Review on COVID-19 Etiopathogenesis, Clinical Presentation and Treatment Available with Emphasis on ACE2.

In December 2019, Wuhan city in the Hubei province of China reported for the first time a cluster of patients infected with a novel coronavirus, since then there has been an outburst of this disease across the globe affecting millions of human inhabitants. Severe acute respiratory syndrome coronavirus type-2 (SARS-CoV-2), is a member of beta coronavirus family which upon exposure caused a highly infectious disease called novel coronavirus disease-2019 (COVID-19). COVID-19, a probably bat originated disease was declared by World Health Organization (WHO) as a global pandemic in March 2020. Since then, despite rigorous global containment and quarantine efforts, the disease has affected nearly 56,261,952 laboratory confirmed human population and caused deaths of over 1,349,506 lives worldwide. Virus passes in majority through respiratory droplets and then enters lung epithelial cells by binding to angiotensin converting enzyme 2 (ACE2) receptor and there it undergoes replication and targeting host cells causing severe pathogenesis. Majority of human population exposed to SARS-CoV-2 having fully functional immune system undergo asymptomatic infection while 5-10% are symptomatic and only 1-2% are critically affected and requires ventilation support. Older people or people with co-morbidities are severely affected by COVID-19. These categories of patients also display cytokine storm due to dysfunctional immune response which brutally destroys the affected organs and may lead to death in some. Real time PCR is still considered as standard method of diagnosis along with other serology, radiological and biochemical investigations. Till date, no specific validated medication is available for the treatment of COVID-19 patients. Thus, this review provides detailed knowledge about the different landscapes of disease incidence, etiopathogenesis, involvement of various organs, diagnostic criteria's and treatment guidelines followed for management of COVID-19 infection since its inception. In conclusion, extensive research to recognize novel pathways and their cross talk to combat this virus in precarious settings is our future positive hope.

Blood Lead Levels in Occupationally Exposed Workers Involved in Battery Factories of Delhi-NCR Region: Effect on Vitamin D and Calcium Metabolism.

Workers involved in battery manufacturing or recycling factories are occupationally exposed to high concentrations of lead. In humans, lead can cause a wide range of biological effects depending upon the level and duration of exposure. The purpose of this study was to find out the blood lead levels (BLL) in occupationally exposed workers involved in battery industry in Delhi NCR region and to study whether lead affected the vitamin D (vit D) and calcium metabolism. For this study 100 occupationally lead-exposed battery workers (LEBW) and 100 non-lead exposed controls (NLEC) were recruited. BLL were measured using inductively coupled plasma optical emission spectrometer (ICP-OES) technique while ELISA was performed to quantify the serum vit D levels in the study subjects. Routine biochemical parameters were measured by chemistry autoanalyzers. Statistical analysis was done using appropriate statistical tools. Results showed that BLL were significantly higher in LEBW as compared to NLEC (p < 0.0001). Serum vitamin D, calcium and phosphorus levels were significantly decreased in battery workers as compared to controls (p < 0.005). Spearman's rank correlation analysis showed significant negative correlation of BLL with serum Vitamin D and calcium levels. Significant positive correlation was observed between BLL and duration of lead exposure. Weak negative correlation was also observed between BLL and vit D even after adjusting for smoking status. In conclusion, this study demonstrated that higher BLL significantly alters the vit D and calcium metabolism.

Increasing Glucose Concentrations Interfere with Estimation of Electrolytes by Indirect Ion Selective Electrode Method.

