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J H Rapp

Publications and source records attributed to J H Rapp.

At least 37 records · Page 2Linked to original sources
PubMed1994

Endotoxin and cytokines increase hepatic messenger RNA levels and serum concentrations of apolipoprotein J (clusterin) in Syrian hamsters.

Infection and inflammation induce alterations in hepatic synthesis and plasma concentrations of the acute phase proteins. Our results show that apolipoprotein (apo) J is a positive acute phase protein. Endotoxin (LPS), tumor necrosis factor (TNF), and interleukin (IL)-1 increased hepatic mRNA and serum protein levels of apo J in Syrian hamsters. Hepatic apo J mRNA levels increased 10- to 15-fold with doses of LPS from 0.1 to 100 micrograms/100 g body weight within 4 h and were elevated for > or = 24 h. Serum apo J concentrations were significantly increased by 16 h and further elevated to 3.3 times that of control, 24 h after LPS administration. Serum apo J was associated with high density lipoprotein and increased fivefold in this fraction, after LPS administration. Hepatic apo J mRNA levels increased 3.5- and 4.6-fold, with TNF and IL-1, respectively, and 8.2-fold with a combination of TNF and IL-1. Serum apo J concentrations were increased 2.3-fold by TNF, 79% by IL-1, and 2.9-fold with a combination of TNF and IL-1. These results demonstrate that apo J is a positive acute phase protein.

Amino Acid Sequence↗
PubMed1993

Limb salvage and wound coverage in patients with large ischemic ulcers: a multidisciplinary approach with revascularization and free tissue transfer.

PURPOSE: Large ischemic wounds, particularly with exposed bone or tendons, may not heal even after successful revascularization. We have taken an aggressive approach for limb salvage that uses autogenous vein grafting and simultaneous microvascular free tissue transfer. METHODS: In the past year, seven patients (average age 67 years; range 56 to 79) with ischemic disease and distal ulceration underwent revascularization for limb salvage and free tissue transfer. Each had a nonhealing wound (average size 80 cm2), present for 8.6 months (range 2 to 24 months). Simultaneous vein bypass and free tissue transfer was performed in four (57%) of the seven patients. RESULTS: All flaps were initially viable; however, one was lost on day 4 because of hypotension and congestive heart failure. One patient with a successful flap died at 1 month of pneumonia. Minor wound complications were seen in four (57%) of seven patients. Five of the seven patients had the wounds heal completely and are ambulatory at an average follow up of 10 months. CONCLUSIONS: Our aggressive approach was successful in preserving limb length and function in 71% of our patients. We perform simultaneous procedures whenever possible to minimize operative and hospitalization times. We believe that this combined approach optimizes the treatment of ischemic limbs with large ulcers.

Aged↗
PubMed1993

Chylomicrons enhance endotoxin excretion in bile.

Chylomicrons prevent endotoxin toxicity and increase endotoxin uptake by hepatocytes. As a consequence, less endotoxin is available to activate macrophages, thereby reducing tumor necrosis factor secretion. To determine whether the chylomicron-mediated increase in hepatocellular uptake of endotoxin results in increased endotoxin excretion into bile, we examined bile after endotoxin administration. A sublethal dose (7 micrograms/kg) of 125I-endotoxin was incubated with either rat mesenteric lymph containing nascent chylomicrons (500 mg of chylomicron triglyceride per kg of body weight) or an equal volume of normal saline (controls) for 3 h and then infused into male Sprague-Dawley rats. Bile samples were collected via a common bile duct catheter for 24 h. Infusion of endotoxin incubated with chylomicrons increased biliary excretion of endotoxin by 67% at 3 h (P < or = 0.006) and by 20% at 24 h (P < or = 0.01) compared with infusion of endotoxin incubated in saline. Endotoxin activity, as measured by the Limulus assay, was not detected in the bile of test animals. However, endotoxin activity was detected after hot phenol-water extraction of bile, demonstrating that endotoxin is inactive in the presence of bile but retains bioactivity after hepatic processing. Since the majority of an intravenous endotoxin load has been shown to be cleared by the liver, acceleration of hepatocyte clearance and biliary excretion of endotoxin may represent a component of the mechanism by which chylomicrons protect against endotoxin-induced lethality.

