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PubMed2006

Bonding of dual-curing resin cements to dentin.

PURPOSE: The purpose of the study was three-fold: 1) to determine the strength of the bond between a number of dual-curing resin cements and dentin treated with corresponding adhesive systems, 2) to determine the effect on bond strength of not light curing the cements, and 3) to investigate whether application of a solution of sodium sulfinate or ascorbic acid would increase the bond strength in the cases where the manufacturer's version of an adhesive system resulted in low bond strength with chemically cured cement, ie, cement cured without light. MATERIALS AND METHODS: The adhesive systems comprised 5 simplified systems (Adper Scotchbond 1 XT, ED Primer II, Excite DSC, OptiBond Solo Plus, and Prime and Bond NT), and as controls, two three-step etch and rinse systems (Adper Scotchbond Multi-Purpose Plus and Gluma Solid Bond). The corresponding dual-curing resin cements were RelyX ARC, Panavia F 2.0, Variolink II, Nexus 2, Calibra, RelyX ARC, and 2Bond2. The cements were either light and chemically cured or only chemically cured. The adhesive systems were used as recommended by the manufacturers, which for some systems involved inclusion of a so-called activator or catalyst when used with chemically cured cement. Sodium sulfinate and ascorbic acid were applied as a 1% ethanol solution. The bond strengths were measured in shear after storing specimens for 24 h in 37 degree C water. RESULTS: When the dual-curing resin cements had been both light and chemically cured, the bond strengths increased in this order: Gluma Solid Bond < ED Primer II < Prime and Bond NT < Adper Scotchbond Multi-Purpose Plus < Excite DSC < Adper Scotchbond 1 XT < OptiBond Solo Plus. Omission of light curing of the cements decreased the bond strengths with OptiBond Solo Plus and Prime and Bond NT. The use of activator in conjunction with OptiBond Solo Plus and Prime and Bond NT increased the bond strength to chemically cured cement, but not to the level obtained when the cement was both light and chemically cured. The use of the catalyst of Adper Scotchbond Multi-Purpose Plus did not increase the bond strength with chemically cured cement. Pretreatment with a solution of sodium sulfinate or ascorbic acid increased the bond strength with chemically cured cement in the case of OptiBond Solo Plus, whereas only the solution of sodium sulfinate was effective with Prime and Bond NT. CONCLUSION: Clinicians should be aware that in situations where a dual-curing resin cement cannot be light cured, some adhesive systems suffer a loss of efficacy, even when respective activators are used. Pretreatment with a 1% ethanol solution of sodium sulfinate may restore much of the lost bond strength.

Ascorbic Acid↗

PubMed1989

Morphology, distribution and its significance of intrahepatic HBV DNA in liver disease: a study by in situ hybridization.

A biotin-labeled DNA probe specific for hepatitis B virus (HBV) nucleotide sequences was hybridized in situ to liver tissue of 129 cases with liver disease. It was found that HBV DNA was predominantly visualized in cytoplasm of hepatocytes in three patterns: cytoplasmic compact, discrete and inclusion pattern. Its distribution in parenchyma in the sections of specimens may be defined as lobular, focal and spotty. The detection of intrahepatic HBV DNA depended on two factors, at least in the present study: 1) liver disease activity; chronic active hepatitis (CAH) group had a significant higher prevalence (81%) as compared to cirrhosis, chronic lobular hepatitis (CLH), acute hepatitis and hepatocellular carcinoma (HCC) groups; 2) HBV infection state: HBV DNA was more easily detected in HBeAg positive or intrahepatic HBcAg positive patients than in single HBsAg positive or anti-HBc cases. The findings that hepatocytes expressing HBV DNA, particularly in focal distribution, were closely related to hepatic necrosis sites suggested that HBV replication might occur in conjunction with hepatic necrosis.

DNA Replication↗

PubMedDate not supplied

Diagnosis and incidence of fetal parvovirus infection in an autopsy series: II. DNA amplification.

