Whiteley Clinic

There is an urgent need for reference methodologies to assign SI traceable values to quality control (QC) materials for protein biomarkers to validate biochemical tests currently used in disease diagnosis and patient-specific therapeutics. Here we describe a novel methodology specifically developed for the SI traceable quantification of human serum ferritin light chain (FTL), an established biomarker for the diagnosis of iron-related disorders such as hemochromatosis. Natural and 34S isotopically enriched human FTL standards were recombinantly expressed using the HEK-293 mammalian cell system. Both standards were fully characterized for their total sulfur content, isotopic abundance, species distribution and primary sequence before using them for isotope dilution analysis (IDA). Treatment of serum spiked with FTL was optimized to selectively remove high abundant serum proteins without affecting significantly the integrity of the FTL. This was achieved by using methanol protein precipitation in combination with heat treatment and ultrafiltration. Complementary asymmetrical field-flow-fractionation (AF4) and anion-exchange high performance liquid chromatography (AE-HPLC) coupled to inductively coupled plasma mass spectrometry (ICP-MS) were used to monitor the impact of sample treatment on protein removal and FTL recovery. Both standards, natural and enriched, were used with the optimal sample treatment in a double species-specific isotope dilution analysis (SS-IDA) workflow for the determination of FTL in the WHO "4th International Standard for Ferritin" (NIBSC 19/118) resulting in a protein mass fraction of 11.0 with an expanded uncertainty (U, k = 2) of 1.0 μg mL-1 (RSU of 9.4%). The method was validated by standard addition experiments, and a full uncertainty budget was established. For the first time sulfur SS-IDA has been used to assign an SI traceable value to a relatively low abundance serum protein biomarker at supraphysiological concentrations in a WHO standard. This methodology will be invaluable for adding SI traceability to existing QC materials and for the certification of new biomarker reference materials.

Inadvertent intra-arterial injection of sclerosants is an uncommon adverse event of both ultrasound-guided and direct vision sclerotherapy. This complication can result in significant tissue or limb loss and significant long-term morbidity. To provide recommendations for diagnosis and immediate management of an unintentional intra-arterial injection of sclerosing agents. An international and multidisciplinary expert panel representing the endorsing societies and relevant specialities reviewed the published biomedical, scientific and legal literature and developed the consensus-based recommendations. Actual and suspected cases of an intra-arterial sclerosant injection should be immediately transferred to a facility with a vascular/interventional unit. Digital Subtraction Angiography (DSA) is the key investigation to confirm the diagnosis and help select the appropriate intra-arterial therapy for tissue ischaemia. Emergency endovascular intervention will be required to manage the risk of major limb ischaemia. This includes intra-arterial administration of vasodilators to reduce vasospasm, and anticoagulants and thrombolytic agents to mitigate thrombosis. Mechanical thrombectomy, other endovascular interventions and even open surgery may be required. Lumbar sympathetic block may be considered but has a high risk of bleeding. Systemic anti-inflammatory agents, anticoagulants, and platelet inhibitors and modifiers would complement the intra-arterial endovascular procedures. For risk of minor ischaemia, systemic oral anti-inflammatory agents, anticoagulants, vasodilators and antiplatelet treatments are recommended. Inadvertent intra-arterial injection is an adverse event of both ultrasound-guided and direct vision sclerotherapy. Medical practitioners performing sclerotherapy must ensure completion of a course of formal training (specialty or subspecialty training, or equivalent recognition) in the management of venous and lymphatic disorders (phlebology), and be personally proficient in the use of duplex ultrasound in vascular (both arterial and venous) applications, to diagnose and provide image guidance to venous procedure. Expertise in diagnosis and immediate management of an intra-arterial injection is essential for all practitioners performing sclerotherapy.

We describe a technique to use endovenous thermal ablation to treat a very superficial vein in the forearm, lying 1.0 – 1.4mm deep to the skin surface, without burning or damaging the overlying skin. The technique has been developed from our previous work in treating prominent vertical veins of the forehead, and subsequent in-vitro work showing the advantages or 1940nm over 1470nm in terms of less thermal spread in biological tissues at lower powers.

