Decreased and abnormal left ventricular filling in acute heart failure: role of pericardial constraint and its mechanism. Pericardial constraining force is minimal in normal hearts; however, it is considered to be prominent in moderate to severe heart failure. Thus, effects of the pericardium on pulsed Doppler transmitral flow velocity pattern were examined in 17 dogs with acute left ventricular dysfunction. Left ventricular dysfunction with left ventricular end-diastolic pressure > or = 15 mm Hg was produced by injection of microspheres into the left coronary artery. Transmitral flow velocity pattern, left atrial and left ventricular diameters, and high-fidelity left atrial and left ventricular pressures were recorded before and after pericardiectomy. In five of the 17 dogs, mitral regurgitation with giant "v" wave of left atrial pressure occurred with reductions of left ventricular systolic pressure and peak rate of the left ventricular pressure fall (dP/dt) after pericardiectomy. In the other 12 dogs, peak early and late diastolic filling velocities increased with a decrease in left ventricular minimal pressure and increases in left arterial and left ventricular diameters and left atrial and left ventricular compliance after pericardiectomy. In these 12 dogs, left atrial to left ventricular crossover pressure, left ventricular end-diastolic pressure, and references for left ventricular relaxation did not change after pericardiectomy. Thus the release from pericardial constraining force in severe heart failure may increase chamber compliance of the left ventricle and left atrium and, in turn, increase peak early and late diastolic filling velocities through an increment in forward transmitral pressure gradient. Increased pericardial constraining force is a possible cause limiting left ventricular filling and hence cardiac output in heart failure.


Regulation of expression of transforming growth factor-beta 2 by transforming growth factor-beta isoforms is dependent upon cell type. The effect of three different isoforms of transforming growth factor-beta (TGF-beta) on the expression of TGF-beta 2 mRNA was studied in several continuous tumor cell lines. As previously reported for the mouse fibroblast cell line AKR-2B, the expression of TGF-beta 2 mRNA transcripts of 5.4, 4.7, 3.7 and 3.0 kb was decreased after a 24 hr treatment with 5 ng/ml of TGF-beta 1, TGF-beta 2 or TGF-beta 3. In A549, HBL-100 and BSC-1 epithelial cell lines, five distinct TGF-beta 2 mRNA transcripts of 5.8, 5.1, 4.0, 3.8 and 2.8 kb were detected by Northern blot analysis. Treatment of these cells with TGF-beta 1, TGF-beta 2 or TGF-beta 3 for 24 hr resulted in a 2-3 fold increase in the 5.8, 4.0 and 3.8 kb transcripts, with little detectable change in abundance of the 5.1 and 2.8 kb transcripts. The effect of the TGF-beta proteins was dose (5 ng/ml) and time (3-6 hr) dependent. A similar 2-3 fold increase in the level of secreted TGF-beta 2 was observed following treatment of A549 cells with TGF-beta 1. Basal level and induced expression of TGF-beta 2 mRNA in response to TGF-beta isoforms was decreased in the presence of actinomycin D. In all cell lines studied, the expression of the 2.5 kb TGF-beta 1 mRNA was relatively unchanged or markedly increased in response to treatment with TGF-beta.(ABSTRACT TRUNCATED AT 250 WORDS)


Distribution of transforming growth factor beta in a two-week-old human embryo. Using immunohistochemical methods we have investigated the presence of transforming growth factors beta 1, beta 2 and beta 1 precursor in a two-week-old bilaminar human embryo. TGF-beta 1 precursor was seen in both the epiblast and the hypoblast. In contrast to the widespread localization of TGF-beta 1 precursor in the embryo proper, antibodies to the mature TGF-beta 1 peptide localized preferentially to the hypoblast with only weak staining in the epiblast. Staining with antibodies to TGF-beta 2 was generally weak in both the epiblast and hypoblast layers of the embryo proper. These results show that TGF-beta 1 and beta 2 peptides are detectable as early as the second week of human development.


Diagnostic pitfalls in transesophageal echocardiography. The technology of transesophageal echocardiography is now widely available and has proved extremely useful in evaluating cardiovascular anatomy and pathology. Unfortunately, the enhanced echocardiographic detail and multiple transesophageal imaging planes may sometimes be confusing and cause misinterpretations. The majority of these problems are simply the result of operator inexperience. To help prevent misdiagnoses, we have collected a series of the more common diagnostic and technical "pitfalls" of transesophageal echocardiography.


Molecular cloning of CSF-1 receptor from rat myoblasts. Sequence analysis and regulation during myogenesis. We have isolated and sequenced a cDNA (mrfms) encoding rat c-fms gene (CSF-1 receptor) from proliferating L6 alpha 1 myoblasts. The predicted amino acid sequence was highly identical with the c-fms protein found in monocytes and macrophages (98, 76 and 84% identity from mouse, cat and human c-fms proteins, respectively). The mechanisms responsible for the regulation of mrfms gene expression during myogenesis were examined. Mrfms products were observed during proliferation of L6 alpha 1 myoblasts and were downregulated during differentiation. Run-on transcription assays demonstrated that the mrfms gene was transcriptionally active only in undifferentiated myoblasts. These findings suggested that mrfms levels in L6 alpha 1 myoblasts are controlled by transcriptional mechanisms. The half-life of mrfms transcripts was found to be at least 5 hr while inhibition of protein synthesis with cycloheximide (CHX) decreased this half-life to 30 min without changes in the rate of mrfms gene transcription. In addition oncogenic transformation of L6 alpha 1 myoblasts by the v-fms induced constitutive upregulation of mrfms mRNAs, and nuclear run-on assays demonstrated that mrfms transcription was not growth-factor dependent. Furthermore, these findings with others previously published indicate that mrfms gene products may play a role in the normal and neoplastic growth of muscular cells.


The expression of PDGF alpha- and beta-receptors in subpopulations of PDGF-producing cells implicates autocrine stimulatory loops in the control of proliferation in cytotrophoblasts that have invaded the maternal endometrium. In order to explain the high proliferative potential of human placental cytotrophoblasts, we have addressed the potential involvement of platelet-derived growth factor (PDGF) ligand and receptors. Although PDGF is usually described as a mitogen for cells of mesenchymal origin, we show in this report that extra-villous term placental cytotrophoblasts express the PDGF alpha- and beta-receptor genes, both in vivo and in vitro. In addition, cytotrophoblasts produce significant amounts of PDGF-B protein. By immunohistochemical analysis of receptor expression, we found that the PDGF alpha-receptors could be detected at the cell surface, while the PDGF beta-receptors were only detected intracellularly. In addition, double immunostaining analysis showed that the PDGF alpha- and beta-receptor molecules are expressed in different subpopulations of cytotrophoblasts. The addition of PDGF-AA and PDGF-BB homodimers to cytotrophoblast primary cultures induced a significant increase in DNA synthesis. We conclude, therefore, that PDGF is a growth factor for placental cytotrophoblasts and suggest that the growth of cytotrophoblasts can partly be explained by a PDGF autostimulatory loop, limited by the number of receptor-positive cytotrophoblasts.


Transthoracic echocardiography documents prompt resolution of right atrial thrombus after thrombolytic therapy. Right atrial thrombi represent pulmonary emboli in transit, and they may be fatal in patients treated conservatively with anticoagulation. This case provides an opportunity to review echocardiographic findings and management decisions in this disease entity. As the literature now favors thrombolytic therapy in suitable patients, we present a case in which transthoracic echocardiography provided rapid assessment of the outcome of this form of therapy.


Detection of central pulmonary artery thromboemboli by transesophageal echocardiography in patients with severe pulmonary embolism. Transthoracic echocardiography generally provides only indirect signs of pulmonary embolism. In contrast, with transesophageal echocardiography the thromboembolus itself can be visualized in the central parts of the pulmonary artery. The aims of our study were to evaluate, first, the incidence of central pulmonary artery thromboemboli in patients with severe pulmonary embolism, and second, the accuracy of the echocardiographic diagnosis. Our study group comprised 60 patients with proved severe pulmonary embolism. All patients were examined by transthoracic and transesophageal echocardiography. The echocardiographic findings concerning the absence or presence of central pulmonary artery thromboemboli were compared with the results of different reference methods. Central pulmonary thromboemboli were found in 35 patients (58.3%) by echocardiography. Two types of thrombus were differentiated. Type A is a long, highly mobile thrombus, and type B is an immobile wall-adherent thrombus. In comparison with the reference methods, we determined a sensitivity of 96.7% and a specificity of 88% for the echocardiographic detection of central pulmonary artery thromboemboli in patients with severe pulmonary embolism. Transesophageal echocardiography seems to be a useful method for the diagnosis of severe pulmonary embolism. In our series, central pulmonary artery thromboemboli were present in more than half of the patients. In these cases, transesophageal echocardiography can clarify the diagnosis within a few minutes without further invasive diagnostic procedures.


Blood cyst of the mitral valve: detection by transthoracic and transesophageal echocardiography. Two-dimensional transthoracic and transesophageal echocardiography have become important modalities in the evaluation of the mechanism of symptomatic mitral regurgitation. We report the use of echocardiography in the detection of an unusual cause of mitral regurgitation, that of multiple large blood cysts involving the posterior leaflet of the mitral valve.


Survival of the myeloid progenitor cell line FDC-P1 is prolonged by interferon-gamma or interleukin-4. Continuous proliferation of the immortalized myeloid progenitor cell line FDC-P1 depends on stimulation with either interleukin-3 (IL-3) or granulocyte-macrophage colony stimulating factor (GM-CSF). Two other cytokines, interferon-gamma (IFN-gamma) and IL-4, were found to prolong FDC-P1 survival for several days. Surviving cells incorporated [3H]thymidine and a minority completed up to 3 cell divisions before dying. This transient proliferative response was a direct effect of IFN-gamma and IL-4 since these cytokines did not induce production of detectable IL-3 or GM-CSF and the response was unaffected by cell concentration. IL-6, a constitutive product of FDC-P1 cells whose secretion was increased by IL-3, GM-CSF and IL-4 but not by IFN-gamma, was not responsible for the proliferative response. FDC-P1 lines that constitutively expressed the cell cycle-associated oncogene myc or the survival-associated oncogene bcl-2 also responded only transiently to IFN-gamma or IL-4, indicating that expression of these genes did not complement the signals delivered by IFN-gamma or IL-4. By contrast, the protein kinase C activator phorbol 12-myristate 13-acetate (PMA) prolonged survival of FDC-P1 cells on its own and potentiated the response to IFN-gamma or IL-4, although the combination of stimuli did not support long-term growth. It is concluded that IFN-gamma and IL-4 trigger only some of the signalling events that lead to mitogenesis; these events are complemented by stimulation with PMA but additional signals are required for sustained proliferation.


