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Biomedical subjects

P S Mortimer

Publications and source records attributed to P S Mortimer.

At least 37 records · Page 2Linked to original sources

Impairment of lymph drainage in subfascial compartment of forearm in breast cancer-related lymphedema.

BACKGROUND: In arm lymphedema secondary to axillary surgery and radiotherapy (breast cancer-related lymphedema), the swelling is largely epifascial and lymph flow per unit epifascial volume is impaired. The subfascial muscle compartment is not measurably swollen despite the iatrogenic damage to its axillary drainage pathway, but this could be due to its low compliance. Our aim was to test the hypothesis that subfascial lymph drainage too is impaired. METHODS AND RESULTS: Quantitative lymphoscintigraphy was used to measure the removal rate constant (local lymph flow per unit distribution volume) for technetium-99m-human immunoglobulin G injected intramuscularly in the forearms of nine women with unilateral lymphedema. The removal rate constant was on average 31% lower in the ipsilateral swollen forearm than in the contralateral forearm (swollen arm: -0.096+/-0.041% min(-1), contralateral arm: -0.138+/-0.037% min(-1); mean+/-SD, p = 0.037). The decrease in subfascial rate constant correlated strongly with increase in arm volume (r = -0.88, p = 0.002), even though the swelling is mainly epifascial. There was no convincing evidence of dermal backflow. CONCLUSIONS: Lymph flow in the subfascial muscle compartment is decreased in breast cancer-related lymphedema. The correlation between impairment of subfascial drainage and epifascial arm swelling could be because both depend on the severity of axillary damage, or because loss of function in subfascial lymphatics impairs drainage from the epifascial to the subfascial system.

Aged↗

Lymphoedema: an underestimated health problem.

BACKGROUND: Lymphoedema/chronic oedema is an important cause of morbidity in the population, but little is known of its epidemiology and impact on patients or health services. AIM: To determine the magnitude of the problem of chronic oedema in the community, and the likely impact of oedema on use of health resources, employment and patient's quality of life. DESIGN: Questionnaire-based survey. METHODS: Health professionals from dedicated lymphoedema services, specific out-patient clinics, hospital wards and community services (GP clinics and district nurses) were contacted to provide information on patients from within South West London Community Trust. A subset of the identified patients was interviewed. RESULTS: Within the catchment area, 823 patients had chronic oedema (crude prevalence 1.33/1000). Prevalence increased with age (5.4/1000 in those aged > 65 years), and was higher in women (2.15 vs. 0.47/1000). Only 529 (64%) were receiving treatment, despite two specialist lymphoedema clinics within the catchment area. Of 228 patients interviewed, 78% had oedema lasting > 1 year. Over the previous year, 64/218 (29%) had had an acute infection in the affected area, 17/64 (27%) being admitted for intravenous antibiotics. Mean length of stay for this condition was 12 days, estimated mean cost pound 2300. Oedema caused time off work in > 80%, and affected employment status in 9%. Quality of life was below normal, with 50% experiencing pain or discomfort from their oedema. DISCUSSION: Chronic oedema is a common problem in the community with at least 100 000 patients suffering in the UK alone, a problem poorly recognized by health professionals. Lymphoedema arising for reasons other than cancer treatment is much more prevalent than generally perceived, yet resources for treatment are mainly cancer-based, leading to inequalities of care.

Adolescent↗

Rarefaction of skin capillaries in normotensive offspring of individuals with essential hypertension.

BACKGROUND: Rarefaction of skin capillaries in people with intermittent borderline essential hypertension suggests a primary or an early abnormality that may antedate the onset of sustained hypertension. OBJECTIVE: To compare skin capillary density in subjects with and without a family history of essential hypertension. SUBJECTS: 21 normotensive individuals, one or both of whose parents had essential hypertension (mean age 39.3 years; blood pressure 124/79 mm Hg); 21 normotensive controls with no family history of hypertension (age 46.3 years; blood pressure 124/78 mm Hg). METHODS: The skin of the dorsum of the fingers was examined by intravital capillary microscopy before and after venous congestion at 60 mm Hg for two minutes. RESULTS: By analysis of variance, both baseline and maximum skin capillary density were lower in subjects with a family history of essential hypertension than in those with no family history (baseline: 67 v 79 capillaries per field, p = 0.008; maximum: 74 v 93 capillaries per field, p < 0.0005). CONCLUSIONS: Capillary rarefaction in essential hypertension may occur before the increase in blood pressure and could, at least in part, reflect a primary rather than a secondary abnormality.

