Clinical and molecular study of DiGeorge sequence.

DiGeorge sequence (DGS) is a developmental field defect of the third and fourth pharyngeal pouches. The cardinal features of the syndrome are hypo- or aplasia of the thymus and parathyroids, congenital heart defect of the conotruncal type and characteristic facial dysmorphism. Such a pattern of malformations has been associated with various conditions but it is now well established that most cases of DGS are due to haplo-insufficiency of the chromosome 22q11 region. We report here a series of 16 patients, including a familial case. Minimal criteria for inclusion in this series were two or more of the following features: conotruncal heart defect, hypocalcaemia, hypoplastic/absent thymus and typical facial dysmorphism. Molecular analysis with specific probes of the 22q11 region was conducted in all patients according to two methods, fluorescent in situ hybridization and DNA dosage analysis. A deletion was found at the molecular level in all patients. We emphasize the fact that clinical analysis remains an important step of the diagnosis. The implication of these molecular techniques on diagnosis, prognosis and genetic counselling of DGS are discussed.

Hyperhomocysteinaemia in heart transplant recipients.

The aim of this study was to determine the prevalence of hyperhomocysteinaemia in cardiac transplant recipients. Three groups of subjects were studied: 27 heart transplant recipients, 14 to 63 months (mean = 36.5) after transplantation; 10 patients with moderate chronic renal insufficiency without clinical evidence of vascular disease; 17 apparently healthy individuals. Twenty-five out of 27 transplanted patients had a coronaroangiography within 6 months of homocysteine measurement. Plasma homocysteine was measured both while the subject was fasting (t0) and 6 h after administration of 0.1 g.kg-1 of methionine (t6). Hyperhomocysteinaemia was present in 14/27 fasting transplanted patients and after methionine loading. Mean plasma levels of homocysteine at t0 were higher (P = 0.03) in transplanted heart recipients (15.4 +/- 7 mumol.l-1) than in the renal patients (9.9 +/- 5 mumol.l-1) despite similar mean plasma creatinin. In eight transplanted patients with angiographic coronary abnormalities of the cardiac graft, homocysteinaemia was at t0 17.1 +/- 9 mumol.l-1 and at t6 47.8 +/- 25 mumol.l-1. In 17 transplanted patients with angiographically normal coronary arteries, plasma homocysteine levels were at t0, 13.2 +/- 4 mumol.l-1 and at t6, 46.8 +/- 25 mumol.l-1. We conclude that hyperhomocysteinaemia is common in transplanted heart recipients, and partly related to renal insufficiency. No correlation was found between hyperhomocysteinaemia and angiographic evidence of coronary atherosclerosis of the graft, but the population of the study was possibly too small to establish this correlation.

Thallium perfusion and myocardial hypertrophy in transplanted heart recipients with normal or near-normal coronary arteriograms.

In patients with hypertrophic cardiomyopathy or systemic hypertension, exercise thallium perfusion defects have been observed but without significant angiographic stenoses. Hypertension and myocardial hypertrophy are common in transplanted heart recipients, and the aim of this study was to determine if exercise thallium scintigraphy false-positives are frequent in transplanted heart recipients. Thirty-four transplanted heart recipients were evaluated by exercise thallium single emission computed tomography and subsequently had a normal or near normal coronary arteriogram. At the time of the exercise, the patients (28 men and six women) had a mean age of 48.9 +/- 12 years and 29 had been previously treated for systemic hypertension. The mean duration between transplantation and the exercise test was 31.6 +/- 13 months. In all patients left ventricular mass was obtained by echocardiography within 3 months of thallium 201 SPECT and was > or = 130 g.m-2 in nine males and > or = 110 g.m-2 in four females. M-mode septal + posterior end-diastolic thickness was > 23 mm in 14 patients, all of whom had been previously treated for systemic hypertension. These patients were older and endured a longer period during which the heart was kept cold but ischaemic before being grafted ('cold ischaemia') but a shorter exercise duration than patients without left ventricular hypertrophy. During exercise testing, 26 of 34 patients achieved at least 80% of their maximal predicted heart rate and two developed significant ECG changes.(ABSTRACT TRUNCATED AT 250 WORDS)

Achieving a passive fit for a screw-retained implant-supported maxillary complete arch ceramometal prosthesis: clinical report.

A technique is described for the fabrication of a full arch maxillary passive-fitting, screw-retained, rigid ceramometal prosthesis. The two posterior segments containing Screw-Bloc attachments are cast initially. The waxed anterior segment with its attachments is then aligned to the cast posterior segments and cast. Porcelain is fired to the individual segments in an attempt to reduce deformation, which occurs when large ceramometal restorations are constructed. When the prosthesis is completely fabricated, the segments are assembled on the master cast and the attachments on the posterior segments are tapped to receive the screws, which rigidly attach them to the anterior segment. The Screw-Bloc attachment has an irregular configuration that resists rotation of the individual segments. The segments are united once the passively aligned screws are tightened. A clinical report is presented.

Immunolocalization of an extracellular domain of connexin43 in rat heart gap junctions.

