Sociodemographic factors of Pap smear screening in Taiwan

We report the differences between using either EDTA plasma or serum in a turbidimetric assay for quantitation of C-reactive protein (CRP). A systematic discrepancy was found for these two sample materials. This was most pronounced in the low concentration range (below 20 mg1(-1)) at which lower values were found in serum than in EDTA plasma. Conversely, in the high concentration range, serum showed slightly higher values. Addition of K3-EDTA to the reaction buffer improved the kinetics for sera with low concentrations of CRP, thus increasing the sensitivity of the assay. We found an overall constant discrepancy of approximately 8% lower values in plasma than in serum (equally for low and high levels of CRP) after the addition of K3-EDTA. The most probable explanation for this effect seems to be the differing water content of serum and EDTA plasma. We discuss the role and function of EDTA in the CRP assay and suggest some hypothetical mechanisms.     

Percutaneous fluoroscopic screw fixation of acetabular fractures

Over a 2-year period eight patients underwent percutaneous fluoroscopic fixation of their acetabular fractures. Average patient age was 43 and mean ISS was 27. Mean blood loss was less than 100 ml. There were five transverse fractures, one affecting both columns, one anterior column-posterior hemitransverse and one T-type fracture. There were two ipsilateral femoral and two ipsilateral tibial fractures. Mean follow-up was 15 months. Three broad patient groups were identified. One patient died, one was lost to follow-up, four had full range of motion of the affected hip, one had good range with Brooker II heterotopic ossification and one was wheelchair-bound with Brooker IV heterotopic ossification. The technique, which requires only cannulated screws and fluoroscopy, is described.     

Subependymal astrocytic hamartomas in the Eker rat model of tuberous sclerosis

Tuberous sclerosis (TSC) is an autosomal dominant syndrome that is linked to two genetic loci: TSC1 (9q34) and TSC2 (16p13). Brain manifestations such as cortical tubers and subependymal hamartoma/giant cell astrocytomas are major causes of TSC-related morbidity. In this study, we describe the central nervous system involvement in a unique rodent model of tuberous sclerosis. The Eker rat carries a spontaneous germline mutation of the TSC2 gene and is predisposed to multiple neoplasia. In a series of 45 adult Eker carriers (TSC2 +/-), three types of focal intracranial lesions were found, of which the subependymal and subcortical hamartomas were most prevalent (65%). There exist remarkable phenotypic similarities between the Eker rat and human subependymal lesions. Our study indicates that the predominant cellular phenotype of the subependymal hamartomas is astroglial and suggests that the neuronal contribution within these lesions is, in part, the result of pre-existing myelinated axons. The hamartomas did not show evidence of loss of the wild-type TSC2 allele; it remains to be determined whether TSC2 inactivation is necessary for their pathogenesis. This genetically-defined rodent model may be useful in elucidating the molecular and developmental basis of the subependymal giant cell astrocytoma in humans.     

Pentoxifylline therapy in human immunodeficiency virus-seropositive persons with tuberculosis: a randomized, controlled trial

Macrophage activation and tumor necrosis factor-alpha (TNF-alpha) production are critical in tuberculosis immunity but may result in increased human immunodeficiency virus (HIV) expression and accelerated HIV disease progression in HIV-infected persons. Pentoxifylline inhibits expression of TNF-alpha and HIV. A double-blind, placebo-controlled study of adjunctive therapy with pentoxifylline (1800 mg/day) as a timed-release formulation was done in Ugandan HIV-infected patients with pulmonary tuberculosis. Subjects had early HIV disease (mean CD4 cell count, 380/microL) and did not receive other antiretroviral drugs. Pentoxifylline resulted in decreased plasma HIV RNA and serum beta 2-microglobulin and, in a subset of moderately anemic patients, improved blood hemoglobin levels. Trends were noted toward reduced TNF-alpha production in vitro and improved performance scores, but these did not reach statistical significance. No effect was noted on body mass, CD4 cell count, or survival. Additional studies of more potent TNF-alpha inhibitors in HIV-positive subjects with tuberculosis are warranted.     

Toward congruence between theory and practice in small area analysis and local public health data

Advances in computer hardware, software and database interfaces have provided opportunities for collation, manipulation, analysis and display of spatial data on an unprecedented scale. Demands for small area data in public health, fuelled in part by an increasing emphasis on benchmarking in relation to Year 2000 objectives but also in response to state and federal programmes to involve local communities in the assessment and planning process have simultaneously generated an unprecedented demand for these analyses and data presentations. This paper discusses four areas where geographic, cartographic and statistical theory and methodology need to be brought to bear on the development of applications involving small area health data. These areas are: (i) the theoretical conceptions of space; (ii) managing the inherent variability of rates and frequencies; (iii) attribution of events or cases to areas or to points; and (iv) the application of sound principles of cartographic design to the presentation of results.     

