Genetic variability of wild-type measles viruses, circulating in the Russian Federation during the implementation of the National Measles Elimination Program, 2003–2007

Genetic characterization of wild-type measles viruses (MVs) is an important component of laboratory surveillance of measles. In this study, a phylogenetic analysis was performed of the nucleoprotein gene sequences of 228 MVs isolated in the Russian Federation between 2003 and 2007. Five genotypes, D4, D5, D6, D8, and H1, were detected. From 1999 through the first 6 months of 2003, the most prevalent genotype in the European part of Russia was D4. All genotype D4-type viruses were closely related to each other (with overall sequence diversity of ≤0.9%), suggesting the presence of a single endemic MV strain. After 2003, viruses with closely related sequences within genotype D6 (≤0.9% sequence diversity) were prevalent. During this time, there was a low level of indigenous transmission of genotype D6, and genotype D6 viruses were imported from neighbouring countries, which led to the identification of two lineages of genotype D6, i.e. D6a and D6b. Lineage D6a was closely related to viruses isolated in Turkey, Kazakhstan, and Uzbekistan, whereas lineage D6b was linked to a large outbreak in Ukraine in 2005–2006. Genotypes H1, D5 and D8 were associated with sporadic cases and clusters of transmission linked to importations. Enhanced vaccination interrupted the transmission of the previous endemic lineage D4 in 2003 and of lineage D6a in 2005, although an accumulation of susceptible individuals in the population allowed for prolonged circulation of lineage D6b. These data on MV genotype distribution, in conjunction with the epidemiological data for measles, show considerable progress in measles control and suggest that regional elimination is possible.     

Return of gonadotropic function in postpartum women during bromocriptine treatment

The rapid postpartum return of gonadotropic function during bromocriptine treatment was investigated through hormonal measurements in 15 women. Luteinizing hormone (LH) was measured by a novel and specific assay that does not cross-react with human chorionic gonadotropin (hCG). Prolactin was effectively suppressed by bromocriptine and hCG was cleared within 2 weeks. During the first week, both follicle-stimulating hormone (FSH) and LH were undetectable. The return of FSH and LH secretion occurred in the second postpartum week and initially was characterized by a high FSH/LH ratio. The causes of the 1-week delay in resumption of pituitary gonadotropin secretion are not known, but endogenous opioids may play a role. The possible relation between the high FSH/LH ratio and low LH pulse frequency also is discussed.     

Congenital orbital vascular malformation complicated by massive retrobulbar hemorrhage

A 2-year-old female infant with a presumed diagnosis of infantile hemangioma of the left eyebrow developed acute proptosis of the left eye several days after a mild orbital trauma. Computerized axial tomography (CAT) and carotid angiography confirmed the presence of a vascularized mass in the retrobulbar space, spreading anteriorly to the orbital rim and the frontal area. Due to progression of the proptosis and the development of exposure keratitis, surgical intervention was necessary. A large vascular tumor and a massive hemorrhage occupying the orbit were removed. The pathological examination confirmed the diagnosis of a vascular malformation of the orbit, most probably orbital varices. A relatively good visual acuity was achieved after surgery by occlusion therapy.     

Relation of shyness in grade school children to the genotype for the long form of the serotonin transporter promoter region polymorphism

OBJECTIVE: Studies have shown that genetic factors are significant in predisposing individuals to shyness and social phobia. Toward further elucidating the genetic structure of shyness, the authors examined four functional polymorphisms that make biological sense for contributing to the development of this phenotype: serotonin transporter promoter region 44 base pair insertion/deletion (5-HTTLPR), dopamine D(4) receptor exon III repeat (DRD4), catechol O-methyltransferase (COMT), and monoamine oxidase A promoter region repeat (MAO(A)). METHOD: The authors assessed shyness after recruitment of a nonclinical sample (N=118, unscreened second-grade children) using a composite scale derived from questionnaires administered to the children, parents, and teachers. DNA from buccal smears successfully obtained from 98 children was genotyped by polymerase chain reaction methods for the 5-HTTLPR, DRD4, COMT, and MAO(A) polymorphisms. RESULTS: Significant correlations were observed for parents', teachers', and children's ratings of shyness, and Cronbach's alpha reliability was high for all three scales. A significant association was observed between the long 5-HTTLPR polymorphism and shyness, both by the functional classification of Lesch as well as by consideration of all three genotypes. No significant association was observed for the DRD4, COMT, or MAO(A) polymorphisms. CONCLUSIONS: This study provisionally identifies a common genetic polymorphism, 5-HTTLPR, that modestly (effect size=7%) contributed to greater shyness scores in a nonclinical group of second-grade students. These first findings may be relevant to previous reports that have shown an association between the 5-HTTLPR long form and obsessive-compulsive disorder and autism.     