Acquired coronary-to-left ventricle fistula: evidence by myocardial contrast echocardiography. The case report subject is a patient with an old anteroseptal myocardial infarction and postinfarction angina who developed, over the years, a small left coronary-to-left ventricle fistula. The first coronary angiogram, performed 4 months after the infarction, was negative for coronary fistula. The diagnosis was made 3 years later, at repeat cardiac catheterization with myocardial contrast echocardiography. Left and right coronary injections of 0.2 cc of sonicated 5% human albumin microbubbles generated a bright cloud of contrast entering the left ventricular cavity at the level of the distal third of the interventricular septum. Conversely, cineangiography failed to show on-line the fistulous communication that was evident only after careful cineangiographic reviewing. This case demonstrates the high efficacy of myocardial contrast echocardiography in identifying very small coronary fistulae.


Effects of epidermal growth factor on calf renal glomerular cells in vitro. Epidermal growth factor (EGF) stimulates the mitosis and differentiation of a variety of cellular types. It also delays the cell senescence in vitro. Because of its multiple functions, the effects of EGF on cells from isolated, explanted calf renal glomeruli have been studied. The cell types emerging from glomeruli cultured with and without EGF were compared and identified by morphological, immunofluorescence and electron microscopy criteria. Two cell types: visceral epithelial cells or podocytes (type I) and mesangial cells (type II) emerged from glomeruli cultivated without EGF. A third cell type, called type III cells, appeared only in the presence of EGF. These cells divided, were mobile and had prolonged lifespan in culture. They appeared pavement-like, and acquired progressively the morphological features and cytoskeletal components of type I cells. They also showed certain characteristics of podocytes in vivo. We suggest that type III epithelial-like cells are precursor cells of podocytes, that EGF triggers their emergence from glomeruli and their subsequent proliferation and differentiation in vitro. EGF also prolongs their lifetime in culture.


Terminal differentiation of mouse preadipocyte cells: the mitogenic-adipogenic role of growth hormone is mediated by the protein kinase C signalling pathway. The role of growth hormone (GH) in the differentiation process of Ob1771 mouse preadipocyte cells has been studied under culture conditions that were serum-free and hormone-supplemented and which were previously shown to lead to terminal differentiation. In the absence of GH, a dramatic decrease in the adipogenic activity of the culture medium could be observed, as indicated 12 days after confluence by the low levels of glycerol-3-phosphate dehydrogenase activity and the sharp reduction of the number of triacylglycerol-containing cells. This decrease in adipogenic activity was accompanied by a parallel loss of the mitogenic potency of the culture medium. Determination of the half-maximal and maximal concentrations of GH required for the restoration of growth and differentiation were identical, 0.5 and 2 nM, respectively. Despite the presence of insulin-like growth factor-I (IGF-I) to substitute for supraphysiological concentrations of insulin and to saturate IGF-I receptor, GH was still required to induce terminal differentiation of a maximal number of cells. However, protein kinase C activators such as prostaglandin F2 alpha, phorbol esters and diacylglycerol were able to mimic GH in promoting a maximal mitogenic-adipogenic response, indicating that the ability of GH to induce diacylglycerol production (Doglio et al., 1989; Catalioto et al., 1990) plays a prominent role in this process. Furthermore, in agreement with the fact that the mitoses which precede terminal differentiation of Ob1771 preadipocytes are strictly controlled by cAMP and only modulated by protein kinase C, terminal differentiation of Ob1771 preadipocytes occurred in the absence of GH upon supplementation with high concentrations of carbaprostacyclin, added as a cAMP-elevating agent or with 8-Br-cAMP, added as a cAMP analogue. It is concluded that the control exerted by GH on terminal differentiation of mouse preadipocytes corresponds to a modulating mitogenic effect mediated through protein kinase C activation and leading to a potentiation of the cAMP and IGF-I mitogenic signalling pathways.


Recovery of end-organ failure during mechanical circulatory support. To evaluate organ recovery during mechanical assistance, respiratory, hepatic and renal function parameters of 40 patients who underwent bridge-to-transplant procedures were reviewed retrospectively. Mechanical circulatory support was indicated if the hemodynamic and clinical status deteriorated despite pharmacotherapy with catecholamines, vasodilators, and intravenous use of the phosphodiesterase inhibitor enoximone. Sequelae of cardiogenic shock such as renal, hepatic and respiratory insufficiency were not considered a contraindication for mechanical support. The analysis of preimplant data such as serum creatinine, liver enzymes and pulmonary gas exchange did not identify any predictive indicator of irreversible organ damage. Functional recovery of preexisting respiratory, hepatic and renal dysfunction was found in 91%, 90%, and 85%, respectively. Subsequent transplantation, however, was affected by the number of failing organs prior to mechanical support. Of 17 patients with isolated organ failure prior to assist, 14 (82%) were transplanted. By contrast, 9 (75%) of 12 with combined failure of two organs, and only 6 (54%) of 11 patients with clinical patterns of three failing organ systems received transplants. In all patients who underwent successful transplantation, transplantability was associated with rapid organ recovery within 10 to 15 days after initiating mechanical assistance.


Early prediction of septic complications after cardiac surgery by APACHE II score. In 110 patients admitted to the intensive care unit after cardiac surgery, daily monitoring [clinical parameters, cardiac index (CI), left ventricular stroke work index (LVSWI) and APACHE II score] was performed in regard to its usefulness in the early prediction of septic complications, a major cause of postoperative mortality. Septic complications (defined as Elebute sepsis score of > or = 12 on > or = 2 days) occurred in 16 patients and were associated with a significantly worse prognosis (mortality 69% vs 1%, P < 0.0001) than was seen in patients without sepsis. While preoperative APACHE II score values did not differentiate between the patients with an uneventful postoperative course and those with septic complications, patients who ultimately developed septic complications had significantly (P < 0.001) higher scores as early as on the evening of the operation day ("day 0"). In addition, in contrast to patients without sepsis, whose scores dropped markedly (P < 0.001) between day 0 and day 1, patients with septic complications invariably had high scores. Compared to single parameters (fever, leucocyte count, CI, LVSWI), the APACHE II score proved to be superior in differentiating between patients who developed sepsis and those who did not. A score of 19 or more on the 1st postoperative day had a sensitivity of 75%, a specificity of 98%, a Youden index of 0.73, a positive predictive value of 86%, and a negative predictive value of 96% in regard to prediction of septic complications.(ABSTRACT TRUNCATED AT 250 WORDS)


Complications from intra-aortic balloon counterpulsation: a review of 303 cardiac surgical patients. From January 1980 to January 1990 all patients undergoing cardiac surgery at the Royal North Shore Hospital, Sydney, and requiring intra-aortic balloon counterpulsation (IABCP) were retrospectively reviewed. A total of 99 patients (32.6%) developed complications. Vascular/haemorrhagic complications occurred in 46 patients (15.2%); 79 patients (26%) required platelet transfusions. We have found that only a history of hypertension was predictive of an increased incidence of developing vascular complications. Surgical intervention was required in 17 patients (5.6%), or 47% of the patients who developed a vascular complication. The mortality among patients requiring IABCP was 36.6%. Intra-aortic balloon pump-related deaths occurred in 6 patients (2%). Use of the intra-aortic balloon pump can be a life-saving procedure, but it carries a significant morbidity and mortality rate. This makes it imperative to temper our indications to those patients who demonstrate a need for it.


"Very long" aortic grafts.

"Very long" aortic grafts. During the past 2 decades, we have been using the so-called "very long" (ascending to infrarenal aorta or ascending aorta to common femoral artery) bypass grafts in selected patients. Our experience with this method includes patients with dissecting as well as arteriosclerotic aneurysms of the descending aorta, thoracoabdominal aneurysms, patients in need of aortic surgery with previous abdominal aortic surgery, radiation treatment, aortic thrombosis, and complex aortic coarctation in the adult. The technique proved to be relatively easy to perform, was well tolerated by most patients and replaced more complicated and higher risk "conventional" operations. The advantages and shortcomings of the method as well as long range clinical observations are presented.


Ruptured congenital aneurysm of the sinus of Valsalva: surgical technique and long-term follow-up. Congenital ruptured aneurysm of the sinus of Valsalva is a rare anomaly usually causing decrease of cardiac performance. Eight patients with a ruptured congenital aneurysm of the sinus of Valsalva were operated upon at the University Hospital Zurich between 1970 and 1991. There were four female and four male patients aged from 15 to 48 years (mean, 36 years). Three patients were asymptomatic and five symptomatic. Associated congenital cardiac defects were found in six patients. Surgical techniques consisted of direct suture in seven patients and closure with a Dacron patch in one. A secondary Dacron patch closure was performed on the second postoperative day in a patient with suture insufficiency after direct closure. Associated operations were closure of ventricular septal defect in two patients, aortic valve replacement in two, aortic valve reconstruction in one and aortic valve commissurotomy in one patient. There were no operative deaths. The mean follow-up was 9 years, range 7 months to 17 years. There were two late deaths due to endocarditis and recurrent cerebral embolisation. An operation for a ruptured aneurysm of the sinus of Valsalva has a low operative risk, but patients remain prone to development of late valvular complications.


Pulmonary venous obstruction following correction for total anomalous pulmonary venous drainage: a challenge. Pulmonary venous obstruction after surgical correction of total anomalous pulmonary venous drainage (TAPVD) is a serious condition. Pulmonary venous obstruction can be the result of a primary developmental error or is due to post-operative anastomotic stricture and is usually manifest within 6 months of surgery. Prompt restudy is indicated and if a stricture is present, urgent surgical relief is indicated. However, the results are often disappointing with a high early mortality and a significant chance of restenosis.


