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Biomedical subjects

G D Abrams

Publications and source records attributed to G D Abrams.

At least 19 recordsLinked to original sources
PubMed1992

Shock-wave thrombus ablation, a new method for noninvasive mechanical thrombolysis.

Successful experimental and clinical experience with thrombus ablation has been attained with high-power acoustic energy delivered in a catheter. The goal of this study was to investigate the feasibility of noninvasive thrombus ablation by focused high-power acoustic energy. The source for high-power acoustic energy was a shock-wave generator in a water tank equipped with an acoustic lens with a fixed focal point at 22.5 cm. Thrombus was prepared in vitro, weighed (0.24 +/- 0.08 g), and inserted in excised human femoral artery segments. The arterial segments wer ligated, positioned at the focal point and then randomized into either test (n = 8) or control (n = 7). An x-ray system verified the 3-dimensional positioning of the arterial segment at the focal point. A 5 MHz ultrasound imaging system continuously visualized the arterial segment at the focal point before, during and after each experiment. The test segments were exposed to shock waves (1,000 shocks/24 kv). The arterial segment content was then flushed and the residual thrombus weighed. The arterial segment and thrombus were fixed and submitted to histologic examination. The test group achieved a significant ablation of thrombus mass (0.25 +/- 0.15 vs 0.07 +/- 0.003 g; p = 0.0001) after application of shock waves. Arterial segments showed no gross or microscopic damage. Ultrasound imaging revealed a localized (1.9 +/- 0.5 cm2), transient (744 +/- 733 ms), cavitation field at the focal point at the time of application of focused shock waves. Thus, focused high-power acoustic energy can effect noninvasive thrombus ablation without apparent damage to the arterial wall.(ABSTRACT TRUNCATED AT 250 WORDS)

Femoral Artery↗
PubMed1992

Hypoxia-induced bacterial translocation in the puppy.

Because hypoxia is one of the most common major stresses to which a neonate is exposed, we postulated that it alone might be the cause of intestinal bacterial translocation, which could be the underlying etiology of neonatal sepsis. An animal model, in which hypoxia is the sole stress, was developed in our laboratory and tested in 18 puppies to determine the effect of hypoxia and reoxygenation on intestinal bacterial translocation. In group I (n = 8), following laparotomy and cannulation of the superior mesenteric vein (SMV), the FIO2 was decreased from 21% to 9% for 90 minutes followed by reoxygenation at 21% for 120 minutes. The abdomen was closed and the animals were allowed to recover. After 24 hours the mesenteric lymph nodes (MLNs), spleen, and liver were harvested for bacterial determination and the ileum and jejunum for histological evaluation. Group II (n = 7) was treated the same as group I with the FIO2 maintained at 21%. Group III (n = 3) animals were killed, without intervention, for bacterial analysis. In group I, the systemic PO2 decreased by 75%, SMV PO2 decreased by 64%, and oxygen delivery to the small bowel decreased by 80% in comparison with group II. The mean arterial pressure and cardiac output were not significantly different between group I and group II; however, the mucosal blood flow was decreased by 60% (P less than .001) in group I. Arterial and SMV blood lactic acid levels were unchanged in group I in comparison with group II, suggesting that anaerobic metabolism was not initiated in the splanchnic circulation during hypoxia.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Intramural methotrexate therapy for the prevention of neointimal thickening after balloon angioplasty.

