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Biomedical subjects

W J Mergner

Publications and source records attributed to W J Mergner.

At least 19 recordsLinked to original sources
PubMed1992

Cocaine: an independent risk factor for aortic sudanophilia. A preliminary report.

Several recent autopsy reports indicate an increased prevalence of coronary atherosclerosis in ischemic heart disease temporally associated with cocaine abuse. The objective of this study was to conduct a retrospective analysis of sudanophilic lesions in young asymptomatic individuals who abused cocaine. Twenty-six cases (15-34-year-old black males) were examined from the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study. Sixteen subjects (mean age 25 +/- 1 years) had a positive toxicologic screen for cocaine and/or its major metabolites at autopsy and were confirmed habitual cocaine abusers. The remaining 10 cases (mean age 24 +/- 2 years) were subjects with a negative toxicologic screen at autopsy and no history of illicit drug abuse. Post-mortem blood was collected for lipoprotein analysis and determination of smoking status. The aorta and right coronary arteries were stained with Sudan IV and the degree and extent of sudanophilia was quantitated by image analysis. Multiple linear regression analysis of cocaine, age, smoking status, VLDL+LDL-C/HDL-C ratio and HDL-C as predictor variables of percentage intimal surface involvement, revealed an association between cocaine abuse and the extent of sudanophilia in both the thoracic and abdominal aorta (P = 0.002 and 0.049, respectively). Analysis of risk factors or of cocaine abuse as predictors of sudanophilia did not achieve statistical significance in the right coronary artery. These preliminary results suggest that habitual use of cocaine, through unknown mechanism(s), increases aortic sudanophilia independent of traditional risk factors.

Adolescent↗
PubMed1991

Effect of aging on aortic morphology in populations with high and low prevalence of hypertension and atherosclerosis. Comparison between occidental and Chinese communities.

A comparative morphologic study of aortic changes with aging was conducted in different populations in an attempt to separate the effects of hypertension and atherosclerosis. Chinese and the occidental populations were chosen, as they are known to have a high prevalence of hypertension and atherosclerosis, respectively. Aortic tissue was collected from occidental (American and Australian) and Chinese populations from three geographic locations. Postmortem specimens were obtained from four fixed locations: ascending aorta (A), descending thoracic aorta (B), and abdominal aorta (suprarenal [C] and above the aortic bifurcation [D]). Histologic sections were used to measure aortic circumference, medial thickness, intimal thickness, and grade of atherosclerosis. Kidney sections were used to confirm the presence or absence of hypertension. A total of 302 cases (age range, 19 to 104 years; Male-to-female ration, 2:1) were studied: 112 Americans, 80 Australians, and 110 Chinese. Cases were divided into three age groups: 19 to 44; 45 to 64; and 65 years and older. The aortic circumference progressively decreased from sites A to D in all populations and age groups. The aortic circumference increased with age, and the increase was independent of the aortic location. When the populations were separated, however, the greater increase was at location A in the Chinese (P = .008) and locations D in the occidental (P = .13), a population contrast that was significant only in location A. Intimal thickness increased with advancing age and was maximal in the abdominal aorta. The population differences also were significant for intimal thickness and were significantly greater in the occidental population in B, C, and D locations, whereas for atherosclerosis significance was only seen in location D. Hypertension (as defined by the morphologic changes in the kidney) after adjusting for age, height, and weight resulted in no statistical significant effect on aortic circumference or on intimal thickness, but did show a significant increase in atherosclerosis score at locations B, C, and D. Also after adjusting for age, height, and weight, the Chinese had a significantly larger aortic circumference in location A compared with the occidental population, whereas in location D the occidentals with hypertension had a significantly larger circumference compared with Chinese, probably due to an interaction of atherosclerosis and hypertension. After similar adjustments, the medial thickness in locations A and C, the intimal thickness in B, C, and D, and atherosclerosis score in D were significantly greater in occidental than Chinese populations.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1990

Recovery of heart tissue following focal injury induced by dietary restriction of potassium.