The estimation of electrolytes like sodium (Na(+)), potassium (K(+)) and chloride (Cl(-)) using direct and indirect ion-selective electrodes (ISE) is a routine laboratory practice. Interferents like proteins, triglycerides, drugs etc. are known to affect the results. The present study was designed to look into the effect of increasing glucose concentrations on estimation of Na(+), K(+) and Cl(-) by direct and indirect ISE. Pooled sera was mixed with glucose stock solution (20 g/dL) prepared in normal saline to obtain glucose concentrations ranging from ~100 to ~5000 mg/dL. Na(+), K(+) and Cl(-) levels were estimated by direct and indirect ISE analyzers and results were statistically analysed using ANOVA and Pearson's correlation. Similar experiment was also performed in 24 h urine sample from healthy subjects. Significant difference was observed between Na(+) and Cl(-) measurements by direct and indirect ISE, with indirect ISE values being consistently higher than direct ISE. Besides this, significant difference was observed amongst Na(+) and Cl(-) values from baseline values obtained by indirect ISE at glucose concentrations ≥2486 mg/dL. However, no such difference was observed with direct ISE. Na(+) and Cl(-) estimation by indirect ISE showed significant negative correlation with glucose concentration, more so, above ~2000 mg/dL. K(+), however, showed no significant difference with varying glucose. Similar results were observed in 24 h urine samples with a significant difference observed amongst Na(+) and Cl(-) values at ≥2104 mg/dL glucose. Thus we conclude that high glucose concentrations interfere significantly in estimation of Na(+) and Cl(-) by indirect ISE in serum as well as urine.

Quantitative Proteomics of COVID-19 Recovered Patients Identifies Long-Term Changes in Sperm Proteins Leading to Cellular Stress in Spermatozoa.

Following an initial recovery, COVID-19 survivors struggle with a spectrum of persistent medical complications, including fatigue, breathlessness, weight loss, hair loss, and attention deficits. Additionally, there is growing evidence of adverse effects of COVID-19 on the male reproductive system. This investigation seeks to understand the long-term ramifications on male fertility by examining hormonal profiles, semen parameters, and sperm proteome of recovered COVID-19 patients compared to controls. The serum hormone profiles between the two groups showed minimal variations except for prolactin, cortisol, and testosterone levels. Testosterone levels were slightly lower, while prolactin and cortisol were elevated in COVID-19 cases compared to controls. Though semen parameters exhibited no significant disparities between the COVID-19 and control groups, quantitative proteomics analysis revealed changes in sperm proteins. It identified 190 differentially expressed proteins, of which 161 were upregulated and 29 downregulated in COVID-19 cases. Western blotting analysis validated the differential expression of serpin B4 and calpain 2. Bioinformatics analysis signifies cellular stress in the spermatozoa of COVID-19 recovered patients and thus, SOD and MDA levels in semen were measured. MDA levels were found to be significantly elevated, indicating lipid peroxidation in COVID-19 samples. While the effects of COVID-19 on semen parameters may exhibit a potential for reversal within a short duration, the alterations it inflicts on sperm proteome are persisting consequences on male fertility. This study paves the path for further research and emphasizes the significance of comprehending the complex molecular processes underlying the long-term consequences of COVID-19 on male reproductive health.

Validation of a Clinical Tool to Predict Neurological Outcomes in Critically Ill Children-A Prospective Observational Study.

OBJECTIVES: To evaluate the performance of the empiric tool by Gupta et al. in predicting neurological outcomes in children admitted to the pediatric intensive care unit (PICU) and to evaluate the association of biomarkers S100B and NSE with neurological outcomes. METHODS: This prospective observational study was conducted in 163 critically ill children aged 2 mo to 17 y admitted to the PICU from June 2020 to July 2021. The authors used the prediction tool developed by Gupta et al.; the tool was applied at admission and at PICU discharge/death. Samples for NSE and S100B were collected at admission and discharge. The performance of the new tool was assessed through discrimination and calibration. Risk factors for "unfavorable outcomes" (decline in PCPC score by > 1) were evaluated by multivariate analysis. RESULTS: The PICU mortality was 28% (n = 45). When the tool developed by Gupta et al. was used at the time of admission, favorable neurological outcomes were predicted for 69% (112) children. The area under the curve for the new tool at admission was 0.72 and at discharge/death it was 0.99, and the calibration was excellent at both time points. Independent factors associated with unfavorable neurological outcomes were higher PCPC scores and organ failure. As the number of samples processed for NSE and S100B was less, statistical analysis was not attempted. CONCLUSIONS: The new tool by Gupta et al. has good discrimination, calibration, sensitivity, and specificity and can be used as a prediction tool. NSE and S100B are promising biomarkers and need further evaluation.