OBJECTIVES: The study was performed to test the hypothesis that high local, intramural concentrations of antineoplastic agents at the site of balloon injury inhibit vascular smooth muscle cell proliferation without systemic toxicity. BACKGROUND: The predominant mechanism for recurrent stenosis after coronary balloon angioplasty is neointimal thickening due to medial smooth muscle cell proliferation. The clinical use of potent antiproliferative agents to prevent restenosis has been limited by the potential for severe systemic side effects. Local therapy with these agents may be effective and free of systemic complications. METHODS: After bilateral balloon angioplasty of the carotid arteries of 14 juvenile farm pigs, the dilated arterial segments were treated locally with methotrexate (6.25 mg/ml, total dose 25 mg) or 0.9% saline solution through a perforated balloon catheter. The animals were then killed 30 days after balloon injury to determine the effects of this therapy on neointimal thickness. In an additional six animals, tritium-labeled methotrexate was used to determine the concentration and duration of detectability of methotrexate in the wall of the treated arteries and in the systemic circulation. RESULTS: Two hours after drug instillation the concentration of labeled drug was greater than 1,000-fold greater in the wall of the treated artery than in circulating blood, and this ratio remained between 50 and 100 for at least 7 days. Despite this difference, the mean intimal thickness 30 days after the procedure was similar in the 10 methotrexate-treated arteries and the 18 saline-treated arteries (59 +/- 30 vs. 56 +/- 25 microns, p = 0.6). The morphologic appearance of the neointima was similar in each group and suggested an important role for mural thrombus in the genesis of the intimal thickening. CONCLUSIONS: Treatment with intramural methotrexate, delivered through a perforated balloon catheter at the selected concentration and total dose, failed to prevent intimal thickening after balloon injury. Nonetheless, the perforated balloon catheter appears to be a promising means of delivering a high local concentration of drugs with potentially life-threatening systemic side effects. The optimal concentrations and combinations of candidate drug therapies warrant further evaluation.

Angioplasty, Balloon↗
PubMed1992

Design and testing of a high-flow autoperfusion catheter: an experimental study.

An autoperfusion catheter is similar to an angioplasty balloon catheter with side holes in the guide-wire lumen proximal to the balloon. When the balloon of the autoperfusion catheter is deployed and inflated in an artery, the guide wire is removed, and the hub of the guide-wire lumen is capped. The catheter then allows passive distal perfusion by using ambient pressure to drive blood into the guide-wire lumen, through the balloon, and out the end hole. This article discusses the requirements and constraints of a high-flow autoperfusion catheter, summarizes attempts to modify standard angioplasty catheters for use as an autoperfusion catheter, and describes the design and testing of a custom autoperfusion catheter capable of delivering approximately 3 mL/sec at physiologic pressures. In a model of canine acute renal artery occlusion lasting 90 minutes, the custom autoperfusion catheter provided marked protection from acute tubular necrosis compared with conventional percutaneous transluminal angioplasty catheters. The authors conclude that the high-flow autoperfusion catheter may be useful as a temporary stent in cases of rupture, dissection, or penetrating wounds involving large arteries.

Angioplasty, Balloon↗
PubMed1991

Hemodynamics versus biopsy findings during cardiac transplant rejection.

Before the use of cyclosporine as the major component for immunosuppression after cardiac transplantation, rejection was accompanied by catastrophic hemodynamic decompensation. However, the hemodynamic changes that occur during rejection after cardiac transplantation in patients treated with cyclosporine have not been clearly described. Between July 1986 and October 1989, 89 adults underwent orthotopic heart transplantation at the University of Michigan Medical Center. All patients received triple-drug therapy immunosuppression consisting of steroids, cyclosporine, and azathioprine. Cardiac hemodynamics were measured and correlated with the histologic assessment of rejection. There have been ten deaths among these 89 patients for an overall survival of 89%. There were no deaths from rejection. One hundred fifty-three of the biopsy specimens were read as grade 0, 31 were grade 1, 75 were grade 2, 103 were grade 3, and 9 patients had grade 4 biopsy specimens. No hemodynamic differences were noted in patients with increasing grade of rejection. Five patients (5/9, 55%) with severe rejection (grade 4) had symptoms of congestive heart failure at the time of biopsy. These symptomatic grade 4 patients differed from asymptomatic grade 4 patients only in cardiac output (2.9 versus 5.2 L/min). Overall hemodynamic decompensation was not evident as rejection grade increased. Routine serial endomyocardial biopsies remain the procedure of choice in the diagnosis of rejection in the asymptomatic patient after cardiac transplantation as hemodynamics do not predict degree of rejection.

Adult↗
PubMed1991

Penetrating atherosclerotic aortic ulcer with dissecting hematoma: control of bleeding with percutaneous embolization.

