Biomedical subjects
Publications and source records attributed to J V White.
Precise tissue apposition and edge eversion are essential for tissue fusion with the CO2 laser. A microtenaculum has been designed to accomplish this without the placement of horizontal mattress stay sutures. This instrument permits tissue orientation and approximation for primary laser fusion as well as for the repair of small gaps present after initial welding.
This is a prospective analysis of 351 patients in two distinct groups undergoing ascending phlebography, impedance plethysmography (IPG), and/or phleborheography (PRG) within the same 24-hour period. One hundred twenty patients also had a 125I-fibrinogen uptake test (RFUT). The two patient groups consisted of the following: those patients evaluated because of suspicion of deep vein thrombosis (DVT) (diagnostic) and those patients at high risk for postoperative DVT (total joint replacement) who had routine noninvasive testing and ascending phlebography (surveillance). The overall sensitivities for IPG and PRG were significantly better in the diagnosis group (71% [69 of 97 patients] and 78% [82 of 105], respectively) compared with the surveillance group (20% [14 of 71] and 27% [17 of 63], respectively) (p less than 0.0001). The sensitivities for IPG and PRG detecting proximal (A/K) thrombi was 83% (68 of 82 patients) and 92% (79 of 86) in the diagnosis group compared with 32% (11 of 34) and 33% (9 of 27) in the surveillance group (p less than 0.0001). Although there was no difference in overall incidence of DVT between the diagnosis group (56%, 118 of 212 patients) and the surveillance group (55%, 76 of 139), the results can be explained by the difference in A/K thrombi (84% [99 of 118] and 47% [36 of 76]) (p less than 0.001) and occlusive A/K thrombi (84% [58 of 69] and 23% [7 of 31]) (p less than 0.0001), respectively. Of the patients with A/K thrombi, 97% (67 of 69) in the diagnosis group had hemodynamically detectable thrombi compared with only 48% (12 of 25) in the surveillance group (p less than 0.001). Combining the RFUT with the noninvasive studies for surveillance significantly improved the sensitivity for both A/K and distal thrombi. Patient selection also appears to have a significant influence on the results of the combination of IPG and RFUT when the current surveillance group is compared with similarly performed studies in a previously reported diagnosis group. The location and magnitude of thrombi in any patient population can be skewed depending on indications and timing of testing, thereby significantly affecting the sensitivity of noninvasive tests. IPG and PRG are reliable for evaluating patients with suspected DVT. However, patients with postoperative DVT have a high incidence of nonocclusive thrombi. Because noninvasive hemodynamic tests cannot identify accurately postoperative DVT, they cannot be used to generate epidemiologic data or as end points for studies evaluating efficacy of prophylaxis in patients undergoing total joint replacement, and anatomic studies of the deep venous system continue to be required.
Human platelet-rich plasma (PRP) was aggregated with ADP to produce varying degrees of reversibility and platelet release, and then the chemical stimulation (as evidenced by optical transmittance) was compared with the flow resistance of physiologically-significant microaggregates, determined by constant-pressure filtration. The aggregate flow resistance was attributed to "weak" aggregates (which occluded the micropore filter at 20 mm Hg but which passed through the filter at 80 mm Hg) and "strong" aggregates (which occluded the filter at 80 mm Hg). As the ADP concentration was increased from 1 microM to 10 microM, the flow resistance of both the "weak" and "strong" aggregates generally increased, as did the maximum transmittance. No consistent trend was seen as the time after ADP addition increased from 5 to 30 minutes. Pretreatment of the PRP with epinephrine increased the maximum transmittance during ADP aggregation, produced less-reversible aggregates (less subject to deaggregation by PGE1), and increased the aggregate flow resistance over the range of filtration pressures tested. The addition of PGE1 to the aggregated sample before filtration nearly eliminated the flow resistance of the aggregates at all filtration pressures tested and partially reversed the optically-apparent aggregation. Pretreatment of PRP with PGE1 before epinephrine or ADP addition inhibited both the optically-detected aggregation and the development of flow resistance. The physical (hydrodynamic) strength of platelet aggregates is apparently related to the chemical stimulation of the release reaction and to aggregation irreversibility, possibly through the mediation of adenylate cyclase and cyclic AMP.
