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J H Rapp

Publications and source records attributed to J H Rapp.

At least 55 records · Page 3Linked to original sources

Chylomicrons can inhibit endotoxin activity in vitro.

Trauma, thermal injury, and nonlethal doses of endotoxin can promote the translocation of endotoxin across the mucosal barrier of the colon into the mesenteric lymphatics and systemic circulation. Bacterial endotoxemia induces changes in lipid metabolism, including an increase in circulating triglyceride-rich lipoproteins. Because cholesterol-rich lipoproteins can neutralize the toxic activity of endotoxin, both in vitro and in vivo, we asked whether triglyceride-rich chylomicrons can inhibit endotoxin activity in vitro as measured by a chromogenic Limulus assay. We tested the effect of intact versus heat-denatured chylomicrons on the in vitro activity of increasing concentrations of Escherichia coli (055:B5) endotoxin. Intact chylomicrons inhibited up to 12-fold the detection of as much as 1 microgram of endotoxin/mg of chylomicron triglyceride, compared to denatured chylomicrons (P less than 0.001). This study shows that chylomicrons are potent inhibitors of endotoxin activity in vitro. Because translocated endotoxin from the colon associates with gut-derived chylomicrons in the mesenteric lymphatics, this may represent a natural defensive mechanism against endotoxemia of enteric origin.

Chylomicrons↗

Chronic visceral ischemia. Three decades of progress.

Symptomatic visceral atherosclerosis is a major surgical challenge because of its life-threatening course and the complexity of its definitive operative treatment. Evolution in the operative approach to the visceral aorta and progress in the intraoperative management of patients undergoing complex vascular reconstructions prompted a review of the authors' cumulative experience in the surgical management of chronic visceral ischemia. Among all patients undergoing visceral revascularization at the University of California, San Francisco during the past three decades, 74 patients were identified whose primary reconstruction used transaortic endarterectomy (TA TEA) (n = 48) or antegrade bypass (AB) (n = 26), the authors' preferred revascularization techniques. The two treatment groups were comparable in gender distribution, age, presenting symptoms, and physical findings, although the amount of preoperative weight loss was greater in the AB group (35.8 +/- 19.5 versus 22.4 +/- 12.0, p = 0.003). The groups were also comparable in the prevalence of atherosclerosis risk factors, symptomatic vascular disease at other sites, and previous vascular operations. However associated renal artery atherosclerosis was slightly greater in the TA TEA group (58.3% versus 23.1%, p = 0.07) when compared to the AB group. Antegrade bypass was usually performed transabdominally (88.5%), while TA TEA was approached thoracoretroperitoneally (75.0%). Celiac revascularization was almost universal in both treatment groups, but the TA TEA group underwent significantly more frequent superior mesenteric artery (SMA) revascularization (93.8% versus 46.2%, p = 0.0001) and slightly more frequent inferior mesenteric repair (18.8% versus 3.8%, p = 0.07) than the AB group. In addition the frequency of combined renal and visceral repair (25.0% versus 0.0%, p = 0.01) as well as combined aortic, renal, and visceral repair (22.9% versus 3.8%, p = 0.03) was significantly greater in the TA TEA group. The obligatory interval of renal and visceral ischemia did not differ between the two approaches. The perioperative mortality rate was 12.2% and was the same for TA TEA (14.6%) and AB (7.7%). Overall the incidence of complications was the same with either operative approach, although patients in the TA TEA group tended to have multiple complications (17.1% versus 0.0, p = 0.03) and all significant pulmonary complications occurred in this group. Two patients were lost to follow-up. The cumulative percentage of patients who remained asymptomatic following AB or TA TEA was (respectively) 95.8% and 97.3% at 1 year and 86.5% and 86.1% at 5 years. Both of these operative approaches provide durable symptom relief with acceptable operative morbidity and mortality rates.(ABSTRACT TRUNCATED AT 400 WORDS)

Aged↗

Lower-extremity vascular grafts placed for peripheral vascular disease: prospective evaluation with duplex Doppler sonography.

