Dexmedetomidine as an Anesthetic Adjuvant in Intracranial Surgery.

BACKGROUND: The basic principle of neuroanesthesia is to provide hemodynamic stability, provision of optimal operative conditions, maintenance of cerebral perfusion pressure, and cerebral oxygenation. AIM: This study was undertaken to see the effect of dexmedetomidine infusion on hemodynamics and its ability to act as an anesthetic adjuvant in patients undergoing supratentorial tumor surgery. SETTING AND DESIGN: Prospective randomized control double blind study. SUBJECTS AND METHODS: In this study, we compared two groups with 25 patients in each group. Group C patients received saline infusion during surgery and 4 µg/kg of fentanyl intravenously (i.v.) at the induction and at pin head application. Group D patients received dexmedetomidine infusion during surgery at the rate of 0.4 µg/kg/h and 2 µg/kg of fentanyl i.v. at the induction and at pin head application. STATISTICAL ANALYSES USED: Parametric data were analyzed using Student's t-test. The categorical data were studied using Chi-squared test or Fisher's test as appropriate. RESULTS: The vitals remained within 20% of baseline in both groups during the study period except at the time of extubation where the rise in heart rate was more than 20% in control group. The requirement of thiopentone for induction was significantly less in dexmedetomidine group. In dexmedetomidine group, less number of patients required intraoperative fentanyl (P < 0.05), and the time to rescue analgesic was also more in Group D (P < 0.05). CONCLUSION: Dexmedetomidine infusion started before surgery maintains hemodynamic stability intraoperatively and is effective in attenuating the cardiovascular responses to intubation, skull pin application, and extubation. It decreases the requirement of other anesthetic agents as well.

Determination of minimum inhibitory concentrations of itraconazole, terbinafine and ketoconazole against dermatophyte species by broth microdilution method.

PURPOSE: Various antifungal agents both topical and systemic have been introduced into clinical practice for effectively treating dermatophytic conditions. Dermatophytosis is the infection of keratinised tissues caused by fungal species of genera Trichophyton, Epidermophyton and Microsporum, commonly known as dermatophytes affecting 20-25% of the world's population. The present study aims at determining the susceptibility patterns of dermatophyte species recovered from superficial mycoses of human patients in Himachal Pradesh to antifungal agents; itraconazole, terbinafine and ketoconazole. The study also aims at determining the minimum inhibitory concentrations (MICs) of these agents following the recommended protocol of Clinical and Laboratory Standards Institute (CLSI) (M38-A2). METHODOLOGY: A total of 53 isolates of dermatophytes (T. mentagrophyte-34 in no., T. rubrum-18 and M. gypseum-1) recovered from the superficial mycoses were examined. Broth microdilution method M38-A2 approved protocol of CLSI (2008) for filamentous fungi was followed for determining the susceptibility of dermatophyte species. RESULTS: T. mentagrophyte isolates were found more susceptible to both itraconazole and ketoconazole as compared to terbinafine (MIC50: 0.125 µg/ml for itraconazole, 0.0625 µg/ml for ketoconazole and 0.5 µg/ml for terbinafine). Three isolates of T. mentagrophytes (VBS-5, VBSo-3 and VBSo-73) and one isolate of T. rubrum (VBPo-9) had higher MIC values of itraconazole (1 µg/ml). Similarly, the higher MIC values of ketoconazole were observed in case of only three isolates of T. mentagrophyte (VBSo-30 = 2 µg/ml; VBSo-44, VBM-2 = 1 µg/ml). The comparative analysis of the three antifungal drugs based on t-test revealed that 'itraconazole and terbinafine' and 'terbinafine and ketoconazole' were found independent based on the P < 0.005 in case of T. mentagrophyte isolates. In case of T. rubrum, the similarity existed between MIC values of 'itraconazole and ketoconazole' and 'terbinafine and ketoconazole'. CONCLUSION: The MIC values observed in the present study based on standard protocol M38-A2 of CLSI 2008 might serve as reference for further studies covering large number of isolates from different geographic regions of the state. Such studies might reflect on the acquisition of drug resistance among isolates of dermatophyte species based on MIC values.

BAR domains, amphipathic helices and membrane-anchored proteins use the same mechanism to sense membrane curvature.

