Prevention of postoperative pericardial adhesions by closure of the pericardium with absorbable polymer patches. An experimental study. Pericardial adhesions after cardiac operations are a widely known phenomenon. They may severely complicate reoperations, making reentry hazardous, increasing bleeding, and prolonging the operation time. The anatomic orientation and visibility of both bypass grafts and coronary arteries are also impaired. With the aim of minimizing pericardial adhesions after cardiac operations, we studied the course of tissue regeneration after implantation of a new absorbable patch made from poly-hydroxy-butyrate. A total of 23 sheep were studied. Of these, 18 formed the test group and five served as control animals. The animals were killed at intervals of 2 to 30 months after the operation. In 14 of the 18 test animals no adhesions developed. In three animals loose adhesions were found, and in one with signs of postoperative infection there were moderate, generalized adhesions. All control sheep showed moderate adhesions; no infection was noted in this group. Light microscopy in the test group revealed a layer of mesothelium-like cells facing the epicardial side; this was already present in the early specimens. Poly-hydroxy-butyrate appeared to be slowly phagocytosed by polynucleated macrophages, which were still found occasionally in the late samples. Lymphocytes and platelets were rare. Scanning electron microscopy showed, on the epicardial side of the regenerated tissue, a mesothelium-like lining that completely covered the underlying collagen layer. The surface cell morphology grossly resembled that of native pericardium. It was concluded that in this animal model poly-hydroxy-butyrate pericardial patches decreased adhesions and preserved coronary anatomy. The findings in the control group demonstrated that pericardial surgery in the sheep was associated with adhesion formation.


Myocardial protection during cardiac operations. Decreased morbidity and lower cost with blood cardioplegia and coronary sinus perfusion. The efficacy of myocardial protection with a single aortic crossclamp and blood cardioplegia was evaluated in 819 consecutive patients stratified for preoperative condition by means of a new clinical risk scoring system. A protocol using either antegrade or antegrade/retrograde blood cardioplegia was compared with antegrade crystalloid cardioplegia in 2582 similar, consecutive, and concurrent patients. In the blood cardioplegia cohort, 97 (11.8%) patients had 129 complications compared with 407 (15.8%) patients and 675 complications in the crystalloid cardioplegia group (p = 0.006). In high-risk patients, combined antegrade/retrograde cardioplegia significantly reduced myocardial infarction, stroke, and respiratory and wound complications. Despite the significantly longer aortic crossclamp time required for blood cardioplegia, patients undergoing crystalloid cardioplegia were 1.7 (95% confidence interval 1.3, 2.1) times more likely to have a morbid event. Time in the intensive care unit, length of hospitalization, and length-of-stay outlier status were significantly decreased in the blood cardioplegia compared with the crystalloid cardioplegia group. The net savings in hospital cost amounted to $2196 per case. When compared separately with crystalloid cardioplegia, combined antegrade/retrograde blood cardioplegia accounted for most of the morbidity reduction by significantly reducing perioperative myocardial infarction, wound complications, and length of stay in patients having reoperations. Antegrade/retrograde blood cardioplegia did not influence 1-year survival or event-free survival, even when risk was considered.


Salvage of ischemic myocardium by nonsynchronized retroperfusion in the pig. Salvage of ischemic myocardium, with the aid of a nonsynchronized coronary sinus retroperfusion system, was studied in a pig infarct model. In anesthetized open chested animals, the left anterior descending coronary artery was occluded for 4 hours and then reperfused for 1 hour before the animals were killed. In the control group (n = 12) no therapy was used. In the experimental group (n = 13), nonsynchronized retrovenous coronary sinus perfusion was applied during the 4 hours of coronary artery occlusion. Therapy consisted of intermittent balloon occlusion of the coronary sinus (5-second inflation, 5-second deflation) with retroperfusion of arterial blood at 60 ml/min during the inflation part of the cycle. Infarct size, expressed as a percentage of the area at risk (+/- standard deviation), was significantly smaller in the experimental group (41.5% +/- 15.0%) than in the control group (80.5% +/- 6.1%) (p less than 0.001). Mean coronary sinus pressure (+/- standard deviation) was 51 +/- 12 mm Hg in the experimental group but was not elevated in the control animals. We conclude that nonsynchronized retrovenous coronary sinus perfusion was able to significantly salvage ischemic myocardium in a model of minimal intercoronary collateral circulation.


Topical cardiac hypothermia in patients with coronary disease. An unnecessary adjunct to cardioplegic protection and cause of pulmonary morbidity. This retrospective analysis tests the hypothesis that topical cardiac hypothermia is an unnecessary adjunct to intraoperative myocardial protection and an avoidable cause of pulmonary morbidity in patients with coronary disease receiving blood cardioplegia. The hospital records of 150 nonrandomized consecutive patients undergoing elective and emergency isolated coronary revascularization were reviewed. All patients received multidose cold blood cardioplegia followed by warm blood cardioplegic reperfusion distributed through grafts. Fifty patients received iced slush, 50 received topical 4 degrees C saline, and no topical cooling was used in 50 others. Patients groups were comparable in number of grafts (3.7 versus 3.5 versus 3.5) and crossclamp time (61 versus 62 versus 61 minutes). More emergency operations were performed in the patients receiving no topical hypothermia (12/50 versus 8/50 versus 7/50). Postoperative x-ray films were reviewed by a radiologist who did not know of patient grouping. Postoperative results were comparable in hemodynamics, inotropic requirements (10/50 ice versus 8/50 saline versus 5/50 no cooling), myocardial infarction (1/50 versus 2/50 versus 2/50), and enzymes (aspartate aminotransferase myocardial band creatine kinase). No patient died. Ice topical hypothermia (versus no topical cooling) was associated with more left pleural effusions (25/50 versus 9/50; p less than 0.05), atelectasis (33/50 versus 18/50; p less than 0.05), elevated left hemidiaphragms (13/50 versus 0/50; p less than 0.05), and longer postoperative hospitalization (11.2 versus 8.5 days; p less than 0.05). Topical 4 degrees C saline reduced diaphragmatic elevation and pleural effusion (versus topical ice) but was associated with more atelectasis (34/50 versus 18/50; p less than 0.05) than no topical cooling. These data suggest that routine topical hypothermia is an unnecessary adjunct to blood cardioplegic protection in patients with coronary disease, since supplemental topical cooling does not improve postoperative hemodynamics or reduce inotropic requirements, enzyme release, or prevalence of postoperative myocardial infarction, and it increases pulmonary morbidity, which can be reduced by its avoidance.


Effects of oxygenated cardioplegic solutions on myocardial aerobic metabolism. Oxygenated cardioplegic solutions can deliver sufficient oxygen to support aerobic metabolism of heart tissue during cardiac arrest, but little is known about oxygen use after cardioplegic solution infusion. Exhaustion of myocardial oxygen stores after infusion of oxygenated crystalloid cardioplegic solution or Krebs-Henseleit buffer was measured in rat hearts. Since nicotinamide adenine dinucleotide accumulates when mitochondria become anaerobic, the epicardium was monitored during perfusion and ischemia. As ischemia progressed, nicotinamide adenine dinucleotide fluorescence increased, indicating exhaustion of oxygen. After buffer perfusion, at 37 degrees C, 50% of peak fluorescence was seen at 13 +/- 1 seconds and 90% at 37 +/- 3 seconds. Oxygenated cardioplegic solution increased these intervals to 57 +/- 6 and 114 +/- 9 seconds, respectively. Oxygenated cardioplegic solution at 10 degrees C increased the time to 50% fluorescence to 238 +/- 12 seconds and to 90% to 320 +/- 14 seconds. Differences between buffer and cardioplegic solution were less at 10 degrees C. Aerobic metabolism was completely abolished 6 minutes after infusion of 10 degrees C oxygenated cardioplegic solution. Maintenance of continuous aerobic metabolism during surgical cardiac arrest would require frequent administration of oxygenated crystalloid cardioplegic solution.


Transesophageal echocardiographic evaluation of aortic valve integrity with antegrade crystalloid cardioplegic solution used as an imaging agent. Forceful intravascular injection of crystalloid causes microbubble (cavitation) formation. The resulting ultrasound-opaque medium is widely used in echocardiography as a source of contrast. The following study was performed to determine the feasibility of using antegrade crystalloid cardioplegic solution as a transesophageal two-dimensional echocardiographic imaging agent to evaluate aortic valve integrity. In patients with preexisting aortic regurgitation (n = 12), cardioplegic solution administration (driving pressure 150 to 200 mm Hg) was associated with the appearance of intracardiac cavitations in 12 of 12 patients. Among patients without preexisting valve dysfunction (n = 22), intracardiac cavitations were manifested in 20 of 22, with extension of the cavitations to the left atrium in 17. Associated cardiac dimensions (left ventricular outflow tract area and left ventricular diameter) did not exceed preceding cardiopulmonary bypass values in these patients (2.0 +/- 1.6 cm2 versus 2.6 +/- 1.2 cm2 and 1.4 +/- 0.7 cm versus 1.5 +/- 0.8 cm, respectively). It was concluded that antegrade crystalloid cardioplegic solution can be used as an echocardiographic contrast agent in this context. The inability to establish a relationship between the extent of cardioplegic intracardiac penetration and left ventricular dimensional changes limits the technique, as presently employed, to qualitative analysis of valve dysfunction.


Pulmonary hamartoma.

Pulmonary hamartoma. Eighty-nine cases of pulmonary hamartoma were studied. There were 51 men and 38 women, with a mean age of 57.5 years (range 14 to 76 years). A histologic diagnosis from examination of the resection specimens was obtained in all patients who had operations. Moreover, transthoracic needle aspiration biopsies were performed in 40 patients, with a diagnostic result in 34 (85%). The hamartomas were equally distributed in the pulmonary lobes; mean transverse diameter at the time of diagnosis was 21.7 +/- 16.2 mm. Tumor size was independent of the anatomic localization, but it correlated with the age of the patients (p less than 0.01). Tumor growth was recorded in 15 of 31 patients who had follow-up (45%); mean expansion in transverse diameter was 3.2 +/- 2.6 mm per year during an average observation time of 4.1 years (range 1 to 20 years). Pulmonary symptoms were present in 35 patients (39%). Seventy-five patients underwent operations as follows: enucleation (54), resection (11), lobectomy (5), pneumonectomy (4), and bronchoscopic removal (1). Since most pulmonary hamartomas are nonexpanding or slowly growing neoplasms, it is concluded that operation is necessary only when expansion is recorded in young or middle-aged patients and in patients with pulmonary symptoms.


