Vinod K Grover

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.

Caudal neostigmine with bupivacaine produces a dose-independent analgesic effect in children

PurposeTo evaluate the analgesic efficacy and duration of varying doses of caudal neostigmine with plain bupivacaine and its side effects in children undergoing genito-urinary surgery.MethodsIn a randomized double-blind prospective study 80 boys aged two to eight years scheduled for surgical repair of hypospadias were allocated randomly to one of four groups (n = 20 each) and received either only caudal 0.25% plain bupivacaine 0.5 mL · kg−1 (Group 1) or 0.25% plain bupivacaine 0.5 mL · kg−1 with neostigmine (Groups II-IV) in doses of 2, 3 and 4βg · kg−1 respectively. Postoperative pain was assessed for 24 hr using an objective pain score. Blood pressure, heart rate, oxygen saturation, total amount of analgesic consumed and adverse effects were also recorded.ResultsThe duration of postoperative analgesia in Group I (5.1 ± 2.3 hr) was significantly shorter than in the other three groups (II–16.6 ± 4.9 hr; III — 17.2 ± 5.5 hr; IV-17.0 ± 5.8 hr; P < 0.05). Total analgesic (paracetamol) consumption was significantly more in Group 1 (697.6 ± 240.7 mg) than in the groups receiving caudal neostigmine (II — 248.0 ± 178.4; III — 270.2 ± 180.8 and IV − 230.6 ± 166.9 mg; P < 0.05). Groups II, III and IV were comparable with regards to duration of postoperative analgesia and total analgesic consumption (P > 0.05). Incidence of nausea and vomiting were comparable in all four groups. No significant alteration in vital signs or any other adverse effects were observed.ConclusionsCaudal neostigmine (2, 3 and 4μg · kg−1) with bupivacaine produces a dose-independent analgesic effect (≈ 16–17 hr) in children as compared to those receiving caudal bupivacaine alone (approximately five hours) and a reduction in postoperative rescue analgesic consumption without increasing the incidence of adverse effects.RésuméObjectifÉvaluer l’efficacité analgésique et la durée de différentes doses de néostigmine caudale avec bupivacaïne simple et ses effets secondaires chez des enfants qui subissent une intervention génito-urinaire.MéthodeDans une étude randomisée, prospective et à double insu, 80 garçons de deux à huit ans devant subir la réparation chirurgicale d’un hypospadias ont été répartis au hasard en quatre groupes (n = 20 chacun) et ont reçu: seulement de la bupivacaïne caudale simple à 0,25 % (0,5 mL · kg−1 Groupe I) ou de la bupivacaïne simple à 0,25 % avec néostigmine (0,5 mL · kg−1, Groupes II-IV) en doses respectives de 2, 3 et 4 μg · kg−1. La douleur postopératoire a été évaluée pendant 24 h selon des scores de douleur objectifs. La tension artérielle, la fréquence cardiaque, la saturation du sang en oxygène, la quantité totale d’analgésiques consommés et les effets secondaires ont été aussi enregistrés.RésultatsLa durée de l’analgésie postopératoire a été significativement plus courte dans le Groupe I (5,1 ± 2,3 h) que dans les autres groupes (II — 16,6 ± 4,9 h; III — 17,2 ± 5,5 h; IV-17,0 ± 5,8 h; P < 0,05). La consommation totale d’analgésique (paracétamol) a été significativement plus élevée dans le Groupe I (697,6 ± 240,7 mg) que dans les groupes avec néostigmine caudale (II — 248,0 ± 178,4; III-270,2 ± 180,8 et IV — 230,6 ± 166,9 mg; P < 0,05). La durée de l’analgésie postopératoire et la consommation totale d’analgésique (P > 0,05) étaient comparables dans les groupes II, III et IV. Lincidence de nausées et de vomissements a été similaire dans les quatre groupes. Aucune modification significative des signes vitaux ou tout autre effet indésirable n’ont été observés.ConclusionChez des enfants, la néostigmine caudale (2, 3 et 4 μg · kg−1) avec bupivacaïne, comparées à la bupivacaïne caudale seule (≈ 5 h), produit une analgésie non reliée à la dose (≈ 16–17 h) et une réduction de la consommation postopératoire d’analgésique de secours sans augmenter l’incidence d’effets indésirables.

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.

Perioperative vision loss: A complication to watch out

Postoperative vision loss, a rare but devastating complication, has been reported after spine, cardiac, and head–neck surgeries. Its incidence following spine surgeries exceeds that after cardiothoracic surgeries. Various causes attributed to postoperative blindness include ischemic optic neuropathy, central or branch retinal artery occlusion, cortical blindness, and rarely external ocular injury. Other contributory factors described are microvascular diseases and intraoperative hemodynamic compromise. However, the exact association of these factors with postoperative blindness has not yet been confirmed. In this review, we describe causes, presentation, and treatment of postoperative blindness and also recommend practical guidelines to avoid this complication. The search strategies for this review included both search of electronic databases as well as manual search of relevant articles.

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.

Comparison of Small Dose Ketamine and Dexmedetomidine Infusion for Postoperative Analgesia in Spine Surgery--A Prospective Randomized Double-blind Placebo Controlled Study.

