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PubMed1993

A new composite model of objects for Monte Carlo simulation of radiological imaging.

A composite object model is proposed for Monte Carlo simulation of radiological imaging systems. The composite model contains four components: a set of regular and 'voxelized' primitives, a 'modular' inclusion tree, a set of designated constructive solid geometry (CSG) trees, and a mapping from the set of CSG trees to the inclusion tree. The voxelized primitive is a primitive containing a stack of voxels whose intersections with a photon path are calculated based on Siddon's method. The inclusion tree is employed to describe the inclusion relationships of homogeneous subregions of material characteristics in larger regions in an object. The model is designed so that the 'divide-and-conquer' principle for modular software design can be used to construct an inclusion tree for a complex object. The designated CSG trees are used to model source distributions. The mapping from the inclusion tree to the CSG trees provides the fundamental information for the initial location of a photon history in the tree. Computational issues are addressed for the new model. For the modular inclusion tree, a computationally efficient algorithm is proposed in conjunction with the determination of the photon-ray intersections with primitive and voxel boundaries as well as with the identification of the material characteristics for each ray segment between two adjacent intersections. For source distributions, the designated CSG trees are defined based on the set intersections-difference-unions (IDU) operation sequence. The IDU operations present computation advantages over existing source modelling based on a single inclusion tree. For voxelized primitives, a new sampling technique called the fractional photon emission technique is introduced to reduce sampling computations for existing techniques based on single photon emission. The composite model is an extension of existing simple-geometry, solid-geometry, and voxel-based models and hence provides greater flexibility for model optimization. Based on the composite model, two objects were simulated: an anthropomorphic thorax with lesion inserts for transmission studies and a 3D Hoffman brain phantom with lesion inserts for emission studies. The simulations demonstrate the flexibility of the composite approach in modelling objects for clinically significant applications.

Computer Simulation↗
PubMed2005

Primary Sjögren's syndrome in children and adolescents: are proposed diagnostic criteria applicable?

OBJECTIVE: To compare the proposed criteria for the diagnosis of primary Sjögren's syndrome (pSS) in childhood to the validated American-European Consensus Group (AECG) classification criteria for pSS in adults. METHODS: Charts of 7 children with pSS seen at British Columbia's Children's Hospital (BCCH) and data on 128 children identified through Medline in the English language literature between 1963 and 2003 were reviewed for pediatric and AECG criteria for pSS. The presence of > or = 4 criteria was required to satisfy the respective classification criteria. The expert clinical opinion of pediatric rheumatologists was considered the gold standard for diagnosis. RESULTS: A total of 24/62 (39%) cases satisfied the AECG criteria; 47/62 (76%) satisfied the proposed pediatric criteria. Inclusion of recurrent parotitis increased the sensitivity of the pediatric clinical criteria. From the cases, 78/133 (59%) satisfied the pediatric oral symptom criteria; only 6/78 (8%) had xerostomia in the absence of recurrent parotitis. There was no reported case of recurrent conjunctivitis in the absence of keratoconjunctivitis sicca. We found 101/130 (78%) cases had at least one positive autoantibody test result [antinuclear antibodies (ANA), rheumatoid factor (RF), SSA, SSB]; 78/123 (63%) had autoantibodies to SSA or SSB. CONCLUSION: The AECG adult criteria for pSS should not be applied to children as the sensitivity is unacceptably low. The inclusion of recurrent parotitis increases the sensitivity of the pediatric criteria, and recurrent parotitis should alert the clinician to the possibility of pSS. The inclusion of recurrent conjunctivitis did not improve the sensitivity over the AECG ocular criteria. The addition of ANA and RF to the AECG criteria did not change the number of patients satisfying the criteria for pediatric pSS.

Adolescent↗
PubMed2005

Rheological and dielectric characterization of monoolein/water mesophases in the presence of a peptide drug.