Carcinoma of the superior pulmonary sulcus. Results of irradiation and radical resection. Fifty-six patients with superior sulcus syndrome were evaluated at the First Surgical Department of the University of Padua between 1981 and 1990. Forty-two patients with the characteristic of Pancoast's tumor received preoperative irradiation and then en bloc resection of the tumor, chest wall, and adjacent structures. Seven lobectomies and 35 segmentectomies or wedge resections were performed. There was one early postoperative death. Median survival was 14 months, and actuarial survival was 25% at 5 years. Patients with pain relief had better 5-year survival (36.4%) than patients without pain relief (9%). We have no patients with vertebral invasion who survived more than 1 year. Of the five patients with subclavian artery invasion, only one survived more than 1 year. Of five patients with N2 disease, only one survived more than 1 year. Our results suggest that pain relief after irradiation is a good prognostic factor, whereas N2 involvement and vertebral body and great vessel invasion are ominous factors. Another ominous prognostic factor is the Claude Bernard-Horner syndrome even if it is not a contraindication to resection.


Pulmonary resection for fungal infection in children undergoing bone marrow transplantation. Recipients of bone marrow transplants for hematologic malignancies are at risk for a variety of infectious complications. We have reviewed our experience with six patients 2 to 15 years of age who developed significant fungal infections of the lungs before or after bone marrow transplant. No patient was known to have active fungal or bacterial infection at the time bone marrow transplant was performed. In two patients fungal infections were diagnosed before bone marrow transplant, and operations were performed to permit bone marrow transplant under optimal conditions. Four patients had pulmonary mycoses discovered after bone marrow transplant, and underwent operation 12 to 24 days following transplant. Operations consisted of lobectomy (three), multiple unilateral wedge resections (one), staged segmentectomy and contralateral wedge resection (one), and staged bilateral wedge resection (one). Survival following bone marrow transplant was achieved for 6 months and 11 months in patients undergoing lung resection before transplant, and for 24, 30, 39, and 60 days in patients undergoing lung resections after transplant. Bone marrow transplant recipients are at high risk of pulmonary mycoses, and a vigorous search for occult fungal infections should be carried out before transplant. Aggressive operative treatment of fungal infections of the lungs combined with antifungal chemotherapy before transplant may offer the best hope of extended survival.


Repair of hypoplastic or interrupted aortic arch via sternotomy. Herein we describe our experience with repair of interrupted aortic arch and coarctation plus hypoplastic aortic arch in 55 consecutive infants (1984 to 1990). Median age at operation was 6 days and median weight 3.1 kg. Associated severe intracardiac anomalies were the rule. All patients had significant congestive cardiac failure, and the majority required prostaglandin E1 resuscitation and inotropic support (with or without ventilation) before the operation. All operations were performed via sternotomy with core cooling and circulatory arrest. Isolated myocardial perfusion was used in 13 patients during arch repair. A complete intracardiac (biventricular) repair was performed except in patients expected to require a Fontan operation as definitive treatment. The operative mortality overall was 14.5% (confidence limits 10% to 22%). For arch repair plus biventricular intracardiac repair, the operative mortality was 9% (confidence limits 5% to 15%), and for arch repair plus palliative intracardiac repair, 40% (confidence limits 22% to 60%). The mortality in the isolated myocardial perfusion group was 0% (confidence limits 0% to 14%), which may be related to reduced myocardial ischemic time (p less than 0.05). Actuarial survival was 75% (confidence limits 65% to 83%) at 12 months, with no subsequent deaths over 1294 patient-months (mean 28 months) of follow-up. Actuarial freedom from recurrent arch obstruction was 69% (confidence limits 48% to 85%) at 46 months' follow-up. Primary repair of interrupted aortic arch and coarctation plus hypoplastic arch compares favorably with a staged approach and is recommended even when complex intracardiac anatomy is present.


Risk factors for perioperative mortality in children with anomalous origin of the left coronary artery from the pulmonary artery. The present study was conducted on 33 children (median age at initial cardiac catheterization 0.4 years [0.1 to 11.8]) with anomalous origin of the left coronary artery from the pulmonary artery, without associated hemodynamically significant cardiovascular anomalies, who were treated throughout a period of 18 years in our hospital. A two coronary artery circulation was reestablished in 31 of 33 children. One child died before the intended operation, and in one child the left coronary artery was ligated. There were six operative deaths, five intraoperative and one 12 hours after operation. The purpose of the study was to assess which preoperative clinical and angiographic features were associated with a higher perioperative mortality. The following preoperative factors were associated with a statistically significant higher perioperative mortality: young age at operation (p less than 0.03), left and balanced type of coronary circulation (p less than 0.01), and electrocardiographic signs of extensive acute myocardial infarction, namely, marked ST elevation (greater than or equal to 0.2 mV in at least two leads) (p less than 0.03). Left axis deviation on the electrocardiogram was associated with an extreme right dominant type of coronary circulation (p less than 0.005). The latter was also linked with adequate perfusion of the posterolateral left ventricular wall (p less than 0.005). At autopsy, severe increase of heart weight to two or three times the normal heart weight was established in six of seven children. Thus the perioperative mortality was determined primarily by the extent of myocardial ischemia. This in turn is decisively influenced by the dominant type of coronary circulation and the extent of inter-arterial collateralization. Young age, in addition, proved to be a risk factor for mortality at corrective surgery.


The influence of coronary anatomy on the arterial switch operation in neonates. To determine whether coronary anatomy influences the outcome of the neonatal arterial switch operation, we examined the results in all newborn infants (n = 70) with D-transposition of the great arteries who had a corrective operation at our institution between March 1987 and April 1991. The origin and distribution of coronary arteries were identified preoperatively by echocardiography, aortic root angiography, or selective coronary arteriography and intraoperatively by direct inspection. However, the arterial switch operation was performed independent of the coronary anatomy in all but two candidates for the operation. Four early deaths occurred and five surviving patients had symptoms of impaired cardiac function. No late deaths have occurred in patients followed up for 2 to 50 months. Evidence of myocardial ischemia was present in three of the four deaths and in four of the five patients with cardiovascular symptoms. Patients with commissural or intramural coronary origins between the great arteries had significantly greater cardiovascular morbidity and mortality because of coronary ischemia than patients with the most common coronary pattern. Thus coronary anatomy may influence surgical management and the postoperative course of newborn infants with transposition.


Right submammarian thoracotomy in female patients with atrial septal defects and anomalous pulmonary venous connections. Comparison between the transpectoral and subpectoral approaches. A right submammarian incision with anterior thoracotomy was performed in 89 female patients to repair simple and complex forms of atrial septal defects. Patients' ages ranged from 8 to 38 years (mean 21.5 years). Seventy-seven had secundum-type atrial septal defects, one had the primum type, and 11 had an associated partial anomalous pulmonary venous connection. The patients were divided into two groups: 57 patients in group A, in whom, after a breast flap was elevated, a transpectoral approach was used to enter the chest; 32 patients in group B, in whom the pectoral muscle was not divided and a subpectoral approach was used. Aortic cannulation was accomplished without difficulty in all 89 patients. There were no early or late deaths in either group. Follow-up ranged from 24 to 108 months (mean 63.7 months) and included 86 patients, who were free of symptoms. In group A, however, among 54 patients examined, the volume of the right breast and pectoral muscle was smaller than the left in four patients (7.4%), and 21 (38.8%) had persistent right periareolar numbness. In 32 patients evaluated in group B, no difference was noted in the size of the breasts, and persistent numbness was present in four patients (12.5%). In summary, atrial septal defects or anomalous pulmonary venous connections can be safely repaired through a right submammarian thoracotomy in female patients. The subpectoral approach offers better results because breast asymmetry and paresthesias are significantly less prevalent (p less than 0.01).


Quantitative analysis of pulmonary vascular disease in total anomalous pulmonary venous connection in sixty infants. A quantitative analysis of small pulmonary arteries, pulmonary veins, and lymphatic vessels was conducted in autopsy cases of total anomalous pulmonary venous connection. The materials were obtained from 60 cases of total anomalous pulmonary venous connection without asplenia or pulmonary stenosis, ages ranging from 2 days to 19 months at the time of death (mean age 2.2 months). Pulmonary arterial pressure had been measured in 32 of these patients before death. Twenty cases of ventricular septal defect with pulmonary hypertension and 15 normal individuals were used as the control group. The mean thickness of the media of small pulmonary arteries and veins was 12.7 and 7.6 microns, respectively, in the total anomalous pulmonary venous connection cases, both values being significantly larger than those for normal and ventricular septal defect cases. No changes in thickness with aging were found. Medial thickness in the arteries and veins was greater in the cases of pulmonary venous obstruction than in those without such obstruction. The medial thickness of small pulmonary arteries in total anomalous pulmonary venous connection cases correlated with increased pulmonary arterial pressure. When the patients with the same pulmonary arterial pressure levels were compared, the medial thickness was always greater in those who had total anomalous pulmonary venous connection than in those who had ventricular septal defect. The medial thickness of pulmonary veins was also highly correlated with increased pulmonary arterial pressure in total anomalous pulmonary venous connection. The severity of the intimal lesions was milder in those who had total anomalous pulmonary venous connection than in those who had ventricular septal defect, suggesting the protective role of the thickened pulmonary arterial media against development of intimal lesions. Intimal fibrous thickening of pulmonary veins was not seen in the cases of ventricular septal defect, but it was present in 45% of the total anomalous pulmonary venous connection cases. Lymphangiectasia was characteristically present in 62% of the total anomalous pulmonary venous connection cases. Interstitial emphysema was often a complication of lymphangiectasia, and it led to eight postoperative deaths.


