Ridge number density: A new parameter for in vivo bone structure analysis

An advanced analysis of the mechanical properties of bone should include information about the microarchitecture of cancellous bone in addition to its density. It has recently been shown that high-resolution quantitative computed tomography and magnetic resonance imaging have the potential to assess such information in a noninvasive way in patients. Both techniques, however, lack sufficient spatial resolution to image the individual trabeculae with true precision. In this work, a new parameter, Ridge number density (RND), is introduced. RND is a measure for the trabecular number, which can be extracted directly from high-resolution three-dimensional (3D) images of patients. We applied the RND technique to a test group of nine healthy, postmenopausal women measured repetitively with a high-resolution 3D peripheral quantitative computed tomography (3D-pQCT) system with 165 × 165 × 165 μm³ voxel size. Simultaneously with the RND determination, the trabecular bone density (TBD) was also assessed in the same volume of interest. The examination site was the distal radius. The intersubject variability of the measured test group was 10.5% for RND and 26.3% for TBD. The root mean square error between first and second examinations (midterm reproducibility) was 1.6% and 1.1%, respectively. RND is determined independently from TBD and pertains to the structure of the cancellous bone. As such, it might add crucial information in cases where bone mass or bone density measurements alone give ambigous results.     

Effect of ozonized normal saline on biochemical parameters of the liver in malignant growth

Injection of ozonized normal saline to animals with transplanted sarcoma-45 normalized energy metabolism in the liver, which is important for this organ's function under conditions of malignant growth. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 126, No. 8, pp. 207–209, August, 1998     

Voltage Oscillations in Xenopus Spinal Cord Neurons: Developmental Onset and Dependence on Co-activation of NMDA and 5HT Receptors

The development of intrinsic, N-methyl-D-aspartate (NMDA) receptor-mediated voltage oscillations and their dependence on co-activation of 5-hydroxytryptamine (5HT) receptors was explored in motor neurons of late embryonic and early larval Xenopus laevis. Under tetrodotoxin, 100 μM NMDA elicited a membrane depolarization of around 20 mV, but did not lead to voltage oscillations. However, following the addition of 2–5 μM 5HT, oscillations were observed in 12% of embryonic and 70% of larval motor neurons. The voltage oscillations depended upon co-activation of NMDA and 5HT receptors since they were curtailed by selectively blocking NMDA receptors with D-2-amino-5-phosphonovaleric acid (APV) or by excluding Mg²⁺ from the experimental saline. 5HT applied in the absence of NMDA also failed to elicit oscillations. Oscillations could be induced by the non-selective 5HT_1a receptor agonist, 5-carboxamidotryptamine (5CT) and both 5HT- and 5CT-induced oscillations were abolished by pindobind-5HT₁, a selective 5HT_1a receptor antagonist. To test whether 5HT enables voltage oscillations by modulating the voltage-dependent block of NMDA channels by Mg²⁺, membrane conductance was monitored under tetrodotoxin. Although 5HT caused membrane hyperpolarization of 4–8 mV, there was little detectable change in conductance. NMDA application caused an approximate 20 mV depolarization and an ‘apparent’ decrease in conductance, presumably due to the conductance pulse bringing the membrane into a voltage region where Mg²⁺ blocks the NMDA ionophore. 5HT further decreased conductance, which we propose is due to its enhancement of the voltage-dependent Mg²⁺ block. When the membrane potential was depolarized by ～20 mV via depolarizing current injection (to mimic the NMDA-induced depolarization), 5HT increased rather than decreased membrane conductance. Furthermore, 5HT did not affect the increase in membrane conductance following NMDA applications in zero Mg²⁺ saline. The results suggest that intrinsic, NMDA receptor-mediated voltage oscillations develop in a brief period after hatching, and that they depend upon the co-activation of 5HT and NMDA receptors. The enabling function of 5HT may involve the facilitation of the voltage-dependent block of the NMDA ionophore by Mg²⁺ through activation of receptors with 5HT_1a-like pharmacology.     

A cost evaluation of implementing a quality-oriented, regional perinatal data system.

We evaluated the cost impact of implementing a perinatal data system (PDS) on birth certificate (BC) processing and perinatal quality improvement (QI) reporting. Relevant staff in all birthing hospitals in the 15-county Central New York region (N = 23) were interviewed at baseline prior to implementation of the PDS and one year after implementation of the PDS to ascertain the time and costs of BC processing and of QI report generation. The average time and cost to collect and complete BCs did not change significantly from baseline to year 1. The time and costs to complete QI reports decreased significantly by 70 percent during this same period. Hospitals fully using the PDS for QI reporting purposes took, on average, six percent of the time it took other hospitals to generate comparable QI reports. The PDS significantly reduced the time and cost of generating perinatal reports from a consolidated database over what hospitals had done previously. Given the richness of the reports and the efficiency with which they are produced, hospitals are encouraged to adopt electronic means of BC processing and accessing these data for QI reporting purposes.     

