Mild Pelizaeus-Merzbacher disease caused by a point mutation affecting correct splicing of PLP1 mRNA.

We describe a 28-year-old male patient with a mild course of Pelizaeus-Merzbacher disease (PMD) who presented with developmental delay in his second year of life and was able to walk until 12 years of age. Several computed tomography scans in infancy and youth were normal, the diagnosis of PMD was eventually suggested by magnetic resonance imaging at the age of 24 years. Analysis of the proteolipid protein gene (PLP1) revealed a nucleotide exchange (c.762G>T) at the 3' border of exon 6, which did not entail an amino acid exchange but adversely affected splicing. PCR analysis of fibroblast cDNA showed that c.762G>T resulted in partial skipping of exon 6 in the PLP1 mRNA. Exclusion of exon 6 does not alter the reading frame but leads to absence of amino acids 232-253 that constitute a main part of the fourth transmembrane helix of the PLP protein. Remarkably, residual wild-type splicing was also detected in the patient's cultured fibroblasts. This might explain the mild phenotype in this case, as exon 6 skipping mutations resulted in a severe course of disease in other patients.

Developments in cardiac surgery in Stockholm during the mid and late 1950s.

In 1951 in our laboratory in Stockholm, we successfully used our experimental pump oxygenator: the first dogs survived 40 minutes of total cardiopulmonary bypass with right ventricular cardiotomy. In the same year extracorporeal circulation was combined with hypothermia (26 degrees to 28 degrees C) to allow lower perfusion flows, thus diminishing blood trauma and the risk of perfusion complications. To avoid air emboli during cardiotomies, the heart was "arrested" with electrically induced ventricular fibrillation (1952). Our standard perfusion technique used cooling and rewarming with left ventricular bypass, the oxygenator was used only during intracardiac manipulations and when the right ventricle was unable to maintain a sufficient pulmonary circulation. Left ventricular bypass was continued until normal body temperature was reached and the heart could be weaned off the pump. In July 1954 we successfully extirpated a left atrial myxoma in our first patient undergoing open heart surgery, a 40-year-old woman, who is still alive today. Other successful applications of open heart surgery involved resection of a huge left ventricular aneurysm after infarction in 1955, correction of supracardiac total anomalous venous return in 1956, and the first hemodynamic correction of transposition of the great arteries by atrial switch method in 1958. Also in 1958, the first totally implantable pacemaker was inserted in a patient with total atrioventricular block to eliminate the infections that occurred along the percutaneous pacemaker leads. In October 1958, we also operated on a patient with severe angina pectoris with stenosis of the left anterior descending and circumflexed arteries and occluded right coronary artery. Endarterectomy of the left coronary arteries was performed, and the arteriotomies were repaired with saphenous vein patches.

Long-term outlook after atrial correction of transposition of great arteries.

Late results were reviewed in 220 survivors after atrial correction of transposition of the great arteries who were operated between 1964 and 1985. Senning's procedure and its various modifications have been used; all patients who survived 30 days after correction were included in this analysis. Average follow-up for the whole group was 10.3 years; 113 patients were observed for 10 years, 26 patients for 15 years, and 8 patients for 20 years. The actuarial survival rate for the whole group was 89% at 10 years, 87% at 15 years, 82% at 20 years. It was higher in simple than in complex transposition (92% versus 84% at 10 years). Sudden deaths (8 patients) and late heart failure (6 patients) were the principal causes of death, predominantly in the complex transposition group (10/13 deaths). Late survival was more common in the latter part of the study, with 95% of patients operated on after 1978 surviving 9 years as opposed to 84% of patients operated on earlier. Late reoperation was necessary in 18 patients (8%), with 12 reoperations occurring within 2 years after correction. Cumulative reoperation rate reached 11.7% after 10 years. Reoperations were more common in complex than in simple transposition (14% versus 6%, p less than 0.05). Late arrhythmias can occur after atrial correction, and the cumulative incidence of pacemaker implantations was 8% at 10 years. Most of the survivors are functionally free of symptoms (83% of the simple and 75% of the complex transposition group). Significant tricuspid valve incompetence was encountered in only three patients, with two valve reconstructions being possible. In summary, long-term outlook for survivors of atrial correction for transposition of the great arteries remains encouraging, although complex transposition does seem to engender more late problems. Atrial correction is still warranted in simple transposition, but close cardiological surveillance is necessary.

Transcaval liver resection with hepatoatrial anastomosis for treatment of patients with the Budd-Chiari syndrome. Late results.

