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Biomedical subjects

J Metz

Publications and source records attributed to J Metz.

At least 55 records · Page 3Linked to original sources
PubMed1995

Low-dose radioactive endovascular stents prevent smooth muscle cell proliferation and neointimal hyperplasia in rabbits.

BACKGROUND: Restenosis induced by smooth muscle cell (SMC) migration and proliferation and neointimal thickening limits the clinical success of balloon angioplasty and stent implantation. In this study, the long-term effect of endovascular irradiation via low-dose radioactive stents on neointima formation was compared with conventional stent implantation in a rabbit model. METHODS AND RESULTS: Palmaz-Schatz stents were made radioactive in a cyclotron. The stents had a very low activity (maximum, 35 microCi), and thus, manipulation did not require extensive radiation protection. One, 4, 12, and 52 weeks after the implantation of nonradioactive stents and radioactive stents in rabbit iliac arteries, neointimal thickening was analyzed by quantitative histomorphometry. Immunostaining for endothelial cell von Willebrand factor, macrophages, SMC alpha-actin, collagen type I, and proliferating cell nuclear antigen (PCNA) was performed to determine radiation-induced changes in the arterial wall. SMC proliferation was quantified by computer-assisted cell counting of PCNA-immunoreactive cells. Neointima formation was markedly suppressed by the implantation of radioactive stents in a dose-dependent fashion at all observed time points. At peak proliferative activity of SMCs 1 week after nonradioactive stent implantation, 30 +/- 2% of SMCs in the neointima were proliferating, compared with 0.5 +/- 0.1% of SMCs after implantation of stents with an initial activity of 35 microCi (P < .001). The neointima covering radioactive stents was characterized by decreased smooth muscle cellularity and increased extracellular matrix formation. Further, we observed a delayed endothelialization depending on the radiation dose. No difference in vascular thrombosis was found after nonradioactive and radioactive stent implantation. CONCLUSIONS: The results of this study clearly indicate that low-dose radioactive endovascular stents potently inhibit SMC proliferation and neointimal hyperplasia in rabbits.

Animals↗
PubMed1995

Appropriateness of transfusions of red cells, platelets and fresh frozen plasma. An audit in a tertiary care teaching hospital.

OBJECTIVE: To determine how current hospital practice for transfusions of red cells, platelets and fresh frozen plasma conformed with published criteria. DESIGN: Elaboration of criteria for transfusion from a review of the current literature; and analysis of the medical records of patients receiving transfusions of red cells (200), platelets (215), and fresh frozen plasma (260) during defined time periods in 1993. SETTING: A large tertiary care teaching hospital. OUTCOME MEASURES: Inappropriateness rates for transfusion episodes and numbers of individual units of blood products administered. RESULTS: Inappropriateness rates for transfusion episodes and numbers of individual units administered were 16% and 10% for red cells, 13% and 11% for platelets, and 24% and 16% for fresh frozen plasma (31% and 21% when transfusions for thrombotic thrombocytopenic purpura were excluded). Red cells and fresh frozen plasma were used inappropriately most frequently in association with a surgical procedure; for platelets, it was their use for bleeding. In many of the transfusions deemed inappropriate, deficiencies of red cells, platelets and/or coagulation factors were documented, but the degree of deficiency did not meet the stringent appropriateness criteria. Twenty-six transfusions were deemed inappropriate because the indication was not documented in the medical record. CONCLUSIONS: Specific problem areas in which blood product use was inappropriate were identified. Guidelines for transfusion appropriateness, education of hospital staff, and a monitoring system to ensure adherence to the guidelines, are required.

Anemia↗
PubMed1995

Biochemical indices of vitamin B12 nutrition in pregnant patients with subnormal serum vitamin B12 levels.

