The outcomes of laparoscopic omentum-preserving gastrectomy compared to open surgery with omentectomy in gastric cancer patients: a propensity score matched study of 249 UICC stage 0-IV gastric cancer patients.

BACKGROUND: We performed a propensity score matched study comparing patients' short- and long-term results after laparoscopic omentum-preserving gastrectomy and open surgery with omentectomy with UICC stages 0-IV. METHODS: Between 2015 and 2022, 311 patients with gastric cancer underwent surgery at the University Clinical Centre Maribor. Of these, 249 met the inclusion criteria and 198 were included in the study group after PSM. RESULTS: Patients in both groups were well-balanced in demographic and pathological characteristics after PSM. There was no significant difference in the 5-year survival between groups (LAP: 62.2% vs. OPN: 54.4%; p = 0.950). The Cox regression model identified UICC stage and age as significant predictors for survival. In both groups, peritoneal dissemination was the most common site of recurrence. The multivariate analysis identified the UICC stage as a significant predictor for peritoneal recurrence, while omental preservation was not associated with a higher risk of peritoneal dissemination. Omentum preservation was not associated with more intestinal obstruction. Patients in the LAP group had significantly shorter hospital stays (LAP: 9(6) vs. OPN: 10(5); p = 0.009), less postoperative morbidity (LAP: 17% vs. OPN: 23.4%; p = 0.009), and significantly more extracted LNs per operation compared to open surgery (LAP: 31 ± 11 LNs vs. OPN: 25 ± 12 LNs; p = 0.002). CONCLUSION: Based on our results, we recommend the use of laparoscopic omentum-preserving gastrectomy in patients with early and advanced gastric cancer.

Multi-city comparative PM2.5 source apportionment for fifteen sites in Europe: The ICARUS project.

PM2.5 is an air pollution metric widely used to assess air quality, with the European Union having set targets for reduction in PM2.5 levels and population exposure. A major challenge for the scientific community is to identify, quantify and characterize the sources of atmospheric particles in the aspect of proposing effective control strategies. In the frame of ICARUS EU2020 project, a comprehensive database including PM2.5 concentration and chemical composition (ions, metals, organic/elemental carbon, Polycyclic Aromatic Hydrocarbons) from three sites (traffic, urban background, rural) of five European cities (Athens, Brno, Ljubljana, Madrid, Thessaloniki) was created. The common and synchronous sampling (two seasons involved) and analysis procedure offered the prospect of a harmonized Positive Matrix Factorization model approach, with the scope of identifying the similarities and differences of PM2.5 key-source chemical fingerprints across the sampling sites. The results indicated that the average contribution of traffic exhausts to PM2.5 concentration was 23.3% (traffic sites), 13.3% (urban background sites) and 8.8% (rural sites). The average contribution of traffic non-exhausts was 12.6% (traffic), 13.5% (urban background) and 6.1% (rural sites). The contribution of fuel oil combustion was 3.8% at traffic, 11.6% at urban background and 18.7% at rural sites. Biomass burning contribution was 22% at traffic sites, 30% at urban background sites and 28% at rural sites. Regarding soil dust, the average contribution was 5% and 8% at traffic and urban background sites respectively and 16% at rural sites. Sea salt contribution was low (1-4%) while secondary aerosols corresponded to the 16-34% of PM2.5. The homogeneity of the chemical profiles as well as their relationship with prevailing meteorological parameters were investigated. The results showed that fuel oil combustion, traffic non-exhausts and soil dust profiles are considered as dissimilar while biomass burning, sea salt and traffic exhaust can be characterized as relatively homogenous among the sites.

Mercury concentrations in biota in the Mediterranean Sea, a compilation of 40 years of surveys.

The Mediterranean Region has a long lasting legacy of mercury mining activities and a high density of sub-marine volcanoes that has strongly contributed to its mercury budget. In the last forty years, there have been recorded increases in mercury concentrations in biota that have spurred a growing number of research activities to assess the impact of mercury pollution on human health and environment. Field investigations that quantify mercury concentrations in marine biota have led to a large amount of experimental data scattered in many peer-reviewed publications making it difficult for modelling applications and regional environmental assessments. This paper reviews existing peer-reviewed literature and datasets on mercury concentration in marine flora and fauna (Animal, Plants and Chromista Kingdoms) in the Mediterranean basin. A total of 24,465 records have been retrieved from 539 sources and included in Mercury in Mediterranean Biota (M2B). Well-defined specimens account for 24,407 observations, while a few records include generic plankton and unidentified fish species. Among all considered species, we selected Diplodus sargus, Sardina pilchardus, Thunnus thynnus and Xiphias gladius to show trends of mercury concentration against WHO and EU limits. Few notes on how M2B is intended to support the implementation of the Minamata Convention on Mercury by a user-driven Knowledge Hub are finally reported.

