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Notes: An analytical study of the on-axis aperture defect (spherical aberration) convolved with diffraction, for a simple spheric-based Kirkpatrick–Baez (KB) grazing incidence x-ray microscope, indicates the optimum performance is achieved by using a short object plane to mirror distances, steep grazing angles, and high x-ray energies. Other aberrations occur for off-axis field points, but if the spherical aberration can be reduced significantly the image improvement of an extended object should be dramatic. In the quest for ultrahigh x-ray spatial resolution, the Los Alamos one-dimensional (1D) KB (at the time of writing, under fabrication) fully exploits these facts in a 40 mm working distance, steep grazing angle multilayer mirror, 4.316 keV design. A rigorous analysis of Zernike surface deformations, and all other fabrication/assembly errors indicates negligible image degradation of the predicted very high resolution performance; a similar study of existing KBs closely models the 3–5 μm resolutions over the relevant field sizes. In addition, a novel analytical and ray trace optimization technique allows larger working distances at even higher resolutions. Due to instrument length constraints, however, this approach was not incorporated into the 4.316 keV 1DKB; although, in the future such designs could be easily accommodated on The National Ignition Facility. © 1999 American Institute of Physics.

Notes: To overcome the fundamental limitations of coronary arteriography to assess the functional significance of coronary artery disease, it is necessary to obtain direct information about coronary blood flow. Recently we validated three pressure flow equations, which enable calculation of maximum coronary, myocardial, and collateral flow by merely measuring aortic, central venous, and distal coronary pressures under the condition of maximum vasodilation and using an ultra thin pressure monitoring guide wire for distal coronary pressure recording. In this paper, the first clinical experiences of this method are described. For that purpose, the concept of fractional flow reserve (FFR) is important. Fractional coronary flow reserve (FFRcor) is defined as the maximum achievable blood flow in a stenotic artery, divided by normal maximum flow in that same artery, i.e. maximum flow in that artery in the case that it would be completely normal. Fractional myocardial flow reserve (FFRmyo) is defined in a similar way, and recruitable collateral blood flow is expressed as a fraction of normal maximum myocardial flow. Fractional flow reserve, defined in this way, is easy to obtain at percutaneous transluminal coronary angioplasty (PTCA) by the pressure-flow equations, is independent of pressure changes, applicable to three vessel disease, and enables calculation of the separate contribution of coronary and collateral flow to total myocardial perfusion. In 18 patients a very close correlation was demonstrated between FFRmyo, calculated by pressure recordings at PTCA by the first pressure flow equation, and FFRmyo obtained by positron emission tomography, which is considered the gold standard for myocardial perfusion. In 60 other patients, maximum recruitable collateral blood flow at balloon inflation (Qc/QN) was calculated according to the third pressure-flow equation and correlated to the presence or absence of ischemia. It could be demonstrated that QC/QN exceeds 22% in all 23 patients without ischemia, whereas Qc/QN was less than 22% in 34 out of 37 patients who experienced ischemia during balloon inflation. This margin value of 22% is very close to the theoretically expected value of 20%. based upon a coronary flow reserve of 5 under standard physiologic conditions. It can be concluded that the concept of fractional flow reserve provides a rapid, accurate, and elegant way for quantitative assessment of maximum coronary and myocardial blood flow before and after PTCA. Moreover, this is the first method that enables quantitative calculation of collateral blood flow in clinical practice. (J Interven Cardiol 1993; 6:331–344)

Notes: Background  Since 1991, children with sensori-neural deafness and their families within Southern Derbyshire have been supported by a multiagency approach to their diagnosis and management.Results  One hundred and twenty-two children were seen at the Child Development Centre for an holistic assessment, and 110 of these children have had an ophthalmic assessment, of whom 48 (43.6%) were found to have ophthalmic abnormalities. These included 43 children (39.1%) with refractive errors, ranging from mild to severe. Of 82 children with uncomplicated deafness, 26 (31.7%) had refractive errors. The prevalence of ophthalmic problems was higher than the prevalence in hearing school children in the literature and in local pre-school children. There were six cases of Usher syndrome. Twenty-one children had more than one eye defect. The findings indicate that deaf and hearing impaired children are two to three times more likely to develop ophthalmic abnormalities than their hearing peers, which makes early detection of paramount importance. An important local outcome has been the establishment of guidelines for ophthalmic assessment to include assessment of vision and screening for Usher syndrome by electro-physiological testing at aged 7 years and above. Screening has been completed to date in 78 children with congenital sensori-neural deafness.Conclusions  Sensitive and efficient ophthalmic assessment and management are essential for all deaf and hearing impaired children and national guidelines need to be established for both assessment of vision and screening for Usher syndrome, based on further evaluated research.

Notes: Lysosomal storage diseases are rare and coexistence of more than one in a family can present a diagnostic challenge as illustrated by this study. The index case born to consanguineous Asian parents presented with developmental delay. Investigations led to an incidental finding of Fabry disease. After numerous additional investigations over a year, a second diagnosis of aspartylglucosaminuria (AGU) was made. A family history of renal disease and developmental delay was disclosed. The sister and first cousin of the index case were diagnosed as homozygous for AGU, but do not have Fabry disease. The younger brother has since been diagnosed with both Fabry disease and AGU. Another cousin has learning difficulties and fits, but is heterozygous for AGU, and possibly has another uncharacterised autosomal recessive disorder. In a family with consanguinity when the clinical picture in an individual is not fully explained by the presence of one rare metabolic disease, it is essential to investigate further for the presence of others.

Notes: The ability of cells to control the balance between the generation and quenching of reactive oxygen species is important in combating potentially damaging effects of oxidative stress. One mechanism that cells use to maintain redox homeostasis is the antioxidant response pathway. Antioxidant response elements (AREs) are cis-acting elements located in regulatory regions of antioxidant and phase II detoxification genes. Nuclear factor-erythroid 2 p45-related factor 2 (Nrf2) is a member of the Cap ‘n’ Collar family of transcription factors that binds to the ARE and regulates the transcription of specific ARE-containing genes such as NAD(P)H:quinone oxidoreductase 1, glutamylcysteine synthetase and heme oxygenase. Activation of Nrf2 results in release from its negative repressor, Kelch-like ECH-associated protein 1 (Keap1), and allows Nrf2 to translocate into the nucleus to induce gene expression. In this study, we demonstrate that increasing Nrf2 activity by various methods, including chemical induction, Nrf2 overexpression or Keap1 siRNA knockdown, protects cells against specific types of oxidative damage. Cells were protected against 6-hydroxydopamine- and 3-morpholinosydnonimine-mediated toxicity but not against 1-methyl-1-4-phenylpyridinium toxicity. As oxidative stress is a hallmark of several neurodegenerative disorders, including Parkinson's disease, pharmacological agents that selectively target the Keap1-Nrf2 pathway may provide a novel neuroprotective strategy for the treatment of these diseases.

Notes: Sebaceous gland development and function is regulated by an expanding array of molecules including transcription factors, hormones, retinoids, growth factors, cytokines and nuclear hormone receptors. We have reviewed the literature to present the current understanding of sebaceous gland development and physiology, with particular emphasis on the control of the sebaceous gland and its implications for acne management. Interestingly, retinoids, cytokines and nuclear hormone receptors appear to be promising inhibitors of sebum synthesis, thus offering new approaches to acne management.