A high-density SNP linkage scan with 142 combined subtype ADHD sib pairs identifies linkage regions on chromosomes 9 and 16

As part of the International Multi-centre ADHD Genetics project we completed an affected sibling pair study of 142 narrowly defined Diagnostic and Statistical Manual of Mental Disorders, fourth edition combined type attention deficit hyperactivity disorder (ADHD) proband-sibling pairs. No linkage was observed on the most established ADHD-linked genomic regions of 5p and 17p. We found suggestive linkage signals on chromosomes 9 and 16, respectively, with the highest multipoint nonparametric linkage signal on chromosome 16q23 at 99 cM (log of the odds, LOD=3.1) overlapping data published from the previous UCLA (University of California, Los Angeles) (LOD>1, approximately 95 cM) and Dutch (LOD>1, approximately 100 cM) studies. The second highest peak in this study was on chromosome 9q22 at 90 cM (LOD=2.13); both the previous UCLA and German studies also found some evidence of linkage at almost the same location (UCLA LOD=1.45 at 93 cM; German LOD=0.68 at 100 cM). The overlap of these two main peaks with previous findings suggests that loci linked to ADHD may lie within these regions. Meta-analysis or reanalysis of the raw data of all the available ADHD linkage scan data may help to clarify whether these represent true linked loci.     

Regional radiotherapy versus an axillary lymph node dissection after lumpectomy: a safe alternative for an axillary lymph node dissection in a clinically uninvolved axilla in breast cancer. A case control study with 10 years follow up

Background

To correlate the metabolic changes with size changes for tumor response by concomitant PET-CT evaluation of lung cancers after radiotherapy.

Methods

36 patients were studied pre- and post-radiotherapy with¹⁸FDG PET-CT scans at a median interval of 71 days. All of the patients were followed clinically and radiographically after a mean period of 342 days for assessment of local control or failure rates. Change in size (sum of maximum orthogonal diameters) was correlated with that of maximum standard uptake value (SUV) of the primary lung cancer before and after conventional radiotherapy.

Results

There was a significant reduction in both SUV and size of the primary cancer after radiotherapy (p < 0.00005). Among the 20 surviving patients, the sensitivity, specificity, and accuracy using PET (SUV) were 94%, 50%, 90% respectively and the corresponding values using and CT (size criteria) were 67%, 50%, and 65% respectively. The metabolic change (SUV) was highly correlated with the change in size by a quadratic function. In addition, the mean percentage metabolic change was significantly larger than that of size change (62.3 ± 32.7% vs 47.1 ± 26.1% respectively, p = 0.03)

Conclusion

Correlating and incorporating metabolic change by PET into size change by concomitant CT is more sensitive in assessing therapeutic response than CT alone.     

A preliminary biomechanical evaluation in a simulated spinal fusion model. Laboratory investigation

OBJECT: A preliminary in vitro biomechanical study was conducted to determine if the pressure at a bone graft-mortise interface and the load transmitted along a ventral cervical plate could be used as parameters to assess fusion status. METHODS: An interbody bone graft and a ventral plate were placed at the C3-4 motion segment in six fresh cadaveric goat spines. Polymethylmethacrylate (PMMA) was used to simulate early bone fusion at the bone graft site. The loads along the plate and the simultaneous pressures induced at the graft-endplate interfaces were monitored during simulated stages of bone healing. Each specimen was nondestructively tested in compression loading while the pressures and loads at the graft site were recorded continuously. Each specimen was tested under five conditions (Disc, Graft, Plate, PMMA, and Removal). RESULTS: The pressure at the interface of the bone graft and vertebral endplate did not change significantly with the addition of the ventral plate. The interface pressure and segmental stiffness did increase following PMMA augmentation of the bone graft (simulating an intermediate phase of bone fusion). The load transmitted along the ventral plate in compression increased after the addition of the bone graft, but decreased after PMMA augmentation. Thus, there was an increase in pressure at the graft-endplate interface and a decrease in load transferred along the ventral plate after the simulation of bone fusion. Upon removal of the ventral plate, the simulated fusion bore most of the axial load, thus explaining a further increase in graft site pressure. CONCLUSIONS: These observations support the notions of load sharing and the redistribution of loads occurring during and after bone graft incorporation. In the clinical setting, these parameters may be useful in the assessment of fusion after spine surgery. Although feasibility has been demonstrated in this preliminary study, further research is needed.     