Antipeptide antibodies directed to residues 55 to 66 (NTQQPGCENVCY) of connexin43 (cx43) specifically recognize this protein on Western blots of intact and urea-split gap junctions isolated from rat heart. These antibodies detect a single protein of 43 kDa, corresponding to cx43, on Western blots of whole fractions of various vertebrate hearts. Immunogold labeling by electron microscopy shows that the epitopes recognized by these antibodies are not localized on the cytoplasmic surfaces of intact gap junctions but only at the edges of these junctions. In urea-split gap junctions the gold particles are seen in the junctional space, associated with the extracellular faces of junctional membranes. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) analyses of rat heart gap junctions treated with trypsin show that they are constituted with either two polypeptides of Mr 12,000 and 14,000 or a single polypeptide of Mr 22,000 according to whether the analyses are performed under reducing or non-reducing conditions, respectively. The antibodies directed to residues 55 to 66 of cx43 cross-react with both the 12 and 22 kDa polypeptides. These results suggest that the two protected domains of 12 and 14 kDa which contain the first extracellular loop and a putative second extracellular loop, respectively, are linked by disulfide bonds. In adult rat heart sections analyzed by indirect immunofluorescence the intercalated discs are labeled with antibodies directed to a cytoplasmic carboxy-terminal domain of cx43 (El Aoumari et al., J. Membr. Biol. 115, 229-240 (1990)). The same intercalated discs are also labeled in adjacent sections incubated with the antibodies directed to residues 55 to 66. Two hypotheses might explain these results: either the antibodies have access to the extracellular domain of cx43 molecules localized at the edges of the gap junctions, or cx43 molecules are present in the non-junctional membranes of the intercalated discs.

[Development of echocardiographic and Doppler parameters after orthotopic cardiac transplantation, except during rejection periods]. / Evolution des paramètres échocardiographiques et Doppler, après transplantation cardiaque orthotopique, en dehors des périodes de rejet.

The aim of this study was to evaluate spontaneous changes of Doppler and echocardiographic parameters of cardiac transplants in the absence of rejection. Based on 258 recordings representing the follow up of 30 patients after orthotopic cardiac transplantation in the absence of histological signs of rejection on biopsy within 24 hours, we tried to define: the evolution of these parameters from the first postoperative week to after the 30th month (average 12 months); the Doppler echocardiographic values of "normal" transplants: the values observed one year after surgery were compared with a control group age-matched to the donors.(ABSTRACT TRUNCATED AT 250 WORDS)

[Surgical excision of giant venous angioma of the face under extracorporeal circulation: apropos of a case by a multidisciplinary team]. / Exérèse chirurgicale d'un angiome veineux géant de la face sous circulation extra-corporelle: a propos d'un cas traité en équipe pluri-disciplinaire.

Because of the risk of haemorrhage related to their resection, deep angiomas of the face are often considered to be inaccessible to treatment. The use of cardiopulmonary bypass with profound hypothermia allows the surgeon to operate in a bloodless field, enabling almost oncological resection of the tumour. The authors report a case of venous angioma of the submaxillary region treated in this way after failure of limited surgery and embolisation. Complete resection of the lesion was achieved and the defect was repaired with a pectoralis major flap and a latissimus dorsi flap. The authors stress the value of a multidisciplinary approach: a cardiac surgeon for CPB, an ENT surgeon for resection and a plastic surgeon for reconstruction.

Conservation of a cytoplasmic carboxy-terminal domain of connexin 43, a gap junctional protein, in mammal heart and brain.

According to the sequence of connexin 43, a cardiac gap junctional protein, the domain contained within residues 314-322 is located 60 amino acids away from the carboxy-terminus. Antibodies raised to a peptide corresponding to this domain label a unique 43-kD protein on immunoblots of both purified gap junctions and whole extracts from rat heart. Immunofluorescence investigations carried out on mammal heart sections reveal a pattern consistent with the known distribution of intercalated discs. Immunogold labeling performed with ultrahin frozen sections of rat heart or partially purified rat heart gap junctions demonstrate that antigenic determinants are associated exclusively with the cytoplasmic surfaces of gap junctions. The antibodies were shown to cross-react with a 43-kD protein on immunoblots of whole extracts from human, mouse and guinea pig heart. However, no labeling was seen when heart of lower vertebrates such as chicken, frog and trout, was investigated. These results, confirmed by immunofluorescence investigations, were interpreted as a loss of antigenic determinants due to sequence polymorphism of cardiac connexin 43. Proteins of Mr 43 and 41 kD, immunologically related to cardiac connexin 43, were detected in immunoblots of mouse and rat brain whole extracts. mRNAs, homologous to those of cardiac connexin 43 and of the same size (3.0 kb), are also present in brain. Immunofluorescence investigations with primary cultures of unpermeabilized and permeabilized mouse neural cells showed that the antigenic determinants recognized by the antibodies specific for connexin 43 are cytoplasmic and that the labeling observed between clustered flat cells, is punctate, as expected for gap junctions. Double labeling experiments demonstrated that the immunoreactivity is associated with GFAP-positive cells, that is to say, astrocytes.