The influence of pulmonary artery banding on outcome after the Fontan operation. Thirty-eight patients were selected from a total of 120 patients who underwent the Fontan operation between 1974 and 1988. They were classified into two groups. Group 1 consisted of 18 patients with previous pulmonary artery banding at a mean age of 7 months (2 days to 59 months), and group 2 comprised 20 patients with native pulmonary stenosis. In group 1, 10 children had tricuspid atresia (seven with normally connected and three with transposed great arteries), six had double-inlet ventricle, and two had complex heart malformations. Group 2 consisted of 12 patients with tricuspid atresia and normally connected great arteries, six with double-inlet ventricle, and two with complex malformations. The following clinical and hemodynamic parameters at cardiac catheterization and cineangiocardiography were determined in both groups before the Fontan operation: age and body surface area, hemoglobin concentration and hematocrit value, atrial and pulmonary artery pressures, end-diastolic pressure of the systemic ventricle, arterial oxygen saturation, pulmonary/systemic flow ratio, end-diastolic volume, ejection fraction and mass of the systemic ventricle, cardiac index, and Nakata index. After the Fontan operation in all patients, the presence or absence of pericardial and pleural effusions, ascites, protein-losing enteropathy, and liver and kidney dysfunction was assessed and the clinical status was classified according to New York Heart Association criteria. All preoperative and postoperative parameters were tested for differences between the two groups, and they were compared with normal values. Hematocrit value was higher in group 2 than in group 1 (57.8% versus 53.1%; p less than 0.05). Ventricular mass index was increased in group 1 when compared with group 2 (125.8 gm/m2 versus 87 gm/m2; p less than 0.05). Severe pericardial effusions in the early postoperative period were significantly more frequent in group 1 and were particularly prevalent in the subgroup with long-standing pulmonary artery banding (p less than 0.01). Subaortic stenosis was observed more frequently in group 1. The remaining parameters were not statistically different between the two groups. We conclude that the significant increment in ventricular mass after pulmonary artery banding may represent a risk for unfavorable outcome after the Fontan operation, which increases with time. Therefore, long-standing pulmonary artery banding as a palliative procedure for candidates for the Fontan operation should be avoided.


Repair of left ventricular aneurysm. Changes in ventricular mechanics, hemodynamics, and oxygen consumption. Anteroapical left ventricular aneurysms were produced in 23 sheep by coronary arterial ligation. Plication of the aneurysm does not change stroke volume or cardiac output and does not significantly change left ventricular oxygen consumption from the preoperative value of 5.1 +/- 2.6 ml/100 gm per minute. Plication, however, does increase left ventricular end-systolic elastance from 3.2 +/- 0.9 to 4.4 +/- 1.5 mm Hg/mm (p = 0.005). In nine of these sheep the midsagittal plane of the left ventricle was imaged by means of an array of sonomicrometry crystals before and after plication of the aneurysm. Regional wall stresses at end-systole and end-diastole and changes in diastolic function were calculated for anterior and posterior ventricular walls in the border zone adjacent to the aneurysm and in more basilar myocardium remote from the infarct. Plication significantly reduced end-systolic wall stresses and systolic stress integrals in the posterior border zone and remote myocardium, but it did not significantly change anterior wall systolic stresses or stress integrals. Plication also decreased diastolic stretching of border zone myocardium. Plication of anteroapical left ventricular aneurysm produced a shorter, more spherical ventricle and removed the dyskinetic segments but altered deformation (strain) in both circumferential and longitudinal directions. The changes in ventricular wall geometry and deformation provide an explanation for the increased ventricular end-systolic elastance and unchanged stroke volume observed after aneurysm plication.


Rapid endothelialization of vascular prostheses by seeding autologous venous tissue fragments. A method was developed to obtain rapid endothelialization of a fabric vascular prosthesis by seeding autologous venous tissue fragments into its wall. In an animal study, complete endothelialization was observed in the entire inner surface of the prosthesis within 2 weeks after implantation. A piece of peripheral vein was minced with scissors and then stirred into saline to create a tissue suspension. This suspension was enmeshed into the wall of a highly porous fabric vascular prosthesis by repeated pressurized injections with a syringe. The prostheses (7 mm inside diameter and 5.7 cm in length), seeded with tissue fragments, were implanted into the descending thoracic aorta of 25 dogs, and they were removed from 1 hour to 2 months after implantation. Twenty-five prostheses, preclotted with fresh blood, were used as control prostheses. In the seeded graft, a thin fibrin layer covered the inner surface just after implantation, but countless numbers of endothelial cells migrated from the fragments and came up to the luminal surface like multiple "mushrooms" under the fibrin layer. Smooth muscle cells made multiple layers underneath the endothelial cell layer. The healing proceeded equally at every part. By this active migration and proliferation, the inner surface was completely healed within 2 weeks.


In vitro closing behavior of the St. Jude Medical heart valve in the pulmonary position. Valve incompetence originating in the prosthesis itself. We examined the in vitro closing behavior of the St. Jude Medical heart valve, simulating (1) a low-pressure system, (2) the anatomic peculiarity of the right ventricular outflow tract and the main pulmonary artery, and (3) disturbed diastolic compliance of the right ventricle. The variables in the experiment were the load impedance to the pump and the valve orientation. The results were as follows. The sequence of closure of the two semidiscs was based on the valve orientation; reduction in impedance caused the semidisc that closed last to remain open, while the other semidisc continued its open-close motion; further reduction in impedance prevented the semidisc, which continued its open-close motion, from closing completely. These results highlight the forces involved in semidisc closure and the existence of a threshold of force for completion of semidisc closure. Further, the results demonstrate that under certain circumstances the threshold cannot be exceeded via those forces. Therefore this incompetence must originate in the prosthesis itself. In this regard, we suggest an urgent need to reconsider the indications for St. Jude Medical heart valve pulmonic implantation. Finally, we advocate the necessity for an in vitro assessment of valve prostheses in a low-pressure system, to evaluate the safety of right-sided placement.


Analysis of left ventricular motion after mitral valve replacement with a technique of preservation of all chordae tendineae. Comparison with conventional mitral valve replacement or mitral valve repair. The postoperative regional left ventricular motion of 22 patients with a diagnosis of mitral regurgitation, and who underwent mitral valve replacement with preservation of chordae tendineae, were retrospectively analyzed by cineangiography in the early postoperative period and by multiple-gated cardiac blood pool scintigraphy in the mid-to-late postoperative period. The operation consisted of the division of the anterior leaflet into anterior and posterior segments, the shifting and reattachment of the divided segments to the mitral ring of the respective commissural areas, and the use of a low-profile bileaflet prosthetic valve. Control groups consisted of 28 patients with mitral regurgitation who underwent mitral valve replacement with a conventional technique and 16 patients who underwent mitral valve repair. Compared with the conventional mitral valve replacement group, the radial shortening of the left ventricle of the chordae-preserved mitral valve replacement group was greater at the apical septal, inferoapical, anterobasal, and anterolateral portions, whereas the radial shortening of the repair group was greater than that of the chordae-preserved group only at the inferolateral portion. The ejection fraction of the whole left ventricle was statistically greater in the chordae-preserved group, and also regional ejection fraction of the chordae-preserved mitral valve replacement group was greater at the apical septal, inferoapical, inferolateral, anterobasal, and anterolateral portions than that of the conventional mitral valve replacement group at these portions. On the other hand, the postoperative regional and global motion was identical to that of the mitral valve repair group except at the inferolateral portion. The result of this study supports a concept that maintenance of continuity between the mitral anulus and the papillary muscle has a beneficial effect on postoperative left ventricular performance.


The vanishing tricuspid annuloplasty. A new concept. A tricuspid De Vega annuloplasty with absorbable 2-0 polydioxanone sutures was performed on 16 sheep supported by cardiopulmonary bypass. The anulus diameter was reduced by 2 to 6 mm. Four sheep died perioperatively. The 12 survivors were electively killed at 2-week intervals during a period of 6 months. Infective endocarditis was not observed. At the time of death no gradient was found on simultaneous pressure measurements of the right atrium and ventricle. Epicardial echocardiography did not reveal tricuspid stenosis or regurgitation. Macroscopically there was no thrombus and the tricuspid leaflets were of a normal appearance. A thin white cord was observed at the anulus in all animals killed after 12 weeks. The annular size remained as surgically induced until the fourth month, but it reverted to its preoperative size after 5 months. Histologically there was granulation tissue initially only around the foreign material, but then progressively it appeared also between the foreign filaments, with the development of multinucleated foreign body giant cells. At approximately 5 months most of the foreign material had been disrupted or absorbed, leaving a tenuous ring of granulation tissue, which allowed expansion of the tricuspid ring to its original circumference. By 6 months most of the foreign material had disappeared and was replaced by loose collagenous tissue. The concept of a "vanishing annuloplasty" is advanced, with particular application in children and in patients with functional tricuspid insufficiency.


Wolff-Parkinson-White syndrome. A quantitative morphometric analysis of surgical anatomy. Previous descriptions of the four anatomic regions of dissection in Wolff-Parkinson-White syndrome have been largely qualitative. In this study quantitative data describing this anatomy are presented, together with statistical analysis of selected anatomic relationships. Fourteen human hearts were dissected. The borders of the posteroseptal dissection along the mitral anulus, tricuspid anulus, and epicardium were measured. A positive correlation between the mitral and tricuspid annular dimensions was found (r = 0.55; p = 0.04); however, the length of epicardial dissection was more variable. The dimensions of the anteroseptal space and the position of the right coronary artery within this space were measured. These measurements emphasize the proximity of the aortic sinuses of Valsalva to the right atrial endocardium near the posteromedial extent of the dissection. The dimensions of the right and left free walls and the position of the coronary arteries within these spaces were measured. A positive correlation was found between the width of the atrioventricular groove and the length of the dissection necessary to separate the atrioventricular groove fat from the ventricular surface (r = 0.89; p = 0.0001, right free wall; r = 0.87; p = 0.0001, left free wall). The quantitative data presented in this article are intended to enhance the surgeon's appreciation of the anatomy relevant to the treatment of Wolff-Parkinson-White syndrome. The knowledge gained from this quantitative analysis may improve accuracy in the electrophysiologic localization and surgical disruption of accessory atrioventricular connections.


