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Biomedical subjects

C A Morton

Publications and source records attributed to C A Morton.

At least 19 recordsLinked to original sources
PubMed2002

Photodynamic therapy: applications in dermatology.

Photodynamic therapy (PDT) offers the potential of an effective new treatment in several areas of medicine. Topical photodynamic therapy is practical and non-invasive and is particularly suited to dermatological indications. A variety of pre-malignant and malignant skin lesions including Bowen's disease, actinic keratoses (AKs) and basal cell carcinoma (BCC) have been treated with success. The role of PDT in inflammatory dermatoses remains to be established. The currently available literature is reviewed.

Animals↗
PubMed2001

Treatment of multiple scalp basal cell carcinomas by photodynamic therapy.

The use of surface protoporphyrin IX fluorescence detection to delineate multiple superficial basal cell carcinomas on a patient's scalp is described. Photodynamic therapy (PDT) was subsequently performed with clearance of six and partial clearance of the remaining two tumours. The treated lesions have not recurred during 12 months of follow-up. The opportunity to combine diagnostic fluorescence detection with subsequent treatment by PDT offers an effective and practical management option. PDT is a tissue-sparing modality with low morbidity and good cosmesis, leading us to propose 5-aminolaevulinic acid-PDT for multiple superficial basal cell carcinomas of the scalp.

Aged↗
PubMed2001

Platelet-conditioned medium increases endothelial electrical resistance independently of cAMP/PKA and cGMP/PKG.

Platelets release a soluble factor into blood and conditioned medium (PCM) that decreases vascular endothelial permeability. The objective of this study was to determine the signal-transduction pathway that elicits this decrease in permeability. Permeability-decreasing activity of PCM was assessed by the real-time measurement of electrical resistance across cell monolayers derived from bovine pulmonary arteries and microvessels. Using a desensitization protocol with cAMP/protein kinase A (PKA)-enhancing agents and pharmacological inhibitors, we determined that the activity of PCM is independent of PKA and PKG. Genistein, an inhibitor of tyrosine kinases, prevented the increase in endothelial electrical resistance. Because lysophosphatidic acid (LPA) has been proposed to be responsible for this activity of PCM and is known to activate the G(i) protein, inhibitors of the G protein pertussis toxin and of the associated phosphatidylinositol 3-kinase (PI3K) wortmannin were used. Pertussis toxin and wortmannin caused a 10- to 15-min delay in the characteristic rise in electrical resistance induced by PCM. Inhibition of phosphorylation of extracellular signal-regulated kinase with the mitogen-activated kinase kinase inhibitors PD-98059 and U-0126 did not prevent the activity of PCM. Similar findings with regard to the cAMP protocols and inhibition of G(i) and PI3K were obtained for 1-oleoyl-LPA. These results demonstrate that PCM increases endothelial electrical resistance in vitro via a novel, signal transduction pathway independent of cAMP/PKA and cGMP/PKG. Furthermore, PCM rapidly activates a signaling pathway involving tyrosine phosphorylation, the G(i) protein, and PI3K.

Alkaloids↗
PubMed2001

Platelet lipid(s) bound to albumin increases endothelial electrical resistance: mimicked by LPA.

The objectives were to determine whether the permeability-decreasing activity of platelet-conditioned medium (PCM) is associated with a lipid bound to albumin and whether lysophosphatidic acid (LPA) is present in the PCM. A decrease in permeability was assessed by an increase in electrical resistance across endothelial cell monolayers derived from bovine pulmonary arteries and microvessels. The Sephacryl S-200 fraction of PCM that contained albumin, the albumin immunoprecipitate from the PCM, and the methanol extract from the albumin immunoprecipitate all increased endothelial electrical resistance. Increased electrical resistance induced by PCM was not abolished by boiling and was mimicked by 1-oleoyl-LPA and 1-palmitoyl-LPA. Analysis of a methanol-chloroform extract of one sample of PCM by electrospray mass spectrometry revealed many fatty acids, ceramide, diacylglycerol, phosphatidic acid, and palmitoyl-LPA, but analysis of a second sample of PCM and the methanol extract of its albumin immunoprecipitate revealed no LPA, only lipids. These findings indicate that a bioactive lipid(s), possibly LPA, released from platelets and subsequently bound to albumin forms an active complex that decreases endothelial permeability.

Albumins↗
PubMed2001

Photodynamic therapy for large or multiple patches of Bowen disease and basal cell carcinoma.

