Primary pulmonary hypertension after amfepramone (diethylpropion) with BMPR2 mutation.

Primary pulmonary hypertension (PPH) is characterised by sustained elevations of pulmonary arterial pressure without a demonstrable cause, leading to right ventricular failure and death. Hereditary mutations in the bone morphogenetic protein receptor type II (BMPR2) gene result in familial PPH transmitted as an autosomal dominant trait, albeit with low penetrance. The causes in cases without a BMPR2 mutation are unknown, but a syndrome of pulmonary arterial hypertension (PAH) similar to hereditary PPH is associated with systemic connective tissue disease, congenital heart disease, portal hypertension, and human immunodeficiency virus infection, or with the use of appetite-suppressant drugs. The authors identified a BMPR2 gene mutation in a 27-yr-old female who developed PAH after a short course of the appetite-suppressant drug amfepramone (diethylpropion). This allowed molecular genetic counselling and prevention of potentially harmful drug exposure in the patient's son treated for attention deficit disorder with methylphenidate, an amphetamine-related drug. No BMPR2 mutation was found in four additional, unrelated patients with appetite suppressant-related PPH. The findings provide strong evidence that amfepramone can trigger primary pulmonary hypertension in a bone morphogenetic protein receptor type II gene mutation carrier, and indicate that other genes are probably implicated in genetic susceptibility to appetite suppressants.

Medical thoracoscopic lung biopsy in interstitial lung disease: a prospective study of biopsy quality.

The aim of this study was to analyse the quality and diagnostic value of lung biopsies for the diagnosis of interstitial lung disease (ILD), taken with diathermy coagulation cup forceps during medical thoracoscopy. Patients with ILD, not specified after thorough clinical assessment, high-resolution CT (HRCT), bronchoalveolar lavage and transbronchial biopsy, were studied. Medical thoracoscopy was performed in an endoscopy suite under neuroleptic anaesthesia with spontaneous ventilation. Biopsy specimens were analysed prospectively by one lung pathologist blinded to the clinical findings. Over 2 yrs, 118 samples were analysed from 24 consecutive patients. A good quality biopsy was obtained in 23 patients, and 78% of the samples were of good quality. Biopsy findings plus clinical and HRCT data revealed a relevant diagnosis in 18 patients and some diagnostic clues in four patients, for whom further examinations were needed. No major complications occurred. Chest tube drainage averaged 5.3+/-4.7 days, and was related to the total lung capacity (p=0.008), which mirrors the severity of ILD. Separate sampling of biopsies from different lobes proved to be useful in one third of the cases. In conclusion, lung biopsy sampling can be performed safely by interventional pulmonary endoscopists and has a good diagnostic yield in interstitial lung disease of unknown origin.

Long-term treatment with cyclosporin A and coumarin in pulmonary thromboembolic Behçet's disease.

Long-term favourable effects of a treatment with both cyclosporin A and coumarin in a 35 year old Caucasian female patient with Behçet's disease, presenting with haemoptysis caused by pulmonary thromboemboli and a single major pulmonary artery aneurysm, are reported. All disease activity and complications were well controlled during 9 years of follow-up.

Chronic lymphocytic alveolitis with migrating pulmonary infiltrates after localized chest wall irradiation.

In a number of patients, radiotherapy following surgery for breast carcinoma may induce radiation injury to the lungs. This has classically been divided into an early radiation pneumonitis and a late fibrosis, both confined to the irradiated lung volume. However we observed a female patient who similarly to other recent reports in the literature developed a recurring pneumonitis migrating from one lung to the other after radiotherapy for breast carcinoma. This migratory BOOP (bronchiolitis obliterans organizing pneumonia) was characterized by a lymphocytic alveolitis and responded well to corticosteroids. Clinicians should be aware of the possibility of a lymphocytic pneumonitis in both lungs after unilateral thoracic irradiation and recognize the distinctive features of fever, cough, dyspnoea and malaise in order to start an effective treatment with corticosteroids. They should also be aware of the high tendency for recurrence when tapering off.

Vitamin K prophylaxis in less developed countries: policy issues and relevance to breastfeeding promotion.