Permanent pacing following cardiac transplantation. Permanent pacemakers were inserted in 20 of 439 patients who had received 453 orthotopic cardiac allografts since 1980 at the Columbia-Presbyterian Medical Center. Mean age at transplantation was 45 +/- 4 (SEM) years (range 10 to 64). Pacemakers were inserted an average of 2.4 +/- 1 months after transplantation (range 0.4 to 29), 16 of 20 (80%) within the first month. Indications included sinus bradycardia or sinus arrest in 15 (75%), third-degree heart block in 2 (10%), and both sinus node and atrioventricular node dysfunction in 3 (15%). Rejection episodes and pacemaker insertion were associated in 8 patients (40%). Pacing modes included DDD (7 patients, 35%), AAI,R (7 patients, 35%), VVI,R (3 patients, 15%), DDD,R (2 patients, 10%), and VVI (1 patient, 5%). There was no pacing-related morbidity or mortality. Fourteen of 20 patients (70%) are alive and well 3 to 48 months (mean 24 +/- 4) after transplantation. Late follow-up indicated that atrioventricular node dysfunction resolved in one of two patients, sinoatrial node dysfunction improved or resolved in 7/13 patients, and no atrioventricular block developed in 11 (8 to 37 months, mean 22 +/- 3). Permanent pacing can be safely performed following orthotopic cardiac transplantation, predominantly for sinus node dysfunction. The requirement for pacing may reflect ongoing or new onset rejection and patients should therefore be evaluated accordingly. Dual-chamber pacing is probably not necessary unless atrioventricular node dysfunction is coexistent. Further, as most transplant recipients return to an active life-style, AAI,R may be the preferred mode of pacing.


Improved recovery of heart transplants by combined use of oxygen-derived free radical scavengers and energy enhancement. Oxygen free radical injury during reperfusion of ischemically stored heart transplants may further impair the ability of the transplanted heart to reuse substrate for recovery. We compared the effects of oxygen free radical scavengers, superoxide dismutase and catalase, either alone or combined with glucose-insulin-potassium, in an improved model of the heterotopically transplanted rat heart. Group 1 hearts (n = 8) received no preservation before transplantation and were transplanted immediately. Hearts in four other groups (n = 8 for each group) underwent cold storage (4 degrees to 6 degrees C) for 3 1/2 hours before transplantation. Five minutes before reperfusion of the transplanted hearts, recipient rats received one of the following intravenous treatments: saline (group 2), glucose-insulin-potassium (group 3), superoxide dismutase/catalase (group 4), and superoxide dismutase/catalase plus glucose-insulin-potassium (group 5). Left ventricular end-diastolic pressure, rate of rise of left ventricular pressure, myocardial blood flow, coronary resistance, and tissue adenosine triphosphate content of the heart transplants were assessed during or at the end of 2 hours of reperfusion. Hearts treated with superoxide dismutase/catalase alone showed improvement of end-diastolic pressure and myocardial blood flow. The use of glucose-insulin-potassium alone did not facilitate the recovery of transplanted hearts. In contrast, the combined use of superoxide dismutase/catalase plus glucose-insulin-potassium resulted in a superior recovery of all functional and hemodynamic parameters. These results indicate that free radical scavengers in the presence of glucose-insulin-potassium significantly improve functional recovery in the setting of heart transplantation.


A personal computer-based spike detector and sorter: implementation and evaluation. Many studies of neuronal activity require isolation of the extracellular wave form (spike) of a single neuron from the potentials generated by nearby cells. A variety of methods for spike sorting exists, but most are expensive and require specialized hardware and software. Moreover, there is no easy and objective way for evaluating and comparing the performance of spike sorting devices. We describe here a system for on-line spike sorting that is implemented on an IBM PC/AT computer using commercially available hardware and C-language software. Spikes are detected after crossing an amplitude threshold and are sorted or rejected by template matching. The templates are constructed in a learning phase, using a fast manual sorting of all detected spikes. Later, each detected spike is matched against all defined templates. A detected spike which does not match any template, or matches more than one, is rejected. A continuous display of the wave forms of the last 256 sorted, double-matched, and rejected spikes is used as the main tool for parameter adjustment and error detection. Also described is a new and highly versatile tool for generating appropriate wave forms for critical evaluation of sorter performance. Using the same hardware and software tools, a simulation program mimics the extra-cellular activity of several neurons by linear combination of two vectors and added random noise. The size, shape and the variability of the action potential, as well as its firing pattern, can be adjusted. Comparison of the sorter output with the known simulated activity is used to examine the sorter performance and limitations.


An immunocytochemical method for marking microelectrode tracks following single-unit recordings in long surviving, awake monkeys. We describe an immunocytochemical method for marking microelectrode tracks made during single-unit recordings in long surviving, awake monkeys. This procedure detects the increase in glial fibrillary acidic protein in the glial cells along a microelectrode track using commercially available antibodies. We have successfully marked electrode tracks in tissue from preparations having postrecording survival times ranging into months even though the gliosis can no longer be detected with conventional stains for cell bodies. When this method is combined with data from electrophysiological recordings in chronic preparations it will be possible to reconstruct functional architecture using chronic preparations, as has been done previously with acute preparations.


Kinetics of diffusion in a spherical cell. I. No solute buffering. Realistic neuron models that involve effects of concentration changes of second messengers on ion channels must include processes such as diffusion and solute buffering. These processes, which span a wide range of spatial and temporal scales, may impose a severe computational burden. In this paper and its companion, we examine the kinetics of diffusion and present methods for stimulating it accurately and efficiency. The problem of calcium diffusion in a spherical cell is used as a device to demonstrate the practical application of our analysis. However, the scope of these papers is not limited to this problem. The same analysis that we apply and concerns that we raise are germane to the spread of any second messenger, and can be adapted to other geometries. The focus of this paper is the simplest case: diffusion in the absence of solute buffering. This analysis also applies whenever buffering is so fast that it is instantaneous compared to diffusion, or so slow that concentration gradients have dissipated before substantial buffering takes place. The second paper investigates the more difficult situation where diffusion and buffering occur at comparable rates. In the absence of buffering, concentration changes produced by diffusion can be fit by an infinite series of exponential terms. We show how to design a model with N + 1 compartments that fits the N slowest terms of this series exactly in a shell just inside the cell membrane.


Epi-polarization and incident light microscopy readily resolve an autoradiographic or heavy metal label from an obscuring background or second label. Difficulty encountered in resolving grains of exposed photographic emulsion in autoradiographs of the densely melanized retinal pigment epithelium was solved by using epi-polarized or incident light microscopy. The apparatus used included a metallurgical illuminator specifically designed for epi-polarization microscopy or, as a less expensive but only slightly less effective alternative, a modified fluorescence illuminator. The black melanin granules absorb incident light (as they do in vivo) while the silver grains reflect it producing a "darkfield-like" representation. Brightfield and darkfield-like images can be alternated easily and quickly, or both can be viewed simultaneously. Epi-polarization microscopy has wider application in resolving a reflective label over any opaque background staining or dark second label.


Flattening the cerebral cortex by computer. A computer program was developed for unfolding the cerebral cortex so that it could be viewed as a 2-dimensional surface. Input to the program consisted of tissue sections cut in a standard plane of section. Each section was represented by one line, which corresponded to a contour line in the flattened map. From these data, the computer constructed a 3-dimensional surface representation, which it then flattened. Because the cerebral cortex has considerable intrinsic curvature, flattening required that some regions be expanded and others shrunken. These changes occurred as a natural consequence of local decisions made by the computer as it laid down successive contours. The user could intervene during both surfacing and flattening in order to shape the developing map. The program has been used to generate 37 flattened maps from various regions of cat cortex, and 1 from monkey cortex. The local topography of cortical features such as gyri, sulci, architectonic boundaries, and patches of transported tracer, appeared to be conserved fairly faithfully. Areal distortion was also modest, with an average change in surface area of only 12%.


Pharmacological basis of the therapeutic effect of (-)deprenyl in age-related neurological diseases. (-)Deprenyl (Selegiline, Jumex, Eldepryl, Movergan), a close structural relative to phenylethylamine (PEA), is a drug of a unique pharmacological spectrum. (a) It is highly potent and selective irreversible inhibitor of B-type monoamine oxidase (MAO), a predominantly glial enzyme in the brain, the activity of which significantly increases with age. (-)Deprenyl was the first selective inhibitor of MAO-B described in literature, became the worldwide research tool used for blocking selectively B-type MAO, and is still the only MAO-B inhibitor in clinical use. (b) (-)Deprenyl interferes with the uptake of catecholamines and indirectly acting sympathomimetics because it is handled by the catecholaminergic neuron similarly to the physiological substances transported through the axonal end-organ and vesicular membrane. The unique behavior of (-)deprenyl is that, in striking contrast to PEA and its relatives, it does not push the transmitter from the storage places, i.e., it is not a releaser. The net result is that (-)deprenyl inhibits the releasing effect of tyramine and is presently the only safe MAO inhibitor which can be administered without dietary restrictions. (c) Maintenance on (-)deprenyl enhances selectively superoxide dismutase (SOD) and catalase activity in the striatum. This effect is unrelated to the MAO and uptake inhibitory effects of the drug. (d) Maintenance on (-)deprenyl facilitates the activity of the nigrostriatal dopaminergic neurons with remarkable selectivity. This effect is also unrelated to either the MAO or the uptake inhibitory effects of the drug. All in all, (-)deprenyl maintains the activity of the nigrostriatal dopaminergic machinery on a higher activity level and slows down its age-related decline. Male rats maintained on (-)deprenyl lost their capacity to ejaculate later, retained their learning ability longer, and lived longer than their saline-treated peers. Parkinsonians on levodopa plus (-)deprenyl (10 mg daily) lived significantly longer than those on levodopa alone. (-)Deprenyl is the first drug which retards the progress of Parkinson's disease. Freshly diagnosed parkinsonians maintained on (-)deprenyl did not require levodopa until significantly later than their placebo-treated peers. Maintenance on (-)deprenyl significantly improved the performance of patients with Alzheimer's disease. It is concluded that in Parkinson's disease and Alzheimer's disease patients need to be treated daily with 10 mg (-)deprenyl from diagnosis until death, irrespective of other medication.(ABSTRACT TRUNCATED AT 400 WORDS)


Influence of buffered and unbuffered acetylsalicylic acid on dental enamel and dentine in human teeth: an in vitro pilot study. An in vitro study was conducted to investigate the erosive effect of buffered and unbuffered acetylsalicylic acid (ASA) on dental enamel and dentine in human teeth by scanning electron microscopy. In order to standardize the specimens and to improve comparability the dental enamel and dentine were superficially abraded. The enamel and dentine specimens were therefore particularly sensitive to the influences of acid agents. Concentrated solution of buffered chewable ASA tablets (500 mg ASA and 300 mg calcium carbonate in 5 ml water) showed no changes in the enamel surface structure after exposure times of 1 min, 5 min and 60 min. In contrast, minimal corrosive effects were already seen after exposure of the enamel surface to the unbuffered ASA solutions for 1 min. After exposure times of 5 min and 60 min erosion of the enamel was more pronounced. Immersion in the unbuffered ASA solution led to clearly visible micromorphological changes on the dentine surfaces even after exposure for 1 min. Exposure of the dentine specimens to the buffered ASA solutions led to only very slight changes in the surface morphology. Therefore, the scanning electron micrograph after exposure to buffered ASA is comparable to the picture of untreated dentine.