Sixty-four Sprague-Dawley rats (initially weighing 200-225 grams) were divided into three groups. Group 1, the experimental group, was fed a potassium depleted diet for 42 days, followed by a potassium repleted diet for up to an additional 14 days. Group 2, the dietary control group, received a potassium deficient diet, but was continuously supplemented by drinking water containing potassium chloride 150 meq/L. Group 3, the control group remained on normal rat chow and tap water during the entire investigation. Quantitative morphometric analysis was used to assess the percent of myocardium occupied by lesion. These data were analyzed by an analysis of variance (ANOVA) for repeated measures, comparing the three groups with one another; a second analysis compared the myocardial lesions of the dietary experimental group during the potassium depletion and repletion periods. At the end of the dietary depletion period (day 42) focal areas of cardiac myocyte necrosis and mononuclear infiltrate were found in the experimental group. Morphometric assessment on day 42 revealed a volume fraction (Vv) of 8.61 (+/- 4.41)%, which was significantly greater (p = 0.0018), as compared with both control groups. Lesion area significantly regressed in two and one half days after potassium was supplemented in the dietary experimental group to 0.58 (+/- 0.34)% Vv (p = 0.0005). Six days after potassium was replaced in the diet, there was no significant difference between the experimental and control groups, and only a limited connective tissue scar was noted in the experimental group. The mechanism of the rapid regression of lesions and the production of only limited connective tissue scar is suggested but requires further elucidation.

Analysis of Variance↗
PubMed1990

Measurement of ATP synthesis and flocculent matrix densities in mitochondria as a function of 'in vitro' ischemia in the heart and liver of rats.

We intended to determine the levels of adenosine triphosphate (ATP) synthesis at the time when mitochondria ultrastructurally show flocculent densities in the matrix space. For this purpose, mitochondria were isolated from rat heart and rat liver after the tissues have been maintained under controlled ischemic conditions in vitro at 37 degrees C for intervals of 15, 30, 45, 60, 120, 180, and 240 (heart) min. The isolated mitochondria were tested for new ATP synthesis by luciferin/luciferase luminescence in the presence of substrate and adenosine 5'-diphosphate (ADP). The luminescence peaks were standardized and related to an external measure by measuring absorbance of ATP at 259 nm where the extinction coefficient is 15,400. Mitochondrial yield was monitored by measuring succinate dehydrogenase activity in the first homogenate and in the final mitochondrial pellet. Alternatively, cytochrome oxidase activity was used and the protein in the mitochondrial pellet was also determined. We found that the yield of mitochondria was above 53-54% in both liver and heart at 2 h of ischemia. Longer intervals were accompanied by lower yields. The ability to synthesize new ATP declined at different time intervals in ischemia of the heart compared to the liver. After 30 min ischemia, the synthesis in heart mitochondria is 18% of control, while the synthesis of liver mitochondria reaches 16% of control after 45 min of in vitro ischemia. Flocculent densities in heart mitochondria appeared at 45 min ischemia in vitro and in vivo, and at 60 min in liver mitochondria. We conclude that the decline of ATP synthesis is a significant early change in mitochondria and antedates the appearance of flocculent densities.

Adenosine Triphosphate↗
PubMed1990

Postmortem viability and early changes in organ culture of human and rabbit aortic endothelial cells.

In order to understand the role of the postmortem interval (PMI) on endothelial cell changes both in human and rabbit aortas, we have examined the ultrastructural cytomorphologic alterations of these cells. Human aorta (HA) and rabbit aorta (RA) were maintained in calcium-free, glucose-supplemented Hank's balanced salt solution (HBSS). Rabbit endothelial cells (REC) on the aorta (organ culture) assayed morphologically survive for at least 12 h in culture solution. The predominant morphological change in the RA was the formation of multiple subendothelial vacuoles (SEV). These vacuoles may form as the results of increased permeability of endothelial cells to ions and fluid or cell contraction. Cell to cell connection remained intact. Individual and dispersed endothelial cells were observed 8 h after removal from the animal when incubated in calcium-free HBSS. These necrotic endothelial cells were scattered among viable endothelial cells. Human aortic endothelial cells were also well preserved in the same media for periods of 6-8 h postmortem. Increased extracellular calcium (1.3 mM) in the incubation media caused accelerated cell death. These findings suggest that aortic endothelial cells can be preserved for longer periods of postmortem time than would be expected and that the use of calcium-free HBSS media supplemented with glucose improves endothelial cell viability in vitro.

Adult↗
PubMed1990

Vascular reactivity during the progression of atherosclerotic plaque. A study in Watanabe heritable hyperlipidemic rabbits.

