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Background: This study assessed the diagnostic accuracy of cone-beam computed tomography (CBCT) with a modified grayscale range for the detection of buccal cortical plate defects adjacent to dental implants. Materials and Methods: In this in vitro experimental study, titanium implants were inserted in 168 fresh bovine bone blocks with 1-1.5 mm of buccal cortical plate thickness. The blocks were randomly divided into four groups (n = 42). No defect was created in the control blocks. In the three experimental groups, cortical plate defects were randomly created in the cervical, middle, or apical third by a round bur with a 2-mm diameter (n = 42). All blocks underwent CBCT with and without change in the grayscale range. Two observers evaluated all images regarding the presence/absence of defects. Kappa test is used for the agreement of the observers. The diagnostic accuracy of the two modalities was compared by calculating the area under the receiver operating characteristic curve (AUC) (P ≤ 0.05). The sensitivity and specificity values were also compared. Results: The AUC was not significantly different between the two modalities with and without altered grayscale range (0.754 vs. 0.762, respectively, P = 0.716). The diagnostic sensitivity of CBCT with and without change in the grayscale range was 51% and 52%, respectively, with a specificity of 100% for both. The diagnostic accuracy of CBCT with and without altered grayscale range had no significant difference for apical and middle third defects (P > 0.05) and was significantly higher than that for the cervical third defects (P < 0.05). Conclusion: Changing the grayscale range does not improve the diagnostic accuracy of CBCT for the detection of buccal cortical plate defects adjacent to dental implants. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is a neurodegenerative disease with a complex etiology. Several factors are known to contribute to the disease onset and its progression. However, the complete underlying mechanisms are still escaping our understanding. To evaluate possible correlations between metabolites and metallomic data, in this research, we combined a control study measured using two different platforms. For the different data sources, we applied a Block Sparse Partial Least Square Discriminant Analysis (Block-sPLS-DA) model that allows for proving their relation, which in turn uncovers alternative influencing factors that remain hidden otherwise. We found two groups of variables that trace a strong relationship between metallomic and metabolomic parameters for disease development. The results confirmed that the redox active metals iron (Fe) and copper (Cu) together with fatty acids are the major influencing factors for the PD. Additionally, the metabolic waste product p-cresol sulfate and the trace element nickel (Ni) showed up as potentially important factors in PD. In summary, the data integration of different types of measurements emphasized the results of both stand-alone measurements providing a new comprehensive set of information and interactions, on PD disease, between different variables sources. [ABSTRACT FROM AUTHOR]

The underlying mechanisms of Parkinson´s disease are not completely revealed. Especially, early diagnostic biomarkers are lacking. To characterize early pathophysiological events, research is focusing on metabolomics. In this case-control study we investigated the metabolic profile of 31 Parkinson´s disease-patients in comparison to 95 neurologically healthy controls. The investigation of metabolites in CSF was performed by a 12 Tesla SolariX Fourier transform-ion cyclotron resonance-mass spectrometer (FT-ICR-MS). Multivariate statistical analysis sorted the most important biomarkers in relation to their ability to differentiate Parkinson versus control. The affected metabolites, their connection and their conversion pathways are described by means of network analysis. The metabolic profiling by FT-ICR-MS in CSF yielded in a good group separation, giving insights into the disease mechanisms. A total number of 243 metabolites showed an affected intensity in Parkinson´s disease, whereas 15 of these metabolites seem to be the main biological contributors. The network analysis showed a connection to the tricarboxylic cycle (TCA cycle) and therefore to mitochondrial dysfunction and increased oxidative stress within mitochondria. The metabolomic analysis of CSF in Parkinson´s disease showed an association to pathways which are involved in lipid/ fatty acid metabolism, energy metabolism, glutathione metabolism and mitochondrial dysfunction. [ABSTRACT FROM AUTHOR]

Background: A drug must reach the central nervous system (CNS) in order to directly cause CNS adverse effects (AEs). Our current study addressed the pharmacokinetic (PK) background of the assumption that CNS concentrations of hydrochlorothiazide (HCT) and ramiprilate may directly cause CNS AEs such as headache and drowsiness. Methods: In neurological patients, paired serum and cerebrospinal fluid (CSF) samples were withdrawn simultaneously. Some of them were treated with HCT (n = 15, daily chronic doses 7.5–25 mg) or ramipril (n = 9, 2.5–10 mg). Total concentrations of HCT and ramiprilate were quantified in these samples. To this end, sensitive liquid chromatography/tandem mass spectrometry methods were developed. Results: CSF reached 4.1% (interquartile ranges 2.5–5%) of total serum concentrations for HCT and 2.3% (1.7–5.7%) for ramiprilate, corresponding to about 11.3% and 5.5% of respective unbound serum concentrations. Conclusion: The PK/Pharmacodynamic characteristics of HCT and ramiprilate in the CNS are unknown. However, since the CSF levels of these agents, both free and bound, were much lower than the corresponding concentrations in serum, it is unlikely that the observed CNS AEs are mediated primarily via direct effects in the brain. [ABSTRACT FROM AUTHOR]

