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Biomedical subjects

W N O'Connor

Publications and source records attributed to W N O'Connor.

At least 19 recordsLinked to original sources

The autopsy in the 21st century: time for reconsideration.

In recent years, the autopsy rate has dramatically declined. Using three cases, we attempt to explore the current questions concerning the value of the autopsy. The discussion centers around the importance of the autopsy to medicine and family members of the deceased, the impact of technological advances on the autopsy, and discordant pre- and post-mortem diagnoses. We conclude that the decrease in autopsy rates is secondary to underutilization of the autopsy as a diagnostic and educational tool.

Adult↗

Surfactant disposition in rats with monocrotaline-induced pneumotoxicity.

Monocrotaline (MCT)-treated rats exhibit airways and gas exchange abnormalities which precede development of sustained pulmonary hypertension (Lai et al., 1991). Because the density of type II pneumocytes is reduced in MCT-treated rat lungs (Wilson and Segall, 1990), decreased abundance or activity of type II pneumocyte-derived surfactant may contribute to pulmonary dysfunction. On the other hand, since the remaining type II pneumocytes undergo an apparent hypertrophic response, it is possible that they compensate for the reduction in population density by elaborating more surfactant or surfactant with enhanced surface activity. As an initial means of discriminating between these possibilities, the amount, surface activity, and synthesis rate of surfactant was examined in rats at 1, 2, and 3 weeks after MCT administration. The amounts of surfactant phospholipid and protein recovered in bronchoalveolar lavage fluid did not differ substantially between control and MCT-treated rats at any time post MCT administration. Similarly, neither the initial rate of surface tension reduction nor the maximum reduction in surface tension differed between surfactant preparations recovered from control and MCT-treated rats. The rate of surfactant synthesis in lung explants, as determined by incorporation of [3H]glycerol into phospholipid, also was not different between MCT-treated and control rats at any time after MCT administration. MCT treatment failed to alter the distribution of [3H]glycerol into surfactant phospholipid. Collectively, these data indicate that airways abnormalities in MCT-treated rats cannot be ascribed to a reduction in the abundance or the activity of surfactant. Furthermore, in light of previous studies indicating that the density of type II pneumocytes is reduced in MCT pneumotoxicity, the present findings suggest that surfactant regulatory pathways must undergo a compensatory response that preserves normal functional status.

Animals↗

Pulmonary hypertension in a murine model of the acquired immunodeficiency syndrome.

Rapidly accumulating evidence suggests that a proportion of patients with acquired immunodeficiency syndrome (AIDS) develop hypertensive pulmonary vascular disease reminiscent of primary pulmonary hypertension. As an initial step to explore the link between AIDS and hypertensive pulmonary vascular disease, the present study determined whether pulmonary hypertension is present in a well-characterized murine model of retrovirus-induced immunodeficiency. In agreement with previous reports, mice infected with the LP-BM5 murine leukemia virus developed polyclonal B and T cell activation followed by progressive and severe B and T cell immunodeficiency. At 12 wk postinfection, when persistent immunodeficiency was established, mice were anesthetized, and right ventricular systolic pressure was determined in open-chest, mechanically ventilated animals. Mean right ventricular systolic pressure was 14.7 +/- 1.3 mm Hg in control animals and was increased significantly to 22.5 +/- 3.2 mm Hg in virus-infected mice. Right ventricular hypertrophy was also present in infected mice as evidenced by a 27% increase in the ratio of right to left ventricular weights; there were no group-dependent differences in the left ventricular to total-body weight ratio. Morphometric evaluation indicated that medial thickness in muscularized pulmonary arteries, expressed as a percentage of the external diameter, was 9.6 +/- 0.4% in control lungs and increased to 14.4 +/- 0.5% in lungs from infected animals. Qualitative histopathologic analysis suggested increased perivascular collagen deposition in lungs from infected animals relative to control animals. Unlike AIDS patients with pulmonary hypertension, infected mice did not exhibit plexiform lesions or intimal fibrosis of the pulmonary arteries.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Autoperfused heart-lung preparation: one reason for unsuccessful lung preservation.