Between 1980 and 1990 transcaval liver resection with hepatoatrial anastomosis was performed in 17 patients with the Budd-Chiari syndrome. There were two early deaths (early mortality 11.7%). Hepatic function returned to normal and hepatosplenomegaly disappeared in all but two patients with preexisting cirrhosis. All survivors regained normal working capacity after the operation. During an average follow-up of 6 years (7 months to 11 years) there were three late deaths due to progression of the underlying disease. The actuarial 1-, 5-, and 10-year survivals were 82%, 76%, and 57%, respectively. Hepatoatrial anastomosis represents an optimal treatment for patients with the Budd-Chiari syndrome and obstruction of major hepatic veins. Patients with compression of the inferior vena cava, very common in this disease, were treated by simultaneous transcaval stenting. The late results are very satisfactory, with excellent quality of life. With adequate hepatic function, results of hepatoatrial anastomosis are superior to those of liver transplantation, which represents the only alternative for patients with the advanced form of the Budd-Chiari syndrome.

Psychomotor and intellectual development after deep hypothermia and circulatory arrest in early infancy.

Somatic, psychomotor, and intellectual development were studied in 11 patients who had total correction of congenital cardiac malformation in early infancy by the method of surface-induced deep hypothermia and circulatory arrest up to 43 minutes. Time between operation and re-evaluation ranged from 3 to 11 years (average 7 years). Somatic development was normal in all children. Psychomotor and intellectual behavior, measured by a battery of specially adapted test methods, failed to show a statistically significant difference when compared between the study group, a matched control group, and the normal population. Normal scores in psychomotor tests and normal intelligence quotients (I.Q.) were present in 8 patients; mental retardation was found in 2 patients: and unstable behavior, evident from different tests, was present in one. Except for the last case, in none of the patients was the method was found to be the primary cause of the abnormal behavior. Deep hypothermia and circulatory arrest in early infancy does not appear to have a negative influence on somatic, psychomotor, or intellectual development.

Left anterior thoracotomy for pulmonary embolectomy with 29-year follow-up.

Pulmonary embolectomy is usually performed in cardiopulmonary bypass. In acute situations too much time can be lost in setting up and connecting the pump oxygenator; this delay can cause cerebral damage in a patient with circulatory arrest. In such a situation left anterior thoracotomy can provide an ideal approach. An emergency thoracotomy can be performed in a few seconds. The lung automatically retracts. The phrenic nerve, pulmonary artery, and pericardium are clearly seen, and they outline the area for embolectomy. A case in which such an approach was successfully used is described.

The role of the surgeon in percutaneous transluminal dilation of coronary stenosis.

Percutaneous transluminal dilation (PTD) of coronary artery stenosis is performed by means of a balloon-tipped catheter introduced from a peripheral artery. It was attempted in 45 patients; stenosis was passed in 33 and was successfully dilated in 28 patients (62%). The method failed in 17 patients: in 6 of them an abrupt closure of a stenosed artery or a beginning infarction necessitated an emergency revascularization. There were no deaths or serious complications, but an infarction developed in 1 patient despite immediate bypass grafting. PTD was successful in 5 out of 7 patients who had recurrent angina after previous coronary bypass grafting: in 2 of them stenosis of a distal coronary artery and in 3 a stenosed bypass graft were dilated. PTD is a new method of treatment of coronary artery disease and is an addition rather than an alternative to coronary bypass grafting. The best results can be expected in patients with single-vessel disease, with a short history of angina (less than 1 year), and with narrow, noncalcified proximal stenosis. Some late complications of bypass grafting are also amenable to this method of treatment.

The ascending aortic aneurysm: replacement or repair?

Between 1971 and 1980, 100 patients underwent operation for ascending aortic aneurysm. Acute dissection was present in 29, chronic dissection in 11; 56 had dilatation only, and 4 had inflammatory disease of the ascending aorta. Four different operative procedures were applied independent of the type of disease: repair and reduction aortoplasty (21), reduction aortoplasty reinforced by nylon net (17), supracoronary graft replacement (42), and composite graft replacement with reimplantation of both coronary ostia (20). Early mortality was 10%, and late mortality was 12% after a mean follow-up of 45 months. Retrospective comparative analysis of the four operative methods led to the following conclusion: reduction aortoplasty supported by a tightly wrapped synthetic net is a suitable method in patients with a normal sinus of Valsalva and without dissection or inflammatory disease. Particular attention needs to be drawn to the proximal anchor stitches to avoid late net displacement. Compared with supracoronary or composite graft replacement, this method carried a lower complication rate, particularly in regard to cerebrovascular accidents and myocardial infarction. For patients with acute and chronic dissection with intact aortic root, supracoronary graft replacement is preferred, whereas in those with annuloaortic ectasia with dilated sinus of Valsalva and in all patients with Marfan's syndrome, composite graft replacement has become the procedure of choice.

