Doppler ultrasonography of peripheral vascular disease: the potential for ultrasound contrast agents.

Noninvasive diagnosis of peripheral vascular disease started with the introduction of Doppler technology. The development of high frequency ultrasound and color Doppler imaging allows continuous assessment of vascular disorders along the arterial tree. However, the technique remains operator dependent. It also suffers from anatomic limitations, such as bowel gas and ultrasound attenuation due to depth or wall calcification. Ultrasound contrast agents increase the Doppler signal intensity and should therefore reduce the rate of technical failures. They are useful for detecting the flux in cases of attenuated ultrasound beam and reduced blood flow. Their administration using continuous infusion protocols increases the duration of the effect. New imaging modalities such as harmonic imaging and pulse inversion imaging reduce Doppler artifacts and allow real time detection of the microbubbles flowing in the blood stream. Future directions include ultrasound-guided therapy of occlusion using encapsulated drugs targeted to the thrombus.

[Transcranial pulsed Doppler]. / Le Doppler pulsé transcrânien.

Transcranial Doppler ultrasonography is the only non invasive examination enabling the reliable measurement of the blood flow velocity in the intracranial arterial trunks. However, it cannot be constantly perfect. It is fully realized in about 10% of the patient. Even incomplete it remains a useful complementary exploration in the management of the cerebral vascular disease.

Genetic restriction of murine hepatitis virus type 3 expression in liver and brain: comparative study in BALB/c and C3H mice by immunochemistry and hybridization in situ.

To study the host-dependent genetic variations in murine hepatitis virus type 3 (MHV 3) induced diseases, we localized the sites of MHV 3 (Mill Hill strain) expression within liver and brain by immunohistochemistry or hybridization in situ. Two strains of mice were studied: BALB/c mice, which develop an acute and lethal hepatitis and C3H mice which develop a chronic brain infection. In BALB/c mice, viral RNA and antigens appeared during the first 24h post infection (p.i.) in liver, whereas viral RNA was barely detectable in brain, up until death at day 3 p.i. In C3H mice, viral RNA and antigens were detected simultaneously in liver and brain only at day 2 p.i. In brain, the virus was detected in meningeal and ependymal cells and in perivascular cortical areas (days 5 and 7 p.i.). After day 49, the virus was no longer detected in brain parenchyma, but persisted in meningeal cells. Two host-dependent genetic differences in viral processing were observed in the liver: (1) the virus was first detected in Kupffer cells in BALB/c mice and mostly in hepatocytes in C3H mice; (2) in BALB/c mice, the 180 kDa S viral glycoprotein appeared more frequently cleaved in 90 kDa form than in C3H mice.

Human immunodeficiency virus type 1-infected monocytic cells can destroy human neural cells after cell-to-cell adhesion.

Primary cultures of human embryonic neurons and astrocytes have been used to test the interactions between neural cells and either human immunodeficiency virus type 1 (HIV-1) or HIV-1-infected monocytes. After direct infection with HIV-1, neither morphological alteration of neurons and astrocytes nor signs of viral replication were observed. Similarly, cultured human neurons and astrocytes were resistant to incubation with the supernatant of HIV-1-infected U937 cells, a human monoblastoid cell line. In contrast, HIV-1-infected U937 monocytic cells adhered to neural cells and induced large plaques of necrosis surrounding them. This cytopathic effect began at the time of viral replication (day 16 after infection). Its intensity depended on that of viral replication, and its range was identical to the region of diffusion of viral antigens, as judged by immunocytochemistry. The cytopathic effect was not dependent on the release of free radicals. It could not be induced by cytokines or cytokine-stimulated U937 cells. It is likely that this cytopathic effect depends on the release of viral antigens either within the site of adherence itself or within close range of the astrocyte membrane.

[Transcranial pulsed Doppler. Problems posed by the temporal window (834 patients)]. / Le Doppler pulsé transcrânien. Problèmes posés par les fenêtres temporales (834 patients).

The absence of temporal windows represents an indisputable limitation of transcranial pulse Doppler (13% of 834 patients). We wanted to specify the elements causing this condition. The patient's age is a determinant factor, especially after 60 years of age. The sex also plays a role, as the window is absent in 23% of women and 6% of men. The use of one device as a rule (95%) does not allow appreciating the results according to the respective qualities of the various systems, which have been diversified as the study was in progress. On the other hand, the technician's experience (this person being experimented with the method) has no significant influence on the results.

[Encephalitis with viral replication. Clinical aspects, prognosis and treatment]. / Encéphalites avec réplication virale. Aspects cliniques, pronostic et traitement.