This study was undertaken to determine the significance of graft lumen exposure to blood-borne organisms in the development of graft infection. Three groups of dogs were studied. In group I (n = 20), the infrarenal aorta was dissected from surrounding tissue, divided, and reconstructed with a Dacron tube interposition graft. In group II (n = 9) the aorta was similarly isolated, but Dacron graft material was wrapped around the intact aorta. In group III (n = 13) the infrarenal aorta was isolated, but no graft material was placed. All dogs were given intravenous 1 X 10(7) Staphylococcus aureus at the completion of surgery. Group I grafts were harvested 8 hours, 1 day, or 21 days after bacterial challenge. Group II and III grafts were harvested 1 day or 21 days after infusion. At the time of harvest, selective cultures of the periaortic tissue (PAT), periaortic graft (PAG), and interposition graft lumen (GL) were taken. The overall infection rates were similar, with 17 of 20 (85%) dogs in group I, 6 of 9 (67%) in group II, and 11 of 13 (85%) in group III found to be culture positive. In group I, 3 of 3 dogs at 8 hours, 2 of 2 on day 1, and 12 of 15 on day 21 had positive PAT cultures. Only 4 of 15 on day 21 had positive GL cultures. In group II, 4 of 5 dogs on day 1 and 2 of 4 on day 21 had positive PAT and PAG cultures. In group III, 9 of 9 animals on day 1 and 2 of 4 on day 21 had positive PAT cultures. All aortic lumen cultures were negative in groups II and III. The difference between GL and PAT cultures was statistically significant in all groups (I, p = 0.01; II, p = 0.05; III, p = 0.01). Serial quantitative blood cultures revealed a mean bacterial load of 10.5 +/- 4.5 CFU/ml at 15 minutes postinfusion, which fell steadily until no bacteria were detected at 3.5 hours. Lymphangiography demonstrated periaortic pooling of lymph in the immediate postoperative period. These data suggest that the bacteremia in this model is transient and rapidly clears. Periaortic tissues quickly sequester bacteria, possibly because of lymphatic leakage. The GL appears to be secondarily infected.
This is a prospective analysis of patients undergoing 34 treatments for arterial thromboses and emboli with intra-arterial thrombolytic therapy. These included acute arterial thromboses, graft thromboses, arterial emboli and pulmonary emboli. Twenty-seven of 34 patients treated had evidence of lysis, 14 had complete lysis, 13 had partial lysis and seven had no lysis. Both patients with occlusions for longer than three weeks failed to respond to treatment. Thirty-two patients presented with ischemia of the extremity. Twenty-four of 32 patients had limb salvage with eight subsequently undergoing amputation. No patient who was treated for claudication or who had a patent popliteal artery distal to the acute thrombosis failed to respond. Extensive tibioperoneal occlusion generally responded poorly compared with femoropopliteal or more proximal thrombi. Complications are divided into direct (drug related) and indirect (technique related). Four of 34 patients had an extensive hemorrhagic event with two suffering intracranial bleeding who ultimately died. All of the patients with extensive hemorrhagic episodes had serum fibrinogen levels of less than 50 milligrams per cent. During infusion, extensive distal emboli occurred in three with two of these patients requiring thrombectomy; one instance resolved with infusion. Minor distal emboli occurred in three and all resolved with continued infusion. We believe that intra-arterial thrombolytic therapy is a valuable adjunct in the treatment of acute arterial occlusion. The local infusion of lytic agents appears to be more efficient than systemic therapy. The tip of the infusion catheter should be placed into the thrombus for optimal lysis, but not advanced too far. The fibrinogen level is a sensitive indicator of systemic lysis and should be maintained above 50 milligrams per cent. Systemic lysis is obtained even with low dose infusion when therapy exceeds six hours. Intra-arterial infusion of thrombolytic agents can be performed safely in the immediate postoperative period as well as intraoperatively if specific guidelines are followed. Patients with massive unilateral pulmonary embolism can be efficiently treated with intra-arterial lytic therapy.