A case is presented in which left subpleural hematoma and hemothorax resulted from a penetrating atherosclerotic aortic ulcer with an aortic pseudoaneurysm and intramedial hematoma. Percutaneous transfemoral embolization of the ulcer with use of coils and thrombin resulted in stabilization of the patient's hemodynamic status. The patient died 6 days later of pneumonia. In certain clinical situations, treatment of bleeding from penetrating aortic ulcers with percutaneous embolization may stabilize the patient's condition, allowing elective surgical intervention.

Aged↗
PubMed1991

Evidence for regional catecholamine uptake and storage sites in the transplanted human heart by positron emission tomography.

Positron emission tomography in combination with the newly introduced catecholamine analogue [11C]hydroxyephedrine ([11C]HED) enables the noninvasive delineation of sympathetic nerve terminals of the heart. To address the ongoing controversy over possible reinnervation of the human transplant, 5 healthy control subjects and 11 patients were studied after cardiac transplant by this imaging approach. Regional [11C]HED retention was compared to regional blood flow as assessed by rubidium-82. Transplant patients were divided into two groups. Group I had recent (less than 1 yr, 4.4 +/- 2.3 mo) surgery, while group II patients underwent cardiac transplantation more than 2 yr before imaging (3.5 +/- 1.3 yr). [11C]HED retention paralleled blood flow in normals, but was homogeneously reduced in group I. In contrast, group II patients revealed heterogeneous [11C]HED retention, with increased uptake in the proximal anterior and septal wall. Quantitative evaluation of [11C]HED retention revealed a 70% reduction in group I and 59% reduction in group II patients (P less than 0.001). In group II patients, [11C]HED retention reached 60% of normal in the proximal anterior wall. These data suggest the presence of neuronal tissue in the transplanted human heart, which may reflect regional sympathetic reinnervation.

Blood Pressure↗
PubMed1990

Effect of gastrointestinal flora on body temperature of rats and mice.

The purpose of these experiments was to test the hypothesis that gut flora influences the body temperature of rodents. Rats and mice were implanted with biotelemetry transmitters that enabled us to record both abdominal temperature and activity for long periods of time. Rats given nonabsorbable antibiotics in their drinking water, which reduced their gut flora, had a marked decrease in both their daytime and nighttime temperatures. Similar results were found with germfree mice. The circadian rhythms in body temperature of germfree and conventionalized mice were not different. However, the body temperatures of the germfree mice were lower than those of the conventionalized mice during both the daytime and nighttime. The decrease in body temperature in the germfree mice was not related to changes in activity. These results support the hypothesis that gut flora has a tonic stimulatory effect on both the daytime and nighttime body temperature of rodents.

Abdomen↗
PubMed1989

Treatment of Wilson's disease with zinc. V. Changes in serum levels of lipase, amylase, and alkaline phosphatase in patients with Wilson's disease.

We noted a frequent increase in the serum enzymes amylase, lipase, and alkaline phosphatase in patients with Wilson's disease who are receiving zinc acetate therapy (25 or 50 mg elemental zinc three times daily). Typically, values are normal before the initiation of zinc therapy, increase to slightly above normal after a few weeks of therapy, and stabilize at the high normal range after approximately a year of treatment. Very large dosages of zinc (800 mg/day) produce even further elevation of serum lipase and amylase without the symptoms of pancreatitis. Pancreatic pathologic studies of a zinc-treated rat model receiving dosages equivalent to up to 25 times the effective dosage in a human being, which is based on milligrams of zinc per kilogram of body weight, reveal that no lesions are induced by zinc treatment in the pancreas. We interpret these findings to indicate that extended maintenance therapy with zinc does not pose a risk of pancreatic damage in patients with Wilson's disease.

Adolescent↗
PubMed1988

Protection of reperfused ischemic canine myocardium by CI-922, a new inhibitor of leukocyte activation.

