Deficiency of the 5-hydroxytryptamine transporter gene leads to cardiac fibrosis and valvulopathy in mice.

BACKGROUND: Serotonin (5-hydroxytryptamine; 5-HT) overproduction is responsible for cardiac valvular disease in patients with carcinoid tumors. Reduced 5-HT inactivation is one proposed mechanism of the valvulopathy observed in individuals treated with the appetite suppressants fenfluramine and phentermine. One key protein limiting systemic availability of 5-HT is the 5-HT transporter (5-HTT) expressed by platelets and pulmonary vascular cells; 5-HTT is responsible for 5-HT uptake and subsequent inactivation of the amine passing through the lung. Here we investigated whether 5-HTT-deficient (5-HTT-KO) mice developed structural and/or functional cardiac abnormalities and valvulopathy. METHODS AND RESULTS: Cardiac endothelial cells expressed large amounts of 5-HTT in wild-type mice. 5-HTT deficiency appeared to be associated with marked interstitial, perivascular, and valvular fibrosis as evidenced by staining of cardiac collagen in 5-HTT-KO mice. Histological analysis provided evidence for valvulopathy characterized by valvular hyperplasia and prominent fibrosis at the attachment site and base of the leaflets. Echocardiography revealed an increase in left ventricular lumen diameter and a decrease in left ventricular diameter fractional shortening. Although 5-HT1B receptors mediated the 5-HT-induced collagen secretion by human cardiac myofibroblasts, the contribution of this receptor type to valvulopathy was ruled out because double-KO mice deficient in both 5-HTT and 5-HT1B receptors showed the same cardiac alterations as 5-HTT-KO mice. CONCLUSIONS: The present results establish a link between 5-HTT and the development of cardiac fibrosis and valvulopathy in vivo. 5-HTT-KO mice represent an especially relevant model for studying the mechanisms by which 5-HT induces valvulopathy.

Acute myopericarditis after diphtheria, tetanus, and polio vaccination.

We report the first case of myopericarditis after triple vaccination against diphtheria, tetanus, and poliovirus in a young adult. He presented with fever, acute chest pain, and diffuse ST-segment elevation 2 days after vaccination. Two-dimensional echocardiography findings were normal. Endomyocardial biopsy showed interstitial edema with diapedesis of erythrocytes. Laboratory findings showed inflammatory syndrome and elevated circulating immune complexes. He recovered within a few days with high-dose aspirin treatment and was without complications at 3-month follow-up. We discuss the different hypotheses for infective or hypersensitivity myocarditis.

Haemorrhagic acoustic neuroma with features of a vascular malformation. A case report.

A 55-year-old man with hearing loss presented with vertigo and vomiting. CT tomography and MRI demonstrated a cerebellopontine angle mass with foci of haemorrhage. An angiomatous tumour, with large abnormal veins adhering to the capsule, was completely removed. Histologically, the tumour was an acoustic neuroma with abnormal vascularisation and limited intratumoral haemorrhage.

Myocardial recovery after mechanical support for acute myocarditis: is sustained recovery predictable?

BACKGROUND: At present, myocardial recovery with mechanical support for acute myocarditis is a more frequently observed issue. However, predictive parameters of a sustained myocardial recovery are still under investigation. METHODS: Two recent cases of mechanical support for acute lymphocytic myocarditis with two different outcomes are reported. Literature about this disease and predictability of a sustainable myocardial recovery are reviewed. RESULTS: Acute lymphocytic myocarditis is an individual entity whose outcome is associated with the importance of healed cell damage. Unfortunately, there are no available means of quantifying the fibrotic scar and endomyocardial biopsy has a high percentage of false-negative results. Echocardiographic assessment of systolic and diastolic cardiac function is difficult while under mechanical support and its significance is not obvious. Forthcoming development of Doppler could better correlate myocardial contractility and histology to be predictive of a sustained recovery after acute myocarditis under mechanical support. CONCLUSIONS: Long-lasting recovery after mechanical support for acute myocarditis remains unpredictable in our experience. More predictive factors are needed.