The discriminatory value of cardiorespiratory interactions in distinguishing awake from anaesthetised states: a randomised observational study.

Depth of anaesthesia monitors usually analyse cerebral function with or without other physiological signals; non-invasive monitoring of the measured cardiorespiratory signals alone would offer a simple, practical alternative. We aimed to investigate whether such signals, analysed with novel, non-linear dynamic methods, would distinguish between the awake and anaesthetised states. We recorded ECG, respiration, skin temperature, pulse and skin conductivity before and during general anaesthesia in 27 subjects in good cardiovascular health, randomly allocated to receive propofol or sevoflurane. Mean values, variability and dynamic interactions were determined. Respiratory rate (p = 0.0002), skin conductivity (p = 0.03) and skin temperature (p = 0.00006) changed with sevoflurane, and skin temperature (p = 0.0005) with propofol. Pulse transit time increased by 17% with sevoflurane (p = 0.02) and 11% with propofol (p = 0.007). Sevoflurane reduced the wavelet energy of heart (p = 0.0004) and respiratory (p = 0.02) rate variability at all frequencies, whereas propofol decreased only the heart rate variability below 0.021 Hz (p < 0.05). The phase coherence was reduced by both agents at frequencies below 0.145 Hz (p < 0.05), whereas the cardiorespiratory synchronisation time was increased (p < 0.05). A classification analysis based on an optimal set of discriminatory parameters distinguished with 95% success between the awake and anaesthetised states. We suggest that these results can contribute to the design of new monitors of anaesthetic depth based on cardiovascular signals alone.

A pilot study on the feasibility of European harmonized human biomonitoring: Strategies towards a common approach, challenges and opportunities.

In 2004 the European Commission and Member States initiated activities towards a harmonized approach for Human Biomonitoring surveys throughout Europe. The main objective was to sustain environmental health policy by building a coherent and sustainable framework and by increasing the comparability of data across countries. A pilot study to test common guidelines for setting up surveys was considered a key step in this process. Through a bottom-up approach that included all stakeholders, a joint study protocol was elaborated. From September 2011 till February 2012, 17 European countries collected data from 1844 mother-child pairs in the frame of DEMOnstration of a study to COordinate and Perform Human Biomonitoring on a European Scale (DEMOCOPHES).(1) Mercury in hair and urinary cadmium and cotinine were selected as biomarkers of exposure covered by sufficient analytical experience. Phthalate metabolites and Bisphenol A in urine were added to take into account increasing public and political awareness for emerging types of contaminants and to test less advanced markers/markers covered by less analytical experience. Extensive efforts towards chemo-analytical comparability were included. The pilot study showed that common approaches can be found in a context of considerable differences with respect to experience and expertize, socio-cultural background, economic situation and national priorities. It also evidenced that comparable Human Biomonitoring results can be obtained in such context. A European network was built, exchanging information, expertize and experiences, and providing training on all aspects of a survey. A key challenge was finding the right balance between a rigid structure allowing maximal comparability and a flexible approach increasing feasibility and capacity building. Next steps in European harmonization in Human Biomonitoring surveys include the establishment of a joint process for prioritization of substances to cover and biomarkers to develop, linking biomonitoring surveys with health examination surveys and with research, and coping with the diverse implementations of EU regulations and international guidelines with respect to ethics and privacy.

Interpreting biomarker data from the COPHES/DEMOCOPHES twin projects: Using external exposure data to understand biomarker differences among countries.