There is increasing evidence that activated neutrophils cause myocardial injury during reperfusion of ischemic myocardium. This study was performed to assess the effect of Ci-922, an inhibitor of neutrophil activation, in a canine preparation of myocardial infarction. Dogs received 15-min infusions of CI-922 1 mg/kg or 5% dextrose beginning 30 min before occlusion of the left circumflex coronary artery. After occlusion for 90 min and reperfusion for 6 h, infarct size was determined by ex vivo perfusion of the left circumflex coronary artery with triphenyltetrazolium chloride. The percentage of the area at risk infarcted was: control, 42 +/- 5; and CI-922, 23 +/- 4 (p less than 0.05 vs. control). There were no significant inter-group differences in heart rate or mean arterial pressure, and CI-922 did not enhance collateral blood flow to the ischemic bed. After incubation with CI-922 (100 microM), production of superoxide anions by canine neutrophils activated by opsonized zymosam decreased from 3.5 +/- 0.2 to 2.0 +/- 0.4 nmol/10 min/10(6) cells (p less than 0.05). Thus, inhibition of neutrophil-mediated damage may explain the cardioprotective effect of CI-922.

Animals↗
PubMed1988

Pathogenesis of gastrointestinal infections.

The normal gastrointestinal tract is constantly "infected" by a large and varied microbial population. This normal flora plays a significant role in establishing and maintaining the normal state of the digestive tract. Although the digestive ecosystem thus constituted has a high degree of stability, some microbes have evolved virulence factors or characteristics that allow them to gain a foot-hold in the tract. Given the variety of virulence factors found in different organisms, gastrointestinal infectious diseases are characterized by a broad spectrum of patterns which differ with respect to the relationship between microbe and host, i.e., the degree of tissue penetration by the organism. Genetic analysis of virulence factors promises to deepen our understanding of the pathogenesis of these diseases and to lead ultimately to effective means of prevention.

Bacteria↗
PubMed1987

Prostacyclin protects ischemic reperfused myocardium in the dog by inhibition of neutrophil activation.

Prostacyclin (PGI2) and the stable PGI2 analogue SC39902 (6,9 alpha-epoxy,5S-fluoro-11 alpha, 15S-dehydroxyprosta-6,13E-dien-1-oic acid, sodium salt) were studied in anesthetized open-chest dogs subjected to 90 minutes of left circumflex coronary artery (LCCA) occlusion and 6 hours of reperfusion. PGI2 (50 ng/kg/min, infused into the left atrium) reduced infarct mass by 59% compared to control, but SC39902 (1.5 micrograms/kg/min) failed to produce a significant reduction in infarct size. Both PGI2 and SC39902 reduced mean arterial blood pressure, heart rate, and rate-pressure product to the same extent. Regional myocardial blood flow measured with radiolabelled tracer microspheres did not demonstrate an increase in regional blood flow to the ischemic myocardium during the 90 minutes of LCCA occlusion in the PGI2 and control treatment groups. Canine neutrophils were isolated from whole blood and activated with opsonized zymosan. PGI2 produced a concentration-dependent inhibition of neutrophil activation as measured by superoxide production in vitro, whereas SC39902 failed to effectively inhibit neutrophil activation. Neutrophil migration into inflammatory skin lesions was effectively attenuated when dogs were pretreated with PGI2 (50 ng/kg/min, intravenously). Therefore, it is suggested that the cytoprotective effect of PGI2 during myocardial ischemia and reperfusion is related to an inhibition of neutrophil migration and the production of cytotoxic activated oxygen species.

Animals↗
PubMed1987

Superoxide dismutase does not cause scar thinning after myocardial infarction.

Previous studies demonstrated that treatment with superoxide dismutase, a scavenger of superoxide anions, limits the extent of myocardial injury in a canine preparation of regional myocardial ischemia and reperfusion. Little is known, however, about the effects of superoxide dismutase on the healing of a myocardial infarct. Therefore, this study was performed to determine whether treatment with superoxide dismutase during myocardial ischemia impairs formation of scar tissue after infarction. Dogs received 2 hour infusions of superoxide dismutase or albumin (controls) by way of the left atrium beginning 15 minutes before and ending 15 minutes after a 90 minute occlusion of the left circumflex coronary artery. Six weeks later the animals were killed. Two-dimensional echocardiography was performed before surgery and before induced death. Wall thickening in the central ischemic zone was decreased at 6 weeks compared with baseline studies (p less than 0.05), but the decrease was similar for both groups. The hydroxyproline concentrations (microgram/mg dry weight) of the scar tissue in the superoxide dismutase and control groups, respectively, were 35.3 +/- 3.8 and 28.7 +/- 5.0 (p less than 0.05). The ratios of the scar thickness to normal wall thickness were superoxide dismutase 0.91 +/- 0.03 and control 0.89 +/- 0.03 (p greater than 0.05). Thus, superoxide dismutase had no adverse effect on wall thickening or scar formation assessed 6 weeks after myocardial infarction, and may be useful to limit oxygen radical-mediated damage during reperfusion of the ischemic myocardium.

