Effect of riluzole on the neurological and neuropathological changes in an animal model of cardiac arrest-induced movement disorder

Posthypoxic myoclonus and seizures precipitate as secondary neurological consequences in ischemic/hypoxic insults of the central nervous system. Neuronal hyperexcitation may be due to excessive activation of glutamatergic neurotransmission, an effect that has been shown to follow ischemic/hypoxic events. Therefore, riluzole, an anticonvulsant that inhibits the release of glutamate by stabilizing the inactivated state of activated voltage-sensitive sodium channels, was tested for its antimyoclonic and neuroprotective properties in the cardiac arrest-induced animal model of posthypoxic myoclonus. Riluzole (4-12 mg/kg i.p.) dose-dependently attenuated the audiogenic seizures and action myoclonus seen in this animal model. Histological examination using Nissl staining and the novel Fluoro-Jade histochemistry in cardiac-arrested animals showed an extensive neuronal degeneration in the hippocampus and cerebellum. Riluzole treatment almost completely prevented the neuronal degeneration in these brain areas. The neuroprotective effect was more pronounced in hippocampal pyramidal neurons and cerebellar Purkinje cells. These effects were seen at therapeutically relevant doses of riluzole, and the animals tolerated the treatment well. These findings indicate that the pathogenesis of posthypoxic myoclonus and seizure may involve excessive activation of glutamate neurotransmission, and that riluzole may serve as an effective pharmacological agent with neuroprotective potential for the treatment of neurological conditions associated with cardiac arrest in humans.     

Hepatectomy in intrahepatic lithiasis

STUDY AIM: The aim of this study was to report the immediate results of a series of 65 hepatic resections for hepatolithiasis performed in Vietnam. PATIENTS AND METHOD: From 1986 to 1998, 44 men and 21 women (mean age: 40 years) underwent hepatic resection for hepatolithiasis. Fourty patients had previously undergone one or several operations for hepatolithiasis. The procedure was performed on emergency in 25 patients. Indications for hepatic resection were: angiocholitis and liver abscess in 22 cases, stones closely inserted in the biliary duct in 20 cases, hemobilia in 12 cases, stones located above a biliary stricture in 8 cases and stones associated with a postoperative biliary fistula in 3 cases. Liver resections (minor in 61 patients, including 55 left lobectomies, and major in 4 patients) were performed through transhepatic approach according to the Ton That Tung technique and followed by an external biliary drainage with a Kehr tube. RESULTS: There were 6 postoperative deaths (9%), 3 due to septic shock, 2 to cachexia, and 1 to liver failure. The 15 patients with complications recovered with conservative therapy. Bile infection was present in 93%, mostly with Escherichia coli and Enterobacter. Pigmented stones were usually found. CONCLUSION: Vietnam is a country with high incidence of hepatolithlasis. Hepatic resection is an adequate treatment for localized intrahepatic bile duct stones when the involved segment including biliary strictures and calculi can be completely removed. The procedure may be performed on emergency for liver abscess, or hemobilia.     

An alternative approach: antegrade catheter-directed thrombolysis in a case of phlegmasia cerulea dolens

Phlegmasia cerulea dolens is an uncommon sequela of severe deep venous thrombosis of the lower extremities. Characterized by massive edema, arterial and venous compromise, and threats to limb and life, this clinical entity is a clear indication for thrombolytic therapy. We report an innovative approach to conventional thrombolysis via a lesser saphenous vein cut-down. This simple technique is a safe, reliable alternative to present methods of achieving deep venous access. Hence, it should be considered as an addition to the treatment armamentarium for massive deep venous thrombosis of the lower extremity.     