Vitamin K prophylaxis prevents hemorrhagic disease of the newborn. The present review estimates the potential magnitude of this problem in less developed countries, assessing the need for prophylaxis, along with its cost-effectiveness and feasibility. Late hemorrhagic disease, occurring between 2 and 12 weeks, often leads to death or permanent disability. Its median incidence in developed countries is 7 per 100,000 births. Incidences in less developed countries may be much higher. Three incidence scenarios are proposed and the corresponding losses of disability-adjusted life-years (DALYs) calculated. Under the intermediate scenario, late hemorrhagic disease accounts for 0.1% to 0.2% of DALYs lost to children less than 5 years of age. Assuming a cost of +1.00 per injection, each DALY saved would cost +133. Decisions on prophylaxis must be made on a national basis, considering mortality levels and causes, health budgets, and feasibility. Comparison with the impact of diseases prevented by breast-feeding shows that concern with hemorrhagic disease should not affect breast-feeding promotion efforts, although strategies for supplementing breast-fed infants must be explored.

[Prevention of gas microemboli during cardiac surgery. Numerical control of cardiac cavity purging by an ultrasonic detector]. / Prévention des micro-embolies gazeuses en chirurgie cardiaque. Contrôle numérique du débullage des cavités cardiaques par détecteur à ultra-sons.

Despite all precautions taken by cardiac surgeons to eliminate air remaining in the cardiac cavities and pulmonary veins at the end of cardiopulmonary bypass, many micro bubbles probably remain and pass into the systemic circulation with a risk of deteriorations of cerebral or myocardial function. Over the last four years we have used ultrasound to try to prevent the risk of preoperative gas microemboli: the machine is equipped with a detector (a quartz oscillator coupled to a piezoelectric transducer emitting a continuous beam of ultrasound at a frequency of 5 Mhz) which allows the following variables to be determined: the time interval from the onset of detection, the total quantity of bubbles (arbitrary units) in the examined regions, the quantity of bubbles detected over a given time interval which can be adjusted from 15 to 120 seconds. The passage of bubbles is also indicated by light and sound alarms. The smallest diameter of bubbles which can be detected is about 10 mu. There are periaortic probes adaptable to the calibre of the ascending aorta, transcutaneous probes for carotid artery detection and a left ventricular probe. In a preliminary series of 74 valve replacements in adults, this apparatus was used immediately after terminating cardiopulmonary bypass after we had thought that the cardiac cavities had been satisfactorily purged of air, and whilst active aspiration was continued in the ascending aorta distal to the periaortic probe: the total quantity of bubbles detected varied from less than 50 to more than 2000 AU, over a variable period of time which may exceed 20 min after termination of cardiopulmonary bypass. The total quantity of bubbles recorded after mitral valve (582 +/- 154 AU) or combined mitral and aortic valve replacement (685 +/- 167 AU) was generally greater than after isolated aortic valve replacement (335 +/- 126 AU). Therefore, after cardiopulmonary bypass, and despite all efforts at purging the air, we showed that numbers of microbubbles were ejected into the ascending aorta for a variable period of time: only some of them were eliminated by active aspiration through a trocar placed distal to the periaortic probe. The right coronary ostium was poorly protected against microbubbles because of its anatomical situation (6 cases in this series). We therefore established a protocol for the use of this apparatus to aid the purging of the cardiac cavities and pulmonary veins before stopping cardiopulmonary bypass: the manoeuvres, guided by the ultrasound probes, are performed before the left ventricle is allowed to eject blood into the ascending aorta.(ABSTRACT TRUNCATED AT 400 WORDS)

[Use of the Kimray-Greenfield filter in the prevention of pulmonary embolism]. / Utilisation du filtre de Kimray-Greenfield dans la prévention de l'embolie pulmonaire.

The authors analyse the results of the application of 14 Kimray-Greenfield filters; there was neither pulmonary embolism, nor thrombosis of the vena cava inferior nor any other complication. These good results, like those of much more important series which have recorded, prompt us to use the Kimray-Greenfield filter in normal cases. The authors also think that the qualities of the filters mean that they can be used systematically in a preventive capacity, in certain cases where the risk of serious thrombo-embolic illness is especially high and impossible to prevent effectively, owing to specific circumstances.