Epithelioid Schwannoma of the acoustic nerve.

A 25-year-old woman presented with left progressive deafness due to an intracranial tumor of the cerebello-pontine angle. Biopsy and subsequent total surgical excision indicated origin from the acoustic nerve. Histologically, the tumor showed typical feature of Schwannoma associated with a population of epithelioid cells. Three years after surgery no local invasion, no relapse, and no metastasis were noted. Immunohistochemistry showed a strong positivity for S100 protein in the cytoplasm of Schwannian and epithelioid tumoral cell components. This positivity in the epithelioid cells correspond to a well differentiated cell population derived from a Schwann cell precursor explaining the benign course of the tumor. In the absence of similar cases of epithelioid Schwannoma of the acoustic nerve in literature, we will discuss the differential diagnosis, potential evolutivity, and origin of the epithelioid cells.

[Cerebral infarctions in a drug addict inhaling heroin]. / Infarctus cérébraux chez un toxicomane inhalant l'héroïne.

Cerebral infarcts complicating heroin abuse have been seldom reported and only clinically and radiologically documented. We report a pathological case of cerebral infarct in a heroin sniffer. A 31 year old, male, heroin sniffing addict for several years, with no known past neurological history, was found dead one morning. The evening before, he had presented the usual signs of recent heroin intake. Opiates were found in large amounts in blood and urine. Post mortem HIV serology was negative. Post mortem examination revealed the usual signs of heroin addiction, but no cutaneous signs of IV drug use. Myocardial ischemic lesions of various ages involved the anterolateral part of the left ventricle; coronary arteries were normal. Neuropathological study revealed, partly cystic infarcts involving both cerebral hemispheres. They were mostly cortical with an intralaminar pattern and a watershed distribution at the boundaries between the territories of the anterior and middle cerebral arteries and the middle posterior cerebral arteries. Intracerebral vessels, large intracranial and cervical arteries were normal.

In vitro and in vivo evaluation of a small caliber vascular prosthesis fixed with a polyepoxy compound.

A small caliber vascular prosthesis obtained from an ovine internal thoracic artery (3.8-4.5 mm ID) fixed with a polyepoxy compound and treated with heparin has been evaluated. Cytocompatibility was evaluated in vitro using human endothelial cells (HEC). HEC were obtained from human saphenous vein and cultivated in culture medium supplemented with 25% human serum. Graft segments were rinsed using a standard protocol proposed by the manufacturer. Tissue reaction was tested on a rabbit model of subcutaneous implantation. The patency rate and healing patterns were evaluated comparatively with polytetrafluorethylene (PTFE) 4 mm ID prosthesis in a canine model of carotid interposition. Cytocompatibility assay showed that there was low adhesion on vascular grafts (20 +/- 2% of endothelial cells seeded) and no growth of HEC on the graft surface. The graft patency rate was 55% in both groups, and actuarial freedom from occlusion was not different at 3 months (37.7 +/- 15% in Denacol-fixed grafts versus 38.1 +/- 14% in PTFE). Histological studies on the biological grafts shows a frequent neointimal hyperplasia at the anastomosis (5/12), a lack of endothelial cells lining the graft surface, a good preservation of the media, and a moderate inflammatory response in the adventicia. The Denacol-fixed graft has presented excellent surgical properties and preservation of the histological structure. Nevertheless, the patency rate was not improved when compared with the PTFE control graft.

Donor/recipient aorta size mismatch in heart transplantation: a technical alternative.

A technical alternative is proposed to enable transplantation in cases of considerable size mismatch between donor and recipient aorta: interposition of a Dacron graft of intermediate diameter. This procedure was performed in a 56-year-old patient weighing 75 kg in whom a heart from a 40-kg donor was implanted.