Association between baseline insulin resistance and hospital mortality in moderate-to-severe coronavirus disease 2019 patients without diabetes mellitus: An observational study.

Background: Insulin resistance is often implicated as a risk factor of cell-mediated immune dysfunction in sepsis patients and results in poor clinical outcome. However, it is unclear whether early insulin resistance is contributory to T-cell dysfunction and poor clinical outcome in coronavirus disease 2019 (COVID-19) patients. Methods: Adult patients with moderate-to-severe or critically ill COVID-19 infection were included in this study. Serum samples were collected at the time of diagnosis for fasting plasma glucose, serum insulin, serum cortisol, and serum glucagon measurements, and the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) score was calculated. Results: One hundred and twenty-six subjects with a mean (standard deviation) age of 49.6 (16.3) years were recruited in this study, and 62.4% (78 of 125 patients) were male. HOMA-IR was a predictor of inhospital mortality with the area under the receiver operating characteristics curve (AUROC) (95% confidence interval [CI] of 0.61 [0.49-0.73]). With a cutoff value of 1.91, sensitivity was 75.5% and specificity was 45.2%. Higher serum insulin was associated with higher survival with AUROC (95% CI) of 0.65 (0.53-0.76), and the best cutoff was 7.15, with a sensitivity and specificity of 62.1% and 64.5%. Serum cortisol was also a predictor of inhospital mortality with an AUROC (95% CI) of 0.67 (0.56-0.77). Conclusion: An independent association between baseline serum cortisol and poor outcome in moderate-to-severe COVID-19 patients was observed. Hyperglycemia and HOMA-IR can also predict poor outcome in these patients with some accuracy.

Proteomic changes in human spermatozoa during in vitro capacitation and acrosome reaction in normozoospermia and asthenozoospermia.

BACKGROUND: The cellular and molecular mechanisms of the events that help spermatozoa acquire their fertilizing capability during capacitation and acrosome reaction are not completely understood. OBJECTIVE: This study was performed with a postulation that the identification of sperm proteins and their changes during in vitro capacitation and acrosome reaction will unravel unknown molecular aspects of fertilization that impact male fertility. MATERIALS AND METHODS: Spermatozoa collected from sequential conditions, that is, separation of ejaculated spermatozoa by Percoll gradient centrifugation, in vitro capacitation, and acrosome reaction were processed for tandem mass spectrometric analysis, followed by protein identification, label-free quantitation, and statistical analysis. RESULTS AND DISCUSSION: Collectively, a total of 1088 sperm proteins were identified. In comparison to ejaculated spermatozoa, 44 and 141 proteins were differentially expressed in capacitated and acrosome reacted spermatozoa, respectively. A large number of proteins were found downregulated, including clusterin, pyruvate dehydrogenase E1 component, semenogelin-1 and 2, heat shock protein 90, beta-microseminoprotein, and keratin. It was expected as sperm-membrane-associated proteins are removed during capacitation. There were significant proteomic alterations in asthenozoospermia compared to normozoospermia; however, variation was more noticeable among proteins of acrosome reacted spermatozoa and those released during the acrosome reaction. The processes enriched among downregulated proteins in asthenozoospermia included acrosome assembly, binding of spermatozoa to zona pellucida, nucleosome assembly, flagellated sperm motility, protein folding, oxidative phosphorylation, tricarboxylic acid cycle, chromatin silencing, gluconeogenesis, glycolytic process, and glycolysis. CONCLUSION: The dynamic information generated about proteomic alterations in spermatozoa during capacitation and acrosome reaction and their variability in asthenozoospermia will contribute not only to enhancing our understanding of processes that prepare spermatozoa to acquire fertilization capability but also help in deciphering novel factors of male infertility.

