Molecular epidemiology of spinocerebellar ataxias in Cuba: Insights into SCA2 founder effect in Holguin

The objective of this study was to determine the prevalence of hereditary ataxias in Cuba, with a special focus on the clinical and molecular features of SCA2. Clinical assessments were performed by neurological examinations and application of the SARA scale. Molecular analyses of genes SCA1–3, SCA6, SCA17 and DRPLA identified 753 patients with SCA and 7173 asymptomatic relatives, belonging to 200 unrelated families. 86.79% of all SCA patients were affected with SCA2. In the Holguin province, the average population prevalence of SCA2 is 40.18 × 10⁵ inhabitants, with the remarkable figure of 141.66 × 10⁵ in the Baguanos municipality. The high prevalence of the SCA2 mutation in Holguin reflects most likely a founder effect. The stabilization of the prevalence along time suggests the existence of premutated chromosomes with pure CAG, acting as reservoir for further expansions. CAG repeat length correlated inversely with age at onset, accounting for 80% of the variability. Genetic anticipation was observed in the 80% of transmissions. Repeat instability was greater in paternal transmissions whereas CAG expansions without anticipation was observed in 10.97% suggesting the effect of CAA interruptions in the CAG segment, which decrease the toxicity of the abnormal ataxin-2, and/or other protective factors.     

Scleral fixation of posterior chamber intraocular lenses using fascia lata to cover the knots

BACKGROUND AND OBJECTIVE: To describe the use of fascia lata to cover the polypropylene knots of scleral fixated posterior chamber intraocular lenses (PCIOL). PATIENTS AND METHODS: Fascia lata was used to cover the knots of scleral fixated PCIOL in 5 eyes with significant scleral thinning. Four of the 5 eyes had the PCIOL insertion and the fascia lata patching in the same setting. The fifth eye previously had scleral fixated PCIOL with late suture erosion through a partial thickness scleral flap. RESULTS: There was no suture exposure or graft thinning throughout a follow-up period of 8 to 16 months. The eyes tolerated the fascia lata well with no early or late postoperative complications. CONCLUSION: Fascia lata provides an effective means to cover the knots of scleral fixated PCIOL, especially in aphakic patients with significant scleral thinning.     

Immunohistochemical localization of three different prepro-GnRHs in the brain and pituitary of the European sea bass (Dicentrarchus labrax) using antibodies to the corresponding GnRH-associated peptides

The distribution of the cells expressing three prepro-gonadotrophin-releasing hormones (GnRH), corresponding to salmon GnRH (sGnRH), seabream GnRH (sbGnRH), and chicken GnRH-II (cGnRH-II) forms, was studied in the brain and pituitary of the sea bass (Dicentrarchus labrax) by using immunohistochemistry. To circumvent the cross-reactivity problems of antibodies raised to GnRH decapeptides, we used specific antibodies generated against the different sea bass GnRH-associated peptides (GAP): salmon GAP (sGAP), seabream GAP (sbGAP), and chicken-II GAP (cIIGAP). The salmon GAP immunostaining was mostly detected in terminal nerve neurons but also in ventral telencephalic and preoptic perikarya. Salmon GAP-immunoreactive (ir) fibers were observed mainly in the forebrain, although sGAP-ir projections were also evident in the optic tectum, mesencephalic tegmentum, and ventral rhombencephalon. The pituitary only receives a few sGAP-ir fibers. The seabream GAP-ir cells were mainly detected in the preoptic area. Nevertheless, sbGAP-ir neurons were also found in olfactory bulbs, ventral telencephalon, and ventrolateral hypothalamus. The sbGAP-ir fibers were only observed in the ventral forebrain, innervating strongly the pituitary gland. Finally, chicken-II GAP immunoreactivity was only detected in large synencephalic cells, which are the origin of a profuse innervation reaching the telencephalon, preoptic area, hypothalamus, thalamus, pretectum, posterior tuberculum, mesencephalic tectum and tegmentum, cerebellum, and rhombencephalon. However, no cIIGAP-ir fibers were detected in the hypophysis. These results corroborate the overlapping of sGAP- and sbGAP-expressing cells in the forebrain of the sea bass, and provide, for the first time, unambiguous information on the distribution of projections of the three different GnRH forms expressed in the brain of a single species.     

