Medicine in the nineties. Expectations, priorities, and realities.
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Biomedical subjects
Publications and source records attributed to J L Glover.
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Forty-four patients undergoing femoropopliteal angioplasty were studied by magnetic resonance blood flowmetry to determine quantitative limb perfusion. Baseline limb perfusion averaged 0.52 +/- 0.15 mL/min per 100 cc of tissue. Perfusion values for successful angioplasties rose within 72 hours to a mean of 1.40 +/- 0.31 mL/min per 100 cc of tissue. There were five early failures (less than 30 days), in which perfusion fell to 0.54 +/- 0.10 mL/min per 100 cc of tissue; at 6 months, 12 additional angioplasties had failed, with limb perfusion values of 0.68 +/- 0.16 mL/min per 100 cc of tissue. At 6 months, perfusion in four additional limbs had decreased to between 0.7 and 1.0 mL/min per 100 cc of tissue, with a mean change of 0.59 mL/min per 100 cc of tissue; duplex ultrasound imaging at these sites showed restenoses ranging from 50% to 75%. We conclude that lower-leg limb perfusion appears to be a reliable measure of hemodynamic improvement after femoropopliteal angioplasty and may provide an early indicator of impending failure.
This study evaluated the hemodynamic changes associated with patch angioplasty compared to primary closure of the canine carotid artery. A standard arteriotomy was closed either primarily, with a 5x28 mm expanded polytetrafluoroethylene (ePTFE) patch, or with a 10x28 mm ePTFE patch. Measurements for the primary closure group showed a systolic pressure gradient of 17 mmHg across the closure and a peak systolic velocity increase of 58% at mid-closure compared to proximal inflows. Flow turbulence increased at mid-closure in the 10 mm patch group, with the percent spectral window lowered from 0.50 to 0.36. These data show that primary vessel closure creates a mild local stenosis with flow acceleration but no flow turbulence. No significant hemodynamic disturbances are caused by a moderate sized patch; however, a large patch relative to native vessel dimensions creates marked flow disturbances throughout the cardiac cycle. As turbulence and flow separation are felt to contribute to restenosis, care should be taken in the selection of patch size when used following carotid endarterectomy.
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The current theory of myocardial development holds that after a limited number of divisions, the myocardiocytes of the developing heart are irreversibly withdrawn from the generation cycle. It is, therefore, considered impossible to grow adult human myocardiocytes in culture, making it necessary for studies of cardiac muscle in culture to be carried out using animal or fetal human models. Recently, we developed a method for isolating, culturing, and characterizing myocardiocytes derived from explanted adult human atrial myocardium. A highly pure fraction (93%) of one of four morphologically discrete cell populations was separated using selective attachment techniques. These cells possessed features consistent with those seen in animal and fetal myocardiocytes. Using immunoperoxidase stains, these cells stained positive for actin, myoglobin, and atrial natriuretic peptide, proving the cells are myocardial muscle cells. Electron microscopy showed numerous bundles of myofibrils with interspersed dense Z-bodies and pleomorphic mitochondria. Bromo-deoxyuridine incorporation confirmed that the cells were replicating their DNA. Thus, cell morphology, immunoperoxidase stains, electron microscopy, and cell proliferation testing showed these cells to be myocardiocytes undergoing DNA replication and mitosis. We must now reconsider our current thinking about myocardial development and investigate what factors contribute to the inhibition of myocardial cell proliferation after injury in vivo.
The records of all patients who had a cerebrovascular accident (CVA) following coronary artery bypass surgery were reviewed to determine the incidence, etiology, and outcome following such an event. Between January 1, 1987, and December 31, 1990, 3,428 patients underwent bypass grafting and 46 had a CVA, documented by head computed tomography (CT) after neurologic findings were appreciated, for an incidence of 1.3 per cent. In 16 patients, a neurologic deficit was documented less than 12 hours after surgery and was presumed to have been an intraoperative event. The remaining 30 patients became symptomatic between postoperative days 2 and 7. Twenty-five patients (54%) exhibited neurologic and CT findings suggestive of an embolic event, while the remaining 21 patients appeared to have sustained an infarct as a result of cerebral hypoperfusion. Nine patients with CVA had a carotid bruit documented in the preoperative period, and seven of these suffered their ischemic event in the ipsilateral distribution. Five patients had a documented CVA previously, and four were shown to have extended areas of previous infarction. The mortality following CVA was 35 per cent. Of the survivors, 70 per cent had some improvement in symptoms at the time of discharge; 60 per cent of survivors were discharged to their homes and the remainder to extended care facilities. Although CVA following coronary bypass grafting is an uncommon event, some patients at increased risk may benefit from more aggressive preoperative noninvasive evaluation and intraoperative monitoring. A better understanding of the etiology of postoperative stroke may help to prevent its high morbidity and mortality, which has been demonstrated.
