Automatic registration between reference and on-board digital tomosynthesis images for positioning verification

The authors developed a hybrid multiresolution rigid-body registration technique to automatically register reference digital tomosynthesis (DTS) images with on-board DTS images to guide patient positioning in radiation therapy. This hybrid registration technique uses a faster but less accurate static method to achieve an initial registration, followed by a slower but more accurate adaptive method to fine tune the registration. A multiresolution scheme is employed in the registration to further improve the registration accuracy, robustness, and efficiency. Normalized mutual information is selected as the criterion for the similarity measure and the downhill simplex method is used as the search engine. This technique was tested using image data both from an anthropomorphic chest phantom and from eight head-and-neck cancer patients. The effects of the scan angle and the region-of-interest (ROI) size on the registration accuracy and robustness were investigated. The necessity of using the adaptive registration method in the hybrid technique was validated by comparing the results of the static method and the hybrid method. With a 44 degrees scan angle and a large ROI covering the entire DTS volume, the average of the registration capture ranges in single-axis simulations was between -31 and +34 deg for rotations and between -89 and +78 mm for translations in the phantom study, and between -38 and +38 deg for rotations and between -58 and +65 mm for translations in the patient study. Decreasing the DTS scan angle from 44 degrees to 22 degrees mainly degraded the registration accuracy and robustness for the out-of-plane rotations. Decreasing the ROI size from the entire DTS volume to the volume surrounding the spinal cord reduced the capture ranges to between -23 and +18 deg for rotations and between -33 and +43 mm for translations in the phantom study, and between -18 and +25 deg for rotations and between -35 and +39 mm for translations in the patient study. Results also showed that the hybrid registration technique had much larger capture ranges than the static method alone in registering the out-of-plane rotations.     

Delivery of a hammerhead ribozyme specifically down-regulates the production of fibrillin-1 by cultured dermal fibroblasts

The hammerhead ribozyme is a small catalytic RNA molecule. Potential hammerhead ribozymes that possess a catalytic domain and flanking sequence complementary to a target mRNA can cleave in trans at a putative cleavage site within the target molecule. We have investigated the potential of hammerhead ribozymes to down-regulate the product of the fibrillin-1 gene (FBN1). Fibrillin is a 347 kDa glycoprotein that is a major constituent of the elastin-associated microfibrils. Mutations in the FBN1 gene are responsible for Marfan syndrome (MFS), a common systemic disorder of the connective tissue. Many FBN1 mutations responsible for MFS appear to act in a dominant-negative fashion, raising the possibility that reduction of the amount of product from the mutant FBN1 allele might be a valid therapeutic approach for MFS. A trans-acting hammerhead ribozyme (FBN1-RZ1) targeted to the 5' end of the human FBN1 mRNA has been designed and synthesized, and shown to cleave its target efficiently in vitro. FBN1-RZ1 cleavage is magnesium dependent and efficient at both 37 and 50 degrees C. Delivery of the FBN1-RZ1 ribozyme into cultured dermal fibroblasts, by receptor- mediated endocytosis of a ribozyme-transferrin-polylysine complex, specifically reduces both cellular FBN1 mRNA and the deposition of fibrillin in the extracellular matrix. These results suggest that the use of hammerhead ribozymes is a valid approach to the study of fibrillin gene expression and possibly to the development of a therapeutic approach to MFS.      

Predictors of unknown HIV serostatus at the time of labor and delivery in Kampala,Uganda

Objective

To determine factors associated with an unknown HIV serostatus among pregnant women admitted in labor to Mulago Hospital, Kampala, Uganda.

Methods

In total, 665 pregnant women admitted to Mulago Hospital were interviewed about their sociodemographic characteristics, obstetric history, access to prenatal care, fears regarding HIV testing, and knowledge about modes of mother-to-child-transmission (MTCT). Knowledge of the HIV serostatus was assessed by self-report and verified by prenatal card review.