Normothermic autoperfused heart-lung preparation has the advantages of avoiding ischemic time and allowing continuous monitoring of organ function during preservation. When this technique is used, the lungs deteriorate quickly, but the reasons for this deterioration have not been investigated. This study was designed to explore the possible cause of rapid lung deterioration. Three groups of mongrel dogs were used. In Group 1 (N = 5), a buffer bag was used in the heart-lung preparation. In Group 2 (N = 6), a 20 mu filter was incorporated between the buffer bag and the right atrium. In Group 3 (N = 5), no buffer bag was used. Average survival time was 15.0 +/- 3.1 hours in Group 1, 13.5 +/- 0.7 hours in Group 2, and 21.6 +/- 2.3 hours in Group 3. Heart function was comparable among the three groups, but the arterial pulse pressure was lower and the heart rate higher in Group 3. Both white blood cell and platelet counts decreased contonuously during the preservation period. Examination of the filters in Group 2 revealed numerous aggregates consisting of platelets, white blood cells, red blood cells, and fibrin. Small thrombi were also found in the lungs in Groups 1 and 2. The results indicated that one important reason for quick lung deterioration was numerous aggregates, which were formed in the buffer bag, returned from the venous line, and trapped in the lungs. Removal of the buffer bag reduced the production of aggregates but tended to de-stabilize the hemodynamics of the preparation.

Animals↗

Two-day preservation of the lungs by normothermic perfusion.

Lung function was studies during a 2-day preservation period. The lungs were removed along with the heart, liver, pancreas, duodenum, and both kidneys while they were still perfused by the heart and oxygenated by the lungs. In 12 experiments the organs survived an average of 49.2 hours. Arterial blood pressures were maintained at 74-95 mmHg, and no inotropic drugs were used. When a gas mixture of 50% O2 + 3% CO2 + 47% N2 was used, arterial oxygen tension ranged from 239 +/- 23 to 305 +/- 16 mmHg; carbon dioxide tension ranged from 17.6 +/- 1.8 to 24.9 +/- 2.9 mmHg; and pH ranged from 7.31 +/- 0.03 to 7.49 +/- 0.04. Maximum airway pressure ranged from 12.5 +/- 1.7 to 28.0 +/- 2.2 mmHg. Airway resistance ranged from 0.020 +/- 0.006 to 0.049 +/- 0.007 mmHg/ml and increased after 40 hours. Lung tissue wet/dry weight ratio was stable during the preservation period. The results showed that the lungs were well preserved in the normothermic perfusion preparation for up to two days with minimal functional changes.

Airway Resistance↗

Spontaneous coronary arterial dissection and isolated eosinophilic coronary arteritis: sudden cardiac death in a patient with a limited variant of Churg-Strauss syndrome.

Isolated eosinophilic coronary arteritis expressed as a limited variant of the Churg-Strauss syndrome (allergic granulomatosis and angiitis) is a rare condition. Equally as rare is the entity of isolated spontaneous coronary arterial dissection associated with eosinophilic arteritis. A 57-year-old woman with a history of asthma and recurrent hypersensitivity (anaphylactoid) reactions to various exogenous allergens was found dead in her home; no premonitory complaints had been noted during the preceding days. Autopsy revealed focal occlusion of the left anterior descending and first diagonal coronary arteries by discrete dissecting hematomas of the media as the cause of sudden and unexpected death. Histologically, the affected arterial wall showed eosinophilic inflammation characteristic of this limited expression of the Churg-Strauss syndrome. To our knowledge, sudden cardiac death caused by arterial dissection in isolated eosinophilic coronary arteritis has not previously been reported.

Arteritis↗

Endomyocardial ultrastructural findings in preeclampsia.

Ultrastructural findings in endomyocardial biopsy specimens obtained during cardiac catheterization in a patient with severe preeclampsia are described. Intramyocardial vessels revealed prominent swelling of the endothelial cell cytoplasm. In addition, cardiac myocyte mitochondria showed swelling and clearing within the matrix. Endomyocardial ultrastructural injury occurs in severe preeclampsia.

Adult↗

Intraoral sebaceous carcinoma.