[Experimental study in anesthetized dogs of the harmful effects of coronary microemboli and their prevention by drugs]. / Etude expérimentale chez le chien anesthésié de la nocivité des microembols coronaires et de leur prévention pharmacologique.

The present experiments have been performed in anesthetized dogs. They have allowed to determine the nocivity of air microembolus introduced directly in the circumflex branch of the left coronary artery. It has been suggested that to reduce post-operative disease due to microembolus at the end of an extracorporal circulation it is necessary to forbid the injection of isoprenalin and to realize a perfusion of papaverine.

[Prognosis following mitral valve replacement with the Starr-Edwards 6120 prosthesis]. / Facteurs pronostiques après remplacement valvulaire mitral par la prothèse de Starr-Edwards modèle 6120.

Between 1970-78, 302 mitral valve replacements with the SE 6120 prosthesis were performed, with an average postoperative follow-up of 50,7 months, using the 3 M size (206 cases) and 2 M (96 cases with small left ventricles). Early postoperative mortality was 5,6%, late postoperative mortality: 17,2%, the 5 year actuarial survival rate: 77,4% and the 9 year survival rate 71,8% (early mortality included). There was no significant difference in survival after mono- (143 cases) and polyvalvular replacement (159 cases); only a voluminous left atrium (p less than 0,05) and left atrial thrombosis (p less than 0,01) were statistically significant prognostic factors of global mortality. Late haemorrhage due to anticoagulant therapy (3%) (0,6 per 100 patient years). The most common complication was systemic embolism (3,7 per 100 patient years). Actuarial studies showed that 86,6% at 5 years and 80,1% at 9 years, escaped this complication. Statistically the favorising roles of permanent atrial fibrillation (p less than 0,05), the size of the left atrium (p less than 0,02) of isolated demonstrated. 90,4% of the survivors were clinically improved: the functional result was better when that 86,6% at 5 years and 80,1% at 9 years, escaped this complication. Statistically the favorising roles of permanent atrial fibrillation (p less than 0,05), the size of the left atrium (p less than 0,02) of isolated demonstrated. 90,4% of the survivors were clinically improved: the functional result was better when that 86,6% at 5 years and 80,1% at 9 years, escaped this complication. Statistically the favorising roles of permanent atrial fibrillation (p less than 0,05), the size of the left atrium (p less than 0,02) of isolated demonstrated. 90,4% of the survivors were clinically improved: the functional result was better when the valve replacement was not a reoperation (p less than 0,02), when the patient was not in functional Class IV (p less than 0,01), in permanent excessively dilated (p less than 0,01) and in patients without severe tricuspid regurgitation (p less than 0,01). There was no significant difference in global mortality, the percentage of embolic events and the quality of the functional postoperative result between patients with the 3 M and those with the 2 M SE 6120 prosthesis.

[Early and late term results of triple valve replacements. Use of a tricuspid bioprosthesis]. / Résultats précoces et tardifs des triples remplacements valvulaires. Utilisation d'une bioprothèse en position tricuspidienne.

Triple valve replacement (TVR) is associated with an increased operative and long-term mortality rate. The aim of this study was to reduce operative mortality by effective myocardial protection (coronary perfusion with moderate hypothermia) and to improve long-term results by the optimal choice of valve prosthesis and, in particular, by the systematic use of xenografts for tricuspid valve replacement. Twenty TVR were performed between 1970 and 1977. Björk-Shiley prostheses were used for aortic valve replacement, Starr Edwards 6120 valves for mitral valve replacement and xenografts (7 aortic valve and 13 Hancock xenografts) for tricuspid valve replacement. This series represented 3.2% of the total number of valve replacements carried out during this period. The average postoperative follow-up was 52.6 +/- 15.2 months. Only one patient died in the first postoperative month (early mortality 5%). There were 2 late deaths, one from heart failure and one from accidental causes; the actuarial 5 year survival rate was 87.9%. Seventeen long-term survivors were studied; 6 were functionally improved. Significant (p less than 0.02) but moderate regression of cardiomegaly was observed. Abnormal auscultatory findings in the tricuspid area were found in 64.7% of survivors, and signs of mild right ventricular failure were elicited in 30.4%. There were no early or late complications due to the tricuspid valve xenograft. Thirteen patients had cardiac catheterisation over one year after operation: right atrial and mean pulmonary artery pressures were significantly reduced (p less than 0.001 and p less than 0.01 respectively); there was a moderate increase in cardiac index( p less than 0.001). Late clinical complications were rare, only one regressive cerebral embolism was observed. Triple valve replacement, when necessary, carried a limited early postoperative risk, and satisfactory functional and haemodynamic results may be obtained in the long term.