Animals↗
PubMed1993

Effect of dietary lipid peroxides on metabolism of serum chylomicrons in rats.

We have found that in rats the peroxide content of chylomicrons (CM) is determined by the lipid peroxide concentration in the diet, indicating that dietary lipid peroxides are incorporated into the lymph CM. Moreover, these incorporated lipid peroxides influence the normal CM metabolism. When radiolabeled CM were injected into rats, there was no difference in the initial plasma removal between CM prepared from oil with low peroxide content (control CM) and CM prepared from oil with high peroxide content (oxidized CM). However, the tissue distribution of the labels indicated that the hepatic uptake of CM decreased with increasing lipid peroxide content of CM. At 10 min after injection of CM, liver uptake of cholesterol label was 48.39 +/- 3.08% for control CM and 31.41 +/- 10.73% for oxidized CM. Vitamin E enrichment of control CM increased their hepatic uptake to 61.07 +/- 0.83%. Additionally, binding of oxidized CM to the heart endothelium increased from 2.55 to 3.60% compared with binding of control CM. When the hydrolysis of control and oxidized CM by endothelial lipoprotein lipase (LPL) was tested in a heart perfusion system, we found that after 30 min, 56.51 +/- 5.81% of control and 76.82 +/- 1.75% of oxidized CM were not hydrolyzed and remained in the perfusate. Thus our results indicate that the altered metabolism of oxidized CM may be related to a reduced hydrolysis rate by endothelial LPL.

Animals↗
PubMed1993

Chylomicrons alter the fate of endotoxin, decreasing tumor necrosis factor release and preventing death.

The hypertriglyceridemia of infection was traditionally thought to represent the mobilization of substrate to fuel the body's response to the infectious challenge. However, we have previously shown that triglyceride-rich lipoproteins can protect against endotoxin-induced lethality. The current studies examine the mechanism by which this protection occurs. Rats infused with a lethal dose of endotoxin preincubated with chylomicrons had a reduced mortality compared with rats infused with endotoxin alone (15 vs. 76%, P < 0.001). Preincubation with chylomicrons increased the rate of clearance of endotoxin from plasma and doubled the amount of endotoxin cleared by the liver (30 +/- 1 vs. 14 +/- 2% of the total infused radiolabel, P < 0.001). In addition, autoradiographic studies showed that chylomicrons directed more of the endotoxin to hepatocytes and away from hepatic macrophages. Rats infused with endotoxin plus chylomicrons also showed reduced peak serum levels of tumor necrosis factor as compared with controls (14.2 +/- 3.3 vs. 44.9 +/- 9.5 ng/ml, mean +/- SEM, P = 0.014). In separate experiments, chylomicrons (1,000 mg triglyceride/kg) or saline were infused 10 min before the infusion of endotoxin. Chylomicron pretreatment resulted in a reduced mortality compared with rats infused with endotoxin alone (22 vs. 78%, P < 0.005). Therefore, chylomicrons can protect against endotoxin-induced lethality with and without preincubation with endotoxin. The mechanism by which chylomicrons protect against endotoxin appears to involve the shunting of endotoxin to hepatocytes and away from macrophages, thereby decreasing macrophage activation and the secretion of cytokines.

Animals↗
PubMed1993

The effect of oxidized lipids in the diet on serum lipoprotein peroxides in control and diabetic rats.

The levels of oxidized serum lipoproteins are increased in humans and animals with diabetes. We have examined the contribution of dietary oxidized lipids on the levels of oxidized lipoproteins. In both control and streptozocin induced diabetic rats, the oxidized lipid content of mesenteric lymph chylomicrons (CM) increased when increasing quantities of oxidized lipids were administered intragastrically. However, at all levels of administered oxidized lipids, the quantity of oxidized lipids in CM was greater in the diabetic animals. These results indicate that oxidized lipids are absorbed and packaged into CM and suggest that there is increased absorption of oxidized lipids in diabetic animals. In nondiabetic rats fed a fat-free diet, the levels of oxidized lipids in their serum lipoproteins were very low. When oxidized lipids were added to the diet, the quantity of peroxides in serum lipoproteins increased about fivefold. In diabetic animals fed a fat-free diet, there were also very low levels of oxidized lipids in their serum lipoproteins, and there was no difference between control and diabetic rats. However, when diabetic animals were fed a diet containing oxidized lipids, the quantity of oxidized lipids in their serum lipoproteins increased 16-fold and were significantly greater than in controls. Thus, in both control and diabetic rats the quantity of oxidized lipids in the diet largely determines the levels of oxidized lipids in circulating lipoproteins. However, in diabetic animals the effect of diet is more pronounced. Together with the CM studies, these results demonstrate that dietary oxidized lipids make a major contribution to the levels of oxidized lipids in circulating lipoproteins and indicate that increased absorption of oxidized lipids in diabetic animals may play a role in the elevation of oxidized lipoproteins observed in this disorder.

