Perfluorochemicals as US contrast agents for tumor imaging and hepatosplenography: preliminary clinical results

In animals, perfluorochemicals (PFCs) are effective ultrasound (US) contrast agents that produce hepatic, splenic, and tumor enhancement. The use of Fluosol-DA 20%, an emulsion of perfluorodecalin and perfluorotripropylamine, was studied in nine non-critically ill patients with cancer who had liver lesions. US studies without Fluosol were compared with studies obtained 24, 48, and 72 hours after Fluosol infusion. Vital signs and extensive laboratory analyses are performed before and after Fluosol infusion. Liver metastases from colonic, pancreatic, and gastric carcinoma exhibited rim or diffuse enhancement after a Fluosol dose of 1.6 g/kg or greater. Fluosol produced echogenic enhancement of the liver and spleen relative to kidney at a dose of 2.4 g/kg, allowing the detection of nonenhancing lesions. In addition, Fluosol at a dose of 1.6 g/kg or greater allowed detection of lesions not seen before contrast medium was administered in three of the seven patients studied. There was a mild increase in the level of serum glutamic oxaloacetic transaminase in two patients, one given 2.4 and the other 3.2 g/kg of Fluosol. Mild and transient allergic reactions without change in vital signs were experienced by two patients.     

Efficacy and safety of xaliproden in amyotrophic lateral sclerosis: results of two phase III trials.

Amyotrophic lateral sclerosis (ALS) is a relentlessly progressive and fatal motor neuron disease. We carried out two randomized, double-blind, placebo-controlled, multi-centre, multi-national studies with xaliproden (a drug with neurotrophic effect) to assess drug efficacy and safety at two doses. Patients with clinically probable or definite ALS of more than 6 months and less than 5 years duration were randomly assigned to placebo, 1 mg or 2 mg xaliproden orally once daily as monotherapy in Study 1 (n=867); or to the same regimen with addition of riluzole 50 mg bid background therapy in Study 2 (n=1210 patients). The two primary endpoints were defined as: 1. Time to death, tracheostomy, or permanent assisted ventilation (DTP), and 2. Time to vital capacity (VC)<50% or DTP before (log-rank test) and after adjustment using a Cox proportional hazard model for prespecified prognostic factors. Secondary endpoints were rates of change of various functional measures. In Study 1, primary outcome measures did not reach statistical significance. For the 2 mg group, for time to VC<50% analysis (without DTP) a significant 30% RRR was obtained (95% confidence interval [CI]: 8.46, P=0.009). In Study 2, no significant results were obtained. However, there was a trend in favour of add-on 1 mg dose xaliproden vs. placebo (RRR 15% [-6.31, ns] for time to VC<50%; RRR 12% [CI: -6.27, ns] for time to VC<50% or DTP). Adjusted RR ratios were consistently more favourable for the xaliproden groups. Tolerability was good, and dose-dependent side effects were largely associated with the serotonergic properties of xaliproden. An effect of xaliproden on functional parameters, especially VC, was noted. Although this effect did not reach statistical significance, xaliproden had a small effect on clinically noteworthy aspects of disease progression in ALS.     

Role of percutaneous endoscopic gastrostomy in amyotrophic lateral sclerosis

Percutaneous endoscopic gastrostomy (PEG) is an enteral nutritional assistance technique using a simple device compatible with conventional feeding and thus enabling the patient to be integrated into his or her social and familial surroundings. This inexpensive device is quickly and easily inserted under local anaesthesia. It causes little morbidity and virtually no mortality and has many advantages for patients with amyotrophic lateral sclerosis (ALS). We report the results of PEG in 28 ALS patients with bulbar involvement. Three of these patients developed minor complications during 6 consecutive months of PEG-assisted nutrition (2 had periostomial infection, 1 had mild haematemesis). There were no major complications, and mortality directly ascribable to PEG was nil. All patients put on weight or had their weight stabilized, and GEP was well accepted in all cases.     