Nitric oxide and thromboxane A2-mediated pulmonary microvascular dysfunction

OBJECTIVES: To examine whether the lung releases nitric oxide (NO) in response to thromboxane A2 and to examine the local release of NO as a protective compensatory mechanism by which the lung responds to the proinflammatory and vasoactive effects of thromboxane A2. DESIGN: The lungs of anesthetized Sprague-Dawley rats were perfused in vitro with Krebs-Henseleit buffer that contained an inhibitor of NO synthase (nitroglycerinenitro-L-arginine methyl ester [L-NAME]) (10(-4) mol/L), an NO donor (sodium nitroprusside) (10(-8) mol/L), or perfusate alone. Following equilibration, the thromboxane A2 receptor agonist 9,11-dideoxy-11alpha, 9alpha-epoxymethanoprostaglandin F2alpha(U-46619) (7.1 X 10(-8) mol/L) was added to the perfusate. Fifteen minutes later, the capillary filtration coefficient, pulmonary arterial pressure, and vascular resistance were measured. Pulmonary NO release was assessed by quantitating the release of cyclic guanosine monophosphate into the perfusate. RESULTS: The capillary filtration coefficient of lungs exposed to U-46619 was 3.5 times greater than that of lungs perfused with buffer alone (P<.05). The addition of sodium nitroprusside reduced the increase in capillary filtration coefficient associated with U-46619 by 50% (P<.05) whereas L-NAME had no effect. The addition of U-46619 to the perfused lung caused a 3.0+/-0.4 mm Hg increase in pulmonary artery pressure (P<.01) with a corresponding rise in total vascular resistance (P<.05). This effect was exacerbated by L-NAME (P<.05) and inhibited by sodium nitroprusside (P<.05). Exposure of the isolated lungs to U-46619 caused a 4-fold increase in cyclic guanosine monophosphate levels within the perfusate. CONCLUSION: These data are consistent with the hypothesis that NO release may be an important protective mechanism by which the lung responds to thromboxane A2.     

In vitro and in vivo characterisation of [3H]ANSTO-14 binding to the sigma 1 binding sites

N-(4-phenylbutyl)-3-hydroxy-4-azahexacyclo[5.4.1.0(2,6).0(3, 10).0(5,9) .0(8,11)]dodecane (ANSTO-14) showed the highest activity for the sigma 1 site (Ki = 9.4 nM) and 19-fold sigma 1/sigma 2 selectivity. The present study showed that [3H]ANSTO-14 binds to a single high-affinity site in guinea pig brain membranes with an equilibrium Ki of 8.0 +/- 0.3 nM, in good agreement with the kinetic studies (Kd = 13.3 +/- 5.4 nM, n = 4), and a Bmax of 3.199 +/- 105 fmol/mg protein (n = 4). The in vivo biodistribution of [3H]ANSTO-14 showed a high uptake in the diencephalon. Pretreatment of rats with sigma ligands including (+)-pentazocine (sigma 1), ANSTO-14 (sigma 1), and DTG (sigma 1 and sigma 2) did not significantly reduce radiotracer uptake in the brain, but did in the spleen. A labelled metabolite was found in the liver and brain. Due to its insensitivity to sigma ligands, the accumulation of [3H]ANSTO-14 in the brain indicates high nonspecific binding. Therefore, [3H]ANSTO-14 is a suitable ligand for labelling sigma 1 sites in vitro but is not suitable for brain imaging of sigma binding sites in vivo.     

One and the same androgen for all? Towards designer androgens

The introduction of designer oestrogens as a treatment modality in hormone replacement in women has invited to consider the concept of compounds with selective androgenic effects for male hormone replacement therapy. The full spectrum of the actions of testosterone may not be necessary of even undesired for certain indications for testosterone treatment. To define for what indications certain androgenic properties are desired and undesired more insight in basic androgen (patho)physiology is required. There is convincing evidence that aromatization of androgenic compounds to oestrogens might be an advantage for maintenance of bone mass and it might also mitigate negative effects of androgens on biochemical parameters of cardiovascular risks; the potentially negative effects of oestrogens on prostate pathology in ageing men needs further elucidation. While the role of dihydro-testosterone (DHT) for the male sexual differentiation and for pubertal sexual maturation is evident, its role in mature and ageing males seems less significant or may even be harmful. It is, however, of note that a negative effect of DHT on prostate pathophysiology is certainly not proven. For male contraception a progestational agent with strong androgenic properties might be an asset. For most of the androgenic actions the critical levels of androgens are not well established. The latter is relevant since the large amount of androgen molecules required for its biological actions (as compared to oestrogens) is an impediment in androgen replacement modalities. There may be room for more biopotent androgens since delivery of large amounts of androgen molecules to the circulation poses problems for treatment modalities.     