Bilateral single lung transplantation. Complications and results in 14 patients. Between November 1989 and April 1991, 14 bilateral single lung transplantations (BSLT) were performed at our institution using the technique we have described without omentoplasty and rarely cardiopulmonary bypass. The indications included emphysema (8), cystic fibrosis (3), infected fibrosis (1), alveolar microlithiasis (1) and lymphocytic interstitial pneumonitis (1). Maximum mean pulmonary artery pressure was 53 mmHg and minimal right ventricular ejection fraction was 15%. Two patients experienced bronchial complications: 1 complete left bronchial dehiscence, 1 late partial stenosis which required a temporary insertion of a stent. One patient had a posterior dehiscence which healed spontaneously. Five patients died postoperatively (3 of infection, 1 after a volume mismatch and 1 after a circulating anticoagulant). BSLT is the technique of choice for double lung transplantation in adults and heart lung transplantation has very few indications in infected end-stage pulmonary disease. We hope that modification of our immunosuppressive regimen will decrease postoperative mortality.


Self-expanding metal stent for tracheobronchial strictures. To determine the role of expandable metal stent (Wallstent) in treating tracheobronchial strictures, 12 patients with recurrent symptoms of airway obstruction due to either benign or malignant strictures were studied. The seven benign strictures were anastomotic stricture following sleeve resection (2) and single lung transplant (1), tracheal amyloidosis (1), idiopathic chondritis (2), and post-tracheostomy stricture (1). The five malignant strictures were due to recurrent adenoid cystic carcinoma of trachea (1), large-cell carcinoma of lung (1), recurrent laryngeal squamous carcinoma (1), squamous carcinoma of the trachea (1), and malignant melanoma (1). The placement of stents was performed under rigid bronchoscopic guidance with no complications. All patients with benign strictures derived subjective and functional improvement with stenting. No evidence of restenosis within the stented segment in six of the seven benign strictures was found within up to 24 months. Repeated diathermy resection was required in the patient with recurrent amyloidosis through the distal end of the stent. Among the malignant strictures, symptomatic relief was achieved in four of the five patients. One metal stent migrated proximally and was replaced by a Montgomery T tube. One patient with relief of stridor died at 4 months due to carcinomatosis. Tumour ingrowth through the metal stent remains problematic in two patients. However, the incidence of palliative interventions required has markedly reduced after stenting.


Antibiotic prophylaxis in oesophageal surgery. A prospective randomised study to assess the efficacy of antibiotic prophylaxis in oesophageal surgery was performed, in which 226 consecutive patients (113 male and 113 female, age range 24-86 years, mean age of 65 years) were included. The study patients were in two groups: group 1, in which the upper alimentary tract was opened during surgery, and group 2, in which it was not. The group 1 patients (n = 129) were randomised to one of three antibiotic prophylaxis regimes prior to surgery. Group A patients (n = 42) were treated with cefuroxime (CFX) 1.5 g at induction of anaesthesia and then CFX 750 mg b.i.d. for 4 days. Group B patients (n = 46) were treated with CFX 1.5 g and metronidazole (MTR) 1.0 g at induction of anaesthesia, then CFX 750 mg b.i.d. and MTR 500 mg qds for 4 days. Group C (n = 41) treated with CFX 1.5 g and MTR 1.0 g at the induction of anaesthesia. Group 2 (n = 97) was divided into two groups, group D (n = 47) treated with CFX 1.5 g on induction of anaesthesia alone. Group E (n = 50) treated with CFX 1.5 g on induction of anaesthesia then CFX 750 mg bd for 2 days. We found a significantly higher incidence of infective complications in subgroup C (43.9%) and subgroup A (21.4%) compared to subgroup B (8.6%). This difference was most marked in patients undergoing oesophagectomy. We found significantly higher infection rates of infective complications in subgroup D (10.6%) as compared to subgroup E (2%).


Foreign body perforation of the normal oesophagus. Over an 11-year period, 12 patients with foreign body perforation of a previously normal oesophagus were treated in our institution. The foreign bodies were most commonly bones (10 cases), 5 of which were chicken bones; other species were pigeon, rabbit, veal, pork and fish (one each); 2 perforations were due to swallowed dentures. The mean age was 60 years (range 42-73) and 6 patients were female. A degree of psychosocial dysfunction was present in 3 patients. Seven patients presented late (> 48 h after ingestion). The commonest presenting symptoms were fever and pain (8 patients). Other symptoms included dysphagia (7), respiratory distress (3), and late cervical abscess formation (3). The diagnosis was established by contrast oesophagography or rigid oesophagoscopy. A third of the perforations were cervical, the remainder intrathoracic. All patients were treated by surgical drainage with or without primary closure of the perforation. There were no operative deaths. Five patients developed postoperative oesophageal leaks which required reoperation in 1 patient. All patients were well and swallowing normally on discharge from hospital. Follow-up endoscopy or oesophagography was carried out in all patients and confirmed the absence of oesophageal disorders. Foreign body perforation of the oesophagus is a rare but important subentity of oesophageal perforation which responds well to surgical treatment.


Left lower lobe transplantation during a bilateral single lung transplantation (pulmonary lobe transplantation). An isolated left lower lobe was used as a left graft, during a bilateral single lung transplantation procedure, in a patient with infected fibrosis. This technique is suitable for patients with small lung volume (especially cystic fibrosis) or asymmetric retraction.


Pulmonary autograft failure after aortic root replacement in a patient with juvenile rheumatoid arthritis. We report a 12-year-old girl suffering from juvenile rheumatoid arthritis with severe aortic valve incompetence who died 5 months after an initially successful Ross procedure. Pulmonary autograft failure was a result of recurrence of aggressive valvulitis.


Biocompatibility of extracorporeal circulation with autooxygenation. Platelet damage, complement activation and neutropenia during cardiopulmonary bypass are the result of blood contact with artificial surfaces, mainly in the oxygenator. To evaluate biocompatibility of this kind of bypass we compared two techniques of extracorporeal circulation in 40 patients undergoing elective coronary bypass operations. In 20, a standard technique with a bubble oxygenator was used (group 1), and in the remaining 20 patients with autooxygenation, the patients' own lungs were included in the perfusion circuit (group 2). Several blood samples were taken before, during and after perfusion to estimate the corrected platelet numbers and pulmonary leucocyte sequestration in all patients, and additionally in 6 patients from each group, complement C3a and C5a anaphylatoxins were measured (radioimmunoassay). At the end of cardiopulmonary bypass, the decline of platelet number corrected to haematocrit platelet number in group 1 was significantly higher than in group 2 (P less than 0.01). There was a significant increase in circulating white blood cells when compared to pre-bypass time in both groups (P less than 0.05). However, comparison of differences between leucocyte counts in the blood of the patients' right and left atria showed enhanced leucocyte sequestration in group 1, 1.46 +/- 0.5 x 10(3)/mm3 vs only 0.34 +/- 0.2 x 10(3)/mm3 in group 2. The C3a rose progressively during extracorporeal circulation: in group 1 from 268 +/- 46 ng/l to 521 +/- 65 ng/l, and in group 2 from 244 +/- 46 ng/l to 418 +/- 34 ng/l (P less than 0.05). No characteristic changes in C5a activation were observed in either group.(ABSTRACT TRUNCATED AT 250 WORDS)


The relevance of the microbiological flora of the upper alimentary tract to postoperative infection in major oesophageal surgery. A prospective study to investigate the source of pathogenic organisms responsible for infective complications of patients undergoing major oesophageal surgery was undertaken in 138 consecutive patients (38 female and 100 male) with obstructive lesions of the oesophagus, aged 24 to 86 years (mean 67 years). In all patients, the upper alimentary tract (UAT) was opened as part of the surgical procedure and 20.3% had pathogens present in their sputum before surgery. On direct culture of the contents of stomach or oesophagus at operation, 61% showed pathogenic organisms. Twenty-five patients suffered from 28 infections, predominantly pleuropulmonary infection (n = 19) but also wound sepsis (n = 8) and generalised infection (n = 1). Pathogenic organisms could not be cultured from the tracheobronchial tree immediately postoperatively. There was no correlation between preoperative sputum microbiology and postoperative infection. There was, however, a definite correlation (66% of cases) between pathogens of UAT content collected at operation and those responsible for postoperative infection. We conclude that it is relevant and important to regularly obtain samples of UAT content at operation to plan antibiotic regimes.


Surgical treatment of acute purulent mediastinitis. During the last 15 years we have treated 147 patients with acute purulent mediastinitis (APM). According to the aetiology of the disease, 2 major groups were defined. The first group included the cases of oesophageal origin--112 patients (dilatation--38 patients, foreign body extraction--29 patients, lye injuries--11 patients, oesophagoscopy--8 patients, sharp foreign body--6 patients). The second group consisted of patients with mediastinitis of non-oesophageal origin--35 patients (tracheo-bronchial disease--21 patients, tooth infection--8 patients, cervical infection). Symptoms of the mediastinal infection were typical; nevertheless, early diagnosis (within first 12 h) was obtained in only 43.5% of cases. Therapy for all patients included general stabilisation, broad spectrum antibiotics and immunotherapy. In 86 patients, mediastinal drainage was performed with additional suture of the oesophageal wall or plication with a gastric or diaphragmatic patch in 9 cases. Oesophagectomy and delayed colon transplant was the method used in 61 patients. Mortality included 21 patients (14.3%). The cause was broncho-pneumonia in 9 patients, endotoxic shock in 7 and renal failure in 3 patients.


