Determination of Response Factors for Analytes Detected during Migration Studies, Strategy and Internal Standard Selection for Risk Minimization.

Migration studies are one of the few domains of pharmaceutical analysis employing wide-scope screening methodologies. The studies involve the detection of contaminants within pharmaceutical products that arise from the interaction between the formulation and materials. Requiring both qualitative and quantitative data, the studies are conducted using Liquid Chromatography or Gas Chromatography coupled to a mass spectrometer (LC-MS and GC-MS). While mass spectrometry allows wide-scope analyte detection and identification at the very low Analytical Evaluation Threshold (AET) levels used in these studies, MS detectors are far from "universal response" detectors. Regulation brings the application of uncertainty factors into the picture to limit the risk of potential analytes detected escaping report and further evaluation; however, whether the application of a default value can cover any or all relevant applications is still debatable. The current study evaluated the response of species usually detected in migration studies, generating a suitable representative sample, analyzing said species, and creating a strategy and evaluation mechanism for acceptable classification of the detected species. Incorporating novel methodologies, i.e., Design of Experiments (DoE) for Design Space generation, the LC-MS-based methodology is also evaluated for its robustness in changes performed.

Chemometrically Assisted Optimization of Pregabalin Fluorescent Derivatization Reaction with a Novel Xanthone Analogue and Validation of the Method for the Determination of Pregabalin in Bulk via a Plate Reader.

Quantitation of chromophore-free analytes is always a challenge. To this purpose, derivatization of the analyte constitutes a common strategy, leading to a product with a strong signal. In the current study, a novel xanthone analogue was utilized for the first time for the derivatization of pregabalin, a model analyte with a primary amine moiety that lacks a chromophore. The fact that only the xanthene-based derivative, formed after the derivatization reaction fluoresces, enables avoiding its chromatographic separation from the reagent and thus reducing the analysis time of a series of samples in 1-2 min via a plate reader. The reaction conditions were optimized via a central composite design (CCD), with fluorescence signal as the measure of the yield. The following factors that affect the derivatization reaction were chosen: (a) temperature, (b) reaction time, and (c) triethylamine solution volume used to drive the reaction to completion. After the identification of the optimal conditions, the method was validated according to ICH guidelines, using a fluorescence plate reader for signal measurement (λex = 540, λem = 615 nm). Finally, the newly developed high-throughput method was applied to the determination of drug content in pregabalin bulk.

The role of paroxetine in fatigue and depression of patients under chemotherapeutic treatment.

We evaluated paroxetine for the treatment of fatigue and depression in patients with solid tumors after chemotherapy, and we found that paroxetine is effective for the treatment of depression during chemotherapy but has no benefit for the treatment of fatigue.

A comparative study of intravenous ibandronate and pamindronate in patients with bone metastases from breast or lung cancer: effect on metastatic bone pain.

We compared the effects of ibandronate and pamindronate in patients with bone metastases from breast or lung cancer and we found that ibandronate is superior to pamindronate in alleviating pain, improving mobility and quality of life, and reducing bone resorption indices in patients with bone metastases from breast or lung cancer.

Correlation of radiation dose and heart rate in dual-source computed tomography coronary angiography.

BACKGROUND: Computed tomography coronary angiography (CTCA) has been widely used since the introduction of 64-slice scanners and dual-source CT technology, but the relatively high radiation dose remains a major concern. PURPOSE: To evaluate the relationship between radiation exposure and heart rate (HR), in dual-source CTCA. MATERIAL AND METHODS: Data from 218 CTCA examinations, performed with a dual-source 64-slices scanner, were statistically evaluated. Effective radiation dose, expressed in mSv, was calculated as the product of the dose-length product (DLP) times a conversion coefficient for the chest (mSv = DLPx0.017). Heart rate range and mean heart rate, expressed in beats per minute (bpm) of each individual during CTCA, were also provided by the system. Statistical analysis of effective dose and heart rate data was performed by using Pearson correlation coefficient and two-sample t-test. RESULTS: Mean HR and effective dose were found to have a borderline positive relationship. Individuals with a mean HR >65 bpm observed to receive a statistically significant higher effective dose as compared to those with a mean HR ≤65 bpm. Moreover, a strong correlation between effective dose and variability of HR of more than 20 bpm was observed. CONCLUSION: Dual-source CT scanners are considered to have the capability to provide diagnostic examinations even with high HR and arrhythmias. However, it is desirable to keep the mean heart rate below 65 bpm and heart rate fluctuation less than 20 bpm in order to reduce the radiation exposure.

Effect of combined treatment methods on quality of life in patients with pancreatic cancer.