This study evaluates the practical utility of the polymerase chain reaction (PCR) as a diagnostic method for intrauterine fetal parvovirus infection in cases of hydrops fetalis. Paraffin-embedded, formalin-fixed fetal tissues from cases of hydrops fetalis were assessed for parvovirus B19 by histology and PCR in conjunction with 32P hybridization. Of 673 fetal and neonatal autopsies performed at Women and Infants' Hospital for the years 1985 through 1990, 32 cases were determined to have hydrops fetalis, of which five were positive for parvovirus infection by both histology and the PCR. PCR was not used in seven (22%) of the 32 hydrops cases because 1 microgram of DNA was not available for study. Histology was as sensitive as PCR in detecting parvovirus B19 in fetal autopsy tissues from cases of hydrops fetalis, and could be used reliably in each case to diagnose parvovirus infection. In our hands, histology is as sensitive as PCR and less labor-intensive. We would reserve PCR for cases without inclusions and with a strong suspicion of parvovirus infection, or for fluids in which histological analysis is not available.

Autopsy↗

PubMed1994

Notice regarding section 602 of the Veterans Health Care Act of 1992 inclusion of outpatient hospital facilities--PHS. Notice.

Section 602 of Public Law 102-585, the "Veterans Health Care Act of 1992" (the "Act"), enacted section 340B of the Public Health Service Act ("PHS Act"), "Limitation on Prices of Drugs Purchased by Covered Entities." Section 340B provides that a manufacturer who sells covered outpatient drugs to eligible entities must sign a pharmaceutical pricing agreement (the "Agreement") with the Secretary, Department of Health and Human Services, in which the manufacturer agrees to charge a price for covered outpatient drugs that will not exceed the amount determined under a statutory formula. Section 340B(a)(4) lists the entities eligible to receive discount outpatient drug pricing (i.e., certain disproportionate share hospitals (DSHs) and PHS grantees). The definition of a disproportionate share hospital found in section 340B(a)(4)(L) provides criteria to determine which such hospitals are eligible to participate in the program. However, the definition does not include criteria to determine which outpatient facilities (including off-site or satellite clinics) working in conjunction with the eligible hospital would be considered part of the hospital for purposes of eligibility for section 340B drug discounts. The Office of Drug Pricing, which administers this program with PHS, is proposing certain procedures to determine which outpatient hospital facilities are included as part of an eligible disproportionate share hospital.

Drug Costs↗

PubMed2002

Cytoplasmic dynein/dynactin mediates the assembly of aggresomes.

Aggresomes are pericentrosomal cytoplasmic structures into which aggregated, ubiquitinated, misfolded proteins are sequestered. Misfolded proteins accumulate in aggresomes when the capacity of the intracellular protein degradation machinery is exceeded. Previously, we demonstrated that an intact microtubule cytoskeleton is required for the aggresome formation [Johnston et al., 1998: J. Cell Biol. 143:1883-1898]. In this study, we have investigated the involvement of microtubules (MT) and MT motors in this process. Induction of aggresomes containing misfolded DeltaF508 CFTR is accompanied by a redistribution of the retrograde motor cytoplasmic dynein that colocalizes with aggresomal markers. Coexpression of the p50 (dynamitin) subunit of the dynein/dynactin complex prevents the formation of aggresomes, even in the presence of proteasome inhibitors. Using in vitro microtubule binding assays in conjunction with immunogold electron microscopy, our data demonstrate that misfolded DeltaF508 CFTR associate with microtubules. We conclude that cytoplasmic dynein/dynactin is responsible for the directed transport of misfolded protein into aggresomes. The implications of these findings with respect to the pathogenesis of neurodegenerative disease are discussed.

Antigens↗

PubMed1995

Key elements of a highly efficient intracytoplasmic sperm injection technique: Ca2+ fluxes and oocyte cytoplasmic dislocation.

OBJECTIVE: To analyze the mechanism by which modifications of the intracytoplasmic sperm injection (ICSI) technique influence success rates. DESIGN: Prospective clinical study supplemented with an experimental analysis of Ca2+ fluxes provoked by the injection procedure. SETTING: Private hospital and public research center. PATIENTS: Patients treated by IVF and ICSI. INTERVENTIONS: Intracytoplasmic sperm injection. MAIN OUTCOME MEASURES: Fertilization and pregnancy rates and intracellular free Ca2+ concentration. RESULTS: The inclusion of vigorous aspiration of oocyte cytoplasm improved outcomes of ICSI. In a series of 100 consecutive cases treated with this technique, the fertilization and pregnancy rates were 87% of total metaphase II oocytes injected and 52% of total treatment cycles, respectively. Enhanced Ca2+ influx into the injected oocytes and dislocation of the oocyte cytoplasm, including the development of a focus of persistent Ca2+ discharge around the injected sperm head, were the main characteristics of this highly successful technique. CONCLUSIONS: Vigorous aspiration of oocyte cytoplasm may facilitate fertilization after ICSI by increasing the oocyte Ca2+ load at the time of injection, by establishing a more intimate contact of the injected sperm head with oocyte intracellular Ca2+ stores, or by a conjunction of these mechanisms.