In 2011 and 2012, the COPHES/DEMOCOPHES twin projects performed the first ever harmonized human biomonitoring survey in 17 European countries. In more than 1800 mother-child pairs, individual lifestyle data were collected and cadmium, cotinine and certain phthalate metabolites were measured in urine. Total mercury was determined in hair samples. While the main goal of the COPHES/DEMOCOPHES twin projects was to develop and test harmonized protocols and procedures, the goal of the current paper is to investigate whether the observed differences in biomarker values among the countries implementing DEMOCOPHES can be interpreted using information from external databases on environmental quality and lifestyle. In general, 13 countries having implemented DEMOCOPHES provided high-quality data from external sources that were relevant for interpretation purposes. However, some data were not available for reporting or were not in line with predefined specifications. Therefore, only part of the external information could be included in the statistical analyses. Nonetheless, there was a highly significant correlation between national levels of fish consumption and mercury in hair, the strength of antismoking legislation was significantly related to urinary cotinine levels, and we were able to show indications that also urinary cadmium levels were associated with environmental quality and food quality. These results again show the potential of biomonitoring data to provide added value for (the evaluation of) evidence-informed policy making.

Gender differences in cadmium and cotinine levels in prepubertal children.

Susceptibility to environmental stressors has been described for fetal and early childhood development. However, the possible susceptibility of the prepubertal period, characterized by the orchestration of the organism towards sexual maturation and adulthood has been poorly investigated and exposure data are scarce. In the current study levels of cadmium (Cd), cotinine and creatinine in urine were analyzed in a subsample 216 children from 12 European countries within the DEMOCOPHES project. The children were divided into six age-sex groups: boys (6-8 years, 9-10 years and 11 years old), and girls (6-7 years, 8-9 years, 10-11 years). The number of subjects per group was between 23 and 53. The cut off values were set at 0.1 µg/L for Cd, and 0.8 µg/L for cotinine defined according to the highest limit of quantification. The levels of Cd and cotinine were adjusted for creatinine level. In the total subsample group, the median level of Cd was 0.180 µg/L (range 0.10-0.69 µg/L), and for cotinine the median wet weight value was 1.50 µg/L (range 0.80-39.91 µg/L). There was no significant difference in creatinine and cotinine levels between genders and age groups. There was a significant correlation between levels of cadmium and creatinine in all children of both genders. This shows that even at such low levels the possible effect of cadmium on kidney function was present and measurable. An increase in Cd levels was evident with age. Cadmium levels were significantly different between 6-7 year old girls, 11 year old boys and 10-11 year old girls. As there was a balanced distribution in the number of subjects from countries included in the study, bias due to data clustering was not probable. The impact of low Cd levels on kidney function and gender differences in Cd levels needs further investigation.

Evaluation of focused sentinel lymph node RT-qPCR screening for micrometastases with the use of the Maruyama computer program.

BACKGROUND: In this preliminary study, we investigated the sensitivity and specificity of reverse transcriptase (RT)-qPCR lymph node (LN) metastases detection, the accuracy of intraoperative dye navigation, and the incidence of micrometastasis (MM) detection with this protocol, compared to other published studies. METHODS: A total of 23 patients were enrolled in the study. The first stained LN was analyzed using RT-qPCR for carcinoembryonic antigen (CEA) and cytokeratin 20 (CK-20) expression, as markers for MM involvement. The Maruyama computer program was used to determine the most likely first metastatic site. These results were compared with the actual staining patterns to evaluate whether the first draining LN was extracted. We analyzed the correlations between MM and tumor characteristics. The incidence of MM detected with the present method was compared to other studies, as markers of the accuracy of the present protocol. RESULTS: At 35 threshold cycles, the RT-qPCR had a negative predictive value of 100 % and a positive predictive value of 83.3 %. MM were detected in 4 out of 14 node-negative patients (28.6 %). The extracted sentinel LN coincided in 76.9 % of cases with the most probable first metastatic LN predicted by the Maruyama program. MM were found more frequently in these 'high-risk' LNs. Significant differences were found in the Lauren's histological type distribution and the age distribution among the MM-positive and MM-negative groups. CONCLUSION: Our preliminary results confirm that RT-qPCR is an accurate method of MM detection, that the dye navigation enables the determination of the first draining LN, and that the incidence of MM detection with this focused sentinel LN protocol is comparable to other studies.

The influence of dual-task conditions on movement in young adults with and without Down syndrome.