Neuromuscular disease: health care accessibility in the Nord-Pas-de- Calais region

A survey was conducted to estimate accessibility to current diagnostic techniques for patients with neuromuscular disease living in the Nord-Pas-de-Calais. In association with the "Association fran?aise contre les myopathies", we invited 200 adults with neuromuscular disease to fill out a questionnaire concerning diagnosis of their neuromuscular disease and medical and paramedical follow-up. Each subject answered the questionnaire anonymously providing data on sociodemographic items, diagnosis and medical and paramedical follow-up. The results showed a lack of follow-up for lung disease whereas respiratory failure is known as a frequent complication of neuromuscular disease. Genetic counselling was not suggested often enough. A large proportion (80 p. 100) of the patients had had physiotherapy. Whereas cardiomyopathy and orthopedic buckling with subsequent decreased autonomy are observed in 90 p. 100 of patients with Duchenne muscular dystrophy, only 42 p. 100 of the patients with this disease were followed by a cardiologist and a physical therapists. We suggest more cooperation between specialists in order to improve medical care for patients with neuromuscular diseases.     

Development of receptoral responses in pigmented and albino guinea-pigs (Cavia porcellus)

We describe the postnatal development of the electroretinogram (ERG) receptoral response in the guinea pig. In addition, the time course and nature of maturation was compared between albino and pigmented strains to consider the role that melanogenesis might have in this process. Electroretinograms were collected on groups of albino and pigmented animals from postnatal day (PD) PD1 to PD60. A-wave amplitudes and implicit times were extracted from filtered data (0–75 Hz). Receptoral components were modelled using the delayed gaussian model of Hood and Birch [1] fitted as an ensemble to the raw data. Guinea pigs show saturated amplitudes (Rm_P3) that are 50% of adult values at birth, these mature by PD12. Receptoral delay (t_d) also undergoes some postnatal maturation, while phototransduction gain (log S) is adult-like at birth. Albino animals had significantly (p<0.05) larger Rm_P3 and log S across all ages. Guinea pigs have significant postnatal development in their receptoral response. Maturation of Rm_P3 implies a postnatal increase in rod outer segment length. Whereas the adult values of log S implies a mature phototransduction process at birth. We argue that the likely cause for the larger log S of albino eyes is compatible with theories of increased levels of internal light. Whereas the larger Rm_P3, even after allowing for increased light effectiveness, may reflect a lower ocular resistance in albino eyes due to their lower levels of melanin. Furthermore, decreased Rm_P3 and log S with age is observed in the pigmented group only and is consistent with increased ocular resistance due to melanin development in this strain. This revised version was published online in July 2006 with corrections to the Cover Date.     

Conversion factor for comparison of data from Humphrey and Medmont automated perimeters

Background : Clinical experience has shown that the sensitivity indices reported by the Humphrey Field Analyser (HFA) are generally higher than those given by the Medmont Automated Perimeter (M600). It is the purpose of this paper to determine a conversion factor for the two perimeters and to confirm this prediction using clinical data. Theory predicted that HFA_sensitivity ? 5 dB = M600_sensitivity. Methods : Sensitivity versus eccentricity profiles were measured over the central visual field on 10 young subjects using both perimeters. Results : Both the HFA and the M600 operate within the realms of the Weber law and measure similar Weber fractions. The sensitivity profiles had similar slopes (about ?0.2 dB/degree) and were separated by about six decibels with the HFA reporting higher sensitivity values. This result confirmed the theoretical prediction. Conclusion : The difference in threshold sensitivities between the two perimeters is a result of differences in scaling factors and instrument luminances. A suggested clinical conversion factor is to subtract 5 dB from the HFA data to approximate those of the M600.