To determine the significance of the commonly observed fall in serum vitamin B12 levels during pregnancy, serum levels of the B12 metabolites methylmalonic acid (MMA) and homocysteine (Hcy) were measured in a group of 50 pregnant patients with subnormal serum B12 (range 45-199 pg/ml) and the results compared with those of 25 pregnant controls (serum B12(208-580) pg/ml). Mean values for serum MMA and total Hcy in the subnormal B12 group were 445.4 nmol/L and 7.03 mumol/L, respectively, which were not significantly different from the mean MMA of 440.5 nmol/L and Hcy of 6.88 nmol/L in the controls. For the total group of patients, neither serum MMA nor serum Hcy levels correlated with serum B12. One-third of pregnant patients showed elevated serum MMA values, independent of B12 status. Significant elevation of serum Hcy was detected in only two patients, both with subnormal serum B12 and hematological evidence of B12 deficiency. We conclude that the usual fall in serum B12 concentration in pregnancy does not reflect B12 deficiency at the biochemical level. In establishing true B12 deficiency in pregnancy, the serum Hcy level (in the absence of folate deficiency) but not serum MMA, is of value.

Female↗
PubMed1995

Etofibrate suppresses neointima formation of the ballooned common carotid artery of rats.

The inhibition of neointima formation by drugs is a major goal to prevent restenosis following angioplasty. In the present study, the effect of etofibrate on blood lipids and vessels wall was investigated using a balloon injury rat model. Two weeks after ballooning the common carotid artery neointima formation was quantified by morphometric measurement of the neointimal area and cellularity in vessel cross sections, and by fluorometric evaluation of the DNA content. Etofibrate (160 mg/kg/day) had no effect on plasma triglyceride levels, but reduced serum cholesterol by about 25%. The injury-induced increase of both the neointimal area and the DNA-content was significantly inhibited by 47% (P < 0.005) and 34% (P < 0.05), respectively, in the drug-treated animals in comparison to the untreated control rats. The ratio of neointima and media was significantly (P < 0.001) reduced from 152.9 +/- 11.6% (controls) to 82.84 +/- 12.59% in the etofibrate-treated group. The cellularity (numerical profile and volume density of nuclei) in the neointima was similar in both groups. In conclusion, injury-induced neointima formation is reduced in etofibrate-treated animals, which could be due to an inhibition of smooth muscle cell proliferation.

Animals↗
PubMed1995

Hypercholesterolemia increases manganese superoxide dismutase immunoreactive macrophages in myocardium.

The effect of hypercholesterolemia on manganese superoxide dismutase (MnSOD)-containing macrophages was investigated in male New Zealand white rabbits. Macrophages from control animals, which were marked with the RAM-11 antibody, demonstrated co-localization with MnSOD immunoreactivity, e.g. in the peri- and paravascular space within the myocardium, but not in the bone marrow. In rabbits fed a 0.5% cholesterol-enriched diet for 42 days, a significant increase (P < 0.01) of MnSOD-immunoreactive macrophages within the myocardium was found concomitant to the drastic elevation of serum cholesterol level. In the bone marrow, MnSOD immunoreactivity did not change after cholesterol feeding. Thus in cholesterol-fed rabbits, the increase of MnSOD-containing macrophages seems to parallel that of lipoproteins. MnSOD is considered as being protective against the cytotoxic effects of those superoxide anions, possibly generated in macrophages, which are involved in the metabolism of modified lipoproteins.

Animals↗
PubMed1995

Incidence, severity, and mortality of acute respiratory failure in Berlin, Germany.

A prospective multicenter study was carried out from October 1 to November 30, 1991, to determine the incidence, severity, and mortality of acute respiratory failure (ARF) in Berlin, Germany, a metropolis with a population of 3.44 million. Adult patients from 72 intensive care units (ICUs) were evaluated. ARF was defined as: (1) intubation and mechanical ventilation (I+MV) > or = 24 h; age > or = 14 yr. Incidence of ARF was assessed as the number of patients fulfilling ARF criteria within the 2-mo study period. Severity of ARF was defined as "no lung injury" (NLI), "mild-to-moderate lung injury" (MMLI), and "severe lung injury" (SLI) according to Murray and coworkers' proposals. Mortality was assessed as number of patients with ARF dying during ICU stay. During the study period, 508 patients were diagnosed as having ARF, representing an incidence of ARF of 88.6 per 100,000/yr. Twenty-four h after I+MV, MMLI occurred in 94% and SLI in 3.6% of the ARF patients. Overall mortality rate was 42.7%. Mortality rate in the NLI group was 36.4%; in patients with MMLI, 40.8%; and in patients with SLI, 58.8%. Our data offer novel information on incidence, severity, and mortality of ARF in a major urban population.