We aimed to analyze the effect of combined treatment methods on quality of life (QoL) in patients diagnosed with pancreatic cancer. Therefore, we prospectively analyzed 30 patients with unresectable, without distant metastases, pancreatic cancer. Patients were randomized to 1 of 2 treatment arms: radiotherapy with 5-fluorouracil or radiotherapy with gemcitabine. QoL was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) questionnaire in both treatment groups. QoL was evaluated before and after treatment. We found that that both concomitant chemoradiation methods have similar impact on QoL in patients with unresectable pancreatic cancer.

Efficacy and safety of capecitabine and oxaliplatin combination as second-line treatment in advanced colorectal cancer.

The aim of this study was to determine the efficacy and safety of administering a combination of capecitabine and oxaliplatin in patients with advanced colorectal cancer, resistant to leucovorin/5-fluorouracil and irinotecan. Fifty-four patients with advanced colorectal cancer were prospectively evaluated (mean age 63 years, male/female 2:1) who had been previously treated with schemes containing fluoropyrimidines and irinotecan. All patients received oxaliplatin (130 mg/m2 as 2-hour intravenous infusion) the first day of the cycle and capecitabine (1000 mg/m2) twice daily, days 1-14. Cycles were repeated every 21 days until either disease progression or unacceptable toxicity. Patients were evaluated regarding their response to treatment every 9 weeks (toxicity was evaluated every 3 weeks). Total response rate was 28.3%. Median total survival was 13.5 months, and median time to progression was 5.3 months in a follow up of 24 months. Major adverse events were neutropenia, nausea, diarrhea, hand/foot syndrome, and neurotoxicity. No treatment-related or grade 4 toxicity-related deaths were observed. Additionally, no dosage decrease was required, and only 4 cycles were withheld for 1 week because of neutropenia. The combination of oxaliplatin and capecitabine is efficient and safe for patients with advanced colorectal cancer who have been previously treated with other therapeutic schemes. Furthermore, this is a convenient and well-tolerated scheme.

Increasing awareness of physicians against severe leptospirosis: A treatable but potentially fatal zoonotic infection.

Leptospirosis is a worldwide, often severe and potentially fatal zoonotic infection. Here, we present the case of a 35-year-old man with severe leptospirosis infection that was identified early and was treated effectively, with a quite impressive complete recovery. Delaying of early diagnosis and treatment is crucial for the development of an unfavorable clinical course and increases the risk of a lethal outcome.

Nuclear medicine techniques in Merkel cell carcinoma: A case report and review of the literature.

Merkel cell carcinoma (MCC) is a rare and aggressive type of neuroendocrine cancer of the skin. It predominantly affects the elderly, with a predilection for the sun-exposed skin of the head and neck. Risk factors include immune-suppressing diseases, such as human immunodeficiency virus (HIV), chronic lymphocytic leukemia and multiple myeloma, organ transplantation, and the presence of the newly-identified Merkel cell polyomavirus (MCPyV). Diagnosis is based on pathological findings, primarily the immunohistochemical determination of cytokeratin 20 positivity. By contrast, staging relies on conventional imaging methods, such as ultrasonography, computed tomography (CT) and magnetic resonance imaging, and nuclear medicine techniques, such as sentinel lymph node scintigraphy, somatostatin receptor scintigraphy (SRS), and positron emission tomography (PET)/CT with 18F-fluorodeoxyglucose (FDG) or alternative radiopharmaceuticals. The treatment of MCC is primarily surgical, with possible adjuvant radiation, while the use of chemotherapy appears to be an alternative therapeutic option that is used only in specific cases. The present study describes the case of a 43-year-old HIV-positive Caucasian man with MCC located on the posterior surface of the left thigh, which was identified by cytological and histological examination of tissue sampled by fine needle aspiration and biopsy performed under CT. SRS demonstrated a high uptake of 111In-diethylene triamine pentaacetic acid-octreotide at the affected site. Therefore, the lesion was surgically excised, and the patient received chemotherapy and adjuvant radiotherapy. Three months subsequent to treatment, the patient underwent a PET/CT scan with 18F-FDG that demonstrated uptake in the cervical lymph nodes and the area of the excised lesion. These findings indicated that the disease was in remission. The aim of the present study was to highlight the value and contribution of nuclear medicine in the diagnosis, staging and follow-up, using PET/CT, octreoscan and sentinel lymph node scintigraphy, of patients with MCC, as well as the therapeutic strategy of radiolabelled somatostatin analogue scintigraphy.

Liquid chromatography coupled to quadrupole-time of flight tandem mass spectrometry based quantitative structure-retention relationships of amino acid analogues derivatized via n-propyl chloroformate mediated reaction.