A series of glyceryl monoolein/water gel systems containing 10%, 22%, and 30% w/w water has been investigated using two complementary techniques, oscillatory rheology and dielectric analysis, in order to establish the utility of these two techniques in conjunction and to investigate the influence of the inclusion of a model peptide, cyclosporin A, on the properties of the gels. Oscillatory rheology was performed in two modes; frequency sweeps at 20, 37, and 70 degrees C and temperature sweeps from 20 to 70 degrees C. Dielectric spectroscopy was performed in the kHz to mHz frequency range over a temperature range of 20-70 degrees C. Both rheology and dielectric spectroscopy were able to identify structural changes in the systems analyzed, with the 10% and 30% (w/w) water sample showing typical features of the lamellar and cubic phase respectively at 20 degrees C, while the 22% (w/w) system showed intermediate behavior. The thermotropic phase transitions could be monitored using rheological temperature sweeps. Drug loading resulted in marked changes in rheological and dielectric response of the 10% w/w water system, causing a decrease in both elasticity and permittivity values, while a less marked effect was observed for the 22% and, in particular, the 30% w/w systems. The investigation has demonstrated that rheological and dielectric measurements yield distinct yet complementary information and that the inclusion of a model peptide may alter the properties of the gel, the extent of the effect being dependent on the phase composition of the system.

Cyclosporine↗
PubMed1994

Thiopyrano[2,3,4-cd]indoles as 5-lipoxygenase inhibitors: synthesis, biological profile, and resolution of 2-[2-[1-(4-chlorobenzyl)-4-methyl-6-[(5-phenylpyridin-2-yl)methoxy]-4,5 -dihydro-1H-thiopyrano[2,3,4-cd]indol-2-yl]ethoxy]butanoic acid.

Leukotriene biosynthesis inhibitors have potential as new therapies for asthma and inflammatory diseases. The recently disclosed thiopyrano[2,3,4-cd]indole class of 5-lipoxygenase (5-LO) inhibitors has been investigated with particular emphasis on the side chain bearing the acidic functionality. The SAR studies have shown that the inclusion of a heteroatom (O or S) in conjunction with an alpha-ethyl substituted acid leads to inhibitors of improved potency. The most potent inhibitor prepared contains a 2-ethoxybutanoic acid side chain. This compound, 14d (2-[2-[1-(4-chlorobenzyl)-4-methyl-6-[(5-phenylpyridin-2-yl)methox y]- 4,5-dihydro-1H-thiopyrano[2,3,4-cd]indol-2-yl]ethoxy]-butanoic acid, L-699,333), inhibits 5-HPETE production by human 5-LO and LTB4 biosynthesis by human PMN leukocytes and human whole blood (IC50s of 22 nM, 7 nM and 3.8 microM, respectively). The racemic acid 14d has been shown to be functionally active in a rat pleurisy model (inhibition of LTB4, ED50 = 0.65 mg/kg, 6 h pretreatment) and in the hyperreactive rat model of antigen-induced dyspnea (50% inhibition at 2 and 4 h pretreatment; 0.5 mg/kg po). In addition, 14d shows excellent functional activity against antigen-induced bronchoconstriction in the conscious squirrel monkey [89% inhibition of the increase in RL and 68% inhibition in the decrease in Cdyn (0.1 mg/kg, n = 3)] and in the conscious sheep models of asthma (iv infusion at 2.5 micrograms/kg/min). Acid 14d is highly selective as an inhibitor of 5-LO activity when compared to the inhibition of human 15-LO, porcine 12-LO and ram seminal vesicle cyclooxygenase (IC50 > 5 microM) or competition in a FLAP binding assay (IC50 > 10 microM). Resolution of 14d affords 14g, the most potent diastereomer, which inhibits the 5-HPETE production of human 5-LO and LTB4 biosynthesis of human PMN leukocytes and human whole blood with IC50s of 8 nM, 4 nM, and 1 microM respectively. The in vitro and in vivo profile of 14d is comparable to that of MK-0591, which has showed biochemical efficacy in inhibiting ex vivo LTB4 biosynthesis and urinary LTE4 excretion in clinical trials.

Animals↗
PubMedDate not supplied

Adaptation of the nursing audit to community health nursing.