Adult↗
PubMed1995

Myocardial contrast echocardiography for assessment of papaverine vasodilator response in patients with angiographically normal coronary arteries and in patients after orthotopic heart transplantation.

Myocardial contrast echocardiography has the potential for assessing changes in regional myocardial perfusion. We used this method to compare papaverine vasodilator response in 10 patients after orthotopic heart transplantation without acute rejection of left ventricular hypertrophy (HTX) and in 15 patients with angiographically normal coronary arteries (control group). Injections of 2 ml of sonicated iopromid (9 paired injections in HTX and 24 paired injections in the control group) were performed before and after intracoronary application of papaverine (8 or 10 mg) into the left or right coronary artery. From regional time-intensity curves, alpha (variable of curve width), area under the curve (area), peak contrast intensity (Imax) and contrast decay half-time (T1/2) were derived by from a gamma variate function. T1/2 increased from 4.2 +/- 1.2 to 7.2 +/- 4.0 s (p < 0.01) after papaverine in HTX compared to a change from 4.8 +/- 1.0 to 6.0 +/- 1.7 s (p < 0.001) in normal subjects. Alpha decreased in HTX from 0.44 +/- 0.15 to 0.27 +/- 0.10 s-1 (p < 0.01) after intracoronary papaverine injection. In the control group alpha was 0.37 +/- 0.08 s-1 at rest compared to 0.30 +/- 0.08 s-1 at hyperemic conditions (p < 0.002). Area increased in HTX from 444 +/- 261 to 910 +/- 732 U.s (p < 0.01) and in normal subjects from 352 +/- 171 to 585 +/- 262 U.s (p < 0.001). Hyperemic to baseline flow ratios for area varied from 0.9 to 3.8 (mean 2.17 +/- 1.11) in HTX compared to 1.76 +/- 0.52 (1.03 to 2.71) in normal subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Influence of surface texture and charge on the biocompatibility of endovascular stents.

BACKGROUND: The mechanical behaviour and the surface characteristics of endovascular stents are key factors determining stent patency. In-vitro studies have suggested that surface texture and charge alter the biocompatibility of metallic stents. In this study, the influence of surface texture and charge of metallic stents on thrombosis and neointima formation was evaluated in a rabbit model. METHODS: Twenty-four stainless steel Palmaz-Schatz stents were coated either by an electrochemical deposition of metal on the stent surface or were coated with a metallic film which was implanted into the stent surface by argon ion bombardment. The coatings consisted of platinum, gold, or copper. Coated and uncoated control stents were implanted in rabbit iliac arteries. As antithrombotic therapy, 500 IU heparin and 60 mg aspirin was given intravenously before stent implantation, followed by 60 mg aspirin intravenously every third day for 4 weeks. Thrombus and neointima formation in arterial cross-sections of 24 coated stents were compared with 19 uncoated stents using quantitative, computer-assisted histomorphometry and transmission electron microscopy. RESULTS: A higher stent surface porosity and more surface cracks after stent expansion were found after galvanization than after ion implantation. The in-vitro surface potentials of uncoated steel, copper-, and gold-coated or platinized stents were +150, +120, +180, and +180 mV, respectively. Four weeks after implantation, six of 14 galvanized stents, but none of the uncoated or ion bombarded stents, were occluded by a thrombus. Neointimal hyperplasia was increased in stents coated by galvanization compared with stents coated by ion implantation. In both study groups, the most electropositive coating (platinum or gold) induced markedly less neointima formation than the least electropositive (copper). CONCLUSION: Stent surface texture was the most important factor determining biocompatibility of coated Palmaz-Schatz stents in this study. In contrast to suggestions derived from in-vitro studies, the charge of stents does not seem to play a major role with respect to stent thrombogenicity. Low stent charge correlates with an increased neointima formation.

