Adrafinil-induced orofacial dyskinesia.

We describe the first case of orofacial abnormal movements induced by adrafinil, a vigilance promoting agent of the same pharmacological class as modafinil. The dyskinesias did not spontaneously recover despite adrafinil withdrawal for a 4-month period. They were secondly dramatically improved by tetrabenazine, a presynaptic dopaminergic depleting drug which was introduced after the 4-month adrafinil-free period.     

Anatomic variations of the spermatic vein and endovascular treatment of left varicoceles: a pediatric series]

OBJECTIVE: To report on the high incidence of anatomical variants of the origin and course of the internal spermatic vein (ISV) discovered at the time of percutaneous embolization of left varicoceles in a pediatric population. METHODS: We reviewed retrospectively the 65 cases of left varicocele treated by percutaneous embolization (grade II and III) in our institution between 1990 and 2000. The course of the left renal vein (LRV), the origin of the ISV, and the number of ISVs and their pathway were recorded in all cases, according to the B?hren classification. RESULTS: In 37/65 (57%), the ISV was single and arose from a normal LRV (type I). The following variants were encountered: type V--circumaortic LRV 9/65 (14%); type IVb--intrarenal origin of ISV 8/65 (12%); type II--multiple ISV 5/65 (8%); and pelvic collaterals 6/65 (9%). CONCLUSION: Venous anatomical variants are frequently encountered (43%) at the time of left varicocele embolization in children. Such variants often impose some adjustments to the technique of embolization and, at times, hamper the procedure.     

Impact of photon energy recovery on the assessment of left ventricular volume using myocardial perfusion SPECT

BACKGROUND: Photon energy recovery (PER) is a spectral deconvolution technique validated for scatter removal in patients and phantom studies. The purpose of this study was to examine the impact of PER on left ventricular volume measurement based on myocardial perfusion single photon emission computed tomography (SPECT). METHODS AND RESULTS: SPECT acquisitions were performed by use of a static cardiac phantom and in 25 patients after a rest injection of technetium 99m sestamibi by use of multiple energy windows (126-136, 137-144, and 145-154 keV). Data were successively reconstructed with and without PER, by use of iterative reconstruction and post-processing filtering (Butterworth filter; order, 5; cutoff, 0.30 cycles/pixel). Image contrast was evaluated in reconstructed data, and volumes were calculated by use of QGS. PER increased reconstructed image contrast from 62% +/- 2.7% to 84.3% +/- 5.7% in the phantom studies (P <.0001) and from 49% +/- 2% to 73% +/- 2% in patients (P <.0001). Although it remained underestimated (P <.0001), phantom volume was higher after PER correction compared with uncorrected data (50.9 +/- 0.8 mL vs 44.6 +/- 1 mL, P <.0001). The error in volume measurement was decreased by PER correction (16.6% +/- 1.3% vs 27% +/- 1.7% [uncorrected data], P <.0001). In patients, left ventricular volume increased from 83 +/- 10 mL to 91 +/- 10 mL (P <.0001), and the PER-induced volume increase was correlated with the image contrast increase (r = 0.61, P =.001). Finally, the percentage of volume increase was higher in patients with small left ventricular volumes. CONCLUSIONS: PER has a significant impact on image contrast and left ventricular volume measurement by use of perfusion SPECT. PER improves the accuracy of phantom volume assessment. In patients, volume increase is correlated to image contrast increase and is higher in those with small ventricles.     

Endolymphatic mastoid shunt versus endolymphatic sac decompression for Ménière's disease.