A selected literature review has revealed some of the ways in which the audit can be adapted to effectively evaluate the quality of care provided by community health professionals. Although a complex issue, the strengths of the audit can outweigh its limitations when a shared philosophy is adhered to and a review of the quality monitoring process occurs on a regular basis. But its success depends both on the approach and on the action taken. One requirement for an effective audit is a strong commitment of staff to reflect accurately nursing practice in nursing documentation. As the audit is neither inclusive nor exclusive, it should be used in conjunction with other quality assurance mechanisms, and in collaboration with other disciplines. Commitment at all levels--consumer, provider, administrator--is essential for success. There is no doubt that the variety of nursing audit instruments and techniques in existence have served to enhance the effectiveness and efficiency of community health nursing audit programs as well as contributing to community health nursing quality assurance. However, the audit clearly remains a challenging issue, requiring further research to establish the reliability and validity of current audit measures and to develop innovative approaches to future community-based audits.

Canada↗
PubMed1994

Probable transmission of Chlamydia psittaci from a macaw to a cat.

A 5-year-old Siamese cat developed unilateral mucopurulent ocular discharge and conjunctivitis 1 month after the introduction of a macaw into the household. Despite treatment with antimicrobial ophthalmic ointment, the conjunctivitis became bilateral and other systemic signs developed. Intracellular inclusions consistent with a Chlamydia psittaci infection were detected in conjunctival epithelial cells stained with a fluorescein-labeled monoclonal antibody. Chlamydia psittaci was isolated from samples obtained by conjunctival scraping. Subsequently, C psittaci was recovered in samples obtained from the feces of the bird. The cat and the bird were successfully treated with doxycycline. Historic and epidemiologic findings supported the theory of orthozoonotic transmission of C psittaci from the bird to the cat.

Animals↗
PubMed2000

Estimating treatment effects in randomized clinical trials in the presence of non-compliance.

In clinical trials where patients are randomized between two treatment arms, not all patients comply with the treatment they were randomly assigned to. The reasons for (non)compliance may be associated with the outcome variable and thereby act as confounders. The standard way of analysing such trials is by the 'intention-to-treat' principle, which allows the use of permutation tests. Conclusions drawn from such tests do not depend on untested assumptions such as absence of confounding. However, this approach may yield biased estimators for the causal effects of treatments. We consider the estimation of such effects for clinical trials where non-compliers can be considered to have switched to the other trial arm. The most important example of this is the placebo-controlled clinical trial where no substantial placebo effects are anticipated. We consider the situation where the relationship between compliance, and thus treatment received, and outcome is influenced by unobserved confounders. The residual of the regression of the actual treatment indicator variable on the randomization arm indicator variable is shown to 'intercept' the effect of such confounders. Inclusion of this residual in a multivariate analysis, in conjunction with the treatment indicator variable, should thus adjust for confounding. Examples are given. In those examples, the results are similar to those obtained by more complex methods.

Anticholesteremic Agents↗
PubMed2006

Exonization of Alu-generated splice variants in the survivin gene of human and non-human primates.

Survivin is a member of the inhibitor apoptosis family that is overexpressed in many malignancies. It has five known alternative splice forms, some of which differ in their antiapoptotic properties and expression levels in human cancers. Here we describe a novel donor splice site (DSS), 2B+32 DSS, which is used in conjunction with survivin alternative exon 2B, resulting in the inclusion of 32 additional nucleotides from intron 2 at the 3' end of this exon. Sequence analysis showed that both the classical exon 2B DSS and 2B+32 are provided by an Alu sequence, which is inserted in intron 2 downstream of a functional acceptor splice site, leading to the exonization of part of the repetitive element. Minor transcripts including the 2B+32 alternative exon, or retaining the whole intronic region comprised between exons 2B and 3, were detected in several human cell lines and in some human tissues. Survivin 2B+32 containing variants acquire a premature stop codon (PTC) and may therefore be degraded by the nonsense mediated decay pathway. The implication of these novel isoforms, as well as other PTC+ survivin variants, in the overall regulation of survivin expression is discussed. Sequence analysis of intron 2 which contains the Alu Y element was performed on different primate species in order to trace its insertion and exonization during primate evolution.

