Malgorzata Roos

Topical photodynamic therapy in the treatment of actinic keratoses and Bowen’s disease in transplant recipients

Background. Transplant recipients (TR) have a dramatically increased risk for widespread epithelial neoplasms of the skin. Thus, there is a need to treat initial stages of these neoplasms such as actinic keratoses (AK) and Bowen’s disease (BD) to prevent progression to invasive and potentially fatal squamous cell carcinoma. Topical photodynamic therapy (PDT) has been proven to be an effective treatment for AK and BD in immunocompetent patients, but no prospective trials in immunocompromised TR have been performed so far. Methods. Twenty TR and 20 controls with histologically confirmed AK or BD underwent either a single or two consecutive treatments of topical PDT in an open trial. The application of 20% 5-aminolevulinic acid (ALA) for 5 hours was followed by illumination with 75 J/cm2 of visible light delivered at 80 mW/cm2 by an incoherent light source. Results. The overall complete response rates in TR at 4, 12, and 48 weeks were 0.86, 0.68, and 0.48, respectively. The cure rates in both patient groups were comparable at 4 weeks but were significantly lower in TR than in controls at 12 and 48 weeks (P <0.05). Side effects included erythema, edema, and crust formation after illumination. Cosmetic results were excellent without scar formation or alterations in pigmentation. Conclusions. Topical PDT with 20% 5-ALA is an effective and safe treatment for AK and BD in immunosuppressed TR, with initial response rates comparable with those in immunocompetent patients. It is particularly useful in TR because of the possibility for repeated treatment of large lesional areas.

Incidence of drug-induced liver injury in medical inpatients

ObjectivesDrug-induced liver injury (DILI) is a common concern. However, data on DILI epidemiology in inpatients are sparse.MethodsTo investigate the incidence of DILI, we screened all patients in the pharmacoepidemiological inpatient database according to the CIOMS (Council for International Organisation of Medical Science) criteria, which consist of the evaluation of some clinical chemistry laboratory liver parameters (CIOMS laboratory criteria) and the exclusion of any disease-related causes for the liver injury. Thus, only cases with probable or certain causality according to the World Health Organization criteria were included.ResultsAmong a total of 6383 patients, liver parameters were determined in 4610, and 489 among them fulfilled the CIOMS laboratory criteria. However, 401 patients had to be excluded because of disease-related liver injury and, thus, the study cohort consisted of 4209 patients at risk for DILI. Among a total of 88 DILI cases, 31 had no documented normal baseline liver parameters and, thus, represented prevalent cases. The remaining 57 represented incident DILI cases. Thus, the incidence of DILI was 1.4% (95% CI 1.0, 1.7). The drug classes most frequently causing DILI were heparins, antibacterials, tuberculostatics and antineoplastic agents. Among those, antineoplastic agents and tuberculostatics showed the highest incidence. Liver injury was not mentioned among the diagnoses or in the physician’s discharge letter in about 52–68% of all cases.ConclusionApproximately 1 in 100 patients develops DILI during hospitalisation in a department of medicine. Incidences of DILI were highest for antineoplastic agents and tuberculostatics. DILI is frequently missed and, therefore, DILI detection by diagnoses will result in misleadingly low incidence rates.

Optimizing Photodynamic Therapy: In vivo Pharmacokinetics of Liposomal meta-(Tetrahydroxyphenyl)Chlorin in Feline Squamous Cell Carcinoma

Purpose: The aim of the present study was to optimize and simplify photodynamic therapy using a new liposomal formulation of the photosensitizer meta-(tetrahydroxyphenyl)chlorin [m-THPC (Foscan); liposomal m-THPC (Fospeg)] and to reduce systemic reactions to the photosensitizer. Experimental Design: To examine the pharmacokinetics of liposomal m-THPC, we determined tissue and plasma variables in feline patients with spontaneous squamous cell carcinoma. In vivo fluorescence intensity measurements of tumor and skin were done with a fiber spectrophotometer after i.v. injection of m-THPC or liposomal m-THPC in 10 cats. Blood samples, drawn at several time points after photosensitizer administration, were analyzed by high-performance liquid chromatography. Results: None of the liposomal m-THPC–treated cats showed side effects during or after drug injection. Fluorescence intensities, fluorescence ratios (tumor fluorescence divided by skin fluorescence), and bioavailability in the tumor were 2 to 4 times higher with liposomal m-THPC compared with m-THPC. Liposomal m-THPC concentration in the tumor increased constantly to reach a maximum at 4 hours after injection. Plasma concentration and bioavailability were ∼3 times higher with liposomal m-THPC compared with m-THPC measured at the time points of highest plasma concentration. The distribution half-life was shorter with liposomal m-THPC, resulting in maximal tumor accumulation up to 5.5 times earlier. Maximal tumor accumulation and maximal fluorescence ratio with liposomal m-THPC occurred at the same time point, indicating maximal selectivity. In both groups, all cats responded to therapy. Conclusions: Liposomal m-THPC was well tolerated by all cats and seems to have superior pharmacokinetic properties compared with m-THPC. The efficacy of the drug warrants further study.