Animals↗
PubMed1987

Surgical pathology of the infected gut.

In the normal digestive tract, interaction of the mucosa with a large and varied microbial flora is inevitable. In fact, the "normal" state of the digestive tract reflects the impact of the resident flora to a significant degree. The pathogenesis of various infectious conditions encountered by the surgical pathologist in the gut is understood more readily when the gastrointestinal tract is viewed as a complex ecosystem. Significant disease may result from perturbation of the normal flora, as well as from exogenous infection, and susceptibility of the host may vary with disturbances of the digestive ecosystem. An ecologic perspective is essential in the consideration not only of the "infected" gut, but of conditions as diverse as ischemia or even carcinogenesis in the gastrointestinal mucosa.

Animals↗
PubMed1986

Reduction of the size of infarction by allopurinol in the ischemic-reperfused canine heart.

This study was performed to assess the effect of allopurinol in a canine preparation of myocardial infarction. Dogs underwent occlusion of the left circumflex coronary artery for 90 min, followed by reperfusion for 6 hr. Three groups were studied: (1) control, (2) dogs receiving 25 mg/kg allopurinol 18 hr before occlusion and 50 mg/kg 5 min before occlusion, and (3) dogs receiving allopurinol as above plus 5 mg/kg superoxide dismutase over 1 hr beginning 15 min before reperfusion. Infarct size expressed as a percentage of the area at risk was 40 +/- 4 in the control group, 22 +/- 5 in the allopurinol group (p less than .05 vs control), and 17 +/- 4 in the allopurinol plus superoxide dismutase group (p less than .05 vs control). The differences in infarct size were not due to differences in myocardial oxygen supply or demand. Neutrophil superoxide anion production was not altered by allopurinol treatment. The results suggest that myocardial xanthine oxidase may generate oxygen radicals that play a role in myocardial injury due to ischemia and reperfusion.

Allopurinol↗
PubMed1986

Cytomegalovirus cholangitis in a homosexual man with acquired immune deficiency syndrome.

A 29-year old white homosexual man with acquired immune deficiency syndrome presented initially with right upper quadrant pain and progressive cholestasis. Diffuse mucosal irregularities were seen at endoscopic retrograde cholangiography. Histopathological examination of the gallbladder and wedge liver biopsy showed evidence of cytomegalovirus infection. A repeat endoscopic retrograde cholangiography for persistent symptoms of right upper quadrant pain and cholestasis showed progressive mucosal irregularities of the intra- and extrahepatic bile ducts consistent with progressive cholangitis. Subsequently the patient developed evidence of disseminated infection and died. Postmortem examination revealed histologic features of cytomegalovirus infection in lungs, pancreas, small bowel, adrenal glands, and liver. Immunohistochemical staining of liver confirmed the presence of cytomegalovirus infection of the biliary duct system.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Malignant fibrous histiocytoma of the heart presenting as unilateral pulmonary thromboembolism and infarct.

A malignant fibrous histiocytoma of the heart located at the pulmonic valve and thrombotic occlusion of branches of the left pulmonary artery with pulmonary infarct were found at autopsy in a 77-year-old man. The thrombi contained malignant cells. The patient had undergone left upper lobectomy four years earlier for thromboembolism with infarct, and review of the slides from that procedure revealed similar malignant cells within thrombi. This case is remarkable for the slow growth of the neoplasm and the prolonged survival of the patient, without specific therapy.

Aged↗