Retrospective Analysis of Clinical Laboratory Parameters, Therapeutics and Outcome in Patients Infected with SARS-CoV2.

SARS-CoV-2 is the third coronavirus to have caused severe disease in humans in the last two decades, with approximately 5% of all patients and 20% of hospitalized patients experiencing severe symptoms, necessitating intensive care. The occurrence of Cytokine Storm has been implicated in the immune-pathogenesis of severe COVID-19. This is associated with cardiac injury, precipitated by cytokine mediated imbalance of coagulation and fibrinolysis, in the lung alveoli. In the absence of proven therapeutic agents, combinations of anti-viral drugs, immune-modulators and other adjunctive therapies have been tried in different clinical settings. A total of 128 confirmed cases of severe COVID-19 admitted to BLK-MAX Super Speciality Hospital between 16th of June to 31st of July, 2020 were included in this study. The correlation of age, gender, first value (on admission) of serum IL-6 and D-dimer, and impact of Tocilizumab and Remdesivir therapy on clinical outcome (28-day mortality), was evaluated in confirmed cases of severe COVID-19. The mortality rate was highest in the age group above 70 years. The incidence of death was significantly higher in males above 50 years, when age and gender were considered together. IL-6 and D-dimer levels >70 pg/mL and > 0.5µg FEU/mL respectively, were associated with poor outcome. 85.3% of patients treated with Remdesivir showed clinical improvement. When Tocilizumab and Remdisivir were administered together, 44.0% of patients survived while 56% expired. 79.7% of patients survived while 20.3% expired when neither Tocilizumab nor Remdesivir was administered.

Reduction in pulmonary and hepatic respiratory cytochrome contents by fly ash inhalation in rats.

Exposure of rats to fly ash for 15 days, 6 hours daily, inhibited pulmonary and hepatic NADH-oxidase activity. The content of cytochrome b and cytochromes a + a3 was significantly lower in the lungs of the fly-ash-exposed group. However, in liver, fly ash exposure reduced the cytochrome a + a3 level without affecting the cytochrome b content, indicating a tissue-specific effect. Mitochondrial protein content in both organs was the same in both groups.

Effects of preformed immune complexes on liver enzymes & their serum clearance in mice.

Two different performed HSA-anti-HSA immune aggregates, insoluble complex at equivalence (IC-E) and soluble complex with 5 times antigen excess (IC-S)-were administered iv in experimental mice to study their interaction with liver cells. Both complexes produced no appreciable change in the levels of liver enzymes like acid phosphatase, cathepsin D and gamma-glutamyl transferase. However, marked reduction in the level of liver pseduocholinesterase (as much as 93%) was recorded in the treated animals under identical conditions of administration of both the complexes. Hepatic uptake studies revealed that within 5 min, maximal sequestration of IC occurred within the liver (10 to 18%) and the blood (70 to 82%) when computed in terms of total injected radioactive IC. After 4 h, radioactivity dropped to 3 per cent in liver and 50-40 per cent in blood. The liver seemed to be incapable of scavenging all the serum complexes at a time. Significant consumption of serum complement occurred, when freshly prepared complexes were administered to the animals, but the reduced complement level showed a tendency to reach normalcy after 2 h. The soluble and equivalence zone IC failed to exhibit identifiable discrimination facets with respect to handling by liver. The complexes IC-E and IC-S also behaved in a similar manner.

Improving the yield and quality of DNA isolated from white-rot fungi.

A new simple method used to eliminate polysaccharides that cause problems during DNA isolation was established for 6 different white-rot fungi using 1% hexadecyltrimethylammonium bromide (CTAB) as wash buffer and followed by centrifugation. Variation in the DNA yield and quality was ascertained using precipitating agents, detergents and cell-wall-hydrolyzing chitinase. Considerable amount of exopolysaccharides from fungal biomass was removed with the use of 1% CTAB wash buffer followed by centrifugation. The DNA varied in terms of yield and quality. For the DNA extraction use of 2% SDS in extraction buffer worked best for Pycnoporus cinnabarinus, Cyathus bulleri, Cyathus striatus and Cyathus stercoreus, while 2% CTAB worked best for Phanerochaete chrysosporium and Pleurotus ostreatus. Elimination of phenol and use of absolute ethanol for precipitating DNA resulted in good yield and quality of DNA. This DNA was amenable to restriction endonuclease digestion.