Aniline Compounds↗

PubMed2002

The combined use of pollen and soil analyses in a search and subsequent murder investigation.

This case report shows how soil analyses (particularly petrology) can be used in conjunction with pollen in order to refine or strengthen an association. Soil samples from a car believed to have been used by the suspect in a missing persons case was subjected to soil and pollen analyses. The soil characteristics and petrology were used to redefine the search area using geology and soils maps, the pollen and vegetative remains were used to target woodlands with a particular species mix. As a result two bodies were located and the environmental evidence was used in the subsequent trial. In this case the history of the vehicle was well known and the wheel arches and footwells provided reliable soil traps. The advantage of combining the techniques is that soil evidence (both mineralogy and other inclusions) provides a geological/soils match while the pollen provides independent evidence of vegetation type providing a combination that may be rare or unique.

Journal Article↗

PubMedDate not supplied

Does cartoon movie distraction decrease burned children's pain behavior?

The purpose of this study was to evaluate cartoon movie viewing as a practical and low-cost intervention to decrease burned children's pain behavior during dressing changes. Thirteen children, 4 to 12 years of age, with a mean TBSA burn of 7.9% were assessed using a reversal, single-subject experimental design. The experimental condition consisted of the presentation of a cartoon movie as a nonpharmacologic intervention in conjunction with a standardized analgesic medication. In the control condition children's pain was treated with the standardized analgesic medication only. Behavioral distress was measured during the first six dressing changes postburn with the Observational Scale of Behavioral Distress. No significant effect of cartoon movie distraction on observed behavioral distress in patients was found. Interrater reliability of the Observational Scale of Behavioral Distress was good (kappa =.87-.98). Wound debridement was found to be the most painful part of the dressing change. A simple, easily applicable, and low-cost distraction intervention such as presenting cartoon movies does not seem to be sufficiently powerful to measurably reduce burned children's distress during dressing changes. Findings are based on purely observational data. Inclusion of self-report measures in future studies might reveal intervention effects on anxiety and subjective pain perception.

Attention↗

PubMed2004

Conducting elastomer surface texturing: a path to electrode spotting. Application to the biochip production.

A new active support for electro-chemiluminescent biochip preparation has been developed. This material was based on an original material composed of graphite modified polydimethyl siloxane (PDMS). The addressed inclusion of Sepharose beads at the surface of this elastomeric electrode generated interesting local high specific surface. The electrode was characterised by electrochemical (cyclic voltametry, chronoamperomatry) and imaging (scanning electron microscopy (SEM)) methods, and a surface area increase factor of 50 was found, linked to the texturing of the surface generated by the presence of the Sepharose beads. The consequence of this increase was shown to be a jump of the local electrochemical activity which induced a well defined and localised electro-chemiluminescent signal. The new material was used to design biochips based on the electro-chemiluminescent reaction of luminol with enzymatically produced hydrogen peroxide. Thus, when using beads bearing bio-molecules such nucleic acid or human IgG, in conjunction with glucose oxidas-labelled DNA or antibody, sensitive biochips could be obtained with detection limits of 10(11) and 10(10) molecules, respectively. Multi-parameter enzyme-based biochips could also be achieved by locally adsorbing, at the PDMS-graphite surface, either glucose oxidase, lactate oxidase or choline oxidase. Detection limits of 10 microM for lactate and choline and 20 microM for glucose were found, with detection ranging over two decades at least.

Biosensing Techniques↗

PubMed1998

The Bacillus SpoIIGA protein is targeted to sites of spore septum formation in a SpoIIE-independent manner.