BACKGROUND: Photodynamic therapy (PDT) using topical delta-aminolevulinic acid (delta-ALA) is an effective treatment for Bowen disease and certain basal cell carcinomas (BCCs), but its place in clinical practice remains to be established. Patients with large and/or multiple lesions of Bowen disease or BCC can represent a considerable therapeutic challenge. We suggest that delta-ALA PDT may be of particular benefit in such patients. OBSERVATION: In an open study, 35 (88%) of 40 large patches of Bowen disease, all with a maximum diameter greater than 20 mm, cleared following 1 to 3 treatments of delta-ALA PDT, although 4 patches recurred within 12 months. delta-Aminolevulinic acid PDT was also used to treat 40 large BCCs, with an identical 88% initial clearance (after 1-3 treatments), with 4 recurrences within 34 months (range, 12-60 months). In 10 further patients with multiple (> or =3) patches of Bowen disease, 44 (98%) of 45 patches cleared following delta-ALA PDT, although 4 lesions recurred over 12 months. In 3 patients with multiple BCCs, PDT cleared 52 (90%) of 58 lesions, with 2 recurrences during 41 months (range, 12-52 months). Treatments were well tolerated, with only 5 patients with solitary large lesions requiring local anesthesia. CONCLUSIONS: delta-Aminolevulinic acid PDT is an effective tissue-sparing modality achieving good cosmesis. We propose that delta-ALA PDT be considered as a first-line therapy for large and/or multiple areas of Bowen disease and superficial BCCs.

Adult↗
PubMed2001

Topical photodynamic therapy in dermatology.

ALA-PDT is an effective therapy for non-hyperkeratotic facial actinic keratoses, Bowen's disease and superficial basal cell carcinoma. Additional applications remain at the experimental stage, with early potential suggested in acne and refractory warts. PDT offers the advantages of being non-invasive, well tolerated in slow healing sites, and tissue sparing, leaving the skin surrounding the tumour intact and functional. ALA-PDT may be particularly useful for large superficial tumours and for lesions in anatomical sites where disfigurement from conventional therapies may be a particular risk. The development of powerful filtered non-laser sources, along with the topical application of photosensitizer, makes ALA-PDT a more easily accessible therapy.

Administration, Topical↗
PubMed2000

Comparison of red and green light in the treatment of Bowen's disease by photodynamic therapy.

BACKGROUND: A variety of protocols exist for the treatment of Bowen's disease by photodynamic therapy (PDT) using topical 5-aminolaevulinic acid (5-ALA). OBJECTIVE: To determine the optimal wavelength (red or green light) for this treatment. METHODS: A randomized comparison study of ALA-PDT using red (630 +/- 15 nm) or green (540 +/- 15 nm) light in the treatment of Bowen's disease. RESULTS: The initial clearance rate for lesions treated by red light was 94% (30 of 32) in comparison with 72% (21 of 29) for those lesions receiving green light (P = 0.002). Over the following 12 months, there were two recurrences in the red light group and seven in the green light group reducing the clearance rates to 88% and 48%, respectively. The frequency and severity of pain experienced were similar between the two treatment groups. No hyperthermia, nor significant difference in lesional temperatures, was observed between the wavelengths studied. CONCLUSION: Green light is less effective than red light, at a theoretically equivalent dose, in the treatment of Bowen's disease by topical ALA-PDT.

Aged↗
PubMed2000

Oxidant-increased endothelial permeability: prevention with phosphodiesterase inhibition vs. cAMP production.

The present objective was to determine whether hydrogen peroxide (H(2)O(2)) increases transvascular albumin clearance and lung weight in an isolated rat lung and whether posttreatment with cAMP-enhancing agents can prevent these increases. Transvascular albumin clearance was assessed by (125)I-labeled albumin clearance ((125)I-albumin flux/perfusate concentration of (125)I-albumin) at a given fluid filtration. Nonlinear regression analysis of transvascular albumin clearance vs. fluid filtration yielded values for the permeability-surface area product (PS) and the reflection coefficient (sigma). H(2)O(2) decreased sigma from a control value of 0.93 to 0.38, did not change PS, and increased lung weight. Posttreatment with isoproterenol, a beta(2)-adrenergic-receptor agonist, reduced the H(2)O(2)-induced decrease in sigma to 0.65 and augmented the increase in lung weight. Posttreatment with CP-80633, a phosphodiesterase 4 inhibitor, further reduced the H(2)O(2)-induced decrease in sigma to 0.79 and blocked the rise in lung weight. In the presence of isoproterenol or CP-80633, H(2)O(2) increased PS. Therefore, H(2)O(2) increased the convective and diffusive clearances of albumin across an intact pulmonary vasculature. Furthermore, inhibition of cAMP metabolism more effectively attenuated the H(2)O(2)-induced increases in convective albumin clearance and lung weight as compared with stimulation of cAMP production.

Adrenergic beta-Agonists↗
PubMed1999

Guidelines for management of Bowen's disease. British Association of Dermatologists.

These guidelines for management of Bowen's disease have been prepared for dermatologists on behalf of the British Association of Dermatologists. They present evidence-based guidance for treatment, with identification of the strength of evidence available at the time of preparation of the guidelines, and a brief overview of epidemiological aspects, diagnosis and investigation.