Results

The prevalence of unknown HIV serostatus at the time of labor was 27.1%. Factors associated with an unknown HIV serostatus included high parity (odds ratio [OR] 1.9; 95% confidence interval [CI], 1.16–3.14), preterm delivery (OR 2.60; 95% CI, 1.06–6.34), prenatal care at a private clinic (OR 12.87; 95% CI, 5.68–29.14), residence more than 5 km from the nearest prenatal clinic (OR 2.86; 95% CI, 1.18–17.9), high knowledge about MTCT (OR 0.25; 95% CI, 0.07–0.86), and fears related to disclosing the test result to the partner (OR 3.60; 95% CI, 1.84–7.06).

Conclusion

The high prevalence of unknown HIV serostatus among women in labor highlights the need to improve accessibility to HIV testing services early during pregnancy to be able to take advantage of antiretroviral therapy.     

Increased thymic B cells but maintenance of thymic structure, T cell differentiation and negative selection in lymphotoxin-alpha and TNF gene-targeted mice

TNF, lymphotoxin (LT) and their receptors are expressed constitutively in the thymus. It remains unclear whether these cytokines play a role in normal thymic structure or function. We have investigated thymocyte differentiation, selection and thymic organogenesis in gene targeted mice lacking LTalpha, TNF, or both (TNF/LTalpha-/-). The thymus was normal in TNF/LTalpha-/- mice with regard to cell yields and stromal architecture. Detailed analysis of alphabeta and gammadelta T cell-lineage thymocyte subsets revealed no abnormalities, implying that neither TNF nor LT play an essential role in T cell differentiation or positive selection. The number and distribution of thymic CD11c+ dendritic cells was also normal in the absence of both TNF and LTalpha. A three-fold increase in B cell numbers was observed consistently in the TNF/LTalpha-/- thymus. This phenotype was due entirely to the LTalpha deficiency and associated with changes in the hemopoietic compartment, rather than the thymic stromal compartment of LTalpha-/- mice. Finally, specific Vbeta8+ T cell deletion within the thymus following intrathymic injection of staphylococcal enterotoxin B (SEB) was TNF/LT independent. Thus, despite the presence of these cytokines and their receptors in the normal thymus, there appears no essential role for either TNF or LT in development of organ structure or for those processes associated with T cell repertoire selection.     

Two novel fibrillin-2 mutations in congenital contractural arachnodactyly

Congenital contractural arachnodactyly (CCA) is an autosomal dominant connective tissue disorder, comprising marfanoid habitus, flexion contractures, severe kyphoscoliosis, abnormal pinnae, and muscular hypoplasia. It is now known that mutations in the gene encoding fibrillin-2 cause CCA. Interestingly, mutations described to date cluster in the fibrillin-2 region homologous to the so-called neonatal Marfan syndrome region of fibrillin-1. Thus, it has been hypothesized that the relative infrequency of CCA compared with the Marfan syndrome is due to the limited region of the gene targeted for mutations. In support of the above hypothesis, we report here the finding of two additional FBN2 mutations in CCA, C1141F (exon 26) and C1252W (exon 29). In addition, a new 3' UTR polymorphism is also described.     

The molecular genetics of Marfan syndrome and related microfibrillopathies

Mutations in the gene for fibrillin-1 (FBN1) have been shown to cause Marfan syndrome, an autosomal dominant disorder of connective tissue characterised by pleiotropic manifestations involving primarily the ocular, skeletal, and cardiovascular systems. Fibrillin-1 is a major component of the 10-12 nm microfibrils, which are thought to play a role in tropoelastin deposition and elastic fibre formation in addition to possessing an anchoring function in some tissues.
  Fibrillin-1 mutations have also been found in patients who do not fulfil clinical criteria for the diagnosis of Marfan syndrome, but have related disorders of connective tissue, such as isolated ectopia lentis, familial aortic aneurysm, and Marfan-like skeletal abnormalities, so that Marfan syndrome may be regarded as one of a range of type 1 fibrillinopathies.
  There appear to be no particular hot spots since mutations are found throughout the entire fibrillin-1 gene. However, a clustering of mutations associated with the most severe form of Marfan syndrome, neonatal Marfan syndrome, has been noted in a region encompassing exons 24 to 32. The gene for fibrillin-2 (FBN2) is highly homologous to FBN1, and mutations in FBN2 have been shown to cause a phenotypically related disorder termed congenital contractural arachnodactyly. Since mutations in the fibrillin genes are likely to affect the global function of the microfibrils, the term microfibrillopathy may be the most appropriate to designate the spectrum of disease associated with dysfunction of these molecules.
  The understanding of the global and the molecular functions of the fibrillin containing microfibrils is still incomplete and, correspondingly, no comprehensive theory of the pathogenesis of Marfan syndrome has emerged to date. Many, but not all, fibrillin-1 gene mutations are expected to exert a dominant negative effect, whereby mutant fibrillin monomers impair the global function of the microfibrils. In this paper we review the molecular physiology and pathophysiology of Marfan syndrome and related microfibrillopathies.