Induction and termination of afterdepolarizations and triggered arrhythmias by drugs in cat heart in vivo. In order to investigate some anti-triggered arrhythmic drugs, the afterdepolarizations and triggered arrhythmias were induced by cesium chloride and the monophasic action potentials of the left ventricular epicardium in vivo were recorded by using a contact electrode in 58 cats. These results suggested that a) early- and afterdepolarizations, oscillatory afterpotentials and some different kinds of triggered arrhythmias were induced by cesium chloride, b) sodium valproate (150 mg/kg) could prevent CsCl-induced triggered activities, c) lidocaine (5 mg/kg), ethmozine (5 mg/kg) and sodium valproate (150 mg/kg) could terminate CsCl-induced ventricular tachycardias. The present studies provide a basically experimental evidence for treating triggered arrhythmias in clinic.


Interactions between digitoxin and some antiarrhythmic drugs. In the present study the pharmacokinetic interactions between digitoxin and the antiarrhythmic drugs amiodarone, mexiletine and propafenone have been examined. Experiments were performed on rabbits in which serum digitoxin concentration was used as indicator to detect drug interactions. The radioimmunoassay "Coat-A-Count" procedure of DPC was used for the quantitative measurement of digitoxin. It was determined that in order to achieve a considerable level of serum digitoxin, it was necessary to administer a multiple dose rather than the one tolerated by humans. It was also observed that serum contained digitalis like immunoreactive factor(s) (DLIF) measured as digitoxin. The mean (+/- SE) digitoxin equivalent value of the DLIF, measured by the "Coat-A-Count" radioimmunoassay in the serum of rabbits (n = 34) was 4.15 +/- 0.059 ng/ml. Each of the three antiarrhythmic drugs increased serum digitoxin levels; its values were almost double in relation to the control group where only digitoxin was administered. This increased digitoxin value was detected one hour after administration of the first dose of the antiarrhythmic drug and remained at a higher level than that of the control group for 6-8 hours. Rabbits given a single high dose of digitoxin and some of the antiarrhythmic drugs and those given a small dose of digitoxin for only four days, presented a retrogressive increase of digitoxin level in serum 5-6 days later. This mechanism needs to be further investigated.


Enhancement of systemic delivery of met-enkephalin and leu-enkephalin eyedrops with permeation enhancers. It was found that methionine enkephalin (Met-Enk) and leucine-enkephalin (Leu-Enk) can be delivered efficiently into the systemic circulation through the outer route in rabbits. When 50 mcl of 1% Met-Enk eyedrops without absorption enhancers were instilled into eyes, the rabbits' blood concentration rose from 92 pg/ml to 153 pg/ml in 10 min. When either of two permeation enhancers (BL-9 or Brij-78) was added at a 0.5% concentration to the ophthalmic solution, the systemic absorption of 1% Met-Enk was markedly improved. Its blood level was increased to approximately 3.4 times that without the enhancer. When the eyedrops of 0.3% Met-Enk plus 0.5% absorption enhancer were administered, the blood concentration reached higher than that reached by 1% Met-Enk without permeation enhancers. Similar results were obtained with Leu-Enk except the systemic absorption was enhanced by BL-9 and Brij-78 even further to 10-fold and 8.3-fold, respectively. These results indicate that the systemic delivery of Met-Enk and Leu-Enk through eyes, especially with the addition of permeation enhancers, is a feasible alternative route to parenteral injection.


Absorption of various erythromycin esters and salts in mice after intragastric intubation. Erythromycin base and its different salts and esters were given intragastrically to mice. Serum concentrations of erythromycin and its 2'-esters were determined by the bacterial growth inhibition method. Acetyl and propionyl erythromycin were the best absorbed 2'-esters, and differed significantly from butyryl erythromycin and erythromycin base. Erythromycin estolate yielded a larger area under the concentration curve than acistrate or stearate. Among the syrup preparations, erythromycin acistrate was significantly better absorbed than 2'-ethylsuccinyl erythromycin. Absorption of 2'-esters decreased with increasing number of esterified carbon atoms and increasing hydrophobicity and increasing log P value (the logarithm of octanol-water partition coefficient). In addition to sufficient lipophilicity, the optimum absorption of erythromycin esters seems to require a high hydrophilicity.


Pharmacokinetics and bioavailability of papaverine HCl after intravenous, intracorporeal and penis topical administration in beagle dogs. Bioavailability and pharmacokinetics of papaverine HCl was studied in beagle dogs following intravenous injection, intracorporeal injection and topically applied gel on the penis. Also the effect of the sorption promoter Labrafil M-1944 CS on the permeation of papaverine from two gel formulations (PT and PTL) containing the co-solvent Transcutol was evaluated. Blood samples were analyzed by high performance liquid chromatography (HPLC). The pharmacokinetic parameters were determined using either curve-fitting (RE-SID) or compartment model independent method (AUC-RPP). The plasma concentration-time profiles show that papaverine HCl pharmacokinetics is best described by an open two-compartment model. The absolute bioavailability of papaverine HCl was determined to be 102.4%, 9.1%, and 12.4%, respectively, following intracorporeal injection, gel PT and gel PTL administration.


Influence of cisapride, metoclopramide and loperamide on gastric emptying of normal volunteers as measured by means of the area under the curve of the cumulative fraction absorbed-time profiles of paracetamol. The present study with paracetamol was designed to compare the effects of 40 mg cisapride, 20 mg metoclopramide and 4 mg loperamide given orally on gastric emptying under fasting conditions in normal volunteers. The well known bioavailability parameters of absorption and the area under the curve of the fractional absorbed time profiles up to 30 min were used as an index of gastric emptying. As reflected by the AUC of the fractional absorbed time profiles, it was concluded that pretreatment with cisapride speeded up the gastric emptying under fasting conditions. Tmax was the only normal bioavailability parameter that showed any significant change after cisapride treatment. Pretreatment with therapeutic doses of loperamide and metoclopramide did not significantly modify stomach emptying.


Hypotensive anesthesia for middle ear surgery: a comparison of propofol infusion and isoflurane. An infusion of propofol (2,6-diisopropylphenol) was compared with isoflurane to induce hypotension for middle ear surgery. Forty patients (ASA physical status I-II, 16-55 years) scheduled for elective surgery were included in an open randomized study. The pharmacokinetics of propofol infusion were also studied in 6 patients. Both agents produced controlled hypotension (MAP reduction of 30% from the baseline values) with an acceptable visibility of the surgical field. No major complications occurred. The mean total dose of propofol infusion was 6.4 +/- 2.7 mg/kg and the mean concentration of isoflurane was 0.9 +/- 0.4%. Considerable interindividual pharmacokinetic variability was found and propofol was extensively distributed and rapidly cleared from the body after the infusion. Propofol infusion may be a new alternative as a hypotensive agent in middle ear surgery.


Pain sensitivity range: a useful parameter to measure experimentally induced pain? Although the Pain Sensitivity Range (PSR) has been presented as a useful parameter to measure pain in the laboratory, it has not received much attention from pain researchers. The goals of the present investigation were to analyze the reliability and stability of the PSR with the cold pressor test method. Results of our study indicate that useful data can be obtained from this parameter. The PSR is a reliable measure which has not shown any variability due to the cyclic changes in pain perception nor due to the supposedly greater pain sensitivity on the left side of the body. The authors postulate that PSR might be a good measure in laboratory research to evaluate the effectiveness of analgesic therapies, for its resemblance to the acute pain experience.


Digoxin therapeutics: straightening out the facts. This article is essentially a review of the pharmacokinetic rationale behind digoxin therapeutics. It covers the various approaches to digoxin therapeutics including the therapeutic endpoint and the use of plasma concentrations of digoxin, the various problems involved in dosage design (particularly pharmacokinetic variability), prescribing aids (and their total impact on the variability in plasma concentrations achieved), and finally, the alternative use of blood-level data to separate and identify the variation in absorption-disposition from the variation in the relationship of plasma concentration to effect. On the basis of available data, it is concluded that by both turning to prescribing aids that have been formulated from clinical data gathered under more nearly ideal conditions and selecting the dosage to give a target concentration based on single measurements of serum digoxin concentrations, may not result in much improvement over fixed or intuitive dosing as far as achieving a predetermined target level is concerned. The probable causes for this lack of precision are explored, and finally an optimum approach to digoxin therapeutics is defined.


Influences of roxithromycin on cell-mediated immune responses. We investigated the effects of roxithromycin (RXM), a synthesized macrolide antibiotic on murine cellular immune responses by examining the in vitro proliferative response of lymphocytes, interleukin 1 (IL-1) production and interleukin 2 (IL-2) production. RXM was orally administered to BALB/c mice at a dose of 5 mg/kg once a day for 42 days. Spontaneous blastic activity of lymphocytes prepared from mice administered with RXM for 7 days was higher than those from control mice. The activity peaked at the 14th day, and then decreased gradually to control levels by the 42nd day. Time kinetics of lymphocyte blastogenesis to concanavalin A showed a pattern similar to that observed in spontaneous blastic activity. Oral administration of RXM also influenced cytokine production; short-term (for 14 days) administration of RXM enhanced both IL-1 and IL-2 production but long-term (for 42 days) administration inhibited them.