OBJECTIVE: This study compares the efficacy of endolymphatic mastoid shunt (EMS) versus endolymphatic sac decompression (ESD) without sac incision for the treatment of Ménière's disease. STUDY DESIGN AND SETTING: The AAO-HNS Guidelines for the Diagnosis and Evaluation of Therapy in Ménière's disease were used to retrospectively identify suitable candidates for the study. All patients who failed medical management and underwent either endolymphatic-mastoid shunt (EMS) (n = 88) or endolymphatic sac decompression (ESD) (n = 108) were selected for review using the AAO-HNS guidelines. The study was carried out at a tertiary care neurotology private practice. RESULTS: EMS and ESD were equally effective in reducing the incidence and severity of vertigo attacks with significant improvement in 67 percent and 66 percent of patients, respectively. CONCLUSION: Both EMS and ESD are effective, nondestructive alternatives for patients who have failed medical management of Ménière's disease with similar long-term hearing outcomes. SIGNIFICANCE: This is the only study within the same institution using AAO-HNS guidelines comparing EMS versus ESD.     

Association of HLA-DQA1*03011-DQB1*0301 haplotype with the development of respiratory scleroma.

OBJECTIVE: Respiratory scleroma (RS) is a progressive, chronic, granulomatous disease caused by Klebsiella rhinoscleromatis. There is only one report of RS association with HLA-DQ3. In this study, molecular association of HLA class II and RS was determined. STUDY DESIGN AND SETTING: Nine RS patients and 163 healthy controls were compared. DQA1, DQB1, and DRB1 loci were typed. RESULTS: Statistical analysis demonstrated association between DQB1*0301 and susceptibility to RS (P(c) = 0.004). Haplotype analysis showed an association of DQA1*03011-DQB1*0301 (P = 1.21E-19) and DRB1*0407-DQA1*03011-DQB1*0301 (P = 0.0002). CONCLUSIONS: Results established that DQA1*03011-DQB1*0301 haplotype is a strong risk factor for development of RS.     

Alterations in the ultrastructure of cardiac autonomic nervous system triggered by crotoxin from rattlesnake (Crotalus durissus cumanensis) venom.

This study explored the toxic effects of crotoxin isolated from Crotalus durissus cumanensis venom on the ultrastructure of mice cardiac autonomic nervous system. Mice were intravenously injected with saline (control group) and crotoxin diluted in saline venom (study group) at a dose of 0.107 mg/kg mouse body weight. Samples from the inter-ventricular septum were prepared for electron microscopy after 6 h (G1), 12 h (G2), 24 h (G3) and 48 h (G4). The G1 group showed some cardiomyocyte with pleomorphic mitochondria. Capillary swollen walls, nerve cholinergic endings with depleted acetylcholine vesicles in their interior and other depletions were observed. A space completely lacking in contractile elements was noticed. The G2 group demonstrated a myelinic figure, a subsarcolemic region with few myofibrils and nervous cholinergic terminal with scarce vacuoles in their interior. The G3 group demonstrated a structure with a depleted axonic terminal, mitochondrias varying in size and enhanced electron density. In addition, muscular fibers with myofibrillar structure disorganization, a depleted nervous structure surrounded by a Schwann cell along with an abundance of natriuretic peptides, were seen. An amyelinic terminal with depleted Schwann cell and with scarce vesicles was also observed. Finally, axonic lysis with autophagic vacuoles in their interior and condensed mitochondria was observed in the G4 group. This work describes the first report of ultrastructural damage caused by crotoxin on mice cardiac autonomic nervous system.     

In vitro studies of the carotid rete mirabile of Artiodactyla

The carotid rete of Artiodactyla, an intracranial arterial plexus which supplies blood to the brain, has intrigued investigators for a long time. This study was designed to examine the responsiveness of isolated retial arteries (250-700 microns in external diameter) of goat, pig, and cattle. The findings in these arteries were compared to those observed in cerebral arteries (250-650 microns in external diameter) of the same animal species. The magnitude of the arterial responses to potassium chloride varied with the resting tension applied to the tissue. The two types of vessels exhibited similar resting tension values (0.3 g) for maximal tension development in response to potassium chloride; however, the ability of retial vessels to contract in the presence of potassium chloride was consistently smaller than that of cerebral arteries. The contractile response of retial arteries to norepinephrine (10(-9) to 10(-4) M), tyramine (10(-8) to 10(-3) M), and field electrical stimulation (2-16 Hz) was negligible. The same retial arteries exhibited dose-dependent contractions in response to 5-hydroxytryptamine (10(-9) to 10(-5) M) and histamine (10(-9) to 3 X 10(-4) M). Cerebral arteries exhibited larger responses to the vasoactive agents than retial arteries. Our findings indicate that retial arteries have a small vasomotor activity in response to adrenergic stimulation or to vasoactive agents. Therefore, the carotid rete of Artiodactyla may have a low ability to change resistance to blood flow under neural or hormonal influences.     

