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Biomedical subjects

P S Mortimer

Publications and source records attributed to P S Mortimer.

At least 55 records · Page 3Linked to original sources

Spectrophotometric assessment of pigmented skin lesions: methods and feature selection for evaluation of diagnostic performance.

This study documents the optical reflectance characteristics of pigmented skin lesions and evaluates their potential for improving the differential diagnosis of malignant melanoma from benign pigmented skin lesions. Optical reflectance spectra in the wavelength range 320-1100 nm were obtained from 121 lesions already selected by expert dermatologists as suspicious of malignancy. Characteristic differences in spectra from benign and malignant lesions were studied. Feature extraction showed significant differences between lesion groups classified by histology. Seven of the most relevant features were used in the discriminant analysis of reflectance spectra from 15 melanoma and 32 compound naevi which resulted in a sensitivity of 100% and specificity of 84.4% when compared with histology. This simple objective technique appears to perform as well as the expert dermatologist and may improve the diagnostic accuracy of non-specialists such as trainees and GPs. Further prospective clinical study of reflectance spectrophotometry in a larger patient group is now required.

Adolescent↗

Implications of the lymphatic system in CVI-associated edema.

Lymph drainage is intimately linked with venous drainage in health and disease. Evidence exists to support the view that lymphatics frequently fail in venous disease, particularly in its advanced stages. The implications of this are to increase the risk of infection and the amount of edema, events which can only further the morbidity of venous disease.

Bacterial Infections↗

Increased dermal lymphatic density in the human leg compared with the forearm.

During orthostasis, capillary filtration pressure is higher in the leg than in the arm due to the effect of gravity. We investigated the possibility that the lymphatic network in leg skin might be adapted to cope with a greater fluid load. The dermal lymphatics of the forearm and lower leg were studied in white-skinned and brown-skinned men using fluorescence video microscopy. From video print lymphangiograms the following were determined: lymphatic length density at a series of radii from the centre of the lymphangiogram (LDr); maximum lymphatic density (LDmax); total length of lymphatic vessel (LL); maximum spread of lymphatic vessel; number and size of lymphatic rings (continuous circuits of vessel); and vessel diameter. There were no differences between the two racial types, but clear differences between the arm and leg. In the leg, mean (+/- SD) peak LDr (25.13 +/- 5.65 cm-1), LDmax (32.95 +/- 6.89 cm-1), LL (40.17 +/- 27.42 cm), and spread (1.39 +/- 0.08 cm) were all significantly higher than in the arm (18.03 +/- 5.48 cm-1, 23.91 +/- 7.21 cm-1, 11.76 +/- 5.47 cm, and 1.00 +/- 0.05 cm respectively, P </= 0.001). In the region of maximum lymphatic density there were 2.4 times more rings in the leg than in the arm, ring size being similar. Vessel image diameters were 89.6 +/- 26.3 micron (leg) and 94.8 +/- 10.9 micron (arm). Leg skin thus has a denser and more extensive lymphatic network than arm skin. This supports the hypothesis that lymph transport capacity in the leg is enhanced to compensate for a greater gravitational fluid loading.

Adult↗

Systemic candidiasis with candida vasculitis due to Candida kruzei in a patient with acute myeloid leukaemia.

Candida kruzei-related systemic infections are increasing in frequency, particularly in patients receiving prophylaxis with antifungal triazoles. A Caucasian male with newly diagnosed acute myeloid leukaemia (AML M1) developed severe and persistent fever associated with a micropustular eruption scattered over the trunk and limbs during induction chemotherapy. Blood cultures grew Candida kruzei, and biopsies of the skin lesions revealed a candida vasculitis. He responded to high doses of liposomal amphotericin B and was discharged well from hospital.

Acute Disease↗

An in vivo study of the microlymphatics in psoriasis using fluorescence microlymphography.

Angiogenesis is a recognized event in psoriasis. Previous ultrastructural studies have demonstrated lymphatic capillaries extending high into the dermal papillae. Using the novel method of fluorescence microlymphography which permits visualization of upper dermal initial lymphatics in vivo we tested the hypothesis that lymphangiogenesis exists within plaque psoriasis. Six patients underwent fluorescence microlymphography with fluorescein isothiocyanate-dextran administered intracutaneously within a psoriatic plaque on the leg. Stereological analysis permitted quantification of the lymphatic network opacified both within (lesional) and without (perilesional) the plaque. Results showed a greater spread of tracer from the depot into perilesional skin than into the plaque (P < 0.006). The mean length of lymphatics per unit area at increasing distance from the centre of the depot was also increased for the perilesional skin, 10.5 +/- 1.9/cm2 (mean +/- SEM), compared with lesional skin, 3.06 +/- 0.8/cm (P < 0.001). The cumulative lymphatic length was also greater in perilesional, 22 +/- 7.3 cm2, compared with lesional skin, 3.6 +/- 0.3 cm (P < 0.006). Fluorescence microlymphography has proved to be an effective in vivo technique for the assessment of the dermal microlymphatics in psoriasis. Stereology provided quantitative analysis of the lymphatic network visualized. Overall, there is a greater network of lymphatics in perilesional compared with lesional skin in patients with plaque psoriasis. This finding is at odds with the accepted view that the lymphatic dermal vessels are increased within the psoriatic plaque.