Acute thrombosis of prosthetic valves: a multivariate analysis of the risk factors for a lifethreatening event. In 3231 prosthetic valves implanted between January 1975 and November 1990, we observed 61 cases of prosthetic obstruction of biological origin with clinical and laboratory findings of severe functional impairment which required surgery as emergency treatment. The hospital mortality was 19.67% (12/61). The obstruction was due to a primary thrombosis in all 5 bioprostheses which were not anticoagulated and in 11/56 (19.64%) mechanical prostheses of which 3 were not anticoagulated and 4 were not properly anticoagulated. The obstruction was due to fibrous tissue overgrowth in the other 45 mechanical prostheses (80.35%) with secondary thrombosis in 34 cases (60.71%) and no thrombosis in 11 (19.64%); 71.11% of these prostheses were adequately anticoagulated. Of the 61 obstructed prostheses, 53 were mitral and 8 were aortic. No tricuspid obstruction was observed. A statistical assessment by multiple correspondence, cluster and chi square analysis was performed in two groups of patients with different models of mechanical mitral prostheses. The 5-year actuarial incidence of obstruction was 6.08%. Significant risk factors were: tilting disc prostheses, prostheses without pyrocarbon coating, large prostheses, tilting disc prostheses with a small orifice posteriorly oriented, atrial fibrillation, enlarged left atrium, time from implant greater than 4 years, age between 40 and 50 years. In our opinion, prosthetic obstruction may be referred to a primary thrombosis only in cases where it may be prevented by adequate anticoagulation. In most cases, the obstruction is produced by periprosthetic fibroblastic proliferation which may develop in spite of adequate anticoagulation in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)


Effect of aspirin on intimal proliferation and tissue cholesterol in long-term experimental bypass grafts. A single daily dose of aspirin (ASA) reduces the incidence of early graft thrombosis after coronary bypass operations. Recent data indicate that aspirin may not prevent intimal proliferation and cholesterol uptake in experimental bypass grafts which suggests that aspirin may not improve long-term graft patency. To further clarify the effects of aspirin on intimal proliferation and cholesterol metabolism, we performed femoral interposition vein grafts in 12 dogs receiving a 2% cholesterol diet. Six controls (CON) received the diet alone while the remaining animals received the diet with 160 mg aspirin daily before and for 9 months following operation. A segment of each graft was removed at 3 months for measurement of intimal thickness and tissue cholesterol. The entire graft was then harvested at 9 months. Intimal thickness increased rapidly during the first 3 months. A slow and progressive increase in intimal thickness was observed between 3 and 9 months. There was, however, no difference in intimal thickness between the two groups. Tissue cholesterol increased similarly in both groups. Rapid cholesterol uptake occurred within the first 3 months and then decreased between 3 and 9 months. (1) ASA failed to reduce intimal proliferation and cholesterol uptake in experimental bypass grafts suggesting that ASA may not prevent late graft failure, (2) Accelerated intimal proliferation and cholesterol uptake occurred within the first 3 months emphasizing the importance of developing and instituting anti-proliferative therapy immediately after aortocoronary bypass.


Surgery for bullous disease of the lung. Between July 1986 and December 1990, 22 patients underwent 23 operative procedures for bullous disease at Harefield Hospital. Their ages ranged from 21 to 71 years (mean 49.8 years). There were 18 males and 4 females. All patients were operated upon for symptoms of exertional dyspnoea. Four patients belonged to functional class IV, 11 to class III and 3 to class II. In 80% of patients, computed tomography was performed as part of the preoperative assessment. The bullae were dealt with in 13 patients on the right side, in 7 on the left and in 2 bilaterally. Six patients were treated by a modified Monaldi procedure and 17 by bullectomy. There was no operative mortality. Mean hospital stay was 14.8 days. Two patients required a second operative procedure during their hospital stay for persistent air leak and pneumothorax. One of these had a Monaldi procedure in the first instance but underwent bullectomy later. All patients improved symptomatically, 10 patients moving up two grades and 12, one grade. Mean FEV1, FVC and MVV were significantly improved postoperatively, but there were no significant changes in RV or TLC. A graduated exercise test was performed in 4 patients. Improvements were seen in ventilation and oxygen consumption at anaerobic threshold and maximum exercise. Surgery for bullous disease improves symptoms by reducing airway obstruction and increasing ventilatory capacity on exercise.


Acute traumatic isthmic aortic rupture. Long-term results in 49 patients. Forty-nine patients who sustained acute traumatic rupture of the aorta at the level of the isthmus were treated in our hospital between 1976 and 1990. Four patients died before surgery and 45 patients were operated upon using a pump oxygenator partial bypass in all but 2 cases (1 clamp and sew and 1 shunt). The tear was circumferential in 33 and partial in 12 cases. Direct suture was used in the 12 partial and in 21 of the circumferential tears. A dacron tube was used in 12 patients. Hospital mortality was 3 resulting from brain damage, prolonged shock before surgery and necrosis of the colon 4 weeks after operation. No paraplegia was observed. There were 2 cases of neurological disturbance (2 spinal cord dysfunction 5 and 8 days, respectively, after surgery). These complications were transient. Among the 42 survivors, 1 was lost to follow-up. The clinical aortic status of the remaining 41 was excellent. Aortic reconstitution as assessed by digital aortic angiography was excellent in the 33 cases examined with 2 exceptions (graft stenosis, false aneurysm). Our experience and review of a large series indicate: the use of a partial bypass with pump oxygenator decreases the probability of medullary ischemia, but the risk of spinal cord ischemia is not eliminated. When intra-abdominal lesions are life-threatening, laparotomy must preceed thoracotomy. Clinical results assessed in long-term survivors are excellent, especially after direct repair.


Histological evaluation of the inferior epigastric artery in patients with known atherosclerosis. Comparative histological studies have been performed on the various arterial conduits available for myocardial revascularization including the inferior epigastric artery which has recently become the focus of intense investigation. In this study, 10 patients with known risk factors for atherosclerotic disease had their inferior epigastric artery harvested and the entire specimen examined for the microscopical presence of atherosclerosis or its precursors. Histopathological findings that have been shown to be theoretically protective against the progression of atherosclerosis were observed. These include the paucity of fenestrae in the internal elastic lamina, no medical calcification, the absence of foam cells and the absence of intimal smooth muscle cells. No specimen had atherosclerotic disease and only 3 specimens showed changes consistent with minimal intimal hyperplasia. Morphometric analysis of the 3 diseased specimens revealed only minimal luminal narrowing. These findings suggest that the inferior epigastric artery may not be prone to atherosclerosis. Thus, the inferior epigastric artery appears to be a safe myocardial conduit and long-term patency can be anticipated.


A study of the stability of orientation in the CarboMedics bileaflet heart valve prosthesis. A total of 25 CarboMedics bileaflet prostheses was studied in the immediate postoperative period and at 1 week, 1 month and 3 months after surgery. No evidence of rotation was found on visual comparison of valve orientation and there were no significant differences between successive studies for the distance between the septum and either the anterior (P = 0.92) or posterior leaflet (P = 1.00) of valves in the mitral position. The possibility of spontaneous rotation is a potential drawback not only of the CarboMedics prosthesis, but also of designs currently being developed. This study suggests that major rotation does not occur commonly.


The place for bilobectomy in bronchogenic carcinoma. From 1978 to 1988, 148 bilobectomies (21 upper and middle and 127 lower and middle) were performed for bronchogenic carcinoma. A conservative procedure was mandatory in 29 patients in whom a pneumonectomy was not functionally feasible while bilobectomy was deliberately performed in 119 patients with near normal lung function. Overall mortality was 6% compared to 4% and 3%, respectively, following pneumonectomies and lobectomies. Preoperative functional status did not significantly influence mortality. The complication rate was 55%. The incidence of bronchopleural fistula electively observed after lower and middle lobe resection was significantly higher (11%) compared to 4% after pneumonectomy and 1.4% after lobectomy (P less than 0.01). The overall 5-year survival was 43% and was similar to that observed at comparable TNM stage after other pulmonary resections. Residual right pulmonary function demonstrated by perfusion isotopic scan was 24% +/- 10 in 21 long-term survivors. These results indicate that bilobectomy can reasonably be considered in patients requiring more than a lobectomy but in whom lung conservation is mandatory despite a significant increase in morbidity. The risk appears justifiable regarding late survival results and functional benefit of the remaining right lobe.


Severe tricuspid regurgitation following blunt chest trauma: indication for emergency surgery. A 24-year-old man with polytrauma and severe posttraumatic tricuspid regurgitation due to rupture of all three papillary muscles was subjected to emergency operation 3 days after a car accident. At operation, all three papillary muscles of the tricuspid valve were reinserted. Severe tricuspid regurgitation after blunt chest trauma is an indication for emergency surgical treatment, and can be performed with a low operative risk.


Normothermic arrest with continuous hyperkalaemic blood: initial experience. The requirement for hypothermia in myocardial protection has recently been questioned. Between October 1990 and May 1991, diastolic arrest was achieved using continuous perfusion with normothermic, hyperkalaemic blood in 257 consecutive patients undergoing cardiac surgery. The mean age was 59.8 +/- 9.3 years (range 28-84 years). Coronary artery surgery was performed in 210 patients, valve replacements in 18, combined procedures in 22, and 7 patients had miscellaneous procedures. Eleven patients (4.3%) had undergone previous cardiac surgery, and 65 (25.3%) required urgent or emergency operations. Hyperkalaemic blood (7-20 mmol/l) was delivered antegradely in 190 (72.8%) patients (mean aortic root pressure 60-80 mmHg), retrogradely in 62 (25.3%) patients (mean coronary sinus pressure less than 40 mmHg), and by a combined route in 5 (1.9%). Sinus rhythm returned immediately after removal of the aortic clamp in 235 (91.4%) patients. Weaning from bypass was achieved without circulatory support in 207 (82.5%) patients. Of 233 patients undergoing non-emergency coronary artery surgery, single valve or combined procedures, 11 died, giving an operative mortality of 4.7%. Of 155 patients with good left ventricular function requiring coronary artery surgery, 3 (1.9%) died. The in-hospital mortality for the group as a whole was 7.3%. Sixteen (6.2%) patients sustained perioperative myocardial infarctions; of these 6 died. We conclude that continuous, normothermic, hyperkalaemic arrest is a simple and safe method of myocardial protection. It may avoid the damage associated with hypothermia, ischaemia and reperfusion.


An immunocytochemical analysis of rapidly progressive atherosclerosis in human vein grafts. Aortocoronary vein grafts are known to develop atherosclerotic plaques usually superimposed on intimal hyperplasia. The cellular characteristics of these lesions have been studied with immune cytochemical techniques and compared with those in native coronary arteries. Fifteen stenosed grafts showed concentric intimal hyperplasia characterized by massive proliferation of smooth muscle cells (HHF-35+). The subendothelial layer contained numerous T lymphocytes (UCHL-1+, MT-1+) and to a lesser extent macrophages (HAM-56+). Eleven grafts had superimposed atherosclerotic plaques characterized by atheroma but otherwise showing the same cellular constituents. The atherosclerotic plaques in the venous grafts resembled those in the coronary arteries, the main difference being the occurrence of multiple atheromas (up to 4 in a single section), the high number of T lymphocytes and macrophages related to these sites and the presence of atheromas bordering directly onto the luminal surface. It thus appears that the development of atherosclerotic plaques in vein grafts is accompanied by a similar immune inflammatory reaction as in native coronary atherosclerosis, presumably in a more aggravated form. The latter phenomenon could relate to the more enhanced and rapidly progressive nature of vein graft atherosclerosis.