Clinical study of the internal gaps of zirconia and metal frameworks for fixed partial dentures

The aim of this clinical study was to compare the internal gaps between abutment teeth and posterior fixed partial dentures (FPDs) fabricated utilizing milled zirconia and cast gold-alloy frameworks. As part of an ongoing randomized controlled clinical trial, 32 three-unit FPDs (16 zirconia and 16 metal-ceramic) in 25 patients were randomly selected for adaptation measurements. During the bisque-stage ceramic try-in, an A-silicone impression material was placed between the abutment teeth and the framework. The internal gap, corresponding to the thickness of the replica, was measured under magnification at the following locations: cervical, axial, and occlusal (cusp-tips and central). The internal gaps of FPDs with zirconia frameworks were significantly larger in cervical, axial, and centro-occlusal regions (cervical: 189.6 +/- 71.8 mum vs. 118.6 +/- 31.5 mum; axial: 140.5 +/- 38.3 mum vs. 95.7 +/- 18.1 mum; and centro-occlusal: 192.0 +/- 66.5 mum vs. 153.1 +/- 69.8 mum). The cervical gaps next to the pontics were significantly larger compared with those of the outer walls in both types of FPDs (zirconia: mean difference 67.7 +/- 114.7 mum; metal-ceramic: mean difference 30.0 +/- 71.2 mum). Posterior three-unit FPDs incorporating milled zirconia frameworks exhibited larger internal gaps than those constructed using conventional metal-ceramic techniques.

Irradiation of Brain Tumors in Dogs with Neurologic Disease

Radiation therapy is the treatment of choice for many primary canine brain tumors. The radiation dose tolerated by surrounding healthy brain tissue can be a limiting factor for radiation treatment and total dose as well as fractionation schedules, and volume effects may play a role in the outcome of patients undergoing radiation therapy. The purpose of this retrospective study was to evaluate the efficacy of radiation therapy in dogs with brain tumors that showed signs of neurologic disease. Forty-six dogs with brain tumors were included in the analysis. In 34 dogs, computer-generated treatment plans were available, and dose-volume data could be obtained. The totally prescribed radiation therapy doses ranged from 35 to 52.5 Gy (mean = 40.9 [SD +/- 2.91) applied in 2.5- to 4-Gy fractions (mean = 3.2). The median overall survival time calculated for deaths attributable to worsening of neurologic signs was 1,174 days (95% confidence interval [CI], 693-1,655 days). Assuming that all deaths were due to disease or treatment consequences, the median survival time was 699 days (95% CI, 589-809 days). No prognostic clinical factors such as the location or size of the tumor or neurologic signs at presentation were identified. With computerized treatment planning and accurate positioning, high doses of radiation (> 80% of the total dose) could be limited to mean relative brain volumes of 35.3% (+/- 12.6). These small volumes may decrease the probability of severe late effects such as infarction or necrosis. In this study, very few immediate or early delayed adverse effects and no late effects were noted, and quality of life was good to excellent.

Polyetheretherketone—A suitable material for fixed dental prostheses?