Animals↗
PubMed1993

The protective effect of serum lipoproteins against bacterial lipopolysaccharide.

Lipoproteins bind and inactivate bacterial endotoxin, both in vitro and in vivo. Both cholesterol ester-rich and TG-rich lipoproteins, and TG-rich lipid emulsions can prevent death in mice when pre-incubated with a lethal dose of endotoxin before intraperitoneal administration. Chylomicrons can also prevent death when given intravenously after endotoxin in rats. The metabolic fate of lipoprotein-bound endotoxin appears to be directed by the lipoprotein particle. When administered with chylomicrons, the plasma clearance and hepatic uptake of endotoxin are enhanced. Endotoxin is shunted preferentially to hepatocytes and away from hepatic macrophages, thereby increasing endotoxin excretion [corrected] in bile. The survival benefit and alterations in metabolism afforded by chylomicrons correlate with a reduction in peak serum levels of tumour necrosis factor (TNF), providing a possible mechanism by which lipoproteins protect against endotoxin-induced death. These findings suggest a possible role for lipoproteins or lipid emulsions in the body's defence against endotoxaemia.

Animals↗
PubMed1993

Cigarette smoke alters chylomicron metabolism in rats.

PURPOSE: Cigarette smoking may exert its atherogenic effect by delaying the plasma clearance of dietary fat and cholesterol, allowing more time for their interaction with the artery wall. To study the effects of smoke on chylomicron metabolism in rats, we examined the metabolic effects of smoke on both whole animals and chylomicron particles in vitro. METHODS: Carbon 14- and hydrogen 3-labeled chylomicrons were injected intravenously into smoke-treated rats and control rats that were not exposed to smoke (sham smoked). Plasma clearance, hepatic uptake, and heart binding were measured. In a second set of experiments, chylomicron particles were exposed to cigarette smoke in vitro by either: (1) passing smoke through chylomicrons suspended in saline solution (SCM) or (2) passing smoke through saline solution alone, then mixing the saline solution with chylomicrons (CM + SS). Normal (non-smoke exposed) rats were infused with either SCM, CM + SS, or control chylomicrons (CCM). Plasma clearance, hepatic uptake, and heart binding were again measured. RESULTS: The initial plasma clearance time of labeled chylomicrons did not differ between smoke-treated and control animals. However, hepatic uptake of chylomicron cholesterol was slower in smoke-treated animals (46.1% +/- 0.9% of injected dose) than in controls (61.5% +/- 2.1%, p < 0.001). In contrast, more labeled chylomicrons remained in the heart of smoke-treated rats than controls (0.89% +/- 0.18% vs 0.45% +/- 0.05%, p < 0.05). Disappearance of 14C-labeled cholesterol from blood was delayed in rats injected with SCM (half-life = 9.0 +/- 0.4 minutes) and CM + SS (half-life = 8.0 +/- 0.4 minutes), compared with the time in rats injected with CCM (6.6 +/- 0.3 minutes, p < 0.05). Hepatic uptake of SCM (40.6% +/- 1.9% of injected dose) and CM + SS (45.0% +/- 1.9%) was less than that of CCM (60.7% +/- 4.4%, p < 0.05). In addition, the binding to the heart increased from 0.97% +/- 0.29% (CCM) to 2.45% +/- 0.30% with the infusion of SCM (p < 0.05). The binding in the heart of CM + SS (0.95% +/- 0.04%) was not different from that of CCM. CONCLUSIONS: These data demonstrate for the first time that cigarette smoke exposure prolongs chylomicron residence time in tissues (heart) and delays hepatic uptake of chylomicron cholesterol in rats. The effect is present when either the animal or the chylomicron particle is exposed to smoke. We hypothesize that prolonged binding of relatively cholesterol-rich chylomicron remnants to endothelial surfaces could create a more atherogenic postprandial milieu.