The internal membranes of eukaryotic cells are all twists and bends characterized by high curvature. During recent years it has become clear that specific proteins sustain these curvatures while others simply recognize membrane shape and use it as "molecular information" to organize cellular processes in space and time. Here we discuss this new important recognition process termed membrane curvature sensing (MCS). First, we review a new fluorescence-based experimental method that allows characterization of MCS using measurements on single vesicles and compare it to sensing assays that use bulk/ensemble liposome samples of different mean diameter. Next, we describe two different MCS protein motifs (amphipathic helices and BAR domains) and suggest that in both cases curvature sensitive membrane binding results from asymmetric insertion of hydrophobic amino acids in the lipid membrane. This mechanism can be extended to include the insertion of alkyl chain in the lipid membrane and consequently palmitoylated and myristoylated proteins are predicted to display similar curvature sensitive binding. Surprisingly, in all the aforementioned cases, MCS is predominantly mediated by a higher density of binding sites on curved membranes instead of higher affinity as assumed so far. Finally, we integrate these new insights into the debate about which motifs are involved in sensing versus induction of membrane curvature and what role MCS proteins may play in biology.

A comparative study of two different doses of epidural neostigmine coadministered with lignocaine for post operative analgesia and sedation.

BACKGROUND: Adjuvants have been used to prolong analgesic effects of epidural local anaesthetics. We studied two different doses of neostigmine. PATIENTS #ENTITYSTARTX00026; METHODS: A randomized double blind study was conducted on ninety adult females scheduled for lower intra abdominal surgeries. The study was designed to compare two doses of epidural neostigmine co administered with lignocaine, with regard to its analgesic efficacy and its effect on sedation in postoperative period. Patients were divided into three groups of 30 each. Group I received lignocaine 1% (9ml) with normal saline (1ml), group II lignocaine1% (9ml) with neostigmine 100µg in saline (1ml) and group III received lignocaine 1% (9ml) with neostigmine 200µg in NS (1ml). Group I served as a control. In operating room, after putting epidural catheter, general anesthesia was administered with propofol (2mg kg(-1)), succinylcholine (2mg kg(-1)) and maintained with O2, N2O, relaxant technique. At the end of surgery, patients were reversed. Epidural analgesic medication was administered to after proper recovery from anesthesia. Intensity of pain relief on VAS, duration of analgesia, level of sensory block, motor blockade, sedation by sedation score and complications were assessed. RESULTS: The addition of neostigmine resulted in significant longer duration of analgesia (dose independent) and sedation (dose dependent). Sensory and motor blockade were identical in all three groups. There was no incidence of respiratory depression, pruritus, bradycardia or hypotension in any group. Two patients in control group and one, receiving neostigmine (200µg), developed nausea/vomiting. CONCLUSION: Co administration of epidural neostigmine and lignocaine appears to be a useful technique for postoperative analgesia as it increases the duration of analgesia and provides desirable sedation at the same time.

Thoracic epidural for post-thoracotomy pain: a comparison of three concentrations of sufentanil in bupivacaine

ABSTRACT. Background:The aim of this prospective, double blind, randomised trial was to compare the analgesic and adverse effectsof three concentrations of the thoracic epidural sufentanil with bupivacaine in patients undergoing thoracotomy.Methods:We studied 60 (randomised) patients who were to receive a 10 ml bolus dose of sufentanil, 1µg/ml, 2 µg/ml and3 µg/ml, in bupivacaine 0.125%, via thoracic epidural. Postoperatively, pain at rest, on coughing and with ambulation wasassessed using a visual analogue scale (VAS) and observer verbal ranking score (OVRS) at 2, 6, 12 and 24 hours. Adverseeffects were simultaneously assessed.Results:There was no significant difference in the baseline characteristics between the three groups. The number of patientswith episodes of unsatisfactory pain, i.e. a VAS scores ≥ 40 and OVRS ≥ 2, at each of the four assessments postoperatively,was significantly higher with sufentanil 1 g/ml than with sufentanil 2 µg/ml or µ3 g/ml (p < 0.05). In the 3 µg/ml sufentanilgroup, four patients (20%) had a sedation score ≥ 3 compared with one (5%) and no (0%) patients in the 2 µg/ml and1 µg/ml sufentanil groups, respectively (p < 0.05). In addition, 30% patients experienced pruritus in the 3 µg/ml sufentanilgroup compared with 10% and 5%, respectively, in the 2 µg/ml and 1 µg/ml sufentanil groups. In the sufentanil 3 µg/ml,2 µg/ml and 1 µg/ml groups, 30%, 20% and 5% patients, respectively, had emetics symptoms (p < 0.05).Conclusions:We conclude that a thoracic epidural bolus of 10 ml sufentanil 2 µg/ml with bupivacaine 0.125% provides theoptimal balance between pain relief and side-effects following thoracotomy

Darwin and the survival of the fittest in modern interventional cardiology.

