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Biomedical subjects

A Watkinson

Publications and source records attributed to A Watkinson.

At least 19 recordsLinked to original sources
PubMed2005

Inter- and intralaboratory variation of in vitro diffusion cell measurements: an international multicenter study using quasi-standardized methods and materials.

In vitro measurements of skin absorption are an increasingly important aspect of regulatory studies, product support claims, and formulation screening. However, such measurements are significantly affected by skin variability. The purpose of this study was to determine inter- and intralaboratory variation in diffusion cell measurements caused by factors other than skin. This was attained through the use of an artificial (silicone rubber) rate-limiting membrane and the provision of materials including a standard penetrant, methyl paraben (MP), and a minimally prescriptive protocol to each of the 18 participating laboratories. "Standardized" calculations of MP flux were determined from the data submitted by each laboratory by applying a predefined mathematical model. This was deemed necessary to eliminate any interlaboratory variation caused by different methods of flux calculations. Average fluxes of MP calculated and reported by each laboratory (60 +/- 27 microg cm(-2) h(-1), n = 25, range 27-101) were in agreement with the standardized calculations of MP flux (60 +/- 21 microg cm(-2) h(-1), range 19-120). The coefficient of variation between laboratories was approximately 35% and was manifest as a fourfold difference between the lowest and highest average flux values and a sixfold difference between the lowest and highest individual flux values. Intralaboratory variation was lower, averaging 10% for five individuals using the same equipment within a single laboratory. Further studies should be performed to clarify the exact components responsible for nonskin-related variability in diffusion cell measurements. It is clear that further developments of in vitro methodologies for measuring skin absorption are required.

Clinical Laboratory Techniques↗
PubMed2005

Acute traumatic aortic rupture: a comparison of surgical and stent-graft repair.

OBJECTIVE: The study's objective was to comparatively evaluate surgery and stent-graft repair of acute or subacute traumatic aortic rupture. METHODS: A total of 76 patients (14-76 years old; mean, 37 years; male/female ratio, 63/11) with a traumatic aortic injury were admitted to our hospital between 1981 and 2003. Six patients died within 1 to 9 days of another associated severe traumatic lesion. The 70 remaining patients were divided according to the type of rupture repair. In group 1, 35 patients were treated surgically: 28 with immediate repair and 7 with delayed repair (average time interval 66 days, 5-257 days). In group 2, 29 patients were treated with stent grafting of the aortic isthmus. In group 3, 6 patients with minor aortic lesions were treated medically with a close follow-up. RESULTS: In the 28 patients treated surgically in the emergency department, the mortality and paraplegia rates were 21% and 7%, respectively. No death or paraplegia was observed in the group with delayed surgical repair. With stent grafting, complete exclusion of the pseudoaneurysmal sac was observed in all patients. Except for 1 iliac rupture treated during the same procedure, there was no major morbidity or mortality during the mean follow-up of 46 months (13-90 months). No major complication was observed in group 3. CONCLUSIONS: In stable rupture of the aorta, initial conservative treatment is safe and allows management of the major associated lesions. Stent grafting of the aortic isthmus is a valuable therapeutic alternative to surgical repair, especially in patients considered high risk for conventional thoracotomy.

Accidents, Traffic↗
PubMed2003

Histamine induced responses are attenuated by a cannabinoid receptor agonist in human skin.

OBJECTIVE AND DESIGN: In the present study we examined the effects of the cannabinoid receptor agonist HU210 on histamine-evoked somatosensory and vascular responses in humans. SUBJECTS: Two sets of experiments were performed, in which twelve (Study 1, iontophoresis) and six participants (Study 2, microdialysis) were recruited. TREATMENT: HU210 was administered peripherally by skin patch (50 mM) or dermal microdialysis (5 mM), whereas histamine was applied by iontophoresis (50 microAmps) or dermal microdialysis (5 microM). METHODS: Skin blood flow was monitored by laser Doppler, widespread flare reaction was evaluated planimetrically, extravasation of plasma proteins was measured in the dialysate and perceived itch was recorded using a visual analogue scale. Data were evaluated by analysis of variance. RESULTS: Experimentally induced itch was significantly reduced by peripheral administration of HU210 (p < 0.05). Additionally, skin blood flow and neurogenic mediated flare responses were attenuated (p < 0.003 and p < 0.03, respectively), whereas protein extravasation due to histamine was enhanced by co-administration of HU210, as investigated by dermal microdialysis. CONCLUSIONS: In humans peripheral administration of a cannabinoid receptor agonist attenuates histamine-induced itch. The observation that protein extravasation was not decreased demonstrates that the alleviation of itch is not due to an anti-histaminergic property of HU210. The reduced neurogenic flare reaction indicates an attenuated antidromic nerve fibre activation and neuropeptide release.

