Clinical assessment of human lymph flow using removal rate constants of interstitial macromolecules: a critical review of lymphoscintigraphy.

Edema is a common clinical problem, and the daily avoidance of edema depends critically on the lymphatic system, which clears leaked plasma proteins and fluid from the interstitial compartment. There is often confusion as to the difference between chronic edema and lymphedema. Lymphedema is by definition primarily a disease of impaired lymphatic drainage and lymph flow, and progress in lymphedema research, currently an increasingly active field, requires a clinically viable method for the quantitative assessment of lymph drainage rate in patients. Measurement of the rate of clearance of a new protein marker, radiolabelled human immunoglobulin, from skin, subcutis, and muscle provides a way of measuring human lymph flow quantitatively and is the only viable clinical method currently available. Considerable strides have been made over the last 5-10 years in evaluating the method and its pitfalls, including potential complications such as vascular clearance, peripheral lymphovenous communications and label dissociation. The review assesses critically, for the first time, the evidence relating to the method: its pitfalls; human lymph flow in various healthy and oedematous tissues; and how this is altered in hyperfiltration edemas, inflammation, vasoconstriction and various primary and secondary human lymphedemas.

Assessment of truncal edema following breast cancer treatment using modified Harpenden skinfold calipers.

After initial treatment for breast cancer, lymphedema often affects the trunk as well as the arm. Evaluation of truncal swelling by the clinical "pinch test" of the posterior axillary fold is unreliable. Our aim was to develop an objective measurement, using modified Harpenden skinfold calipers. Standard Harpenden skinfold calipers exert a pressure of 12.6 g.mm-2, which rapidly squeezes edema fluid out of the skinfold. Springs were substituted to exert a lighter but relatively constant load (3.7 g.mm-2). Repeated skinfold thickness measurements on the same, normal subject then gave a relative standard deviation (r.s.d.) or coefficient of variation of 5%. The posterior axillary folds of 14 patients (age 56 +/- 13 (s.d.) years) with an average 30% arm swelling were measured using the same procedure. Readings were taken at 10 s, and again after 60 s of sustained application to assess the rate of creep, or deformation with time, attributed to displacement of pressurized interstitial fluid. Two patients had clinically observable axillary fold swelling. Eight patients, including the above two, showed axillary fold swelling by caliper measurement, defined as a 10% increase over the contralateral side (2 r.s.d.'s). Creep was greater on the affected side in all 14 patients. Thus, modified calipers can detect axillary fold edema, and thereby provide an objective method for assessing changes in swelling after lymphedema treatment.

Assessment of noninvasive tests of cutaneous vascular control in the forearm using a laser Doppler meter and a Finapres blood pressure monitor.

The control of human forearm cutaneous vascular resistance was examined using a combination of laser Doppler perfusion measurement and continuous Finapres blood pressure measurement. Tests which provoke changes in blood flow via different control mechanisms (local and neural) were applied in a group of ten healthy subjects. The purpose was to select from them a suitable (i.e. statistically significant) group to apply in cases where a disease process is suspected of interfering with the control of the skin circulation. Deep inspiration, immersion of the feet in water at 15 degrees C (both eliciting sympathetic vasoconstrictor nerve activity) and arm dependency (eliciting the local veni-arteriolar response) produced statistically significant, symmetrical increases in cutaneous vascular resistance in both arms (p < 0.05, Wilcoxon's test for paired differences). Similarly, post-ischaemic reactive hyperaemia (mediated by local vasodilator mechanisms) and indirect heating of the body (eliciting increased sympathetic vasodilator nerve activity) resulted in significant decreases in cutaneous vascular resistance (p < 0.01). When deep inspiration was repeated from a vasodilated baseline after indirect heating, the increases in cutaneous vascular resistance were smaller than those obtained before heating. Isometric handgrip exercise failed to produce a significant change in contralateral cutaneous vascular resistance (p > 0.05). There were no differences between right and left arms for any test (p > 0.05). The successful tests were subjected to power analysis in order to predict likely patient sample sizes required to demonstrate altered responsiveness at sites of microcirculatory disturbance compared with normal skin.