Adult↗

Evidence for dermal angiogenesis in breast cancer related lymphedema demonstrated using dual-site fluorescence angiography.

OBJECTIVE: To determine whether the skin expansion associated with breast cancer related lymphedema (BCRL) reduces microvessel density or causes a compensatory angiogenesis. METHODS: Dermal microvessel density was measured by simultaneous fluorescence video angiography in the ipsilateral and contralateral forearms of 25 patients treated for breast cancer, 12 with BCRL (excess volume 30 +/- 20%) and 13 without. RESULTS: Microvessel density was as high in the swollen arm (27.2 +/- 7.2 mm(-2)) as in the contralateral arm (24.2 +/- 6.2 mm(-2)) despite a 16 +/- 12% increase in local circumference. Total microvessels in a 1-mm annulus of skin was 30% greater in the swollen arm (752 +/- 211) than the contralateral arm (578 +/- 157; p = 0.005, t-test). Microvessel density was similar in each arm in control patients (ipsilateral 24.1 +/- 6.2 mm(-2), contralateral 26.1 +/- 8.8 mm(-2)). CONCLUSIONS: The number of microvessels increased in the expanded skin to maintain microvessel density at a normal level. Therefore, angiogenesis occurs during chronic limb swelling. The control group results indicate that angiogenesis is not caused by the cancer treatment.

Aged↗

A randomized controlled crossover study of manual lymphatic drainage therapy in women with breast cancer-related lymphoedema.

This paper describes a randomized controlled crossover study examining the effects of manual lymphatic drainage (MLD) in 31 women with breast cancer-related lymphoedema. MLD is a type of massage used in combination with skin care, support/compression therapy and exercise in the management of lymphoedema. A modified version of MLD, referred to as simple lymphatic drainage (SLD), is commonly taught as a self-help measure. There has been limited research into the efficacy of MLD and SLD. The study reported here explores the effects of MLD and SLD on a range of outcome measures. The findings demonstrate that MLD significantly reduces excess limb volume (difference, d=71, 95% CI=16-126, P=0.013) and reduced dermal thickness in the upper arm (d=0.15, 95% CI=0.12-0.29, P =0.03). Quality of life, in terms of emotional function (d=7.2, 95% CI=2.3-12.1, P=0.006), dyspnoea (d=-4.6, 95% CI=-9.1 to -0.15, P=0.04) and sleep disturbance (d =-9.2, 95% CI=-17.4 to -1.0, P=0.03), and a number of altered sensations, such as pain and heaviness, were also significantly improved by MLD. The study provides evidence to support the use of MLD in women with breast cancer-related lymphoedema. The limitations of the study are outlined and future areas for study are highlighted.

Breast Neoplasms↗

Lymphatics in leprosy: relationship to elastic fibres and observations following intra-lesional injections of colloidal carbon.

An investigation of skin lymphatics in leprosy has been undertaken. Examination of 62 skin biopsies from 31 patients with various classifications of leprosy has revealed dilated initial lymphatics within granulomas of lepromatous leprosy, but no significant abnormalities in non-lepromatous disease or in non-granulomatous skin. Colloidal carbon injected intra-lesionally failed to appear within granulomas, but could be seen in lymphatics in non-granulomatous dermis. Elastic fibres were also absent within granulomas. AFB were clearly identified within endothelial cells of initial lymphatics. We suggest lymphatic malfunction may be compartmental, existing only within the granulomas and not in the surrounding normal appearing dermis.

Carbon↗

Immunohistochemical evaluation of psoriatic plaques following selective photothermolysis of the superficial capillaries.