A Comparative Review of ICMR, WHO, and EMA Guidelines for Good Clinical Laboratory Practices.

With the advancement of clinical research and the increased burden on laboratory services, there is an unmet need for guidelines regarding proper laboratory functioning and reliable data generation. Several organizations from all over the world have published guidelines for these clinical and research laboratories. Good Clinical Laboratory Practices (GCLP) are stepwise procedures aimed at strengthening the quality of test results produced by all clinical laboratories engaged in human sample analysis. In this article, we attempt a comparison of the GCLP guidelines recently issued by the Indian Council of Medical Research with the guidelines released by the World Health Organization and the European Medicines Agency. Also, we have included and discussed several suggestions that, if included, will lead to the strengthening of the laboratory practices used for both research and patient care for overall improvement in the Indian healthcare system.

Impact of Life Cycle Costing in Procurement of Robotic Track-Based Central Laboratory at Apex Medical Institute in India.

Introduction Life cycle costing is an important management tool that takes into account the implications of planning, acquiring, operating, maintaining, and disposing of an asset during its complete life cycle. A major hindrance to the procurement of expensive equipment in developing countries is the lack of a reliable framework combining and integrating all the equipment life cycle aspects into procurement process. Methods The study was conducted from the data collected from the bids that were received for procurement of two robotic track-based central laboratories which were installed at All India Institute of Medical Sciences (AIIMS), New Delhi. The procurement was done as per the guidelines laid down under General Finance Rules (GFR) 2017 following the two bid systems: technical bid and price/commercial bid. Results A complete financial analysis of the robotic laboratory was done that involved gathering of all the pertinent financial information into one place and then using that data to analyze the feasibility of the bid. The life cycle costs of both the labs were calculated by assuming the life of equipment as 10 years and by factoring in cost of equipment including 5-year warranty, comprehensive maintenance from years 6 to 10, indicative cost of all reagents for 10 years, and indicative cost of all other consumables for 10 years. Conclusion Results showed that the cost of equipment alone should not be the sole predictor of making purchase decisions of equipment. Further research may additionally explore differences between processes being followed in government versus private organizations, as well as national guidelines and subnational practices.

A Combination of Inflammatory and Hematological Markers is Strongly Associated with the Risk of Death in Both Mild and Severe Initial Disease in Unvaccinated Individuals with COVID-19 Infection.

Background: Inflammatory and hematological markers are used extensively for early prognostication and monitoring in COVID-19.We aimed to determine whether routinely prescribed laboratory markers can predict adverse outcome at presentation in COVID-19. Methods: This retrospective observational study was performed on 401 samples collected between July to December 2020 from COVID-19 positive subjects, admitted at All India Institute of Medical Sciences, Delhi, India. Clinical details and laboratory investigations within 3 days of COVID-19 positivity were obtained. Clinical outcomes were noted from patient medical records, till discharge or death. Laboratory parameters, with individually defined cut-offs, were used, either singly or in combination to distinguish survival and death for those having severe and non-severe disease at initial presentation. Findings: Total Leukocyte count, Absolute neutrophil count, Neutrophil to Lymphocyte ratio, C-Reactive Protein (CRP), Interleukin-6 (IL-6), Lactate Dehydrogenase, Ferritin and Lymphocyte to CRP ratio (LCR) were significantly altered at presentation in severe COVID-19 as compared to non-severe cases; and, also in those who died due to COVID-19 compared to those who survived. A combination of four markers, CRP (≥3.9mg/dL); IL-6 (≥45.37pg/ml); Ferritin (≥373ng/mL); 1/LCR ≥0.405 was found to strongly predict mortality in cases with non-severe presentation as also in severe cases. Conclusion and Interpretation: The combination of routinely used markers, CRP, IL-6, Ferritin and 1/LCR can be used to predict adverse outcomes, even in those presenting with mild to moderate disease. This would identify subset of patients who would benefit from closer monitoring than usual for non-severe disease.