<Emphasis Type=Italic>CYP2C19</Emphasis> and <Emphasis Type=Italic>ABCB1</Emphasis>gene polymorphisms are differently distributed according to ethnicity in the Brazilian general population

Background  

Recent studies have reported the clinical importance of CYP2C19 and ABCB1 polymorphisms in an individualized approach to clopidogrel treatment. The aims of this study were to evaluate the frequencies of CYP2C19 and ABCB1 polymorphisms and to identify the clopidogrel-predicted metabolic phenotypes according to ethnic groups in a sample of individuals representative of a highly admixtured population.     

Blast cells in child and adult AML: comparative study of morphocytochemical, immunological and cytogenetic characteristics

Bone marrow blast cells of 174 child and 188 adult patients with AML were examined and characterized in terms of their FAB type, immunological phenotype (102 children, 123 adults) and karyotype (69 children, 95 adults). The incidence of FAB variants of AML proved similar in children and adults. In patients under 15 and over 60, peroxidase activity in myeloblasts was lower than in middle-aged patients. Similar rates of HLA-Dr, Thy-1, CD11a, T-cell antigens, CD19, Gly-A and Eb antigens were found in cells of child and adult patients. The frequency of CD11b, CD38 and CD10 antigen expression on blast cells was higher in children than in adults. Abnormal blast karyotype was noted in 81.8% of children and 73.7% of adults. Translocation (8;21) was usually found in cases of M2 type (82%), significantly more frequently in children, predominantly in the group aged 6-10. t(15;17) was detected in all age groups only in M3 type of cells (86%), t(9;22) occurred more frequently in adults than in children; t(11q23) incidence rates were somewhat higher in children than in adults. Three cases of AML in children are described with deletion of chromosome 5 in their leukaemic cells. The data obtained indicate different biological characteristics of blast cells in children and adults. It is likely that haemopoietic cell involvement in children under 2 years and adult patients over 60 occurs at earlier stages than in middle-aged patients.     

Biomechanische Zustand der Hornhaut als neuer Indikator für pathologische und strukturelle Veränderungen

Aim

Several methods permit the measurement of geometric parameters of the cornea, but until now biomechanical conditions of the cornea have been ignored (e.g. in refractive corneal surgery). Besides the geometric condition, biomechanical properties of the cornea have been shown to influence applanation measurement of intra-ocular pressure (IOP) and epidemiological studies have identified corneal thickness as an independent risk factor for the development and progression of glaucoma. The aim of this investigation was to characterize the biomechanical properties of the cornea using the ocular response analyzer (ORA).

Methods

The ocular response analyzer (ORA) is a new method available for non-contact measurement of the biomechanical properties of the cornea. We evaluated the reproducibility of measurements, the difference between static and dynamic factors and the impact of independent factors (e.g. IOP, age, CCT, swelling of the cornea) on 2,500 measurements of corneal hysteresis (CH) and corneal resistance factor (CRF).

Results

In a large sample size we observed changes in CH and CRF after refractive surgery procedures (LASIK, UV-A cross-linking, keratoplasty) and in other corneal disorders (keratoconus, corneal dystrophies).

Conclusions

CRF and CH changes may reflect structural changes of the cornea. Thus, the ORA provides valuable information for a better understanding and characterization of the biomechanical condition of the cornea, especially with regard to diseases such as keratoconus and glaucoma.     

Gentamicin interval in newborn infants as determined by renal function and postconceptional age

We evaluated the relationship between gentamicin pharmacokinetics and glomerular filtration rate in newborn infants to estimate the appropriate interval of administration in neonates with renal insufficiency. Gentamicin half-life (Gt 1/2) could be predicted from plasma creatinine concentration (Pcr) (r=0.78); the prediction was minimally but significantly increased (r=0.81) by adding postconceptional age to a multiple regression analysis. Infants with a postconceptional age of 29 weeks or more and a Pcr of 1 mg/dl or more had significantly greater trough and peak gentamicin levels than those with a Pcr less than 1 mg/dl. If gentamicin is indicated in a patient with renal insufficiency, the interval of administration should be 2–3 G_t 1/2, which can be estimated from Pcr (Gt 1/2=2.0+7.7 Pcr). The interval can then be adjusted according to peak and trough gentamicin levels.     

Liquidation wahlärztlicher Leistungen

Ohne Zusammenfassung