Adult↗

Quantitative study of capillary density in the skin of the foot in peripheral vascular disease.

BACKGROUND: The aim of this study was to investigate possible differences in capillary density of the skin of the foot between normal subjects and patients with peripheral vascular disease. METHODS: Using in vivo video microscopy, a method was developed to measure the average capillary density (ACD) of the skin of the foot and toes. In a cross-sectional observational study, 21 patients with intermittent claudication and 23 patients with rest pain or ischaemic ulceration were compared with 19 age- and sex-matched controls. RESULTS: Mean(s.e.m). values of ACD of the foot were 33.7(1.9) and 34.4(1.7) per mm2 in the right and left sides respectively for controls, 31.2(1.8) per mm2 (P not significant) and 31.9(2.6) per mm2 (P not significant) in the symptomatic and contralateral sides respectively for patients with claudication, and 22.0(1.8) per mm2 (P < 0.001) and 24.3(1.7) per mm2 (P < 0.001) in the symptomatic and contralateral sides respectively for patients with rest pain or ulceration. CONCLUSION: Capillary density of the skin of the foot is significantly reduced in patients with arterial ulceration compared with that in patients with claudication and healthy subjects.

Adult↗

Visualization of dermal blood vessels--capillaroscopy.

Intravital capillaroscopy is the only noninvasive method available that visualizes directly the nutritional dermal capillaries. It can determine (in vivo): capillary morphology, including size, shape and tortuosity; capillary density; intercapillary distance; volume fraction (the percentage of skin occupied by microvessels); and changes in red cell velocity within capillaries. When capillaroscopy is performed using a video recording system, this permits real-time imaging of the cutaneous capillaries with retrospective analysis of capillary dynamics. Furthermore, when fluorescent dyes are injected intravenously, plasma-perfused capillaries are delineated allowing the calculation of several perfusion indices. Intravital capillaroscopy therefore permits the assessment of static as well as dynamic aspects of the skin microcirculation.

Aging↗

Control of cutaneous blood vessels in psoriatic plaques.

The aim of this study was to compare local blood flow in psoriatic plaques before and after provocations known to alter cutaneous vascular resistance, in order to determine whether plaque hyperemia is caused by a failure of normal vascular control mechanisms. Cutaneous blood flow was recorded using a laser Doppler flowmeter over plaque skin (plaque site) and clinically normal skin (nonplaque site) on the opposite arm, at least 5 cm away from the nearest plaque. It is important to note that most of the laser Doppler signal comes from the subpapillary plexus of the skin and only a small portion (2%-10%) is produced by capillary blood flow. In the psoriatic plaques the basal flux was between nine and 13 times greater than nonplaque skin. The biologic zero (a signal independent of perfusion, which also persists after complete proximal arterial occlusion) was also significantly greater at plaque sites compared with nonplaque sites. Sympathetic and local vasoconstriction in psoriatic skin was shown to be intact and responses to vasodilator tests were likewise intact, i.e., there was no failure of response to normal vascular control mechanisms, albeit some quantitative differences. Tests of vasodilatation indicated that, although basal flux is high in plaque compared with nonplaque skin, arterioles supplying plaque skin can dilate further, i.e., lesional arterioles are not normally maximally dilated but have a basal constrictor tone. Interestingly, the red cell flux at maximum dilatation in nonplaque skin is less than even the basal flux in plaque skin. This means that in plaque skin either there are more arterioles than in nonplaque skin, or there is chronic, structural widening of the existing arterioles in plaque skin.

Adult↗

In vivo microscopic study of microcirculatory perfusion of the skin of the foot in peripheral vascular disease.

OBJECTIVES: the aim of this study was to determine the proportion of perfused capillaries in the skin of the foot in patients with peripheral vascular disease, and compare it with that in normal subjects. DESIGN: experimental study comparing capillary perfusion in nine patients with severe peripheral vascular disease (group 2) with seven age- and sex-matched control subjects (group 1). MATERIALS AND METHODS: using in vivo video microscopy, a method was developed to measure the ratio of perfused to total capillaries, by comparing the numbers of corresponding capillaries before and after intravenous injection of sodium fluorescein. RESULTS: the mean percentage ratio of perfused to total capillaries was 54.7% (range 41-87%, standard deviation 16.5) in group 1, and 86.0% (range 62-100%, standard deviation 13.2) in group 2 (p<0.001, t-test). CONCLUSION: a significantly higher proportion of capillaries is perfused in the skin of the foot of patients with severe peripheral vascular disease than in that of normal subjects. This is of important pathophysiological significance and may have clinical implications with regard to the role of pharmacological intervention in severe limb ischaemia.