BACKGROUND: Elongated and tortuous capillary loops are distinctive features of psoriasis. The significance of these microvascular changes in the pathogenesis of plaques, however, remains unclear. OBJECTIVES: To determine what part the expanded superficial capillary bed plays in the pathogenesis of clinical lesions by selectively thermolysing psoriatic capillaries with a pulsed dye laser (PDL). METHODS: Cutaneous lesions were biopsied before and after treatment and sections assessed by standard immunohistochemical techniques for changes in known indicators of angiogenesis, including endothelial surface area, endothelial cell proliferation and endothelial cell expression of adhesion molecules. We also measured lymphocytic infiltration and epidermal thickness, and quantified the presence of a marker of keratinocyte proliferation before and after treatment. RESULTS: The effect of the PDL was limited to the superficial capillary bed, with no changes in the microvessels (including venules and arterioles) of the upper reticular dermis. Although there was significant clinical improvement in plaques after treatment (P = 0.02), complete clearance of lesions was not achieved. Thermolysis of psoriatic capillaries caused a reduction in both endothelial surface area (P < 0.01) and endothelial cell proliferation in the superficial dermis (P = 0.04). Endothelial expression of surface adhesion molecules (integrins and E-selectin) important in angiogenesis was not, however, altered by treatment. The CD4+ and CD8+ T-cell infiltrate was significantly reduced in the superficial papillary dermis (P = 0.02 and P = 0.04, respectively), but not in the epidermis or upper reticular dermis. Laser treatment significantly reduced epidermal thickness (P = 0.001), but did not alter epidermal keratinocyte proliferation (P = 0.2). CONCLUSIONS: The results demonstrate that dermal capillary changes alone are unlikely to be causal in psoriasis. They indicate that the expanded psoriatic capillaries may be important in facilitating the access of activated T cells to the skin and in maintaining the psoriatic plaque. These results do not refute the consensus view that plaque formation may be mediated by the release of growth factors/cytokines from activated epidermal T cells/keratinocytes.

Adult↗

Differences in lymph drainage between swollen and non-swollen regions in arms with breast-cancer-related lymphoedema.

Recent research indicates that the pathophysiology of breast-cancer-related lymphoedema (BCRL) is more complex than simple axillary lymphatic obstruction as a result of the cancer treatment. Uneven distribution of swelling (involvement of the mid-arm region is common, but the hand is often spared) is puzzling. Our aim was to test the hypothesis that local differences in lymphatic drainage contribute to the regionality of the oedema. Using lymphoscintigraphy, we measured the removal rate constant, k (representing local lymph flow per unit distribution volume, VD), for 99mTc-labelled human immunoglobulin G in the oedematous proximal forearm, and in the hand (finger web) in women in whom the hand was unaffected. Tracer was injected subcutaneously, and the depot plus the rest of the arm was monitored with a gamma-radiation camera for up to 6 h. VD was assessed from image width. Contralateral arms served as controls. k was 25% lower in oedematous forearm tissue than in the control arm (BCRL, -0.070+/-0.026% x min(-1); control, -0.093+/-0.028% x min(-1); mean+/-S.D.; P=0.012) and VD was greater. In the non-oedematous hand of the BCRL arm, k was 18% higher than in the control hand (BCRL, -0.110+/-0.027% x min(-1); control, -0.095+/-0.028% x min(-1); P=0.057) and 59% higher than forearm k on the BCRL side (P=0.0014). VD did not differ between the hands. Images of the BCRL arm following hand injection showed diffuse activity in the superficial tissues, sometimes extending almost to the shoulder. A possible interpretation is that the hand is spared in some patients because local lymph flow is increased and diverted along collateral dermal routes. The results support the hypothesis that regional differences in surviving lymphatic function contribute to the distribution of swelling.

Aged↗

A randomized, controlled, parallel-group clinical trial comparing multilayer bandaging followed by hosiery versus hosiery alone in the treatment of patients with lymphedema of the limb.

