Kajal Jain

Apo-E4 Allele in Conjunction with Aβ42 and Tau in CSF: Biomarker for Alzheimers Disease

The objective of this study was to elucidate an association between Apo- E4 allele and CSF biomarkers Aβ42 and tau for the diagnosis of Alzheimers Disease (AD) patients. Aβ42 and tau protein concentrations in CSF were measured by using ELISA assays. The levels of Aβ42 were found to be decreased where as tau levels increased in AD patients. Moreover in AD patients Apo-E4 allele carriers have shown low Aβ42 levels (328.86 ± 99.0 pg/ml) compared to Apo- E4 allele non-carriers (367.52 ± 57.37 pg/ml), while tau levels were higher in Apo-E4 allele carriers (511 ± 44.67 pg/ml) compared to Apo-E4 allele non-carriers (503.75 ± 41.08 pg/ml). Combination of Aβ42 and tau resulted in sensitivity of 75.38% and specificity of 94.82% and diagnostic accuracy of 84.30% for AD compared with the controls. Therefore low Aβ42 and elevated tau concentrations in CSF may prove to be a better diagnostic marker for AD along with the Apo-E4 allele.

CSF p-Tau levels in the prediction of Alzheimer's disease

Summary The two hallmarks of Alzheimers disease (AD) are neurofibrillary tangles and amyloid plaques. Neurofibrillary tangles are formed due to the hyperphosphorylation of tau protein. There is an urgent need to develop a reliable biomarker for the diagnosis of AD. Cerebrospinal fluid (CSF) is surrounding the brain and reflects the major neuropathological features in the AD brain. Diagnosis, disease progression and drug actions rely on the AD biomarkers. Mainly CSF tau and phosphorylated tau (p-Tau) have been observed to serve the purpose for early AD. Keeping in view the early appearance of p-Tau in CSF, we analyzed p-Tau levels in 23 AD, 23 Non AD type dementia (NAD), 23 Neurological control (NC) and 23 Healthy control (HC) North Indian patients. The levels of p-Tau were found to be increased in AD patients (67.87±18.05 pg/ml, SEM 3.76) compared with NAD (47.55±7.85 pg/ml, SEM 1.64), NC (34.42±4.51 pg/ml, SEM 0.94) and HC (27.09±7.18 pg/ml, SEM 1.50). The resulting sensitivity for AD with NAD was 80.27% whereas with respect to the NAD, NC and HC was 85.40%. Therefore elevated levels of p-Tau in AD can be exploited as a predictive biomarker in North Indian AD patients.

CSF ubiquitin as a specific biomarker in Alzheimer's disease.

Alzheimers disease (AD) is the most common cause of dementia worldwide. Although, many putative biomarkers are reported for AD, only a few have been validated in the clinical setting. Ubiquitin levels increase in cerebrospinal fluid (CSF) of patients with AD, but its diagnostic value is not clear. In this present study we evaluate the performance of ubiquitin as a diagnostic marker and deduce a statistical association with disease pathology in AD. Ubiquitin levels were estimated in subjects with AD, other forms of dementias, neurological disorders and healthy age matched population. The levels of ubiquitin were significantly higher in subjects with AD when compared with other groups (p<0.0001). A significant positive correlation was observed between ubiquitin, tau and apolipoprotein Eε4 genotype; with Aβ42 the correlation was negative. By comparing the effect size of the association between ubiquitin and a diagnosis of AD, we find that high ubiquitin levels are specific for AD. We obtained an odds ratio of 5.6 (95% CI 5.0-7.7) for ubiquitin, towards a diagnosis of AD based on clinical criteria, CSF biomarker signature (Aβ42+tau) and apolipoprotein Eε4 genotype. Hence, all our findings taken together provide a strong statistical association linking ubiquitin to the pathology in AD. We also find that, the performance of ubiquitin as a diagnostic marker is comparable to that of CSF Aβ42 or tau or apolipoprotein Eε4 genotype considered individually.

Efficacy of ketamine and midazolam as co‐induction agents with propofol for laryngeal mask insertion in children

Objectives:  Use of midazolam and ketamine lowers the induction dose of propofol (co‐induction) producing hemodynamic stability.