This investigation compared spatial and temporal movement parameters of a sample of young adults with Down syndrome (DS) (N=12) and individuals without disabilities (IWD) (N=12) under dual-task conditions. Subjects performed a walking task at a preferred speed in isolation and again while holding a plate and cup, carrying tray and cups, talking on a phone, or buttoning a shirt. Spatial and temporal values were compared using a 2 (group) × 5 (conditions) repeated measures analysis of variance. Analysis of spatial components separately indicated that step length, step width, stride length and stride width revealed significant group and condition interactions (p ≤.01). Temporal components yielded significance in velocity and single-leg support time (p ≤.01). The current results support the notion that along with impairments to qualitative motor skills, individuals with DS are also impaired in higher order executive functioning (EF), as measured by a dual-task paradigm. It was concluded that movements are less efficient and functional in individuals with DS when an additional task is encountered while walking. We theorized that the motor program was sufficient for general locomotion but was not sufficiently developed to allow individuals with DS to modify or alter their movements to changing cognitive conditions that increasingly taxed EF. As gait and balance are trainable in this population, we recommend developing appropriate exercise and motor skill interventions during childhood and adolescents to increase strength, stability, and more "robust" ambulatory motor schema.

Neuropsychological assessment at school-age and prenatal low-level exposure to mercury through fish consumption in an Italian birth cohort living near a contaminated site.

The relative effects of prenatal and postnatal low-level mercury exposure and fish intake on child neurodevelopment are still controversial. Limited evidence is available from Mediterranean populations. In this prospective study, we measured the Verbal and Performance IQ in Italian children at school-age who were resident in an area declared as a National contaminated site because of mercury pollution, taking into account the possible beneficial effect of fish consumption and potential confounders. A mother-child cohort made up of 242 children was established at birth in Northeastern Italy in 2001. Their mothers were interviewed approximately 2 months after delivery to determine type, quantity, and origin of fish consumed during pregnancy and about a number of mother, child and family characteristics. Total mercury (THg) and methyl mercury (MeHg) were assessed in maternal hair and breast milk and in the child's hair. When children reached 7-9 years of age, 154 (63.6%) parents gave consent to participate in a follow-up evaluation. On that occasion, a child's hair sample was collected to determine the current concentration of THg, mothers were asked to complete a self-administered questionnaire, and children underwent neuropsychological testing. Verbal IQ, performance IQ and full scale IQ were measured by the Wechsler Intelligence Scale for Children (WISC III) administered by psychologists at school or local health centers. Demographic, socioeconomic and lifestyle information, medical information of the child's family and the child's dietary habits were collected using a questionnaire filled in by mothers. Multivariable linear regression models were used to evaluate the association between prenatal THg exposure through fish consumption of mothers in pregnancy and children's IQ after adjustment for possible confounders such as fish consumption of mothers in pregnancy, child's fish consumption at follow-up, child's birthweight, maternal cigarette smoking during pregnancy, house size and property place of residence during pregnancy and gender. THg in the child's hair at 7 years of age was fairly correlated with THg in maternal hair at delivery (rs=0.35; p<0.0001) and was strongly correlated with child's seafood consumption (rs=0.50, p<0.0001). No differences in maternal THg levels were found when comparing children with low or extremely low or high or extremely high scores vs others, considering separately full scale, verbal, and performance IQs. Children born from mothers with hair THg levels greater than or equal to 2000ng/g had full scale, verbal and performance IQs which were 4-5 points lower than children born from women with lower THg levels, but these differences were not statistically significant. Fresh fish intake of mothers in pregnancy was slightly positively associated with full scale and performance but not so with verbal IQs. Canned fish showed to be negatively associated with all the outcome variables. Unexpectedly, children born to mothers from one town showed IQ scores significantly lower than the other children; however, none of the many variables considered in these analyses could explain this result. The relatively low Hg levels found in the biological samples did not provide evidence of high and extensive Hg exposure in this population. Although THg levels in maternal and child's biological samples are correlated with fish consumption, the effects of THg and fish on neurological outcomes go in opposite directions. These results do not allow to develop recommendations regarding fish consumption in pregnancy but suggest that keeping THg hair levels<2000ng/g might be desirable.

Evaluation of a focused sentinel lymph node protocol in node-negative gastric cancer patients.

