International consensus for a definition of disease flare in lupus.

The Lupus Foundation of America (LFA) convened an international working group to obtain a consensus definition of disease flare in lupus. With help from the Paediatric Rheumatology International Trials Organization (PRINTO), two web-based Delphi surveys of physicians were conducted. Subsequently, the LFA held a second consensus conference followed by a third Delphi survey to reach a community-wide agreement for flare definition. Sixty-nine of the 120 (57.5%) polled physicians responded to the first survey. Fifty-nine of the responses were available to draft 12 preliminary statements, which were circulated in the second survey. Eighty-seven of 118 (74%) physicians completed the second survey, with an agreement of 70% for 9/12 (75%) statements. During the second conference, three alternative flare definitions were consolidated and sent back to the international community. One hundred and sixteen of 146 (79.5%) responded, with agreement by 71/116 (61%) for the following definition: "A flare is a measurable increase in disease activity in one or more organ systems involving new or worse clinical signs and symptoms and/or laboratory measurements. It must be considered clinically significant by the assessor and usually there would be at least consideration of a change or an increase in treatment." The LFA proposes this definition for lupus flare on the basis of its high face validity.

Changes in hepatocyte NADH fluorescence during prolonged hypoxia.

Deprivation of oxygen reduces oxidative phosphorylation and rapidly causes an increase in cellular NADH which can be monitored by fluorimetry. Previous studies have established that increases in NADH fluorescence accurately reflect the impairment in oxidative phosphorylation which occurs during brief periods of acute hypoxia. However, the potential usefulness of fluorimetry for following longer, clinically relevant periods of ischemia has not been explored. We studied changes in NADH fluorescence in rat hepatocyte suspensions and in isolated-buffer-perfused rat livers during hypoxia (pO2 < 50 mm Hg) for periods as long as 180 min. NADH fluorescence of hepatocyte suspensions consistently increased by about 15% after 13 to 15 min of hypoxia and coincided with a marked decrease in tissue ATP levels. Reoxygenation after 15 or 30 min of hypoxia resulted in recovery of ATP and NADH with minimal loss of viability, as measured by trypan blue exclusion. After 60 to 180 min hypoxia, the initial increase in NADH fluorescence was followed by a progressive, irreversible decline which correlated with decreased cell viability. Similar changes in NADH fluorescence were observed in isolated-perfused rat livers in which NADH fluorescence was monitored at the liver surface with a fiberoptic probe. Hypoxia for 30 min had no effect on NADH fluorescence, but hypoxia for longer periods caused a steady increase in fluorescence after 45-60 min. When hypoxia was prolonged (120 or 180 min), fluorescence peaked after 60-75 min and then declined progressively to levels below baseline. The greatest decrease in fluorescence was seen after 180 min of hypoxia.(ABSTRACT TRUNCATED AT 250 WORDS)

A prospective, randomized trial of Unna's boot versus Duoderm CGF hydroactive dressing plus compression in the management of venous leg ulcers.

Leg ulcers caused by chronic venous insufficiency plague an estimated 500,000 Americans, but there have been few improvements in conservative treatment in this century, and Unna's boot continues to be a mainstay of therapy. A recent report suggests that Duoderm CGF dressing provides greater patient comfort and enhanced compliance, but Duoderm alone (without compression) resulted in slower healing compared with Unna's boot. We enrolled 30 patients (30 ulcers) in a clinical trial to compare Duoderm CGF plus compression (Coban wrap) to Unna's boot. No significant difference was observed between the two groups with respect to age, sex, initial ulcer area, ulcer duration, or extent of venous insufficiency by duplex scan. Eight of 16 ulcers (50%) in the Duoderm group healed completely versus 6 of 14 ulcers (43%) in the Unna's boot group (p = 0.18). Healing rates (square centimeters per week) correlated significantly with initial ulcer area and initial ulcer perimeter for both groups but best correlated with initial ulcer perimeter (r = 0.88 with Duoderm, p less than 0.0001; r = 0.80 with Unna's boot, p less than 0.002). After adjusting for differences in initial ulcer perimeter, healing rates were significantly faster for patients on Duoderm than patients on Unna's boot during the first 4 weeks of therapy (0.384 +/- 0.059 cm2/wk/cm perimeter for Duoderm versus 0.135 +/- 0.043 cm2/wk/cm perimeter for Unna's boot; p = 0.002). At 12 weeks patients on Duoderm again appeared to heal faster than those on Unna's boot, although the result did not reach statistical significance (0.049 +/- 0.007 cm2/wk/cm perimeter for Duoderm versus 0.020 +/- 0.017 for Unna's boot, p = 0.11).(ABSTRACT TRUNCATED AT 250 WORDS)

Distribution of valvular incompetence in patients with venous stasis ulceration.