Animals↗
PubMed1993

Comparison of cardiac morbidity rates between aortic and infrainguinal operations: two-year follow-up. Study of Perioperative Ischemia Research Group.

PURPOSE: We have previously prospectively compared the differences in perioperative cardiac ischemic events in 140 patients undergoing major abdominal (n = 53) versus infrainguinal (n = 87) vascular operations. This study was designed to extend these observations by determining the 2-year cardiac prognosis of patients at high risk undergoing abdominal aortic versus infrainguinal vascular operations. METHODS: Data included historical, clinical, and laboratory data collected during the in-hospital period, and at 6 months, 1 year, and 2 years after surgery. This information was collected independently of the usual clinical care visits. Data were analyzed with Cox's proportional hazards model. RESULTS: There were 11 in-hospital deaths overall (five [9%] aortic; six [7%]) infrainguinal). 628 days (median 726 days). Fifteen patients (12%) had fatal myocardial infarctions, two (4%) of which occurred in patients who underwent aortic procedures and 13 (16%) of which occurred in patients who underwent infrainguinal operations. Nonfatal myocardial infarctions befell one (2%) patient undergoing aortic surgery and four (5%) patients undergoing infrainguinal surgery. One (2%) patient undergoing aortic surgery and three (4%) patients undergoing infrainguinal surgery were admitted to the hospital with unstable angina during the follow-up period. In all, adverse cardiac outcomes occurred in 20 of 81 (25%) patients who had infrainguinal procedures compared with four of 48 (8%) patients who had aortic operations (p = 0.04). Multivariate analysis showed that a history of diabetes (p = 0.001) and definite coronary artery disease (p = 0.01) are independently associated with adverse outcomes after both types of peripheral vascular operations. CONCLUSIONS: The incidence of long-term adverse cardiac outcomes in patients at high risk undergoing infrainguinal operations is substantially greater than in those undergoing aortic operations, mostly because of a greater prevalence of diabetes, and definite coronary artery disease in the former group.

Aged↗
PubMed1992

Adverse effects of aspirin in the treatment of asymptomatic carotid artery stenosis. The VA Cooperative Asymptomatic Carotid Artery Stenosis Study Group.

We prospectively analyzed adverse effects of aspirin in a multicentered cooperative study undertaken to determine the role of endarterectomy in the treatment of asymptomatic carotid artery stenosis. Persons with active peptic ulcer disease or known intolerance to aspirin were excluded from the study. Patients initially received 650 mg aspirin twice daily. After a 54-month recruitment period, 444 patients in 11 centers were followed up for as many as 8 years (mean 47.9 +/- 27.9 months). Patients intolerant to 650 mg aspirin twice daily could be switched to enteric-coated aspirin or "low-dose" aspirin (80 to 325 mg daily). At the conclusion of the study, we performed a cross-sectional analysis of aspirin usage and complications. Overall, there were 757 episodes reported wherein adjustments in study medications were made, including cessation and change in formulation or dosage. At the conclusion of the study, at the time of death, or at occurrence of a neurologic end point, 16% of patients were off medication entirely, 51% had been converted to enteric-coated aspirin, and only 33% were taking regular aspirin with 27% of those having been placed on a reduced dosage. Adverse reactions were ascertained from 4954 patient visit records. In all there were a total of 837 adverse reactions reported, or one in every 5.9 visits. The most frequently reported reaction was heartburn or stomach pain for which 372 episodes were reported in 184 (42%) patients. Nausea or vomiting occurred on 79 occasions in 58 patients, and bloody stools were reported 52 times in 41 patients. We conclude that high-dose aspirin therapy for asymptomatic carotid artery stenosis is poorly tolerated and that adverse reactions even to low-dose enteric-coated aspirin are common even in patients screened for aspirin intolerance.

Aged↗
PubMed1992

Relation of plasma lipid and apoprotein levels to progressive intimal hyperplasia after arterial endarterectomy.