Keywords: Marfan syndrome; fibrillin; microfibrillopathies     

Is paradoxical hair growth caused by low-level radiant exposure by home-use laser and intense pulsed light devices?

Introduction and objectives: This qualitative review of paradoxical hair growth, following professional treatments reviews, clarifies whether low fluence is the most probable cause of unwanted hair regrowth after at home light-based treatments. Materials and methods: The proposed causes of unexpected hair regrowth are examined, and our scientific understanding of absorption and scattering of light in turbid tissue is reviewed. Published reports of paradoxical hair growth are assessed. Results: Early laser hair removal studies failed to record the occurrence of hair induction despite the significant numbers of subjects treated. Neither published paradoxical hair growth studies following home-based laser or intense pulsed light (IPL) hair removal treatments, nor randomised or controlled studies documenting paradoxical hair growth following professional treatments could be found. Several authors directly proposed inflammatory response to be the primary cause of hair growth induction. Conclusions: It is unlikely that hair regrowth several centimetres or more away from the irradiated tissue can be attributed to the laser or IPL used. In many cases of paradoxical hair growth, other causes may be responsible for the unexpected hair growth. The primary cause of instances of ‘true’ paradoxical hair growth is probably limited to darker phototypes with one or more other characteristics including polycystic ovarian syndrome or other androgen hormonal irregularities following high energy treatments with the corresponding inflammatory sequelae.     

Diffusion-tensor imaging for the detection and quantification of treatment-induced white matter injury in children with medulloblastoma: a pilot study

BACKGROUND AND PURPOSE: Treatment-induced white matter (WM) injury in medulloblastoma survivors, as manifested by deterioration of cognitive function, is prevalent. However, no reliable imaging method exists for early detection and quantification. Our goal was to determine whether anisotropy of WM is reduced in medulloblastoma survivors and whether fractional anisotropy (FA) can be used as an index for evaluation of treatment-induced WM injury. METHODS: We evaluated nine medulloblastoma survivors treated with surgery, cranial irradiation, and chemotherapy by use of diffusion-tensor (DT) imaging and compared FA findings in selected WM sites (cerebellar hemispheres, pons, medulla oblongata, frontal periventricular WM, parietal periventricular WM, and corona radiata) with those of healthy age-matched control subjects. FA maps were compared with conventional T2-weighted images. FA was also compared with age at treatment, time interval since treatment, and deterioration of school performance. The two-tailed paired t test was used to determine statistical significance (P <.05). RESULTS: Significant reduction of FA (P <.05) was seen in all anatomic sites in the patient group compared with FA in control subjects, except in the frontal periventricular WM, even in areas with normal appearance on T2-weighted images. FA reduction ranged from 12.4-19% (mean, 16.5%). Compared with control subjects, posterior fossa and supratentorial WM FA in patients were reduced by 14.6% (SD 1.9%) and 18.4% (SD 0.55%), respectively (P =.029). Reduction of supratentorial WM FA correlated with younger age at treatment (< 5 years), longer interval since treatment (> 5 years), and deterioration of school performance. CONCLUSION: DT imaging and use of the index FA is potentially useful for early detection and monitoring of treatment-induced WM injury in children with medulloblastoma.