Intraoperative evaluation of the resected bone margin in mandibular cancers using a trephine drill and frozen section analysis.

The objective of this study was to evaluate the accuracy and feasibility of intraoperative frozen section analysis of samples harvested with a trephine drill from the bone resection margins to identify malignancy. Thirty-five patients who were diagnosed with locally advanced oral squamous cell carcinoma involving the mandible were included in this study. After tumour resection, bone samples were collected from the resection margin of the specimen using a trephine drill. Sampling yielded a cylindrical specimen of bony tissue that included both cortical and cancellous areas. A second sample was obtained from the area where bone invasion was evident; this was used as a positive control. Frozen section analysis was performed intraoperatively to check for malignancy. The sensitivity of this technique was found to be 81.8%, with specificity of 87.5%, a positive predictive value of 75%, negative predictive value of 91.3%, and accuracy of 85.7% when compared to standard histopathology as the gold standard. In conclusion, the evaluation of bone margins using the trephine drill technique and frozen section analysis proved to be fast and reliable.

Functional Outcome of Open Latarjet Procedure in Non-Athletic Middle-Aged Patients.

INTRODUCTION: The movement and steadiness of the shoulder joint is due to both the dynamic and static stabilisers. Recurrent anterior shoulder instability is common due to the Bankart lesion or the Hill Sachs lesion. The bone loss and soft tissue failure due to these lesions causing instability is well compensated by Latarjet procedure which acts by triple blocking effect of the bone graft, the sling effect of the conjoint tendon of subscapularis and the ligament of the coracoacromial ligament stump. MATERIALS AND METHODS: Middle-aged patients with recurrent anterior shoulder dislocation and a mid-range instability on clinical assessment with an isolated glenoid bone loss of 20% or Bankart lesion with engaging Hill Sachs lesion were selected for the study. The surgical procedure included a subscapularis split to expose the glenoid. The coracoid graft harvested was prefixed with Kirschner wires and placed flush over the glenoid ensuring no medial or lateral overhang and fixed with 4.0mm cancellous screws with the washer. The functional outcome was measured with the ROWE score and ASES score and the movements were evaluated. RESULTS: A total of 24 patients fulfilled the inclusion criteria. Post-operatively at final follow-up, the mean ROWE score was 97.08 ±8.45 and the mean ASES score was 94.4±9.10. One patient had screw breakage as a complication and another had restriction of movement which was managed with physiotherapy. CONCLUSION: Open Latarjet is an effective procedure for recurrent anterior shoulder instability in non-athletic middle-aged patients as a excellent functional outcome was achieved with this technique. We therefore recommend open Latarjet as an alternative to arthroscopic treatment in developing countries where patient affordability and the availability of the resources are the issues.

Cemento-ossifying Fibroma of Mandible: A Case Report with Review of Literature

ABSTRACT Cemento-osseous dysplasia (COD) is a non-neoplastic process usually confined to the tooth-bearing areas of the jaws or edentulous alveolar processes. It is mostly seen in women during the third and fourth decades of life. The mandible is the most common location in 70% of cases in the premolar-molar region. This case report presents a case of cemento-ossifying fibroma with clinical features and radiographic features in a 23-year-old female patient.

Coffee straw can replace Hader bar for bar retained overdentures--a clinical report.

Bar attachment system provides retention and support for the overdenture. Retention of a mandibular denture can be achieved by an implant-retained or natural tooth-retained bar and stud attachment in the anterior segment of the mandible. A simple and cost effective treatment for more complex implant overdenture is the concept of conventional tooth-retained overdentures. The authors present a clinical report of a patient treated with a mandibular tooth-borne overdenture with a bar. The bar was fabricated using a coffee straw.

Chronic exposure of neural cells to elevated intracellular sodium decreases mitochondrial mRNA expression.

