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Biomedical subjects

P S Mortimer

Publications and source records attributed to P S Mortimer.

At least 73 records · Page 4Linked to original sources

The pathophysiology of lymphedema.

BACKGROUND: All edemas result from an imbalance between capillary filtration and tissue (lymph) drainage. This basic approach was adopted to investigate mechanisms for chronic arm edema following breast carcinoma treatment. METHODS: A review of causes of lymphedema is presented plus the traditional pathophysiology of breast carcinoma related lymphedema (postmastectomy edema; PME). A summary of recent research that explored capillary filtration as a surrogate for lymph flow in the steady state is presented. RESULTS: A reduced interstitial protein concentration (relative to plasma) argues against lymphatic obstruction. Evidence exists that total arm blood flow (in some patients) and vascular bed size are increased in PME. CONCLUSIONS: The primary insult to the axillary lymphatic system by surgery and radiotherapy presumably is the root cause of PME; however, there is strong evidence to suggest that hemodynamic factors are contributory to the chronic swelling.

Breast Neoplasms↗

Forearm blood flow measured by venous occlusion plethysmography in healthy subjects and in women with postmastectomy oedema.

A chronic swelling of the arm may develop following damage to axillary lymph vessels during breast cancer treatment. Certain unusual pathophysiological features of postmastectomy oedema indicate that factors additional to lymphatic damage are important. One factor postulated previously is a haemodynamic abnormality. Forearm blood flow was therefore measured by venous occlusion plethysmography using both a conventional mercury strain gauge and a newer optical volumeter (Perometer). The latter was initially assessed in healthy subjects. When forearm blood flow was measured using the two methods simultaneously, the strain gauge and Perometer did not differ significantly for healthy or oedematous arms. Dominant and non-dominant arm blood flow in healthy subjects was similar but with greater variation between sides with the Perometer. Using the strain gauge, blood flow in the oedematous arm (2.51 +/- 1.33 ml/100 ml per min) was significantly lower than in the opposite unaffected arm (3.77 +/- 2.29 ml/100 ml per min; p = 0.026). The Perometer results showed a similar but nonsignificant trend (p = 0.105). Taking into account the greater limb volume on the affected side, total forearm blood flow was essentially the same in each arm (unaffected: 40.72 +/- 28.70 micromilligrams/min; oedematous: 41.78 +/- 22.11 ml/min). The reduced blood flow per unit volume of arm was therefore likely to be due to a simple 'dilution' effect of the increase in volume. The results indicate that it is unlikely that raised blood flow contributes to oedema formation, contrary to the haemodynamic concept.

Adult↗

Quantification of the initial lymphatic network in normal human forearm skin using fluorescence microlymphography and stereological methods.

Fluorescence microlymphography enables the visualization of the initial lymphatic network in human dermis in vivo. In order to determine which objective, measurable parameters are likely to be of value in future studies, microlymphangiograms were obtained from normal forearm skin of eight men and nine women of a range of ages and analyzed stereologically to calculate: (1) lymphatic length density at a specified radial distance, r, from the site of injection of the fluorescent dye (LDr, cm-1); (2) maximum lymphatic density (LDmax, cm-1); (3) total length of filled lymphatic (LL, cm); (4) maximum radial spread of vessels (mm). There was no significant difference between the right and left arms for peak LDr, LDmax, LL, or spread. Mean values (+/-SD) for the right and left arms combined (n = 24) were 13.34 +/- 7.61 cm-1; 19.31 +/- 8.96 cm-1; 12.04 +/- 10.04 cm; and 7.58 +/- 3.30 mm, respectively. Unexpectedly, three of the four parameters were significantly lower in women compared to men. For women LDmax was 30% lower than for men (P = 0.04), LL was 59% lower (P = 0.032), and spread was 39% lower (P = 0.007). Peak LDr did not differ significantly. Stereological analysis of fluorescent microlymphangiograms enables quantification of the dermal initial lymphatic network and hence the objective study of the influence of gender, age, and disease (including treatment interventions).