BACKGROUND/AIMS: A specific preoperative work-up was used to access a limited number of high-risk lymph nodes with RT-qPCR for micrometastatic sentinel lymph node involvement. We validated our protocol with IHC screening for micrometastases and long-term survival analysis. METHODOLOGY: From the 32 patients included 22 were node-negative patients. With a specific preoperative protocol sentinel lymph nodes (1-2 per patient) were extracted for further RT-qPCR analysis for CEA and CK20 expression. In 10 patients from the study group, the remaining lymph nodes around the extracted sentinel lymph node from the first compartment were additionally screened using IHC for missed micrometastases. RESULTS: Micrometastases were detected in seven of 22 (31.8%) node-negative patients. RT-qPCR identified micrometastases in four of 10 haematoxylin-eosin-negative lymph nodes (40%), and in three of eight IHC negative lymph nodes (37.5%). The cumulative 3-year survival for the study group was 80.8%. The 3-year survival in the RT-qPCR-negative group was 90%, compared with 66.7% in the RT-qPCR-positive group (p=0.289). CONCLUSIONS: Encouraged by these results, we will include more patients in our focused sentinel lymph node protocol. With a refinement of our method, we believe the focused sentinel lymph node protocol can be implemented for intraoperative tailoring of extent of lymphadenectomy.

Spatial and temporal variability of movement parameters in individuals with Down syndrome.

This investigation compared spatial and temporal gait movement parameters of a sample of individuals with Down syndrome (n=12) and one of individuals without disabilities (n=12). All participants were evaluated on responses to a preferred pace and fast walk with the GAITRite Electronic Walkway. Spatial outcomes included step and stride length, step and stride width, toe-in/toe-out, and base of support. Temporal outcomes included step time, velocity, single and double leg support time, stance, and swing time. There were significant group differences for step length, step width, stride length, and velocity in the preferred walk condition. Significant group differences for step length, step width, and stride length were observed in the fast walk condition. Percentage differences also indicated lower scores for all spatial and temporal variables in relation to the control group. The ability to control gait movements appears to reflect earlier movement experiences, so it may be possible to use variable sensory feedback and specific training to modify and adjust movement responses and improve gait performance in Down syndrome.

SU-E-J-106: Atlas-Based Segmentation: Evaluation of a Multi-Atlas Approach for Lung Cancer.

PURPOSE: Previous studies have shown atlas-based segmentation using a single best matched (SBM) atlas subject can significantly reduce contouring time. A new multi-atlas approach has been shown to provide greater accuracy than SBM for cancer of the head and neck. The goal of this study was to evaluate the multi-atlas technique for lung cancer treatment planning. METHODS: An institution's SBRT lung atlas containing 82 subjects was utilized for atlas segmentation. Each atlas subject contained manually defined contours of the esophagus, cord, heart, left lung, right lung, and trachea. CT scans and contours for 16 subjects were evaluated. SBM used the one automatically determined best match for segmentation. Multi-atlas used multiple automatically determined best matches: 3, 4, and 5, respectively. The final segmentation for multi-atlas was generated using Majority Vote which comprises the area of overlap for at least half of the individual segmentations (2 of 3, 2 of 4, and 3 of 5, respectively). Average Dice Similarity Coefficients (DSC) were calculated for each structure to compare against manually defined 'gold' standard contours for that subject. Overall percent improvement was calculated as the proportion of the error corrected by the method, or % difference on 1-DSC. RESULTS: All multi-atlas methods were significantly more accurate than SBM (p-value < 0.0005) with average DSC of 0.802 +/- 0.172, 0.809 +/ 0.163, 0.802 +/- 0.182 respectively for Multi-3, Multi-4, and Multi-5 compared to 0.773 +/- 0.187 for SBM. No significant differences existed between the different multi-atlas approaches. Overall, Multi-4 showed the greatest improvement over SBM with 16% improvement followed by Multi-3 and Multi-5 at 12%. CONCLUSIONS: Each multi-atlas approach resulted in significantly more accurate contours compared to the SBM. While still requiring some editing, this method for segmentation using multiple atlases shows promise for further decreasing the contouring time required for lung cancer. MIM Software Inc.

Biomarkers of low-level mercury exposure through fish consumption in pregnant and lactating Slovenian women.