Eighty-five men with 92 vascular grafts placed for peripheral vascular disease of the lower extremity underwent a total of 264 examinations with duplex Doppler over a 2.5-year period. In 64 patients who underwent more than one examination, the total follow-up encompassed 740 months. In 220 native femoral arteries (96.0%) the peak systolic velocity (PSV) was higher than that in the graft. Arteriovenous shunting was associated with a normal PSV and a markedly elevated diastolic component at spectral analysis. Focal fluid collections were common initially near the graft and usually disappeared uneventfully. An average PSV of 32 cm/sec or less was always associated with impending occlusion. The sensitivity of an average PSV of 40 cm/sec or less to indicate impending graft occlusion by the next visit was only 33%; the specificity, 94%. At initial examination, stenoses were associated with high PSV focally in the graft or low PSV with absent diastolic flow.

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Detection of endotoxin in triglyceride-rich lipoproteins in vitro.

Numerous investigations have been performed in which volunteers have received infusions of triglyceride-rich lipoproteins without apparent screening of the infusates for bacterial endotoxin. This study was designed to examine the capacity of triglyceride-rich lipoproteins to mask their endotoxin content in vitro as measured by a chromogenic modification of the standard Limulus assay. Lipoproteins and lipoprotein-deficient plasma were isolated from normal human plasma by sequential ultracentrifugation under apyrogenic conditions. Individual lipoproteins and a synthetic lipid emulsion were suspended in 10% lipoprotein-deficient plasma. Samples were then incubated at 37 degrees C for 4 hours with increasing concentrations of E. coli (055:B5) endotoxin and assayed for detectable endotoxin activity. The capacity to inhibit detection of endotoxin in 10% lipoprotein-deficient plasma was significantly increased (10 to 100 times) by the addition of VLDL (1.0 mg triglyceride/ml), chylomicrons (1.0 mg triglyceride/ml), or the synthetic lipid emulsion (2.5 mg triglycerides/ml). These data demonstrate that triglyceride-rich lipoproteins, and the synthetic lipid emulsion, can markedly inhibit the detection of endotoxin by the Limulus assay in vitro. In addition to the potential of harm to experimental subjects, infusion of endotoxin could vitiate kinetic studies by direct alteration of lipoprotein metabolism and by inducing changes in hepatic blood flow. Thus experimental protocols that involve the infusion of humans with triglyceride-rich lipoproteins should include detailed testing for the presence of endotoxin.

Chylomicrons↗

A prospective randomized trial of autologous platelet-derived wound healing factors for treatment of chronic nonhealing wounds: a preliminary report.

Previous studies have suggested that topically applied platelet-derived wound healing factors (PDWHF) accelerate wound healing by stimulating angiogenesis, fibroblast proliferation, and collagen synthesis. To assess the ability of platelet factors to facilitate healing of chronic cutaneous ulcers we performed a randomized, prospective, double-blind, placebo-controlled study of topical PDWHF in 18 patients with 26 lower extremity wounds refractory to conventional therapy. Wounds were present for at least 8 weeks (mean, 5.5 +/- 4.3 months). They were extensively debrided initially and were measured and photographed at weekly intervals for 12 weeks. Eight patients with nine wounds were treated with placebo solution (controls), and 10 patients with 17 wounds were treated with PDWHF (treatment group). Seventy-eight percent of patients had diabetes mellitus, 72% had occlusive peripheral vascular disease, and 28% had venous disease; distribution of these disorders was equivalent in both groups. Ankle-brachial indexes, which were often spuriously elevated, averaged 0.93 +/- 0.54 in controls and 1.04 +/- 0.56 in patients treated with PDWHF (p greater than 0.5). Mean transcutaneous oxygen tension was 37.8 +/- 11.9 mmHg in controls and 37.1 +/- 9.1 mmHg in patients treated with PDWHF. Initial wound area was larger in controls than in the patients treated with PDWHF (28.9 +/- 45.2 cm2 vs 13.0 +/- 4.4 cm2), but this difference was not statistically significant (p = 0.19). Three (33%) wounds (in two patients) healed in controls, and four (24%) wounds (in three patients) healed in the PDWHF group (p greater than 0.5). The rate of healing in controls was 1.9 +/- 2.7 cm2/week.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Cutaneous↗