Adult↗

Therapy approaches for lymphedema.

Lymphedema, regardless of etiology, is essentially incurable but different therapy approaches exist which serve to contain swelling. The objectives of treatment are to reduce swelling, restore shape, and prevent inflammatory episodes, eg, recurrent cellulitis. There are essentially three main approaches to lymphedema treatment: physical therapy, drug therapy, and surgery. Any edema arises from an imbalance between capillary filtration and lymph drainage. The principle of physical therapy is to a) reduce excessive capillary filtration and b) improve drainage of interstitial fluid and macromolecules from congested regions to normally draining lymph node sites. This is achieved through a combination of compression, exercise, and if possible, massage. Control of recurrent inflammatory episodes can only be achieved through diabetic type skin care, a reduction in swelling, and if necessary, prophylactic antibiotics. Drug therapy comprises diuretics or the coumarin/flavonoid group of drugs. The use of diuretics for pure lymphedema is physiologically unsound but may be of use in edema of mixed origin and in palliative (cancer) circumstances. Coumarin/flavonoids have been shown to reduce swelling in all types of lymphedema. Surgery is indicated at an early stage for facial swelling, where vision is compromised, or genital lymphedema, where genitourinary function is affected. Otherwise, reducing operations should only be performed when alternative therapy has failed. Microsurgery for certain forms of lymphedema continues to be evaluated.

Anticoagulants↗

Chronic arm edema following breast cancer treatment.

Chronic edema of the arm (postmastectomy edema, PME) is a common and incurable complication of breast cancer treatment, often developing without warning months or years later. Although the original cause of PME is damage to axillary lymph drainage routes by surgery and radiotherapy, many observations suggest that additional factors are involved. Recent attention has focused on the Starling forces in the skin and subcutis in PME. An important finding was that the protein concentration, and hence colloid osmotic pressure, of the subcutaneous interstitial fluid of the PMF arm is unexpectedly lower than in the unaffected arm, correlating negatively with the degree of swelling. There are several possible explanations for this, such as a rise in capillary filtration rate, or interstitial proteolysis. A systemic component to PME is suggested by the finding of a lower plasma protein concentration in affected women compared with a matched postmastectomy group without swelling. A recent study using intra-vital capillaroscopy has indicated that angiogenesis occurs in the skin in PME, and an increased capillary surface area for filtration could result in an increased fluid load on a compromised lymph drainage system. Further elucidation of the pathophysiological processes in PME, in particular the adjustments to Starling forces, will enable more effective therapy of this distressing condition.

Arm↗

Validation of an optoelectronic limb volumeter (Perometer).

The Perometer, a device designed for the measurement of limb volume, has been rigorously assessed by comparison with other methods. Differences in the volume of geometric shapes and limbs determined by the Perometer and a tape measure/meter rule (i.e., Perometer minus direct measurement) were -0.8 to 2.4% (cylinders), -4.6% (truncated cone), -3.3% (mannequin limbs), 6.1% (normal human arms) and 6.8% (lymphedema arms). The larger differences were likely to be due to deviation from circular or elliptical cross-section (Perometer or tape method) and compression of the arm (tape method). Errors arising from incorrect positioning within the measuring frame were generally small, but large errors occurred when a cylinder was partially rotated within the frame (i.e., no longer perpendicular to the light beams). The Perometer was highly reproducible, each measurement taking only a few seconds. When recording the change in volume with time of a segment of arm during venous occlusion (blood flow measurement by venous occlusion plethysmography) using the Perometer plus a mercury strain gauge, between-method differences for individual blood flow recordings were apparent. The source of these differences is discussed. However, using the average of a number of blood flow recordings the Perometer and the strain gauge agreed fairly closely for both the normal and lymphedema arms. The Perometer is thus a reliable and convenient tool for the measurement of limb volume, and may also be used to measure the rate of swelling during venous occlusion plethysmography.

Adult↗

Cutaneous vascular control in the arms of women with postmastectomy oedema.