Interference in Ion-Selective Electrodes Due to Proteins and Lipids.

BACKGROUND: Ion-selective electrodes (ISE) have become the mainstay of electrolyte measurements in the clinical laboratory. In most automated analyzers used in large diagnostic laboratories, indirect ISE (iISE) -based electrolyte estimation is done; whereas direct ISE (dISE) -based equipment are mostly used in blood gas analyzers and in the point-of-care (PoC) setting. CONTENT: Both the techniques, iISE as well as dISE, are scientifically robust; however, the results are often not interchangeable. Discrepancy happens between the two commonly due to interferences that affect the two measuring principles differently. Over the last decade, several studies have reported discrepancies between dISE and iISE arising due to abnormal protein and lipid contents in the sample. SUMMARY: The present review endeavors to consolidate the knowledge accumulated in relation to interferences due to abnormal protein and lipid contents in sample with the principal focus resting on probable solutions thereof.

Planning and Setting Up of a Communication Program for Hospitalized COVID-19 Patients: Challenges and Potential Solutions in Resource Constrained Setting.

Background The recent onset of COVID-19 pandemic has necessitated many patients to be hospitalized in the COVID-19 treating centers. Owing to the need for isolation of these patients and minimizing the risk of transmission to healthy people, COVID-19-positive patients are completely restricted from meeting their friends and families. This gives rise to anxiety amongst the patients' relatives as they are not able to monitor the progress of the patients and have to depend entirely on the healthcare staff for any updates regarding the patient. In contrast, the treating doctors are undergoing severe stress due to the unknown nature of the virus and the risks involved in treating patients. They are thoroughly exhausted after the long hours donning the personal protection equipment (PPE). Objective To structure and form an interface for communication between the treating physician and the families, as a "communication team," to decrease the workload on the treating physicians and minimize their contact time in a COVID-19 setting. Results The addition of a communication team improved the physicians' efficiency of patient management and family satisfaction. Several challenges were faced during the setting up of this interface effectively. However, most of these were dealt with along the way. The communication team was instrumental in allaying the anxiety of the family with respect to their patients' clinical condition. This also ensured engagement of doctors from non-clinical and laboratory-based departments in the COVID-19 treatment process. Conclusion Adding up a communication team for communicating clinical updates to the family in a resource-limited scenario greatly improved communication and thus family satisfaction of the COVID-19-positive patients.

Alteration of Mitochondrial Function in Oxidative Stress in Parkinsonian Neurodegeneration: A Cross-Sectional Study.

CONTEXT: Appropriate mitochondrial function and oxidative balance are critical to neuronal survival. Accumulation of reactive oxygen species leads to oxidative stress that can cause free radical damage to biomolecules of the cell components and the molecules in the cellular milieu that eventually lead to a variety of chronic diseases including neurodegenerative disorders. Mitochondrial dysfunction initiates neuronal apoptosis thereby leading to neurodegenerative diseases including Parkinson's disease (PD). AIM: To evaluate oxidative stress vis-a-vis mitochondrial function (Cytochrome C oxidase activity) in PD patients, Parkinson plus syndrome (PPS) patients in comparison with healthy controls (HCs). SETTINGS AND DESIGN: Cross-sectional Study. METHODS: We assessed oxidative stress by chemiluminescence using luminol, and cytochrome c oxidase activity (CCO) by CCO kit using spectrophotometry in PD patients (n = 80), PPS patients (n = 40), and HCs (n = 40). STATISTICAL ANALYSIS: Data were presented as number (%) or mean ± SD/median as approximate. Quantitative baseline variables were compared among the groups using one-way ANOVA and qualitative variables were compared using Chi-square test. The difference in median was compared using Kruskal-Wallis test followed by Post-hoc Bonferronni correction. RESULTS: Compared to HCs (Median 7.53 ± 15.58 RLU/sec/cell), ROS level in PD (14.13 ± 29.5), and PPS (17.43 ± 15.91) patients was significantly higher (P = 0.0029: HC vs, PD & P = 0.0500: HC vs. PPS). Also, ROS in PD patients (14.13 ± 29.5) was higher that PPS patients (17. 43 ± 15.91) but the difference was not statistically significant (P = 0.84). The CCO activity was found to be diminished in PD (Median: 0.025 ± 0.013 units/ml) and PPS patients (0.027 ± 0.008) in comparison to HCs (0.117 ± 0.049). CONCLUSION: Mitochondrial dysfunction and oxidative stress is associated with PD and PPS and may play an important role in etiopathogenesis. Though the cause-effect conundrum has not been comprehensively probed but addressing oxidative stress and mitochondrial damage may serve as an adjunctive therapy for PD and PPS. Iron metabolism as reflected in the red cell indices may aid in differentiating PD from PPS.