In order to assess the mercury exposure of pregnant and lactating women in Slovenia, levels of total mercury (THg) and methylmercury (MeHg) were determined in hair, cord blood and breast milk. In addition, the frequency of fish consumption was estimated, because fish is generally the main pathway for human exposure to MeHg. Hair samples were collected from 574 women participating in this study, while cord blood and breast milk samples were collected from 446 and 284 women, respectively. As expected, the levels of THg in hair (median (Med)=297 ng/g, 10th percentile (P10)=73 ng/g, 90th percentile (P90)=781 ng/g), cord blood (Med=1.5 ng/g, P10=0.5 ng/g, P90=4.2 ng/g) and breast milk (Med=0.2 ng/g, P10=0.06 ng/g, P90=0.6 ng/g) were low, due to low consumption of fish (X=25 g/day). A significant linear correlation was found between levels of lnTHg in hair and lnTHg in cord blood (r=0.87, 95% confidence interval (CI): 0.84-0.89), between levels of lnTHg in hair and lnMeHg in cord blood (r=0.94, 95% CI: 0.90-0.96) and between lnTHg levels in cord blood and lnTHg levels in breast milk (r=0.36, 95% CI: 0.25-0.47). Spearman's rank correlations between the frequency of fish consumption and THg in hair (rs=0.35, 95% CI: 0.28-0.42), and between the frequency of fish consumption and THg in cord blood (rs=0.43, 95% CI: 0.36-0.51) or MeHg in cord blood (rs=0.31, 95% CI: 0.06-0.52) were weak. This could be due to the approximate information on fish consumption obtained from the questionnaires, the high variability of MeHg concentrations in fish and a relatively high proportion of inorganic mercury in the biomarkers which originates from sources other than fish. In conclusion, THg levels in cord blood, THg levels in hair and MeHg levels in cord blood are suitable biomarkers of low-level Hg exposure through fish consumption. Compared to cord blood, hair samples are easy to collect, store and analyse.

Relationship between the prenatal exposure to low-level of mercury and the size of a newborn's cerebellum.

Exposure to methylmercury at any stage of central nervous system development could induce alterations and result in severe congenital abnormalities. Total mercury level in maternal hair during pregnancy correlates well with blood levels of methylmercury and with total mercury levels in fetal brain. A prospective study has been conducted and a total of 137 childbearing women living at the coastal region with term, normal pregnancies were included and their newborns evaluated by ultrasonography. Mothers and their newborns are divided in two groups according to their hair mercury levels; examined group with high body levels of mercury (≥ 1 µg/g) and control group with low body levels of mercury (<1 µg/g). Neurosonographic examination was conducted to all newborns. Two dimensions of cerebellum in the sagital-medial plane have been measured: maximum height and width starting from the roof of the fourth chamber. Majority of mothers had hair mercury levels lower than 1 µg/g (N = 107). Mean value was 0.88 µg/g (SD 1.24), ranging from 0.02 to 8.71 µg/g. There was no significant difference between the two groups when it comes to the width of cerebellum (Mann-Whitney test: Z = 1471; p = 0.141). However, comparison related to the length of cerebellum shows statistically significant smaller cerebellum in newborns whose mother had hair mercury levels higher than 1 µg/g (Mann-Whitney test: Z = 2329; p = 0.019). Our results lead to a conclusion that prenatal exposure to, what we consider to be, low-levels of methylmercury does influence fetal brain development detected as decreased size of newborn's cerebellum. From a clinical point of view, a question related to the influence of prenatal low-level methylmercury exposure on fetal neurodevelopment remains open. Our further objectives are to direct the research towards performing detailed neuropshychological tests on children at the age of 18 months. Such tests could indicate the presence of subtle neurological or neuropsychological deficits.

An investigation into the thermal behaviour of a model drug mixture with amorphous trehalose.

The thermal and structural properties of amorphous trehalose mixed with a model drug, paracetamol, have been studied with a view to developing understanding of the thermal events undergone by such binary systems. A physical mixture of paracetamol and spray dried trehalose (1:9 weight ratio) was studied using differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), hot stage microscopy (HSM), and variable temperature powder X-ray diffraction (VTPXRD). The presence of the drug resulted in a lower temperature recrystallization exotherm for the trehalose compared to the disaccharide alone. Evidence is presented for the trehalose recrystallization being triggered by the melting rather than simply the presence of the paracetamol particles. HSM studies indicated that the trehalose recrystallized around the drug on heating, with the recrystallization temperature again corresponding to the melting of the drug. VTPXRD indicated that the presence of the drug again lowered the recrystallization temperature of the trehalose, although the trehalose anhydrate diffraction peaks were discernible at a lower temperature for both the pure trehalose and the mixed systems than was observed for the DSC studies, suggesting that the association between recrystallization and drug melting was not apparent when using this approach. It is suggested that while the trehalose recrystallization process is not significantly influenced by the presence of the drug when studied over relatively long time periods such as those used for the VTPXRD studies, the process is triggered by the melting of the paracetamol when short experimental times and scanning conditions are used such as those relevant to DSC studies. These data have implications for the quality control of trehalose products using DSC, the characterisation of the physical structure of the binary systems and the prediction of the corresponding physical stability.