Alternative Splicing↗
PubMed2003

Nanostructural features of demosponge biosilica.

Recent interest in the optical and mechanical properties of silica structures made by living sponges, and the possibility of harnessing these mechanisms for the synthesis of advanced materials and devices, motivate our investigation of the nanoscale structure of these remarkable biomaterials. Scanning electron and atomic force microscopic (SEM and AFM) analyses of the annular substructure of demosponge biosilica spicules reveals that the deposited material is nanoparticulate, with a mean particle diameter of 74+/-13 nm. The nanoparticles are deposited in alternating layers with characteristic etchant reactivities. Further analyses of longitudinally fractured spicules indicate that each deposited layer is approximately monoparticulate in thickness and exhibits extensive long range ordering, revealing an unanticipated level of nanoscale structural complexity. NMR data obtained from differentially heated spicule samples suggest that the etch sensitivity exhibited by these annular domains may be related to variation in the degree of silica condensation, rather than variability in the inclusion of organics. In addition, AFM phase imaging in conjunction with results obtained from HF and alkaline etching experiments suggest that at various stages in spicule biosynthesis, regions of unusually low silica condensation are deposited, indicating a possible interruption in normal spicule formation. While this discovery of nanoparticulate silica aggregation in demosponge skeletal elements is likely to reflect the intrinsic kinetic tendency of silica to form such particles during polycondensation, the heirarchical organization of these nanoparticles is biologically unique.

Animals↗
PubMedDate not supplied

Cytologic diagnosis of florid peritoneal endosalpingiosis. A case report.

The cytologic findings in a case of endosalpingiosis presenting in peritoneal washings taken at the time of staging laparotomy for endocervical adenocarcinoma are described. Dense papillary epithelial clusters with distinct ciliated cell borders were found in the cytologic specimens. Cell nuclei were oval, with finely dispersed chromatin and uniform nuclear membranes. These findings, in conjunction with the discovery of tubal-type epithelial inclusions in pelvic and periaortic lymph nodes, established a diagnosis of endosalpingiosis or benign glandular inclusions involving the pelvic peritoneum and lymph nodes.

Adenocarcinoma↗
PubMed1989

Human BF*F-subtypes: segregation analysis with inclusion of MHC haplotypes.

The segregation of factor B(BF)F subtypes was analyzed in conjunction with other MHC markers in 15 families with 89 offspring. Informative data for BF F subtypes were obtained from 11 families, 6 of them with known recombinant individuals for the HLA-B/DR/GLO region. The subtypes did not contribute further to the localization of the cross-overs, but followed the known segregation of conventional BF allotypes. In 2 families of one kinship, the recognition of heterozygous BF*FAFB individuals could be established following the inclusion of three generations. The rarer of the two BF F subtype alleles, BF*FA, is positively associated with the HLA haplotypes BW62, CW3, C4A*3 and A29, CWX, B44, C4A*3, B*1, DR7. BF F subtypes are regarded as a very useful additional tool for studies of MHC organization and disease association.

Alleles↗
PubMed2003

Local anti-infective therapy: mechanical and physical approaches. A systematic review.