The "natural history" of segmental wall motion abnormalities in patients undergoing noncardiac surgery. S.P.I. Research Group.

Intraoperative segmental wall motion abnormalities (SWMA) detected by transesophageal echocardiography (TEE) are sensitive, but not always specific, markers of myocardial ischemia. To determine their incidence, characteristics, and relation to postoperative cardiac morbidity, we continuously recorded the left ventricular short-axis view and 12-lead ECG in 156 high-risk patients undergoing non-cardiac surgery. Monitoring was clinically blinded. Wall motion was scored at predefined clinical, hemodynamic, and ECG events and at periodic intervals (26 +/- 11 samples per patient). We detected 44 episodes of new or worsened SWMA in 32 patients (20%). The severity of most episodes was limited to severe hypokinesis (24/44, 55%) followed by akinesis (16/44, 36%) and dyskinesis (4/44, 9%). The remaining 124 patients had normal wall motion or only mild hypokinesis (56/156, 36%) or chronic SWMA (68/156, 44%). The incidence of new SWMA did not differ for patients with known coronary artery disease (CAD) and those with cardiac risk factors only (22% vs. 19%, P = not significant), although CAD patients had a significantly greater incidence of chronic SWMA (62% vs. 41%, P = 0.02). The incidence of new or worsened SWMA was significantly greater during aortic vascular surgery (38% vs. 17%, P = 0.05). Approximately 40% of all new TEE changes occurred in the absence of either an apparent clinical event or a significant change in systolic blood pressure or heart rate. Ten patients had new or worsened SWMA persisting until the end of surgery, 8 with new akinesis, only 1 developing myocardial infarction. The distribution of new or worsened SWMA and significant intraoperative ST-T changes (n = 19) in this cohort was discordant: temporal overlap between modalities was present in only 5 patients. Major cardiac complications occurred in 5 patients (3.2%), all of whom underwent peripheral vascularization. All patients with cardiac complications and new or worsened SWMA also had intraoperative or early postoperative ST-T changes. We conclude that: 1) continuous TEE recording with offline analysis in this high-risk group of patients revealed a relatively low incidence of new or worsened SWMA (20%), most episodes of which were characterized by severe hypokinesis (55%); 2) episodes were more common in patients undergoing aortic vascular surgery; 3) approximately 40% of episodes were unaccompanied by clinical events or significant hemodynamic changes; 4) episodes were poorly correlated with postoperative cardiac complications; and 5) the discordant relation between TEE and ECG changes observed here necessitates careful monitoring of the ECG when TEE is used clinically.

Aged↗

Human very low density lipoproteins and chylomicrons can protect against endotoxin-induced death in mice.