Encephalites with viral replication are due to multiplication of a virus within the central nervous system. Diagnosis and initial therapeutic decisions rest on simple clinical and paraclinical findings: age of the child, presence of high-grade fever, presence and localization of seizures, CSF characteristics, and EEG findings. Acyclovir is always indicated in a drowsy child with a high fever who has even a brief seizure and CSF abnormalities.

[Acute hydrocephalus due to Candida meningitis in a 2-month-old infant]. / Hydrocéphalie aiguë révélatrice d'une méningite à Candida à l'âge de deux mois.

A case of triventricular acute hydrocephalus is reported in a 2 month-old male. The etiology was a Candida sepsis with neonatal onset and subacute course of meningitis and arthritis. No immune deficiency was detected and antibiotic treatment appeared to be the only predisposing factor to systemic candidiasis in this neonate. The condition was treated successfully with amphotericin B, fluocytosin and ketoconazole. At follow up, 17 months later, the development of the child appeared normal.

[Popliteal vein entrapment, popliteal cyst, desmoid tumor and fabella syndrome]. / Veine poplitée piégée, kyste poplité, tumeur desmoïde et syndrome de la fabella.

The popliteal fossa is a relatively small, muscle-bound strategic anatomical area where is found, on the posterior aspect of the knee, a vasculonervous pedicle and where both vascular and pseudovascular disease may develop, the latter originating from wall-constituting parts. Among non-typical popliteal diseases, the authors have singled out four rare syndromes. The popliteal vein may be trapped due to fibrous strangulation or, more often, to compression by the hypertrophied gastrocnemius muscle. This requires proper diagnosis and surgical management prior to thrombosis onset. Synovial cysts raise no diagnostic problems, unless they mimic an episode of phlebitis; echotomography has now become essential for diagnosis. Desmoid tumors for which predominant extra-abdominal occurrence sites are the popliteal fossa, the leg and thigh, are difficult to excise completely, especially at the popliteal level, and are a major technical challenge because of the inclusion of the vasculonervous pedicle. Lastly, in sports pathology, one must be able to recognize the painful fabella syndrome (osteochondritis of sesamoid fibrocartilage in lateral head of gastrocnemius), so as not to mistakenly implicate vascular disease. New developments in imaging (namely, real time CT-echography) are of major help to clinicists, who should, nonetheless, remain chiefly responsible for detecting these diseases.

Effect of cyclosporin A on an experimental chronic viral infection of the central nervous system.

The effects of cyclosporin A (CsA) on neuropathological lesions induced by a chronic viral infection have been tested in the experimental model of the mouse hepatitis virus 3 (MHV3) infection. Daily injections of CsA (50 mg/kg) inhibited the expression of the MHV3-induced ependymitis, meningitis, hydrocephalus and vasculitis. The effect was preserved even if CsA treatment was initiated 15 days after virus infection but was lost if CsA treatment was given later on or for a shorter period of time. Viral titers in brains of chronically infected mice were not affected by CsA treatment. During the first week following MHV3 infection, CsA treatment increased both the percentage of acute death (31 vs. 10%) and the viral titers in brain and liver of infected mice. In this model, the timing of CsA treatment appeared critical for the balance between its beneficial effect on CNS lesions and the risk of increased acute mortality.

[Transcranial Doppler: first results of exploration of the circle of Willis]. / Le Doppler transcrânien: premiers résultats de l'exploration du polygone de Willis.

Over a two year period, 500 intracranial examinations were performed to explore the arteries at the base of the skull (middle, anterior and posterior cerebral) as well as the basilar artery. Exploration of the carotid siphons by the transorbital route is not systematic but used when approach to the vessels by the temporal windows is impossible. The transcranial Doppler examination is particularly indicated in the following circumstances: (1) In patients presenting a tight stenosis on the extracranial internal carotid artery (50 cases). The intracranial effects of extracranial lesions depend on the degree of obstruction and blood supply values at the level of the circle of Willis. (2) During cerebral vascular accidents without extracranial lesions in order to detect possible intracranial involvement (15 cases). Occlusions (5 cases) raised more diagnostic problems than did tight stenoses. (3) In meningeal haemorrhages, in which the degree of spasm can be measured, to provide elements to prognosis (8 cases). (4) In angiomas and intracranial malformations (5 cases). To a certain extent, the examination makes it possible to determine the region concerned by the fistula and, especially, to assess the effects on locoregional circulation. The main drawback of the method is the absence of a temporal window, preventing direct access to vessels at the base of the skull. Moreover, certain arteries are not easily accessible and thus not always found or at least recognized with certitude. However, reliability has improved with experience, and accurate diagnoses can now be made.