BACKGROUND: To examine the relation of plasma lipoproteins to the proliferative response after arterial injury in humans, we examined the plasma lipid, lipoprotein, and apoprotein levels of 20 patients with early recurrent stenosis caused by intimal hyperplasia after carotid endarterectomy. These were compared with 20 controls who had no evidence of recurrent stenosis by duplex ultrasound scanning. METHODS AND RESULTS: By univariate analysis, the reoperated patients had higher levels of plasma cholesterol (251 versus 225 mg/dl, p less than 0.05), total triglycerides (173 versus 105 mg/dl, p less than 0.03), and low density lipoprotein (LDL) apoprotein B (99.8 versus 77.2 mg/dl, p less than 0.003). The ratio of cholesterol to apoprotein B in LDL was lower in patients with restenosis (p less than 0.04), suggesting LDL of smaller diameter. High density lipoprotein (HDL) cholesterol level was reduced (45 versus 55 mg/dl, p less than 0.01) in patients with restenosis. With statistical adjustment for the correlations between these variables by multivariate analysis, both LDL apoprotein B and HDL cholesterol were independent predictors of the risk of restenosis. Ten patients with restenosis but only two controls had one or two apolipoprotein E4 alleles. CONCLUSIONS: Elevated lipid levels usually associated with an increased risk of atherosclerosis may predispose patients to an increased incidence of intimal hyperplasia after endarterectomy.

Aged↗
PubMed1992

Chylomicron and chylomicron remnant metabolism in STZ-induced diabetic rats.

The small intestine is an important source of plasma lipoproteins in various diabetic animal models. This increase in intestinally derived lipids originate from diet and/or primary lipid synthesis, and these lipids are transported to the plasma as chylomicrons (CM). The understanding of the metabolism of these triglyceride-rich particles has assumed considerable importance. When [14C]cholesterol and [3H]triglyceride-labeled normal CM were injected into rats, we found no difference in either initial plasma clearance or in the hepatic uptake between control and diabetic rats. However, the clearance rate and hepatic uptake were dependent on the triglyceride concentration administered. Both the initial clearance and hepatic uptake in control and diabetic rats slowed to a similar extent with increasing triglyceride dose demonstrating the influence of the size of the endogenous triglyceride pool on the metabolic rate of CM. No difference was found in the clearance of CM remnants between control and diabetic rats when examined both in vivo and in liver perfusion experiments. Furthermore, with affinity chromatography, we found that the increase in serum triglycerides levels in diabetic rats was due to triglyceride-rich very-low-density lipoproteins and/or CM and not to the accumulation of remnants, which supports the observation that remnant clearance is not impaired. Despite the absence of alterations in bulk CM metabolism, we observed an increase in CM-CM remnant binding to the endothelium in hearts of diabetic rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Magnetic resonance angiography of the carotid artery combining two- and three-dimensional acquisitions.

To assess the agreement between magnetic resonance angiography and conventional angiography in the evaluation of carotid stenosis, 61 carotid arteries of 40 patients were studied by combined two- and three-dimensional magnetic resonance angiography and conventional angiography. Stenosis of the internal carotid artery was categorized as mild, moderate, severe, critical, or complete occlusion. In 42 arteries, the degree of stenosis according to magnetic resonance angiography correlated exactly to that found by conventional angiography. In the remaining 19 carotid arteries, the magnetic resonance angiographic measurement of stenosis differed from the conventional angiographic measurement by only one size category. The Spearman rank correlation coefficient was 0.95 (p < 0.001). This study showed that by combining information from two- and three-dimensional magnetic resonance angiographic studies and making use of the advantages of each method, magnetic resonance angiography was comparable to conventional angiography in determining carotid stenosis. Magnetic resonance angiography tended to demonstrate a higher level of stenosis when there was a discrepancy. These data demonstrate that magnetic resonance angiography is a steadily improving technology. Although additional studies need to be done, it seems clear that magnetic resonance angiography will be an imaging modality comparable in accuracy to conventional angiography.

Aged↗
PubMed1992

Inhibition of injury induced intimal hyperplasia by saralasin in rats.