BACKGROUND: Although mechanical non-surgical therapy (scaling and root planing) is the most common means of initial treatment of periodontal diseases, the relative clinical efficacy of various methods, including manual versus machine-driven, with or without adjunctive agents, has not been determined. RATIONALE: This systematic review analyzes the literature in an effort to identify the most effective therapies, based on both clinical and patient-centered outcomes. FOCUSED QUESTION: In patients with periodontitis, what is the effect of mechanically-driven instrumentation (e.g., power-driven) and/or subgingival irrigation with and without manual instrumentation compared to manual instrumentation alone? SEARCH PROTOCOL: Two investigators examined MEDLINE and the Cochrane Oral Health Group specialized registry for clinical trials published in English. Hand searches were performed of the International Journal of Periodontics & Restorative Dentistry, Journal of Clinical Periodontology, Journal of Periodontology, and Journal of Periodontal Research. Searches were performed for articles published through April 2002. Editors of these journals were asked to provide information on articles currently under review. In addition, an electronic discussion group on periodontal diseases and treatment was contacted, as were manufacturers of manual and mechanical instruments and of adjunctive agents. SELECTION CRITERIA INCLUSION CRITERIA: Only randomized clinical trials, cohort studies, or case-control studies at least 3 months long were included. All studies had to compare manual instrumentation (MI; scaling and root planing [SRP]) alone with some other form of non-surgical therapy. These included MI versus mechanically-driven instruments (MDI) alone; MI versus MI plus MDI; MI versus MDI plus an agent (e.g., chlorhexidine); and MI versus subgingival irrigation (SGI) delivered in conjunction with MI or MDI. EXCLUSION CRITERIA: Studies not meeting the inclusion criteria or those treating periodontal diseases as a manifestation or complication of some other disease or disorder were not included. DATA COLLECTION AND ANALYSIS: Probing depth, clinical attachment level, bleeding on probing, and gingival recession were the primary outcomes. Because of the heterogeneity of the patient populations, treatments, and outcome measures, meta-analysis was not appropriate. Only in-study data were compared. Four of the studies required extrapolating data from figures and graphs, resulting in questionable accuracy. MAIN RESULTS: 1. Nine studies, representing a study population of 129, were included in the review. 2. Five studies compared MI with MDI alone. The other 4 compared MI alone to MI plus SGI or subgingival tissue treatment. 3. There was comparable efficacy between MI and MDI when treating single-rooted teeth. 4. The use of SGI or subgingival tissue treatment as an adjunct to MI provided no additional benefit compared to MI alone. 5. Findings reported in the review must be interpreted with considerable caution, as lack of study heterogeneity made meta-analysis unfeasible and the need to extrapolate outcomes values from graphs and figures may have resulted in some inaccuracy. REVIEWERS' CONCLUSIONS: 1. Manual and mechanically-driven instrumentation appears comparable in affecting improved clinical outcomes. 2. Instrumentation time for MI and MDI were similar, except for 1 study in which MDI was significantly shorter. 3. Adjunctive SGI plus MI and subgingival tissue treatment result in similar clinical outcomes when compared to MI alone. 4. If study data are to be effectively and analytically combined to facilitate meaningful comparisons of treatment outcomes, detailed and standardized study designs must be developed and used consistently in clinical trials.

Anti-Infective Agents, Local↗
PubMed2005

Oral anti-oestrogens and medical adjuncts for subfertility associated with anovulation.