Correlation between increased cranial and peripheral norepinephrines and increased cranial to systemic renin ratio has been observed in a small number of patients with postcarotid endarterectomy hypertension. In an effort to confirm these findings, we studied cranial and peripheral levels of catecholamines and peripheral renin activity in 120 consecutive carotid endarterectomies. Samples were taken before carotid clamping (Sample I) and just after clamp release (Sample II). Norepinephrine, epinephrine and dopamine values did not correlate with postcarotid endarterectomy hypertension. There was no association between peripheral renin values and postcarotid endarterectomy hypertension.
One hundred eighty-seven patients who presented with symptoms consistent with biliary colic but had no ultrasonic evidence of cholelithiasis were observed in an effort to identify those with a functional gallbladder disorder that might benefit from surgical intervention. All patients underwent quantitative evaluation of gallbladder emptying using cholecystokinin biliary scanning, and ejection fractions less than 35% were considered abnormal. One hundred twenty-nine patients (69%) had abnormal ejection fractions, and 88 (68%) of these subsequently underwent cholecystectomy. Sixty of the surgical specimens revealed pathologic changes. Eighty-four percent of patients successfully contacted for follow-up experienced complete relief, and another 13% had partial relief of preoperative symptoms. Only two patients reported no change in symptom complex. Twenty-nine patients with abnormal ejection fractions elected not to undergo surgery. Fifty-nine percent of these patients continued to experience symptoms of biliary colic at a mean follow-up of 22 months. Of the 44 patients with normal ejection fractions, 35 (80%) reported resolution of symptoms during follow-up of medical treatment. Cholecystokinin biliary scanning can help identify patients with acalculous, functional gallbladder disease who may benefit from cholecystectomy.
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Myocardial cell culture methods are now well established for animal and fetal human tissue. We present here a method for harvesting and culturing adult human atrial myocardiocytes. Cells are obtained from fresh atrial tissue normally discarded after being removed to cannulate the right atrium during open heart surgery. The atrial tissue is minced and then digested using collagenase. The single cell suspension is initially cultured in serum-containing growth medium, then transferred to defined medium, selective for myocardial cell growth. The cells are characterized by immunoperoxidase stains and transmission electron microscopy. The cultured cells stain positive for myoglobin, whereas control cultured fibroblasts and endothelial cells do not. Electron microscopy shows the presence of numerous myofibrils, Z-bodies, pleomorphic mitochondria, and secretory granules. The chronological age of the donor was an important factor in culturing the adult tissue, the younger tissue correlated with a higher success rate. This method provides a means for in vitro study of human adult myocardial cells and provides guidelines for appropriate atrial tissue to use.
This study is the first to compare chronic healing characteristics of immediately seeded grafts with those of grafts lined by autogenous venous endothelial cells in tissue culture prior to implantation. Ten mongrel dogs had a segment of external jugular vein excised for enzymatic harvest of endothelial cells. After approximately 21 days growth in tissue culture, 4 X 10(6) cells/ml were inoculated into a 6-cm length of 4 mm i.d. ePTFE for formation of a confluent lining in culture media. The remaining external jugular vein had its endothelial cells enzymatically harvested for immediate seeding of an identical length of preclotted ePTFE. Both grafts were implanted end-to-end in the carotid position and excised after 30 days. In 6 of the 10 dogs, grafts were patent bilaterally; all others were occluded. Planimetric measurements on patent grafts with immediate seeding showed a thrombus-free surface area of 56 +/- 39% compared to 86 +/- 15% for culture-lined grafts (P = 0.046). Endothelial coverage was 70 +/- 24% for immediately seeded grafts and 29 +/- 21% for culture-lined grafts (P = 0.016). We conclude that immediate seeding and culture lining of autogenous endothelial cells in small diameter ePTFE grafts produce equivalent short-term patency. While culture-lined grafts have an initially less thrombogenic luminal surface, subsequent development of a confluent endothelial lining is slower than that with an immediate seeding preparation, and thus would appear to offer no significant clinical benefit, especially in light of the complexity culture lining adds to the procedure.
Endothelial cell seeding procedures have been developed to line prosthetic bypass grafts used in peripheral vascular disease; however, because of current inefficient cell harvest techniques a high ratio of vein-to-graft area is necessary. This study was done to determine if the use of papaverine, a smooth muscle cell relaxant, would affect the number or viability of endothelial cells harvested from canine external jugular veins. Using a 0.12 mg/ml solution of papaverine in tissue culture medium to bathe the veins during dissection and excision, the viable cell yield was 2.20 +/- 1.16 (cells x 10(4)/cm2). A control group of veins using standard dissection technique gave a yield of 0.97 +/- 0.40 (p = 0.025). A second group of veins dissected while bathed in tissue culture medium alone gave a yield of 1.82 +/- 0.75, compared to a yield of 2.73 +/- 0.45 for papaverine harvested veins (p = 0.009). Percent cell viability was not significantly different for any of the groups: 73, 70, and 76% for papaverine, control and media only veins, respectively. The papaverine-harvested cells and those harvested with medium alone grew to 95% confluence in tissue culture in 9.8 +/- 1.1 and 9.9 +/- 0.9 days, respectively. Compared to conventional surgical techniques, use of papaverine more than doubled the endothelial cell yield from excised vein segments without adversely affecting viability or rate of growth in cell culture.