Hydroxypropyl methylcellulose microspheres with piroxicam and piroxicam-hydroxypropyl-beta-cyclodextrin inclusion complex.

Inclusion complexation between piroxicam (PX) and hydroxypropyl-beta-cyclodextrin (HPbetaCD) in the presence of hydroxypropyl methylcellulose (HPMC) was studied in aqueous solution and in the solid state. Phase solubility studies were used to evaluate the HPbetaCD complexation in the presence of HPMC. Stability constants, Ks, of the complexes were determined. The stability of the inclusion complex was improved in the presence of HPMC. Solid microspheres were obtained by spray drying, and were characterized by differential scanning calorimetry (DSC), regarding drug content, and particle size distribution. Scanning electron microscopy (SEM) was also used to characterize the systems prepared. In the solid system HPMC facilitated to some extent the drug dissolution due to increased solubility. The presence of HPMC and HPbetaCD in the microspheres promoted dissolution rate. Cyclodextrin complexation increased PX flux through a semipermeable membrane. Presence of HPMC in the system additionally increased the drug flux more than 80%, by increasing the drug solubility and consequently the affinity of the ternary complex for the aqueous diffusion layer in the donor compartment.

Macromolecular prodrugs XI. Synthesis and characterization of polymer-estradiol conjugate.

Estradiol-3-benzoate (EB), an ester derivative of the main oestrogen hormone estradiol, was chemically modified and bound to poly(alpha,beta-(N-2-hydroxyethyl-DL-aspartamide))-poly(alpha,beta-(N-2-aminoethyl-DL-aspartamide)) copolymer (PAHA). EB was first converted to estradiol-3-benzoate-17-(benzotriazole-1-carboxylate), which readily reacted with amino groups in PAHA affording the polymer-drug conjugate PAHA-EB. In PAHA-EB estradiol moiety was covalently bound to the polymeric carrier by carbamate linkage, through non-toxic ethylenediamine spacer. The synthesized compound is a potential hydrosoluble estradiol prodrug.

Emphysematous gastritis -- case report and review of the literature.

Emphysematous gastritis is a rare form of phlegmonous gastritis caused by invasion of the stomach wall by gas-forming bacteria. This clinical entity was first described by Fraenkel in 1889. The authors report the case of a 58-year-old patient with end-stage renal failure under treatment with hemodialysis for the past year. He was admitted on account of pain in the lower abdomen. During the diagnostic procedure, emphysematous gastritis and acute cholecystitis were confirmed. An acute abdomen developed and an emergency laparotomy was performed. During the procedure, the necrotic gallbladder was removed. The patient died on the following day due to multiorgan failure and septic shock. According to the literature, emphysematous gastritis is generally a fatal disease. Air in the wall of the stomach is a rare finding with a broad differential diagnosis.

Periprostatic local anesthesia eliminates pain of office-based transrectal prostate biopsy.

Up to 96% of patient who undergo prostate biopsy report pain. We performed periprostatic local anesthesia injection in an effort to improve patient acceptance of prostate biopsy. Sixty patients were randomized to receive either local injection of lidocaine in the periprostatic nerves or no anesthetic. Lidocaine was injected through a 7-inch spinal needle placed through a transrectal ultrasound biopsy guide. Ten-core biopsies were immediately performed. Following biopsy, all patients gave a Visual Analog Scale (VAS) assessment of their pain experienced during biopsy.A majority of patients reported Visual Analog Scale (VAS) scores in the moderate (28.6%) or severe (28.6%) ranges unless local anesthesia was given. Only one of 27 patients (3.7%) receiving local anesthetic reported moderate pain, and none reported severe pain. Mean VAS pain scores were 1.4 in the anesthetic group and 4.5 in the control group (P<0.0001). No difficulty was encountered from scarring in the five patients who underwent nerve spring radical retropubic prostatectomy following local anesthetic injection. Periprostatic injection of local anesthetic essentially eliminates pain from prostate biopsy. Nerve-sparing radical retropubic prostatectomy is not more difficult as a result.