The process of bacterial cell division involves the assembly of a complex of proteins at the site of septation that probably provides both the structural and the cytokinetic functions required for elaboration and closure of the septal annulus. During sporulation in Bacillus subtilis, this complex of proteins is modified by the inclusion of a sporulation-specific protein, SpoIIE, which plays a direct role in gene regulation and also has a genetically separable role in determining the gross structural properties of the specialized sporulation septum. We demonstrate by both green fluorescent protein (GFP) fusions and indirect immunofluorescence microscopy that SpoIIGA, a protein required for proteolytic cleavage of pro-sigmaE, is also targeted to the sporulation septum. Septal localization of SpoIIGA-GFP occurred even in the structurally abnormal septum formed by a SpoIIE null mutant. We also report the isolation of a spoIIGA homologue from Bacillus megaterium, a species in which the cells are significantly larger than those of B. subtilis. We have exploited the physical dimensions of the B. megaterium sporangium, in conjunction with wide-field deconvolution microscopy, to construct three-dimensional projections of sporulating cells. These projections indicate that SpoIIGA-GFP is initially localized in an annulus at the septal periphery and is only later localized uniformly throughout the septa. Localization was also detected in a B. subtilis spo0H null strain that fails to construct a spore septum. We propose that SpoIIGA is sequestered in the septum by an interaction with components of the septation machinery and that this interaction begins before the construction of the asymmetric septum.

Amino Acid Sequence↗

PubMed1997

Future directions in the adjuvant treatment of colon cancer.

Adjuvant chemotherapy has been shown to alter the natural history of patients with resected colon cancer. Two regimens (fluorouracil [5-FU] plus levamisole (Ergamisol) and 5-FU plus leucovorin) have been found most successful in prolonging disease-free and overall survival. When these two regimens were directly compared in randomized clinical trials, it appeared that a small disease-free survival and overall survival advantage had emerged in favor of 5-FU plus leucovorin. This advantage, in conjunction with an increased understanding of the mechanism of leucovorin's biochemical modulation of 5-FU, makes this regimen a logical choice for studies designed to further optimize and augment the clinical efficacy of chemotherapy for colon cancer. The introduction of oral tegafur and uracil (UFT) and the demonstration of significant antitumor activity with the combination of oral UFT and oral leucovorin, provide an excellent opportunity to optimize treatment with 5-FU plus leucovorin. The National Surgical Adjuvant Breast and Bowel Project has recently implemented a new clinical trial (Protocol C-06) comparing oral UFT plus leucovorin with 5-FU plus leucovorin in the treatment of patients with resected stage II and III colon cancer. The rationale for the design of the trial, inclusion and exclusion criteria, treatment regimens, and statistical considerations are reviewed.

Antidotes↗

PubMedDate not supplied

Is ICH exportable outside the European Union?

This article sets out to explore whether or not the International Conference on Harmonisation (ICH) Good Clinical Practices (GCP) Guidelines are exportable outside the European Union (EU). It is not a question of whether the Guidelines per se are exportable but rather can studies outside the EU be performed to the same, or a better standard? It is well known that the ICH Guidelines are accepted worldwide in the countries where International Clinical Trials are carried out. Likewise with the signatories to the Step 5 document being the major players--the USA, Japan, and Europe--the guidelines are already enshrined in national legislation. The author therefore sets out to address whether clinical trials can be conducted to the ICH GCP standard outside Western Europe. The facts and opinions presented here are based on a 16 centre (of which eight of the centres were required to be audited by the Sponsor) clinical study that was carried out in both the Czech Republic and Poland for nonseasonal rhinitis. The recruitment of patients was required to take place in a short period of time and had strict inclusion and exclusion criteria. The overall concept of the study and the compliance with internationally accepted ICH GCPs was found to be of a very high standard. In addition, several other studies from totally different therapeutic areas, clearly show that the standard in non-EU countries is equally high and in most cases of a higher standard than is seen at the principal investigators sites within the EU. In what Western Europeans like to call "developing countries," an understanding of the international GCPs has already been grasped and extremely high quality clinical trials are being carried out. To demonstrate this, attention is drawn to a large head and neck cancer study that was part device and part pharmaceutical product and was conducted in conjunction with photodynamic therapy (PDT), carried out in several countries, but of note in India.

Clinical Protocols↗

PubMed2006

Atypical squamous cells of undetermined significance, human papillomavirus, and cervical intraepithelial neoplasia 2 or 3 in adolescents: ASC-US, age, and high-grade cervical neoplasia.