Brainstem auditory evoked response in tuberculous meningitis.

Brainstem auditory evoked response (BAER) abnormalities in tuberculous meningitis (TBM) were determined in 50 cases of tuberculous meningitis (36 male and 14 female) and 50 normal healthy children. Fifty six per cent cases had abnormal BAER findings. The commonest BAER abnormality observed in 32% was a combination of prolonged latency and prolonged interval while unilateral and bilateral absent response was observed in 4% cases. Prolonged latency was observed in 16% patients. Seizure activities, modified glasgow coma scale (GCS), raised intracranial pressure (ICP) and TBM stage III were significantly correlated with abnormal BAER, while age, sex, duration of illness, depressed sensorium, neurological deficit and CSF findings did not have a significant correlation with abnormal BAER. Follow up could be done in ten patients only. All the three patients with only prolonged latency had a normal BAER on follow up, two out of four patients with prolonged latency and prolonged interval had normalization of BAER while in three patients, initial as well as follow up BAER was normal. The present study shows that BAER abnormalities are observed in more than fifty per cent of the patients of tuberculous meningitis.

Brainstem auditory evoked response (BAER) in childhood bacterial meningitis.

Brainstem auditory responses were recorded in 50 children of bacterial meningitis and age matched 50 normal children. Abnormal BAER was found in 32 (64%) patients of bacterial meningitis. These abnormalities included prolonged latency (56.2%); unilateral absent response (25%); bilateral absent response (25%) and prolonged interwave interval (25%). Follow-up could be done in 23 patients of 46 survivors. All the patients with prolonged latency either became normal or improved. In majority of the patients having absent response, the abnormality persisted. Abnormal BAER was significantly associated with age < 2 years (p < 0.02), Modified GCS Score < or = 8 (p < 0.001), Seizures (p < 0.02), raised Intracranial Pressure (ICP) (p < 0.02) and CSF sugar < 20 mg% (p < 0.05).

Renal failure in symptomatic perinatal asphyxia.

The study included seven term newborns developing acute renal failure due to symptomatic perinatal asphyxia in early neonatal period. Its diagnosis was based on clinical and biochemical indices. Urinary output, serum and urinary sodium, potassium and creatinine, and blood urea nitrogen were evaluated in all of them. All the patients had oliguria not responding to fluid challenge and/or diuretic therapy, high serum K, FeNa of greater than 2.5% and RFI of greater than 3 indicative of intrinsic renal disease. The condition was associated with a very high mortality.

Outcome in relation to Apgar score in term neonates.

Sixty four asphyxiated term babies (Apgar score of 6 or less at 5 minutes) and 90 non-asphyxiated term babies (controls) were studied. Of these, 40 cases and 48 controls could be followed up. Mortality and neurodevelopmental outcome were studied in both the cases and controls. Mortality and poor neurodevelopmental outcome correlated inversely with the Apgar scores at 5 and 10 minutes. The outcome of babies with low 5 minute Apgar scores was significantly better than those with the same scores at 10 minutes. Symptomatic neonates when compared to asymptomatic neonates with same Apgar score showed significantly poorer outcome. Babies with Apgar scores of 6 at 5 or 10 minutes behaved like the controls both in terms of mortality and neurodevelopmental outcome.

PIP: In India, pediatricians followed 64 term asphyxiated newborns (Apgar score =or 6) and 90 term nonasphyxiated newborns born at Queen Mary's Hospital in Lucknow to compare their outcomes in terms of mortality and neurodevelopment. They determined their Apgar scores at 5 and 10 minutes. Neonatal mortality increased as the 5-minute Apgar score decreased (5.6% for controls [=or 7], 6.3% for 6, 20% for 5, 25% for 4, and 63.3% for 0-3). It was significantly higher for the 10-minute Apgar groups (16.7% for 6, 33.3% for 5, 40% for 4, and 77.8% for 0-3). 100% and 33.3% of newborns with 5-minute Apgar scores of 0-3 and 4-6, respectively, were symptomatic. Their neonatal mortality rates were 66.6% and 33.3%, respectively. None of the asymptomatic newborns with 5-minute Apgar scores of 4-6 died. At 3, 7, and 11 months follow-up, the neurodevelopmental outcome of infants whose 5-minute Apgar score was 6 was similar to that of the controls. It was better than those with lower 5-minute Apgar scores, especially scores of 0-3 at 3 months (normal development, 91.7% vs. 42.8%; p 0.05). These findings suggest that a 5-minute Apgar score of 6 should not be considered asphyxia (i.e., scores of 5 or less should denote asphyxia). They also show that the Apgar score should be repeated at 10 minutes so health providers can better predict neurodevelopmental outcome.