Cardiac pacing in retrospect.

As precursors of permanent pacemakers, Lidwill (1929) and Hyman (1932) introduced temporary pacemakers for resuscitation. Callaghan (1950) intravenously paced the sinus nodal region for bradycardia in hypothermic dogs. Zoll (1952) used external electrodes to treat Adams-Stokes attacks, and Lillehei (1957) fixed stainless steel electrodes to the myocardium, successfully treating iatrogenic total atrioventricular block with a percutaneous pacemaker. Since 1951, by experimental and clinical use of ventricular fibrillation to obtain a functional cardiac standstill during open heart surgery, we used all known methods of stimulation to treat asystole or bradycardia after defibrillation. Since 1957, percutaneous stimulation by Adam-Stokes attacks has been performed. The most serious complication is infections along the electrodes causing death from sepsis. The solution of the problem was the implantation of the pacemaker and its energy supply. Percutaneous leads were used to study the different parameters for electric stimulation and to find the lowest frequency (to spare energy) with the best variation of cardiac output. In October 1958 in Stockholm a fixed rate pacemaker was implanted by thoracotomy. At present, the patient is living with his 23rd pacemaker. Four additional patients had pacemaker implantations until 1960. In 1961, Chardack and Greatbach successfully implanted pacemakers with mercury batteries. Johanson and Lagergren connected the pacemaker to an intravenous electrode to avoid thoracotomy. The enormous development in the electronic field made more elaborate pacemakers possible, and eliminated the risk of the fixed rate (interference, repetitive firing, and ventricular fibrillation).

Enzymatic and nonenzymatic in vitro hydrolysis of 2-methyl-2-[2-(methoxy)phenoxy]-4H-1,3-benzodioxin-4-one and 2-methoxyphenyl O-acetylsalicylate.

This paper is concerned with the synthesis and physical properties as well as the enzymatic and nonenzymatic in vitro hydrolysis of the potential aspirin prodrug MR 693 (5) and the salicylic acid prodrug guacetisalum (6). The half-lives of both prodrugs and the amount of aspirin regenerated in each hydrolytic run for 5 have been estimated over a wide range of pH values.

Late failure of systemic ventricle after atrial correction for transposition of great arteries.

The incidence of late systemic ventricular failure (SVF) was determined in 220 early survivors of atrial correction for transposition of great arteries (TGA), operated upon between 1964 and 1985. SVF was defined as either severe heart failure (NYHA class III or IV) or death due to the same cause, in the absence of other haemodynamic disturbances. The actuarial survival rate was 96% after 1, 94% after 5 and 87% after 10 years. SVF occurred in 16/220 patients (7.2%). SVF was more common in complex TGA (TGA + VSD or PS or both) with 11/99 patients (11%) than in simple TGA with 5/121 patients (4.1%), P less than 0.01. Actuarial freedom from SVF was 97% at 5, and 92.5% at 10 years. SVF caused 10/25 (40%) late deaths. SVF occurred from the 1st postoperative year up to 20 years after correction (average interval 6.3 years). In 1 of 2 patients a systemic atrioventricular (AV) valve annuloplasty did not improve SVF. Heart transplantation was performed in 2 patients and 1 is on the waiting list. SVF is a rare late complication of atrial correction for TGA with a constant incidence in the late course. SVF is more common in complex TGA.

[Angio-follicular lymph node hyperplasia (Castleman's lymphoma)]. / Angiofollikuläre Lymphknotenhyperplasie. (Castleman-Lymphom).

Two patients with angio-follicular lymph node hyperplasia are described, and the literature is reviewed. In one symptom-free man, the chest x-ray showed a tumour of the upper mediastinum the size of a fist (which is known to have been present for 20 years), in another man there was a 4 cm. node in the right hilum, which was shown by computer tomography not to be due to vessels. In each case the tumour was removed. Histologically they proved to be a hyaline-vascular type of angio-follicular lymph node hyperplasia. This is probably an inflammatory-reactive process.

[Spurious aneurysm after myocardial infarct]. / Das Aneurysma spurium nach Myokardinfarkt.

False aneurysms of the left ventricle after myocardial infarction arae the result of perforation, which usually require early surgical treatment. The clinical features are not characteristic. The chest x-ray may provide important evidence for the diagnosis. Non-invasive diagnosis is possible by means of echocardiography and computer tomography; it is confirmed by angiocardiography. The authors experience with nine cases is described.