BACKGROUND: Multilayered, low stretch bandages (MLB) combined with exercises, skin care, and manual lymphatic drainage therapy are recommended as an intensive phase of treatment for lymphedema patients. The relative efficacy of each of the components of this comprehensive treatment program have not been determined. This study aimed to compare the effect of multilayer bandaging as an initial phase of lymphedema treatment followed by elastic hosiery versus hosiery alone. METHODS: A randomized, controlled, parallel-group trial was undertaken in the setting of the Lymphedema Clinic, The Royal Marsden Hospital, London. Ninety women with unilateral lymphedema (of the upper or lower limbs) were enrolled in the study. The interventions consisted of 18 days of multilayer bandaging followed by elastic hosiery or hosiery alone, each for a total period of 24 weeks. The main outcome measure was the percentage reduction in excess limb volume. RESULTS: The reduction in limb volume by MLB followed by hosiery was approximately double that from hosiery alone and was sustained over the 24-week period. The mean overall percentage reduction at 24 weeks was 31% (n = 32) for MLB versus 15.8% (n = 46) for hosiery alone, for a mean difference of 15. 2% (95% confidence interval, 6.2-24.2) (P = 0.001). CONCLUSIONS: Multilayer bandaging as an initial phase of treatment for lymphedema patients, followed by hosiery, achieves greater and more sustained limb volume reduction than hosiery alone.

Adult↗

Distichiasis-lymphoedema: clinical features, venous function and lymphoscintigraphy.

Distichiasis-lymphoedema is a rare variant of the genetically determined lymphoedemas; distichiasis is the abnormal development of the meibomian glands causing aberrant growth of eyelashes. However, a better understanding of this clinically distinct subgroup may provide useful information on the genetic inheritance of all types of lymphoedema. This report provides phenotype data on a very large family with distichiasis-lymphoedema. Lymphoscintigraphy and light reflection rheography (venous function) were undertaken to identify the phenotype more clearly. As a result of lymphoscintigraphy several subjects were reclassified phenotypically (unaffected or affected) with implications for genetic linkage studies. Associated congenital abnormalities were found and venous abnormalities were almost always present in affected limbs. A dominant inheritance with incomplete penetrance was confirmed.

Adolescent↗

Differentiation of common benign pigmented skin lesions from melanoma by high-resolution ultrasound.

BACKGROUND: There are potential clinical benefits if non-invasive methods can be used to diagnose or exclude melanoma. OBJECTIVES: We investigated high-resolution ultrasound (HRU) as a potential non-invasive diagnostic aid for pigmented skin lesions. METHODS: Using a 20-MHz ultrasound B-scan imaging system interfaced to a computer, we assessed acoustic shadowing and entry echo line enhancement (EEE) for 29 basal cell papillomas (BCPs) and 25 melanomas. Acoustic shadowing was estimated by the dermal echogenicity ratio (DER), comparing mean echogenicity below the lesion with that of adjacent dermis. Histological features were scored independently. RESULTS: DER < 3 correctly distinguished melanoma from BCP with 100% sensitivity and 79% specificity. Specificity increased to 93% if the presence of EEE was included as a discriminator. Shadowing correlated most significantly with histological extent of hyperkeratosis (P < 0.0001). Consequently, this method falsely identified non-keratotic acanthotic BCP (n = 3) as melanoma. Highly significant differences between benign naevi (n = 15) and melanomas (n = 24) were found. The SD of retrolesional echogenicity was higher for naevi than melanomas (P < 0.0001), but such an analysis was poorly specific for the diagnosis of melanoma (30%). CONCLUSIONS: Overall, HRU has considerable potential as a high-performance screening tool to assist in the discrimination between BCP, but not benign naevi, and melanoma. In particular, it may be possible to exclude melanoma with 100% certainty in the differentiation of BCP from melanoma.

Diagnosis, Differential↗

Classification of reflectance spectra from pigmented skin lesions, a comparison of multivariate discriminant analysis and artificial neural networks.

Successful treatment of skin cancer, especially melanoma, depends on early detection, but diagnostic accuracy, even by experts, can be as low as 56% so there is an urgent need for a simple, accurate, non-invasive diagnostic tool. In this paper we have compared the performance of an artificial neural network (ANN) and multivariate discriminant analysis (MDA) for the classification of optical reflectance spectra (320 to 1100 nm) from malignant melanoma and benign naevi. The ANN was significantly better than MDA, especially when a larger data set was used, where the classification accuracy was 86.7% for ANN and 72.0% for MDA (p < 0.001). ANN was better at learning new cases than MDA for this particular classification task. This study has confirmed that the convenience of ANNs could lead to the medical community and patients benefiting from the improved diagnostic performance which can be achieved by objective measurement of pigmented skin lesions using spectrophotometry.

Algorithms↗