OBJECTIVES To study the surface properties of polyetheretherketone (PEEK) and its bond strength with two veneering resins after different conditioning methods as well as fracture load of PEEK three-unit fixed dental prostheses (FDPs). METHODS Two hundred and twenty five PEEK specimens were fabricated and divided into five groups: no treatment (A), etching with 98% sulfuric acid for 1 min (B), air-abrasion for 10 s with either 50 or 110 μm alumina (C and D, respectively), and silica coating using the Rocatec System (E). On 15 specimens of each conditioning method, contact angle and surface roughness were determined. The remaining 150 specimens of each conditioning method were divided into two groups for the veneering procedure with the composites Gradia (GC Europe) and Sinfony (3M ESPE). Shear bond strength (SBS) was measured and failure types were assessed. In addition, 15 FDPs were milled and the fracture load was tested. Data were analyzed using descriptive statistics, one-way ANOVA (Scheffé test), two sample Students t-test, and Weibull statistics (p < 0.05). RESULTS Silica-coated PEEK surfaces showed the highest wettability. The highest roughness and lowest contact angles were observed for 110 μm air-abraded and silica-coated PEEK surfaces. The highest SBS values were, however, achieved in the acid-etched group. PEEK three-unit FDPs showed a mean fracture load of 1383 N with a plastic deformation starting approximately at 1200 N. CONCLUSIONS Acid etching should be applied when PEEK is used as substructure material and composite veneering material is applied. In this combination, PEEK might be a suitable material for FDPs, especially in load-bearing areas.

Two-body wear of monolithic, veneered and glazed zirconia and their corresponding enamel antagonists

OBJECTIVE This study tested whether the two-body wear of monolithic zirconia and their corresponding enamel antagonists was higher compared to monolithic alloy and veneered zirconia. MATERIALS AND METHODS Cylindrical specimens (N = 36, n = 6) were prepared out of (A) veneered zirconia (VZ), (B) glazed zirconia using a glaze ceramic (GZC), (C) glazed zirconia using a glaze spray (GZS), (D) manually polished monolithic zirconia (MAZ), (E) mechanically polished monolithic zirconia (MEZ) and (F) monolithic base alloy (control group, MA). Wear tests were performed in a chewing simulator (49 N, 1.7 Hz, 5°C/50°C) with enamel antagonists. The wear analysis was performed using a 3D profilometer before and after 120,000, 240,000, 640,000 and 1,200,000 masticatory cycles. SEM images were used for evaluating wear qualitatively. The longitudinal results were analysed using linear mixed models (α = 0.05). RESULTS Materials (p < 0.001) and number of masticatory cycles (p < 0.001) had a significant effect on the wear level. The least enamel antagonist wear was observed for MAZ and MEZ (27.3 ± 15.2, 28 ± 11.1 μm, respectively). GZC (118 ± 30.9 μm) showed the highest wear of enamel antagonists. The highest wear rate in the material was observed in GZS (91.3 ± 38.6 μm). While in the groups of MA, VZ, GZC and GZS 50% of the specimens developed cracks in enamel, it was 100% in MAZ and MEZ groups. CONCLUSION Polished monolithic zirconia showed lower wear rate on enamel antagonists as well as within the material itself but developed higher rates of enamel cracks.

Detection of Methicillin-Resistant Staphylococcus aureus (MRSA) in Specimens from Various Body Sites: Performance Characteristics of the BD GeneOhm MRSA Assay, the Xpert MRSA Assay, and Broth-Enriched Culture in an Area with a Low Prevalence of MRSA Infections

ABSTRACT Universal surveillance upon patient admission is important in reducing the transmission of methicillin-resistant Staphylococcus aureus (MRSA) and associated disease in hospitals. High costs for the health care system in conjunction with MRSA have promoted the development of rapid screening methods to detect MRSA carriers. This study compared two real-time PCR methods, the BD GeneOhm MRSA assay (BDGO) and the Xpert MRSA assay, with broth-enriched culture to define their performance characteristics and rapidity in an area with low MRSA prevalence. In total, 414 swabs from the nose and 389 swabs from the groin from 425 patients were tested. Of those 425 patients, 378 had swabs from both the nose and groin in parallel. Two hundred thirty-one and 194 patients were randomly assigned to the BDGO group and the Xpert MRSA group, respectively. In general, sensitivity, specificity, and negative predictive value (NPV) were high for the BDGO (100%, 98.5%, and 100%, respectively) and the Xpert MRSA (100%, 98.2%, and 100%, respectively), irrespective of whether or not nasal and inguinal specimens were considered alone or combined. In contrast, the positive predictive value (PPV) was lower: before the resolution of discrepant results, the PPVs for nasal and inguinal specimens alone and combined were 87.5%, 86.7%, and 82.4% for the BDGO and 91.7%, 66.7%, and 92.9% for the Xpert MRSA, respectively. After the resolution of discrepant results, PPVs were 93.8%, 93.3% and 94.1% for the BDGO and 91.7%, 88.9% and 92.9% for the Xpert MRSA, respectively. With the BDGO, 4 of 16 carriers were each identified by nasal or inguinal swabs alone, whereas in the Xpert MRSA group, 4 of 13 carriers were exclusively identified by nasal swabs and 2 of 13 were identified by inguinal swabs alone. Both PCR methods showed no significant difference in the number of discrepant results (odds ratio, 0.70 [P = 0.789]), but specimens from wounds and other body sites (axilla, vagina, and throat) produced discrepancies more often than nasal and groin specimens (odds ratios, 4.724 [P = 0.058] and 12.163 [P < 0.001], respectively). The facts that no false-negative PCR results were detected and increased PPVs were found after the resolution of discrepant results point to PCR as the actual gold standard. Since both sensitivity and NPV were exceptionally high for PCR, backup cultures may, therefore, be unnecessary in an area with low prevalence and with a preemptive isolation strategy but may still be useful for PCR-positive specimens because of the lower PPV for both methods and the possibility of susceptibility testing. The median time for analysis, including extraction, hands-on time, and actual PCR was 2 h 20 min for the Xpert MRSA versus 5 h 40 min for the BDGO. Concerning reporting time, including administration and specimen collection, the Xpert MRSA was faster than the BDGO (7 h 50 min versus 17 h).