BACKGROUND: Infertility due to anovulation is a common problem in women. The first line oral treatment is with anti-oestrogens, such as clomiphene citrate. Unfortunately there may be resistance and alternative and adjunctive treatments have been developed. These include tamoxifen, dexamethasone, bromocriptine and aromatase inhibitors (AIs). OBJECTIVES: To determine the relative effectiveness of anti-oestrogen agents, with or without medical adjuncts, in women with WHO group 2 anovulation. SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders and Subfertility Group trial register (searched 5th July 2004), CENTRAL (The Cochrane Library Issue 2 2004), MEDLINE (1966 to June 2004) and EMBASE (1980 to June 2004) for identification of relevant randomised controlled trials (RCTs). Additionally the United Kingdom National Institute for Clinical Excellence (NICE) guidelines and the references of relevant reviews and RCTs were searched. SELECTION CRITERIA: RCTs that compare oral anti-oestrogen agents for ovulation induction (alone or in conjunction with medical adjuncts) in anovulatory subfertility, were considered for inclusion in the review. Metformin and other insulin sensitizing agents were not included. Hyperprolactinaemic infertility was not included. DATA COLLECTION AND ANALYSIS: Data extraction and quality assessment was done independently by two reviewers. The primary outcome was live birth, secondary outcomes were: pregnancy, ovulation, miscarriage, multiple pregnancy, overstimulation, ovarian hyperstimulation syndrome and patient reported adverse effects. MAIN RESULTS: Twelve RCTs were found and included in this review. No trials reported live birth as an outcome. Miscarriage and multiple pregnancy rates were poorly reported. Clomiphene was shown to be effective in increasing pregnancy rate when compared to placebo (fixed OR 5.8, 95% CI 1.6 to 21.5; NNT 5.9, 95% CI 3.6 to 16.7). No evidence of a difference in effect was found between clomiphene and tamoxifen (fixed OR 1.0, 95% CI 0.5 to 2.1). The use of clomiphene in combination with tamoxifen did not find any evidence of effect on pregnancy rate when compared to clomiphene alone (fixed OR 3.3, 95% CI 0.1 to 91.6). The comparison between two AIs (letrozole and anastrozole) did not find any evidence of a difference in effect on pregnancy rate (fixed OR 1.9, 95% CI 0.4 to 8.9). For the intervention of clomiphene plus ketoconazole vs clomiphene no evidence of a difference in effect for pregnancy rate was found (fixed OR 2.4, 95% CI 0.9 to 6.4). For clomiphene plus bromocriptine vs clomiphene no evidence of a difference in effect on pregnancy rate was found (fixed OR 1.0, 95% CI 0.3 to 3.0) rates. However, clomiphene plus dexamethasone treatment resulted in a significant improvement in the pregnancy rate (fixed OR 11.3, 95% CI 5.3 to 24.0; NNT 2.7, 95% CI 2.1 to 3.6) when compared to clomiphene alone as did clomiphene plus pretreatment with combined oral contraceptives (fixed OR 27.2, 95% CI 3.1 to 235.0; NNT 2.0, 95% CI 1.4 to 3.4). AUTHORS' CONCLUSIONS: This review shows evidence supporting the effectiveness of the current first line treatment, clomiphene citrate. No evidence of a difference in effect was found between clomiphene and tamoxifen. The use of dexamethasone as an adjunct to clomiphene therapy appears promising as do combined oral contraceptives. This review has highlighted a gap in the literature on effects of these drugs on outcomes such as miscarriage rate. Evidence in favour of these interventions is flawed. RCTs of adequate power and of high methodological quality are required for the older treatments such as clomiphene, alone and with medical adjuncts, and also for the newer drugs such as the AIs.

Anovulation↗
PubMed1989

Role of substrate binding forces in exchange-only transport systems: II. Implications for the mechanism of the anion exchanger of red cells.

The transition-state theory of exchange-only membrane transport is applied to experimental results in the literature on the anion exchanger of red cells. Two central features of the system are in accord with the theory: (i) forming the transition state in translocation involves a carrier conformational change; (ii) substrate specificity is expressed in transport rates rather than affinities. The expression of specificity is consistent with other evidence for a conformational intermediate (not the transition state) formed in the translocation of all substrates. The theory, in conjunction with concepts derived from the chemistry of macrocyclic ion inclusion complexes, prescribes certain essential properties in the transport site. Separate subsites are required for the preferred substrates, Cl- and HCO3-, to account for tight binding in the transition state (Kdiss congruent to 1 microM). Further, the following mechanism is suggested. A substrate anion initially forms a loose surface complex at one subsite, but in the transition state the subsites converge to form an inclusion complex in which the binding forces are greatly increased through a chelation effect. The conformational change at the substrate site, which is driven by the mounting forces of binding, sets in train a wider conformational change that converts the carrier from an immobile to a mobile form. Though simple, this composite-site mechanism explains many unusual features of the system. It accounts for substrate inhibition, partially noncompetitive inhibition of one substrate by another, and "tunneling," which is net transport under conditions where exchange should prevail, according to other models. All three types of behavior result from the formation of a ternary complex in which substrate anions are bound at both subsites. The mechanism also accounts for the enormous range of substrate structures accepted by the system, for the complex inhibition by the organic sulfate NAP-taurine, and for the involvement of several cationic side chains and two different protein domains in the transport site.

Anion Transport Proteins↗