Background: Cellulite affects 80-90% of post-pubertal females and, although cosmetic, has proven adverse psychological effects. A new compression garment with patented “vari-pad” technology has been developed, aiming to stimulate lymphatic return from the buttocks and thighs. The primary aim of this small pilot study was to assess participant satisfaction after using this garment in the short term and secondarily, to look for any objective improvements.Methods: 18 female participants (mean 47.5y, range 26-60) completed the study. There were 2 weeks of “stabilisation”, 4 weeks of wearing the garment, and 2 weeks of further assessment. With the initial assessment, there were 9 visits for each participant. At each visit, weight, participant satisfaction (0-10), 3D images (Canfield, USA) and transcutaneous water content (LymphScanner, Delfin Technologies, Finland) were recorded.Results:There was no significant weight change in any of the participants during the trial period. After 4 weeks of wearing the garment there was a significant improvement in participant satisfaction of their cellulite (n=15, p=0.0036) with a mean improvement of 18.5%. 3D image analysis of dimple volume showed no significant change in buttock cellulite, a significant decrease in left thigh cellulite (n=17, p=0.0123), but not on the right (p=14, p=0.6890). There was a significant decrease of localised water (n=36, p=0.0041)Conclusion: The vari-padded compression garment produced a significant improvement in participant satisfaction after just 4 weeks of treatment. Objective measurements failed to show a significant difference in cellulite on the buttocks but showed a significant improvement in the thighs by analysis of both dimple volumes and reduced transcutaneous water measurements. Further study is suggested to demonstrate if longer timeframes for use of the apparel will lead to further significant improvement in the appearance of cellulite.

Objective To identify the effects of patient risk factors and pelvic venous reflux (PVR) patterns on treatment outcomes of Pelvic Vein Embolisation (PVE) for Pelvic Congestion Syndrome (PCS). MethodsWe performed a retrospective cohort review assessing population, intervention, comparison and outcomes (PICO) for women undergoing PVE for PCS January 2017–January 2021. We identified 190 patients who had completed both questionnaires and who had given consent for their information to be used for research (Median age 46, IQR 40-52) - 110.The distribution of pathological pelvic venous reflux found on transvaginal duplex ultrasound (TVDUS) was analysed for all patients. Pre- and post-procedure symptom burden scores were studied using a standardised questionnaire protocol. We used inferential univariate non-parametric statistics to describe our data.Results190 cases were reviewed; 62.6% (119/190) premenopausal, 11.1% (21/190) perimenopausal and 25.3% (48/190) postmenopausal; 10.1% (19/188) nulliparous. There was a statistically significant improvement in all symptoms and the appearance of varicosities on TVDUS post-PVE (p<0.05). The locations of veins requiring embolisation were analysed; 82.8% (154/186) required embolisation of at least one internal iliac vein tributary and ovarian vein embolisation. Age, parity, menopausal status and previous laparoscopy did not affect symptom improvement (p>0.05). No significant complications were identified.ConclusionsPVE is an effective treatment for pelvic pain due to PCS. Our results highlight the importance of internal iliac vein reflux as an important predictor in diagnosis and management. PCS should not be limited as a diagnosis for multiparous women of childbearing age as a significant proportion of patients who benefited from PVE were either nulliparous and/or postmenopausal.

Background:Sclerotherapy is used widely for the treatment of varicose veins. Little has been written on the mechanism of action of detergent sclerosants on the vein wall, and very little on osmotic sclerosants. We compared the damage profile inflicted by a detergent sclerosant (3% Sodium Tetradecyl Sulphate (3% STS)) to that of an osmotic sclerosant (70% dextrose) using explanted human veins. Methods:Ten varicose vein samples were harvested during routine phlebectomy surgery. Each sample was divided into three segments that were treated for two minutes with (1) normal saline (control), 3% STS, or 70% dextrose. Treated samples were incubated for 24 hours (37℃, 5% CO2), fixed in buffered formalin, paraffin embedded, and sectioned for staining with haematoxylin and eosin (H&E) and immunohistochemical (IHC) markers (caspase-3 (C3), smooth muscle actin (SMA), and CD31).Results:Both sclerosants produced cell death deep to the endothelium and into the tunica media of the vein. However, 3% STS exerted a significantly greater damage profile than 70% dextrose across all layers, destroying 75% more endothelial cells (P<0.0001) and 30-33% more smooth muscle cells across the tunica media (P<0.01). Efficacy of 70% dextrose in damaging peripheral cells of the tunica media was poor. Patterns of IHC reactivity were consistent with damage observed in H&E-stained sections. Minimal C3 reactivity was detected, and necrosis was the observed cell-death rather than apoptosis in all treated samples.Conclusion:Despite 3% STS showing more efficacy than 70% dextrose in extent and penetration of damage inflicted, both treatments were efficacious in inducing transmural cell death in this ex-vivo study. Therefore, 70% dextrose may be more appropriate for the ablation of thinner-walled veins, and 3% STS for thicker walled veins. In addition, the observation of necrotic cell death challenges the previously reported mechanism of apoptosis after sclerotherapy.