[Radiation-induced intestinal lesions. Prognosis and surgical management (author's transl)]. / Lésions radiques intestinales. Critères pronostiques et attitude thérapeutique.

Thirteen patients with intestinal lesions consecutive to radiotherapy for carcinoma of the uterus were operated upon between 1973 and 1979. The small bowel was involved in 9 patients and the colon and rectum in 4 patients. Urinary tract lesions were associated in 3 patients of each group. Intestinal necrosis, progression of the lesions and extensive pelvic fibrosis were the only criteria of poor prognosis. Twenty-two operations were performed: 4 for urinary tract lesions and 18 for intestinal lesions. Five patients died during the immediate post-operative period and five died within 2 to 30 months after surgery, including 4 whose carcinoma recurred. The operative technique should be selected according to the extent and severity of radiation-induced damage, as determined by pre-operative examination and thorough exploration of the abdominal cavity once opened. Limited lesions of the small bowel can be treated by resection, but intestinal bypass with latero-lateral anastomosis seems to be preferable in cases with extensive lesions. Patients with colorectal lesions should have defunctioning colostomy prior to any other procedure dictated by the state of affairs. Multiple anastomosis, extensive resections and excessive dissections should be avoided.

[Tricuspid valve replacement with aortic valve allograft. Clinical and haemodynamic results more than five years after (author's transl)]. / Remplacement de la valve tricuspide par homogreffe valvulaire aortique. Résultats cliniques et hémodynamiques à plus de 5 ans.

Between 1970 and 1974, twenty-three patients with advanced multivalve lesions underwent tricuspid valve replacement with a human aortic valve allograft (26-28 mm in diameter) mounted on a Shumway ring. The mean follow-up was 76.7 months. Early post-operative mortality was 4.4% and late mortality 17.4%. The actuarial survival rate was 86.6% at 5 years and 74.2% at 8 years. In 1979, 17 out of 18 survivors (one was lost sight of) were reinvestigated by cardiologists. Late functional improvement z found in 82.2% of the cases; two patients failed to improve owing to recurrent mitral stenosis. On clinical examination 12 out of 15 subjects showed no sign of right ventricular failure. In 54% the cases phonocardiography revealed abnormal tricuspid sounds indicating variable and moderate deterioration of the allograft. Haemodynamic studies showed a significant decrease in mean right atrial pressure (p less than 0.001) and mean pulmonary artery pressure (p less than 0.001), and an increase in cardiac index (p less than 0.01). The diastolic gradient through the graft was always inferior to 3 mmHg (mean 1.2 mmHg), with little change on exercise. This was significantly less than the 3.9 mmHg gradient observed with tricuspid valve replacement using Hancok valve. These were the only tricuspid valve replacements performed in our unit in 1970-74. The satisfactory long-term results obtained contrast with the frequent deterioration observed in aortic valve replacements carried out during the same period by the same team, using the same technique

[Stenosis of the left main coronary artery. Results of aorto-coronary by-pass in 67 patients (author's transl)]. / Sténose du tronc coronaire gauche: résultats des pontages aorto-coronaires chez 67 malades.