Effect of nifedipine and S-adenosylmethionine in the liver of rats treated with CCl4 and ethanol for one month. An experimental model of toxic liver injury in rats was employed to assay the effect of Nifedipine (a calcium antagonist blocker) and S-Adenosylmethionine (a precursor of glutathione). An important decrease in both perivenular fibrosis and cirrhosis was found. Furthermore, a significant decrease in lactic acid levels was found in the group of animals treated with pharmacologic therapy, although no correlation was seen between lactic acid levels and the different degrees of perivenular fibrosis. No significant variations in ALT and AST enzymes were observed between both groups, as opposed to a significant decrease in LDH enzyme in the Nifedipine+S-Adenosylmethionine group. The results indicate an improvement in the histologic picture of the liver in rats treated by means of pharmacological association, without any change in inflammatory infiltrate and with a slight decrease in necrosis, indicating an action mechanism via creeping fibrosis (instead of a hepatitis pathway).


Aldose reductase mRNA expression and its activity are induced by glucose in fetal rat aortic smooth muscle (A10) cells. The induction of aldose reductase (AR) mRNA expression and its activity by glucose were investigated in fetal rat aortic smooth muscle (A10) cells. The increase in the expression of AR mRNA was observed at 6 h, and reached a maximum (2.3 fold) at 12 h after exposure to 80 mM glucose. On the other hand, increase in AR activity was observed at 12 h and reached a maximum (2 fold) at 48 h after exposure to 80 mM glucose. AR mRNA levels as well as its activity increased almost linearly in a concentration dependent manner up to 80 mM. Although not significant, there was a consistent increase in AR mRNA level and its activity at 23.75 mM glucose. There was a good correlation between AR mRNA level and AR activity. In the presence of 1 microgram/ml actinomycin D, the increase in the expression of AR mRNA level by glucose was almost completely abolished, suggesting its transcriptional regulation by glucose. Other osmolytes were also effective in inducing AR mRNA expression as well as its activity at 80 mOsm/kg. Therefore, the increase in AR mRNA level and its activity by glucose in A10 cells may be a response to the increase in osmolarity.


The hypertriglyceridemic rat as a genetic model of hypertension and diabetes. Hypertriglyceridemia was demonstrated in untreated hypertensive patients as well as in animals with genetic and experimental hypertension. The main purpose of the present study was to evaluate the possibility to use the hereditary hypertriglyceridemic (HTG) nonobese rats in hypertensive research. Direct measurement of blood pressure demonstrated significantly higher systolic, diastolic and mean arterial pressures in HTG rats in comparison with control Wistar rats. There was significant positive correlation between blood pressure and plasma triglyceride concentration (r = 0.585, n = 40, p less than 0.001). In addition, there were significantly increased plasma norepinephrine and epinephrine concentrations in HTG rats, suggesting that the stimulation of sympathetic nervous system could be one of the pathogenetic mechanisms involved in the increase of blood pressure of HTG rats.


Evidence that histamine-stimulated prolactin secretion is not mediated by an inhibition of tuberoinfundibular dopaminergic neurons. The effects of histamine on prolactin secretion and the activity of tuberoinfundibular dopaminergic (DA) neurons were examined in male rats. Tuberoinfundibular DA neuronal activity was estimated in situ by measuring the metabolism [concentration of 3,4-dihydroxyphenylacetic acid (DOPAC)] and synthesis [accumulation of 3,4-dihydroxyphenylalanine (DOPA) after administration of a decarboxylase inhibitor] of dopamine in the median eminence. Intracerebroventricular (icv) injection of histamine produced a dose- and time-dependent increase in plasma prolactin levels but had no effect on DOPA accumulation or DOPAC concentrations in the median eminence. These results indicate that the stimulation of prolactin secretion following icv histamine is not mediated by an inhibition of tuberoinfundibular DA neurons.


Repeated administration of triiodothyronine enhances the susceptibility of rats to isoniazid- and picrotoxin-induced seizures. In an experimental condition of hyperthyroidism, obtained by repeated administration of triiodothyronine in adult rats (100 micrograms/kg/day, sc for 7 consecutive days), there is an increased susceptibility to the convulsant effect of isoniazid (300 mg/kg, ip) and picrotoxin (4 mg/kg, ip). On the other hand, the characteristics of brain [3H] flunitrazepam binding sites are not modified. These data afford further experimental evidence of the influence of thyroid hormones on brain function.


Down regulation of masked and unmasked insulin receptors in the liver of transgenic mice expressing bovine growth hormone gene. The interaction of insulin with its receptor was studied in microsomes from livers of transgenic mice expressing the bovine growth hormone gene with mouse metallothionein-1 promoter (MT/bGH) and in their normal (non-transgenic) littermates. Specific binding of 125I-insulin was detected in hepatic microsomes from normal and transgenic mice with an apparent Kd of 8 and 200 nM, for high and low affinity sites, respectively. The transgenic MT/bGH mice had a marked hyperinsulinism without significant elevation of plasma glucose levels. Under identical conditions of preparation and incubation, microsomes from the transgenic male and female mice bound 39% and 34% less insulin than those from their litter mates. Scatchard's analysis indicates that this decrease in binding is due to a decrease in the number of receptor sites. In contrast to the marked decrease in insulin binding to unmasked receptors, the levels of masked (also called cryptic) insulin receptors were similar (or slightly increased) in transgenic mice microsomes as compared to those of their normal litter mates.


The comparative effects of propofol, thiopental, and diazepam, administered intravenously, on pentylenetetrazol seizure threshold in the rabbit. The anticonvulsant effects of propofol, thiopental, and diazepam, administered intravenously, on pentylenetetrazol (PTZ) seizure threshold were studied and compared in the rabbit. The PTZ seizure threshold determined in various rabbit groups during the control phase of conducted experiments, was found to be in the range of 10.1 +/- 2.0 to 13.5 +/- 3.7 mg/kg. Intravenous administration of comparable doses of propofol, thiopental, and diazepam resulted in marked and significant increases in PTZ seizure threshold. At all administered doses (1.25-10.0 mg/kg), propofol was found to be more effective than thiopental in increasing the PTZ threshold dose. However, the anticonvulsant effects of diazepam were more marked than those of propofol, except at a dose of 10 mg/kg where both agents exhibited equipotent activities. These data demonstrate that propofol enjoys a considerable degree of anticonvulsant activity in the rabbit. This anticonvulsant action is greater than that of thiopental at doses ranging from 2.5 to 10 mg/kg and equipotent with diazepam at the 10 mg/kg dose.


Stochastic trees: a new technique for temporal medical decision modeling. This paper introduces stochastic trees, a new modeling approach for the class of medical decision problems in which risks of mortality and morbidity may extend over time. A stochastic tree may be regarded as a continuous-time version of a Markov-cycle tree, or alternately, as a multi-state DEALE model. Optimal decisions in stochastic trees can be determined by rollback, much in the same fashion as decision trees. The author discusses how age-dependent mortality rates and declining incidence rates may be modeled using stochastic trees. Concepts are illustrated using examples from the medical literature. It is argued that stochastic trees possess important advantages over Markov-cycle trees for medical decision modeling.


Comparing and optimizing diagnostic tests: an information-theoretical approach. An ideal method for assessing performance of non-binary diagnostic tests would specify each test's optimal operating point and would tell a diagnostician which of many tests was the best one to use in a particular clinical situation. This article shows how information theory and receiver operating characteristic (ROC) analysis can be combined to evaluate and compare diagnostic tests at their optimum cutoffs once disease prevalence and test properties are specified. Though it is not appropriate for all clinical situations, the method can be used for most diagnostic tests whenever information is desired for its own sake or when reducing uncertainty is the goal of testing. The method also is appropriate in those situations where benefits and costs cannot be specified precisely enough to permit test optimization based on a balancing of anticipated goods and evils.


Measuring decision sensitivity: a combined Monte Carlo-logistic regression approach. Modeling of the uncertainty of multiple input variables for a complex decision problem complicates sensitivity analysis. A method of analysis comprising stochastic simulation of the model and logistic regression of the simulated dichotomous decision variable against all of the input variables yields a direct measure of the importance of input variables to the decision. This method is demonstrated on a previously analyzed clinical decision either to continue observation or to immediately treat with anticoagulants a woman presenting with deep vein thrombosis in the first trimester of pregnancy. A relative measure of the importance of each input variable in causing a change of decision is estimated by calculating the change in the log odds attributable to variation of each input variable over its range of uncertain values compared with the total change of log odds from variation of all input variables. This method is compared with alternative measures of input variable importance, and is found to be a simple yet powerful tool for gaining quantitative insight into the nuances of a decision model.


Clinical assessment of the probability of coronary artery disease: judgmental bias from personal knowledge. Probability estimates of angiographic coronary artery disease made by experienced, board-certified staff cardiologists were compared with those of cardiologists in training (fellows). In addition, estimates made before coronary angiography were compared with those made several months later based on written clinical summaries of 15 items of objective clinical and test data. Cardiologists were asked to estimate the probabilities of coronary artery disease, multivessel disease, and triple-vessel or left main disease. The study population consisted of 510 consecutive patients without valvular disease referred for the first time for coronary angiography to three hospitals. Both staff and fellows consistently overestimated the pre-angiographic probability of coronary artery disease. The probabilities estimated from patient summaries were always significantly lower than the pre-angiographic assessments. Only staff cardiologists reliably assessed the probabilities of coronary artery disease during the second assessment (p less than 0.05). Thus, estimates of disease probability based on clinical judgment vary according to the source of information, and these estimates are more accurate when physicians have objective data on hand and do not know the identities of the patients.