An instance of sebaceous carcinoma that presented as a mass in the left buccal mucosa is described. This is the first known report in the English-language literature of a sebaceous carcinoma presenting as an intraoral tumor. The light and electron microscopic findings are described. The histologic differential diagnosis, clinical behavior, and appropriate therapy are discussed. Previously reported intraoral sebaceous neoplasms and sebaceous carcinomas of the parotid are reviewed.

Adenocarcinoma↗

Mechanism of acute myocardial infarction in patients with prior coronary artery bypass grafting and therapeutic implications.

Although acute myocardial infarction (AMI) is usually due to thrombotic occlusion when involving a native coronary artery, the mechanism responsible for AMI in patients with previous coronary artery bypass grafting (CABG) is not well understood. Since knowledge of pathophysiology of AMI may alter subsequent management, angiograms obtained between 1 hour and 7 days of AMI (median 1 day) were reviewed in 50 patients greater than 1 year after CABG. The culprit vessel was identified by the presence of residual stenosis and/or thrombus in the vessel supplying the infarct zone or by reviewing previous angiograms. The infarct vessel was identified as a vein graft in 38 (76%) patients, the native vessel in 8 patients (16%) and could not be accurately determined in 4 patients (8%). Among the 38 vein grafts suspected as the infarct vessel, unequivocal angiographic evidence of residual thrombus (filling defect/persistent staining) was present in 31 (82%) and was greater than 2 cm in length in 15 patients. Successful reperfusion occurred in only 2 of 8 (25%) grafts after intravenous thrombolytic therapy. Intragraft thrombolysis with or without additional angioplasty was successful at restoring flow in 8 of 10 (80%) grafts. Data indicate that in patients who have undergone previous CABG, AMI is usually caused by thrombotic occlusion of a saphenous vein graft and that conventional intravenous thrombolytic therapy may be inadequate to restore flow. The large mass of thrombus and absent flow in the graft may require subselective drug infusion, a higher thrombolytic dose or a mechanical means of recanalization.

Angiography↗

Mediastinal epithelioid hemangioendothelioma.

An epithelioid hemangioendothelioma arising from the innominate vein in the anterior superior mediastinum of a 62-year-old man was treated by wide local excision followed by radiotherapy. This clinicopathologic entity is a rare cause of mediastinal mass and is characterized by an intermediate malignant potential. To our knowledge, very few cases have been reported in the mediastinum; those cases are listed in this report. Gross and microscopic distinguishing features of epithelioid hemangioendothelioma, as well as differential diagnosis, are reviewed from the literature. Finally, clinical behavior is discussed and treatment options are suggested.

Brachiocephalic Veins↗

Eighteen to 37 hours' preservation of major organs using a new autoperfusion multiorgan preparation.

A new autoperfusion preparation was used to preserve six major organs simultaneously. In 7 Yorkshire white swine, the heart and lungs were separated and removed with the liver, pancreas, duodenum, and both kidneys en bloc while they were self-perfused. Fresh blood, glucose, electrolytes, heparin sodium, methylprednisolone, and a fat emulsion (Soyacal) were infused through the portal vein. No inotropic drugs were necessary. The organs survived for 18 to 37 hours (average survival, 24.6 +/- 2.7 hours [+/- standard error of the mean]). Aortic systolic pressure ranged from 78.5 +/- 5.5 to 98.7 +/- 11.8 mm Hg. Arterial oxygen tension ranged from 206 +/- 23 to 266 +/- 15 mm Hg and arterial carbon dioxide tension, from 20.1 +/- 2.7 to 32.1 +/- 4.9 mm Hg. Blood lactic acid levels decreased from 8.75 +/- 2.06 to 5.50 +/- 2.45 mmol/L at 24 hours. Urine output ranged from 25 to 82 mL/h. Blood urea nitrogen levels decreased from 9.17 +/- 0.59 to 4.67 +/- 1.08 mg/dL. Blood creatinine levels decreased from 1.34 +/- 0.10 to 0.57 +/- 0.22 mg/dL. Serum glutamicoxaloacetic transaminase levels increased from 73.4 +/- 26.3 to 194 +/- 179.5 U/L and serum glutamic-pyruvic transaminase levels, from 44.8 +/- 5.7 to 91 +/- 66.4 U/L. Red blood cell count ranged from 6.94 +/- 0.58 to 13.23 +/- 2.30 x 10(6)/microliters. Lung wet/dry weight ratios changed from 5.79 +/- 0.17 at the beginning to 6.25 +/- 0.16 at 24 hours. The technique for simultaneous multiorgan preservation presented here is simple, effective, and highly reproducible. This study appears to have produced one of the longest average survival times for autoperfusion.

