SummaryBackgroundBullous pemphigoid is a blistering skin disorder with increased mortality. We tested whether a strategy of starting treatment with doxycycline gives acceptable short-term blister control while conferring long-term safety advantages over starting treatment with oral corticosteroids.MethodsWe did a pragmatic, multicentre, parallel-group randomised controlled trial of adults with bullous pemphigoid (three or more blisters at two or more sites and linear basement membrane IgG or C3). Participants were randomly assigned to doxycycline (200 mg per day) or prednisolone (0·5 mg/kg per day) using random permuted blocks of randomly varying size, and stratified by baseline severity (3–9, 10–30, and >30 blisters for mild, moderate, and severe disease, respectively). Localised adjuvant potent topical corticosteroids (<30 g per week) were permitted during weeks 1–3. The non-inferiority primary effectiveness outcome was the proportion of participants with three or fewer blisters at 6 weeks. We assumed that doxycycline would be 25% less effective than corticosteroids with a 37% acceptable margin of non-inferiority. The primary safety outcome was the proportion with severe, life-threatening, or fatal (grade 3–5) treatment-related adverse events by 52 weeks. Analysis (modified intention to treat [mITT] for the superiority safety analysis and mITT and per protocol for non-inferiority effectiveness analysis) used a regression model adjusting for baseline disease severity, age, and Karnofsky score, with missing data imputed. The trial is registered at ISRCTN, number ISRCTN13704604.FindingsBetween March 1, 2009, and Oct 31, 2013, 132 patients were randomly assigned to doxycycline and 121 to prednisolone from 54 UK and seven German dermatology centres. Mean age was 77·7 years (SD 9·7) and 173 (68%) of 253 patients had moderate-to-severe baseline disease. For those starting doxycycline, 83 (74%) of 112 patients had three or fewer blisters at 6 weeks compared with 92 (91%) of 101 patients on prednisolone, an adjusted difference of 18·6% (90% CI 11·1–26·1) favouring prednisolone (upper limit of 90% CI, 26·1%, within the predefined 37% margin). Related severe, life-threatening, and fatal events at 52 weeks were 18% (22 of 121) for those starting doxycycline and 36% (41 of 113) for prednisolone (mITT), an adjusted difference of 19·0% (95% CI 7·9–30·1), p=0·001.InterpretationStarting patients on doxycycline is non-inferior to standard treatment with oral prednisolone for short-term blister control in bullous pemphigoid and significantly safer in the long-term.FundingNIHR Health Technology Assessment Programme.

The surgical treatment of an aneurysm of the abdominal aorta is a well-established procedure with fairly clear-cut indications and limitations. Treatment of an aneurysm of the thoracic aorta, on the other hand, is a more hazardous procedure that requires partial or total cardiac bypass with hypothermia, either moderate or profound, with or without local cooling of the heart. The reason for this is that the aortic valves, the coronary arteries, and the three major vessels supplying the head, neck, and upper limbs are frequently involved by the disease. In consequence, special perfusion techniques are required to maintain adequate cardiac, brain, and spinal cord function during a prolonged procedure lasting several hours.In this paper we describe the surgical results in eight consecutive patients with aortic aneurysm. In four of these the ascending aorta was involved with varying degrees of associated aortic incompetence in two, erosion of the sternum and ribs in two, involvement of the innominate artery in one, perforation into the superior vena cava in one, and obstruction of the pulmonary artery and right ventricle in one. In four, varying lengths of the descending aorta were involved, the proximal aorta being affected in three of the four patients, with involvement of the lung and/or thoracic vertebrae in all. Two of these patients had no associated aortic incompetence.CASE REPORTS CASE 1 V.M., a coloured man of 44 years, was admitted on 2 May 1961 in severe distress. Mild inconstant central chest pain, radiating to the shoulders, and dysphagia had commenced fairly acutely one month before. On the day his symptoms began his wife noticed swelling of his face and the right side of his neck, followed by bilateral jugular venous distension. Severe effort dyspnoea and orthopnoea developed rapidly and persisted after the pain and dysphagia had disappeared. Severe bilateral shoulder pain then recurred, requiring admission elsewhere and pethidine administration.At this stage the clinical picture of superior mediastinal obstruction was present, and a continuous murmur was audible in the right parastemal and aortic areas. Treatment with iodide, mercury, penicillin, and mercurial diuretics was begun. When he continued to deteriorate he was referred to the cardiac clinic.On examination he was almost moribund. The face, neck, upper trunk, and upper limbs were very oedematous. The veins draining into the superior vena cava were dilated and non-pulsatile. The blood pressure in both arms was equal, 165/80 mm. Hg. There was no cardiomegaly and no valve murmurs. In the right lower neck and intraclavicular area a continuous thrill and murmur indicative of an arterio-venous fistula was present.Moderate hepatomegaly was noted. The electrocardiogram showed right ventricular dilatation and on radiography (Fig. IA) the superior mediastinal shadow was widened.The diagnosis of ruptured aortic aneurysm into the superior vena cava or innominate vein was made and immediate surgery advised. The serology was positive for syphilis, the sedim...