Administration, Topical↗
PubMed2003

Focal nodular hyperplasia-like areas in cirrhosis.

AIMS: Focal nodular hyperplasia-like lesions have rarely been described in cirrhotic livers. We describe five cases of such lesions. METHODS AND RESULTS: Between 1998 and 2001, 146 liver transplants were performed at the Royal Free Hospital for cirrhosis of the liver. Nodular lesions identified in the livers removed at transplantation were defined histologically according to the International Working Party classification (Hepatology 1995; 22; 983). They were present in 63 of these livers, as follows: 36 dysplastic nodules, 121 macroregenerative nodules, and 71 hepatocellular carcinomas. In five patients, an additional 12 nodules (size range 4-23 mm, median 10.5 mm) showed histological features suggestive of focal nodular hyperplasia including mildly inflamed vascular fibrous septa, and ductular proliferation. Pre-transplantation imaging showed features suspicious for hepatocellular carcinoma, in three of these lesions (12, 23 and 23 mm diameter) from two different patients. These lesions were histologically indistinguishable from focal nodular hyperplasia occurring in non-cirrhotic livers, with fibrous scars and septa which contained vascular and ductular structures. CONCLUSIONS: It is important to recognize that these lesions may occur in the context of cirrhosis and that they should be considered in the differential diagnosis with hepatocellular carcinoma, dysplastic nodules and macroregenerative nodules.

Adult↗
PubMed2003

Treatment of iatrogenic aortic dissection by percutaneous stent placement.

During elective cardiac catheterization via the right femoral artery, difficulty was encountered advancing the guidewire beyond the aortic arch and the procedure abandoned. The patient later developed back pain and hypotension. A contrast-enhanced spiral computed tomography scan confirmed aortic dissection, extending from an entry point in the external iliac artery to the arch. We hypothesized that the entry site was responsible for filling the dissection in the thoraco-abdominal component. A stent was placed in the iliac artery, occluding the entry point. This is the first report of aortic dissection, a rare complication of angiography, managed by percutaneous stenting of the entry point.

Aortic Dissection↗
PubMed2002

Radiological palliation of malignant colonic obstruction.

PURPOSE: To evaluate the efficacy of colorectal stenting in the palliation of irresectable malignant colonic obstruction. MATERIALS AND METHODS: Fifteen patients underwent colorectal stenting for irresectable colonic malignancy. Sixteen stents were placed successfully in 13 patients. Two stent insertions, one a proximal transverse colon lesion, were unsuccessful. Twelve patients (80%) had clinical or radiological features of imminent obstruction. Three patients were completely obstructed. Eighty-six percent of lesions were within the rectosigmoid colon. RESULTS: Technical and clinical success was 88%. Early, minor complications occurred in two patients (13%). Late complications included migration (13%) and ingrowth (19%). The median survival was 2 months (0.5-12 months). CONCLUSION: Stenting should be considered as definitive treatment in the context of an inoperable malignant stricture of the colon. It has low morbidity and a high technical and clinical success rate and avoids emergency defunctioning surgery in high-risk patients.

Adult↗
PubMed2002

Renovascular hypertension. Radiographic methods.

In recent years the choice of radiographic methods available in the investigation of renovascular hypertension has increased significantly. It can be difficult for the clinician to decide which patients will benefit from screening and which modality to choose. This article seeks to address some of these issues. The role of the plain radiograph and intravenous urogram are briefly mentioned. Doppler ultrasound, MR, CT and conventional arteriography are discussed in detail. Their advantages and pitfalls are reviewed. In our institution ultrasound to document renal size and gadolinium-enhanced 3-D MRA are our recommended first-line investigations unless MRA is contraindicated. Digital subtraction arteriography is reserved for the small subgroup in which MRA fails to obtain an answer, for whatever reason.

Angiography↗
PubMed2001

Broad specificity alkaline proteases efficiently reduce the visual scaling associated with soap-induced xerosis.

In xerotic skin, the proteolysis of desmosomes is reduced leading to the accumulation of corneocytes on the surface of the skin. The effect of proteases applied topically to soap-induced xerotic skin was evaluated using a five-point visual scale. The visual scaling associated with soap-induced xerosis could be ameliorated by the topical application of exogenous protease. Bovine pancreatic chymotrypsin, papain, and a bacterial protease from Bacillus licheniformis were all capable of facilitating the reduction in visual scaling in a short time. Alcalase and Optimase, both broad specificity alkaline bacterial proteases, were the most weight-efficient at delivering this clinical effect. The reduction in scaling could be achieved either by occluded application of an aqueous enzyme solution or by a two-step unoccluded application first of an aqueous enzyme solution followed by a commercial moisturizer. Morphological and immunological analysis of bacterial enzyme-treated skin revealed that topically applied protease specifically induced the degradation of the desmosomes thereby promoting desquamation. These results indicate that topical application of protease can significantly and rapidly reduce the visual scaling associated with soap-induced xerosis by promoting desmosome degradation within the corneocyte clumps.

