the electrical discharge which may result in changes in the exact position and strength of the acoustic field. The results reported are considered to be more accurate than those of previous measurements due to the relatively flat frequency response of this type of hydrophone.

Acoustic emission and sonoluminescence due to cavitation at the beam focus of an electrohydraulic shock wave lithotripter.

The acoustic emission from cavitation in the field of an extracorporeal shock wave lithotripter has been studied using a lead zirconate titanate piezoceramic (PC4) hydrophone in the form of a 100-mm diameter focused bowl of 120-mm focal length. With this hydrophone directed at the beam focus of an electrohydraulic lithotripter radiating into water, it is possible to identify signals well above the noise level, at the 1-MHz resonance of the hydrophone, which originate at the beam focus. Light emission, attributed to sonoluminescence, is also shown to originate at the focal region of the lithotripter, and the signal obtained from a fast photomultiplier tube directed at the focus has similarities in structure and timing to the detected acoustic signals. The multiple shock emission resulting from a single discharge of an electrohydraulic source is shown to result in two separate bursts of cavitational activity separated by a period of 3-4 ms. The signal burst corresponding to the primary shock has a duration of about 600 microseconds with little noticeable structure. The signal burst associated with the secondary shock has a reproducible structure with two distinct peaks separated by about 200 microseconds depending on the shock amplitude. THe timing and structure of each burst is shown to be in reasonable agreement with the theoretical predictions made by Church (1989) based on the Gilmore model of bubble dynamics. In particular, it is shown that it is possible to obtain precise measurements of the time delay between the separate peaks within the signal burst detected following the secondary shock and this may, as predicted, provide a method of determining the size of bubbles remaining after the primary shock.

The cavitation threshold of human tissue exposed to 0.2-MHz pulsed ultrasound: preliminary measurements based on a study of clinical lithotripsy.

Evidence of acoustic cavitation was identified in the form of transient echoes in ultrasound B-scan images of patients receiving extracorporeal shock-wave lithotripsy treatment on a Storz Modulith SL20. This lithotripter generates 10-microseconds duration pulses with a centre frequency of 0.2 MHz at a pulse repetition frequency of 1 Hz. The visual appearance of B-scan images was examined in a total of 30 patients and a quantitative analysis of echogenicity changes was carried out in six cases involving lithotripsy treatment of stones in the renal pelvis. In these patients new echoes were identified in images unaffected by movement artefacts and were found to occur in perinephric fat and adjacent muscle and kidney tissue at positions close to the axis of the shock-wave field between 1 and 2 cm in advance of the indicated beam focus of the lithotripter. The echogenicity within each region increased significantly above the background level when the output of the lithotripter was increased above a threshold value. The acoustic pressures corresponding to this threshold were measured in water using a calibrated PVDF membrane hydrophone. After correction for attenuation in tissue the cavitation thresholds, in terms of the temporal peak negative pressure, are found to lie between 1.5 MPa and 3.5 MPa in all six cases. Interpretation of the measured values in terms of the likely threshold at the higher frequencies used in diagnostic ultrasound is considered using a theoretical model.