Differential enamel and osteogenic gene expression profiles in odontogenic tumors.

Odontogenic tumors occur within the jaw bones and may be derived from odontogenic epithelium or ectomesenchyme or contain active components of both tissue types. We investigated the gene expression profile of enamel matrix proteins (EMPs), genes related to osteogenesis, and the mineralization process in odontogenic tumor cell populations focusing on an ameloblastoma (AB-1), a keratocystic odontogenic tumor (KCOT-1), and a calcifying epithelial odontogenic tumor (CEOT-1). All cell populations were shown to be epithelial in origin by CK14 expression. All tested EMPs were expressed by all odontogenic tumor cell types, with higher transcript levels seen in the AB-1 population especially for AMEL, AMBN, and ODAM. CEOT-1 cell populations showed a greater content of ALP-positive cells as well as higher ALP mRNA levels. Using qRT-PCR, we found a higher expression of 8 genes in the CEOT-1 compared to the AB-1 and KCOT-1. In this study we demonstrated the establishment of AB-1, KCOT-1 and CEOT-1 cell populations. The unique gene expression profiles of AB-1, KCOT-1, and CEOT-1 cells and their interactions with the surrounding microenvironment may support their unique tumor development, progression, and survival.

Ventricular defibrillation with triphasic waveforms.

BACKGROUND: It has been reported that triphasic defibrillation waveforms cause less myocardial injury than biphasic waveforms. This study compared the defibrillation thresholds (DFTs) of triphasic and biphasic waveforms. METHODS AND RESULTS: ++DFTs were determined for a transvenous lead system and a 300-microF-capacitor defibrillator. In 8 pigs (group 1), DFTs were determined for 5 triphasic waveforms with tilts of 80%, 83%, and 86% and for 1 biphasic waveform. DFTs were determined in another 8 pigs (group 2) for 2 triphasic and 4 biphasic waveforms with tilts of 43%, 49%, and 56%. In both groups, a biphasic waveform from a 140-microF-capacitor defibrillator was also evaluated, and both shock polarities were tested for each waveform. In group 1, with the 300-microF-capacitor defibrillator, the leading-edge voltage and energy stored at DFT were significantly lower for triphasic waveforms with phase-duration ratios of 50/33/17 and an anode at the right ventricular electrode for phase 1 than for biphasic waveforms (P<0.001). In group 2, the stored energy of triphasic waveforms with 56% and 49% tilt was significantly lower than that of biphasic waveforms with the same tilts for anodal but not cathodal phase 1 at the right ventricular electrode. Electrode polarity significantly affected the DFT of triphasic waveforms for both studies. CONCLUSIONS: Some 80% tilt triphasic waveforms defibrillate more efficiently than biphasic waveforms with a 300-microF-capacitor defibrillator. The triphasic waveforms for both groups were not superior to 140-microF-capacitor biphasic waveforms. The efficacy of triphasic waveforms depends on phase durations and electrode polarity.

Reduction of atrial defibrillation threshold with an interatrial septal electrode.

BACKGROUND: The standard lead configuration for internal atrial defibrillation consists of a shock between electrodes in the right atrial appendage (RAA) and coronary sinus (CS). We tested the hypothesis that the atrial defibrillation threshold (ADFT) of this RAA-->CS configuration would be lowered with use of an additional electrode at the atrial septum (SP). METHODS AND RESULTS: Sustained atrial fibrillation was induced in 8 closed-chest sheep with burst pacing and continuous pericardial infusion of acetyl-ss-methylcholine. Defibrillation electrodes were situated in the RAA, CS, pulmonary artery (PA), low right atrium (LRA), and across the SP. ADFTs of RAA-->CS and 4 other lead configurations were determined in random order by use of a multiple-reversal protocol. Biphasic waveforms of 3/1-ms duration were used for all single and sequential shocks. The ADFT delivered energies for the single-shock configurations were 1.27+/-0.67 J for RAA-->CS and 0. 86+/-0.59 J for RAA+CS-->SP; the ADFTs for the sequential-shock configurations were 0.39+/-0.18 J for RAA-->SP/CS-->SP, 1.16+/-0.72 J for CS-->SP/RAA-->SP, and 0.68+/-0.46 J for RAA-->CS/LRA-->PA. Except for CS-->SP/RAA-->SP versus RAA-->CS and RAA-->CS/LRA-->PA versus RAA+CS-->SP, the ADFT delivered energies of all of the configurations were significantly different from each other (P:<0. 05). CONCLUSIONS: The ADFT of the standard RAA-->CS configuration is markedly reduced with an additional electrode at the atrial SP.