Regulation of expression of mitochondrial DNA- (mtDNA-) encoded genes of oxidative phosphorylation can occur rapidly in neural cells subjected to a variety of physiological and pathological conditions. However, the intracellular signal(s) involved in regulating these processes remain unknown. Using mtDNA-encoded cytochrome oxidase subunit III (COX III), we show that its mRNA expression in a differentiated rat pheochromocytoma cell line PC12S is decreased by chronic exposure to agents that increase intracellular sodium. Treatment of differentiated PC12S cells either with ouabain, an inhibitor of Na/K-ATPase, or with monensin, a sodium ionophore, decreased the steady-state levels of COX III mRNA by 50%, 3-4 h after addition of the drugs. No significant reduction in mtDNA-encoded 12S rRNA or nuclear DNA-encoded beta-actin mRNA were observed. Removal of the drugs restored the normal levels of COX III mRNA. Determination of half-lives of COX III mRNA, 12S rRNA, and beta-actin mRNA revealed a selective decrease in the half-life of COX III mRNA from 3.3 h in control cells to 1.6 h in ouabain-treated cells, and to 1 h in monensin-treated cells. These results suggest the existence of a mechanism of posttranscriptional regulation of mitochondrial gene expression that is independent of the energetic status of the cell and may operate under pathological conditions.

Time course of pharmacodynamic and pharmacokinetic effects of physostigmine assessed by functional brain imaging in humans.

In imaging studies of brain functions using pharmacological probes, identification of the time point at which central effects of intravenously infused drugs become stable is crucial to separate the effects of experimental variables from the concomitant changes in drug effects over time. We evaluated the time courses of the pharmacokinetics and pharmacodynamics, including butyrylcholinesterase inhibition and central neural responses, of physostigmine in healthy young subjects. Ten positron emission tomography (PET) scans that alternated between a rest condition (eyes open, ears unplugged) and a working memory for faces (WM) task were acquired in healthy subjects. Subjects in the drug group received a saline infusion for the first two scans, providing a baseline measure, then received an infusion of physostigmine for all subsequent scans. Subjects in the control group received a placebo infusion of saline for all scans. Physostigmine plasma levels and percent butyrylcholinesterase inhibition increased over time (p < 0. 0001), and both became stable by 40 min. Physostigmine decreased reaction time (RT) (p = 0.0005), and this effect was detected after 20 min of infusion and stable thereafter. Physostigmine also decreased regional cerebral blood flow (rCBF) in right prefrontal cortex during task (p = 0.0002), and this effect was detected after 40 min of infusion and stable thereafter. No change in RT or rCBF was observed in the control group. These results indicate that a 40-min infusion of physostigmine was necessary to obtain stable central effects. More generally, we have demonstrated that experimental effects can vary with time, especially during the initial phases of a drug infusion, indicating that it is critical that these changes are controlled.

Regulation of low density lipoprotein receptor mRNA levels by estradiol 17beta and chorionic gonadotropin in human placenta.

Inhibition of synthesis of estradiol 17beta by the addition of inhibitors of aromatase, a key enzyme in the biosynthesis of estradiol 17beta, or addition of tamoxifen - an estrogen receptor antagonist, to human placental minces resulted in an increase in the level of LDL-receptor mRNA. This increase could be blocked by the simultaneous addition of estradiol 17beta. A concentration dependent effect of estradiol 17beta on the level of LDL-receptor mRNA was seen both in first trimester, and term placenta. Addition of human chorionic gonadotropin (hCG) to term placental minces also increased the LDL-receptor mRNA levels. When hCG and cycloheximide were added together, an additive effect was observed. The results obtained in this study suggest that the LDL-receptor mRNA levels in the human placenta are regulated by estradiol 17beta and hCG.

Cholinergic stimulation alters performance and task-specific regional cerebral blood flow during working memory.