Brainstem auditory evoked response in neonates with birth asphyxia.

OBJECTIVE: To determine the brainstem auditory evoked response (BAER) abnormalities and their reversibility in neonates with birth asphyxia. DESIGN: Prospective case control study. SETTING: Tertiary care teaching hospital. METHODS: 30 term Neonates with 5-min Apgar < 6 and hypoxic ischemic encephalopathy (HIE) underwent BAER testing with follow up at 3 months. An equal number of normal term neonates served as controls. RESULTS: 13 out of 30 (43.3%) neonates with birth asphyxia showed some abnormality in BAER wave form. The commonest type of BAER abnormalities seen were transient prolongation of latencies of various waves (69.2%) and prolonged interside latency difference (69.2%). Other abnormalities observed were prolonged interwave interval (23.1%) and prolonged interside interval difference (7.7%). Abnormalities in BAER were significantly associated with stages of HIE and duration of neurological abnormalities more than 5 days. On follow up of 16 cases at 3 months of age, BAER abnormalities reverted back to normal in all the neonates. The Denver Developmental Screening Test (DENVER II) was suspect in 4 cases but the BAER was normal. CONCLUSION: BAER abnormalities in asphyxic neonates are transient and revert back to normal at 3 months of age. BAER does not appear to be a useful tool for early detection of neurological handicaps.

Cardiovascular responses to treadmill exercise testing in anemia.

OBJECTIVE: To study exercise performance on a treadmill in anemic children. DESIGN: Prospective case control study. SETTING: Department of Pediatrics and Intensive Care Unit, Department of Medicine, King George's Medical College, Lucknow. SUBJECTS: The study population consisted of 41 cases of anemia (10 mild, 21 moderate and 10 severe) and 11 normal age and height matched children aged between 7-12 years. METHODS: These subjects were exercise tested on Quinton Model Q5000 treadmill using Modified Naughton Q5000 protocol. Heart rate, systolic blood pressure, double product, ECG changes, exercise duration and metabolic equivalents achieved during peak exercise were studied. Statistical analysis was performed using analysis of variance (ANOVA) test. RESULTS: No significant difference was observed in values of resting heart rate, heart rate at peak exercise, recovery heart rate, blood pressure response, resting double product, double product at peak exercise, recovery double product and ECG changes in any of the study groups (p > 0.05). However, the gain in heart rate at peak exercise compared to basal value, and double product, total exercise duration and metabolic equivalent (MET) values at peak exercise were significantly low in anemic children on comparison to normal controls (p < 0.001). CONCLUSIONS: Cardiovascular responses are blunted in anemia, mainly because of depleted cardiac reserve.

Pulmonary function tests in normal Indian children and changes in respiratory disorders.

To document the normal values of pulmonary function tests in children and changes occurring in their values with various respiratory disorders, a study was carried over a period of one year in 95 healthy controls (39 females and 56 males) of 8-13 years of age and 51 cases with respiratory disorders (bronchial asthma-31, pneumonia-10, empyema-10) of matched age, sex and height distribution. The lung functions studied were FVC, FEV1, FEV1/FVC, PEFR and FEF25-75%. In children with bronchial asthma, the FEV1/FVC%, PEFR and FEF25-75% were reduced in accordance with the severity of the disease. A typical restrictive pattern of equivalent decrease in FVC and FEV1 along with insignificant lowering of flow rates, i.e., PEFR and FEF25-75% was observed in pneumonia whereas in patients of empyema a combined pattern of significantly decreased FVC and FEV1 along with mildly reduced FEV1/FVC%, PEFR and FEF 25 75% was observed.

Brainstem auditory evoked response in newborns with hyperbilirubinemia.