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Oral and i.v. cyclosporine (Cs) pharmacokinetics determined from radioimmunoassay (RIA) data were compared in normal and pancreatectomized dogs. An altered pharmacokinetics of Cs was observed in the pancreatectomized dogs that include: a 170% larger central compartment volume; a 34% greater total-body clearance; and lower steady-state average serum concentrations relative to the normals. Even though there were marked intersubject variations, both groups displayed a triexponential decline in Cs serum concentrations and disposition kinetics. Following 7 daily oral doses of commercial cyclosporine (CsA) (20 mg/kg) the Cs serum trough concentrations of the pancreatectomized dogs were consistently below 100 ng/ml, while those of the normal dogs were above 400 ng/ml. No alteration of CsA oral absorption was noted following pancreatectomy. This study suggests that frequent serum Cs concentration monitoring, with appropriate dosage adjustments, even in normals, is necessary to assure adequate drug levels. More significantly, the CsA dosage for pancreatectomized dogs should be several times greater to maintain serum concentrations comparable to normal dogs.
Three factors leading to the development of postoperative deep venous thrombosis (DVT) are the hypercoagulable state, stasis, and vein wall injury, which occur in patients undergoing surgical procedures. Vein wall injury is thought to occur as a smooth muscle response to surgical trauma in veins distant from the operative site. Heparin and dihydroergotamine (DHE) were combined in an attempt to decrease the hypercoagulable factor and minimize stasis. We believe that by maintaining venous smooth muscle tone, the degree of endothelial damage is also diminished. Low-dose heparin acts through its effect of factor Xa and activation of antithrombin III; DHE selectively increases venous smooth muscle tone to accelerate venous blood flow velocity and minimize venous pooling. The European experience with combination DHE-heparin prophylaxis shows that this combination is more effective than either agent alone, and studies on orthopedic patients have shown that DHE/5,000 is effective in preventing postoperative DVT in this high-risk group. In the US, the Multicenter Trial evaluated postoperative DVT in general surgical patients. The combination of DHE/5,000 was statistically more effective in the prophylaxis of postoperative DVT than placebo (p = 0.0011). The interim results of an ongoing Multicenter Trial on the prophylaxis of postoperative DVT in patients undergoing total hip replacement indicate that DHE/5000 has significant prophylactic efficacy compared to placebo. It is proposed that the mechanism of action of the DHE-heparin combination is synergistic, since all 3 limbs of Virchow's triad are potentially affected.
Disfiguring facial edema and elevated intracranial pressure often accompany ligation and excision of the internal jugular veins (IJV) during simultaneous or staged bilateral radical neck dissection. To minimize this morbidity, unilateral reconstruction of the IJV was undertaken at the time of second-side neck dissection in 11 patients. Five patients underwent reconstruction with the spiraled saphenous vein (SVG) and in six patients 10 mm externally supported polytetrafluoroethylene (e-PTFE) was used. Prebypass jugular venous stump pressures (JVPs) were measured and ranged from 28/17 to 75/54 mm Hg with mean pressures of 17 to 62 mm Hg. Two patients had simultaneous neck dissections and nine had staged dissections. The staged interval ranged from 0.3 to 33 months. Six of nine staged reconstructions were right-sided and three of nine were left-sided. Low molecular weight dextran was started intraoperatively, regional heparinization was used in all but two cases, and platelet inhibitors were continued postoperatively in all patients. Additional time in the operating room was 45 minutes (mean). All patients have been followed up 2 to 18 months postoperatively. B-mode ultrasonography, Doppler spectrum analysis, CT scan with contrast, and magnetic resonance imaging were used to assess patency. Four of five SVGs and three of six e-PTFE grafts have remained functional, which resulted in an overall patency rate of 64%. Four grafts (one SVG, three e-PTFE) failed in the immediate postoperative period. All grafts in patients who had a mean JVP greater than 30 mm Hg remained patent, whereas those in patients with lower stump pressures thrombosed.(ABSTRACT TRUNCATED AT 250 WORDS)