A comparison of three vasopressors for tight control of maternal blood pressure during cesarean section under spinal anesthesia: Effect on maternal and fetal outcome

Purpose: Maintaining systolic blood pressure (SBP) at 100% of baseline is best for fetal and maternal outcome. We hypothesized that irrespective of the vasopressor used, maintaining SBP at 100% of baseline with phenylephrine (P), metaraminol (M), or ephedrine (E) will produce the best fetal pH after cesarean section (LSCS) under subarachnoid block (SAB). Materials and Methods: Ninety ASA 1 women scheduled for elective LSCS were randomly allocated to receive P, M, or E. SAB was established with patient in left lateral position using 2.5 cc of 0.5% hyperbaric bupivacaine. Immediately following SAB, patients received a bolus of the study drug (E = 5 mg, M = 0.5 mg, P = 30 mcg) followed by infusion (E = 2.5 mg/min, M = 0.25 mg/min, P = 15 mcg/min) to maintain SBP at 100% baseline. Umbilical blood gases, maternal hemodynamic parameters, and complications were recorded. Results: The umbilical pH was comparable in all the three groups (P > 0.05). The mean SBP from spinal block until delivery was similar over time for all the three groups. The incidence of reactive hypertension was more in group M (P < 0.05) than in group E and group P. Total drug consumption to meet target blood pressure till delivery was 39.3 ± 14.6 mg in group E, 1.7 ± 0.9 mg in group M, and 283.6 ± 99.8 mcg in group P. The incidence of nausea and vomiting was comparable in the three groups. Conclusion: All the three vasopressors were equally effective in maintaining maternal blood pressure as well as umbilical pH during spinal anesthesia for cesarean section without any detrimental effects on fetal and maternal outcome.

Apolipoprotein E Levels in the Cerebrospinal Fluid of North Indian Patients With Alzheimer's Disease

The etiology of Alzheimer’s disease (AD) is multifactorial involving both genetic and environmental factors. Apolipoprotein E (ApoE) gene plays a pivotal role in risk and age of onset of AD. Although it is broadly accepted that ApoE genotype is linked to the pathogenesis of AD, there are still controversial results regarding the association of ApoE levels in cerebrospinal fluid (CSF) with the occurrence of AD. Some studies have shown a positive correlation between CSF ApoE levels and AD, whereas others showed no link. In this study, we measured ApoE levels to assess the usefulness of CSF ApoE as a diagnostic marker of AD by comparing the levels in 3 patient groups and in control participants. No significant difference was observed in CSF ApoE concentrations between the patients with AD and the controls. So, it appears that CSF ApoE measurement does not offer any diagnostic advantage for AD.

Efficacy of two oral premedicants: midazolam or a low‐dose combination of midazolam–ketamine for reducing stress during intravenous cannulation in children undergoing CT imaging

Background:  Pain, anxiety and fear of needles make intravenous cannulation extremely difficult in children. We assessed the efficacy and safety of oral midazolam and a low‐dose combination of midazolam and ketamine to reduce the stress and anxiety during intravenous cannulation in children undergoing computed tomography (CT) imaging when compared to placebo.

A randomized trial comparing prophylactic phenylephrine and ephedrine infusion during spinal anesthesia for emergency cesarean delivery in cases of acute fetal compromise

BACKGROUND Previous evidence showed that use of phenylephrine was associated with higher umbilical artery pH (UA pH) than ephedrine after elective cesarean delivery (CD). However, the best choice of vasopressor and its effect on funic gases in cases of acute fetal compromise require additional studies. METHODS Ninety parturients showing acute fetal compromise during intrapartum period and taken up for CD (category II) under spinal anesthesia were randomized to receive prophylactic infusion of ephedrine 2.5mg/min or phenylephrine 30μg/min. Systolic blood pressure was targeted between 90% and 110% of baseline. Incidence of fetal acidosis (UA pH <7.2 and/or base deficit >12mmol/L) was recorded. Other parameters of cord gases, Apgar score, need for immediate resuscitation, maternal hemodynamics, and adverse events were also compared. RESULTS Number of neonates showing acidosis with ephedrine or phenylephrine was comparable (P=.22). Of these, newborns with base deficit >12mmol had low 1-minute Apgar scores (n=15/23). The ephedrine group had higher oxygen content in UA (P=.03). There was no adverse neonatal outcome during the period of observation. Incidence of maternal nausea and vomiting was higher with ephedrine than with phenylephrine (22.2% vs 4.4%; P=.02). Maternal bradycardia was observed with phenylephrine (P=.02). CONCLUSION Our data report similar fetal acidosis with either phenylephrine or ephedrine administered during spinal anesthesia for treating maternal hypotension in cases of emergency CD.