Increasing evidence points toward local production of renin and angiotensinogen in the artery wall. Because angiotensin converting enzyme (ACE) inhibitors have been shown to block intimal hyperplasia after arterial injury in the rat, it has been suggested that angiotensin II is an important mediator of the proliferative response to vascular injury. To prove that previous observations with use of ACE inhibitors are a result of effects on local angiotensin levels versus nonspecific drug effects, we tested the ability of an unrelated drug, the angiotensin II receptor antagonist saralasin, to similarly block intimal hyperplasia after aortic injury in the rat. Balloon catheter aortic denudation was performed in 28 rats pharmacologically treated for 14 days after surgery and split into four groups: group 1, saralasin 360 micrograms/kg/hr intravenously; group two, normal saline 0.5 mm3/hr intravenously; group 3, captopril 100 mg/kg/day orally; and group 4, heparin 50 U/kg/hr intravenously. Animals were killed and aortas were perfusion fixed at physiologic pressure 14 days after denudation. Cross-sectional intima-to-media ratios were calculated by computerized planimetry. Compared with saline controls, saralasin inhibited intimal hyperplasia 45% (p less than 0.001), captopril 59% (p less than 0.001), and heparin 68% (p less than 0.001). A reduction in total intimal area was also evident in animals treated with saralasin (p less than 0.01). Blood pressure in the group treated with captopril decreased from 107.4 +/- 3.9 to 96.3 +/- 4.3 mm Hg (p less than 0.01) after 6 days, whereas saralasin and heparin had no effect on blood pressure. Weight gain during the study was reduced in groups treated with captopril and heparin but not in the group treated with saralasin.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1992

Comparison of cardiac morbidity between aortic and infrainguinal operations. Study of Perioperative Ischemia (SPI) Research Group.

We prospectively compared the differences in perioperative cardiac ischemic events in 140 patients undergoing major abdominal (n = 53) versus infrainguinal (n = 87) vascular operations. Preoperative dipyridamole thallium cardiac scintigraphy was performed in a subset of 38 of these patients, with treating physicians blinded to the test results. Myocardial ischemia was measured during operation with use of continuous 12-lead electrocardiography (ECG) and transesophageal echocardiography. Continuous two-lead ambulatory ECG (Holter monitoring) was performed before, during, and after operation for 4 days. Outcome events were cardiac death, nonfatal myocardial infarction, unstable angina, ventricular tachycardia, and congestive heart failure. Results of the study indicated that most demographic variables, such as age, hypertension, cigarette smoking, serum cholesterol, were comparable between patients having aortic or infrainguinal arterial operations. However, in the infrainguinal group more patients had diabetes, second vascular operations, angina pectoris, heart failure, dysrhythmias, and used digitalis. Abnormalities in preoperative Holter monitoring, ECGs, and thallium scan abnormalities were equivalent between groups. During operation, whereas Holter and ECG abnormalities were comparable, more patients undergoing aortic procedures suffered ischemia as determined by transesophageal echocardiography (26% vs 10%, p = 0.019). After operation there were 21 (24%) outcome events in patients having infrainguinal bypasses compared with 15 (28%) patients having aortic procedures (p = NS). Ischemia by Holter monitoring (n = 133) occurred after operation in 46 (57%) patients having infrainguinal operations compared with 16 (31%) patients having aortic reconstructions (p = 0.005). Because preoperative cardiac disease and adverse cardiac outcomes occurred with similar or even greater frequency in both groups of patients, we conclude that the risk for postoperative cardiac ischemic events in lower extremity vascular operations is at least as great as for aortic operations.

Aged↗
PubMed1991

Simultaneous resection of renal carcinoma and abdominal aortic aneurysm.

A 62-year-old man with a 6.5 cm abdominal aortic aneurysm and coexistent left renal cell carcinoma was treated by simultaneous radical left nephrectomy and abdominal aortic aneurysm repair. Care was taken to avoid potential infection of the bypass graft by inadvertent contamination with urine. Pathologic examination of the left kidney revealed a renal cell carcinoma, clear cell type, with no evidence of invasion into the renal vein or lymph node metastases. The patient had an uncomplicated recovery and is well and free of disease four years after operation. In cases of equivalently life threatening surgical diseases, simultaneous resection is warranted.

Aorta, Abdominal↗