Valvular incompetence associated with venous ulceration can occur in the superficial, deep, or perforating systems. Duplex imaging was used to evaluate 95 extremities (78 patients) with current venous ulceration to determine the location of incompetence in each extremity. In addition, in 91 of the 95 extremities the area of the venous ulcer was evaluated for the presence of perforating veins or any other superficial veins or both conditions. Sixty-three (66.3%) of the 95 extremities had multisystem incompetence (superficial and perforating plus superficial and deep plus perforating and deep plus superficial and perforating and deep), whereas single system incompetence (superficial plus perforating plus deep) was seen in only 26 (27.3%). Isolated deep incompetence was identified in only two extremities (2.1%). Furthermore, 45% (41/91) of the ulcers had no duplex evidence of any venous abnormality in the ulcer bed. These data show that the site of valvular incompetence occurred in multiple locations, that isolated valvular incompetence of the deep venous system was uncommon, and that perforating veins were not always in the ulcer bed itself. Because standard venous surgery has traditionally been directed toward only one system, this may provide one explanation for ulcer recurrence. Therefore complete venous evaluation with duplex imaging allowing for surgical intervention directed specifically to the sites of involvement in each system is recommended.

Patterns of venous insufficiency in patients with varicose veins.

The nature and distribution of venous disease surrounding the development of varicose veins and its treatment is controversial. Using duplex ultrasonography, we evaluated 54 lower extremities in 32 patients with varicose veins who were symptomatic and had obvious varicose veins by clinical examination. Twenty-eight percent had greater saphenous trunk incompetence, 2% had lesser saphenous trunk incompetence, and 96% had branch disease. Deep valvular incompetence was seen in 41%, saphenofemoral junction incompetence in 46%, and incompetence of one or more perforators in 46% of the extremities. Thirty-three percent demonstrated no evidence of associated saphenofemoral junction, deep vein, or perforating vein incompetence, while 20% had concurrent saphenofemoral junction, deep vein, and perforating vein incompetence. These data support the heterogeneity of venous disease seen in patients with varicose veins and suggest that surgical therapy be directed to a patient's specific pattern of incompetence rather than routine saphenofemoral junction ligation or stripping of the greater saphenous trunk.

Liver viability after ischemia-reperfusion.

Lack of a reproducible model to quantitatively assess hepatocellular injury following ischemia has made it difficult to assess new strategies for minimizing hepatic injury. We studied the progression of hepatocellular injury after ischemia and ischemia with reperfusion in rats. Irreversible injury was quantitated using a triphenyltetrazolium chloride assay that was shown to correlate with ultrastructural changes. Adenosine triphosphate decreased to 36% of basal values after 30 minutes, but returned to normal with reperfusion with no decrease in viability. In contrast, viability fell by 30% after 60 minutes of ischemia, and by 64% when 60 minutes of ischemia was followed by reperfusion. We conclude that reperfusion of ischemic liver increases the degree of irreversible damage. The model employed here seems to be useful for studying ischemic and reperfusion injury in the liver.

Evaluation of the perforating veins of the lower extremity using high resolution duplex imaging.

The purpose of this study was to evaluate duplex imaging as a means of assessing perforating veins in patients with longstanding venous stasis ulceration. Thirty patients with nonhealing venous stasis ulcers and twenty normal volunteers serving as controls were evaluated with a standard 8-MHz imaging probe and integrated pulsed Doppler. The internal diameter of perforating veins was measured and perforators were grouped into one of four categories based on functional criteria: competent perforator with venous flow (C); incompetent perforator with venous flow (IC); competent perforator with arteriovenous flow (C-AVC); incompetent perforator with arteriovenous flow (IC-AVC). Sixteen of the patients with ulcers were subsequently studied by ascending venography and in 11 patients, intraoperative identification of perforating veins was made during the Rob procedure. In this subset of patients the vessel was categorized as competent or incompetent regardless of flow signal. There were significant differences in mean perforator diameter between ulcer patients and normal volunteers. Duplex imaging identified 93 perforators and venography a total of 70. In all 16 extremities, duplex imaging made the diagnosis of significant perforating vein incompetence, verified by venography. Intraoperative findings demonstrated an excellent correlation with duplex imaging. We believe duplex imaging to be a promising new modality for evaluation of the perforating veins of the lower extremity.