Since clinical diagnosis of DVT is often inaccurate, it has become accepted that an objective means of diagnosing clot in the deep venous system becomes critically important in the management of these patients. Important to understanding the diagnostic capabilities of any test are the anatomic and physiologic characteristics of the deep venous system. The venous Doppler examination monitors the velocity of blood flowing through a particular vein. Doppler probes in the 5 to 10 mHz range are routinely used. Respiratory variation is a normal finding due to a diminished flow signal during inspiration, followed by a progressive increase in flow signal during expiration. Characteristics of the spontaneous flow signals are the most important part of interpreting the venous Doppler examination. In addition, the response to distal or proximal compression (augmentation) adds important information to the interpretation; however, the response during any augmentation maneuver depends on the rapidity of compression, the force of compression, the quantity of blood in the veins at the time of compression, and the distance between the Doppler probe and the compression point. The literature reports a wide range of sensitivity and specificity for the Doppler examination, but there is uniform agreement and an observable trend that physicians with a large experience and a dedicated interest will obtain much better results than physicians with less experience and less interest. Phleborheography is a six-channel volumetric plethysmographic technique that monitors volume changes in the lower extremities associated with respiration and foot and calf compression. The volumetric tracings obtained are similar to the velocity profiles obtained on the venous Doppler examination. The criteria used in interpreting phleborheographic tracings are respiratory waves and baseline elevation (major criteria), and prominent arterial pulse waves and foot emptying (minor criteria). Previously reported overall sensitivities for detecting DVT are 83 to 93 percent, with sensitivities of detecting proximal vein thrombosis of 92 to 96 percent. Specificities have been reported to be 87 to 97 percent. In a prospective analysis of 126 extremities with phleborheography and phlebography carried out within the same 24 hour period at Temple University Hospital, we found an overall sensitivity of 79 percent (51 of 65 patients); however, the sensitivity for proximal vein thrombosis was 91 percent (49 of 54 patients).(ABSTRACT TRUNCATED AT 400 WORDS)
The cause of postoperative DVT is considered to be changes in blood coagulation, stasis of blood within the veins, and injury to the vein wall. The coagulation changes have been investigated and documented and involve platelet activation, stimulation of the coagulation cascade, and blunting of endogenous fibrinolytic activity. Stasis has been objectively identified by retention of contrast material in soleal sinuses and marked changes in venous flow velocity in patients in the supine position and in those under general anesthesia. Vein wall injury is more controversial, but has been shown to be directly related to venodilation. Such dilation of veins occurs in response to operative trauma, hence venous endothelial damage most likely plays a part in the milieu responsible for postoperative DVT. The prophylaxis provided by the combination of dihydroergotamine and heparin appears to affect each of the three limbs of Virchow's triad. Heparin achieves its prophylactic benefit by activating antithrombin III. Activated antithrombin III affects numerous sites in the coagulation cascade. It has been shown that 1 micrograms of antithrombin III inhibits the formation of 1 unit of thrombin; however, in the presence of heparin, 1 micrograms of activated antithrombin III inhibits 750 units of thrombin. Dihydroergotamine increases venous smooth muscle tone without affecting arteriolar smooth muscle. Hence, it has the effect of preventing stasis without increasing blood pressure. It also affects the platelet membrane, prostaglandin synthesis, and blood distribution, although these findings need to be elucidated. The combination of dihydroergotamine and heparin seems to have a synergistic prophylactic effect in preventing postoperative DVT. Heparin modifies the coagulation changes, whereas dihydroergotamine minimizes stasis and potentially prevents the endothelial damage caused by excessive operative venodilation. Such a combination of effects can explain the synergistic prophylactic efficacy found when dihydroergotamine and heparin were employed in combination in the multicenter trial [42].