Efficacy of Single Low-Dose Rasburicase in Management of Tumor Lysis Syndrome in Leukemia and Lymphoma Patients.

BACKGROUND: Tumor lysis syndrome (TLS) is a metabolic emergency in hematology patients. The recommended dose of rasburicase for the management of TLS is 0.2 mg/kg per day for 5 days, which is cost prohibitive for many patients. We sought to determine the efficacy of single low-dose rasburicase in the prevention and treatment of hyperuricemia in TLS. PATIENTS AND METHODS: We planned a prospective study for the safety and efficacy of fixed (weight based) dose of rasburicase to manage TLS. Patients diagnosed with leukemia/lymphoma with laboratory or clinically confirmed TLS or presence of ≥ 2 high-risk factors and serum uric acid > 7.5 mg/dL were included. The primary endpoint was uric acid normalization (< 7.5 mg/dL) within 24 hours of rasburicase administration. RESULTS: Fifty-five patients were recruited for this study. Pediatric patients (< 18 years) accounted for 43.6% of cases. Rasburicase was provided prophylactically to 43 patients (78.2%) and for treating TLS to 12 (21.8%). Mean ± standard deviation serum uric acid at baseline and 24 hours was 9.2 ± 1.8 mg/dL and 3.2 ± 2.1 mg/dL, respectively. There was significant reduction in the serum uric acid and creatinine (P < .001) within 24 hours of rasburicase administration. The response was maintained up to 72 hours. A single dose of rasburicase was effective in 94.5% of patients. Single low-dose rasburicase led to 95% direct cost savings compared to the recommended dose. CONCLUSION: Single-dose rasburicase with frequent laboratory monitoring is effective in the management of TLS and offers significant cost reductions.

Ethics in Laboratory Medicine: Perspectives and Challenges in Resource Limited Settings.

Currently diagnosis and management of patients in Clinical Practice is very much dependent on laboratory diagnostics. Laboratory Medicine, like any other branch of Medicine, is therefore, mandated with ethical usage of materials and data obtained from patients. Several countries, professional societies and the have developed policies and guidance materials on ethical issues related to laboratory medicine. However, ethical standards and practices vary between different cultures, geographies, legal architecture and according to available resources. In this article, we try to understand the challenges presented in terms of Ethics, where there are constraints of resources.

Discrepancies in Electrolyte Measurements by Direct and Indirect Ion Selective Electrodes due to Interferences by Proteins and Lipids.