OBJECTIVE: To determine the initial Brainstem Auditory Evoked Response (BAER) abnormalities in neonates with hyperbilirubinemia and the possible reversibility of abnormal BAER after therapy. DESIGN: Prospective cohort study. SETTING: Tertiary care hospital. SUBJECTS: 30 term neonates with hyperbilirubinemia (S. bilirubin < 15 mg/dl) as cases and 25 normal term neonates as controls. METHODS: Duration of study was from August 1995 to August 1996. BAER were recorded before therapy at peak hyperbilirubinemia, after therapy, and the age of 2-4 months using electric response audiometer (Nihon Neuropack Four Machine). Denver Development Screening Test (Denver II) was performed at 1 year of age. RESULTS: Seventeen out of thirty (56.7%) neonates with hyperbilirubinemia showed abnormalities on initial BAER. Commonest abnormality seen was raised threshold of wave V in 12 neonates (40%). Other abnormalities observed were absence of all waves at 90 dB (23.3%), prolongation of latencies of various waves (26.7%) and prolongation of various intervals (26.7%). Abnormalities in BAER correlated significantly with bilirubin level. After therapy abnormalities reverted back to normal in 10 cases but persisted in 7 out of 17 (41.17%) cases with initial abnormal BAER. Development screening at 1 yr was abnormal in 3 infants all of whom had persistent abnormalities in BAER. CONCLUSION: Serial BAER is a useful, non invasive tool to detect neurodevelopment delay secondary to neonatal hyperbilirubinemia.

Demasking of subclinical left ventricular dysfunction in anemic children.

OBJECTIVE: To study subclinical left ventricular dysfunction in anemic children. SETTING: Hospital. SUBJECTS: The study population consisted of 52 cases of anemia (16 mild, 14 moderate, 22 severe) and 20 normal age and height matched children aged between 7-12 years. METHODS: These children were subjected to Echocardiography on Ascuson XP model using 3.5 MHz Transducer during rest and immediately after maximum tolerated exercise on Quniton Model Q-5000 treadmill using modified Naughton protocol. Left ventricular end diastolic dimensions, left ventricular systolic dimension, fractional shortening, left ventricular end diastolic volume, systolic volume, stroke volume and ejection fraction were studied on M-mode echocardiography, and E/A ratio on doppler mode. RESULTS: Significant differences were observed in resting heart rate, gain in heart rate at peak exercise compared to basal values and double product, total exercise duration and metabolic equivalents at peak exercise in controls and anemic subjects. Left ventricular dysfunction was present in all severely anemic subjects after maximum tolerated exercise on treadmill. The only evidence of left ventricular diastolic dysfunction was in form of decreased left ventricular end diastolic volume after exercise in moderate and severely anemic subjects. CONCLUSIONS: Exercise is helpful in demasking subtle left ventricular dysfunctions in anemic subjects that are not detected during rest.

Computed tomography of brain in symptomatic birth asphyxia.

Twenty five asphyxiated newborns (seventeen term and eight preterm) with mean gestational age of 37 weeks (range 28-48 weeks) and mean birth weight of 2.4 kg (range 0.75 kg to 3.5 kg), respectively, constituted the cases in present study. Normal CT scan was found in five term (29.4%) and two preterm babies (25%). CT abnormalities noted in term babies included hemorrhage (subarachnoid 5.8%, intracerebral 11.6%), hypodensity (mild 23.2%, moderate 11.6% severe 5.8%); hypodensity with hemorrhage 5.8% and cerebral atrophy 5.8%. In the preterm babies abnormalities included intraventricular hemorrhage in 25%, isolated hypodensity in 37.5% and hypodensity with hemorrhage in 12.5% cases. Where as mild hypodensity on CT scan in the absence of hemorrhage or other gross abnormality was indicative of a favourable outcome, moderate to severe hypodensity was indicative of ischemic brain injury and an unfavourable outcome. The presence of intraventricular hemorrhage irrespective of the size of bleed was associated with mortality in all in the present study.

Perinatal mortality in urban slums in Lucknow.