Background: Mycophenolic acid (MPA), either given as an ester pro-drug or as an enteric-coated sodium salt, is the most commonly prescribed anti-proliferative immunosuppressive agent used following organ transplantation and widely applied in immune-mediated diseases. Clinicians are well aware of common adverse reactions related to MPA treatment, in particular diarrhea, leukopenia and infections. Here we report a case of severe, persistent ascites associated with MPA treatment. The otherwise unexplained and intractable ascites, requiring repeated paracenteses for more than 8 months, rapidly ceased with stopping the MPA treatment. To our knowledge this is the first case of severe ascites associated with MPA treatment reported in the scientific literature.Case Presentation: A 45-year old female with type 1 diabetes mellitus received a simultaneous kidney-pancreas transplant. The surgery was uneventful. However, post-operatively she developed severe transudative ascites requiring in total more than 40 paracenteses treatments draining in the average 2.8 l of ascites fluid. The ascites formation persisted despite exclusion of a surgical complication, fully functioning kidney and pancreas allografts, lack of any significant proteinuria, normalization of circulating albumin levels, intensive use of diuretics and deliberate attempts to increase the intervals between the paracentesis treatments. Various differential diagnoses, including infectious, hepatic, vascular and cardiac causes were ruled out. Nine months after surgery enteric-coated mycophenolate sodium was switched to azathioprine after which ascites completely resolved. When mycophenolate was recommenced abdominal fullness and weight gain reoccurred. The patient had to be switched to long-term azathioprine treatment. More than 1 year post-conversion the patient remains free of ascites.Conclusion: MPA is the most widely used antimetabolite immunosuppressive agent. We suggest to consider MPA treatment in the differential diagnosis of severe and unexplained ascites in transplant and non-transplant patients. [ABSTRACT FROM AUTHOR]

Background: Bisoprolol and metoprolol are moderately lipophilic, beta(1)-selective betablockers reported to cause adverse effects in the central nervous system (CNS), such as sleep disturbance, suggesting that both drugs may reach relevant concentrations in the brain. CNS beta(2)-receptor blockade has been suspected to be related to such effects. The higher molecular size of bisoprolol (325 Dalton) and the higher beta(1)-selectivity compared to metoprolol (267 Dalton) would suggest a lower rate of CNS effects. Methods: To address the pharmacokinetic background of this assumption, we quantified to which extent these beta(1)-blockers are able to enter the cerebrospinal fluid (CSF) in 9 (bisoprolol group) and 10 (metoprolol group) neurological patients who had received one of the drugs orally for therapeutic purposes prior to lumbar puncture. We quantified their total concentrations by liquid chromatography/tandem mass spectrometry in paired serum and CSF samples. Results: Median (interquartile range) in CSF reached 55% (47-64%) of total serum concentrations for bisoprolol and 43% (27-81%) for metoprolol, corresponding to 78% (67-92%) and 48% (30- 91%) of respective unbound serum concentrations. Conclusion: The extent of penetration of bisoprolol and metoprolol into the CSF is similar and compatible with the assumption that both drugs may exert direct effects in the CNS. [ABSTRACT FROM AUTHOR]

Purpose: Analyzing different patterns of maxillary sinus septa in cone-beam computed tomography (CBCT) images and predicting maxillary sinus membrane perforations. Materials and Methods: In this cross-sectional study, CBCT images of 222 patients ranging from 20 to 81 years old were evaluated. One hundred fifty-two patients (93 females and 59 males) who had maxillary sinus septa in axial views were included in this study. Cross-sectional images were used to determine classifications of sinus septa and the risk of membrane perforation using a method modified from Al-Faraje et al. Variables of sex, age, and dental status were considered. Chi-squared and Kruskal-Wallis tests were used for data analysis (P<.05). Results: In this study, 265 maxillary sinus septal patterns were found. The mean age of the patients was 44.1±14.7 years old. The Class I and VII-div II patterns had the greatest and least prevalence, respectively. Furthermore, there was a significant relationship between the location of septa and the frequency of membrane perforation risk (P<.05). In this study, the relationship of different patterns of septa with dental status did not differ significantly (P>0.05). Conclusion: A higher prevalence of moderate risk of membrane perforation in the molar region relative to the premolar region was observed. Furthermore, maxillary sinus septa occur most frequently in the molar region, demonstrating the importance of paying attention to this region during sinus lift surgery. This study did not show any relationship between tooth loss and the presence of septa. [ABSTRACT FROM AUTHOR]