Clinicopathological features of bladder cancer associated with chronic exposure to arsenic.

A high incidence of bladder cancer has been documented in an area of chronic arsenic (As) exposure. This study investigates the characteristics of As-associated (n = 49) and other (n = 64) bladder cancers. A higher histological grading was observed for the As-exposed tumours (P = 0.04), but no other difference in pathobiological features or prognosis was found between the two groups.     

IgA-epidermolysis bullosa acquisita in a child resulting in blindness

Epidermolysis bullosa acquisita (EBA) is an acquired subepidermal bullous disease characterized by IgG autoantibodies directed against type VII collagen, the major component of anchoring fibrils. The classical phenotype of EBA is a non-inflammatory, mechanobullous disease resembling the dystrophic forms of inherited epidermolysis bullosa. Mucous membrane involvement is frequent but usually mild. We report a 1-year-old girl suffering from IgA-EBA, who presented with an initial eruption of disseminated urticarial lesions and tense blisters of the skin but subsequently developed severe oral and ocular lesions reminiscent of cicatricial pemphigoid. Direct immunofluorescence of the skin and buccal mucosa revealed linear IgA and C3 at the basement membrane zone (BMZ). IgA anti-BMZ autoantibodies stained the dermal side of salt-split skin by indirect immunofluorescence and recognized a dermal protein of 290 kDa co-migrating with type VII collagen by immunoblotting. Direct and indirect immunoelectron microscopy revealed IgA deposits overlying the anchoring fibrils. The ocular involvement led to total blindness in spite of intense treatment. This case of childhood IgA-EBA is particularly striking because of the cicatricial pemphigoid phenotype with severe ocular involvement which resulted in blindness. It reinforces the necessity to use modern immunological methods to classify autoimmune bullous diseases in order to allow early and appropriate treatment.     

Three-dimensional fetal echocardiography: gated versus nongated techniques.

The purpose of this study was to compare gated with nongated three-dimensional fetal echocardiography in terms of the ability to demonstrate fetal cardiac anatomy. We examined nine fetuses in utero using conventional two-dimensional sonographic imaging equipment, an electromagnetic position sensor, and a computer-graphics workstation. Free-hand sweeps were performed through the fetal heart and great vessels in either transverse or sagittal orientations with respect to the fetal heart. Seven transverse and five sagittal sweeps were selected for reconstruction and analysis. Cardiac gating was performed by using a temporal Fourier transform to determine the fundamental frequency of cardiac motion. Two-dimensional data from each sweep were reprojected to a series of volume data sets. Each series was then condensed to a single volume, so that each two-dimensional sweep could be compared with its respective gated and nongated volume data sets. The two-dimensional data were reviewed utilizing a display with forward and backward cineloop capability. The gated and nongated volume data sets were displayed interactively as a series of three orthogonal planes, with the ability of the observer to control the location of each image plane within the volume. The gated data were animated with variable display frame rates. Conventional two-dimensional imaging provided a fairly complete evaluation of the fetal heart when scanning included the four-chamber view with a sweep across the outflow tracts. Nongated three-dimensional fetal echocardiography allowed visualization of some structures and views not demonstrated with two-dimensional ultrasonography. Gated three-dimensional fetal echocardiography provided significantly better visualization and comprehension of cardiac anatomy than nongated three-dimensional fetal echocardiography. The superiority of gated over nongated three-dimensional fetal echocardiography appears to come from both improved image quality and the anatomic clues that derive from the ability to view cardiac motion.     

Cochrane Lecture 1997. What evidence do we need for evidence based medicine?

As presently understood, evidence based medicine aims to advance practice from its traditional unverifiable mix of art and science to rational use of measurable inputs and outputs. In practice, however, its advocates accept uncritically a desocialised definition of science, assume that major clinical decisions are taken at the level of secondary specialist rather than primary generalist care, and ignore the multiple nature of most clinical problems, as well as the complexity of social problems within which clinical problems arise and have to be solved. These reductionist assumptions derive from the use of evidence based medicine as a tool for managed care in a transactional model for consultations. If these assumptions persist, they will strengthen reification of disease and promote the episodic output of process regardless of health outcome. We need to work within a different paradigm based on development of patients as co-producers rather than consumers, promoting continuing output of health gain through shared decisions using all relevant evidence, within a broader, socialised definition of science. Adoption of this model would require a major social and cultural shift for health professionals. This shift has already begun, promoted by changes in public attitudes to professional authority, changes in the relation of professionals to managers, and pressures for improved effectiveness and efficiency which, contrary to received wisdom, seem more likely to endorse cooperative than transactional clinical production. Progress on these lines is resisted by rapidly growing and extremely powerful economic and political interests. Health professionals and strategists have yet to recognise and admit the existence of this choice.