Is the internal mammary artery an acceptable graft in the elderly patients with left main coronary artery disease? Age over 70 years and critical stenosis of the left main coronary artery trunk are two situations in which the use of the internal mammary artery has been questioned. Because the coexistence of these two conditions is increasingly seen, we reviewed our experience with 53 patients 70 years of age or older that underwent myocardial revascularization for left main disease. In 17 patients, the left anterior descending coronary artery was grafted with the left internal mammary artery whereas the 36 remaining patients were exclusively revascularized by means of saphenous vein conduits. There was no significant difference in postoperative mortality or morbidity between the two patient groups. We conclude that elderly patients with left main disease should be offered the benefits of a mammary artery graft provided they are hemodynamically stable.


Improvement of severely reduced left ventricular function after surgical revascularization in patients with preoperative myocardial infarction. In recent years, two pathophysiological conditions--stunned and hibernating myocardium--have been described showing how function may be depressed in myocardium that remains viable. The aims of the present study were postoperative assessment of LV function at rest and during exercise after CABG in patients with established previous myocardial infarction and impaired preoperative LV function and evaluation of preliminary experience with positron emission tomography (PET) in the preoperative identification of reversible ischaemic myocardium and its predictivity in postoperative functional improvement. We studied 23 patients with preoperative LV function under 45%. Echocardiography and complete heart catheter were performed pre- and postoperatively. PET was performed in all patients preoperatively. In 21 patients with patent grafts, CABG significantly improved systolic and diastolic function during exercise and at rest. EF improved from 34% +/- 14% to 52% +/- 11% at rest and from 31% +/- 14% to 58% +/- 13% during exercise (P less than 0.01). Time constant of diastolic relaxation was significantly reduced after revascularization. In 2 patients with pathological findings on postoperative coronarangiography, EF remained unchanged. Both global and regional contractility improved following surgery. Regional analysis indicated that improved EF at rest occurred in regions developing ischaemia during exercise before CABG and in regions showing typical mismatch in 82Rubidium-2-fluoro-2-desoxyglucose suggesting the presence of hibernating myocardium.(ABSTRACT TRUNCATED AT 250 WORDS)


Early results of cryopreserved pulmonary allografts as aortic valve substitute. Excellent clinical results with pulmonary autografts and experimental evidence that the pulmonary valve can withstand the higher stress in the systemic circulation led us to use the cryopreserved pulmonary allograft for aortic valve replacement. From September 1988 to March 1991, 45 consecutive patients (59.9 +/- 12.0 years, 25 men and 20 women) received a cryopreserved pulmonary allograft in the aortic position from our hospital based valve bank. All allografts were inserted freehand in the subcoronary position. There were 3 in-hospital deaths (7%) and 1 patient had severe valvular incompetence immediately postoperatively requiring reoperation after 4 weeks. Forty-one patients were followed at 3-6 month interval for 14.7 +/- 7.8 months (3-28 months) and valve performance was assessed routinely by means of color flow Doppler echocardiography: 34 patients (83%) had no or trivial aortic valve regurgitation. Valvular incompetence class II was present in 2 patients (5%) whereas 3 (7%) demonstrated class II-III. Severe aortic regurgitation (class III-IV) could be detected in 2 patients (5%). Both had to undergo reoperation 4 months and 15 months, respectively, postoperatively. Macroscopic and histological evaluation of the explanted valves demonstrated absence of significant degeneration. We assume that a mismatch in size between allograft and aortic annulus could have lead to dilatation of the allograft valve ring and consequently to valvular incompetence. Pulmonary cryopreserved allografts achieve acceptable short-term results which can be improved if initial technical problems can be avoided.


Lung transplantation with bronchial revascularisation. Surgical anatomy, operative technique and early results. Ischaemic anastomotic complications are an important cause of mortality and morbidity after lung transplantation. Anatomical studies have demonstrated that the pattern of bronchial arterial supply is relatively constant and therefore amenable to attempts at revascularisation. From May 1990, 10 patients who had a double lung transplantation (tracheal anastomosis) and 1 patient who had a right lung transplantation underwent concomitant bronchial revascularisation. There were two early and one late deaths. There were no anastomotic complications. Regular endoscopic examination showed satisfactory healing in all patients. Early angiography showed patent grafts in 7 of 9 patients. At a mean follow-up of 11 months (range 6-17 months) 8 patients are well and leading a normal life. This report describes the anatomical basis, technical aspects and early results of a promising operative procedure in the field of lung transplantation.


Classification of airway anastomotic healing. Airway complications remain a major problem after lung transplantation. There is no standardised method of assessment of airway healing. We propose a classification of airway healing based on the anastomotic appearances at endoscopy 15 days postoperatively. The system appears to correlate well with the subsequent development of anastomotic sequelae and can be used to assess the effectiveness of therapeutic modalities designed to reduce airway complications.


Squamous cell carcinoma of the lung: prognostic factors affecting the long-term outcome after surgical resection. From 1976 to 1989, 638 patients with squamous cell carcinoma were operated on. Reliable information concerning survival could be obtained in 540 of these cases via follow-up examinations. All tumors were retrospectively classified according to the TNM system of the fourth edition of UICC classification. The average survival time after potentially curative operation was 7.32 years in patients with stage I tumors, the 5-year survival rate was 55.3%. The corresponding values were 2.42 years and 29.1% respectively in patients with stage II tumors, compared to 1.22 years and 12.0% respectively in those with stage III a tumors. The differences between tumor stages are statistically significant. Analyzing the influence of the T and N factors on the prognosis following potentially curative surgery, the classification in the various tumor stages was largely verified. Stage III a is inhomogeneous in terms of prognosis. T and N factors showed prognostic value in this group. In the group with T3 tumors there was a significant difference in the mean survival times, independently of the lymph node status, when the patients were divided into those with T3 tumors close to the main carina (16 months) and those who had infiltrated adjacent structures (7.5 months). When differentiating the N1 location, a significant difference was found between the group of patients with T2 tumors and true lymph node metastases and the group with T2 and direct tumor infiltration of the lymph node (mean survival time 27.5 vs 42.3 months).(ABSTRACT TRUNCATED AT 250 WORDS)


Antiheart antibodies following open heart surgery: incidence and correlation with postpericardiotomy syndrome. One-dimensional sodium dodecyl sulphate polyacrylamide gel electrophoresis of myocardial proteins followed by Western blotting is a sensitive method for the detection of antiheart antibodies after cardiac transplantation. In a previous study we found that the majority of patients made antiheart antibodies after cardiac transplantation. It is possible that these antibodies were formed in response to cardiac damage caused during the surgical procedure rather than being specific to the transplantation situation. In this study we have evaluated the role of open cardiac surgery in the formation of antiheart antibodies for the first 9 months of the postoperative period using the Western blotting technique and correlated that with the development of post-pericardiotomy syndrome. Only 25% (9/36) of patients showed any increase in the pre-existing level of antiheart antibodies or developed antiheart antibodies with new reactivities. None of the patients in the study developed manifestations specific for post-pericardiotomy syndrome during the period of follow-up. The results support the contention that the high incidence of antiheart antibodies formed after cardiac transplantation is due to a humoral immune response to the presence of alloantigens on the grafted heart rather than as a result of the surgical procedure itself.


Partial brachiocephalic perfusion under hypothermic cardiopulmonary bypass. An experimental study. We studied electrophysiological, oxygen metabolic, and histological variables in dogs to establish the reliability and safety of partial brachiocephalic perfusion (PBP) under hypothermic cardiopulmonary bypass (CPB) at 23 degrees-25 degrees C. Sixteen mongrel dogs were divided into two groups. Six (control group) underwent typical hypothermic CPB for 90 min, and 10 (PBP group) underwent PBP under hypothermic CPB for 90 min. During core cooling on the CPB, a progressive reduction in voltage and slowing of frequency of the electroencephalogram (EEG) was observed. At around 23 degrees C nasopharyngeal temperature the tracing became almost flat and remained so throughout the hypothermic CPB or the PBP under hypothermic CPB. Consistent recovery of the EEG was, however, observed during the period of rewarming on the CPB, and the voltage and frequency of the EEG recovered to control levels on weaning off CPB at 36 degrees C in both groups. In the PBP group, the cerebral arteriovenous oxygen (AVO2) difference was 12.4 +/- 4.0 vol% before beginning the CPB, and it was 5.6 +/- 2.7, 5.7 +/- 3.1, 5.4 +/- 3.3, and 4.9 +/- 2.9 vol% at 10, 30, 60, and 90 min respectively after commencement of the PBP under hypothermic CPB. The cerebral AVO2 difference measured 10 min after commencement of the PBP was significantly less than that in the control group (P less than 0.05), but otherwise there were no significant differences between cerebral AVO2 differences in the two groups. Concentration of serum creatine kinase-BB (CK-BB) gradually increased in proportion to the duration of CPB in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)


Conversion of lusoric artery into right subclavian artery in one-stage neonatal repair of aortic arch anomalies and intracardiac defects. In 2 patients, a lusoric artery was compressing the mediastinal structures during a one-stage repair of type B aortic arch interruption and ventricular septal defect. In order to prevent the long-term complications of sacrifice of the subclavian artery, the lusoric artery was not simply divided but converted into a regular right subclavian artery by re-implantation of the abberant vessel at the origin of the right carotid artery during the one-stage repair. At follow up, both patients have normal right radial arterial pulsations. In one patient, angiography was repeated and confirmed a well functioning right subclavian artery. Conversion of a lusoric artery into a right subclavian artery during one-stage repair of aortic arch anomalies and intracardiac defects is not only feasible but also indicated to preserve subclavian artery function and to prevent compression of the mediastinal structures by a vascular ring.