Maldevelopment of the bulbus cordis may be associated with right ventricular outflow stenosis and a ventricular septal defect. The pathological anatomy in this group of anomalies varies from severe obstruction to the right ventricular outflow, with a small ventricular communication, to a large ventricular septal defect dominating the picture with mild obstruction.When the pulmonary stenosis is mild, whether the ventricular septal defect is small or large, a left-to-right shunt is always present, giving the clinical picture of a ventricular septal defect. On the other hand, if the stenosis is severe and the ventricular septal defect is small, anatomically or functionally (McCord, Van Elk, and Blount, 1958;Vogelpoel and Schrire, 1960a;Hoffman, Rudolph, Nadas, and Gross, 1960), the clinical picture is that of severe pulmonary stenosis with an intact ventricular septum.When the septal defect is large and the stenosis severe, a haemodynamic spectrum develops, dependent on whether the pulmonary stenosis or the systemic resistance is the greater. If the systemic resistance is greater, a dominant left-toright shunt is present, i.e., ventricular septal defect with pulmonary stenosis; if the pulmonary resistance is greater, a right-to-left shunt is present, i.e., Fallot's tetralogy; if the resistances are balanced, acyanotic tetralogy is present.The differentiation of ventricular septal defect with severe pulmonary stenosis and Fallot's tetralogy thus becomes a matter of semantics. Moreover, the haemodynamic state is not static. An infant may present with the dynamics of ventricular septal defect with a large left-to-right shunt. As the crista supraventricularis hypertrophies, progressive infundibular narrowing develops, so that the left-to-right shunt diminishes, the heart becomes smaller, right ventricular hypertrophy develops and, finally, a right-to-left shunt is established, viz., Fallot's tetralogy (Gasul, Dillon, Vrla, and Hait, 1957;Fyler, Rudolph, Wittenborg, and Nadas, 1958;Lynfield, Gasul, Arcilla, and Luan, 1961;Becu, Ikkos, Ljungqvist, and Rudhe, 1961).In this paper, by Fallot's tetralogy we mean severe right ventricular outflow stenosis, i.e., stenosis of the infundibulum of the right ventricle, pulmonary valve area, or pulmonary arteries, with a large ventricular septal defect, and right and left ventricular pressures of the same order. Even in acyanotic patients, the stenosis is relatively severe, permitting bidirectional ventricular shunt or, at most, a small left-to-right shunt at rest (<30%). PATHOLOGYBy the time the heart is examined at operation, the pathological features observed are not only the result of the primary maldevelopment but are also consequent on changes secondary to the abnormal haemodynamics. The important defects, from the surgical point of view, are the right ventricular outflow stenosis and the incomplete development of the ventricular septum.RIGHT VENTRICULAR OUTFLOW STENOSIS.-The normal development of the infundibulum depends on the inclusion of the bulbus cordis into the embryoni...

DESPITE the remarkable advances in cardiac surgery, a suitable operation for the correction of all pathological types of mitral regurgitation has not yet been established. Many ingenious blind techniques have been devised and enthusiastically advocated for the surgical correction of mitral regurgitation in the recent past (Bailey, Jamison, Bakst, Bolton, Nichols, and Geminhardt, 1954;Blalock and Johns, 1954;Davila, The mitral valve is a flat cone (Van Der Spuy, 1958). This cone has as its base the mitral annulus, on which hinge the two cusps which form the sides of the cone. As the anteromedial half of the mitral annulus is closely related to the posterolateral half of the aortic root and the corresponding two aortic cusps, it is thus biconcave. The anteromedial mitral cusp, being hinged in this position, forms an integral Glover, Trout, Mansure, Waad, Janton, and Ioia, 1955; and Kuykendall, Ellis, and Grindlay, 1958), but success was invariably transitory and such operations were short-lived. The trend is now towards surgical treatment of mitral regurgitation by open heart surgery. Surely an intelligent attempt at correction can be made only when the valve is adequately visualized and the various pathological factors appraised, evaluated, and corrected under direct vision, employing a mechanical pump oxygenator ?Before attempting the correction of mitral regurgitation, the surgeon should acquire a clear, three-dimensional concept of the anatomy of the mitral valve region, a sound knowledge of the normal mechanism of mitral valve closure, and also the lesions which may cause the derangement of this mechanism.Anatomy of the Mitral Valve.-Anatomically, the mitral valve mechanism consists of four main parts: the annulus fibrosus, the valve leaflets, the chorde tendinee, and the papillary muscles. It is not within the scope of this paper to discuss the anatomy in detail, but certain observations which concern surgery in this region must be mentioned.

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