Antimetabolites↗
PubMed1998

Clinical accuracy of the diagnosis of cutaneous malignant melanoma.

Diagnostic accuracy for melanoma was determined in a dedicated pigmented lesion clinic. We assessed the impact of duration of experience in dermatology and also the relationship between tumour thickness and accuracy of clinical diagnosis. We reviewed the histopathology request forms and reports for all biopsies generated by the Pigmented Lesion Clinic, Western Infirmary, Glasgow during 1992-94 inclusive. The clinic is staffed by two consultants, one senior registrar and one registrar. Diagnostic accuracy, index of suspicion, sensitivity, specificity and positive predictive value were calculated for the clinic overall, and for each grade of staff. One hundred and sixty-three lesions were diagnosed clinically as melanoma. A histopathological diagnosis of melanoma was made for 128 lesions during this period, 113 of which had been correctly diagnosed before surgery. The diagnostic accuracy for two dermatologists each with > 10 years experience in dermatology was 80%, with sensitivity of 91% and positive predictive value of 86%. Diagnostic accuracy rates for two senior registrars (each with 3-5 years experience) and six registrars (each with 1-2 years experience) were 62% and 56%, respectively. Thin and intermediate thickness melanomas generated the greatest inaccuracy irrespective of clinical experience, although registrars failed to recognize melanoma three times more often than the other groups. We report the diagnostic accuracy for melanoma by trained dermatologists to be higher than previously reported. In comparison with trainees, > 10 years experience in dermatology and exposure to more than 10 melanomas per year appears to be associated with greater diagnostic accuracy. Knowledge of the current clinical diagnostic accuracy at varying levels of experience is essential if the impact of training is to be evaluated. As pigmented lesions of virtually all types can be treated within dermatology departments, dermatologists are the appropriate first point of referral for suspected early melanoma.

Clinical Competence↗
PubMed1996

Pruritus and skin hydration during dialysis.

BACKGROUND: Dry skin is frequently observed in uraemic patients and a link with the common complaint of pruritus has been suggested. Objective data on skin dryness in haemodialysed patients is sparse and equivocal. No such information exists for the many patients now receiving peritoneal dialysis. We assessed the prevalence and severity of both pruritus and skin dryness in a uraemic population receiving maintenance dialysis. METHODS: Forty-eight haemodialysis and 24 peritoneal dialysis patients were examined and skin dryness assessed by clinical grading and measurement of stratum corneum hydration using a corneometer. Forty age- and sex-matched controls were also assessed. Several biochemical parameters with possible relevance to pruritus were measured. Regular emollient therapy was prescribed to pruritic dialysis patients and efficacy assessed. RESULTS: Dialysis patients overall had clinically drier skin than controls, especially the peritoneal dialysis group. Stratum corneum hydration levels were significantly reduced in the peritoneal dialysis (P < 0.004), but not the haemodialysis, population. Twenty-seven per cent of haemodialysed and 54% of peritoneal dialysis patients complained of pruritus. Pruritic patients in each dialysis group had significantly lower hydration than non-pruritic patients (P < 0.05). Regular emollient use in pruritic patients produced a marked reduction in severity of pruritus, abolishing the symptom in nine of 21 patients treated. CONCLUSION: Reduced stratum corneum hydration correlates with pruritus in patients on maintenance haemodialysis and peritoneal dialysis, and may be alleviated by simple emollient therapy.

Adolescent↗
PubMed1996

Thrombin increases fluid flux in isolated rat lungs by a hemodynamic and not a permeability mechanism.

Alpha-Thrombin increases endothelial protein permeability in vitro and induces weight gain in the isolated perfused lung. The objectives of this study were to determine whether thrombin increases endothelial permeability of the isolated perfused rat lung and whether a change in permeability or hemodynamics mediates the gain in lung weight. Endothelial protein permeability was assessed by regression analysis of 125I-labeled albumin clearance vs. fluid flux to determine the permeability-surface area product (PS) and the reflection coefficient (sigma). Thrombin (5 x 10(-8) or 5 x 10(-7) M) did not alter protein permeability from the control values of PS and sigma. Thrombin caused an overall increase in transvascular fluid flux, as depicted by a gain in lung weight. Pulmonary arterial and capillary pressures and arterial and venous resistances increased by 10 min after thrombin injection, and lung weight decreased due to arterial constriction. From 10 to 50 min, pressures and resistances decreased, but capillary pressure and venous resistance decreased to a lesser extent and, as a result, lung weight increased. Pretreatment with BQ-123, an endothelin-receptor antagonist, attenuated the sustained increases in pressures and resistances and the rate of lung weight gain. Indomethacin, a cyclooxygenase inhibitor, had no effect. These findings indicate that the increase in lung weight induced by thrombin results from an elevation of capillary pressure mediated, in part, by endothelin and is not due to an increase in endothelial protein permeability of the isolated perfused rat lung.

Animals↗