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Biomedical subjects

S Raju

Publications and source records attributed to S Raju.

At least 19 recordsLinked to original sources

Durability of venous valve reconstruction techniques for "primary" and postthrombotic reflux.

PURPOSE: The durability of the variety of valve reconstruction techniques in "primary" reflux and postthrombotic reflux was studied. METHODS: A total of 423 valve repairs in 235 patients with a follow-up period ranging from 1 to 12 years were analyzed. End points for assessment consisted of ulcer recurrence and Doppler competence in serial duplex examination. Multivariate analysis with Cox proportional hazards model was used. RESULTS: Ulcer-free survival curves were similar for "primary" and postthrombotic reflux. No significant difference in ulcer recurrence was seen regardless of the technique used. Different results were obtained when valve competence instead of ulcer recurrence was used for assessment of durability. Reconstructions in "primary" reflux were more durable than those in postthrombotic reflux. Durability differences were also noted among different techniques. A cohort of posterior tibial repairs proved extraordinarily durable (0 failures in 23 repairs). CONCLUSION: Valve reconstruction in postthrombotic reflux can yield clinical results similar to those in "primary" reflux. Although any of the several described techniques can produce similar clinical results, Doppler competence suggests the following order for choice of procedures: (1) internal valvuloplasty, (2) prosthetic sleeve in situ, (3) external valvuloplasty, and (4) axillary vein transfer.

Axillary Vein

Light and electron microscopic observations of epithelial shedding in stored canine small intestine.

Simple cold storage of canine small intestine is accompanied by ischemic damage to the intestinal mucosa. Progression of damage observed during cold storage is unique and has not been observed with other organs. The mucosal damage begins within 15 min after the onset of the storage, with progressive involvement of the gut as the storage period lengthens. Cytoplasmic blebs develop from the base of the epithelial cells and detach the epithelium from the basal lamina. While the process begins uniformly along the length of the villus, separation of the epithelium occurs first at the villus tip. The epithelium, which is shed into the intestinal lumen, is otherwise undamaged. Blebbing occurs in enteroendocrine and goblet cells and is not restricted to enterocytes. Early blebs occur in proximity to mucosal mast cells and subepithelial nerves. Tissue damage in cold is possibly related to enzymes that are still active at storage temperatures.

Animals

The pressure/volume relationship of the calf: a measurement of vein compliance?

OBJECTIVES: The role of compliance changes in the patho-physiology of venous disease is not well known mainly because of difficulty to measure compliance of veins in situ. This study suggests a method to determine the calf pressure/volume relationship by utilizing venous occlusion plethysmography combined with dorsal vein pressure. DESIGN: Comparison between two techniques of measuring calf pressure/volume relationship using air plethysmography with validation against popliteal vein diameter changes detected by duplex ultrasound. SETTING Vascular laboratory. MATERIALS: In 6 normal and 6 radiographically confirmed post-thrombotic lower limbs, the calf pressure/volume relationship was determined. The dorsal vein pressure was continuously recorded. Simultaneously calf volume changes were obtained by an air plethysmograph during venous occlusion plethysmography (outflow slope coefficient) and fractionated tilting of the subject from erect to supine position (volume at 40 mmHg). During the tilt, sagittal diameter of the popliteal vein was measured (% change/mmHg = distensibility). RESULTS: The outflow pressure/volume slope coefficient correlated significantly with the volume at 40 mmHg during tilt maneuver (r = 0.92) and the popliteal vein distensibility (r = 0.86). Variations in arterial inflow, venous outflow obstruction, or reflux did not affect the occlusion plethysmographic method. Plethysmographic changes related directly to venous volume changes, i.e. vein expansion suggesting that the pressure/volume relationship described vein compliance. CONCLUSION: The result show a direct relationship between the pressure/volume curve of the calf and deep vein distention. Shifts of the pressure/volume curve are likely to be mainly caused by vein wall changes, but other factors (e.g. condition of surrounding tissue, reduced venous volume) may also contribute and this needs further investigation.

Blood Volume

Compliance of the normal and post-thrombotic calf.