[Can solid state Holter monitoring replace endomyocardial biopsy in patients with heart transplantation?]. / Le Holter à mémoire solide peut-il remplacer la biopsie endomyocardique chez le transplanté cardiaque?

Acute cardiac graft rejection after transplantation, the diagnosis of which is based on the findings of endomyocardial biopsy, is associated with a reduction in coronary reserve due to abnormalities of the microcirculation. But this reduction in coronary reserve cause silent myocardial ischaemia (SMI)? In order to assess the frequency of SMI and ventricular arrhythmias during rejection, 53 consecutive Holter recordings were performed in 32 patients (28 men, 4 women, average age 47 +/- 11 years) 11 months after transplantation and within 24 hours of endomyocardial biopsy. The recorder which was used (Monitor One TC) analysed the ST segment in 2 leads in real time: ST segment depression of more than 1 mm lasting over 40 ms, 0.08 s after the J point were considered to be diagnostic of myocardial ischaemia. Although the frequency of SMI is low and not specific for cardiac rejection, its duration was twice as long (80 mn vs 38 mn) in this condition. On the other hand, ventricular arrhythmias are common in cardiac rejection and correlated with its severity according to Billingham's classification (VES p = 0.045; doublets p = 0.035; non-sustained VT p = 0.006).

In vitro endothelialization of carbon-coated Dacron vascular grafts.

Physical vapour deposition is used to coat vascular prostheses with pyrolytic carbon. This coating may facilitate the development of an endothelial monolayer in grafts implanted in laboratory animals. This in vitro study compared the adherence and growth of cultured porcine aortic endothelial cells (EC) seeded in vitro on carbon-coated Dacron, to uncoated prostheses. The cells were incubated at 5 x 10(4) cells/cm2. Progress was monitored at different times (TO + 2 hours, D 1, D 4, D 8) by microscopic observation, when cell counts were made; and by scanning electronic microscopy (SEM) to evaluate morphological EC-graft interactions. Cell adherence was independent of the carbon coating but cellular growth occurred only on carbon-coated Dacron. The SEM observations showed both the shape of the adherent cells, which were rounded on uncoated Dacron and extensively spread on carbon-coated prostheses, and the morphology of the carbon coating.

[Vertebral hemangioma. Definition, limitations, anatomopathologic aspects]. / Les hémangiomes vertébraux. Définition, limites, aspects anatomo-pathologiques.

Vertebral hemangiomas are benign, malformative vascular tumours composed of newly formed blood vessels with normal (capillary, venous, or veno-capillary) structure and without arterio-venous shunt; they involve firstly the vertebra and may secondary extend to the epidural space. These features allow to separate vertebral hemangiomas from bone lymphangiomas, from true neoplastic vascular tumours such as hemangioendotheliomas, hemangiopericytomas, angiosarcomas, from hemangioblastomas and from arteriovenous malformations with shunt. The latter are usually associated with other vascular malformation of the skin and spinal cord in the same metameric segment(s) (metameric angiomatosis or Cobb syndrome). There are two microscopic types of vertebral hemangiomas which frequently coexist. Cavernous angiomas are composed of large dilated blood vessels closely clustered together, so that they are not separated by normal bone tissue. Capillary angiomas are formed of thin-walled capillary vessels of various sizes separated by normal bone tissue. The vascular malformation is not separated from the bone tissue by a capsule; the surrounding osseous lamellae usually show secondary osteolysis and osteocondensation, and the bone marrow undergo fibrous and/or adipose involution.

Expanding cerebellar lacunes due to dilatation of the perivascular space associated with Binswanger's subcortical arteriosclerotic encephalopathy.