Background: Tonsilloliths are calcified concretions that develop in tonsillar crypts. They are usually small and asymptomatic, so they are found accidentally during routine dental radiography procedure. Large tonsilloliths can occur with clinical signs and symptoms. The purpose of this study was to evaluate the prevalence and patterns of palatine and adenoid tonsilloliths in cone-beam computed tomography (CBCT) images. Materials and Methods: In this cross-sectional study,0.5-mm axial and coronal slices of 134 CBCT images were evaluated to determine the presence of palatine and adenoid calcifications. Their patterns such as being unilateral or bilateral as well as single or multiple and their largest linear sizes were reported. Results: Fifty-four (40.3%) patients with palatine tonsilloliths and 17 (12.7%) with adenoid calcifications were found. Thirty (55.6%) palatine tonsilloliths were unilateral, 19 (35.2%) were detected in the left tonsils. Approximately, 54 cases of 78 palatine calcifications were multiple. Seventeen patients had adenoid calcifications that 41.1% of them were unilateral. Fourteen adenoid calcifications were single. The mean ages of patients with palatine tonsilloliths and adenoid calcifications were 45.59 years and 46.53 years, respectively. The range of linear measurements of palatine tonsil calcifications was 0.9-4.2 mm (2.47-mm mean size) while adenoid calcifications ranged from 0.5 to 2.2 mm (0.95-mm mean size).The level of statistical significant difference was <0.05. Conclusion: Gender did not affect total prevalence, the pattern of tonsilar calcifications and their linear sizes. The prevalence of tonsilloliths increased with aging, but this variable did not have an effect on their linear size. [ABSTRACT FROM AUTHOR]

Background: Pantoprazole is a proton pump inhibitor drug mainly used for treating peptic diseases. Adverse effects of pantoprazole in the occasional central nervous system (CNS) include headache, vertigo and sleep disturbances. Data in rats suggest that proton pumps are expressed in the inner ear and in the epithelium of the choroid plexus, which would be a potential target to mediate such proton pump inhibitor effects. Methods: To assess the distribution of pantoprazole into the human CNS despite its low lipophilicity (log p = 0.5), we quantified pantoprazole concentrations by liquid chromatography/ tandem mass spectrometry in serum and cerebrospinal fluid retain samples withdrawn simultaneously. Twenty-six sample pairs were obtained from 23 neurological patients with therapeutic administration of pantoprazole prior to sampling. Results: Median (interquartile range) serum concentration of total pantoprazole was 142 ng/ml (30.8-622). Cerebrospinal fluid concentration of total panto-prazole was 2.79 ng/ml (1.59-7.3) and reached 2.0% (1.0- 4.5%) of simultaneous serum concentrations. Conclusion: This value corresponds to the unbound fraction of pantoprazole in serum reported previously and indicates that pantoprazole CNS concentrations are high enough to exert some effects on possible CNS targets. [ABSTRACT FROM AUTHOR]

Background: Bisoprolol and metoprolol are moderately lipophilic, beta(1)-selective betablockers reported to cause adverse effects in the central nervous system (CNS), such as sleep disturbance, suggesting that both drugs may reach relevant concentrations in the brain. CNS beta(2)-receptor blockade has been suspected to be related to such effects. The higher molecular size of bisoprolol (325 Dalton) and the higher beta(1)-selectivity compared to metoprolol (267 Dalton) would suggest a lower rate of CNS effects., Methods: To address the pharmacokinetic background of this assumption, we quantified to which extent these beta(1)-blockers are able to enter the cerebrospinal fluid (CSF) in 9 (bisoprolol group) and 10 (metoprolol group) neurological patients who had received one of the drugs orally for therapeutic purposes prior to lumbar puncture. We quantified their total concentrations by liquid chromatography/tandem mass spectrometry in paired serum and CSF samples., Results: Median (interquartile range) in CSF reached 55% (47-64%) of total serum concentrations for bisoprolol and 43% (27-81%) for metoprolol, corresponding to 78% (67-92%) and 48% (30-91%) of respective unbound serum concentrations., Conclusion: The extent of penetration of bisoprolol and metoprolol into the CSF is similar and compatible with the assumption that both drugs may exert direct effects in the CNS., (© 2017 S. Karger AG, Basel.)

Purpose: Analyzing different patterns of maxillary sinus septa in cone-beam computed tomography (CBCT) images and predicting maxillary sinus membrane perforations., Materials and Methods: In this cross-sectional study, CBCT images of 222 patients ranging from 20 to 81 years old were evaluated. One hundred fifty-two patients (93 females and 59 males) who had maxillary sinus septa in axial views were included in this study. Cross-sectional images were used to determine classifications of sinus septa and the risk of membrane perforation using a method modified from Al-Faraje et al. Variables of sex, age, and dental status were considered. Chi-squared and Kruskal-Wallis tests were used for data analysis ( P <.05)., Results: In this study, 265 maxillary sinus septal patterns were found. The mean age of the patients was 44.1±14.7 years old. The Class I and VII-div II patterns had the greatest and least prevalence, respectively. Furthermore, there was a significant relationship between the location of septa and the frequency of membrane perforation risk ( P <.05). In this study, the relationship of different patterns of septa with dental status did not differ significantly ( P >0.05)., Conclusion: A higher prevalence of moderate risk of membrane perforation in the molar region relative to the premolar region was observed. Furthermore, maxillary sinus septa occur most frequently in the molar region, demonstrating the importance of paying attention to this region during sinus lift surgery. This study did not show any relationship between tooth loss and the presence of septa.