The effects of ventricular fibrillation duration and site of initiation on the defibrillation threshold during early ventricular fibrillation.

OBJECTIVES: The purpose of this study was to determine if the defibrillation threshold (DFT) is lower during the first few cycles of ventricular fibrillation (VF) than after 10 s of VF and, if so, if the effect is caused by local or global factors. BACKGROUND: The DFT may be low very early during VF because: (1) for the first few cycles VF arises from a localized region close to a defibrillation electrode where the shock field is strong (local factors), or (2) during early VF the effects of ischemia and sympathetic discharge have not yet fully developed and the heart has not yet completely dilated (global factors). METHODS: Protocol 1 included seven pigs in which a defibrillation electrode and a pacing catheter were both placed in the right ventricular apex. VF was induced by delivering a high current premature stimulus from the pacing catheter that should have caused reentry confined to the right ventricular apex for the first few cycles of VF. A bipolar electrogram was recorded from the tip of the defibrillation catheter. Using a three reversal up-down protocol, the DFT was determined for biphasic shocks delivered after 1, 2, 3, 4, 5, 7, 10, 15, 20 and 25 activations in this electrogram and after 10 s (control). Protocol 2 included seven pigs undergoing the same procedure as in protocol 1 except that an additional pacing catheter was placed in the left ventricle. Defibrillation thresholds were determined after 1, 2, 3, 4 and 5 VF activations following VF induction from the right ventricle (RV) or the left ventricle (LV) and after 10 s (control). RESULTS: In protocol 1, the mean +/- SD DFrs were lower during the first three cycles than after 10 s of VF (3.0 +/- 4.1 J for the first VF cycle vs 15.8 +/- 6.6 J after 10 s of VF, p < 0.05). In protocol 2, the DFF for the first few cycles of VF induced away from the defibrillation electrode in the LV (6.9 +/- 1.4 J for the first VF cycle) was significantly lower than that after 10 s of VF (16.0 +/- 2.2 J), whereas the DFF for the first few cycles induced near the defibrillation electrode in the right ventricular apex was significantly lower (2.3 +/- 2.7 J for the first VF cycle) than that induced from the LV. CONCLUSIONS: This study demonstrates that the DFT is significantly lower during the first few VF cycles of VF than after 10 s of VF and that this decrease may be caused by both local factors and global factors. These results provide an impetus for exploring earlier shock delivery in implantable devices.

Comparison of the internal defibrillation thresholds for monophasic and double and single capacitor biphasic waveforms.

Implantable cardiac defibrillators are now an accepted form of therapy for patients with life-threatening ventricular arrhythmias that cannot be controlled by antiarrhythmic drugs. These devices could be made even more acceptable if they were smaller, had increased longevity and the surgical procedure for implantation was less invasive. Reducing the energy requirements for internal defibrillation with use of a nonthoracotomy system would make all of these goals achievable. Monophasic and double and single capacitor biphasic waveforms were compared in 14 anesthetized dogs (25.5 +/- 2.2 kg) with use of a nonthoracotomy lead system that has previously been shown to distribute the delivered voltage throughout the heart more equally. Cathodal catheter electrodes were placed in the right ventricular apex and outflow tract. The anodal electrode was a large cutaneous R2 patch placed over the left side of the chest. The mean energy requirement for defibrillation when a single capacitor biphasic waveform was used was significantly less (6.4 +/- 2.6 J) than that for either the double capacitor biphasic or the monophasic waveform (18.0 +/- 8.0 and 17.4 +/- 8.0 J, respectively) of the same duration. Unexpectedly, the leading edge voltage for the phase I of the single capacitor biphasic waveform was significantly less (266 +/- 51 V) than that for either the double capacitor biphasic or the monophasic waveform (336 +/- 76 and 427 +/- 117 V, respectively). In conclusion, in large dogs, defibrillation is possible at low energy levels with a single capacitor biphasic waveform.

Theophylline levels and clinical response in asthmatic adults receiving long-term Uniphyl.