Objectives We aim to report the simultaneous effect of different protein and lipid concentrations on sodium (Na + ) and potassium (K + ) measurement by direct and indirect ion selective electrodes (dISE and iISE) in patient samples. Materials and Methods Na + and K + were measured in 195 serum samples received in the laboratory using iISE by Roche Modular P800 autoanalyzer and using dISE by XI-921 ver. 6.0 Caretium electrolyte analyzer. Serum total protein (TP), cholesterol (Chol), and triglycerides (TG) were measured using conventional photometric methods on Roche Modular P800 autoanalyzer. Differences for each pair of results for Na + (Diff_Na + = [Na + dISE- Na + iISE ]) and K + (Diff_K + = [K + dISE- K + iISE ]) were calculated. Patient subgroups with high, normal, or low TP (< 5, 5-7.9, or ≥ 8 g/dL), Chol (< 150, 150-299, or ≥300 mg/dL), or TG (< 150, 150-299, or ≥300 mg/dL) were compared using analysis of variance. Note that 95% confidence interval of Diff_Na + and Diff_K + were calculated to see the number of samples showing clinically significant differences. Results Diff_Na + ( p = 0.007) and Diff_K + ( p = 0.002) were found significant between samples with normal and high TP. However, effect of TG was not significant. Chol concentration affected Diff_Na + significantly between low versus normal ( p = 0.002), and high versus normal ( p = 0.031) Chol groups. Diff_K + was significant ( p = 0.009) between low versus normal Chol. Clinically relevant disagreement of ≥|5| mmol/L for Na + was observed in high percentage of samples including all subcategories; however, for K + only 3.6% of the total samples showed disagreement of ≥ |0.5| mmol/L. A multivariate regression equation based on fit regression model was also derived. Conclusion Summarily, interchangeable use of electrolyte results from dISE and iISE is not advisable, especially in a setting of hyperproteinemia (≥8 g/dL) or hypercholesterolemia (≥300 mg/dL); more so for Na + .

Acute encephalopathy in children in Muzaffarpur, India: a review of aetiopathogenesis.

The acute encephalopathy occurring in children in Muzaffarpur, India, also recognised in other litchi-cultivating areas of India, Bangladesh, Vietnam and China, had previously been linked to litchi consumption. Recently, it has been identified as hypoglycaemic encephalopathy of an unusual aetiology with three key factors: undernutrition, prolonged fasting and litchi consumption. A second set of investigators has independently reconfirmed the diagnosis and the three-factor aetiology. Skipping the evening meal with an intake of large amounts of litchi in undernourished children is causative. Early-morning hypoglycaemia with an inadequate glycogen store leads to initiation of gluconeogenesis and fatty acid ß-oxidation, but methylene cyclopropyl alanine and glycine present in the litchi aril block the fatty acid ß-oxidation cycle. The outcomes are uncorrected hypoglycaemia and encephalopathy due to the entry of metabolic intermediates that cross the blood-brain barrier and affect neuronal function. Suggested measures include early 10% dextrose infusion. Awareness about the disease is of prime importance. The diagnosis and aetiopathogenesis are still under question from a part of the scientific community. This review was undertaken to present a comprehensive view of hypoglycaemic encephalopathy and to remove some of the lingering doubts.

Comparison Between Measured and Calculated Free Calcium Values at Different Serum Albumin Concentrations.

INTRODUCTION: Free ionic calcium is the metabolically active component of total calcium (TCa) in blood. However, most laboratories report TCa levels that are dependent on serum albumin concentration. Hence, several formulae have evolved to calculate free calcium levels from TCa after adjustment for albumin. However, free calcium can directly be measured using direction selective electrodes rather than spectrophotometric methods used in autoanalyzers. OBJECTIVES: This study compares the levels of free calcium obtained by measurement by direct ion selective electrode (ISE) and the one calculated as a function of TCa by formulae. MATERIALS AND METHODS: A total of 254 serum samples submitted to clinical biochemistry laboratory of a tertiary care hospital were analyzed for total protein, albumin, and TCa by standard spectrophotometric methods and for free calcium by direct ISE. Three commonly used formulae viz. Orrell, Berry et al. and Payne et al. were used to calculate adjusted TCa. Calculated free calcium was obtained by taking 50% of these values. RESULTS: A significant difference (P < 0.05) was observed between calculated free calcium by all the three formulae and measured free calcium estimated by direct ISE using paired t-test and Bland-Altman plots. CONCLUSION: Formulae for predicting free calcium by estimating TCa and albumin lacks consistency in prediction and free calcium should be evaluated by direct measurement.