Animals↗

Ventriculocoronary connections in hypoplastic right heart syndrome: autopsy serial section study of six cases.

Myocardial sinusoids communicating with the coronary systems occur in pulmonary atresia with intact ventricular septum. To test the hypothesis that the extent of ventriculocoronary connections correlates with the degree of right ventricular outflow obstruction as evidenced by clinical, angiographic and gross anatomic findings, a serial section study of six human autopsy hearts representing a spectrum of hypoplastic right heart was undertaken. Slides were evaluated for the presence and extent of ventriculocoronary connections, associated developmental abnormalities and secondary changes in the ventricular walls. Whereas extensive blind-ended deep sinusoids were a feature of all five cases with unrelieved obstruction, ventriculocoronary connections were identified in three. Changes that suggested ongoing remodeling provide new evidence for the postnatal temporal evolution of these anomalous communications. The regional distribution of myofiber disarray in hypoplastic right heart supports the concept that vascularization parallels myocardial organization in the developing human heart.

Coronary Vessels↗

Right ventricular hypertrophy long after reversal of severe pressure overload in cats.

To test the hypothesis that alterations in ventricular size and function may persist long after reversal of a severe pressure overload, right ventricular (RV) hypertrophy was produced in cats by abrupt, severe constriction of the pulmonary artery (PA) for 8 wk, after which pressure overload was completely reversed by surgical removal of the PA band (group III). Despite debanding and recovery from pressure overload (RV peak systolic pressure = 22 +/- 4 vs. 66 +/- 20 mmHg before debanding and 25 +/- 4 mmHg in controls), parameters of hypertrophy 8-10 mo later remained substantially increased: e.g., RV/LV (left ventricular) mass ratio was 0.36 +/- 0.06 in group III vs. 0.24 +/- 0.03 in controls (group I) and 0.43 +/- 0.07 in a separate cohort (group II) studied after 8 wk of banding. Maximum RV stroke work during volume loading was computed from RV micromanometry and PA electromagnetic flow: 20 +/- 8 g-cm/g for group III vs. 51 +/- 14 for group I, P less than 0.05, and 21 +/- 7 for group II. Thus severe pressure overload of the RV may produce changes in size and function that are not fully reversed by complete removal of the overload.

Animals↗

New autoperfusion preparation for long-term organ preservation.

The problems in long-term organ preservation are ischemia and toxicity from metabolic waste. A simple self-perfusing self-cleaning system has been developed that kept the heart, lungs, and kidney functioning for a mean time of 24 hours. Nine adult dogs were anesthetized and artifically ventilated. The heart and lungs were removed en bloc while being perfused by the heart. One kidney was connected to the descending aorta and inferior vena cava. No anticoagulant was used. Another group of six dogs without functioning kidneys was used as the control group. In the experimental group, urine output ranged from 26 to 48 ml/hr, aortic systolic pressures were 80-107 mm Hg, heart rate was 85-100 beats/min, serum potassium content was 3.25-4.40 mmol/l, and serum sodium content was 155-163 mmol/l. In the experimental group, blood creatinine levels decreased from 0.95 to 0.47 mg/dl during preservation; in the control group, blood creatinine levels decreased from 0.96 to 0.79 mg/dl. Lung biopsies in the preparation with the longest survival showed good preservation for as long as 24 hours, and no thrombi were present. This preparation has the advantage of no ischemic time, no foreign material in the circulation, and the ability to automatically maintain acid-base balance and blood electrolytes. The simplicity of this autoperfusion preparation may allow greater transport distance in organ procurement for subsequent transplantation.

Animals↗