Endotoxemia stimulates many physiologic responses including disturbances in lipid metabolism. We hypothesized that this lipemia may be part of a defensive mechanism by which the body combats the toxic effects of circulating endotoxin. We tested the effects of mixtures of endotoxin, lipoproteins, and lipoprotein-free plasma and determined the ability of varying concentrations of human very low density lipoproteins (VLDL) and chylomicrons, as well as low density lipoproteins (LDL) and high density lipoproteins (HDL), and of the synthetic lipid emulsion SOYACAL to prevent endotoxin-induced death in mice. This study demonstrates that the triglyceride-rich VLDL and chylomicrons, as well as cholesterol-rich LDL and HDL, and cholesterol-free SOYACAL can protect against endotoxin-induced death. Protection required small amounts of lipoprotein-free plasma, and depended on the incubation time and the concentration of lipoprotein lipid. Despite stringent techniques to prevent exogenous endotoxin contamination eight of ten duplicate VLDL preparations contained endotoxin (5,755 +/- 3,514 ng endotoxin/mg triglyceride, mean +/- SEM) making the isolation of endotoxin-free VLDL difficult. In contrast, simultaneous preparations of LDL and HDL were relatively free of endotoxin contamination (3 +/- 3 and 320 +/- 319 ng/mg total cholesterol, respectively), suggesting that the contamination of VLDL occurs in vivo and not during the isolation procedure. These observations suggest a possible role for increased triglyceride-rich lipoproteins in the host's defense against endotoxemia and infection.

Animals↗

Recurrent carotid stenosis: a consequence of local or systemic factors? The influence of unrepaired technical defects.

To determine the influence of unrepaired technical defects as well as systemic risk factors for atherogenesis on carotid artery healing after endarterectomy, we conducted a prospective study using intraoperative duplex scanning with spectral analysis to establish the initial status of the artery (N = 131 arteries), and then we studied these vessels at regular postoperative intervals with the same technique (N = 108 arteries, 265 studies). The vessels were divided into the operated and nonoperated segments of the common, internal, and external carotid arteries, and both intraoperative image and flow data were tabulated by artery segment. The technical factors that were analyzed included defect size, defect type, adjacent segment defects, number of defects, shunt use, vessel reopening, and peak, mean, and end-diastolic frequency and velocity. The systemic risk factors studied were sex, hypertension, diabetes, smoking, randomly drawn total serum cholesterol and triglyceride levels, and perioperative aspirin and dextran use. Data were analyzed by linear logistic regression analysis. Among the technical factors, only intraoperative defect size was significantly associated with risk of recurrent stenosis (p = 0.0175). Although any defect size adversely affected the condition of the vessel during follow-up, the magnitude of this effect was small for smaller defects (size category 1: less than or equal to 40% stenosis or flap length less than or equal to 25% of vessel diameter). The systemic factors that were associated with risk of recurrent stenosis were hypertension (p = 0.0002), smoking (p = 0.0016), and randomly drawn total serum cholesterol level (p = 0.0116). The fact that the operated segments consistently fared worse during follow-up than did the nonoperated segments (p = 0.0044) undoubtedly reflects the inevitable trauma of the endarterectomy, but also emphasizes the important contribution of systemic risk factors in recurrent carotid stenosis. Risk factor modification may be the most effective method of ensuring the durability of carotid endarterectomy.

Carotid Artery Diseases↗

Saphenous vein bypass to pedal arteries. An aggressive strategy for foot salvage.

Patients with forefoot ischemia and severe tibial artery disease present a major challenge to revascularization and foot preservation. Encouraged by the success of saphenous vein bypass to the more proximal arteries of the lower leg, we extended this technique to the pedal arteries. Between February 1986 and September 1988, we performed 26 bypasses in 24 men (mean age, 66 years) with critical foot ischemia. Sixty-three percent of the patients had diabetes mellitus, 50% had hypertension, and 71% were actively smoking. Angiography invariably revealed multiple tibial artery occlusions with reconstitution of the pedal arteries. The foot salvage rate was 83% (mean survival, 14 months), primary patency was 83% (mean survival, 9 months), and survival was 86% (mean, 12 months). There were 11 wound complications (42%); two resulted in disruptions of the distal anastomosis and eventual graft failure. Bypass to the pedal arteries yields a high rate of foot salvage and is comparable with more proximal bypass procedures; however, wound complications are common and require special technical considerations.

Aged↗

Recombinant human tissue-type plasminogen activator is an effective agent for thrombolysis of peripheral arteries and bypass grafts: preliminary report.