The diabetic patient requires a full armamentarium of proven and developing treatments in order to minimise periprocedural risk as well as improve long term outcome.

MRL/lpr lupus-prone mice show exaggerated ICAM-1-dependent leucocyte adhesion and transendothelial migration in response to TNF-alpha.

OBJECTIVE: Endothelial activation and dysfunctional leucocyte-endothelial interactions are thought to play key roles in the pathogenesis of systemic lupus erythematosus (SLE). The object of this study was to investigate directly the effect of increased endothelial adhesion molecule expression on leucocyte-endothelial cell interactions, using the MRL/lpr mouse model. METHODS: Leucocyte rolling, arrest and transendothelial migration were quantified in the cremaster muscle microcirculation of 20-week-old MRL/lpr mice, using intravital microscopy. Endothelial adhesion molecule expression was quantified using intravenously injected radiolabelled monoclonal antibodies. RESULTS: Basal expression of intercellular adhesion molecule 1 (ICAM-1) by cremaster endothelium was 2-fold greater in MRL/lpr than in MRL/++ mice (P<0.05). There was a 1.6-fold increase in expression of vascular adhesion molecule 1 (VCAM-1), but no increase in E-selectin or P-selectin expression. Following intrascrotal injection of saline, no difference was detected in leucocyte-endothelial interactions between MRL/lpr and control MRL/++ mice. In contrast, intrascrotal injection of tumour necrosis factor alpha (TNF-alpha) (2 h test period) led to significantly increased numbers of adherent and extravasated leucocytes in MRL/lpr (5.98+/-0.71 and 5.45+/-0.34 leucocytes per 100 micro m vessel segment respectively) compared with MRL/++ mice (3.63+/-0.26 and 2.97+/-0.24 respectively, each P<0.05). Treatment of TNF-alpha-stimulated mice with anti-ICAM-1 F(ab')2 (YN1) abolished the difference between MRL/lpr and MRL/++ mice, whereas a negative control anti-DNP F(ab')2 had no effect. CONCLUSIONS: MRL/lpr lupus-prone mice show exaggerated ICAM-1-dependent leucocyte-endothelial interactions in response to TNF-alpha. Increased leucocyte-endothelial interactions due to endothelial priming could contribute to the clinical link between infection and flares of lupus disease activity.

Cost effectiveness of ramipril treatment for cardiovascular risk reduction.

OBJECTIVE: To assess the cost effectiveness of ramipril treatment in patients at low, medium, and high risk of cardiovascular death. DESIGN: Population based cost effectiveness analysis from the perspective of the health care provider in the UK. Effectiveness was modelled using data from the HOPE (heart outcome prevention evaluation) trial. The life table method was used to predict mortality in a medium risk cohort, as in the HOPE trial (2.44% annual mortality), and in low and high risk groups (1% and 4.5% annual mortality, respectively). SETTING: UK population using 1998 government actuary department data. MAIN OUTCOME MEASURE: Cost per life year gained at five years and lifetime treatment with ramipril. RESULTS: Cost effectiveness was pound36 600, pound13 600, and pound4000 per life year gained at five years and pound5300, pound1900, and pound100 per life year gained at 20 years (lifetime treatment) in low, medium, and high risk groups, respectively. Cost effectiveness at 20 years remained well below that of haemodialysis ( pound25 000 per life year gained) over a range of potential drug costs and savings. Treatment of the HOPE population would cost the UK National Health Service (NHS) an additional pound360 million but would prevent 12 000 deaths per annum. CONCLUSIONS: Ramipril is cost effective treatment for cardiovascular risk reduction in patients at medium, high, and low pretreatment risk, with a cost effectiveness comparable with the use of statins. Implementation of ramipril treatment in a medium risk population would result in a major reduction in cardiovascular deaths but would increase annual NHS spending by pound360 million.

Epilepsy in children with cerebral palsy.

