A novel, fast and sensitive supercritical fluid chromatography-tandem mass spectrometry (SFC-MS/MS) method for analysis of arachidonic acid metabolites.

The development of a rapid, sensitive and reliable method for the quantification of bioactive arachidonic acid metabolites (AA-metabolites) in biological samples is quite challenging due to the minute concentration, short half-life and their structural complexity arising from different isomers. In this study, a simple, fast and environmentally friendly supercritical fluid chromatography-tandem mass spectrometry (SFC-MS/MS) method was developed and validated for simultaneous measurement of five (PGD2, PGE2, PGF2α, 6KetoPGF1α and LTB4) AA-metabolites in biological samples. These analytes were extracted by protein precipitation followed by separation and quantification. The analysis was completed within 3 minutes. The matrix matched linear calibration ranged from 0.5-100 ng mL-1 (r2 ≥ 0.995), whilst, the limit of quantification of PGD2, PGE2, PGF2α, and LTB4 was 0.5 ng mL-1 and was 2.5 ng mL-1 for 6KetoPGF1α. The interday and intraday precisions of the method were less than 15% while the accuracy of most of the analytes varied between 83 and 109%. Finally, as a proof of concept, the method was successfully applied for the determination of eicosanoids in human samples, which expands the possibility to explore physiological states, disease phenotypes, and novel biomarkers.

Use of Bedside Ultrasound for Ophthalmic Evaluation in a Case of Traumatic Brain Injury: A Case Report.

BACKGROUND: Ophthalmological examination is an important aspect of the neurological assessment in a patient with traumatic brain injury. However, significant periorbital swelling can make direct visualization of the pupils difficult. Ultrasonic examination can be a valuable bedside tool when direct visualization fails. CASE: A case of a seven-year female child who had presented with a history traumatic brain injury is reported here. OBSERVATIONS: The periorbital swelling prevented the direct visualization of the eyes. Bedside evaluation with a multipurpose ultrasound (USG) was used to monitor the pupillary diameter (PD) and the consensual pupillary light reflex (PLR) at regular intervals. The PD was measured in the B-mode while the PLR was monitored in M-mode of the USG. The optic nerve sheath diameter (ONSD) was also monitored as a correlate of intracranial pressure (ICP). CONCLUSION: Ophthalmic evaluation of PD and PLR can be easily and objectively done on the bedside using USG especially in cases where the direct visualization of the pupils is difficult due to injuries and swelling of the periorbital tissues. Furthermore, ONSD measurements can also be done to monitor the changes in the ICP.

Once was not enough: A case report of the concomitant intoxication of amlodipine (calcium channel blocker) and clonazepam (benzodiazepine).

We report a case of concurrent ingestion of Clonazepam and Amlodipine in a 25-year-old man, in a second attempt to take his life, which resulted in unconsciousness, hypotension, and hypokalemia. The clinical and/or biochemical presentation varied from the individual pattern when ingested. In the scarcity of consensus recommendations, supportive treatment helped.

Loss of Consciousness and Cardiac Arrest as an Atypical Presentation of Tubercular Meningitis: A Case Report.

Tubercular meningitis is a devastating presentation of extra pulmonary tuberculosis, with fatality in each case without treatment. A 39 years male, a regular consumer of alcohol and a known case of major depressive disorder, presented with the alleged history of using an electric heater in a closed room, and presented to emergency with unconsciousness and cardiac arrest. As his neurological status didn't improve over 72 hrs, a magnetic resonance imaging brain was done which was non-conclusive. Electroencephalogram revealed diffuse right fronto-parietal seizure activity ceasing with midazolam injection, hence levetiracetam was started. Lumbar puncture revealed increased adenosine deaminase and nil white blood cells. Repeat lumbar puncture showed lymphocytic-predominant pleocytosis, elevated protein and low glucose. The patient was started on anti-tubercular therapy and an injection of dexamethasone was added. Repeat electroencephalogram didn't show any seizure-like activity. It is important to be aware of variety of presentations of tubercular meningitis. Delay in treatment leads to irreversible neurological damage and even death. Keywords: cardiac arrest; case report; tubercular meningitis; unconsciousness.

Management of nitrobenzene poisoning with oral methylene blue and vitamin C in a resource limited setting: A case report.

Nitrobenzene can cause life threatening methaemoglobinemia. Its management includes the use of intravenous methylene blue to reduce the iron moiety from its ferric to ferrous state. Due to unavailability of intravenous preparation, enteral methylene blue was used in our case. This case report is to highlight that even oral preparations can be successfully used in a resource limited setting where often intravenous preparations are unavailable.

Delayed Neurological Recovery After Ultrasound-Guided Brachial Plexus Block: A Case Report.

INTRODUCTION: Brachial plexus blocks are frequently practiced and safe mode of anaesthsia. Although minor complications may occur, major complications are a rarity. However, we report a rare case of prolonged supraclavicular brachial plexus block which required almost 4 months to recover without a perceivable cause. CASE PRESENTATION: A 22-year-old gentleman posted for open reduction and internal fixation of both forearm bones was administered an ultrasound-guided supraclavicular brachial plexus block. The intra-operative period was uneventful. However, the block persisted for a very prolonged period of time. All perceivable causes were ruled out. A total of 19 weeks was required for the entire block to regress with no residual neurological deficits thereafter. CONCLUSION: Although peripheral neuropathies are known complications of peripheral nerve blocks, such a prolonged brachial plexus block is a rare event. The only plausible cause for the patient's condition could have been the prolonged drug effect; however, it has been rarely documented.