Administration, Topical↗
PubMed2001

Water modulation of stratum corneum chymotryptic enzyme activity and desquamation.

Exposure to a dry environment leads to depletion of water from the peripheral stratum corneum layers in a process dependent on the relative humidity (RH) and the intrinsic properties of the tissue. We hypothesized that by modulating the water content of the stratum corneum in the surface layers, RH effects the rate of desquamation by modulating the activity of the desquamatory enzymes, and specifically stratum corneum chymotryptic enzyme (SCCE). Using a novel air interface in vitro desquamatory model, we demonstrated RH-dependent corneocyte release with desquamatory rates decreasing below 80% RH. Application of 10% glycerol or a glycerol-containing moisturizing lotion further increased desquamation, even in humid conditions, demonstrating that water was the rate-limiting factor in the final stages of desquamation. Furthermore, even in humid conditions desquamation was sub-maximal. In situ stratum corneum SCCE activity showed a dependence on RH: activity was significantly higher at 100% than at 44% RH. Further increases in SCCE activity were induced by applying a 10% glycerol solution. Since SCCE, a water-requiring enzyme, must function in the water-depleted outer stratum corneum, we sought to determine whether this enzyme has a tolerance to lowered water activity. Using concentrated sucrose solutions to lower water activity, we analysed the activity of recombinant SCCE and compared it to that of trypsin and chymotrypsin. SCCE activity demonstrated a tolerance to water restriction, and this may be an adaptation to maintain enzyme activity even within the water-depleted stratum corneum intercellular space. Overall these findings support the concept that in the upper stratum corneum, RH modulates desquamation by its effect upon SCCE activity, and possibly other desquamatory hydrolases. In addition, SCCE may be adapted to function in the water-restricted stratum corneum intercellular space.

Animals↗
PubMed2001

Vascular malformations of the gastrointestinal tract.

Vascular malformations of the gastrointestinal tract may be diagnosed at any age. They may present with bleeding, anaemia, or if they form a mass lesion, with intussusception. Many lesions remain asymptomatic. In a minority of patients there are well-defined genetic conditions present, such as hereditary haemorrhagic telangiectasia. In others, particularly the angiodysplastic lesions that occur in the caecum in elderly patients, the lesions appear to be degenerative. Vascular malformations may affect any section of the gastrointestinal tract, and in some patients there are vascular anomalies elsewhere, particularly in the skin. Diagnosis is usually based on recognition endoscopically, or at angiography. Symptomatic lesions that are discrete and localized respond well to local treatment with laser or heat coagulation or sclerotherapy. Mass lesions, diffuse lesions and severe bleeding may require surgery.

Aged↗
PubMed2001

Successful recanalization of portal vein thrombosis before liver transplantation using transjugular intrahepatic portosystemic shunt.

A frequent complication in patients with end-stage liver disease is portal vein thrombosis (PVT). Although PVT is not considered an absolute contraindication to orthotopic liver transplantation (OLT), more complex surgery is required and patients have more postoperative complications and greater mortality rates. We describe 2 patients who experienced complete PVT either while waiting for liver transplantation or during the workup, resulting in acute deterioration of liver function. Recanalization of the portal vein was successfully performed in both patients using transjugular intrahepatic portosystemic stent shunt (TIPS), and patency was maintained by the addition of anticoagulation therapy. They subsequently underwent successful OLTs and remain well. In conclusion, we believe that TIPS placement can be performed safely in patients with recent PVT, ensuring the patency of the portal vein until OLT.

Budd-Chiari Syndrome↗
PubMed2001

Catheter angiography and angioplasty in patients with scleroderma.

The objectives of this study were (i) to identify patterns of angiographic disease in scleroderma patients with and without other vascular risk factors and (ii) to define patients with scleroderma in whom angiography and angioplasty is useful. The records of 26 patients with scleroderma who underwent angiography and angioplasty over an 8-year period were reviewed. Angiographic disease patterns were assessed using a modified Brewster classification. Angiography of the upper limb demonstrated distal disease alone in 86% of patients, both with and without other vascular risk factors such as smoking. In the lower limb there was a highly significant association between the presence of other vascular risk factors and macrovascular disease potentially amenable to angioplasty, and conversely between the absence of other vascular risk factors and distal disease in the lower limb. Good early but poor late clinical results were achieved in three of five patients who underwent angioplasty. Angiography of the upper limb is likely to demonstrate distal disease alone, and angiography and angioplasty of the lower limb may be useful only if other vascular risk factors are present.

Adult↗