Erosion and abrasion of tooth-colored restorative materials and human enamel

OBJECTIVES The aim of this study was to investigate the effects of erosion and toothbrush abrasion on different restorative materials and human enamel. METHODS Human enamel and 5 kinds of tooth-colored restorative materials were used. The restorative materials included three composite resins (Filtek Silorane, Tetric EvoCeram, and Tetric EvoFlow), a polyacid-modified composite (Dyract Extra), and a conventional glass-ionomer cement (Ketac Fil Plus). For each type of the material, 40 specimens were prepared and embedded in ceramic moulds and divided into four groups (n=10): control group (C), erosion group (E), abrasion group (A), and erosion-abrasion group (EA). The specimens were subjected to six daily erosive attacks (groups E and EA; citric acid, pH 2.3, 1 min) and/or six abrasive attacks (groups A and EA; toothbrush abrasion, 100 strokes, 1 min), while the control specimens (group C) were maintained in artificial saliva. After 10-day treatment, the substance loss and surface changes were determined by surface profilometry and scanning electron microscopy. RESULTS Human enamel presented higher substance loss when compared to restorative materials. Generally, combined erosion-abrasion (EA) caused the highest substance loss, followed by erosion, abrasion, and storage in artificial saliva. Composite resin presented highest durability under erosive and/or abrasive attacks. Enamel and restorative materials showed degradation in groups E and EA through SEM observation. CONCLUSIONS Toothbrush abrasion has a synergistic effect with erosion on substance loss of human enamel, polyacid-modified composite and glass-ionomer cement. The acid- and abrasive-resistance of human enamel was lower compared to restorative materials.

Protective Effect of Different Tetrafluorides on Erosion of Pellicle-Free and Pellicle-Covered Enamel and Dentine

The aim was to analyze the protective effects of titanium, zirconium and hafnium tetrafluorides on erosion of pellicle-free and pellicle-covered enamel and dentine in vitro. Eight groups of 20 specimens each of bovine enamel and bovine dentine were prepared. Half the specimens in each group were immersed in human saliva for 2 h for pellicle formation. Specimens were then left untreated (controls) or were treated for 120 s with TiF4, ZrF4 or HfF4 solutions (0.4 or 1%) or 1.25% AmF/NaF gel. All specimens were eroded by exposure to hydrochloric acid, pH 2.6, for 25 min. Cumulative calcium release into the acid was monitored in consecutive 30-second intervals for 5 min, then at 2-min intervals up to a total erosion time of 25 min using the Arsenazo III procedure. Data were analyzed by ANOVA. 1% TiF4 solution offered the best protective effect, especially in dentine (reduction of calcium loss about 50% at 25 min). 1% ZrF4, 1% HfF4 and 0.4% TiF4 also reduced calcium loss, but to a lesser extent. Long-term effects were limited to dentine, while reduction of enamel erosion (about 25%) was restricted to 1-min erosion. The fluoride gel had a protective effect only in dentine. The efficacy of the tetrafluorides was influenced by the presence of the pellicle layer, in that the protection against dentine erosion by TiF4 and ZrF4 was greater on pellicle-covered specimens. Tetrafluoride solutions, especially 1% TiF4, could decrease dental erosion, but were more effective on dentine than on enamel.