In the current study, quantitative structure-retention relationships (QSRR) were constructed based on data obtained by a LC-(ESI)-QTOF-MS/MS method for the determination of amino acid analogues, following their derivatization via chloroformate esters. Molecules were derivatized via n-propyl chloroformate/n-propanol mediated reaction. Derivatives were acquired through a liquid-liquid extraction procedure. Chromatographic separation is based on gradient elution using methanol/water mixtures from a 70/30% composition to an 85/15% final one, maintaining a constant rate of change. The group of examined molecules was diverse, including mainly α-amino acids, yet also ß- and γ-amino acids, γ-amino acid analogues, decarboxylated and phosphorylated analogues and dipeptides. Projection to latent structures (PLS) method was selected for the formation of QSRRs, resulting in a total of three PLS models with high cross-validated coefficients of determination Q(2)Y. For this reason, molecular structures were previously described through the use of descriptors. Through stratified random sampling procedures, 57 compounds were split to a training set and a test set. Model creation was based on multiple criteria including principal component significance and eigenvalue, variable importance, form of residuals, etc. Validation was based on statistical metrics Rpred(2),QextF2(2),QextF3(2) for the test set and Roy's metrics rm(Av)(2) and rm(δ)(2), assessing both predictive stability and internal validity. Based on aforementioned models, simplified equivalent were then created using a multi-linear regression (MLR) method. MLR models were also validated with the same metrics. The suggested models are considered useful for the estimation of retention times of amino acid analogues for a series of applications.

Neuroendocrine differentiation in castration-resistant prostate cancer: A case report.

The most common type of prostate cancer is acinar adenocarcinoma, which is androgen-dependent and, therefore, treated with chemical or surgical castration and androgen receptor inhibition. However, the disease usually progresses to castration-resistant prostate cancer (CRPC). A neuroendocrine pattern is frequently observed in the cellular composition of CRPC, which is considered to emerge as an effect of androgen deprivation therapy. This is the case report of a 69-year-old patient with prostate adenocarcinoma, who, after an initial period of disease control with radiotherapy and antiandrogens, was diagnosed with CRPC with high levels of prostate-specific antigen (PSA), unresponsive to androgen inhibition, with accompanying lung and osseous metastases. Bronchial biopsy of the lung metastasis revealed infiltration by non-small-cell adenocarcinoma of prostatic origin with neuroendocrine characteristics. On somatostatin receptor scintigraphy with 99mTc-octreotide, there was high uptake by almost all known lung and osseous metastases. The patient was subsequently treated with a combination of docetaxel and octreotide, and a partial response was observed 6 months later, with reduction of the PSA level and the size of the lung metastasis. The aim of the present study was to provide a clinical example of the previously demonstrated, in vitro and in vivo, synergistic antitumor activities of docetaxel and octreotide in cases of CRPC selected by means of histological confirmation of their neuroendocrine nature and somatostatin receptor scintigraphy.

Imaging of coronary artery bypass grafts by computed tomography coronary angiography.

In recent years, computed tomography coronary angiography is commonly performed as a follow-up examination after coronary artery bypass graft surgery. Coronary grafts owing to their minimal motion are well visualized by computed tomography coronary angiography, allowing radiologists to assess their patency noninvasively with very high diagnostic accuracy. The purpose of this pictorial essay is to provide an excellent overview of the anatomy and findings concerning coronary artery bypass grafts.

Coronary artery anomalies in adults: imaging at dual source CT coronary angiography.

Congenital abnormalities of the coronary arteries have an incidence of 1%, and most of these are benign. However, a small number are associated with myocardial ischaemia and sudden death. Various imaging modalities are available for coronary artery assessment. Recently, multi-detector CT has emerged as an accurate diagnostic tool for defining coronary artery anomalies. The purpose of this pictorial essay is to review the dual source CT appearance of congenital anomalies of the coronary arteries in adults.

Smoking among high school students.

INTRODUCTION: There are no recent data on smoking habits of high-school students in Greece. The primary objective of the study was to determine these epidemiological factors. METHODS: The smoking habits of 927 high-school students (471 boys and 456 girls), aged between 15-18 years, in four regions of a Greek area (the island of Cos), were examined. Study data were collected using a questionnaire. RESULTS: It was found that 32.48% of boys and 27.19% of girls are smokers; 43.3% had started smoking before the age of 14. The mean age for starting smoking was 14.4 +/- 1.9 years for the boys and 14.9 +/- 1.6 years for the girls. As many as 22.8% of the students smoke 6 to 10 cigarettes per day and 21.5% 16 to 20 cigarettes per day; 40.2% reported that they smoke out of spite. Students reported that their parents are aware that their offspring smoke in a proportion of 36.7%. Social standards and parental example were found to be the main determinants for starting smoking. The majority of the students (95.2%) stated that they are aware of the hazards associated with smoking. DISCUSSION: Our findings highlight the need for smoking control interventions aimed at young people. Smoking is a major, yet preventable cause of morbidity and mortality. For these reasons, we view that adolescents should be targeted with a well-planned integrated anti-smoking policy and not just an initiative for raising awareness of smoking hazards.