Single motor unit myoelectric signal analysis with nonstationarydata

The information content of the myoelectric signal (MES) is commonly revealed by statistical measures in the time or frequency domain. Empirical analyses of the MES from a single motor unit have generally assumed that features are invariant with time. Theoretical and experimental work has been done to demonstrate how nonstationary behavior in the discharge statistics of a motor neuron may affect estimates of features extracted from the motor unit's contribution to the MES. Specifically, it has been shown that nonstationary behavior can markedly influence estimates of features describing motor neuron firing behavior and consequently, the low-frequency portion of the MES power spectral density. These results may help to explain the discrepancies in the literature which report empirical models of motor neuron firing statistics     

Visualization of plasma turbulence

We have developed a three-dimensional toroidal gyrokinetic particle simulation to study tokamak turbulence. The gyrokinetic equations are a reduced set derived from the Vlasov-Maxwell equations by phase averaging over the ion gyromotion and keeping only the time and space scales relevant for describing tokamak plasmas. These large-scale simulations in complex geometry can produce gigabytes of data consisting of large 3D arrays evolving in time. Visualization plays a critical role in going from the raw nonlinear solution of these complex equations to a simplified theoretical model explaining the essential underlying physics     

Genetic control of differential baseline breathing pattern

The purpose of the present study was to determine the genetic control of baseline breathing pattern by examining the mode of inheritance between two inbred murine strains with differential breathing characteristics. Specifically, the rapid, shallow phenotype of the C57BL/6J (B6) strain is consistently distinct from the slow, deep phenotype of the C3H/HeJ (C3) strain. The response distributions of segregant and nonsegregant progeny were compared with the two progenitor strains to determine the mode of inheritance for each ventilatory characteristic. The BXH recombinant inbred (RI) strains derived from the B6 and C3 progenitors were examined to establish strain distribution patterns for each ventilatory trait. To establish the mode of inheritance, baseline breathing frequency (f), tidal volume, and inspiratory time (TI) were measured five times in each of 178 mature male animals from the two progenitor strains and their progeny by using whole body plethysmography. With respect to f and TI, the two progenitor strains were consistently distinct, and segregation analyses of the inheritance pattern suggest that the most parsimonious genetic model for response distributions of f and TI is a two-loci model. In similar experiments conducted on 82 mature male animals from 12 BXH RI strains, each parental phenotype was represented by one or more of the RI strains. Intermediate phenotypes emerged to confirm the likelihood that parental strain differences in f and TI were determined by more than one locus. Taken together, these studies suggest that the phenotypic difference in baseline respiratory timing between male B6 and C3 mice is best explained by a genetic model that considers at least two loci as major determinants.     

Cleavage of Müllerian inhibiting substance activates antiproliferative effects in vivo

Müllerian inhibiting substance (MIS), an inhibitor of growth and development of the female reproductive ducts in male fetuses, requires precise proteolytic cleavage to yield its biologically active species. Human plasmin is now used to cleave and, thereby, activate immunoaffinity-purified recombinant human MIS at its monobasic arginine-serine site at residues 427-428. To avoid the need for exogenous enzymatic cleavage and to simplify purification, we created an arginine-arginine dibasic cleavage site (MIS RR) using site-directed mutagenesis to change the serine at position 428 (AGC) to an arginine (cGC). The mutant cDNA was then stably transfected into a MIS-responsive ocular melanoma cell line, OM431, followed by cloning for amplified expression to test its biological activity in vitro and in vivo. Media from each clone were assayed for production of MIS RR by a sensitive ELISA for holo-MIS, and high- and low-producing clones were selected for further study. Media from the highest MIS RR producer caused Müllerian duct regression in an organ culture bioassay. Other transfections were done with an empty vector (pcDNAI Neo) or a construct lacking the leader sequence and thus failing to secrete MIS, to serve as controls. The OM431 clones containing the MIS RR mutant were growth inhibited in monolayer culture. The high- and low-producing MIS RR OM431 clones, along with transfected OM431 controls, were injected into the tail veins of immunosuppressed severe combined immunodeficiency mice for in vivo analyses. Four to 6 weeks later, pulmonary metastases were counted in uniformly inflated lungs. OM431 clones containing the more easily cleaved MIS RR displayed a significant dose-dependent reduction in pulmonary metastases when compared to the lungs of animals given injections of OM431 clones containing empty vector, leaderless MIS, or wild-type MIS that requires activation by plasmin cleavage. Since the purification protocol of MIS RR is less complicated than that for wild-type MIS, which requires subsequent enzymatic activation, MIS RR can be used for scale-up production with increased yields for further therapeutic trials against MIS-sensitive tumors.