[Ultrasonic tomography in the study of supra-aortic trunks]. / Echotomographie dans l'exploration des troncs supra-aortiques.

Real time mode B echotomography completes ultrasound exploration of supra-aortic trunks. Continuous Doppler recording is essential for detection of vessels and identification of significant lesions. However, it cannot detect arterial wall lesions that have no effect on arterial blood flow but can be at the origin of migrating emboli. The latter can be visualized by echotomography, which localizes the lesion and allows evaluation of its morphologic and anatomic characteristics. The methodology of the examination and normal anatomic findings are summarized and the different types of lesion occurring in the supra-aortic trunks described. The limitations of echotomography are discussed and a description given of a semiology of vascular ultrasonic structures of emboligenic potential.

[Transcranial Doppler pulse. Methodology, diagnostic value and limitations]. / Le Doppler pulse transcranien (DPTC). Méthodologie, intérêt diagnostique, limites.

Vessels of base of skull were inaccessible to conventional ultrasonic image until 1982, when the use of pulsed Doppler emitting a beam of 2 MHz coupled with a frequency analyzer allowed direct exploration of terminal branches of the internal carotid artery (ICA) and the basilar trunk. It is now possible to measure rate of flow in middle cerebral artery (MCA), anterior (ACA) and posterior (PCA) cerebral arteries, communicating arteries and those of basilar trunk. Practical applications of this new method are numerous in cerebrovascular disease: diagnosis of brain stem lesions, evaluation of effects of extracranial lesions, detection and follow up of arteriovenous malformations, functional value of the circle of Willis prior to carotid surgery. Despite certain limitations due to anatomic factors, angiographic confrontations attest the value and reliability of this new examination.

Selective tropism of a neurotropic coronavirus for ependymal cells, neurons, and meningeal cells.

The ability of a neurotropic virus, mouse hepatitis virus type 3 (MHV3), to invade the central nervous system (CNS) and to recognize cells selectively within the brain was investigated in vivo and in vitro. In vivo, MHV3 induced in C3H mice a genetically controlled infection of meningeal cells, ependymal cells, and neurons. In vitro, purified MHV3 bound to the surface of isolated ependymal cells and cultured cortical neurons but not to oligodendrocytes or cultured astrocytes. MHV3 replicated within cultured cortical neurons and neuroblastoma cells (NIE 115); infected cultured neurons nonetheless survived and matured normally for a 7-day period postinfection. On the other hand, MHV3 had a low affinity for cortical glial cells or glioma cells (C6 line), both of which appear to be morphologically unaltered by viral infection. Finally, MHV3 infected and disrupted cultured meningeal cells. This suggests that differences in the affinity of cells for MHV3 are determinants of the selective vulnerability of cellular subpopulations within the CNS. In vivo, a higher titer of virus was needed for CNS penetration in the genetically resistant (A/Jx) mice than in the susceptible (C57/BL6) mouse strain. However, in spite of viral invasion, no neuropathological lesions developed. In vitro viral binding to adult ependymal cells of susceptible and resistant strains of mice was identical. Genetic resistance to MHV3-CNS infection appeared to be mediated both by a peripheral mechanism limiting viral penetration into the CNS and by intra-CNS mechanisms, presumably at a stage after viral attachment to target cells.

Neurotransmitter changes during development of cortical neuronal cultures.

Benzodiazepine (BDZ) ligands clonazepam (CLO) and Ro5-4864 which preferentially bind to neuronal and non-neuronal elements, respectively, have been used to follow neuronal and non-neuronal development in fetal murine cortical cultures. CLO-displaceable BDZ binding, choline acetyltransferase (CAT) activity, high-affinity delta-aminobutyric acid (GABA) uptake, and glutamic acid decarboxylase (GAD) activity reached a maximum value at the end of the second week in culture reflecting maximum neuronal maturation and development. There is a developmental order of these four functions: CAT activity (main enzyme in the synthesis of acetylcholine, a stimulating neurotransmitter) reached maximal levels first, 3H-GABA uptake and CLO-displaceable flunitrazepam receptor binding reached maximal levels 1 day later, and 4 days later GAD activity (primary enzyme in the synthesis of GABA, an inhibitor neurotransmitter) reached maximal levels.

Ultrasonography of supra-aortic trunks.

Ultrasonography by the Doppler technique combined with B-mode echotomography are useful methods in the investigation of disease of the major arteries in the neck supplying the brain. The investigations are described together with the significance of major findings.