The control of forearm skin blood flow was examined in the swollen arms of twelve women with oedema caused by breast cancer treatment. The swollen arm was compared with the opposite unaffected (control) arm. Using laser Doppler flux (LDF) and continuous finger blood pressure (BP) measurements, vascular control was tested by applying a range of provocations previously shown to alter cutaneous vascular resistance (CVR) in healthy subjects. The tests and the accepted mechanism were: post-ischaemic hyperaemia (locally mediated vasodilatation), inspiratory gasp and cool reflex (both sympathetically mediated vasoconstriction), arm dependency (locally mediated vasoconstriction), and core heat load (sympathetically mediated vasodilatation). CVR was calculated as BP/(LDF-biological zero). Three differences between the control and swollen arms were identified. (i) The laser Doppler biological zero signal was significantly higher on the swollen side (P = 0.005, Student's paired t test). (ii) Baseline LDF was significantly lower on the swollen side (P = 0.002), and apparent CVR correspondingly higher. (iii) Cumulative reactive hyperaemia (area under the LDF curve above baseline) was significantly less on the swollen side (P = 0.03), although peak flux was not significantly different. Inspiratory gasp, cool reflex, arm dependency and core heat load produced changes of similar magnitude in both arms. It appears that sympathetic neural control and local vasoconstrictor control in arm dependency are normal in arm lymphoedema but that locally mediated vasodilator control is impaired. In addition, baseline skin blood flow may be reduced in this condition. The results provide no support for impairment of vascular tone as a contributory factor to the oedematous state.

Aged↗

Lymphatic and venous function in lipoedema.

Lipoedema is a common but infrequently recognized condition causing bilateral enlargement of the legs in women. Although generally considered to be the result of an abnormal deposition of subcutaneous fat with associated oedema, the precise mechanisms responsible for oedema formation have yet to be fully established. In order to evaluate the possible role of lymphatic or venous dysfunction in the pathogenesis of lipoedema, 10 patients were investigated by photoplethysmography (venous function) and quantitative lymphoscintigraphy (lymphatic function). The results were compared with those from patients with primary lymphoedema and those from healthy volunteers. The results demonstrated minor abnormalities of venous function in only two patients. One patient had moderately impaired lymphatic function in both legs and seven patients had a marginal degree of impairment in one or both legs. However, in none of these cases did the impairment attain the low levels seen in true lymphoedema. Lipoedema appears to be a distinct clinical entity best classified as a lipodystrophy rather than a direct consequence of any primary venous or lymphatic insufficiency.

Adipose Tissue↗

Lymphatic function in the yellow nail syndrome.

Peripheral oedema is commonly seen in the yellow nail syndrome (YNS). Contrast lymphangiography has shown abnormal collecting lymphatics in some patients with YNS. In this study, lymphatic function in the upper and lower limbs of 17 patients with YNS, in normal controls, and in patients with established classical lymphoedema, has been assessed using quantitative lymphoscintigraphy. Nine subjects with YNS had swelling of the legs and two had features typical of lymphoedema. The lymphatic drainage was significantly reduced in the legs of patients with YNS but not to the level seen in lymphoedema. Lymphatic function was also reduced in the arms in patients with YNS. Venous insufficiency did not contribute to the leg oedema. These results suggest that the underlying cause of YNS is not primarily a lymphatic abnormality. The lymphatic impairment associated with YNS appears to be secondary, and predominantly functional in nature, rather than due to structural changes.

Adolescent↗

Tumoral calcinosis: an unusual cause of cutaneous calcification.

Tumoral calcinosis is an uncommon ectopic calcification syndrome characterized clinically by the presence of irregular, painless, periarticular soft tissue calcifying masses, and pathologically by fibrous-walled cystic spaces containing structureless calcific debris and associated with a variable inflammatory reaction. The pathogenesis remains obscure but the condition probably represents a disordered tissue reparative process. Of the previous literature reports, almost all have been in patients of African origin. We report a case in a white English woman.

Aged↗