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Postoperative mortality and morbidity of diabetic versus nondiabetic patients undergoing primary coronary artery bypass grafting (CABG) were analyzed. In 1988, 711 patients had CABG procedures, of which 565 were nondiabetic and 146 diabetic. The two groups of patients were statistically similar in regard to age, weight, tobacco and ethanol use, and preoperative levels of cholesterol, triglycerides, blood urea nitrogen (BUN), and creatinine. Preoperative serum glucose levels were significantly elevated in diabetic patients (182 vs. 106, P less than .001). Cardiac output, ejection fraction, and bypass, crossclamp time, and total operating room times were not different for the two groups. Emergent and urgent procedures had a significantly higher mortality rate than elective cases (11.3% and 6.6% vs. 1.7%, respectively; P less than 0.05), but this was independent of the patient's diabetic status. Women had a higher mortality rate than men (6.5% vs. 2.9%; P = 0.05) although within each gender group, there were no differences between diabetics and nondiabetics. There were 27 patients with complications in the diabetic group (18.5%) and 47 in the nondiabetic group (8.3%; P less than .001). The types of complications within the two groups differed in that wound infections (7.5%), postoperative arrhythmias (4.8%), respiratory failure (4.1%), and intra-aortic balloon pump use (4.1%) were significantly greater (P less than .05) in the diabetic patients compared to the nondiabetic (0.9%, 1.8%, 0.4%, and 1.4%, respectively). Occurrences of postoperative pneumothorax, reoperation, myocardial infarction, stroke, urinary tract infection, and pneumonia were similar in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)
The risk of postsplenectomy sepsis has led to increased enthusiasm for preservation of the spleen. From January 1984 to December 1988, 51 consecutive adult patients with ruptured spleen sustained from blunt trauma were examined. Thirty-four patients (67%) had their conditions hemodynamically stabilized at the time of hospital admission and were placed on a regimen of strict bed rest with intensive monitoring. The average hemoglobin value at hospital admission in this group was 126 +/- 18 g/L, with an average drop of 17 +/- 14 g/L during their hospitalization; 14 patients required transfusions averaging 3 U each. Nonoperative treatment was successful in 33 (97%) of 34 patients; one patient whose condition deteriorated clinically underwent splenectomy on the fifth hospital day. These patients have been followed up for an average of 28 months with no sequelae from their splenic injury. We conclude that a nonoperative approach is a viable alternative in stable adult patients with splenic injuries due to blunt trauma when intensive monitoring is available.
The operative approach to primary hyperparathyroidism due to a single adenoma remains controversial. We evaluated our experience with 75 patients presenting with primary hyperparathyroidism between January 1979 and September 1988. Prior to 1985 all patients underwent bilateral exploration. During this period, ultrasonographic localization in 6 patients proved highly accurate. Subsequently, routine preoperative ultrasonographic localization was used and patients were prospectively evaluated for the following: (1) incidence of unilateral exploration, (2) accuracy of ultrasonographic localization, (3) incidence of complications, and (4) operative time. Localization permitted unilateral exploration in 19 of 36 patients, although its accuracy depended on the interest of the radiologist involved. Institution A had an accuracy of 92%, while institution B had an accuracy of only 43%. There were fewer complications with unilateral exploration, and operative time was significantly less. Unilateral exploration based on preoperative ultrasonographic localization is recommended as the initial approach to primary hyperparathyroidism due to a single adenoma.
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In summary, vertebral artery hemodynamics can be readily evaluated both qualitatively and quantitatively. Duplex ultrasonography provides a very reliable noninvasive technique for this assessment. Flow in the vertebral artery system can be noninvasively quantified in greater than 95 per cent of all patients examined using this technique, and such measurements help identify subgroups of patients whose symptoms may be related to posterior circulation ischemia. Further evaluation of the spectral flow patterns is often helpful in diagnosing the cause of these ischemic symptoms. Unfortunately, quantitative flows are rarely obtained during routine carotid ultrasound studies. Such data, however, may provide an objective basis for the following kinds of surgical decisions: 1. Recommendations for carotid surgery in patients with high-grade carotid stenosis but nonlocalizing symptoms. 2. Recommendations for no surgery in patients who have vertebrobasilar symptoms but diminished flow characteristic of poor cardiac output. 3. Recommendations for surgery to augment vertebral artery flow in patients who have vertebrobasilar symptoms, decreased vertebral flow on the basis of proximal stenosis, and normal carotid artery flow. Obviously, there is a need to confirm these hypotheses by studying patients thoroughly before and after surgery. Other investigators must begin gathering data on vertebral artery flow to determine its impact and utility in making surgical decisions.