Oesophageal erosion of an Angelchik prosthesis: surgical management using fundoplication. Complications following insertion of the Angelchik prosthesis are becoming increasingly recognised. We report a 35-year-old patient with both mediastinal migration and intraluminal oesophageal erosion of a prosthesis. Successful management included transthoracic removal combined with a modified onlay fundoplication over the oesophageal defect to prevent gastro-oesophageal reflux.


New developments in clinical testing of medical devices for Europe 1992. The unification of Europe is associated with the introduction of many new regulations aiming at, for example, standardization and quality control. Several of these generally normative regulations are pertinent to clinical investigations of medical devices, such as heart valves, pacemakers and cardiac assist devices. Relevant documents dealing with these regulations are the "Guidance for good clinical practice for trials on medicinal products in the European Community," a standard already passed by the European Parliament, and CEN (Comité Européen de Normalisation) document TC258 dealing with "Clinical investigations of medical devices". The latter standard is in discussion among member states of the European Community. In this present survey the most important issues dealt with in these documents will be summarized with emphasis on the aspects relevant to clinical investigations of medical devices.


Mechanical circulatory support in the 1990s. The current experience in bridging patients to weaning (more than 965 implants) and to transplantation (more than 544 implants) has shown the feasibility of mechanical circulatory support in patients with major cardiac dysfunction, who are unresponsive to optimal medical management. The complications are mostly related to the patient's initial condition at the time of implantation. The rehabilitation of the patient is related to both the extent of recovery from organ dysfunction and the type of device. This analysis proposes some new orientations for research. Firstly, in clinical research, definition of precise indices of the patient condition, not exclusively related to the haemodynamic situation, should allow better patient and device selection. Secondly, in technological research, precise definition of the actual clinical objectives should help in the development of various systems: for resuscitation, for bridging purposes and for long-term or permanent implantation.


In vitro pulsatile flow hemodynamics of five mechanical aortic heart valve prostheses. In vitro measurements of velocity, turbulent shear stress, effective orifice area (EOA), and regurgitant fraction were performed on five new-generation low-profile mechanical aortic heart valve designs under pulsatile flow conditions. These were: Medtronic-Hall tilting disc, St. Jude Medical bileaflet, Björk-Shiley Monostrut tilting disc, Omni-Carbon tilting disc, and Duromedics bileaflet. In general, bileaflet valves have larger EOAs than the tilting disc design, especially in the larger sizes, due to the larger opening angles and lack of obstructive struts. The regurgitant fractions range from 8% for 21-mm valves to 13% for the 29-mm sizes. This increase was largely due to an increase in leakage volume as opposed to closing volume. Furthermore, the leakage volumes increased as the mean aortic pressures increased. The tilting disc valves generally have better regurgitant characteristics compared to the bileaflet valve designs, due to lower leakage volumes and to the smaller opening angle of the occluder providing a more rapid closure of the valve. The velocity and shear stress measurements showed that none of the current valve designs are ideal: all designs create areas of stasis and/or regions of low-velocity reverse flow and regions of elevated turbulent shear stresses capable of causing sublethal and/or lethal damage to the formed elements of blood. It is therefore unlikely that these valve designs will eliminate the problems of hemolysis, thrombosis, and thromboembolic complications.


The Intact porcine bioprosthesis: early world-wide clinical experience and analysis of a single institution's experience. The Intact porcine bioprosthesis is a new-generation valve fixed under stress-free conditions and subjected to a mineralization-inhibiting treatment. The valve is undergoing multi-centre prospective clinical evaluation sponsored by Medtronic, Inc., with 19 centres participating world wide. Since April 1986, 1465 valves have been implanted in the aortic position (AVR, n = 965), mitral position (MVR, n = 438), or both (n = 62), and followed up to 5 years. The data recorded at our participating centre, with 115 valves implanted (AVR n = 93, MVR n = 22) closely match the overall event and death rates in the prospective study. Early mortality in the overall study is 5.6% in AVR and 6.6% in MVR; 3-year actuarial survival rates are 88.5% in AVR and 85.6% in MVR; structural valve-failure-free rates at 3 years are 99.8% in AVR and 98.5% in MVR; 3-year freedom from valve-related reoperation is 97.3% in AVR and 95.8% in MVR. The preferential use of bioprosthetic valves in patients aged 70 years and older with no other indication for anticoagulant treatment entails the not infrequent occurrence of patient/prosthesis mismatch in AVR. Hence, when implanting bioprostheses in old patients, the acceptance of some mismatch has to be weighed against the freedom from anticoagulation treatment and the expected long-term freedom from structural valve failure. Further long-term follow-up will be required to demonstrate the greater durability expected from the stress-free fixation and the anti-mineralization treatment.


Mitral valve repair into the 1990s.

Mitral valve repair into the 1990s. Mitral valvuloplasty has become an increasingly accepted alternative to valve replacement, although the strong learning curve attached to the procedure has deterred many surgeons from adopting it. Since it was developed in the late 1960s by Carpentier, comprehensive valvuloplasty has undergone modifications and additions dictated by the experiences thus acquired, which have contributed to make it a more reproducible and predictable procedure. Mitral valve disease, especially that of rheumatic origin, has a multifactorial pathogenesis, as all the components of the valve apparatus are usually involved. Consequently, valvuloplasty requires a combination of multiple techniques, each one directed at correcting each affected component. The excellent median-term results observed by some of the more experienced groups have contributed to change the indications for surgery, and patients are being referred earlier and in a lower functional class. Hence, in mitral valve prolapse surgery is currently offered to asymptomatic patients with significant regurgitation, before dysfunction of the myocardium and dilatation of the cardiac chambers occur. Valve repair has been possible and successful in virtually all patients with this pathological condition. On the other hand, surgeons are becoming more aggressive towards ischaemic mitral regurgitation of mild or moderate severity. More recently, valvuloplasty has also been performed in some patients with infective endocarditis, with good results. By contrast, the long-term results in rheumatic disease appear favourable, especially in children and young patients with acute carditis. Nevertheless, they have still been proven better than those of valve replacement in these population groups.(ABSTRACT TRUNCATED AT 250 WORDS)


Importance of the mitral apparatus for left ventricular function: an experimental approach. In an experimental study of 31 anesthetized dogs the importance of the mitral apparatus for the left ventricular function was investigated. During extracorporeal circulation bileaflet mitral valve prostheses were implanted preserving the mitral subvalvular apparatus. Flexible wires were slung around the chordae tendineae and exteriorized through the left ventricular wall to cut the chordae by electrocautery from the outside when the heart was beating again. External and internal left ventricular dimensions were measured by sonomicrometry, left ventricular stroke volume by electromagnetic flowmeters around the ascending aorta, left ventricular end-diastolic volume by dye dilution technique, and left ventricular pressure by catheter tip manometers. Different preload levels were achieved by volume loading with blood transfusion before and after cutting the chordae tendineae. When the chordae had been divided peak systolic left ventricular pressure did not change. Heart rate only increased at the lowest left ventricular end-diastolic pressures of 3-4 mmHg, but remained unchanged at higher preload levels. Cardiac output decreased significantly up to -9% at left ventricular end-diastolic pressures of 5-10 mmHg, while left ventricular dp/dtmax showed a consistent reduction of up to -15% at any preload level. Significant reductions were also seen in systolic shortening in the left ventricular major axis (by external measurements -27%, by internal recording -43%). Left ventricular end-diastolic dimensions increased in the major axis by +2% when recorded externally, by +10% when measured internally. Systolic and diastolic changes in the minor axis were not consistent and different in the external and internal recordings.(ABSTRACT TRUNCATED AT 250 WORDS)


Echo Doppler principles, techniques and applications for the cardiac surgeon. Doppler echocardiography is increasingly used not only to identify disease in native heart valves, but also to assess the function of prosthetic valves. The purpose of this paper is to provide a summary of the principles of Doppler echocardiography for the cardiac surgeon which will lead to a discussion of assessment of prosthetic valve function. Solid cardiac structure imaging is first discussed in both one-dimensional (M-mode) and two-dimensional (B-mode) modalities. Measurements of blood cell velocities by conventional spectral Doppler echocardiography are then discussed, leading to two-dimensional flow imaging by color Doppler flow mapping. Assessment of prosthetic valve function is divided into two sections: normal prosthetic valve function and prosthetic valve dysfunction. Subtopics within each of these divisions are discussed in the context of conventional and color Doppler ultrasonography.


Anatomy of aortic heart valve leaflets: the influence of glutaraldehyde fixation on function. The basic function of the aortic valve is reviewed from an engineering perspective. Critical examination of the leaflet morphology can yield insights into how the leaflets function and transmit load to the aortic wall. From an understanding of both the structure and the function it is possible to estimate the impact of stent mounting and glutaraldehyde fixation. It is shown from simple engineering considerations that the major stresses are in the circumferential direction and that the radial components must be very small. Similarly, the largest strains are radial to facilitate the formation of a large coaptation area, while the circumferential strains are explained by the extension to the crimped collagen fibres. Glutaraldehyde fixation can greatly modify the mechanics of the leaflets but this can be minimized by fixation with no pressure differential across the closed valve. Zero-pressure-fixed leaflets are much softer and extensible than those from valves fixed under even low back-pressure (2-4 mmHg). This difference translates into a mode of valve function that more closely approximates that of the native aortic valve.


Valve prosthesis hemodynamics and the problem of high transprosthetic pressure gradients. Recent studies suggest that all prosthetic valves are at least mildly stenotic and may cause relatively high pressure gradients despite normal prosthesis function; such gradients could be due to a mismatch between prosthesis effective orifice area and patient's body size. In order to address this problem more directly, we derived, using a physiologic pulse duplicator system, the theoretical relations between transprosthetic pressure gradients and prosthesis effective orifice areas indexed for body surface area, assuming a normal resting cardiac index of 3.0 l/min m-2 and 10-50% increases in stroke volume such as may occur during maximal upright exercise. These exponential relations show that a small decrease in indexed effective orifice area produces a large increase in pressure gradient, and that the indexed effective orifice area should ideally be not less than 0.9-1.0 cm2/m2 for aortic prostheses and 1.3-1.5 cm2/m2 for mitral prostheses in order to minimize postoperative gradients. Thus, high postoperative gradients do not necessarily indicate intrinsic prosthesis dysfunction but may also be due to patient prosthesis mismatch. Intrinsic prosthetic performance is best assessed by comparing in vivo calculated effective orifice areas to in vitro measurements for same type and size of prosthesis. Patient prosthesis mismatch can be avoided by calculating before operation the projected indexed effective orifice area of the prosthesis being implanted.