Regulation of tissue injury responses by the exposure of matricryptic sites within extracellular matrix molecules

Extracellular matrix (ECM) is known to provide signals controlling cell shape, migration, proliferation, differentiation, morphogenesis, and survival. Recent data shows that some of these signals are derived from biologically active cryptic sites within matrix molecules (matricryptic sites) that are revealed after structural or conformational alteration of these molecules. We propose the name, matricryptins, for enzymatic fragments of ECM containing exposed matricryptic sites. Mechanisms regulating the exposure of matricryptic sites within ECM molecules include the major mechanism of enzymatic breakdown as well as others including ECM protein multimerization, adsorption to other molecules, cell-mediated mechanical forces, and ECM denaturation. Such matrix alterations occur during or as a result of tissue injury, and thus, the appearance of matricryptic sites within an injury site may provide important new signals to regulate the repair process. Here, we review the data supporting this concept and provide insight into why the increased exposure of matricryptic sites may be an important regulatory step in tissue responses to injury.     

Dynamics of the junction between the medulla and the cervical spinal cord: An in vivo study in the sagittal plane by magnetic resonance imaging

Summary Sagittal sections of the brain-stem made by MRI reveal differences in the angle formed by the medulla and the cord. In order to study the normal mobility of this region of the CNS during flexion and extension of the head, sagittal MRI studies were made in the sagittal plane in 18 young volunteers. The volunteers were in dorsal decubitus with the cervical spine first flexed and then extended, with the movement localized to the cranio-cervical junction as far as possible. T1-weighted sequences were used, with body coils in 16 cases and surface coils in two. Measurements were related to global cranio-cervical range of movement, movement at the craniocervical junction and spino-medullary movement. Variations in the depth of the free space in front of the medulla, pons and spinal cord during movement were also noted. We also checked for downward shift of the lower part of the 4th ventricle and modification of the shape of the ventricle during flexion-extension. The global range of cranio-cervical movement was between 31 and 100° (average 63°). The range between the cranium and C1C2 was 4 to 39° (average 19°) and the spino-medullary range was from 1 to 32° (average 14°). During flexion, the free space narrowed in front of the pons 11 times, in front of the medulla 14 times and in front of the cervical cord 11 times. There was a downward shift of the lower part of the 4th ventricle during flexion in 4 cases but no change in shape was noted. Though this study is open to criticism from several aspects, it may be concluded that variations of the spino-medullary angle in the sagittal plane during flexion-extension do occur, that they are closely correlated with movements at the cranio-cervical junction, and that the spino-medullary junction moves forward during flexion.

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Dynamique de la jonction bulbomédullaire et de la moelle cervicale: Étude in vivo dans le plan sagittal en imagerie par résonance magnétique

Résumé Dans le but d'étudier la mobilité normale de la jonction bulbomédullaire durant la flexionextension de la tête, nous avons exploré en IRM dans le plan sagittal 18 jeunes volontaires. L'appareil Magniscan 0,15 Tesla a été utilisé avec des séquences de spin écho courtes, 16 fois en antenne corps et 2 fois en antenne de surface. Dans les limites de notre méthodologie, le secteur global de mobilité cervico-céphalique varie de 31 à 100° (moyenne 63°), le secteur de mobilité O-C1C2 varie de 4 à 39° (moyenne 19°), le secteur de mobilité bulbomédullaire varie de 1 à 32° (moyenne 14°). Lors de la flexion, l'espace libre diminue 11 fois devant la protubérance, 14 fois devant le bulbe et 11 fois devant la moelle cervicale. La partie basse du V4 s'abaisse dans 4 cas en flexion. Aucune modification de la forme du V4 n'a pu être notée. Bien que cette étude soit critiquable à bien des égards, nous pouvons affirmer: que les variations de l'angle bulbomédullaire dans le plan sagittal durant la flexion-extension de la tête sont effectives; qu'elles sont étroitement corrélées à celles de la charnière cranio-rachidienne; que durant le mouvement de flexion, la jonction bulbomédullaire se déplace en avant.