A method to describe physician decision thresholds and its application in examining the diagnosis of coronary artery disease based on exercise treadmill testing. The authors developed a method that utilizes logistic regression analysis to 1) calculate the disease probability with confidence intervals at which any specified proportion of physicians reaches a clinical decision, 2) statistically test whether factors other than disease probability affect this clinical decision, and 3) statistically test whether physician decision making in relation to disease probability varies by other factors. They apply the method to analyze the relationship between disease probability and the proportion of physicians who diagnosed coronary artery disease (CAD) in 127 consecutive subjects who completed the treadmill exercise tolerance test (ETT) at two hospitals. Twenty-five percent of the physicians decided that CAD was possible or definite at a post-ETT disease probability of 0.24 (95% CL= 0.07-0.35); 50% at 0.54 (95% CL = 0.43-0.70); and 75% at 0.82 (95% CL = 0.67-1.0). Multivariate logistic regression analysis revealed three factors significantly and independently related to the diagnosis of CAD: post-ETT disease probability, positive ETT result, and cigarette smoking. The proportion of physicians who reached a diagnosis of CAD did not differ by hospital setting (VA versus university), level of training (attending versus housestaff/fellow), or diagnosing service (cardiology versus other internal medicine). It is concluded that factors other than disease probability may affect physician diagnostic decisions.


Scientific fraud: the McBride case.

Scientific fraud: the McBride case. Scientific fraud has occasionally been reported in Australia. The most recent case involved Dr William McBride, a prominent Sydney obstetrician who became well known in medical research for his part in drawing attention to the teratogenic effects of thalidomide. It is still not clear how much of McBride's later activities were fraud and how much poor quality research. The findings of the Inquiry into the matter (Gibbs et al., 1988) have considerable importance for the conduct of private research organizations, publication procedures of research journals, the role of assistants in research projects, collaboration between laboratories, and methods for inquiring into allegations of malpractice. The present paper is based on the Inquiry report.


Comparing methods of learning clinical prediction from case simulations. Feedback to physicians about how they use information in making judgments can improve the quality of their judgments, but questions remain about which types of feedback are most effective. The authors conducted a controlled study of feedback in 60 medical students learning to predict the risk of cardiovascular death based on the presence or absence of five risk factors. After a pretest of 40 cases abstracted from patient records, the students worked through 173 computer-simulated cases and a posttest of 40 patient cases. The students received no feedback, probability feedback (correct probability of cardiac death for each case), cognitive feedback (the correct cue weights compared with their own weights derived from the previous set of cases), or both types of feedback. Students who received probability feedback markedly improved both base rate calibration and discrimination. Those who received only cognitive feedback showed no improvement over control on any of the measures of learning. All subjects were highly consistent in their weightings. The superiority of probability feedback differed from previous findings that cognitive feedback was essential for mastery of multiple-cue-probability learning tasks. The information on cue-outcome relationships given by cognitive feedback may be more useful when these relationships are complex and the combining rule is not known, while the precise outcome information provided by probabilistic feedback is more useful when the combining rule is known and the cue-outcome relationships are straightforward. Thus, the optimal method of learning depends on the nature of the task.


The reasons why suspects confess during custodial interrogation: data for Northern Ireland. This study looks at the reasons offenders give for having confessed during police interrogation. A number of hypotheses were tested, following the work of Gudjonsson and Petursson (1991) on an Icelandic prison sample. The subjects were 80 offenders who were serving prison sentences in Northern Ireland for violence, sex or property offences. The subjects completed the Gudjonsson Confession Questionnaire. All of the hypotheses tested were supported, indicating that there are three primary factors associated with the reasons why criminals make confessions during interrogation. These factors are referred to as Internal Pressure, External Pressure and Proof. The factors were found to be associated with the type of offence committed and the attitude of the offender towards his confession.


Validation of a model of breast cancer screening: an outlier observation suggests the value of breast self-examinations. As part of a validation of a mathematical model of breast cancer, the Health Insurance Plan of Greater New York (HIP) randomized controlled trial of breast cancer screening and the uncontrolled Breast Cancer Detection Demonstration Projects (BCDDP) trial were simulated. Model predictions were in accord with the nine-year survival experience of women in the HIP trial, and, with the exception of women 40-44 years old, with HIP data on 18-year survival. Five-year survival rates of screen-detected cases in the BCDDP were very close to the model's predictions. However, the model did not predict the high survival rate of women who had interval cancers in the BCDDP. By the end of the BCDDP, almost 85% of the participants performed breast self-examination (BSE) regularly. Consistent with this observation, an appealing hypothesis to explain the high survival rate of women who had interval cancers is that BSE is of value in detecting breast cancers earlier. Consideration of model outliers can be of value in increasing understanding of the phenomena being modeled.


Who commits matricide?

Who commits matricide? The authors studied sixteen men who committed matricide. Fifteen out of sixteen cases had a diagnosis of schizophrenia and the remaining patient had a diagnosis of schizophrenia with personality disorder. All were single at the time of the matricide. Data indicate an intense conflict-laden and ambivalent relationship between the majority of patients with their mothers. Thirteen out of sixteen cases described their mothers as quite domineering and demanding but the EMBU inventory revealed that the Matricidal group differed from the Control group in how tolerant they saw their parents. The sample as a whole saw mothers were more over-involved, overprotective, tolerant, affectionate, stimulating, performance-orientated and shaming. The matricidal group differed from the control group in the way they viewed the difference between mother and father on various scales, like over-involved, tolerant, affectionate and performance-orientated. The matricidal groups' mothers were found to be more over-involved, tolerant, affectionate, and fathers more abusive. Mothers in the control group were more performance-orientated.


Altered collagen (fibrinoid change) at the site of post-mortem injuries. The terms fibrinoid degeneration and fibrinoid substance were first introduced by Neumann in 1880 to describe some alterations in the staining characteristics of collagen. Collagen fibres which have undergone this change are eosinophilic, homogeneous and take some of the tinctorial properties of fibrin. Lendrum et al. (1962) developed Martius-Scarlet-Blue (MSB) stain, which is preferentially taken up by fibrin. The principle of the method described by Lendrum and his colleagues is the use of acid dyes of different molecular size (Martius yellow, Brilliant Crystal Scarlet 6R, methyl blue) in accordance with the alteration in structure of fibrin at different stages of development. The newest fibrin likely to be found in sections is presumably the fine network of postmortem fibrin. Much of this takes a yellow stain with the MSB method, as do erythrocytes. Slightly older fibrin (16 hours) takes a bright red stain with the MSB. Complete validity of the method depends on prolonged fixation in formal-sublimate. It gives brilliant staining with acid dyes and enhances metachromasia. In the Department of Forensic Medicine in Leeds it was noticed that an alteration in collagen staining with MSB stain was taking place in samples collected from different kinds of injuries, e.g. ligature marks, electrical injuries and burns. Similar changes were only occasionally seen in abrasions. It was therefore decided to inflict different kinds of injuries on the skins of rats and to fresh pieces of human skin in vitro, to observe any alterations in collagen staining with MSB and to assess the significance of these changes in relation to the timing of injuries.(ABSTRACT TRUNCATED AT 250 WORDS)


Mental impairment in the West Midlands.

Mental impairment in the West Midlands. The case records of 55 people from the West Midlands (UK) fulfilling the Mental Health Act 1983 criteria for mental impairment or severe mental impairment, were studied. Most were young men with mild mental retardation. 73 per cent were resident in (or on leave from) mental handicap hospitals, and 27 per cent resident in special hospitals. 29 per cent were subject to a Restriction Order. Most had lived in hospital for more than six years. The commonest problem behaviours were aggression, property offences and inappropriate or offending sexual behaviour. 31 per cent were mentally ill or had a past history of mental illness. A diverse range of services appears necessary to meet the needs of this group of people.


Besieged by devils--thoughts on possession and possession states. Aspects of possession are reviewed in historical, cultural and clinical contexts. Consideration is given to differential diagnosis and management. It is suggested that a multi-disciplinary approach is required for a condition that stands at the boundaries of psychiatry. Two quotations from Elizabethan playwrights are relevant to the theme of this paper: 'Beware you do not conjure up a spirit you cannot lay' Ben Johnson, The New Inn (Act III, Scene ii) 'Farewell the tranquil mind: farewell content.' Shakespeare, Othello (Act III, Scene iii).


A study of child homicide over two decades. The child homicides which were notified to the Leeds University Department of Forensic Medicine between 1970 and 1989 were studied. There were 131 cases, and information regarding age of victim, mode of death and post-mortem evidence of previous abuse was noted. The incidences of child homicide varied between 3 and 11 cases per year; the first three years of life providing the majority of cases. Blunt injury accounted for almost half of the deaths, whilst 34 per cent of cases showed evidence of previous physical or sexual abuse. In infant homicide (i.e. under one year of age) a pattern emerged which has previously been described as the 'shaken baby syndrome'.


The Hillsborough football disaster and claims for 'nervous shock'. The article investigates the scope for 'nervous shock' claims consequent on negligently inflicted injury, in the light of the Hillsborough disaster. It analyses the existing case law, including the first instance and Court of Appeal judgments in litigation arising from the disaster (for the House of Lords judgment, see Addendum). Its main purpose is to show that several of the arguments and conclusions in these judgments are driven by considerations of policy rather than principle, and primarily by a concern to prevent the 'floodgates of litigation' from opening. It is submitted that greater attention to medical perspectives on psychiatric illness would reveal that this concern is overstated and that a more principled approach would not have the adverse consequences predicted.


Lethal cardiac tamponade due to aortotomy wound dehiscence after cardiac valve replacement: a forensic presentation. Lethal cardiac tamponade due to aortotomy wound dehiscence after cardiac valve replacement (CVR) are apparently unreported in the recent literature. An uncommon example of delayed non-valvular lethal complication of CVR occurring in the early out-patient period is reported here. The forensic aspects of wound dehiscence in cardiovascular surgery for cardiac valve replacement are discussed, and complemented by a study of the fracture ends of suture material in wound breakdown associated with the suture failure.


XYY genotype and crime: 2 cases.

XYY genotype and crime: 2 cases. The presence of 47, XYY genotype has stimulated much debate as to whether these men are more likely to indulge in criminal and violent behaviour than 46, XY males. Two cases of XYY men who had committed murder are described, and the current literature regarding criminality and psychopathology in XYY males is reviewed. It is important that Forensic Psychiatrists with XYY patients are aware of these issues as the link between XYY genotype and criminality may be raised in court.