The stentless bioprosthesis: surgical challenges and implications for long-term durability. An attempt is made to analyse the factors which are expected to influence clinical results following implantation of a stentless porcine bioprosthesis. Long experience with implantation of allograft aortic valves provides a meaningful basis for comparison with a glutaraldehyde-fixed device. Morphological differences between the two valves involve the aortic wall and muscle shelf, and differences in valve preparation include the strength and stiffness of the aorta and the extensibility of the valve leaflets. As a result of these differences, sizing of the porcine valve is expected to be more critical than the allograft valve and the porcine valve is also expected to be more obstructive. Methods for reducing the obstructive element include the use of a composite aortic valve, a porcine pulmonary valve, or a valve in which the aorta is glutaraldehyde-fixed under pressure while the leaflets are pressure-free. The techniques available for implantation, namely freehand insertion, total root replacement and mini-root replacement, are examined.


Aortic root replacement: modifications of technique with improvements in technology. Potential morbidity remains substantial in aortic root replacement. The tissues are often fragile, contributing to the risk of haemorrhage and postoperative complications. In the past surgery has been directed towards minimising haemorrhage by wraparound techniques and the right atrial fistula method of Cabrol. However, recent use of aortic homografts, collagen-impregnated grafts and tissue glues have reduced bleeding and simplified operative technique. Profound hypothermia and total circulatory arrest allows aneurysm resection to extend into the aortic arch. Between 1986 and 1991 25 aortic root replacements were carried out at the Oxford Heart Centre in 21- to 76-year-olds, 13 for aorto-annular ectasia (4 due to Marfan's syndrome), 7 for aortic dissection (2 Marfan's syndrome) and 2 for complications of previous aortic valve replacement. Three patients had homograft root replacement for aortic root endocarditis. We implanted 14 Medtronic composite grafts, 1 St Jude conduit and 7 collagen-coated Dacron grafts (Hemashield, Meadox) into which a Starr-Edwards valve was sewn, as well as 3 homografts. One patient with a massive chronic dissection following previous aortic valve replacement required an interposition graft to the coronary ostia. In the others, the coronary ostia were mobilised from the native aorta and directly implanted into the conduit. In dissections a ring of pericardium or GoreTex was used to buttress the coronary anastomoses. Six patients also required coronary artery grafting. Native aorta was excised and not wrapped around the conduit. Coagulation defects were corrected aggressively with platelets, fresh frozen plasma and cryoprecipitate.(ABSTRACT TRUNCATED AT 250 WORDS)


The first step to understanding valve failure: an overview of pathology. The most frequent valve-related complications are thromboembolic problems (including anticoagulant-related hemorrhage), infective endocarditis, paravalvular leak, intrinsic degradative dysfunction, and extrinsic interference with function, including tissue overgrowth. Tissue overgrowth, endocarditis, and paravalvular leak are largely prosthesis-independent. Thrombosis, the major cause of mechanical valve dysfunction, is infrequent with bioprostheses; in contrast, the overwhelming cause of bioprosthetic valve failure is primary tissue degeneration.


Techniques of valvular reoperation.

Techniques of valvular reoperation. Valve replacement is simply the exchange of one disease for another. Degeneration of bioprostheses and thrombotic obstruction of mechanical valves, other forms of prosthetic dysfunction and prosthetic valve endocarditis are the main complications leading to reoperation. Repeat valve surgery is more complex than primary surgery and therefore carries a higher mortality and morbidity, even in the hands of experienced surgeons. Several technical details of valve replacement have contributed to the improved results obtained by some surgical groups. Difficulties start with the opening of the sternum, especially in cases where the pericardium was not closed during the initial operation. Cardiopulmonary bypass may be instituted in the usual fashion or may be done by cannulation of the femoral or iliac vessels. The heart need not be completely liberated from the adhesions. Access to the aortic root is usually not difficult, but the left atrium may be less accessible. Removal of the prosthesis also requires precise technique, for disruption of the annulus or damage to other valves or neighbouring structures may occur. Finally, the choice of valve substitute and technique of implantation must be tailored to the patient's characteristics and the type of pathology. One of the most important causes of morbidity and mortality after reoperation is perioperative and postoperative bleeding, resulting from the extensive dissection and from the coagulation disorders, including anticoagulation treatment. Pharmacological manipulation has recently contributed to reduce the severity of this complication. The results of repeat valve surgery have improved markedly and have now reached values which approximate those of primary valve replacement.(ABSTRACT TRUNCATED AT 250 WORDS)


Reoperation and the centrifugal pump?

Reoperation and the centrifugal pump? Postperfusion syndrome is still a problem in long cardiac operations using extracorporeal circulation (ECC). To evaluate whether or not centrifugal blood pumping during open heart surgery is beneficial, a randomized, prospective study was undertaken of 50 consecutive patients undergoing elective coronary artery bypass grafting. The patients were divided into two groups of 25 each. In group 1 a centrifugal pump (Biomedicus) was used as arterial blood pump, while in group 2 a roller pump (Stöckert) was used. The two groups did not differ significantly and the number of variables during surgery was kept low (identical perfusion set, two surgeons, minimal cardiotomy suction). The parameters studied included the cellular elements of the blood and components indicating their functional integrity, such as PMN-elastase, plasma hemoglobin, beta-thromboglobulin, and thrombin-antithrombin III complex and D-dimer as representatives for activated coagulation and secondary fibrinolysis. Blood and urine samples were taken every 15 min during ECC, on arrival in the intensive care unit, and 1, 3, 6, 12, and 24 h thereafter. No difference between the groups was found in regard to bypass time, ECC flow and volume, fluid balance, and clinical outcome. Significant differences in favor of group 1 were found in plasma hemoglobin (P less than 0.05), beta-thromboglobulin (P less than 0.01), D-dimer (P less than 0.05), and platelet counts (P less than 0.5). These differences were clearly ECC-time-dependent and became statistically significant after 90 min bypass. We conclude that roller pumps still can be safely used for standard cardiac procedures.(ABSTRACT TRUNCATED AT 250 WORDS)


The Medtronic-Hall valve: a design in 1977 to improve the results of valve replacement. The prototype Medtronic-Hall valve was developed from improvements to the Lillehei-Kaster and Björk-Shiley valves. The housing was constructed of a single piece of titanium and the disc was composed of pyrolytic carbon; both materials had shown no structural breakdown in previous clinical use. The valve was tested with pulse simulator and electromagnetic flow meter studies and yielded a high effective orifice area. Results in 110 patients were significantly better with the Medtronic-Hall valve than with either of the previous valves. In the 21-mm aortic valve the peak-peak gradient was 12 mmHg; it was 9.2 mmHg in the 23-mm, 3.8 mmHg in the 25-mm, and 2.5 mmHg in the 27-mm. Studies found 5% of forward flow regurgitation in the aortic position and more than desired regurgitation through the mitral valve. After the opening angle of the mitral valve was reduced to 70 degrees, regurgitation reached an acceptable level and the improved hemodynamics resulted in lower transvalvular gradients than in previous mechanical valves. Some patients are naturally more prone to thromboembolism regardless of valve type or anticoagulant therapy; thus the human factor plays a large role in a valve's success. More randomized studies are needed for accurate valve comparison, in addition to investigations of sewing ring factors. Nevertheless, the Medtronic-Hall valve has been used successfully for 15 years and has exhibited no housing fractures.


Review of the global experience with the Medtronic-Hall valve. The Medtronic-Hall cardiac valvular prosthesis has been available for insertion since 1977. This report reviews the English language literature concerning that valve published during the last 14 years. The review is focused on three modes of assessment. First, experience with valve implantation techniques and their results has demonstrated that with careful attention to education of the implanting cardiac surgeon and increasing experience in the clinical use of the prosthesis, the incidence of occluder impingements has steadily fallen to 0.2% of total valve implantations in the United States in 1989. Secondly, hemodynamic assessment of the prosthesis with both invasive catheterization and Doppler echocardiography has demonstrated rest and exercise transvalve gradients and functional valve areas that are as good or better than those in other mechanical cardiac valvular prostheses. Finally, review of the long-term follow-up reports of the Medtronic-Hall prosthesis has demonstrated an acceptably low incidence of late valve-related complications and their consequences.


Original expectations of the Hancock valve and 20 years of clinical reality. The standard (glutaraldehyde-preserved) Hancock porcine bioprosthesis was introduced into clinical practice in order to provide surgeons with a cardiac valve substitute which would be nonthrombogenic and therefore would not require anticoagulation, and would be durable, anatomically suitable, and noiseless. In the present report we have reviewed our long-term experience with Hancock porcine valve recipients in order to verify the original expectations of this bioprosthesis have been met.


Clinical experience with the zero-pressure-fixed Medtronic Intact bioprosthetic valve. The Medtronic Intact porcine valve bioprosthesis was inserted in 219 patients between 1983 and 1990. Mean patient age was 52 years and mean follow up 33.3 months. There was only one example of structural valve degeneration at 25 months, giving an actuarial freedom of 99% at 6 years. Reoperation was performed in 7 patients. Freedom from reoperation was 93% at 6 years, from infective endocarditis 96%, from thrombo-embolism 91% and from valve-related complications 86%. Doppler echocardiography revealed non-significant incompetence in 8 instances and mild leaflet thickening of 5 valves. Valve gradients and areas were unchanged between two Doppler studies 2 years apart of valves in the mitral position, and were reduced in valves in the aortic position from 17 +/- 5.2 mmHg to 13 +/- 2.8 mmHg (P = 0.02). These medium-term results are considered very encouraging. The theoretical considerations underlying the use of zero-pressure glutaraldehyde fixation, which is the technique used for the Intact valve, are detailed elsewhere in this issue [1]. The Intact valve is treated with toluidine blue as a calcium-retarding agent and is mounted on a Dacron-covered acetyl copolymer (Celcon) stent with flexible posts. The normal profile of the porcine aortic valve is maintained.