Animals↗
PubMed1994

A new method for delivering radioactive cytotoxic agents in solid cancers.

PURPOSE: Therapeutic agents such as monoclonal antibodies, radiopharmaceuticals, and radioactive growth factors are limited in effectiveness due to the inability to deposit significant quantities of the agents and for limited periods of time in solid cancer. A new technique based on knowledge of the pathophysiology of solid tumors allows for significant concentration of these agents to accumulate and for a prolonged period of time, thus allowing interaction with the tumor for potentially increased effectiveness. METHODS AND MATERIALS: Three agents have been studied: 131I antiferritin monoclonal antibody, colloidal 32P chromic phosphate, and 131I transferrin. The time required for maximal tumor uptake was determined in vitro in tissue culture and was 10 min, 25 min, and 40 min, respectively. The new method of in vivo tumor infusion consisted of a direct intratumoral injection of macroaggregated albumin (MAA) 10,000 particles, followed by the radioactive agents under study. Tumors were infused in vivo using the new technique and compared to intratumoral infused controls. In the instance of radiolabeled antiferritin antibody, intraperitoneal administration and intratumoral infusion were compared to the new technique. In the other two instances, intratumoral infusion was compared to the new method. RESULTS: In all instances the direct vascular blockade caused by MAA led to greater deposition of the agent under study for at least 24 h. These results were clinically applied with MAA followed by 32P colloidal chromic phosphate and were consistent with the experimental findings. CONCLUSION: A new technique is described that may be carried out in the experimental laboratory and clinic by direct tumor infusion of macroaggregated albumin (MAA), followed by other radioactive agents that will remain localized in solid cancers and will allow for high tumor dose deposition for potentially increased therapeutic efficacy.

Animals↗
PubMed1994

Fluoxetine effects on cerebral glucose metabolism.

In a counterbalanced, double-blind, placebo-controlled trial, 40 mg of fluoxetine was administered to four healthy adult volunteers (three men, one woman; age range 20-39 years), 90 min before injection of 6-7.5 mCi of [18F]-2-deoxyglucose to measure cerebral metabolic rate of glucose (CMRglu). Subjects were engaged in a visual monitoring task shortly before and during scanning with a PETT-VI tomograph. Global CMRglu did not differ when placebo (8.93 +/- 0.96 mg 100 g-1 min-1) was compared to fluoxetine (8.22 +/- 0.86 mg 100 g-1 min-1; paired t-test = 0.82, df = 3, p < 0.48). However, statistical parametric mapping of differences in CMRglu between placebo and fluoxetine conditions revealed regional effects of fluoxetine shown by decreased metabolism in the amygdaloid complex, hippocampal formation and ventral striatum, and by increased metabolism centered in the right superior parietal lobe (Brodmann area 7). Parametric mapping for use in PET studies of glucose metabolism represents a significant new tool for studying drug effects in humans.

Adult↗
PubMed1994

Screening for consumptive coagulopathy in preeclampsia.

OBJECTIVE: To identify a practical and cost-effective profile of tests to screen for consumptive coagulopathy in preeclampsia (PE). METHODS: Retrospective analysis of the results of measurements of platelet count, prothrombin time (PT), activated partial thromboplastin time (APTT), plasma fibrinogen and D-dimers in 100 patients presenting with PE uncomplicated by other disease or antepartum hemorrhage. Twenty-four patients had pregnancy-induced hypertension only, and 76 hypertension with proteinuria. RESULTS: The incidence of abnormal tests on presentation was raised D-dimers 34%, thrombocytopenia 14%, prolonged APTT 12%, prolonged PT 3%, and low fibrinogen 2%. Prolonged APTT without thrombocytopenia occurred in 8% of patients. In 19 patients with elevation of D-dimers alone, only one showed evidence of consumption of coagulation factors on subsequent testing. CONCLUSIONS: A combination of platelet count and APTT is probably a practical and cost-effective combination to screen for consumptive coagulopathy in PE.

