Preemptive analgesia for postoperative pain relief in lumbosacral spine surgeries: a randomized controlled trial.

BACKGROUND CONTEXT: Administration of analgesic medication, before the actual onset of painful stimulus, is more effective than that after the onset of painful stimulus. This is the principle of preemptive analgesia. Although it is often considered superior to other forms of analgesia, its role in postoperative pain relief after lumbosacral spinal surgery has not been fully investigated. PURPOSE: To analyze the efficacy of preemptive analgesia with a single caudal epidural injection for patients undergoing surgeries on the lumbosacral spine by the posterior approach. STUDY DESIGN/SETTING: Randomized, double-blinded and controlled clinical trial. PATIENT SAMPLE: Eighty-two patients who underwent discectomy in the lumbosacral spine by the posterior approach, with or without instrumentation, were randomized to the control group (n=40) and to the study group (n=42). METHODS: Patients in control group received a single caudal epidural injection of 20 ml of normal saline. Patients in study group received a single caudal epidural injection of 20 ml containing bupivacaine and tramadol as the active agents. The time interval between this injection and the surgical incision was never less than 20 minutes in either of the groups. This facilitated enough time for the drug to get fixed to the nerve roots, leading to effective preemptive analgesia. OUTCOME MEASURES: Patients were monitored for postoperative pain immediately after surgery when they had completely recovered and regained consciousness from general anesthesia, and subsequently 4, 8, 12 and 24 hours thereafter. Pain was quantified using the visual analog scale (VAS) and the verbal rating scale (VRS). The time at which supplemental analgesic medication was first demanded in the postoperative period by the patient was also noted. RESULTS: The two groups were comparable for age, sex, body weight and the type of surgery they underwent. Because the data did not have a normal Gaussian distribution, the one-tailed Mann-Whitney test, being a nonparametric test, was adopted for statistical analysis. Accordingly, VAS and VRS values at all time intervals were significantly lower (p<.0001) in the study group as compared with the control group. This indicated significantly better pain relief in the study group. There was also a significant delay (p=.0041) in the first demand for supplemental analgesic medication in the postoperative period in the study group. No complication specific to the procedure was noted except for the development of postoperative urinary retention, which was transient and appropriately managed with urinary catheterization. CONCLUSIONS: Preemptive analgesia with a single caudal epidural injection of bupivacaine and tramadol is a safe, simple and effective method for postoperative pain relief.     

Comparison of hepatitis C viral loads in patients with or without coinfection with different genotypes

Hepatitis C virus genotyping was assessed for 257 chronic hepatitis C patients with viral loads above 1,000 IU/ml. Twelve patients were coinfected with more than one genotype. Their median viral loads did not differ significantly from those observed for monoinfected patients, which in turn did not vary significantly among different genotypes.     

Fixation of subcondylar fractures of the mandible: a randomized clinical trial comparing one trapezoidal plate with two miniplates

Subcondylar fracture of the mandible accounts for 25–35% of all mandibular fractures. In the past, most subcondylar fractures were managed non-surgically. The traditional method of fixation for subcondylar fractures uses two miniplates; however some bench studies have reported that trapezoidal plates are superior. The aim of this study was to compare the outcomes of subcondylar fractures fixed either with two non-parallel straight miniplates or with one trapezoidal plate. A randomized clinical trial was designed and implemented. Fifty-two consecutive patients with subcondylar fractures were recruited. All patients underwent surgery via a retromandibular approach. The time taken for fixation of the plate after fracture reduction and postoperative outcomes and complications were compared between the groups. The trapezoidal plates were superior in terms of ease of adaptation and time taken for fixation (P =  0.0001). Plate fracture was observed only in the two miniplates group, in four (16%) patients. Outcomes were similar in the two groups in terms of occlusion, mouth opening, protrusion, and lateral excursion. In conclusion, both systems – two miniplates and the trapezoidal plate – provide functionally stable fixation. The outcome was significantly better for the trapezoidal plate than for two miniplates regarding the time taken for insertion and ease of adaptation, but not for other parameters.     

Frequent Alterations of MCPH1 and ATM are Associated with Primary Breast Carcinoma: Clinical and Prognostic Implications

Background

MCPH1 is a proximal regulator of DNA damage response pathway that is involved in recruitment of phosphorylated ATM to double-stranded DNA breaks.

Methods

To understand the importance of MCPH1 and ATM in deregulation of DNA damage response pathway in breast carcinoma, we studied m-RNA expression and genetic/epigenetic alterations of these genes in primary breast carcinoma samples.

Results

Our study revealed reduced expression (mRNA/protein) and high alterations (deletion/methylation) (96 %, 121 of 126) of MCPH1 and ATM. Mutation was, however, rare in inactivation of MCPH1. In immunohistochemical analysis, reduced protein expression of MCPH1, ATM and p-ATM were concordant with their molecular alterations (P = 0.03–0.01). Alterations of MCPH1 and deletion of ATM were significantly high in estrogen/progesterone receptor–negative than estrogen/progesterone receptor–positive breast carcinoma samples compared to early or late age of onset tumors, indicating differences in pathogenesis of the molecular subtypes (P = 0.004–0.01). These genes also showed differential association with tumor stage, grade and lymph node status in different subtypes of breast carcinoma (P = 0.00001–0.01). Their coalterations showed significant association with tumor progression and prognosis (P = 0.003–0.05). Interestingly, patients with alterations of these genes or MCPH1 alone had poor outcome after treatment with DNA-interacting drugs and/or radiation (P = 0.01–0.05).

Conclusions

Inactivation of MCPH1-ATM-associated DNA damage response pathway might have an important role in the development of breast carcinoma with diagnostic, prognostic and therapeutic implications.