Inclusion of Endogenous Plasma Dehydroepiandrosterone Sulfate and Mammographic Density in Risk Prediction Models for Breast Cancer.

BACKGROUND: Endogenous hormones and mammographic density are risk factors for breast cancer. Joint analyses of the two may improve the ability to identify high-risk women. METHODS: This study within the KARMA cohort included prediagnostic measures of plasma hormone levels of dehydroepiandrosterone (DHEA), its sulfate (DHEAS), and mammographic density in 629 cases and 1,223 controls, not using menopausal hormones. We evaluated the area under the receiver-operating curve (AUC) for risk of breast cancer by adding DHEA, DHEAS, and mammographic density to the Gail or Tyrer-Cuzick 5-year risk scores or the CAD2Y 2-year risk score. RESULTS: DHEAS and percentage density were independently and positively associated with breast cancer risk (P = 0.007 and P < 0.001, respectively) for postmenopausal, but not premenopausal, women. No significant association was seen for DHEA. In postmenopausal women, those in the highest tertiles of both DHEAS and density were at greatest risk of breast cancer (OR, 3.5; 95% confidence interval, 1.9-6.3) compared with the lowest tertiles. Adding DHEAS significantly improved the AUC for the Gail (+2.1 units, P = 0.008) and Tyrer-Cuzick (+1.3 units, P = 0.007) risk models. Adding DHEAS to the Gail and Tyrer-Cuzick models already including mammographic density further increased the AUC by 1.2 units (P = 0.006) and 0.4 units (P = 0.007), respectively, compared with only including density. CONCLUSIONS: DHEAS and mammographic density are independent risk factors for breast cancer and improve risk discrimination for postmenopausal breast cancer. IMPACT: Combining DHEAS and mammographic density could help identify women at high risk who may benefit from individualized breast cancer screening and/or preventive measures among postmenopausal women.

Undergraduate pharmacy students' attitudes and perceived barriers toward provision of pharmaceutical care: a multi-institutional study in Nepal.

Background: Pharmaceutical care (PC) has a significant impact on optimizing pharmacotherapy and improving patients' quality of life. We aimed to determine the attitudes and perceived barriers of final year pharmacy undergraduates towards provision of PC services in Nepal. Methods: A cross-sectional study was conducted among 232 students using a 13-item-standard PC attitude survey (PCAS) questionnaire and 12-itemed PC barrier questionnaires. Mann-Whitney U test and Kruskal-Wallis tests were used to measure the median difference between groups, at alpha=0.05, and Spearman's rho test was used to measure the strength of the correlation. Results: Majority of students were self-motivated in undertaking the current pharmacy education (178, 76.7%) and had no previous incomplete grades that could delay their graduation (177, 76.3%). Over 80% of students had a positive attitude toward all items of PCAS (agreed and strongly agreed) except for two items. Whereas, 61 (26.3%) disagreed and strongly disagreed that providing PC takes too much time and effort. The major barriers perceived were inadequate PC training (176, 75.9%), inadequate drug information resources in the pharmacy (170, 73.3%), and lack of access to patient medical records in the pharmacy (165, 71.1%). A significant relationship was noticed between positive attitude towards PC and three factors; source of motivation, current employment in pharmacy job, and incomplete grades delaying graduation. Age factor was significant but negatively correlated with the scores of positive attitudes namely "I would like to perform PC as a pharmacist practitioner", "Providing PC is professionally rewarding" and "I feel that the PC is the right direction for the provision to be headed". Conclusion: Nepalese undergraduate pharmacy students had positive attitudes toward PC. Exercising proper pharmacy practice regulations and educational efforts to overcome the perceived barriers may lead to better delivery of PC.

A Novel Targeted Analysis of Peripheral Steroids by Ultra-Performance Supercritical Fluid Chromatography Hyphenated to Tandem Mass Spectrometry.

Ultra-performance supercritical fluid chromatography-tandem mass spectrometry (UPSFC-MS/MS) is an alternative method for steroid analysis. Continuous development of analytical methodologies for steroid profiling is of major importance in the clinical environment to provide useful and more comprehensive data. The aim of this study was to identify and quantify a large number of endogenous steroids from the four major classes (estrogens, androgens, progestogens and corticosteroids) simultaneously within a short analytical time. This novel UPSFC-MS/MS method with electrospray in positive ionisation (ESI+) mode is robust, selective and present sufficiently high sensitivity to profile nineteen steroids in 50 µL human plasma. Under optimised conditions, nineteen different steroids were separated with high efficiency in the multiple reaction monitoring (MRM) mode. The linearity of the method was good with correlation coefficients (R2) in the range of 0.9983-0.9999 and with calibration range from 0.05-500 ng/mL in human plasma. The intraday and interday precision of the method, as RSD, was less than 15%. The accuracy of the nineteen analytes varied between 80 to 116%. Finally, the novel method was successfully applied for the determination of nineteen steroids within 5 minutes providing the possibility to use it for research as well as routine healthcare practice.