OBJECTIVES: To determine the perinatal mortality rate (PNMR) in the urban slums of Lucknow DESIGN: Cross-sectional survey. SETTING: Twenty five Anganwadi centres of urban Lucknow, with a population of 25,901. METHODS: Data was collected on birth and early neonatal deaths, gestational age of the neonate (determined at birth) and maternal variables like socio-economic status, maternal age, parity, and bad obstetrical history from January 1992 to March 1993. RESULTS: There were 966 births with a still-birth rate of 37.2 and PNMR of 59.0 per 1000. The relative risk of perinatal mortality with lower socio-economic status was 1.87, bad obstetrical history 2.18, and gestational age < 37 weeks 1.95. CONCLUSIONS: Further reduction in PNMR may be possible with focussed medical services to women of low socio-economic status having bad obstetrical history and those delivering before term.

PIP: This study examines the nature and extent of perinatal mortality in the urban slums of Lucknow, India. A survey was conducted during 1992-93 among all mothers who had a birth during the study period and were registered in one of 25 Anganwadi centers. Causes of death were determined by verbal autopsy (neonatal jaundice, birth injury, infections, and asphyxia). The study area population numbered 25,901. There were 966 deliveries, of which 930 were live births. There were 36 stillbirths, 21 early neonatal deaths, and 57 perinatal deaths. 99 live born infants were premature births. The stillbirth rate was 37.2/1000 live births. The perinatal mortality rate (PNMR) was 59.0/1000. This rate was lower than findings among slum women in Delhi and Jabalpur. PNMR was higher among older women and higher parities, women of low socioeconomic status, women with a poor obstetric history, women with inadequate prenatal care, and premature infants or those delivered by untrained persons. The highest relative risk of PNMR was associated with a poor obstetric history, followed by prematurity, low socioeconomic status, and no prenatal care. The leading cause of death was asphyxia (42.1%), followed by prematurity (14.03%) and infections (12.3%). Over 50% of deliveries were performed by untrained persons, and 80% were home deliveries, despite the availability of medical facilities. Attainment of the national goal of reducing PNMR to under 30/1000 will be dependent upon registration of pregnant mothers, detection of high-risk cases and timely intervention, delivery by trained medical persons, and limitation of family size.

Diagnosis of tuberculous meningitis by detection of antigen and antibodies in CSF and sera.

OBJECTIVE: To evaluate diagnostic potential of three immunological tests, namely, detection of H37Rv antigen of M. Tuberculosis in CSF, detection of antibodies (IgG) against H37Rv in CSF and detection of antibodies (IgG) against H37Rv in serum for diagnosis of tuberculous meningitis in children. SUBJECTS: 50 children diagnosed as patients of tuberculous meningitis were included as cases and 48 children with CNS diseases of nontubercular etiology [pyogenic meningitis (n = 31), encephalitis (n = 10), seizure disorder of unknown etiology (n = 5), brain tumor (n = 2)] served as controls. METHODS: H37Rv antigen of M. tuberculosis was detected in CSF by Dot ELISA, and antibodies (IgG) against H37Rv in CSF and serum were detected by Plate ELISA. RESULTS: Detection of H37Rv antigen in CSF was the most sensitive (90%) and specific (95.83%) with positive and negative predictive values of 95.74% and 90.19%, respectively, followed by detection of antibodies in CSF (sensitivity-74%, specificity-89.58%, positive predictive value-88.10%, negative predictive value-76.78%). Detection of antibodies in serum had low sensitivity (50%), specificity (91.67%), positive predictive value (86.21%) and negative predictive value (63.76%). CONCLUSIONS: Detection of antigen in CSF is a rapid, sensitive and specific test for diagnosis of tuberculous meningitis in children. Detection of antibody in CSF may be useful in some cases but needs further evaluation. Detection of antibody in serum does not appear to be useful for diagnosis of tuberculous meningitis.

Oxidant stress mechanisms in heart failure.

Evidences clearly indicate that HF is accompanied by excessive generation of OFRs and depletion of endogenous antioxidant system. The resultant oxidant stress depresses myocardial contractility and function by decreasing Ca++ uptake in sarcoplasmic reticulum and by impaired Ca(++)-ATPase in cardiac tissue. The various sources of OFRs production in HF include increased production of nitric oxide, cytokines, prostaglandins, auto-oxidation of catecholamines, activation of polymorph leucocytes and ischemia induced xanthine-xanthine oxidase. The prevention of oxidative stress by antioxidant translates into better metabolism and function of myocytes. It appears that antioxidant drugs may represent a novel adjunct to the existing therapeutic armamentarium in patients of HF irrespective of its etiology and severity.