OBJECTIVE: In addition to degree of outflow obstruction and reflux and poor calf muscle pump function, vein wall compliance changes are important in understanding pathophysiology of venous disease. This study compares the pressure/volume relationship in post-thrombotic and healthy legs. EXPERIMENTAL DESIGN: Prospective and comparative study. SETTING: Vascular laboratory. PARTICIPANTS: Investigations were performed on 24 apparently normal legs and 30 post-thrombotic limbs as confirmed by phlebography. METHOD: Dorsal vein pressure and absolute calf volume decrease were recorded simultaneously during outflow form the leg after release of the cuff during venous occlusion air-plethysmography with and without reactive hyperemia. The slope of the pressure/volume outflow curve was calculated. In addition, the distensibility (= collapsibility) was determined as % volume decrease/mmHg. The popliteal and femoral vein diameters were measured in supine and erect position by ultrasound. RESULTS: With and without induced hyperemia the mean slope coefficients of post-thrombotic legs were significantly higher (0.52 +/- 0.22 and 0.53 +/- 0.18) than in normal (0.15 +/- 0.10 and 0.29 +/- 0.11), i.e., the curve steeper since the calf was stiffer, less compliant. The degree of outflow obstruction and severity of skin changes did not affect the slope measurement substantially. Collapsibility during venous outflow was significantly less in post-thrombotic legs. The post-thrombotic veins were less distended on standing. CONCLUSIONS: Post-thrombotic calves are less compliant than normal legs mainly due to less compliance of the vein wall, although theoretically reduced venous volume may contribute.

Blood Volume

Detection of outflow obstruction in chronic venous insufficiency.

PURPOSE: This study compares three different modes for measuring hemodynamically significant outflow obstruction in chronic venous insufficiency: (1) arm-foot venous pressure differential combined with foot venous pressure elevation to reactive hyperemia, (2) outflow fraction determination with plethysmography, and (3) calculation of resistance from simultaneously obtained foot venous pressure and calf volume curves. METHODS: The three techniques were compared in 15 normal limbs and 19 limbs with documented previous deep venous thrombosis. Outflow fraction and resistance were also measured after reactive hyperemia was induced. RESULTS: The arm-foot venous pressure measurements delineated patients with grades 1 through 4 obstruction (Raju's grading). Resistance calculations correlated well with this grading except in patients with severe grade 4 obstruction, in whom low resistance was found. Outflow fraction determinations had marked overlapping between the different obstruction grades, substantially decreasing sensitivity to detect hemodynamically important outflow obstructions. No correlation with the resistance calculations was shown. Inducing reactive hyperemia did not alleviate these findings. The failure of the outflow fraction and resistance methods to detect significant obstruction is probably attributable to the use of plethysmographic techniques for volume measurement, which appears to give false-negative results as a result of a regional volume shift within the lower limb. CONCLUSIONS: The combination of the arm-foot vein pressure differential and the foot vein pressure elevation after reactive hyperemia seems to be the only reliable test currently available for detecting and grading global chronic obstruction.

Blood Flow Velocity

Persistent sciatic artery: embryology, pathology, and treatment.