Serum theophylline levels were measured in response to a single daily dose of Uniphyl in asthmatic adults who had previously received sustained-release theophylline preparations (usually Theo-Dur). Nine men and 20 women between the ages of 20 and 75 with a one-second forced expiratory volume (FEV1) of 30 to 75 percent of predicted and with at least 15 percent improvement in FEV1 following an inhaled beta-adrenergic agonist were enrolled. Patients with coexisting major organ system dysfunction were excluded. Maintenance prednisone in a dosage of 20 mg or less each morning and inhaled corticosteroids were allowed. The five-week study included a baseline week when the usual sustained-release theophylline was continued; theophylline blood levels were determined at six to 10 hours on the fifth day. Patients then switched to an equivalent dose of Uniphyl with single morning dosing. FEV1 and serum theophylline levels were observed weekly as during the baseline period. Side effects were carefully monitored throughout the study. Concurrent therapy included inhaled beta agonist in 28, oral prednisone in 11, and beclomethasone in one. Serum theophylline levels were remarkably stable during the four Uniphyl weeks and averaged 15 micrograms/ml. During this time, a small improvement in FEV1 occurred in weeks 2 and 4 (p less than 0.05). Only two patients reported substantial side effects--nervousness and slight morning dizziness--which responded to a downward adjustment of Uniphyl dosage. This study indicated that, in asthmatic patients previously receiving twice-daily theophylline therapy, switching to a daily single dose of Uniphyl maintained stable blood levels with a very low incidence of side effects and a modest improvement to FEV1 at the time of the normal serum peak of theophylline. This study suggests that Uniphyl can replace twice-daily theophylline dosing, which may result in improved patient compliance.

Profundaplasty in perspective: limitations in the long-term management of limb ischemia.

The ultimate value of profundaplasty in the management of lower extremity ischemia was determined by multifactoral analysis of 239 operated limbs in 209 patients followed up to 110 months. In patients who underwent operation for claudication (n=83), patency without the need for subsequent revision or distal bypass was achieved in 77% at 5 years. By contrast, profundaplasty patency was maintained in only 23% of 154 limbs operated upon for salvage. The patient survival rate was 75% at 5 years and 56% at 7 years among the claudication group but only 29% at both 5 and 7 years in the limb salvage group. Of the 104 survivors in the limb salvage category, 43 required amputation, 79% within the first year, and 13 limbs were saved by additional revascularization procedures. Profundaplasty is a durable procedure for relief of claudication. However, it is significantly less effective in patients threatened with limb loss. When amputation is inevitable, effective profunda perfusion is essential for preservation of the knee joint.

Fasciotomy: an appraisal of controversial issues.

Fourty-eight fasciotomies performed for conventional indications were analyzed, focusing primarily on the reliability of clinical diagnosis and the effectiveness of the operative technique. Decompression was accomplished immediately after hospital admission or arterial repair in 27 patients and deferred until the appearance of signs and symptoms in 21 others. Myoneural degeneration occurred in the delayed group only as a result of massive trauma or when obvious signs of compartment syndrome were ignored. A high index of suspicion and careful attention to clinical findings were reliable for establishing the diagnosis and indicating the timing of myofascial decompression. Tissue-pressure measurements were not used. The technique of four-compartment fasciotomy through a single lateral incision without fibulectomy was used in 21 limbs and compared with 18 four-compartment fasciotomies utilizing conventional methods. This procedure is rapid, simple, effective, and atraumatic and provides excellent exposure for direct visualization and selective decompression of all compartments and their individual muscles.

Endarterectomized superficial femoral artery as an arterial patch.

Eighty-six patients underwent 90 profundaplasties for lower extremity ischemia using endarterectomized superficial femoral artery (ESFA) or vein as an arterial patch. Standard length profundaplasty was performed in 60 limbs and extended profundaplasty in 28. Seventy-two were performed for limb salvage and 18 for severe claudication. Fifty-four limbs underwent inflow reconstruction and profundaplasty, while 36 others had profundaplasty alone. Three-year cumulative patency rates were employed to compare the type of autogenous patch material to the profundaplasty length, operative indications, and procedures. In all groups, ESFA performed as well as vein. Endarterectomized superficial femoral artery patch angioplasty provides comparable long-term results to vein patch in patients undergoing profundaplasty, and demonstrates its durability as a vascular patch in situations where autogenous tissue is required or preferred while preserving the saphenous vein for later use.