This study was undertaken to assess factors affecting limb salvage after femorodistal bypass in patients with established gangrene. From January 1977 through June 1983, 361 patients underwent infrapopliteal bypasses; 58 patients (59 limbs) had forefoot and/or toe gangrene. There were 33 men and 25 women (mean age 67.6 years), and 40 patients (69%) were diabetic. A total of 71 femorodistal bypass procedures were performed in these patients: a single bypass in 49, repeat procedure in eight, and multiple bypasses in two patients. Graft material was autogenous saphenous vein in 22 cases, polytetrafluoroethylene (PTFE) in 39 cases, and a composite graft in 10 procedures. After bypass 50 patients underwent limited toe or forefoot amputation with uncomplicated healing. Limb salvage by life-table analysis was 70% at 1 year, 60% at 3 years, and 28% at 5 years. The graft patency at 3 years was 65% for vein grafts and 30% for PTFE grafts. In the entire series the operative mortality rate was 1.7%. Age, sex, hypertension, or diabetes mellitus did not influence the result of surgery. Similarly, failure of a previous femoropopliteal or tibial graft did not reduce the likelihood of limb salvage. Graft patency, however, is prerequisite for limb salvage, and graft patency can be maintained by thrombectomy or repetitive bypass. The present study suggests that limb salvage is possible in as many as two thirds of limbs with established gangrene. Although saphenous vein remains the graft material of choice, its absence should not preclude attempts at limb salvage. Repetitive grafting did not jeopardize patient safety but contributed significantly to extended limb survival.
The daily excretion of urinary protein was evaluated in 8 conditioned research dogs and in 10 hospitalized, proteinuric dogs, using 24-hour urine collections. Concurrent with each 24-hour urine collection, a 5- to 10-ml urine specimen was obtained during midday. The ratio of urine protein to urine creatinine concentration was determined from the single urine specimen for each dog. Linear regression analysis was used to calculate the correlation between that ratio and the 24-hour urinary protein loss (mg/kg of body weight). The coefficient of determination was significant (r2 = 0.95, P less than 0.0001). Determination of the protein-to-creatinine ratio in a single urine specimen was found to be a sensitive, rapid, and dependable diagnostic technique for detection and quantitative estimation of proteinuria.
Two simple methods for direct antibacterial protection of synthetic vascular grafts were investigated. In the first protocol the highly protein-bound antibiotics nafcillin (90% protein bound), cefazolin (80%), and cefamandole (70%) were added directly to preclotting blood. Knitted Dacron grafts preclotted in the presence of one of these drugs absorbed significant amounts. Although at high concentrations these antibiotics exhibited anticoagulant effects, significant antibacterial protection was obtained at lower antibiotic levels. Washing treated grafts for 6 hours failed to eliminate the antibacterial activity. Antibiotics remained on the grafts for at least 96 hours. In the second protocol knitted Dacron grafts were soaked in a suspension of silver-pefloxacin, a silver-nalidixic acid analogue with intense antistaphylococcic activity. Using 110Ag-labeled complexes, significant antibiotic activity was documented on the graft after 19 days of washing. Four nafcillin-treated prostheses, six silver-pefloxacin-coated grafts, and 11 control grafts were interposed in the infrarenal aorta of dogs and immediately challenged with an intravenous infusion of 1 X 10(7) Staphylococcus aureus. None of the four nafcillin-treated grafts was infected at 3 weeks. One of the six silver-pefloxacin-coated grafts grew staphylococci, and 9 of 11 controls had positive graft cultures for Staphylococcus when harvested. These studies suggest that prosthetic grafts can be simply coated at the time of implantation with antibiotics selected for appropriate binding and antibacterial characteristics to obtain an infection-resistant prosthesis.
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The use of lasers as surgical tools may open up new possibilities for the treatment of atherosclerotic occlusive vascular disease. However, basic information regarding the effect of laser radiation to the lumen of normal blood vessels is needed prior to clinical application. This work investigates the nature of the CO2 laser-induced vascular wound and the time course of its healing in the rabbit aorta. The chief short-term problem with CO2 laser radiation of the luminal surface of blood vessels is thrombosis.
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