PURPOSE: The purpose of this article is to describe the embryologic development and anomalous persistence of the sciatic artery, pathologic changes that may occur in the persistent sciatic artery, and management of complications related to these pathologic changes. METHODS: Two patients with persistence of the sciatic artery treated in the authors' experience are reported. In addition, the computerized data base of the University of Mississippi Medical Center was searched for patients with other lower extremity arterial aneurysms, and their records were reviewed for possible aneurysm of a persistent sciatic artery. A review of the literature was undertaken to determine the embryologic development of the persistent sciatic artery, the pathologic changes that have been observed in the sciatic artery, clinical findings associated with these pathologic changes, and methods of treatment. RESULTS: Two patients with persistence of the sciatic artery were treated by the authors. No other cases were identified in 43 patients with 66 lower extremity aneurysms treated at our institution. The first patient presented with acute lower extremity ischemia caused by thrombosis of a sciatic artery aneurysm and was treated successfully with intraarterial thrombolytic therapy followed by interposition graft repair. In the second case an incidental unilateral persistent sciatic artery was identified in a patient with bilateral Buerger's disease presenting with digital gangrene of the contralateral extremity in whom below-knee amputation was eventually required. Bilateral tibial artery occlusion was observed on arteriography. Histologic examination of the amputated limb confirmed findings typical of Buerger's disease, and no microemboli were seen. DISCUSSION: The sciatic artery is a continuation of the internal iliac artery and is the primary blood supply to the lower limb bud during early fetal development. The sciatic artery normally involutes during fetal development, but remnants persist as the popliteal and peroneal arteries after the superficial femoral artery develops and establishes continuity with the popliteal artery. Persistence of the sciatic artery as the major blood supply to the lower extremity in adults is a rare vascular anomaly that may be of surgical significance. Failure to appreciate the persistent sciatic artery as the major inflow into the lower extremity may lead to inappropriate bypass of apparent occlusive disease of the superficial femoral artery. The persistent sciatic artery is also frequently aneurysmal, which may cause critical limb ischemia resulting from thrombosis or embolization of aneurysm thrombus. Options for vascular reconstruction include interposition graft replacement and standard femoropopliteal bypass grafting if the common femoral artery is sufficiently developed to provide adequate inflow. As with other peripheral arterial aneurysms resulting in thrombosis and extensive distal arterial embolization and thrombosis, intraarterial thrombolytic therapy may be useful in selected cases before definitive surgical revascularization.

Adult

Observations on the calf venous pump mechanism: determinants of postexercise pressure.

PURPOSE: We investigated the factors determining postexercise pressure and the relationship of venous valve closure and venous column segmentation to ambulatory venous pressure changes. METHODS: Valve closure and venous segmentation were observed during dynamic ascending phlebography in 40 nonrefluxive limbs and by duplex imaging in 25 normal limbs in healthy volunteers. Simultaneous volume (air plethysmography) and pressure studies during calf exercise were also carried out. Some studies used a simple mechanical model comprised of a collapsible latex tube ("calf pump") and a graduated "popliteal" valve. RESULTS: The femoropopliteal venous column above the popliteal valve remains unsegmented and continuous during ambulatory venous pressure changes in response to calf muscle contraction. Therefore ambulatory venous pressure changes cannot be explained purely on the basis of hydrostatic column pressure changes. Postexercise pressure appears to be determined by a complex set of factors: (1) physical segmentation of the venous column below the popliteal valve (i.e., tibial valve closure); (2) tube collapse below the closed valve, which further aids in the breakup of the hydrostatic column pressure and dampens the effect of any reflux through or around the closed valve; (3) ejection fraction, which influences the degree of tube collapse; and (4) the interaction of the resultant pressure forces with the wall properties of the venous pump. CONCLUSIONS: The mechanism of ambulatory venous pressure reduction is complex and multifactorial. The importance of venous wall characteristics as a determinant of postexercise pressure has not been previously appreciated. Changes in venous wall property after a thrombotic process, for example, could conceivably influence ambulatory venous pressure and recovery time in the absence of reflux.

Exercise

A rational approach to detection of significant reflux with duplex Doppler scanning and air plethysmography.

PURPOSE: Several techniques are currently available for the detection of venous reflux. We have attempted to determine the relative value and accuracy of available techniques to develop a logical strategy of investigation in reflux venous insufficiency. METHODS: The morphologic distribution of venous incompetence (erect duplex and descending venography); the results of ambulatory venous pressure measurement, venous refilling time, the Valsalva test, and air-plethysmography (venous refilling index, VFI); and the clinical severity were described in 118 consecutive limbs. In an attempt to validate the tests, results were correlated with the clinical severity classification (class 0, n = 34; class 1, n = 42; class 2, n = 11; class 3, n = 31) and with a standardized quantification of reflux (multisegment score) as seen on standing duplex Doppler scanning with rapid deflation cuffs. RESULTS: Twenty-nine percent of limbs with severe venous disease (class 2/3) had pure deep insufficiency, only 6% had pure superficial disease, and the remainder had a combination. A history of previous thrombosis and the presence of posterior tibial vein incompetence were markedly common with ulcer disease (84% and 42%, respectively). The duplex Doppler multisegment score correlated strongly with clinical severity classification (r = 0.97). The venous refilling time and VFI had the highest sensitivity in identifying severe venous disease (class 2/3), and the ambulatory venous pressure had excellent specificity. CONCLUSIONS: For noninvasive determination of reflux, the combination of VFI and duplex scanning not only localized reflux but also separated severe clinical vein disease from mild, with high sensitivity and specificity. Air plethysmography may also provide valuable information regarding calf muscle pump and outflow obstruction.