The effects of varying degrees of atherosclerotic plaque on vascular responsiveness in aortas of Watanabe heritable hyperlipidemic (WHHL) rabbits and New Zealand White (normal cholesterolemic) rabbits were studied. Ring segments from the aortic arch and thoracic aorta were mounted in organ chambers for isometric tension recording and measurement of endothelium-derived relaxing factor. WHHL rabbits were divided into three groups according to age: group 1, 3-5 months; group 2, 6-9 months; and group 3, 12-14 months. Atherosclerotic changes (expressed as a percent of total surface area) in the aortic arches in groups 1, 2, and 3 were 11 +/- 3% (mild), 28 +/- 6% (moderate), and 54 +/- 8% (severe) respectively; only occasional plaques were present in the thoracic aorta in all groups. Maximal contractions elicited with phenylephrine progressively decreased with increasing degrees of atherosclerotic plaque. Contractions evoked by histamine were augmented in all groups of WHHL rabbits when compared with controls, whereas those to serotonin were augmented only in vessels with mild atherosclerosis. As the severity of the intimal lesions increased, endothelium-dependent relaxations to acetylcholine, ATP, and calcium ionophore A23187 progressively decreased. Endothelium-independent relaxation to nitroglycerin was virtually complete in all segments. However, vessels with severe atherosclerosis were less sensitive to this agent as illustrated by a significant increase in the ED50 value. Scanning electron microscopy revealed a predominant loss of endothelial cells in the central regions of fibrous plaques. Thus, in WHHL rabbits, hypercholesterolemia and atherosclerosis result in an increased responsiveness of vascular smooth muscle to histamine and serotonin. Endothelium-mediated relaxation of vascular smooth muscle is reduced with the progression of atherosclerosis primarily due to a loss of endothelial cells.

Animals↗
PubMed1989

ATP hydrolysis by ischemic mitochondria.

Cellular ATP levels are determined by the rates of ATP production and ATP hydrolysis. Both phenomena are affected by ischemia. Mitochondrial enzymes are damaged, inhibiting this organelle's ability to make ATP. Mitochondria are also uncoupled by ischemia and have the ability to hydrolyze ATP. We designed a series of experiments to determine whether decreased production or increased hydrolysis of ATP was the primary effect of mitochondrial damage. Rat hearts were subjected to 45 min of warm ischemia in order to induce irreversible cell damage. ATP or ADP was injected into cuvettes containing mitochondria isolated from normal myocardium or myocardium damaged by ischemia. Luciferin-luciferase, which fluoresces in the presence of ATP, was also added to the tubes as an indicator of ATP levels. Mixtures of uncoupled and coupled mitochondria were made and compared with the mitochondria damaged by ischemia. The results showed that mitochondria damaged by prolonged ischemia hydrolyze ATP more rapidly than normal mitochondria; however, normal mitochondria can easily compensate for increased ATP hydrolysis when in mixture with equal amounts of uncoupled mitochondria. These data suggests that the low cellular levels of ATP following irreversible ischemia are primarily due to decreased ATP synthesis and not to increased hydrolysis.

Adenosine Triphosphate↗
PubMed1989

The role of the lymphatics in aiding regression of hypokalemic lesions in rat cardiac muscle.

This study describes the role of lymphatics in the removal of macrophages from inflammatory lesions in the heart of hypokalemic rats and rats recovering from hypokalemia. The inflammatory lesions are characterized by focal cardiomyocyte necrosis, edema, and mononuclear infiltrate. The vascular and lymphatic capillaries are maintained along with the basement membrane of the necrotic cardiomyocyte. Through prior investigation, it was revealed that refeeding potassium led to a rapid reduction in lesion area. The purpose of the current investigation was to establish the role of the lymphatics as a means of reducing the lesion area by removal of the cellular infiltrate and edema. Using a limited potassium diet, hypokalemic rats were sacrificed via perfusion fixation during the hypokalemic and the potassium re-supplementation periods. Heart tissue was examined by light and electron microscopy. During the hypokalemic period, phagocytic mononuclear cells were found engulfing necrotic cardiac muscle cells. With refeeding of potassium, these phagocytic cells appeared to be diminished in number, a reduction that coincided with a decrease in the lesion size. Lymphatic channels were dilated and full of mononuclear cells. These channels were differentiated from the vascular capillaries by standard morphological criteria. In conclusion, the lymphatics play an important role in the healing process by reducing the lesion size through the removal of phagocytic cells and the uptake of proteinaceous material.

Animals↗
PubMed1986

Immature renal tissue in colonic wall of patient with caudal regression syndrome.

We report an incidental microscopic finding of ectopic renal tissue in a newborn with multiple congenital anomalies. The ectopic renal tissue was located in the wall of the distal blind end of the colon. The tissue was composed of undifferentiated renal blastema with primitive and well-formed glomeruli and tubules. The potential for malignant transformation of this lesion into extrarenal Wilms' tumor is not known.

Abnormalities, Multiple↗
PubMed1985

Anesthetics influence myocardial infarct size.