The efficacy, safety, and effects on hemostasis and coagulation of two doses of human tissue-type plasminogen activator in patients with acute and subacute peripheral arterial occlusion were compared. Seven patients with lower extremity ischemia and one patient with upper extremity ischemia had peripheral arterial thromboses (five arteries, three grafts) confirmed by clinical history, physical examination, and angiography. The duration of occlusion ranged from 31 hours to 30 days (mean 11.9 days). Tissue-type plasminogen activator was infused via a catheter directly into the thrombus at a randomly assigned dose of 0.05 mg/kg/hr (n = 4) or 0.025 mg/kg/hr (n = 4). Thrombolysis was complete in seven patients and partial in one. Duration of infusion ranged from 1 hour to 21 hours (mean 7.4 hours). The low dose required a longer infusion than did the high dose, but they were both successful in achieving thrombolysis. The one patient with partial thrombolysis had abrupt discontinuation of infusion when extravasation through a recently endarterectomized femoral artery developed. Otherwise there were no significant complications from tissue-type plasminogen activator therapy. Secondary procedures to correct underlying arterial disease were performed in five of the seven patients (71%) who had complete thrombolysis. Even at low dosages, infusion of tissue-type plasminogen activator into arteries or bypass graft thrombus produced complete thrombolysis, and no major complications occurred. This allowed more systematic effects to diagnose and treat underlying arterial disease.

Aged↗

"Angiography" by magnetic resonance imaging: detailed vascular anatomy without ionizing radiation or contrast media.

Using software to transform magnetic resonance imaging (MRI) tomographic data into three-dimensional projections, we have produced "angiograms" of the abdominal aorta in 18 patients with occlusive (15) and aneurysmal (3) disease. This information may be displayed to demonstrate flow, cross-sectional diameter, or aortic surface anatomy. To test the accuracy of the MRI studies, we compared them at selected points with the transected aorta and with routine aortograms. Relative cross-sectional diameter estimated by MRI was within 15% of measured aortic diameter in 14 of the 18 vessels and enabled correct detection of thrombus in 16. We conclude that MRI may accurately image the diseased abdominal aortic wall. In addition, an angiographic display format may aid in the interpretation of these studies. Although MRI is not likely to replace aortography, it could be used adjunctively to define aortic wall thickness and the presence of thrombus.

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Identification of aortic thrombus by magnetic resonance imaging.

The unique properties of magnetic resonance imaging result in the potential to differentiate various components of the diseased arterial wall. In this article four cases are presented in which magnetic resonance imaging showed mural aortic thrombus and its anatomic relationship to the visceral and renal arteries. Once thrombus is identified and localized specific operative strategies can be undertaken to prevent recurrent embolic events and/or avoid perioperative thromboembolic complications.

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Particle size distribution of lipoproteins from human atherosclerotic plaque: a preliminary report.

It is commonly believed that low-density lipoproteins (LDLs) carry cholesterol into the artery wall. In addition, some epidemiologic studies have suggested that triglyceride-rich lipoproteins, such as very-low-density lipoproteins (VLDLs), may be much less important than LDLs in atherogenesis. To determine if VLDLs or their metabolic remnants could have a direct role in the formation of atherosclerotic plaque, we examined lipoproteins isolated from endarterectomy specimens. Atherosclerotic plaque was obtained from eight subjects who underwent aortoiliac endarterectomy (4), aortic aneurysm repair (2), or visceral/renal endarterectomy (2). Plaques were washed extensively, minced, and incubated with a buffered saline solution. Lipoproteins were recovered from this solution via a selected-immunoaffinity column by means of a polyclonal antibody to human LDL (apolipoprotein B-100). Particle sizing from electron photomicrographs of negatively stained specimens indicated that 8% of the lipoprotein particles were the size of plasma VLDL (350 to 800 nm). Thirty-six percent were the size of plasma VLDL remnant particles (250 to 350 nm), and 56% were consistent in size with plasma LDL (175 to 250 nm). We conclude that VLDL- and VLDL remnant-sized particles appear to comprise a significant percentage of the lipoproteins found in human atherosclerotic plaque and could have a direct role in the atherosclerotic process.