A randomised comparison of the effects of low-dose spinal or general anaesthesia on umbilical cord blood gases during caesarean delivery of growth-restricted foetuses with impaired Doppler flow.

Context Hypotension following spinal anaesthesia for caesarean delivery may decrease uteroplacental perfusion and produce foetal acidosis. The optimal anaesthetic technique for mothers with foetal growth restriction and impaired Doppler flow is unclear. Objective To compare the effects of low-dose spinal anaesthesia and general anaesthesia on neonatal outcome and maternal haemodynamics. Design Prospective, randomised clinical trial. Setting Tertiary care hospital. Patients Forty pregnant women with foetal growth restriction and impaired Doppler flow scheduled for elective caesarean delivery. Interventions The women were allocated randomly to receive a low-dose spinal anaesthetic (8-mg hyperbaric bupivacaine 0.5% with fentanyl 20 &mgr;g) or standard general anaesthesia for elective caesarean delivery. SBP was maintained between 80 and 100% of baseline using bolus doses of phenylephrine. The total duration of hypotension, dose of phenylephrine used and any incidence of hypotension, nausea or vomiting were recorded. Main outcome measures The primary outcome variable was arterial and venous umbilical cord base deficit. Neonatal outcome and maternal haemodynamics were analysed as secondary endpoints. Results The mean umbilical artery pH was significantly lower in the low-dose spinal anaesthesia group than in the general anaesthesia group (7.23 ± 0.06 vs. 7.27 ± 0.04, P = 0.01). Cord base deficit was similar in the two groups. Higher partial pressures of oxygen occurred in the general anaesthesia group (20.9 ± 6.5 kPa) than in the low-dose spinal anaesthesia group (13.6 ± 6.1 kPa, P = 0.001). No difference was observed between groups in 1 and 5-min Apgar scores. There appeared to be a greater need for immediate resuscitation of neonates in the general anaesthesia group, but the difference was not statistically significant (P = 0.51). Low-dose spinal anaesthesia was associated with hypotension of short duration (0.7 ± 1.1 min). Conclusion In this study, there was no difference in umbilical cord base deficit between the groups. Larger studies would be required to assess whether the mode of anaesthesia influences the incidence of clinically important neonatal acidosis in neonates with foetal growth restriction.

Cerebrospinal fluid profile of amyloid β42 (Aβ42), hTau and ubiquitin in North Indian Alzheimer's disease patients.

Alzheimers disease (AD) is the most common form of dementia, and is characterized by the degeneration of neurons and their synapses, and a higher number of amyloid plaques and neurofibrillary tangles (NFTs) compared with that found in non-demented individuals. Amyloid-β-peptides (Aβ) are major components of amyloid plaques in AD brain whereas NFTs are composed of Tau and associated with ubiquitin. The aim of the present study was to analyze the levels of Aβ42, hTau (total Tau) and ubiquitin in CSF of North Indian population. CSF Aβ42, Tau and ubiquitin were measured in CSF of AD patients as well as controls using ELISA assays. Here we report low Aβ42 levels in AD patients (324.24±76.38pg/ml) as compared to those in non-AD (NAD) (668.34±43.13pg/ml), neurological controls (NCs) (727.28±46.49pg/ml) and healthy controls (HCs) (976.47±124.46pg/ml). In contrast, hTau and ubiquitin levels were significantly high (568.65±48.89pg/ml and 36.82±4.34ng/ml, respectively) in AD patients compared to those in NAD, NC and HC. The hTau levels were 267.37±36.64pg/ml, 167.34±44.27pg/ml and 107.62±24.27pg/ml in NAD, NC and HC, respectively. Similarly, ubiquitin levels were 23.57±2.32ng/ml, 19.76±3.64ng/ml and 13.24±4.56ng/ml in NAD, NC and HC, respectively. In conclusion, low Aβ42 and high Tau-ubiquitin levels were found in North Indian AD patients.