OBJECTIVE: To determine rates of and factors associated with cervical intraepithelial neoplasia (CIN) 2 or 3 among women with atypical squamous cells of undetermined significance (ASC-US) and oncogenic human papillomavirus (HPV) infection. MATERIALS AND METHODS: This is a retrospective review of 357 women with ASC-US and known high-risk HPV infection. To be eligible for inclusion, patients had to have subsequently undergone colposcopic-directed cervical biopsy and/or endocervical sampling. Univariate and multivariable regression analyses were used to estimate crude and adjusted odds ratios of CIN 2 or 3 by risk factors associated with HPV and CIN. RESULTS: Thirty-three of 215 (15%) women with ASC-US and oncogenic HPV who underwent histological sampling demonstrated CIN 2 or 3. In the adjusted model, only nulliparity (adjusted odds ratio = 2.2, 95% CI = 1.0-4.8) retained a marginal association with the outcome. No significant age-related differences in the prevalence of high-grade disease emerged. The high-grade lesions seen in adolescents consisted of single, small lesions. CONCLUSIONS: In the light of these findings, and in conjunction with the high rate of oncogenic HPV infection among adolescents with ASC-US, both reflex HPV testing and immediate colposcopy do not appear to be of benefit in the initial management of teenagers with this cytological diagnosis.

Adolescent↗

PubMed1990

virG, an Agrobacterium tumefaciens transcriptional activator, initiates translation at a UUG codon and is a sequence-specific DNA-binding protein.

The Agrobacterium tumefaciens Ti plasmid virG locus, in conjunction with virA and acetosyringone, activates transcription of the virulence (vir) genes. Insertional and deoxyoligonucleotide-directed mutagenesis studies showed that both octopine and nopaline Ti plasmid virG genes initiate translation at a UUG codon. VirG protein initiated at this UUG codon was found to be 241 amino acid residues in length and had an apparent molecular mass of 27.1 kilodaltons. A Salmonella typhimurium trp-virG transcriptional fusion was constructed to overproduce VirG. Agrobacterium cells containing this gene fusion showed a large increase in virG activity in the presence of virA and acetosyringone. Since the trp promoter is not under virA-virG control, this result indicates that modification of VirG is necessary for its full activity. VirG overproduced in Escherichia coli was purified from inclusion bodies. It was found to be a DNA-binding protein that preferentially bound DNA fragments containing the 5' nontranscribed regions of the virA, -B, -C, -D, and -G operons. Significant specific binding to the 5' nontranscribed region sequences of virE was not detected. DNase I footprinting of the upstream regions of virC-virD and virG showed that VirG binds to sequences around the vir box region.

Bacterial Proteins↗

PubMed2006

Defining "success" in recruitment of underrepresented populations to cancer clinical trials: moving toward a more consistent approach.

Although medically underserved groups bear a heavy burden of cancer disease and governmental agencies have required inclusion of minorities and women in cancer clinical trials since 1993, many of these groups are underrepresented in cancer prevention or treatment clinical trials. To assess and enhance recruitment of underrepresented populations into cancer-related clinical trials, investigators and governmental agencies need consistent measurement approaches for recruitment that can be applied to diverse settings where trials are conducted. We conducted a systematic review to evaluate what measurement approaches were used to evaluate the success of recruitment of underrepresented groups into cancer prevention or treatment trials, and whether these recruitment goals were stated a priori. Only two articles reported an a priori recruitment goal. The recruitment measurement approaches varied considerably, with no consistent standard, especially for individual trials. By using the empiric evidence from this review in conjunction with the National Institutes of Health (NIH) guidelines, we constructed a framework for choosing consistent a priori recruitment goals for underrepresented groups based on the research question and study location. Using consistent measurement approaches for underrepresented groups will improve comparability of recruitment strategies across trials, improve equity in distribution of benefits and burdens of cancer-related clinical trials, and may improve applicability of trial results to multiple populations.

Clinical Competence↗

PubMed1995

Randomised trial of an asthma self-management programme for adults.