On the role of Ca2+ in the toxicity of alkylating and oxidizing quinone imines in isolated hepatocytes

The cytotoxicity of acetaminophen (paracetamol) has been shown to be associated with a disruption of intracellular Ca2+ homeostasis caused by the interaction of its metabolite N-acetyl-p-benzoquinone imine (NAPQI) with hepatocyte thiols [Moore, M., et al. (1985) J. Biol. Chem. 260, 13035-13040]. Inasmuch as NAPQI can both covalently bind to thiols and oxidize thiols, we investigated the effects of two dimethylated analogues of NAPQI, one of which (2,6-dimethyl-NAPQI) primarily binds to thiols and the other of which (3,5-dimethyl-NAPQI) primarily oxidizes thiols. Of the three compounds, 2,6-dimethyl-NAPQI decreased protein thiols to the greatest extent and also inhibited hepatocyte plasma membrane Ca(2+)-ATPase to the greatest extent. The 3,5-dimethylated analogue decreased protein thiols to the least extent and inhibited the plasma membrane Ca(2+)-ATPase to a lesser extent. The cytotoxicity of all three compounds was preceded by a sustained elevation in cytosolic Ca2+ as compared to the transient rise caused by the alpha-agonist phenylephrine. Again, the 2,6-dimethyl analogue was the most potent of the three compounds. The thiol reagent dithiothreitol (DTT), which reversed the inhibition of the Ca(2+)-ATPase and the rise in cytosolic Ca2+, also protected against cytotoxicity. Agents that are known to inhibit either Ca(2+)-dependent proteases or phospholipases significantly delayed the onset of cytotoxicity caused by NAPQI and its analogues. Our results suggest that both arylation and oxidation of protein thiols may result in the elevation of cytosolic Ca2+ and in cytotoxicity and that arylation of critical thiol groups appears to be the more lethal reaction.     

Kinetic and biologic properties of recombinant ChIFN-gamma expressed via CELO-virus vector.

In this study, a replicative fowl adenovirus serotype 1 (CELO) recombinant expressing chicken interferon-gamma (ChIFN-gamma) was constructed. In the engineered recombinant, the ChIFN-gamma gene was placed under the control of cytomegalovirus (CMV) promoter. The ChIFN-gamma expression cassette was inserted in the right end of the CELO genome (D fragment), which was able to carry the largest insertion of foreign DNA without affecting the replication functions of the vector. The recombinant ChIFN-gamma (rChIFN-gamma) produced in the CELO-virus expression system was characterized by comparing its biologic activities with that of rChIFN-gamma produced via the baculovirus expression system (Bac-ChIFN-gamma). CELO-ChIFN-gamma inhibited the replication of cytolytic virus in chicken embryo fibroblasts (CEFs) and activated macrophages in a better manner than did Bac-ChIFN-gamma . Moreover, the in vitro and in vivo stability of the CELO-derived rChIFN-gamma was considerably higher than that of the Bac-ChIFN-gamma. The CELO-ChIFN-gamma recombinant vector was able to replicate in vitro in the loghorn male hepatoma (LMH) hepatocyte cell line and to produce detectable levels of recombinant cytokine in supernatant as early as 90 min post-infection. Therefore, the CELO-virus expression system is an appropriate system for high-level expression of biologically active and stable ChIFN-gamma.