Results of arterial reconstruction of the foot.

Sixty-five patients with critical ischemia required bypass to foot vessels. These procedures were performed by five different techniques: (1) femoral-foot bypass with in situ saphenous vein; (2) femoral-foot bypass with reversed autogenous saphenous vein; (3) femoral-foot bypass with polytetrafluoroethylene (PTFE); (4) popliteal-foot bypass with reversed autogenous saphenous vein; and (5) popliteal-foot bypass with PTFE. The two-year patency rate of femoral-foot bypass with in situ vein (96%) was significantly higher than femoral-foot bypass with reversed vein (42%), while both procedures demonstrated significantly higher patency than femoral-foot bypass with PTFE (0%). Popliteal-foot bypass with reversed vein (92%) was superior to both popliteal-foot bypass with PTFE (27%) and femoral-foot bypass with PTFE (0%). Femoral-foot bypass with in situ vein and popliteal-foot bypass with reversed vein have appreciably increased vein utilization, graft patency, and limb salvage.

Use of ultrasonic venography in the evaluation of venous valve function.

Forty healthy limbs and 31 limbs with suspected deep venous insufficiency were imaged with real-time B-mode ultrasound to determine valve location, anatomic characteristics, and function. Valve function was evaluated by comparison with Doppler ultrasonographic techniques, and the data clearly indicated that ultrasonic venography accurately localized and determined the extent of deep venous reflux. Ascending contrast venography was performed in 15 postphlebitic limbs for assessment of valve location. The results indicate that ultrasonic venography is a more accurate method for visualization of valves in this group of patients. Therefore, ultrasonographic imaging is a valuable technique for evaluating limbs with chronic venous insufficiency.

Origin of deep vein thrombi in an ambulatory population.

Eighty symptomatic ambulatory outpatients with acute deep vein thrombosis were evaluated with ascending contrast venography and ultrasonic imaging to determine the origin and distribution of thrombosis and to analyze clinical risk factors. Isolated calf vein thrombosis was present in 42.5 percent of the limbs, combined calf and proximal deep vein thrombosis in 47.5 percent, and isolated proximal thrombosis in 10 percent of the limbs. Discontinuity of thrombus was present in 55 percent, whereas 45 percent exhibited a continuous column of thrombus. The results of this study indicate that in the ambulatory outpatient population, acute deep vein thrombosis begins segmentally in the calf and proximal vessels and frequently coalesces into a continuous column of thrombus over several days. We believe that all cases of acute deep vein thrombosis should be treated and patients with evidence of previous acute deep vein thrombosis should be closely monitored for possible recurrences.

Efficacy of femorofemoral bypass for intermittent claudication. Clinical and hemodynamic assessment.

Twenty patients treated by femorofemoral bypass were retrospectively reviewed to determine if femorofemoral bypass was efficacious in the treatment of disabling claudication. The data have clearly demonstrated that two criteria are necessary for the successful outcome of femorofemoral bypass. First, the donor artery should be hemodynamically normal in order to support the recipient limb. This can be determined by either a normal treadmill exercise test result or by a normal preoperative intraarterial papaverine test result. Second, the patient's functional improvement will be dependent on the status of the runoff vessels in the recipient limb; therefore, many patients with patent superficial femoral and popliteal arteries will have excellent results (50 percent in this series), whereas those with occluded superficial femoral or popliteal arteries or both will have less improvement (40 percent in this series). Therefore, femorofemoral bypass should be used in the treatment of intermittent disabling claudication in the properly selected patient.

Ankle bypass: should we go the distance?

This report reviewed the results of 47 distal arterial reconstructions to or below the level of the malleolus. The operations were performed by the techniques of popliteal-to-distal bypass (20 procedures) and in situ bypass (27 procedures). Seventy-five percent of patients had gangrene of ischemic ulceration, and all procedures were performed for limb salvage. Seventy-three percent of all patients were diabetic. The patency rates for popliteal-to-distal bypass with reversed saphenous vein were 92 percent at 24 months and 57 percent at 60 months, with a limb salvage rate of 70 percent at 60 months; the patency rates for popliteal-to-distal bypass with PTFE were 53 percent at 12 months and 0 at 36 months, with a limb salvage rate of 53 percent at 36 months; and the patency rate for in situ saphenous vein bypass was 96 percent at 24 months, with a limb salvage rate of 80 percent at 24 months. Early results are promising for ankle bypass using the techniques of popliteal-to-distal and in situ bypass.