BACKGROUND: A hospital based, community service asthma education programme for adults to improve asthma knowledge, promote compliance with medication, and reduce morbidity was evaluated. METHODS: The programme was evaluated using a randomised experimental and control group design with repeated measurements over 12 months. A volunteer community sample of 192 respondents was recruited of whom 116 satisfied the inclusion criteria. At the 12 month follow up some data were obtained for all subjects. Intervention subjects attended four 2.5 hour education sessions at weekly intervals. An asthma knowledge questionnaire was administered and compliance was assessed from diary records. Morbidity was assessed retrospectively by questionnaire, prospectively by diary, and objectively by spirometry and serial peak expiratory flow rate monitoring. The adequacy of medical treatment was also assessed. Data were collected at baseline, immediately after the intervention, and at three, six, nine, and 12 months after intervention. RESULTS: Improvements occurred in knowledge and compliance in the intervention group but the impact on morbidity was modest; this was due, at least in part, to the inadequacy of medical treatment. CONCLUSIONS: Treatment of asthma should be reviewed and optimised in conjunction with self-management programmes in order to improve health outcomes.

Adolescent↗

PubMed2000

Effect of propofol with and without EDTA on haemodynamics and calcium and magnesium homeostasis during and after cardiac surgery.

OBJECTIVE: To determine the effect of the addition of disodium edetate (EDTA) to propofol on haemodynamics, ionised calcium and magnesium serum concentrations, and adverse events during cardiac surgery. DESIGN: Double-blind, randomised, multicenter trial. SETTING: Operating room and intensive care unit of 5 academic health centres. PATIENTS: A total of 102 evaluable patients, aged 34 to 85 years, undergoing first-time, elective coronary artery bypass graft surgery. INTERVENTIONS: Comparison of propofol with EDTA and propofol without EDTA, each in conjunction with the opioid sufentanil, for intraoperative anaesthesia and postoperative sedation. MEASUREMENTS AND RESULTS: There were no significant differences at any time between the two formulations in any clinical chemistry measurements, including ionised calcium, ionised magnesium, total calcium, parathyroid hormone, blood urea nitrogen, creatinine, sodium, potassium, and phosphate. During bypass, the mean concentration of ionised calcium decreased to below the normal range, but the decrease was similar in both groups (propofol with EDTA, 0.98 +/- 0.07 mmol/L [N = 51]; propofol, 0.99 +/- 0.10 mmol/ L [N = 51]; p = NS). Calcium concentration returned to normal after rewarming. Mean ionised magnesium concentrations remained within normal limits in both groups. Similarly, there were no clinically meaningful differences between treatments with respect to haemodynamic variables, efficacy variables, or incidence of adverse events. CONCLUSIONS: The inclusion of EDTA in the current formulation of propofol appears to have no significant effects on calcium and magnesium profiles, renal function, haemodynamic variables, or other indicators of safety and efficacy during intraoperative anaesthesia and postoperative sedation in patients undergoing cardiac surgery.

Adult↗

PubMed1994

Decreased expression of a glycoprotein component of bladder surface mucin (GP1) in interstitial cystitis.

Interstitial cystitis is a disease of unknown etiology characterized by unremitting urinary frequency, urgency and suprapubic pain. Recently, a change in urothelial permeability has been identified in interstitial cystitis patients that is presumably mediated by aberrations in bladder surface mucin. For this study we evaluated qualitative changes in a previously defined glycoprotein component of this layer (GP1) as it occurs in interstitial cystitis patients and normal controls. Paraffinized bladder biopsies were obtained from 23 interstitial cystitis patients (all meeting National Institutes of Health inclusion criteria) and 11 normal controls. All biopsy tissue was stained with hematoxylin and eosin, and periodic acid, Schiff reaction. The tissues were examined immunohistochemically for GP1 using an anti-GP1 serum. Periodic acid, Schiff staining clearly identified bladder surface proteoglycans in all specimens. Moderate GP1 reactivity was noted in all normal control specimens. Alternatively, GP1 expression was absent in 35% of the interstitial cystitis patient biopsies and decreased in 61%. These data demonstrate qualitative GP1 changes in a majority of interstitial cystitis patients. It is unknown whether these differences have an impact on the pathogenesis of interstitial cystitis. However, our findings suggest that the absence or decreased expression of GP1 in interstitial cystitis bladder biopsies may serve as a marker to characterize the disease further in conjunction with clinical findings.

Adult↗