This article deals with the clinical profile of children with cerebral palsy and epilepsy, and to study the clinical predictors of response to anti-epileptic drugs. It is a prospective hospital based follow-up study. All the children who presented with cerebral palsy and history of seizure (other than neonatal seizures) over a period of one year were included. Seizures were classified according to ILAE classification. An EEG was obtained in all cases. Neuroimaging was done in all patients. Eighty-five patients were studied and followed for minimum of 12 months. Perinatal factors accounted for 62 (72.3%) cases. The motor deficits seen were quadriparesis (n = 64), hemiplegia (n = 12) and diplegia (n = 9). Associated mental retardation was seen in 80.9% patients with quadriparesis. A predominance of generalised epilepsy was seen with generalised tonic clonic seizures (32.9%) followed by mycolonic seizures (30.6%) and localisation related epilepsy (24.7%). The patients with quadriparesis were more likely to have generalised epilepsy and 52.4% of them required two or more anti-epileptic drugs for control of seizures. Patients with hemiplegia had localisation related epilepsy in 83.3% of cases. On multivariate analysis presence of quadriparesis, microcephaly, mental retardation and myoclonic epilepsy were found to predict the poor response to AED. Epilepsy in patients with cerebral palsy is of severe nature and difficult to control. Presence of quadriparesis, mental retardation and myoclonic seizures was predictive of poor response to anti- epileptic drugs.

Crystal-storing histiocytosis: a disorder occurring in plasmacytic tumors expressing immunoglobulin kappa light chain.

Intracellular immunoglobulin crystal formation within plasma cells is an uncommon finding in multiple myeloma and other lymphoplasmacytic tumors. We present 12 cases of plasmacytic tumors with prominent crystal formation, including myeloma (5 cases), lymphoplasmacytic lymphoma (6 cases), and a nonneoplastic plasma cell proliferation. In all cases, crystal formation was associated with the proliferation of variable numbers of histiocytes containing similar inclusions. These cases showed a variety of appearances, sometimes obscuring the underlying plasma cell tumor and raising the differential diagnosis of a storage disorder, hemophagocytosis, or a mesenchymal lesion. In cases of lymphoplasmacytic lymphoma, patients typically presented with marked paraproteinemia and symptoms of hyperviscosity. Crystal-storing histiocytosis was not associated with other immunoglobulin deposition disorders, including amyloidosis, Mott cell tumors, or kappa-light chain deposition. In our cases and those previously reported, we found an overwhelming association of crystal-storing histiocytosis (CSH) with tumors expressing immunoglobulin kappa light chain with no consistent association with a particular heavy chain. These results suggest that CSH results from the ingestion of crystals produced by plasma cell tumors that either overproduce kappa light chain or express a structurally aberrant molecule. CSH persists in the marrow and other sites throughout the course of the disease and in our series was not highly associated with development of the adult Fanconi syndrome or rapid clinical deterioration.

Evaluation of the "monolog" spike and wave monitor: a study on patients with typical absences.

The aim of this study was to evaluate the effectiveness and accuracy of the "monolog," a pocket-size spike and wave monitor, in patients with typical absence seizures. Two observers were scoring independently and blindly from the monitor the number and duration of the 3 Hz spike-wave discharges from the EEG recordings of 10 selected patients having typical absences. High correlation was found between the two observers' scorings for both the number and the mean duration of events (Spearman's rank correlation (r): 0.9970, P < 0.001, and 0.9758, P < 0.001), as well as between each of them and the "monolog" for the mean event duration (r: 0.9848, P < 0.001, and 0.9788, P < 0.001). Conversely, a poor correlation was found between each of the observers and the "monolog" for the number of events (r: 0.7121, P = 0.021, and 0.6939, P = 0.026). In conclusion, the "monolog" accurately measured the duration of 3 Hz spike-wave activity; however, it failed to accurately count the number of events that occurred throughout the recordings. We suggest that this device, with appropriate modification to its memory epochs, may be a useful tool in monitoring patients with typical absences.

Clinical evaluation of chandonium iodide as a nondepolarising muscle relaxant.

The effect of chandonium iodide (as a non-depolarising muscle relaxant) was studied in 50 patients of ASA grade I or II who were scheduled for surgery. The patients were divided into 2 groups according to the dose of chandonium iodide (0.2 and 0.25 mg/kg respectively). The onset and duration of action was found to be dose dependent. Intubation characteristics were good to fair in all the patients, the reaction to intubation being either absent or mild. There was mild and transient rise in pulse and blood pressure. No allergic reaction was observed in any patient and reversal characteristics were good in all the cases.