Reliability and validity of static knee strength measurements obtained with a chair-fixed dynamometer in subjects with hip or knee arthroplasty

OBJECTIVES: To evaluate the reliability (intertrial, interevaluator) and the concurrent validity of strength measurements obtained with a chair-fixed dynamometer and to recommend a clinical protocol that minimizes standard error of measurement (SEM). DESIGN: Within-session repeated measures of maximal static strength of knee flexors and extensors at 30 degrees and 60 degrees of flexion on the chair-fixed and Cybex dynamometers. SETTING: Ambulatory physiotherapy department of a rehabilitation hospital. PARTICIPANTS: Convenience sample of 50 subjects with total hip (n=25) or knee (n=25) arthroplasty. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Reliability was quantified by indices of dependability and corresponding SEMs estimated with the generalizability theory, whereas coefficients of correlation were used to assess the validity. RESULTS: Indices of dependability confirmed excellent intertrial (0.98-1.00) and a very good interevaluator (.92-.99) reliability for the strength measures obtained for different movements and positions. An average of 3 trials minimized the magnitude of the SEMs (>2 Nm for all measurements). When comparing the strength values obtained with the Cybex dynamometer to those measured with the chair-fixed dynamometer, strongest relations were attained when the tested knee was positioned at 60 degrees compared with 30 degrees for subjects with a total knee (.78-.92 vs .87-.93) or hip (.73-.85 vs .86-.91) arthroplasty. CONCLUSIONS: A clinical protocol averaging 3 trials with the knee positioned at 60 degrees after a familiarization period, both for knee flexors and extensors, performed by a trained therapist is recommended to minimize measurement errors on strength values measured with the chair-fixed dynamometer.     

Single-step maternal serum screening for trisomy 21 in the era of combined or integrated screening

Single-step maternal serum screening (MSS) in the first (1MSS) or second (2MSS) trimester at maternal age > or =35 years was evaluated in the North Belgian region Flanders, where difficulties are encountered in the general introduction of combined or integrated screening algorithms. The fetal aneuploidy screening database of General Medical Laboratory AML in Antwerp was searched for 2MSS tests between 1992 and 1999 (alpha-fetoprotein, beta-human chorionic gonadotropin (beta-HCG) and unconjugated estriol, cut-off 1:300) and for 1MSS tests between 1999 and 2003 (free beta-HCG and pregnancy-associated plasma protein A, cut-off 1:85). At > or =35 years, the detection rate for trisomy 21 (DR) was 93.8% (15/16) for 2MSS and the screen-positive rate (SPR) was 24.5% (504/2061). For 1MSS, these figures were 85.7% (6/7) and 17.7% (109/615) respectively. To detect one trisomy 21, missed by MSS at > or =35 years of age, an additional number of 1,557 and 506 primary invasive procedures would be needed for 2MMS and 1MSS respectively. We conclude that the performance of both single-step 1MSS and 2MSS at maternal age > or =35 years in Flanders is excellent, even without the combination with ultrasound parameters or integration of first and second trimester parameters. The simplicity of both methods allows to consider them valuable options for fetal aneuploidy screening at advanced maternal age, until high quality combined or integrated screening is accessible to all pregnant women in Belgium.     

Perioperative cardiorespiratory complications in adults with mediastinal mass: incidence and risk factors