Adult↗

A gene for lymphedema-distichiasis maps to 16q24.3.

Lymphedema-distichiasis (LD) is a dominantly inherited syndrome with onset of lymphedema at or just after puberty. Most affected individuals have distichiasis-fine hairs arising inappropriately from the eyelid meibomian glands-which is evident from birth. A study of three families with LD has shown linkage to chromosome 16q24.3, and subsequent analysis of the region for recombinant genes places the locus between D16S422 and D16S3074, a distance of approximately 16 cM. Possible candidate genes in this interval include the N-proteinase for type 3 collagen, PCOLN3; the metalloprotease PRSM1; and the cell matrix-adhesion regulator, CMAR.

Chromosomes, Human, Pair 16↗

Comparison of microvascular filtration in human arms with and without postmastectomy oedema.

Oedema is caused by impaired lymphatic drainage and/or increased microvascular filtration. To assess a postulated role for the latter in postmastectomy oedema, filtration was studied in the forearms of 14 healthy subjects and 22 patients with chronic, unilateral arm oedema caused by surgical and radiological treatment for breast cancer. A new non-contact optical device (the Perometer) and a conventional mercury strain gauge were used simultaneously to record forearm swelling rates caused by microvascular filtration during applied venous congestion. Filtration rate (FR) per 100 ml tissue was measured over 10-15 min at a venous pressure of 30 cmH2O, a pressure reached in the dependent forearm (FR30), and then at 60 cmH2O (FR60). Apparent filtration capacity of 100 ml soft tissue (CFCa) was calculated from FR60 - FR30/30, after adjustment for bone volume. The Perometer and strain gauge gave similar results in normal and oedematous arms. Mean CFCa in healthy subjects was (3.8+/-0.4) x 10(-3) ml (100 ml)-1 cmH2O-1 min-1, close to literature values. In the patients, FR30 was 47 % lower in the oedematous forearm than in the opposite, unaffected forearm (P = 0.04). FR60 showed a similar trend but did not reach significance (P = 0.15). The values of CFCa of (2.2+/-0.5) x 10(-3) ml (100 ml)-1 cmH2O-1 min-1 in the oedematous arm and (2.8+/-0.5) x 10(-3) ml (100 ml)-1 cmH2O-1 min-1 in the unaffected arm were not significantly different (P = 0.47). When differences in arm volume on the two sides were taken into account, the total fluid load on the lymphatic system of the oedematous forearm was (411.0+/-82.2) x 10(-3) ml min-1 at 30 cmH2O and (1168+/-235.6) x 10(-3) ml min-1 at 60 cmH2O, similar to the normal side, namely (503.7+/-109.3) 10(-3) ml min-1 and (1063+/-152.0) x 10(-3) ml min-1, respectively (P >/= 0.50). The filtration capacity of the entire oedematous forearm (CFCa scaled up by total soft tissue volume), (25.4+/-6.2) x 10(-3) ml cmH2O-1 min-1, was not significantly greater than that of the normal forearm, (18.3+/-2.6) x 10(-3) ml cmH2O-1 min-1 (P = 0.40). The results indicate that no major change occurs in the microvascular hydraulic permeability-area product of the forearm, or in the total filtration load on the lymph drainage system during dependency, in the arm with postmastectomy oedema compared with the normal arm. This argues against a significant haemodynamic contribution to postmastectomy oedema.

Aged↗

Basal cell carcinoma--an in-vivo model of human tumour microcirculation?

The role of angiogenesis in tumour growth and metastasis is well established. However, investigations of tumour microcirculation to date have used either biopsy material from human tumours, or animal models in vivo. We have studied the tumour microcirculation in vivo in human skin cancers using video-microscopy to examine 12 basal cell carcinomas (BCCs) on the head and neck of 11 patients, and compared the vessels with those seen in the peri-lesional skin, and in normal control skin on the opposite side of the body. The vessels seen within the BCCs were markedly abnormal qualitatively, forming bizarre, disorganized patterns. Quantitative analysis revealed that the mean diameter (+/-standard deviation) of the largest vessel was significantly greater within the BCC (0.086+/-0.029 mm) than that in the control skin (0.034+/-0.012 mm) (P<0.001). The area fraction, a measure of the area of tissue occupied by vessels, was increased highly significantly within the BCCs (0.158+/-0.038) compared with both peri-lesional skin (0.029+/-0.012) and control skin (0.027+/-0.010) (P<0.001). Length density, the length of blood vessel per unit area of tissue, was also highly significantly greater within the lesion (210.22+/-66.05 cm(-1)) compared to peri-lesional (27.10+/-15.67 cm(-1)) and control skin (28.27+/-15.81 cm(-1)) (P<0.001). This is the first study to have demonstrated that BCCs possess a distinct tumour microcirculation which can be observed directly, and assessed quantitatively. Prospective studies of tumour progression, possibly after intervention with angiogenesis inhibitors, are possible.

