Disposition of the neuroleptic zuclopenthixol cosegregates with the polymorphic hydroxylation of debrisoquine in humans

The pharmacokinetics of a single oral dose of the neuroleptic drug zuclopenthixol (10 or 6 mg) was studied in 6 extensive and 6 poor metabolizers of debrisoquine. The peak plasma concentrations of zuclopenthixol did not differ between the phenotypes, whereas the plasma elimination half-life was significantly longer in poor than in extensive metabolizers (29.9 +/- 6.6 vs 17.6 +/- 6.9 h). Accordingly, the total oral plasma clearance was lower in poor than in extensive metabolizers (0.78 +/- 0.27 vs 2.12 +/- 0.65 1/h/kg). Ten of the volunteers had previously participated in a similar study in which the kinetics of perphenazine, another neuroleptic drug, were studied in poor and in extensive metabolizers of debrisoquine. There was a significant correlation between the oral clearance of perphenazine and that of zuclopenthixol among these 10 subjects. The study indicates that the disposition of zuclopenthixol, as well as that of perphenazine, is related to the genetically determined capacity to hydroxylate debrisoquine. The significance of this polymorphism for the clinical use of neuroleptics is discussed.     

Regulation of proopiomelanocortin messenger RNA concentrations by opioid peptides in primary cell cultures of rat hypothalamus.

The effects of opioid peptides on a 1.1-kb long proopiomelanocortin messenger RNA (POMC mRNA) have been investigated in rat hypothalamic cells maintained in culture. Most opioid peptides exerted an inhibitory control on POMC mRNA steady-state concentrations. beta-Endorphin caused a 65% maximal inhibitory effect (IC50 = 6.1 x 10(-9) M) while slightly less inhibition was caused by Met- and Leu-enkephalin, dynorphin A and DADLE ([D-Ala2,D-Leu5] enkephalin). The effects of beta-endorphin and of Met-enkephalin were completely reversed by the delta opioid antagonist ICI 174,864 while the kappa-receptor specific antagonist binaltorphimine or the sigma-receptor specific antagonist DTG (1,3-di(2-tolyl) guanidine) respectively blocked the inhibitory actions of dynorphin A and of DADLE. The mu-receptor specific agonist DAGO ([D-Ala2,N-Me-Phe4,Gly5-OL]enkephalin) did not affect POMC mRNA levels. The failure of the dopaminergic D2 antagonist haloperidol to modify the inhibitory effects of opioid peptides argues for a direct inhibitory opioid peptide modulation of hypothalamic POMC mRNA levels mediated by the delta-, kappa- and sigma- (but not mu-) receptors in vivo.     

The role of intraoperative ultrasonic studies in abdominal surgery

Intraoperative echography is a new field of application of the ultrasound diagnostics. With a special intraoperative examination head the parenchymal abdominal organs may be examined directly in the course of the operation. The intraoperative echo-examination of the tumors and cysts of the liver and pancreas as well as of nephroliths and gallstones is routinely applied in several institutions abroad. The authors report on their initial experiences with intraoperative ultrasonography of different abdominal organs.     

Role of envelope glycoprotein carbohydrate in human immunodeficiency virus (HIV) infectivity and virus-induced cell fusion

Human immunodeficiency virus (HIV) envelope glycoprotein interactions with cell surface CD4 are involved in both virion infectivity and virally mediated cell fusion. D-mannose-specific lectins such as Con A specifically blocked virion infectivity and cell fusion. Studies with a recombinant vaccinia virus containing the HIV envelope gene demonstrated that Con A-mediated inhibition of HIV-induced fusion involved lectin binding to the viral envelope glycoprotein. These results indicate the importance of envelope glycosylation in the pathobiology of HIV infection, and suggest potential mechanisms for interfering with HIV infectivity and cytopathology.     

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.