Diagnosis, Differential

Outpatient vascular access surgery: impact of a dialysis unit-based surgical facility.

The present report describes a novel approach to vascular access surgery based on the philosophy that a readily available operating room, staffed by nurses familiar with the unique problems of dialysis patients and their therapy, would reduce dialysis delays and maintain the quality of surgical care. Based on a 28-month experience with more than 1,000 access cases, we conclude that a traditional surgical setting is not necessary for either quality access graft placement or the management of access complications.

Age Factors

A comparison between descending phlebography and duplex Doppler investigation in the evaluation of reflux in chronic venous insufficiency: a challenge to phlebography as the "gold standard".

To evaluate venous reflux in 56 lower limbs of 32 consecutive patients, hemodynamic tests, ascending and descending phlebography, and supine and erect quantitative duplex scanning were performed and the clinical severity was classified (class 0 = 15, class 1 = 19, class 2 = 8, and class 3 = 14). Of the 56 lower limbs, 22 (40%) had severe swelling and hyperpigmentation with or without ulcer (classes 2 and 3). Adequacy of the clinical severity classification was supported by the hemodynamic results. Radiologic and ultrasound findings were described by axial grading, multilevel/multisystem point, and multisegment scoring systems. Applying these evaluation systems, the phlebographic and scan results correlated poorly. There was no relationship between the radiologically obtained average reflux grade or points and the clinical severity. An erect quantitative duplex Doppler test assessed by the multisegment scoring system correlated best with the severity classification. The predictive value of this test to diagnose severe reflux leading to severe symptoms (classes 2 and 3) was 77% compared with 35% to 44% for descending phlebography. The study suggests that erect quantitative segmental duplex Doppler reflects the degree and distribution of venous reflux more accurately than does descending venography.

Humans

Hemodynamic basis of stasis ulceration--a hypothesis.

Approximately 25% of patients with stasis ulceration have normal or below normal ambulatory venous pressures. A reflux index was calculated by multiplying postexercise pressures by Valsalva-induced foot venous pressure elevation. In patients with stasis ulceration, reflux index was found to have an excellent negative predictive value with a clear discriminant line between normal limbs and those with ulcers. Increasing incidence of stasis ulceration was demonstrated with increasing reflux index value. Even when ambulatory venous pressure was within the normal range, the index was found to be abnormal in ulcerated limbs because Valsalva-induced foot venous pressure was elevated in these limbs. Conversely, some patients with stasis ulceration and normal Valsalva foot venous pressure elevation were found to have abnormal ambulatory venous pressure values, yielding an elevated reflux index. Preliminary analysis indicates that reflux index may be a better predictor of surgical outcome after valve reconstruction procedures than either ambulatory venous pressure or Valsalva-induced foot venous pressure elevation. The concept of reflux index is a hypothesis that attempts to explain inconsistencies observed in implicating ambulatory venous hypertension as the sole determinant of venous reflux.

Chronic Disease

Host immunosuppression following orthotopic bowel allotransplantation in rats using low-dose cyclosporine.

This study shows that Le rats bearing total bowel allografts treated with CyA (5 mg/kg for 14 days) demonstrated within one month immunological unresponsiveness to donor and third-party alloantigens as determined by MLR responses. Assays performed in long-term survivors (greater than 100 days) showed a continued depressed MLR response to antigen-specific (BN) alloantigens. The response to third-party (ACI) alloantigens was not significantly depressed. After the long-term bowel recipients rejected donor skin grafts, the MLR responses were increased over control, but the transplanted bowel remained intact.