BACKGROUND: Patients with a mediastinal mass are at risk for cardiorespiratory complications in the perioperative period. The authors' objectives were to evaluate the incidence of life-threatening intraoperative cardiorespiratory and postoperative respiratory complications in adult patients and to study the usefulness of clinical signs and symptoms, radiologic evaluation, and pulmonary function tests in the determination of the perioperative risk. METHODS: The authors reviewed the investigation and treatment of adult patients presenting with anterior or middle mediastinal masses for surgery under anesthesia between January 1994 and July 2000. RESULTS: Ninety-eight patients underwent 105 anesthetic cases. The incidences of intraoperative cardiorespiratory and postoperative respiratory complications were 4 in 105 and 11 in 105, respectively. No collapse of the airways occurred during anesthesia. However, a high incidence of early postoperative life-threatening respiratory complications was observed (7 in 105). In a multivariate logistic regression analysis model, perioperative complications were predicted by the occurrence of cardiorespiratory signs and symptoms at the initial presentation (odds ratio [OR], 6.2) and the presence of combined obstructive and restrictive patterns (mixed pulmonary syndrome) on pulmonary function tests (OR, 3.9). Intraoperative complications were associated with pericardial effusion on computed tomography scan (OR, 19.8). Postoperative respiratory complications were related to tracheal compression of more than 50% on preoperative computed tomography scan evaluation (OR, 7.4) and mixed pulmonary syndrome on pulmonary function tests (OR, 15.1). CONCLUSION: Obstruction of the airway in an adult with a mediastinal mass is a rare event in the intraoperative period. Nevertheless, caution should be observed for the occurrence of early postoperative life-threatening respiratory complications. Patient at high risk of perioperative complications can be identified by the occurrence of cardiopulmonary signs and symptoms at presentation, combined obstructive and restrictive pattern on pulmonary function tests, and computed tomography scan findings (tracheal compression > 50%, pericardial effusion, or both).     

Pharmacogenetics in solid organ transplantation: present knowledge and future perspectives

The promise of pharmacogenetics is to elucidate the inherited basis of differences between individual responses to drugs, in order to identify the right drug and dose for each patient. Genetic polymorphisms are implicated in the interindividual variability of the pharmacokinetic or pharmacodynamic characteristics of immunosuppressive drugs. The first pharmacogenetic trait identified was monogenic, and concerned the prototypic example of thiopurine methyltransferase (TPMT) implicated in azathioprine metabolism. Individuals with low TPMT activity, inherited in an autosomal codominant fashion, are at risk of drug-induced myelosuppression. TPMT activity determination and DNA-based tests are now used in clinical practice. It has been also demonstrated that there is a link between the polymorphisms of the cytochrome P450 3A5, 3A4 and the multidrug resistance-1 (MDR1) genes, and the daily dose necessary to achieve adequate blood tacrolimus levels. Analysis of MDR1 haplotypes or using the association of the different genes might further improve predictions. Since genotyping methods improve rapidly, it will soon be easy to test for thousands of single nucleotide polymorphisms in one assay. Present challenges are to determine the genes of interest and to validate such determination prospectively in clinical practice.     

New insights in developmental origins of different GnRH (gonadotrophin-releasing hormone) systems in perciform fish: an immunohistochemical study in the European sea bass (Dicentrarchus labrax)

The knowledge of the roles and origins of different gonadotrophin-releasing hormone (GnRH) systems could greatly contribute to improve the understanding of mechanisms involved in the physiological control of early development, puberty and spawning. Thus, in this study, we have analyzed the distribution of the cells expressing salmon GnRH, seabream GnRH and chicken GnRH-II forms in the brain and pituitary of developing sea bass using specific antibodies to their corresponding GnRH-associated peptides. The first prepro-chicken GnRH-II-immunoreactive cells arose in the germinal zone of the third ventricle at 4 days after hatching, increasing their number from days 10 to 30, in which they adopted their adult position. The prepro-chicken GnRH-II-immunoreactive fibers became conspicuous in the first week and from day 26 they reached almost all brain areas, especially the hindbrain, being never detected in the pituitary. First prepro-salmon GnRH-immunoreactive cells were detected in the olfactory placode at day 7 after hatching and reached the olfactory bulbs at day 10. Migrating prepro-salmon GnRH cells arrived at the ventral telencephalon at day 15, and became apparent in the preoptic area from day 45. The prepro-salmon GnRH innervation was more evident in the forebrain and increased notably between 10 and 30 days, at which fibers already extended from the olfactory bulbs to the medulla. A few prepro-salmon GnRH-immunoreactive fibers were observed in the pituitary from day 30. The prepro-seabream GnRH-immunoreactive cells were first detected at day 26 in the rostral olfactory bulbs. On day 30, prepro-seabream GnRH-immunoreactive cells were also present in the ventral telencephalon, reaching the preoptic area and the hypothalamus at 45 and 60 days, respectively. The prepro-seabream GnRH innervation appeared restricted to the ventral forebrain, increasing notably during the sixth week, when fibers also reached the pituitary. A significant prepro-seabream GnRH innervation was not detected in the pituitary until day 60.