Profundaplasty: its role in limb salvage.

The concept of the profunda artery as a collateral system is very useful in determining which patients may benefit from profundaplasty. When hemodynamic profunda stenosis is associated with combined aortoiliac and superficial femoral artery occlusive disease, profundaplasty as an adjunct to an arterial inflow procedure is highly successful. It is most efficacious when performed for disabling intermittent claudication and less successful for limb salvage indications. When isolated profundaplasty is performed for limb salvage, it may be an appropriate first procedure to heal ischemic ulcers and relieve rest pain. Ischemic gangrene is less frequently resolved and may require distal bypass. However, if the PPCI is low and/or the arteriographic appearance of the profunda system is favorable, then isolated profundaplasty may be successful. When limb salvage is precluded by extensive pedal necrosis or end-stage arterial disease, profundaplasty may provide effective perfusion of the knee joint so that a more functional below-knee amputation may be performed.

A telemetry system for the study of spontaneous cardiac arrhythmias.

The characteristics of spontaneous cardiac arrhythmias leading to sudden cardiac death are largely unknown. To study arrhythmias in animal models, an eight-channel implantable radio telemetry system has been developed to record continuously cardiac electrograms over a period of weeks to months, with maintenance restricted to changing batteries. The inputs are connected in a unipolar manner. Each channel has a gain of fifty and is AC coupled, band limited to 0.07-260 Hz. The signals are digitized with 12 bits resolution at 1000 samples/s. The amplifiers, analog-to-digital converter, and control logic are packaged in an implantable unit. An umbilical cable is passed through the skin to an external backpack unit for power and data transmission. A custom serial interface card, a PC/104 form factor 25-MHz 80386-based single-board computer with a PCMCIA wireless local area network (WLAN) card, and battery power supply make up the backpack. Data are read into the parallel port of the computer, buffered, then transmitted over the WLAN to the laboratory network where it can be analyzed and archived. Approximately 12 h of 14,000 bytes/s data can be collected with each set of batteries. The system is suitable for continuous monitoring of animal models of spontaneous arrhythmias and sudden cardiac death.

Effect of altering the left ventricular pressure on epicardial activation time in dogs with and without pacing-induced heart failure.

BACKGROUND: The influence of an increased left ventricular end-diastolic pressure (LVEDP) on the development of lethal arrhythmias in chronic heart failure is unclear. We investigated the effect of chronic and acute LVEDP increase on the epicardial activation time of sinus (SB) and paced (PB) beats. METHODS: Six dogs underwent rapid ventricular pacing at 220-280[emsp4 ]beats/min for 6-14 weeks for induction of heart failure. On the study day, baseline (ba) LVEDP was determined for the surviving heart failure animals (HF-ba), and for seven control animals (C-ba). The epicardial activation time (EAT, time between the earliest and latest epicardial activation) for five consecutive SB and five ventricular PB during the baseline hemodynamic state were recorded using a 504 electrode mapping-sock. In the control animals a 2-litre volume (vl) was infused over 10[emsp4 ]min to acutely increase the LVEDP (C-vl) to a level comparable to the chronic increased LVEDP of the HF-ba. The same volume challenge was performed in two HF animals (HF-vl) and the EAT for SB and PB was redetermined. RESULTS: Three of six HF animals died during induction of heart failure. In the three remaining HF animals, chronic LVEDP increased from 6+/-1 to 17+/-10.8[emsp4 ]mmHg (P=0.07), EAT for SB increased by 68 % compared to control animals (HF-ba vs. C-ba, P<0.05). In contrast, in the control animals the acute rise in LVEDP from 6.8+/-4.5 to 14.7+/-6.2 mmHg P<0.05), shortened the EAT for SB (C-ba vs. C-vl, P<0.05). A similar decrease in EAT for SB caused by acute volume load was seen in the HF animals, but did not reach significance due to the small sample size (one of the three remaining HF animals died of spontaneous ventricular fibrillation before the volume load). Chronic LVEDP elevation significantly prolonged the EAT for PB from 72+/-11 to 120+/-31[emsp4 ]ms (C-ba vs. HF-ba) while acute LVEDP increase had no significant effect on EAT for PB. CONCLUSION: Chronic HF increases LVEDP and prolongs EAT, while an acute increase in LVEDP shortens the EAT for sinus beats. A prolongation of EAT in heart failure may make the heart more susceptible to ventricular arrhythmias and electromechanical dissociation.