Adult↗
PubMed1994

The role of elastic recoil after balloon angioplasty of rabbit arteries and its prevention by stent implantation.

Elastic recoil, neointima formation and vessel narrowing after balloon angioplasty or stent implantation were compared in 17 non-atherosclerotic New Zealand White rabbits. The implantation of a balloon-expandable Palmaz-Schatz stent was performed in one iliac artery and a balloon angioplasty alone was performed in the contralateral artery (n = 34 arteries). Quantitative histomorphometry was performed by a computer-assisted analysis 1 h and 4, 10 and 24 weeks after the initial procedure. The histological appearance of the neointima was similar to that of human restenosis. The amount of the neointima was increased within stented vessels as compared to balloon angioplasty alone (1.0 +/- 0.1 vs 0.4 +/- 0.1 mm2 at 4 weeks, P < 0.001). However, the neointimal lumen narrowing was smaller in the stented vessels due to persistent increase in vessel perimeter as compared to balloon angioplasty alone (16.5 +/- 0.9 vs 34.7 +/- 16.5% lumen narrowing at 4 weeks, P < 0.05). In conclusion, stent implantation enhances neointima formation as compared to angioplasty in non-atherosclerotic rabbits. The prevention of elastic recoil after stent implantation, however, reduces the neointimal lumen narrowing. This study supports clinical observations demonstrating lower restenosis rates after stent implantation compared to standard balloon angioplasty.

Angioplasty, Balloon, Coronary↗
PubMed1993

Reproducibility of myocardial contrast echocardiography in human studies.

Experimental and clinical studies were performed to assess the ability of myocardial contrast echocardiography for quantitation of regional myocardial blood flow. To evaluate whether myocardial contrast echocardiography is a reproducible technique in humans, 18 nonselected patients undergoing coronary angiography were studied. A total of 107 intracoronary injections into either the left or the right coronary artery were analyzed by computer assisted videodensitometry for peak intensity, contrast decay half-time, and area under the curve. By means of these parameters intraobserver, interobserver, and interinjection variability were determined. Intraobserver measurements showed lowest variability with correlation coefficients of 0.83 for contrast decay half-time, 0.93 for peak intensity, and 0.95 for area under the curve. Mean percent error varied between 6.8% (peak intensity) and 11.2% (area under the curve). The correlation coefficients for interobserver variability ranged from 0.73 for area under the curve to 0.97 for peak intensity. Mean percent error revealed a range between 7.5% for peak intensity and 19% for area under the curve. For interinjection variability, the correlation coefficient for contrast decay half-time was lower (0.56) than for peak intensity (0.73) and area under the curve (0.84). Mean percent error were higher than for intraobserver and interobserver variability (range 24.1% to 34.2%). Thus, intraobserver and interobserver variability for parameters derived from time-intensity curves after intracoronary injection of echo contrast agent in humans are sufficient and comparable to data from animal studies. Interinjection variability, however, showed a higher mean percent error.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

T cell lymphoid aggregates in bone marrow in idiopathic hypereosinophilic syndrome.

Idiopathic hypereosinophilic syndrome (HES) comprises a heterogeneous group of disorders characterised by prolonged eosinophilia with no obvious cause. A patient with longstanding HES is reported in whom unusual non-neoplastic peritrabecular lymphoid aggregates were present in the bone marrow, a hitherto undescribed association, as far as is known. An eosinophil colony stimulating activity was detected in the serum. The findings in this patient provide further evidence for an important role for eosinophil colony stimulating activity interleukin-5 mediated T lymphocyte control of eosinophil production in the pathogenesis of the HES.

Bone Marrow↗