Heart valve bioprosthesis durability: a challenge to the new generation of porcine valves. Long-term experience with first generation porcine valve xenografts enabled identification of the major limitations to their durability: (1) prosthetic-ventricular mismatch due to the high profile of the stent in patients with mitral stenosis and a small left ventricle; (2) high-pressure fixation with loss of natural collagen crimping in the fibrosa, and wash-out of proteoglycans in the spongiosa; (3) xenograft tissue autolysis, due to the long interval between animal slaughter and aortic valve removal fixation; (4) muscle shelf in the right coronary cusp, which created a gradient and could undergo accelerated calcification and/or spontaneous perforation with time; (5) a flexible polypropylene stent, which could creep or even fracture with consequent inward bending of the stent; (6) progressive time-related dystrophic calcification; (7) host fibrous tissue ingrowth. An awareness of these limitations stimulated technical modifications, which frequently brought about distinct improvements: (1) the reduction of the stent profile eliminated the problem of mismatch, but resulted in a higher tendency towards cusp prolapse and earlier commissural tearing; (2) natural collagen waviness, proteoglycans and cusp extensibility were preserved by employing low or even zero pressure during the fixation process; (3) earlier valve fixation enabled preservation of cell integrity; (4) a new orifice for small valves was designed by replacing the right muscular cusp, thus achieving less gradient and avoiding muscle-shelf-related complications; (5) polypropylene was replaced by Delrin as stent material; (6) calcium-retarding agents like T6 and toluidine blue were applied during commercial processing and storage in order to mitigate tissue mineralization.(ABSTRACT TRUNCATED AT 250 WORDS)


Heart valve bioprostheses: antimineralization. Clinical and experimental studies indicate that calcification of bioprosthetic valves depends on host, implant, and biomechanical factors. The earliest mineral deposits in both clinical and experimental bioprosthetic tissue are localize to transplanted connective tissue cells; collagen involvement occurs later. Passive calcium entry occurs unimpeded in cells modified by aldehyde cross-linking, but the mechanisms for calcium removal are dysfunctional; calcium influx contributes to apatite formation by reacting with compartmentalized, bound phosphorus. Specific strategies for prevention of bioprosthetic tissue mineralization involve modification of either valve preparation details or the local implant environment. Efficacy, mechanisms and safety must be demonstrated for any antimineralization strategy.


Computer modelling of bioprosthetic heart valves. The underlying assumptions and principles of a computer-based model for tissue heart valves are described. The model is used to relate observations of leaflet morphology to the requirements of proper valve function. Stress is the fundamental mechanical factor that limits the longevity of bioprosthetic heart valves--the higher the stress levels in the leaflets, the shorter will be the time over which the leaflets can maintain satisfactory structural integrity. Direct measurement of stress is impractical with real heart valves, but the calculation of stress and the study of its interdependence on other key parameters of tissue valve design is a good alternative. The methodology of computer modelling of heart valves is discussed and the technique is illustrated with some examples. Models of pericardial valves, the aortic allograft and porcine bioprostheses are compared.


[Metachromatic leukodystrophy: an exceptional cause of dementia in the adult]. Hereditary metabolic diseases are an exceptional cause of neurological disorders in adults. Metachromatic leukodystrophy is a hereditary alteration of the metabolism of myelin which may be manifested in adults as intellectual deterioration. A case of metachromatic leukodystrophy presented in adulthood is presented with cognitive deterioration and behavioral alterations as the only clinical manifestation. The patient was a 28 year old male studied for dementia of one year of evolution. Computerized tomography and cranial magnetic resonance demonstrated diffuse and symmetric involvement of the periventricular white matter. The visual evoked potentials were involved while the brain stem auditory potentials were normal. Study of the speed of nerve conductions was compatible with demyelinating neuropathy. The diagnosis of metachromatic leukodystrophy was confirmed by enzyme study revealing very diminished levels of aryl-sulfatase A. Although it is exceptional the adult form of metachromatic leukodystrophy should be included in the differential diagnosis of dementia. Computerized tomography and cranial magnetic resonance together with neurophysiologic studies are the principle procedures orienting diagnosis to this disease.


[Polymicrogyria and ulegyria. Diagnosis by magnetic resonance]. Three patients who had had epilepsy since the second decade of life were studied with cranial magnetic resonance (MR). Two patients had no antecedents of interest during pregnancy and the perinatal period and neurological examination was normal. The third patient had had dystocia and presented left hemiparesia since then, with normal intellectual development. None of the cases had any family history of neurological disease. Cranial magnetic resonance was performed in the three patients demonstrating polymicrogyria in two and ulegyria in the other, in addition to other lesions. The first patient presented an unilateral area of polymicrogyria related with a porencephalic cyst in the distal territory of the right sylvian artery and ipsilateral heterotopia of periventricular location. The second patient presented bilateral periventricular heterotopia, partial agenesis of the corpus callosum and an enlarged cisterna magna in addition to bilateral frontal-occipital polymicrogyria. Finally, ulegyria was observed in the third patient in the edges and neighboring regions of a right rolandic porencephalic cyst, as well as an enlarged cisterna magna.


[Motor fluctuations in Parkinson disease: risk factors]. We studied the histories of 173 patients with Parkinson's disease (1985-1987) chronically treated with levodopa + dopa decarboxylase inhibitor. Ninety four patients had daily motor fluctuations and 79 showed stable motor response. The most significant differences between fluctuating and stable patients were given by age at disease onset and duration of levodopa therapy. Patient with disease onset before 60 had a greater risk (p less than 0.001) of developing fluctuations. Delaying the initiation of levodopa treatment was not associated with a smaller incidence of fluctuations.


[Minimal-intensity carpal tunnel syndrome. Diagnostic sensitivity of various electrophysiological tests]. The most sensitive tests for the electrophysiological diagnosis of the carpal tunnel syndrome (CTS) were studied in asymptomatic hands contralateral to those objectively involved. The presence of dromic potential of "double peak" by stimulation of fingers 1 and 4, with detection of equidistant points of Median and Radial and Median and Cubital respectively, in the wrist, was the test demonstrating the earliest and most constant alterations. The detection of alterations with a frequency of subclinical character is of interest in the quantitative evaluation of CTS and in the recognition of the wide spectrum of the intensity of involvement of this compression syndrome.


[Delayed-action calcium antagonists and therapy of arterial hypertension]. Drug treatment of high blood pressure had important improvements is the last few decades, that allowed an efficiente control of hypertension, avoiding or stabilysing cardiovascular consequences. Non pharmacological management is always important; however most hypertensive patients need also drug treatment that is unavoiable in severe and in most cases of moderate hypertension. Borderline hypertension involves difficult decisions. Quantitative diagnosis of high blood pressure has been based on casual measurement. Non invasive ambulatory blood pressure measurement gives access to much more valures over the whole day and night periods, and has been an important tool for clinical research. However it implicates a correct assessment of the device's accuracy and calibration, and also a correct statistical treatment of the huge range of values obtained. Blood pressure control over the 24 hours is probably obtained with some long acting drugs. So, calcium antagonista are reviewed, exemplofying with slow release diltiazem. It has been prescribed twicely a day, and more recently once a day, what is considered by some authors quite adequate on the point of view of pharmacocinetics and pharmacodynamics. So the benefits depending on patient's compliance and the possible obliteration of hypertensive spikes may be important. There is perhaps, in the overall, reduction of health care costs, in what concerns hypertension.


Antihypertensive treatment and regression of atherosclerosis. Reduction of high blood pressure has an effect on coronary mortality and morbidity lower than expected. One of the possible explanations is the different anti-atherogenic capacity of anti-hypertensive drugs. Reduction of high blood pressure has, by itself, an anti-atherogenic effect, but, for some anti-hypertensive drugs, there is experimental and clinical evidence of anti-atherogenic properties. For calcium antagonists experimental data have been published reporting reduction of aortic lipidic deposition and decrease of arterial proliferation. The INTACT trial has shown that the development of new atherosclerotic lesions was delayed by nifedipine. For beta-blockers, in spite of the negative effect on atherogenic fractions, the experimental evidence, so far collected, suggests a possible anti-atherogenic effect. ACE inhibitors have been experimentally studied and its anti-atherogenic effect reported on studies with the WHHR rabbit and cynomolgus monkey. The different possible mechanisms for these anti-atherogenic properties are analysed. Ketanserine is a serotonin antagonist witch anti-atherogenic capacity is under investigation on the PACK trial. The results that were published so far seem to confirm that capacity.


[Doppler echocardiography in the diagnosis of mechanic complications of acute myocardial infarction]. To evaluate the ability of bedside emergency Doppler/Echocardiographic (ECOCG/DP) studies in the diagnosis of mechanic complications during acute myocardial infarction (AMI). Retrospective analysis of 44 fatal AMI cases, studied by ECOCG/DP and with diagnostic confirmation by surgery and/or necropsy. Patients (pts) with AMI admitted to an Intensive Care Unit of a tertiary Hospital (UCIM), Hospital de Santa Maria. 44 fatal AMI cases were analysed (24 men and 20 women; mean age +/- SD: 72 +/- 9 years) and were divided in two groups according to Killip classification in Group 1 (III/IV): 35 pts and Group 2 (I/II): 9 pts. ECOCG/DP was performed in a routine basis at admission, using all standard views and by subcostal view when in an emergency scenario. In 20 pts with bad left ventricular function (LVF) (Group 1) at admission, ECOCG/DP monitoring showed that death was due to worsening of LVF, which was confirmed by necropsy. In the other 15 pts of this group, ECOCG/DP documented the clinical diagnosis of cardiac rupture (free wall: 4 pts; papillary muscle: 4 pts; interventricular septum: 7 pts) which was confirmed by surgery and/or necropsy. In the 9 pts of Group 2, ECOCG/DP disclosed, at admission, good LVF in all. In 5 pts there was a sudden worsening clinical status, and ECOCG/DP showed a severe pericardial effusion with right chambers collapse, highly suggestive of free wall rupture also confirmed at necropsy. In the other 4 pts, ECOCG/DP showed aggravation of wall motion abnormalities and of LVF without rupture, once again in agreement with necropsy. Five clinical cases are presented for illustration of this issue. In the 44 fatal AMI cases of our study there was complete agreement between the ECOCG/DP and necropsy studies. In AMI patients, ECOCG/DP monitoring can in a routine basis, evaluate wall motion abnormalities and LVF. In an emergency setting ECOCG/DP can diagnose all the mechanic complications with a great certainty.