Electrode impedance: an indicator of electrode-tissue contact and lesion dimensions during linear ablation.

Pre-ablation impedance was evaluated for its ability to detect electrode-tissue contact and allow creation of long uniform linear lesions with a multi-electrode ablation catheter. The study consisted of 2 parts, both of which used the in vivopig thigh muscle model. In part 1, a 7 Fr. multi-electrode catheter was held in 3 electrode-tissue contact conditions: (1) non-contact; (2) light contact with a 30g downward force; and (3) tight contact with a 90g downward force. Impedances were measured in unipolar, modified unipolar and bipolar configurations using a source with frequencies from 100Hz to 500kHz. Compared with non-contact, the impedance increased 35 +/- 22 % with 30g contact pressure and 68 +/- 40% when the contact pressure was increased to 90g across the range of frequencies studied. In part 2, the same catheter was held against the tissue with different forces. Pre-ablation impedance was measured using a 10kHz current. Phased radiofrequency energy was applied to the 5 electrodes simultaneously using 10W power at each electrode for 120s. A total of 32 linear lesions were created. The lesion dimensions correlated with pre-ablation impedance. A unipolar impedance > or = 190 Omega indicates 95% possibility to create a uniform linear lesion of at least 3mm depth with our ablation system. We conclude that pre-ablation impedance may be a useful indicator for predicting electrode-tissue contact and the ability to create a continuous and transmural linear lesion with a multi-electrode catheter.

Comparison of the temperature profile and pathological effect at unipolar, bipolar and phased radiofrequency current configurations.

With a multi-electrode catheter, phased radiofrequency (RF) delivers current between each electrode and a backplate as well as between adjacent electrodes. This study compared the tissue heating and lesion dimensions created by phased and standard RF. Ablation was performed on the in vivo thigh muscles in 5 pigs. Six lesions were created on each thigh muscle using phase angle 0 degrees RF, 127 degrees RF, 180 degrees RF with and without a backplate, and standard RF in bipolar and sequential unipolar configurations. Two plunge needles, each with 6 thermocouples 1 mm apart, were inserted into the tissue with one needle beside an electrode and the other midway between electrodes for tissue temperature measurement. The 0 degrees RF created lower tissue temperatures and smaller lesions between electrodes than those beside electrode. With 127 degrees and 180 degrees RF, tissue temperature and lesion dimensions between electrodes were similar to beside electrode, while the 127 degrees RF created higher tissue temperature and deeper lesions than 180 degrees RF (both with and without a backplate) at both sites. Standard RF bipolar ablation created similar tissue temperatures and lesion depths at both sites, but required greater power than the 127 degrees RF. Standard RF sequential unipolar ablation created only a slight temperature increase and no lesions between electrodes 3 and 4. As judged by tissue temperature, lesion depth and uniformity, and RF power requirement, 127 degrees RF may be a better energy configuration for linear ablation than the other RF modalities tested.

Venous thrombosis: the clinical problem.

Although the exact cause of DVT is not known, venous thrombosis and its sequelae remain important clinical problems. Pulmonary embolism is a significant cause of morbidity and mortality in the hospitalized population, and the postthrombotic syndrome affects a large portion of the general population. While specific screening tests are not readily available to detect those patients who are likely to develop DVT, certain clinical risk factors have been identified that predispose to thrombosis. These groups include patients undergoing a wide variety of surgical procedures, patients with cardiac disease or cancer, pregnant or postpartum women, and individuals with previous history of DVT. The diagnosis of thrombosis is based on clinical findings and must be confirmed with appropriate laboratory tests. While contrast venography remains the gold standard, noninvasive tests have become increasingly more accurate. The recent use of real-time B-mode ultrasonic imaging and duplex sonography for the diagnoses of DVT has been shown to be efficacious. The postthrombotic syndrome with its associated chronic pain and ulcerations remains a significant clinical problem. The general diagnosis of this condition is readily made on clinical grounds in the advanced state. However, exact knowledge of the location and cause of the venous pathology can only be obtained using objective diagnostic tests. Older noninvasive and invasive tests may diagnose the presence of venous obstruction, valvular incompetence, and also may document venous hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)