An 80-year-old hypertensive woman developed right hemiplegia and died 24 hours after admission. Neuropathologic examination revealed multiple cerebral infarcts of various ages and diffuse subcortical arteriosclerotic encephalopathy. Clusters of asymptomatic "expanding" lacunes, due to dilatation of the perivascular spaces, were found in both dentate nuclei. These cavities, which presented as space-occupying lesions, were surrounded by a single layer of flattened cells and contained 1 or more sections of normal-looking arterioles. Such a topographic grouping of lacunes in the dentate nucleus has not been described previously. The mechanism of widening of the perivascular compartment remains unclear; its occurrence in a hypertensive patient and its association with typical Binswanger's subcortical arteriosclerotic encephalopathy and severe atherosclerosis with multiple infarcts suggest a common pathophysiologic mechanism possibly including an alteration of the blood-brain barrier.

Cardiovascular abnormalities in thoracopagus twins: embryological interpretation and review.

The cardiovascular abnormalities of two sets of thoracopagus twins with conjoined heart and liver are described and compared with 27 well documented cases. An embryological interpretation of the cardiovascular abnormalities is suggested. The common heart in both sets showed a common atrium and two ventricles. In case 1 the great arteries were L. malposed in twin A. In case 2 the great arteries originated from their respective double outlet single ventricle. The systemic and pulmonary veins drained directly into the common atrium in case 1 and indirectly via systemic veins in case 2. The type of cardiovascular abnormalities are complex and discordent from one set to another and in the same set. However among 27 published cases of thoracopagus twins, cardiac union, including atrial union with separate ventricles, or atrial and ventricular union, was encountered in 16 cases. Approximately 90% of them are not suitable for surgical separation because of the high degree of cardiac union and the complexity of cardiovascular abnormalities. Surgical separation could be attempted in only two cases, but at the cost of the life of one of the twins.

Arterial healing in rabbits following carbon dioxide laser endarterectomy.

CO2 laser open endarterectomy of small atherosclerotic vessels appears feasible. Under the conditions described, the endarterectomized arterial wall is not smooth but the thrombogenicity of the laser-treated surface is low, and the endothelial healing rapid. These advantages are to be weighed against the consequence of thermal injury, in particular, the late development of aneurysms. Before human clinical trials are made, further experimental studies are required to determine the best type of laser and optimal wave length to limit thermal injury.

Thrombosis of a saccular microaneurysm causing cerebral (pontine) lacunae.

The authors present the case of a hypertensive patient with a thrombosis of a saccular microaneurysm (SMA) and underlying cerebral (pontine) lacunae. This SMA lay at the junction between the main vessel and two small feeding arteries penetrating into the necrotic territory. Microhemorrhages were observed in and outside the aneurysmal wall. Very sinuous narrow channels of recanalization crossed the thrombosis between the upstream and downstream vessels. The anatomical relationship between the SMA and the lacunae has been histologically demonstrated.

Characterization of human pericardial macrophages.

This paper deals with the study of the cell population in 13 samples of normal human pericardial fluid. Large mononuclear cells (LMC) constituted 74.1 +/- 18.5% of the total cell population. These LMC possess the characteristics of macrophages firm adherence to glass intracytoplasmic presence of vimentin without keratin, ultrastructural observation of a lysosomal apparatus cytoenzymatic activities: acid phosphatases, naphthol AS.D acetate esterase and peroxidases, and phagocytosis of Baker's yeasts. All these data clearly show that macrophages are the main component of the pericardial fluid cell population and can be of great significance in the defense mechanisms and physiology of the pericardial space.

A retromedullary arteriovenous fistula associated with the Klippel-Trenaunay-Weber syndrome. A clinicopathologic study.

An intraspinal vascular malformation associated with the Klippel-Trenaunay-Weber (KTW) syndrome initially was thought to be intramedullary on angiographic findings. Postmortem examination revealed an entirely posterior extramedullary arteriovenous fistula (AVF) fed by the anterior spinal artery. The association of the KTW syndrome with a so-called intramedullary AVF has been described in the literature without any pathologic confirmation (11 cases). Our case emphasizes the difficulty of determining the exact morphology and location of spinal AVF on arteriography. The association of the KTW syndrome with a retromedullary AVF can be explained on a developmental basis.