     

Radiological Evaluation of Cochlear Orientation and Its Implications in Cochlear Implantation

To test whether there are variations in cochlear orientation with respect to age and sex, and its relevance in cochlear implant surgery. Implant otologists rely upon the anatomic landmarks including the facial recess and round window niche and round window membrane for accessibility and placement of electrode array into scala tympani of basal turn of cochlea. Anecdotally, surgeons note variations in cochlear orientation with respect to age. Cochlear orientation studied radiologically by pre-operative CT scan of temporal bone can guide a Surgeon’s approach to cochlear implantation. To investigate the changes in cochlear orientation with respect to age and sex; and its relevance in cochlear implantation. A retrospective analytical study was performed on CT scans of temporal bones in patients (of our hospital from July 2013 to January 2015 i.e. for a period of 18 months) with no congenital or radiological abnormalities of cochlea. The basal turn angulations of cochlea varied with age and majority of change occurred during early age. The basal turn angulations of cochlea in difficult situations during cochlear implantation were correlated with the data. There is a significant variation in cochlear orientation as measured radiologically by basal turn angulations relative to midsagittal plane. The more obtuse and acute basal turn angulations have implications like difficulty in cochleostomy and electrode placement during cochlear implantation.     

Changes in sputum cytology,airway inflammation and oxidative stress due to chronic inhalation of biomass smoke during cooking in premenopausal rural Indian women

To perform sputum analysis for verification of pulmonary changes in premenopausal rural Indian women chronically exposed to biomass smoke during cooking.Three consecutive morning sputum samples were collected from 196 women (median age 34 years) cooking with biomass and 149 age-matched control women cooking with cleaner fuel liquefied petroleum gas. Smears made on slides were stained with Papanicolaou and Perl's Prussian blue. Airway oxidative stress was estimated as reactive oxygen species (ROS) generation (by flow cytometry) and superoxide dismutase (SOD) level (by spectrophotometry) in sputum cells. Airway inflammation was measured as sputum levels of interleukin (IL)-6, -8 and tumor necrosis factor- alpha (TNF-α). Particulate matter of diameter less than 10 (PM₁₀) was measured using laser photometer while benzene exposure was monitored by measuring trans, trans-muconic acid (t,t-MA) in urine by HPLC-UV. Compared with control, sputum of biomass users contained more neutrophils, lymphocytes, eosinophils, alveolar macrophages, and showed presence of ciliocytophthoria, Charcot-Leyden crystals, Curschmann's spiral. ROS generation was increased by 2-fold while SOD was depleted by 31% in biomass users. They also had higher sputum levels of IL-6, -8 and TNF-α. Levels of PM₁₀ and t,t-MA were 2.9- and 5.8-times higher in biomass-using women. PM₁₀ and t,t-MA levels were positively associated with cellular changes in the sputum, markers of airway inflammation, and oxidative stress. Cooking with biomass alters sputum cytology, and increases airway inflammation and oxidative stress that might result in further amplification of the tissue damaging cascade in women chronically exposed to biomass smoke.     

Safety and Biocompatibility of Carbohydrate-Functionalized Polyanhydride Nanoparticles

Carbohydrate functionalization of nanoparticles allows for targeting of C-type lectin receptors. This family of pattern recognition receptors expressed on innate immune cells, such as macrophages and dendritic cells, can be used to modulate immune responses. In this work, the in vivo safety profile of carbohydrate-functionalized polyanhydride nanoparticles was analyzed following parenteral and intranasal administration in mice. Polyanhydride nanoparticles based on 1,6-bis-(p-carboxyphenoxy)hexane and 1,8-bis-(p-carboxyphenoxy)-3,6-dioxaoctane were used. Nanoparticle functionalization with di-mannose (specifically carboxymethyl-α-d-mannopyranosyl-(1,2)-d-mannopyranoside), galactose (specifically carboxymethyl-β-galactoside), or glycolic acid induced no adverse effects after administration based on histopathological evaluation of liver, kidneys, and lungs. Regardless of the polymer formulation, there was no evidence of hepatic or renal damage or dysfunction observed in serum or urine samples. The histological profile of cellular infiltration and the cellular distribution and kinetics in the lungs of mice administered with nanoparticle treatments followed similar behavior as that observed in the lungs of animals administered with saline. Cytokine and chemokine profiles in bronchoalveolar lavage fluid indicated surface chemistry dependence on modest secretion of IL-6, IP-10, and MCP-1; however, there was no evidence of any deleterious histopathological changes. Based on these analyses, carbohydrate-functionalized nanoparticles are safe for in vivo applications. These results provide foundational information towards the evaluation of the capabilities of these surface-modified nanoparticles as vaccine delivery formulations.KEY WORDS: biocompatibility, carbohydrate, nanoparticles, polyanhydride, safety     

Global structure and mechanical properties of a 10-bp nucleosome positioning motif

The method of DNA cyclization kinetics reveals special properties of the TATAAACGCC sequence motif found in DNA sequences that have high affinity for core histones. Replacement of 30 bp of generic DNA by three 10-bp repeats of the motif in small cyclization constructs increases cyclization rates by two orders of magnitude. We document a 13 degrees bend in the motif and characterize the direction of curvature. The bending force constant is smaller by nearly 2-fold and there is a 35% decrease in the twist modulus, relative to generic DNA. These features are the likely source of the high affinity for bending around core histones to form nucleosomes. Our results establish a protocol for determination of the ensemble-averaged global solution structure and mechanical properties of any approximately 10-bp DNA sequence element of interest, providing information complementary to that from NMR and crystallographic structural studies.