Evaluation of a fluid-controlled artificial heart.

The Zurich A. H. is a pneumatic drive biventricular cardiac prosthesis with tubular silicone rubber membrane, tilting discvalves, and fluid control system. Membrane position is monitored throughout the cardiac cycle to prevent systolic membrane collapse or insufficient diastolic filling. This A. H. was implanted in 25 dogs weighing 23-50 kg. In five animals, the A. H. performed satisfactorily for more than 24 hr. At an average flow rate of 60-90 ml/min per kg, the aortic pressure ranged from 80 to 100 mm Hg, and both left and right atrial pressures were within normal range. The animals were awake, and they breathed spontaneously after 24 hr; average plasma hemoglobin levels averaged 91 mg/100 ml, and platelet counts decreased to 65,000 cu mm. In three animals subjected to the A. H. pump for 24 hr, the A. H. was removed and replaced with a transplant. Adequate transplant function was obtained, but there were no long-term survivors. Adequate hemostasis, sepsis, and complex organ dysfunctions associated with prolonged pumping are currently the main biologic problems.

Effects of left heart bypass on cardiac performance following myocardial ischemia.

A series of nine dogs underwent 20 minutes of myocardial ischemia by cross clamping the aorta while total cardiopulmonary bypass. The four dogs that did not have subsequent left bypass all showed a deterioration of ventricular function curve 30 minutes after restarting the heart beat when compared to their own preischemic values. The five animals which were supported for 30 minutes in left heart after bypass all showed essentially unchanged cardiac function after bypass. This study suggests that an improvement of myocardial performance after ischemic damage can be achieved with left heart bypass.

The helix filter: a new vena caval filter for the prevention of pulmonary embolism.

The helix caval filter is a continuous band spiral composed of a highly elastic metal alloy. A vertical double-helix coil fixes the filter in the infrarenal vena cava by elastic expansion while a watch spring type horizontal coil works as the filtering element. The diameter of the filter can be reduced by torsion from 32 to 7 mm. Transvenous implantation was performed under fluoroscopy using a newly developed instrument featuring intraoperative angiographic control, high flexibility, a guidance system, and a well-controlled release mechanism. The filter and the implantation technique were tested in a circulation system and in 10 dogs and 4 calves (follow-up 3-91 days). In addition, two filters were released intentionally into the right atrium of a dog and a calf. Flow resistance of the filter is negligible up to more than 10 1/min. Thrombi larger than 3.5 mm were filtered out reliably. Lethal complications, filter migrations or perforations did not occur in animal experiments. Filter coils which are in contact with the vessel wall become firmly incorporated within 3 to 4 weeks. The patency rate of the vena cava was 80% (8/10) for dogs and 100% (4/4) for calves. Implantations in the right atrium did not cause any symptoms. The filter's design allows fixation without hooks or spikes and consequently makes transvenous extraction possible up to 7-10 days after implantation. Comparable clinical results could extend the indications for caval filter implantation, and the decision which is still difficult today could be made easier.

Tetralogy of Fallot: to patch or not to patch?

Angiograms of 11 patients with Tetralogy of Fallot were reviewed before and after total repair, and analyzed with respect to growth of the pulmonary valve annulus. At the operation none of the patients was more than 5-years-old, none received a transannular patch and all were asymptomatic at the last visit. The radiologic diameter of the pulmonary valve annulus was compared to the descending thoracic aorta at the level of the diaphragm. Preoperative ratio averaged 1.09 +/- 0.22 and increased postoperatively to 1.35 +/- 0.20 (p less than 0.02). A "catch-up" growth of small annuli could be demonstrated.

[Results and complications of bronchoplastic operations for bronchial cancer (author's transl)]. / Résultats et complications des opérations bronchoplastiques pour cancer bronchique.

Among 1548 patients hospitalized from 1964 to 1975 for bronchial carcinoma, 779 underwent a brochopulmonary resection. Seventeen patients underwent bronchoplastic resections. The average hospital stay was 45 days which is explained by the frequency of postoperative complications (n = 8). The mortality during hospitalization was 11.5% and the 5 year survival rate was 18%. The survival curved was comparable to that of the patients who underwent a lobectomy or simple or enlarged radical pneumectomy. Actually, the average survival is 26 months and the comfort in these cases is impressive. We consider that the indication for these plastic resections should be extended to patients who are capable of tolerating a pneumectomy.