<p> </p> <p><strong>ABSTRACT</strong></p> <p><br></p> <p>Aims: Endovenous microwave ablation (EMWA) is a relatively new catheter-based endovenous thermoablation (EVTA) system to ablate incompetent truncal veins. Early results suggest that EMWA uses more power than endovenous laser ablation (EVLA) to get the same results. Therefore, we aimed to define the parameters for EMWA, which give the same tissue ablation as EVLA, using the previously validated porcine liver model.</p> <p><br></p> <p>Methods: EVLA (1470nm and 600micron radial fibre) treatments were performed at 6W, 8W and 10W, at each pullback speed of 6, 7, 8 and 9 s/cm, giving a range of Linear Endovenous Energy Densities (LEEDs) between 36 – 90 J/cm. We repeated each combination of power and pullback five times. Following a preliminary screening process to identify parameters that gave similar results, we used EMWA in the same model. Powers of 35-75W and pullback speeds of 4-9 s/cm were used (LEEDs 140-675 J/cm). Ablation tracts from both devices were analysed by two blinded observers, noting thermal spread and carbonisation. </p> <p><br></p> <p>Results: For each of the commonly used parameters for EVLA, we identified a range of power and pullback parameters for EMWA that produced similar tissue ablation in the porcine liver model. To keep the pullback speeds within the usual range, we used powers of 35-75W with EMWA, with mean EMWA LEEDs 3.9 - 5.8 times higher than EVLA LEEDs. We found the quicker the pullback speed, the higher the multiple of EMWA LEED we needed to get the same effect.</p> <p><br></p> <p>Conclusion: We have identified parameters for EMWA that gave equivalent tissue ablation in the validated porcine liver model to commonly used parameters and LEEDs for EVLA. As the power during EMWA is higher than EVLA, EVMA LEEDs are approximately 4-6 times higher than EVLA LEEDs to achieve the same thermal effect on the tissues.</p>

L’article présente la concordance et les accordages entre le travail processuel du psychologue en visite médiatisée et les fonctions maternelles assurées par l’assistant(e) familial(e) auprès de l’enfant accueilli. Dans une approche inter et transdisciplinaire garantie par un métacadre institutionnel sécurisant, le psychologue clinicien se trouve à l’articulation de ces instances complémentaires. Les enfants amenés à rencontrer leur(s) parent(s) en visite médiatisée se sont développés dans une famille aux liens pathologiques. Le clinicien vient assurer une fonction de moi-auxiliaire pour l’enfant, favorisant l’émergence d’une autonomisation psychique possible quant à sa relation avec ses parents. Au sein de l’accueil familial, l’enfant exprimera les modalités relationnelles qui sont siennes, trouvera chez l’assistant(e) familial(e) une nouvelle figure parentale d’identification et d’attachement. La situation de Clémence illustre les effets subjectivants de chacun des cadres d’intervention et par-delà le travail inter et transdisciplinaire mené.

A 48-year-old woman attended to discuss a dilemma. She had suffered a cardiac arrestimmediately following microsclerotherapy of leg telangiectasia with 0.3% aethoxysklerol.She had successful defibrillation and been transferred to hospital. In hospital, despitenormal cardiac tests, she was diagnosed as having idiopathic cardiac arrest. The exposureto aethoxysklerol was discounted by her cardiologists as a cause of her arrest. Followingthe hospital protocol, she was strongly advised to have an implantable defibrillator.Cardiac arrest and myocardial infarction are documented after aethoxysklerol injectionwith proposed mechanisms being anaphylaxis, direct cardiotoxicity or endothelin-1 release.Before consenting to an implantable defibrillator, which may have its own complications inthe long term, doctors and the patient need to be certain that this arrest was not due toa reaction to aethoxysklerol.

In 1978, the FDA Advisory Panel proposed both indoor and natural sunlight SPF testing methods but reverted to indoor testing only in 1993. Today's sunscreen sun protection and broad-spectrum claims are based on mandated clinical tests using solar simulators and in vitro spectrophotometers. This research evaluated the protection of 10 high-SPF (30-110), broad-spectrum sunscreen products, as well as 6 sun-protective fabrics against natural sunlight in Arequipa, Peru. Each of the 17 subjects was exposed to natural sunlight for 1 h and 59 min under clear skies, with temperatures and humidity similar to those in an indoor clinical laboratory. Test sites were photographed 16-24 h later. Four dermatologists evaluated the photographs for erythema and persistent pigment darkening (PPD). Perceptible sun-induced skin injury (sunburn and/or pigmentation) was detected at 97% of the sunscreen-protected scores. The most sun-sensitive subjects obtained the least erythema protection. The higher the SPF was, the higher the erythema protection, but the intensity of PPD was also higher. The 2 sunscreens using only FDA-approved sunscreen filters rated 30 SPF and 45+ SPF performed poorly: Eighty-one percent of the 136 scores were graded 1 minimal erythema dose or higher erythema, achieving, at a maximum, SPF of 5-7 in natural sunlight. Sun-protective fabrics tested provided excellent sun protection. The erythema and PPD observed through the sunscreens in less than 2 h are incongruous with the broad-spectrum, high-SPF sunscreen claims. Reapplying these sunscreens and staying in the sun longer, as stated on the product labels, would have subjected the subjects to even more UV exposure. High-SPF, broad-spectrum sunscreen claims based on indoor solar simulator testing do not agree with the natural sunlight protection test results.