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Preoperative balloon-tipped catheter placement for proximal control in visceral artery aneurysm surgery.

A 13 cm false aneurysm of the common hepatic artery developed after repeated episodes of pancreatitis in a 47-year-old man with diabetes who was undergoing chronic hemodialysis. A balloon-tipped catheter was positioned in the common hepatic artery before operation. This maneuver allowed proximal control of the aneurysm and suture closure of the hepatic artery defect with minimal dissection and blood loss in this high-risk patient.

Aneurysm↗

Recurrent carotid stenosis: operative strategy and late results.

From 1957 to 1985, 116 consecutive operations for recurrent carotid stenosis were performed in 99 patients at the University of California, San Francisco. Ninety-four patients underwent 103 reoperations for primary recurrent stenosis (nine patients had bilateral repairs). Seventy-two operations (70%) were performed to relieve cerebrovascular symptoms whereas the indication for 31 operations (30%) was high-grade stenosis. The cause of primary recurrent stenosis was myointimal hyperplasia (MIH) in 47 cases, whereas 56 were caused by recurrent atherosclerosis (ASO). Secondary recurrent stenosis developed in six patients from our own series (5.8%) and an additional six patients were referred after reoperation elsewhere. The 12 lesions in this group were evenly divided between MIH (six) and recurrent ASO (six). MIH resulted in a single tertiary recurrent stenosis. Myointimectomy or repeat endarterectomy and vein patch angioplasty were the most commonly used techniques for repair of a primary recurrent stenosis. Secondary recurrent stenosis necessitated resection of the carotid bifurcation and graft interposition when caused by MIH. Secondary recurrent stenosis caused by ASO could be treated by repeat endarterectomy and vein patch angioplasty in five of six cases. Five strokes occurred in the entire series (4.3%), resulting in two deaths. There were 23 cranial nerve palsies, which rarely persisted beyond 3 months. The morbidity and mortality rates for primary and secondary carotid reoperation are comparable to the original procedure and should not deter the vascular surgeon from reoperative carotid reconstruction whenever indicated.

Blood Vessel Prosthesis↗

Comparative effects of hypertension and nicotine on injury-induced myointimal thickening.

Although hypertension has been shown to increase myointimal thickening after arterial injury, a similar effect of nicotine has not been demonstrated. To compare the influence of nicotine with the known effect of hypertension, a standard balloon catheter injury was created in the aortas of four groups of experimental animals. A preliminary group (P) (n = 11) consisted of adult Wistar Kyoto rats used to determine the degree of denudation and the time course of arterial healing; group I (n = 10) consisted of adult Wistar Kyoto rats; group II (n = 13) consisted of spontaneously hypertensive rats; and group III (n = 16) consisted of Wistar Kyoto rats fed nicotine. Endothelial denudation was achieved after an identical injury with an aortic balloon catheter; completeness of denudation was confirmed in group P with Evans blue stain. Injured vessels were fixed by perfusion at 2- and 9-week intervals. Intima to media (I/M) ratios were measured at 82 points per animal by use of light microscopy. Computer-assisted statistical analysis was performed with the t test and Wilcoxon nonpaired rank sum test. Serum nicotine levels were maintained in group III at 73.3 +/- 36.7 ng/ml, which is comparable to levels in human smokers. There were no significant differences in I/M ratios between any of the groups at 2 weeks. At 9 weeks both groups II and III had significantly higher I/M ratios than did control subjects (p = 0.039). The nicotine-treated group had greater myointimal thickening than did the hypertensive animals (p = 0.02). Since there was no hypertension or tachycardia in nicotine-treated rats, we postulate that our data reflects the desquamating effect of nicotine.

Animals↗