Pharmacogenetics of antidepressant medication intolerance

OBJECTIVE: The authors sought to identify genetic markers for antidepressant medication intolerance. Genetic variation in drug metabolizing enzymes such as cytochrome P450 2D6 (CYP2D6) has been postulated to underlie antidepressant intolerance (pharmacokinetic effect). However, variation in genes encoding serotonin receptors could also explain antidepressant side effects (pharmacodynamic effect). METHOD: An 8-week, double-blind, randomized pharmacogenetic study compared the widely prescribed antidepressants paroxetine (a selective serotonin reuptake inhibitor [SSRI]) and mirtazapine (not an SSRI) in 246 elderly patients with major depression. Genotypes were determined for the 102 T/C single nucleotide polymorphism (SNP) in the serotonin 2A (5-HT(2A)) locus (HTR2A), previously associated with psychotropic medication treatment outcome. Oligonucleotide microarrays were used to extensively characterize variation in the CYP2D6 gene. Clinical outcomes included treatment discontinuations, adverse events, medication compliance, and change in mood. RESULTS: Survival analysis showed discontinuations due to paroxetine-induced side effects were strongly associated with the HTR2A C/C genotype. There was a significant linear relationship between the number of C alleles and the probability of discontinuation. Side effect severity in paroxetine-treated patients with the C/C genotype was also greater. In contrast, HTR2A 102 T/C genotype had no effect on mirtazapine side effects. CYP2D6 genotype did not predict treatment outcome for either medication. CONCLUSIONS: Pharmacodynamic differences among patients due to variant 5-HT(2A) receptors appear to be more important than pharmacokinetic variation in determining paroxetine intolerance. Pharmacogenetic markers may be useful in predicting antidepressant treatment outcome.     

"Strukturierter Fragebogen Simulierter Symptome"

The current article addresses the psychometric qualities of the German version of the Structured Inventory of Malingered Symptomatology (SIMS), a self-report measure of malingering. The SIMS was administered to a heterogeneous sample of forensic patients (n=62) and undergraduate students (n=204). Within the student sample, some undergraduates were instructed to feign certain pathological conditions, while others were asked to respond honestly to the SIMS items. The findings indicate that the German version of the SIMS demonstrates adequate test-retest stability and internal consistency. In the patient sample, the SIMS was found to correlate strongly with manipulative and antisocial personality features. More specifically, SIMS scores were higher in sexually delinquent patients with antisocial personality disorders. Our findings support the SIMS as a valuable screening tool for malingering of psychiatric symptoms.     

Coronary hybrid revascularization from January 1997 to January 2001: a clinical follow-up

Background. Hybrid revascularization (HyR), combining minimally invasive left internal mammary artery (LIMA) bypass grafting to the left anterior descending coronary artery (LAD) and catheter interventional treatment of the remaining coronary lesions, avoids the disadvantages associated with cardiopulmonary bypass (CPB). We investigated the clinical follow-up of 57 patients with multivessel disease undergoing this procedure in the last 4 years.

Methods. Between January 1997 and January 2001, 57 consecutive patients (41 men and 16 women, aged 65.7 ± 7.9 years) with coronary artery disease (two-vessel, n = 34; three-vessel, n = 23) were treated with off-pump LIMA-to-LAD bypass combined with balloon angioplasty and stenting of the remaining significantly obstructed (> 50%) coronary vessels. Clinical follow-up data included a early postoperative and a 6-month control angiography and a patient interview in January 2001.

Results. All patients underwent LIMA-to-LAD bypass-grafting and balloon angioplasty in 72 coronary lesions without procedural-related complications. However, one early LIMA bypass occlusion was documented during coronary angiography. Postoperatively no deterioration of preexistent organ dysfunction was observed in any patient. The mean follow-up was 100.7 ± 37.9 weeks in 55 of 57 patients (97%). Control angiography 6 months after HyR (n = 34) revealed a patent LIMA bypass in 33 patients and 8 in-stent restenoses (> 50%) in the coronary arteries that were treated interventionally by re-PTCA (n = 6) or by conventional CABG (n = 1). In 1 patient medical treatment resulted in significant reduction of angina so no further intervention was considered necessary. After HyR 1 patient died 18 months later of an intracerebral hemorrhage. All other patients are alive and doing well.

Conclusions. Our results indicate that in selected patients with multivessel disease including left main stem stenosis HyR is an effective and secure procedure with excellent early and good midterm results. Especially elderly patients with severe concomitant diseases appear to benefit from this approach by avoiding CPB.