Body packing presenting as sudden collapse. Cocaine is one of the most rapidly growing drugs of abuse and with it comes an ever-increasing sophistication in concealment from Customs and Police, and may even result in clinicians failing to detect the concealment of packages within the intestinal tract or other body orifices. We present one such case where death arose from rupture of a package of cocaine within the rectum.


[Radionuclide methods of measuring mineral contents in the bone tissue]. Over the recent 10-15 years, osseous densitometers intended for measuring the content of minerals in osseous tissue have become very popular abroad. To record statistically significant changes in an osseous mineral, these devices should have reproducibility (variation rate) exceeding 2%. Mono- and biphoton densitometers may be distinguished by the type of the applied radionuclide. Biphoton densitometers are advantageous since they permit examining any part of the skeletal system of the patient or the whole body. Biphoton absorptiometry is based on measuring the transition of photons of two energies via the medium that largely consists of the two materials bone and soft tissue. The authors describe the results of examining parts of the peripheral skeleton with the aid a laboratory sample of a biphoton osseous densitometer for the peripheral skeleton.


[Characteristics of air retention by different extracorporeal filters during artificial circulation]. The paper concerns the present-day problem of estimating the efficiency of the functioning of extracorporeal filters in artificial circulation. A method for laboratory studies of extracorporeal filters is offered. The results obtained with the use of the method are provided in order to compare air retention by modern filters. The interference-killing feature and practical feasibility with the use of the popular standard equipment should be attributed to undoubtful advantages of the method suggested. The data obtained are of interest both for users of extracorporeal filters and those who are engaged in the development of the equipment for artificial circulation.


[Optimal correlations of design parameters and metrological characteristics of piston spirometers]. Sensitivity parameters, the threshold of response and shift pressure for "rolling-seal" spirometers reach the optimum according to the criterion for minimizing the weight of its moving parts. As the result of this, essential reserves of the design can be used, which permits one to substantially improve the methodological and metrological conditions of lung functional tests.


[Centrifugal blood pumps (new possibilities of design improvement)]. Based on an analysis of 300 world information sources, 19 types of centrifugal blood pumps were ascertained. Five new designs suggested have an idea in common: combination of the inlet of the disk pump and of the outlet of the impeller pump. This allows uniting the merits of the above pumps and excluding their shortcomings. The designs suggested make it possible to solve the two basic problems: hemolysis and thrombogenesis inside the pumps. The use of the pumps designed on such a basis will afford a simple and reliable approach to heart function replacement.


[A method of electric simulation of the radionuclide dilution curve]. The authors demonstrate a possibility of electric simulation of the radionuclide dilution curve for the laminar blood flow. The time required for the indicator mixing, the mean time of blood circulation, and transmission function of circulation in an organ can be derived as a result of such simulation.


[Equipment for artificial purification of physiological fluids: current status and developmental trends]. Modern equipment for artificial purification of physiological fluids is viewed as a multiplicity of constructively and functionally interrelated processors of the bioartificial body. The processors include automated control elements (perfusion, infusion and of normalizing action) and disposable actuating elements (main circuits, dialyzers, hemo- and plasma filters, sorption and ion-exchange columns, heat exchangers). Prospective trends in the development are outlined: preferable use of purification methods with energy controlling media; regeneration of dialysate and ultrafiltrate; universalization of functional potentialities in technically and economically derived constructive redundancy, computerization.


[A device for automatic selection of exposure in photographing endoscopic objects]. The author reviews the basic outfits for exposition automation as applicable to endoscopy. Regards the main technical difficulties that may occur in the development of such outfits. The conclusion is made that validity of colour rendition of endoscopic objects on the film can be attained, provided the light characteristics of the central (priority information bearing) and peripheral areas of an object are taken into account. The structural block diagram of the appropriate outfit for exposition automation in endoscopy is under discussion.


[A device for reproducing lower jaw movements]. A simulator of lower jaw movements is described. The device developed and manufactured by the authors presents a carcass which carries an electric drive, an indexing mechanism, and seats for installation of the models or natural preparations of the lower jaw. The parameters of the movement of the lower bearing seat are as follows: lowering, displacement, lifting, and returning to the initial position. The maximum lateral displacement is 10 mm, the vertical one is 18 mm. The seat is capable of making 12 to 30 movements per minute. The device is intended for trying different treatment methods for mandible diseases and injuries.


Design and evaluation of shielded gradient coils. Techniques are described for the design of shielded gradient coils for superconducting MRI systems. These design methods are suited for constructing the most efficient gradient coil that meets a specified homogeneity requirement. Tradeoffs in coil design of efficiency with coil size and gap size are discussed. Residual eddy currents from coils constructed with a finite number of wires are calculated and give guidelines for the construction of efficient, whole-body gradient coils.


Volume-selective proton MRS in vertebral bodies. Volume-selective 1H magnetic resonance spectra of small volume elements of (13 mm)3 positioned in lumbar vertebral bodies have been investigated in 15 healthy persons of different ages and sexes and in 11 patients with leukemia using double spin-echo sequences. Signal intensities and positions of the spectral lines have been evaluated. Interindividual spectra of VOI located in the center of vertebral bodies, intraindividual spectra of central VOI in different vertebral bodies, and spectra of different localizations within the same vertebral body have been compared as well as spectra before and partly after cytostatic treatment in leukemia patients. Unexpected phenomena of the signal shapes have been found. The water signal distributions in healthy persons compared to patients after bone marrow transplantation show significant differences. The success of the cytostatic treatment in cases of leukemia is accompanied by an increase in the intensity of the lipid signals and a decrease in the water signals.


Dynamic studies of gadolinium uptake in brain tumors using inversion-recovery echo-planar imaging. Echo-planar imaging has been used to observe the dynamics of Gd-DTPA uptake in brain tumors. It has been possible to examine both vascular uptake and diffusion across the blood-brain barrier in a single experiment, by using the IR-MBEST echo-planar sequence which combines a high temporal resolution (approximately 3 s) with strong T1 weighting. To model the uptake it is necessary to know the arterial concentration of Gd-DTPA; in this study the signal in the sagittal sinus was measured to avoid the need to take repeated blood samples. The time constant for transfer across the blood-brain barrier was measured to be between 20 and 1050 s for different tumors. The results of the modeling correlated with the results of other assessments of tumor vascularity.


[A device for measuring nonuniformity of the dose field of ionizing radiation]. The authors describe a device for measuring the dose field in the beam section of ionizing radiation. The device consists of an immovable bench mark detector and the two detectors: a movable one and a photodiode placed on a tele- and separately movable carriage. The device affords defining the correspondence of radiation and light fields.


Analysis of the evolution of focal cerebral ischemia in the rat using the eigenimage filter. The eigenimage filter was used to evaluate the results of a MRI study of cerebral ischemia in a rat model. This linear filter segments a desired feature in an image sequence from other features which may interfere with its observation. The animals were imaged temporally, after occlusion of the middle cerebral artery, to investigate the evolution of the ischemic process. The temporal evolution of ischemia was evaluated by analysis of the "eigenimages," calculated T2 and T1 map images, and images for the angles between signature vectors defined in the eigenimage technique. The eigenimages and angle map images demonstrated an improved visibility of the lesion at all time points, as compared to the original images and T2 and T1 map images. The eigenimages also demonstrated signal intensity changes within the area of ischemia. These changes are speculated to be related to variations in local cerebral blood flow resulting in varying degrees of tissue damage. The eigenimage intensities and the angles between signature vectors demonstrated time-related changes similar to the T2 and T1 values. Since the eigenimage filter and angle calculations are not dependent upon physical models (like T2 and T1), and the errors associated with these models, they may be preferable as methods for tissue characterization.


[A comparative analysis of schemes of the coordinate scale of present-day computerized x-ray tomographs]. A scheme-technical, computational and experimental analysis has been made of different schemes of the coordinate scale of modern computer-aided x-ray tomographs. The authors provide evidence for the concept with the following subdivision: (a) the coordinate scale is divided by a closed ring rule with an insignificant number of bench mark holes; (b) an electronic device which divides the distance between the holes of the rule according to the required number of small-sized samples. The schemes of the indicated concept implementation permit choosing an adequate decision for the scanning systems with different arrangements and parameters.


Direct measurement of spin-lattice relaxation times of phosphorus metabolites in human myocardium. T1 values of phosphorus metabolites visible in human cardiac 31P-MR spectra were determined in 12 volunteers at 1.5 T. Consecutive spectra were acquired with varying pulse repetition time (TR) from 1.6 to 24 s; volume selection was achieved with ISIS. T1's of creatine phosphate (CP), [gamma-P], [alpha-P], and [beta-P]ATP, 2-3 diphosphoglycerate, and phosphodiesters were 6.1 +/- 0.5, 5.4 +/- 0.5, 5.5 +/- 0.5, 5.8 +/- 1.0, 7.6 +/- 1.0, and 5.0 +/- 1.0 s, respectively. CP/ATP ratios showed little change with varying TR; linear regression of CP/ATP vs TR was of borderline significance (r = 0.28, P = 0.06). T1's for CP and ATP were also determined in standard solution (20 mM CP, 10 mM ATP) yielding T1CP of 8.7 +/- 0.2 and T1[gamma-P]-ATP of 9.9 +/- 0.7 s. Thus, T1's for CP and ATP were similar at 1.5 T in both human heart and standard solution. In human cardiac 31P-MR spectra, CP/ATP ratios may need little correction for partial saturation.


Spatial heterogeneity of the metabolic response of RIF-1 tumors to a vasoactive agent evaluated in vivo by one-dimensional 31P chemical-shift imaging. Localized 31P NMR spectroscopy was used to evaluate the spatial heterogeneity of the metabolic response of RIF-1 tumors to hydralazine. Volume localized 31P spectra were obtained from subcutaneous RIF-1 tumors using one-dimensional chemical-shift imaging, before and 20 min after treatment with 5 mg/kg hydralazine, administered intravenously. Following treatment all of the tumors showed an overall decrease in the ratio of nucleoside triphosphate (NTP) to inorganic phosphate (Pi) and a decrease in pH. However, spatial localization revealed that the reduction in NTP/Pi was not uniform within some tumors. This was partly due to regional differences in the levels of metabolites existing before treatment. Normal tissue adjacent to the tumor did not show a significant decrease in high-energy metabolites or pH.