Between 1970 and 1978 sixty-seven patients with > 50% stenosis of the left main coronary artery underwent aorto-coronary by-pass operation. The mean follow-up period was 54.7 months. Early and late post-operative mortality rates amounted to 3% and 9.2% respectively. Severe global alteration of left cineventriculography was the primary factor of survival (p < 0.01). The actuarial survival rates were 90.3% at 5 years and 84.5% at 9 years. All survivors had control ECGs. Late myocardial necrosis was rare (0.6 per 100 patient-years). 60.3% of the patients remained free from angina. Deterioration of the results mainly occured during the first 2 years but continued at a slower pace beyond the 8th year. Recurrence of angina was significantly less frequent in patients with isolated left main stenosis (p < 0.05) and when local conditions were not unfavourable to derivative surgery (p. < 0.01). On the other hand, the patient's age, sex, type of angina, history of previous infarction, number of risk factors and number of by-passes (the latter excluding possibly incomplete revascularisation) has no influence on the functional prognosis. Thirty-two patients had control, usually routine coronary arteriography 13.7 months on average after surgery. Overall patency was found in 85.9% and abnormal grafts in 16.7% of the cases. The main benefits of aorto-coronary by-pass, therefore, were a reduction in the spontaneous mortality rate of patients with left main coronary disease and a pronounced functional improvement.

[Comparative study of myocardial protection by coronary perfusion in deep hypothermia (10 degrees C) with or without potassium cardioplegia. Clinical, electrocardiographic, enzymatic results; biochemical and histological controls]. / Etude comparée de la protection myocardique par perfusion coronaire en hypothermie profonde (10 degrees C) avec ou sans cardioplégie au potassium. Résultats cliniques, électocardiographiques, enzymatiques, contrôles biochimiques et histologiques.

A technique of coronary perfusion with diluted blood, giving homogenous myocardial cooling (10-12 degrees C) under lignocaine perfusion, with or without potassium (K) cardioplegia is presented. The first 75 operated cases were used to adjust the optimal lignocaine (5 mg/min) and K (2 meq/min in continuous coronary perfusion, 5 meq/min in discontinuous coronary perfusion) dosage in the myocardial protection circuit. Then, 123 operated patients (78 aortic valve replacement, 30 mitro-aortic double valve replacement, 15 other operations on the ascending aorta) were classified into four groups prospectively: 1. Continuous coronary perfusion 10 degrees C, 2. Continuous coronary perfusion 10 degrees C with associated K cardioplegia, 3. Discontinuous coronary perfusion 10 degrees C, 4. Discontinuous coronary perfusion 10 degrees C with K cardioplegia. The best return of cardiac activity was observed in Group 1 and this was statistically significant with a high percentage of spontaneous heart beating after declamping the aorta (average 10 minutes), immediate efficacity of left ventricular contraction, and absence of arrhythmias, especially the transient conduction defects observed with K cardioplegia. In Group 1, during mitro-aortic valve replacement, after over 60 minutes aortic clamping, no significant reduction of ATP or myocardial phosphocreatinine or changes of hexosemonophosphates were observed, contrary to the findings after 15 minutes aortic clamping at 28 degrees C in a control group of mitral valve replacements (n = 10). Myocardial changes on electron microscopy in the subendocardial region of the left ventricle were minimal or absent, especially with respect to the mitochondria. The early post-operative course was the same in all four groups: of the 123 patients operated, early mortality was 2.4 p. 100 (1.6 p. 100 from intercurrent causes), severe arrhythmias were observed in 1.6 p. 100, supraventricular arrhythmias in 4.9 p. 100, myocardial infarction in 0.8 p. 100, electrocardiographic ischaemia in 0.8 p. 100, and atrioventricular block in 0.8 p. 100. The average enzyme level (CPK, SGOT, LDH) in the early postoperative period were low, with no correlation with the duration of aortic clamping.

[Myocardial protection by perfusion in deep hypothermia (10 degrees C) with or without cardioplegia (author's transl)]. / Protection myocardique par perfusion en hypothermie profonde (10 degrees C) avec ou sans cardioplégie.

A technique of myocardial protection using a perfusion circuit in deep hypothermia via the ascending aorta or by selective cannulation of the coronaries has been used over a period of 2 years in almost 200 patients undergoing surgery requiring prolonged aortic clamping. It ensures rapid and homogeneous cooling of the myocardium (10-12 degrees C) and meets its reduced oxygen needs. It may be completed by cardioplegia (infusion of potassium chloride or lidocaine using an automatic syringe at a determined level). This simple technique permits a rapid spontaneous return of normal effective cardiac action. No low cardiac output syndromes have been seen since it has been used. Laboratory, histological, biochemical and haemodynamic studies carried out have confirmed its harmless nature.