Aged↗

Structural skin capillary rarefaction in essential hypertension.

A reduction in the density of capillaries (rarefaction) is known to occur in many tissues in patients with essential hypertension. This rarefaction may play a role in increasing peripheral resistance. However, the mechanism underlying this capillary rarefaction is not understood. The aim of this study was to assess the extent of structural versus functional capillary rarefaction in the skin of dorsum of fingers in essential hypertension. The capillary microcirculation was examined with video microscopy before and after maximizing the number of perfused capillaries by venous congestion. The study group comprised 17 patients with essential hypertension (mean supine blood pressure, 155/96 mm Hg) and 17 closely matched normotensive controls (mean blood pressure, 127/77 mm Hg). We used intravital video microscopy with an epi-illuminated microscope to examine the skin of the dorsum of left middle phalanx before and after venous congestion at 60 mm Hg for 2 minutes. A significantly lower mean capillary density occurred at baseline in hypertensive subjects versus normotensive subjects. With venous occlusion, capillary density increased significantly in both groups; however, maximal capillary density remained significantly lower in the hypertensive subjects than in the normotensive subjects. The study strongly suggests that much of the reduction in capillary density in the hypertensive subjects is caused by structural (anatomic) absence of capillaries rather than functional nonperfusion.

Adult↗

Rarefaction of skin capillaries in borderline essential hypertension suggests an early structural abnormality.

We recently showed that rarefaction of skin capillaries in the dorsum of the fingers of patients with essential hypertension is due to the structural (anatomic) absence of capillaries rather than functional nonperfusion. It is not known whether this rarefaction is primary (ie, antedates the onset of hypertension) or secondary (ie, as a consequence of sustained and prolonged elevation of blood pressure [BP]). The aim of the present investigation was to study skin capillary density in a group of patients with mild borderline hypertension to assess whether rarefaction antedates the onset of sustained elevation of BP. The study group included 18 patients with mild borderline hypertension (mean supine BP, 136/83 mm Hg), 32 normotensive controls (mean BP, 126/77 mm Hg), and 45 patients with established essential hypertension (mean BP, 156/98 mm Hg). The skin of the dorsum of the fingers was examined by intravital capillary videomicroscopy before and after venous congestion at 60 mm Hg for 2 minutes. Patients with borderline essential hypertension had the lowest resting capillary density when compared with normotensive controls and patients with established hypertension. Maximal capillary density with venous congestion in the borderline group remained the lowest. The study confirmed that patients with borderline essential hypertension have skin capillary densities that are equally low as or even lower than patients with established hypertension. Both groups had significantly lower capillary densities than normal controls. One explanation for the results is that capillary rarefaction may be due to an early structural abnormality in essential hypertension.

Analysis of Variance↗

Maximization of skin capillaries during intravital video-microscopy in essential hypertension: comparison between venous congestion, reactive hyperaemia and core heat load tests.

Intravital capillary video-microscopy is a dynamic method for studying skin capillaries. The technique of direct intravital microscopy (without dyes) depends on the presence of red blood cells inside capillaries for their identification. The aim of the present study was to compare different techniques to try to establish the best method for maximizing the number of visible perfused capillaries during intravital capillary microscopy. We compared the effects of venous congestion with those of post-occlusive reactive hyperaemia (Study 1). We also investigated venous congestion followed first by post-occlusive reactive hyperaemia and then by a core heat load test (Study 2). Finally we investigated venous congestion followed by post-occlusive reactive hyperaemia combined with venous congestion (Study 3). In Study 1, capillary density increased with venous congestion from a baseline value of 74+/-2 (mean+/-S.E.M.) per field to 82+/-3 per field (P<0.0001; analysis of variance). With reactive hyperaemia, there was an apparent decrease in visible capillary density to 69+/-2 per field. In Study 2, baseline capillary density was 69+/-4 per field, and this increased significantly with venous congestion to 74+/-4 per field (P=0.01). With both reactive hyperaemia and core heat load, the apparent density was 62+/-4 per field. In Study 3 the baseline density was 70+/-2 per field, and this increased significantly with venous congestion to 80+/-3 per field (P<0.0001). With reactive hyperaemia combined with venous congestion, the density was 81+/-3 per field (P=0.328 compared with venous congestion alone). The results show that venous congestion at 60 mmHg for 2 min is the most effective method for visualization of the maximal number of perfused skin capillaries during intravital video-microscopy.

Adult↗