Background: High doses of opioids are frequently used to treat postoperative pain after spine surgery. This leads to opioid-related side effects like nausea, vomiting, respiratory depression, etc. The current study is an attempt to find a safe analgesic adjuvant, which will afford opioid sparing property. Method: Sixty-six patients undergoing spine surgery were randomized into 1 of the 3 groups—group K (ketamine bolus 0.25 mg/kg followed by infusion of 0.25 mg/kg/h with midazolam bolus 10 &mgr;g/kg and infusion of 10 &mgr;g/kg/h mixed in the same infusion pump), group D (dexmedetomidine bolus 0.5 &mgr;g/kg followed by 0.3 &mgr;g/kg/h infusion), and group C (normal saline). Study drugs were started in the postoperative period and continued for 24 hours. Pain-free period, pain scores, rescue analgesic (morphine) requirements, and side effects were noted for 48 hours postoperatively. Result: Mean pain-free periods in the ketamine group (860 min) and the dexmedetomidine group (580 min) were longer than in the saline group (265 min) (P<0.002) during the observation period of 48 hours. There was a significant decrease in the rescue analgesic requirement in both ketamine and dexmedetomidine group (P<0.05) (cumulative morphine requirement at 24 h—group C 15.64±9.31 mg, group D 6.89±5.88 mg, group K 2.45±2.06 mg; at 48 h—group C 21.09±12.88 mg, group D 7.98±7.72 mg, group K 2.59±1.97 mg). Hemodynamics were maintained within normal range in all the groups. Patients in ketamine and dexmedetomidine groups were sedated, but none required assistance for maintaining airway patency. Few patients in the ketamine group had nausea, dizziness, and diplopia, but the difference was insignificant in comparison with other groups (P>0.05). Conclusions: Infusion of low-dose ketamine and dexmedetomidine both provide good postoperative analgesia with minimal side effects. Both of the tested analgesic regimes can be used safely and effectively for postoperative pain relief in patients after spine surgery.

Double-blind comparison of lidocaine, tubocurarine and diazepam pretreatment in modifying intraocular pressure increases.

One hundred and sixty patients, divided randomly into four groups received normal saline (5 ml), d-tubocurarine (0.05 mg· kg-1), diazepam (0.1 mg·kg-1) or lidocaine (1 mg·kg-1) as pretreatment, in a double blind manner, five minutes before anaesthetic induction with thiopentone and succinylcholine (1 mg·kg-1). Succinylcholine caused a significant increase in IOP in all groups. However, in the lidocaine group, this increase was significantly less than that observed in the control group. The post-succinylcholine increase in IOP was further aggravated by tracheal intubation in all except the lidocaine group. A further clinical trial with higher doses of lidocaine is suggested to assess its ability to obtund the succinylcholine-induced increase in IOP. Lidocaine in a dose of 1 mg·kg-1 IV prevents the rise in IOP which follows intubation.RésuméCent soixante patients divisés ďune façon randomisée en quatre groupes ont reçu du salin physiologique (5 ml), de la d-tubocurarine (0.05 mg·kg-1), du diazepam (0.1 mg·kg-1) ou de la lidocaine (1 mg·kg-1) comme pré-traitment à double insu, cinq minutes avant ľinduction de ľanesthésie avec du thiopentone et de la succinylcholine (1 mg·kg-1). La succinylcholine a provoqué une augmentation significative de la pression intraoculaire chez tous les groupes. Cependant, pour le groupe lidocaine, cette augmentation était significativement moindre que celle observée chez le groupe contrôle. Ľaugmentation de la pression intraoculaire post succinylcholine était davantage aggravée par ľintubation trachéale chez tous les groupes à ľexception du groupe lidocaine. Un essai clinique ultérieur avec de plus fortes doses de lidocaine est suggéré afin ďévaluer sa capacité de diminuer ľaugmentation de la pression intraoculaire induite par la succinylcholine malgré qu’elle est suffisante aux doses de 1 mg·kg-1 pour prévenir ľaugmentation de la pression intra-oculaire après ľintubation.

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.

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.

Evaluation of the Effect of Aneurysmal Clipping on Electrocardiography and Echocardiographic Changes in Patients With Subarachnoid Hemorrhage: A Prospective Observational Study.

Background: Electrocardiographic (ECG) and echocardiographic changes that are subsequent to aneurysmal subarachnoid hemorrhage (a-SAH) are commonly observed with a prevalence varying from 27% to 100% and 13% to 18%, respectively. There are sparse data in the literature about the pattern of ECG and echocardiographic changes in patients with SAH after clipping of the aneurysm. Hence, we observed the effect of aneurysmal clipping on ECG and echocardiographic changes during the first week after surgery, and the impact of these changes on outcome at the end of 1 year. Materials and Methods: This prospective, observational study was conducted in 100 consecutive patients with a-SAH undergoing clipping of ruptured aneurysm. ECG and echocardiographic changes were recorded preoperatively and every day after surgery until 7 days. Outcome was evaluated using the Glasgow outcome scale at the end of 1 year. Results: Of 100 patients, 75 had ECG changes and 17 had echocardiographic changes preoperatively. The ECG changes observed were QTc prolongation, conduction defects, ST-wave and T-wave abnormalities, tachyarrhythmias, and bradyarrhythmias. The echocardiography changes included global hypokinesia and regional wall motion abnormalities. Both echocardiographic and ECG changes showed significant recovery on the first postoperative day. Patients presenting with both echocardiographic and ECG changes were found to require higher ionotropic support to maintain the desired blood pressure, and were associated with poor outcome (Glasgow outcome scale, 1 to 2) at 1 year after surgery. There was no association of ECG and echocardiographic changes with mortality (both in-hospital or at 1 year). Conclusions: The ECG changes, such as QTc prolongation, bradycardia, conduction abnormality, and echocardiographic changes, recover on postoperative day-1, in most of the cases after clipping. Patients with combined ECG and echocardiographic changes tend to have poor neurological outcome at the end of 1 year.