Animals

Venous obstruction: an analysis of one hundred thirty-seven cases with hemodynamic, venographic, and clinical correlations.

One hundred thirty-seven limbs with venous obstruction were analyzed. The arm/foot venous pressure differential and reactive hyperemia tests were found to be useful techniques to diagnose and grade venous obstruction. Traditional techniques including venography and ambulatory venous pressure are inferior in this regard. The newer techniques have provided newer insights in venous obstruction which are detailed herein. The hand-held Doppler was surprisingly very sensitive in grade I as well as in more severe forms of obstruction. Neither anatomic locale of obstruction nor its extent determined hemodynamic severity. Extensive proximal lesions could be hemodynamically mild, and conversely distal crural obstructions and single segment lesions could be hemodynamically severe. Phlebographic appearance was a poor index of collateralization. The paradoxical venous pressure response to the reactive hyperemia test in grade IV obstruction was found to be due to suppression or delay of the reactive hyperemia response itself in the presence of severe venous obstruction. The pain of venous claudication may be related to this phenomenon. Skin ulceration in the presence of venous obstruction was related to the associated reflux rather than the hemodynamic severity of the obstruction itself. The Linton procedure was found to be useful in treating such skin ulcerations. After perforator disruption, obstruction did not become hemodynamically worse, but reflux as measured by the Valsalva test improved with ulcer healing. The improvement in reflux related to Valsalva offers for the first time a hemodynamic rationale for the Linton procedure.

Arm

Use of saturation mutagenesis to localize probable functional domains in the NahR protein, a LysR-type transcription activator.

The NahR protein of the Pseudomonas naphthalene degradation plasmid NAH7 encodes a 300-residue transcription activator which is very similar to the NodD transcription activator of Rhizobium and other proteins in the LysR activator family. NahR binds to conserved sequences upstream (nucleotides -80 to -47) of the nah and sal promoters and activates transcription of genes for naphthalene catabolism in response to the inducer salicylate. Transformation of an Escherichia coli gal deletion strain (containing a sal promoter-galK fusion plasmid) with hydroxylamine-treated nahR DNA and selection on galactose/salicylate plates allowed isolation of 30 unique activation-deficient nahR alleles which fell into two classes: class I, defective in both activation and specific binding to the NahR activation site of the sal promoter; and class II, defective in activation, but with wild-type DNA binding activity. DNA sequence analysis showed that the amino acid substitutions eliminating DNA binding activity were mostly clustered in an NH2-terminal helix-turn-helix motif (residues 23-45) or a COOH-terminal domain (residues 239-291). Similar analysis of class II mutants identified a domain (residues 126-206) possibly involved in inducer binding and/or transcription activation functions. The partial trans-dominance of many mutant alleles and the size of NahR-specific DNA binding activity measured by gel filtration suggest that the active NahR protein may be a tetramer.

Alleles

Evaluation of methods for detecting venous reflux. Perspectives in venous insufficiency.

Using 793 limbs with nonobstructive venous reflux, we evaluated a number of techniques used for the assessment of venous reflux. The venous Doppler examination was found to be a reliable screening tool with excellent sensitivity and good specificity. Photoplethysmography was 97% sensitive in patients with ambulatory venous hypertension; however, in milder forms of reflux, it was less sensitive. The major drawback of photoplethysmography was the large number of false-positive results obtained. Ambulatory venous pressure measurement and another pressure-based technique, Valsalva-induced foot venous pressure measurement, defined overlapping but different normal and abnormal limbs. Descending venography, when performed as described by Kistner et al, was found to be a reliable tool to assess reflux with more than a 90% sensitivity. The horizontal technique of performing descending venography and nucleotide descending venographies had unacceptably low sensitivity and were abandoned. Features of venous reflux as outlined by these modern technical tools are described.

Evaluation Studies as Topic