This study compares the effect of three anesthetics on infarct size and regional myocardial blood flow. The anesthetics--fentanyl, Na-pentobarbital, and halothane--differ in their effects on such hemodynamic parameters as blood pressure and heart rate. The mean blood pressure during ligation was 144/91 mm Hg with fentanyl, 141/104 mm Hg with Na-pentobarbital, and 113/82 mm Hg with halothane. The heart rate was 98, 146, and 135 beats/min, respectively. The most significant finding of our study following 90 min of reflow was the infarct size of 26 +/- 8% of the occluded vascular bed under the influence of fentanyl; infarct size under Na-pentobarbital and halothane was 32 +/- 5 and 47 +/- 7%, respectively. The regional flow in relation to the zones of the infarction also differed among the groups. Regional flow under Na-pentobarbital was 24 +/- 6% of normal flow at 90 min of occlusion in the infarcted tissue; regional flow under fentanyl and halothane was 9 +/- 2 and 5 +/- 1%, respectively. The flow in the nitroblue-tetrazolium-staining zone of the occluded vascular bed was 69 +/- 11% (fentanyl), 77 +/- 11% (Na-pentobarbital), and 83 +/- 25% (halothane). It is concluded that anesthetics may well influence infarct size and the outcome of a myocardial infarction following a 90-min ischemia. Hemodynamic effects induced by these anesthetics may well be responsible for this outcome and could be determinants of infarct size, possibly by influencing collateral flow.

Anesthetics↗
PubMed1981

Pathologists' assistant training programs: a report.

This report describes the training of pathologists' assistants in three training programs: at Duke University, at Quinnipiac College associated with Yale University, and at the University of Maryland School of Medicine. The role of this new health profession is described as well as the job situation, experience, and current status of accreditation.

Accreditation↗
PubMed1980

A rapid method of cryofixation of tissues in situ for ultracryomicrotomy.

A device is described for the rapid freezing of tissue in situ by a punch biopsy approach using a specially designed cryogun with a highly thermal conductive specimen holder. The cryogun consists of a sampling device using a double, spring-loaded gun mechanism and a system of cryochambers. Ultrathin freeze-dried sections cut from samples obtained with this cryogun are relatively free of artifacts and have few ice crystals. Organelles are seen by natural contrast when cryosections of approximately 1000 A are observed with a transmission electron microscope or in the transmission mode of a scanning electron microscope. The construction of the cryogun is described along with a method of obtaining improved, ultrafast cryofixation of tissue specimens. The reliability of obtaining x-ray microanalysis measurements of diffusible ions where movement within cell compartments has been retained is discussed.

Basement Membrane↗
PubMed1980

To answer questions. A review of an autopsy service.

Autopsies are important in the quality control of medical practice, in research, and in teaching. We have attempted to realize more of the service, teaching, and research potential from doing autopsies. The key of all efforts is the involvement of the senior staff. This involvement should be made possible by supporting such a person by a qualified team that consists of the mortuary service, pathologist's assistants, and highly trained and qualified residents. Such a staff person can direct his or her attention toward improving communication with clinicians, answering open questions in-depth, encouraging collaborative clinicopathological projects, developing new approaches to the performance of autopsies, such as the immediate autopsy, and using special laboratory modalities, such as electron microscopy and immunofluorescence. Computer storage of autopsy data and retrieval for special studies seem to make autopsy data available and usable. It is most important that autopsies be performed, that they be done well, and that their findings be carefully evaluated using all available scientific tools and, finally, that the results are adequately communicated.

Autopsy↗
PubMed1980

The role of calcium in cell injury. A review.

The role of calcium in cell injury is currently under investigation in many laboratories. It appears that movement of calcium between extra- to intracellular compartments and between various intracellular compartments plays a key role in determining many important reactions of cells both to lethal and sublethal injuries of diverse types as well as in adaptive new steady states. Prevention and/or modification of calcium movements has implication for the control of cell population growth, the prevention of cancer, and the retrieval of victims of shock, myocardial infarction and stroke. Regardless of what type of initial injury occurs, for example ischemia or direct cell membrane damage, the cell undergoes calcium accumulation either by impaired energy metabolism and/or plasmalemmal alterations. This elevated intracellular calcium concentration is responsible for cytoskeletal modifications which alter cell shape, the activation of phospholipases which results in perpetuation of membrane damage and finally, mitochondrial calcification. Although such changes have been partially characterized biochemically and morphologically, some obscure points continue to need clarification. The importance of determing the event(s) responsible for cell death is directly related to the potential capability of their manipulation. Therefore, this could result in the development and/or modification of pharmacologic interventions for the control and prevention of many human diseases. It is the purpose of this paper to review the present state of the art regarding the role of calcium in cell injury, to put it into perspective concerning organelle changes from the standpoint of morphology, and to indicate the present and future role of analytical microscopy in furthering the understanding of these processes.

Animals↗
PubMed1979

Long-term culture of human aortas. Development of atherosclerotic-like plaques in serum-supplemented medium.

Segments of human thoracic aorta were maintained in long-term explant culture for 18 weeks in serum-supplemented medium. The aortas were grossly normal in appearance, and random samples fixed for light microscopy prior to culture revealed a normal morphology. The intima contained no more than five layers of smooth muscle cells. After 7 days in culture, the intima was noticeably thicker than the uncultured segments. The increased thickness was due to proliferating smooth muscle cells and production of extracellular material. After several months in culture, extracellular material consisting of collagen and flocculent material was present in areas resembling atherosclerotic fibrous plaques. A peripheral growth, which formed around the explant, was composed of fibroblastlike cells and added to the overall thickness of the intima. However, aortic segment maintained for up to 2 months in serum-free culture medium showed no cellular proliferation. This study demonstrates that changes resembling early stages of atherosclerosis occur in human aortas maintained in explant culture using routine culture procedures.

Adolescent↗
PubMed1979

The subcellular pathology of shock in trauma patients: studies using the immediate autopsy.

In summary, our immediate autopsy program provides a new tool for investigating the pathophysiologic effects of shock and trauma at the cellular and subcellular levels. By minimizing the time delay between death and tissue sampling with this technique, we have demonstrated the feasibility of validly applying the refinements of electron microscopy, histochemistry and analytical biochemistry to human tissue. Qualitative, semi-quantitative and quantitative data with these techniques have been integrated with clinical, physiologic and chemical studies on these patients during life. Cell injury produces an altered steady state of metabolism within the cell, evidence of which is seen in altered ultrastructure. If the injury is too severe, the cell will pass the "point-of-no-return," at which time the changes in the cell are no longer compatible with life and the cell dies and undergoes necrosis. Although the initiating injury and the patterns of the altered steady state may vary, once the cell has passed the "point-of-no-return," the patterns of cell injury regardless of the initial insult, are similar. We believe that the cellular patterns seen in patients dying from shock and trauma are remarkably similar to those produced by hypoxic tissue injury in experimental systems. Tissue from control patients in whom ischemic injury due to episodes of hypotension did not occur show good morphologic preservation with normal mitochondria and other cell organelles. Tissue from patients who have experienced acute shock consisting of a period of hypotensive ischemia show changes in the mitochondria and ER compatible with the experimental picture of hypoxia: i.e., dilated ER, with loss of ribosomes, swelling of mitochondria and the appearance of flocculent densities in the mitochondria. Tissues taken from the patients who had experienced repeated episodes of shock, whom we designated as those in "chronic shock," showed changes paralleling the acute changes, but also showed much evidence of autophagocytosis as a) the cells attempted to achieve a lower metabolic requirement in order to survive, and b) they attempted to "clean-up" and remove altered and damaged organelles and debris from previous bouts with sublethal ischemic injury. We hope that the increased knowledge of tissue and cellular injury obtained by the immediate autopsy will provide a means of integration, hypothesis formation and testing of the vast knowledge of cell biology and pathology, and the opportunity for developing in the human the potential for testing new hypotheses in model systems resulting in immediate and innovative feedback for the patient in terms of diagnosis, functional monitoring and treatment.

Adult↗
PubMed1979

The role of ion shifts in cell injury.

The present paper reviews studies which utilize x-ray microanalysis to determine intracellular ion shifts following several types of cell injury. New data from our own laboratory on several cell injury systems are discussed. Concentration estimates are made by comparison of data from tissues with a series of standards prepared in 20% albumin followed by cryosectioning. Hemorrhagic shock in rats is followed by rapid changes of ions in both muscle and liver. These include increased levels of sodium and chlorine and decreased levels of potassium which can be correlated with deficits in the energy charge. Measurements made over hepatocellular carcinomas in the mouse, induced by safrole show marked changes in comparison with non-transformed cells. These include striking increases in sodium and chloride and decreases in potassium and phosphorus which may be related to growth control. Studies on ischemia produced by arterial clamping in the rat kidney and the dog heart show somewhat similar changes. Moreover, in these models much interest is directed at early increases of cytoplasmic calcium with decreased mitochondrial calcium levels at later intervals. Following reflow, there is a prominent increase of calcium in the cytosol. These changes in calcium may be related to activation of phospholipases producing permeability changes which may contribute to further ion shifts as well as ultimately to cell death. The paper also comments on the use of cryostat sections for some types of routine pathological analysis.

Animals↗