Modulation of the cholinergic neurotransmitter system results in changes in memory performance, including working memory (WM), in animals and in patients with Alzheimer disease. To identify associated changes in the functional brain response, we studied performance measures and regional cerebral blood flow (rCBF) using positron emission tomography (PET) in healthy subjects during performance of a WM task. Eight control subjects received an infusion of saline throughout the study and 13 experimental subjects received a saline infusion for the first 2 scans followed by a continuous infusion of physostigmine, an acetylcholinesterase inhibitor, for the subsequent 8 scans. rCBF was measured using H215O and PET in a sequence of 10 PET scans that alternated between rest and task scans. During task scans, subjects performed the WM task for faces. Physostigmine both improved WM efficiency, as indicated by faster reaction times, and reduced WM task-related activity in anterior and posterior regions of right midfrontal gyrus, a region shown previously to be associated with WM. Furthermore, the magnitudes of physostigmine-induced change in reaction time and right midfrontal rCBF correlated. These results suggest that enhancement of cholinergic function can improve processing efficiency and thus reduce the effort required to perform a WM task, and that activation of right prefrontal cortex is associated with task effort.

Regulation of expression of the CYP11A (P450scc) gene in bovine ovarian luteal cells by forskolin and phorbol esters.

This study examines the transcriptional regulation of the bovine CYP11A (P450scc) gene by activators of protein kinase A and protein kinase C in bovine ovarian luteal cells. Cells were transfected with reporter gene constructs containing deletion mutations of the 5'-flanking region of the bovine CYP11A gene linked to the minimal beta-globin gene. A construct containing -118/-101 base pairs of CYP11A sequence retains the same degree of stimulation by forskolin and inhibition by co-treatment with phorbol 12-myristate 13-acetate as larger constructs. This sequence contains two putative binding sites for nuclear proteins, an AP1-like sequence and an overlapping GA box element. Gel shift analysis using nuclear extracts of bovine ovarian luteal cells demonstrated that both the wild-type -118/-101-base pair sequence and a consensus GC box bound Sp1 or Sp1-like proteins. Mutation of the GA box element completely suppressed stimulation by forskolin. Absence of binding using the same mutated sequence correlated with the reporter gene transcription results. Mutation of the AP1-like site had little effect on forskolin induction of phorbol 12-myristate 13-acetate inhibition. These results indicate that both stimulation by forskolin and inhibition by phorbol esters are mediated by the same GA box element, which binds Sp1 or an Sp1-like protein.

Development of lipophilic anticancer agents for the treatment of brain tumors by the esterification of water-soluble chlorambucil.

The lipophilic derivatives of the anticancer alkylating agent chlorambucil, chlorambucil-methyl, -isopropyl and -tertiary butyl esters, were synthesized and administered i.v. to anesthetized rats. Plasma and brain concentrations of these agents and of their active metabolites, chlorambucil and phenylacetic mustard, then were determined by high-performance liquid chromatography between 5 and 60 min. Whereas large amounts of chlorambucil-tertiary butyl ester entered and were maintained in brain, lower amounts of chlorambucil-isopropyl ester and no chlorambucil-methyl ester were found in brain. The comparative brain/plasma concentration-time integral ratios of the total active agents generated from chlorambucil-tertiary butyl, -isopropyl and -methyl esters were 0.85, 0.12 and 0.06, respectively, compared to a ratio of 0.02 for chlorambucil. In vitro alkylating activity of each ester was compared to that of equimolar chlorambucil, by reaction with 4-(p-nitrobenzyl)pyridine. Each ester possessed high intrinsic alkylating activity, equal to 38.4, 57.0 and 69.9% of chlorambucil activity, for the -tertiary butyl, -isopropyl and -methyl esters, respectively. Therefore each is an active antineoplastic agent irrespective of whether or not chlorambucil is regenerated. The rates of ester hydrolysis of these derivatives to chlorambucil were measured in fresh rat blood and in liver and brain homogenates at 37 degrees C. Chlorambucil-methyl and -isopropyl esters were hydrolysed quickly within 30 s in blood and liver, whereas chlorambucil-tertiary butyl ester was more stable with half-lives of approximately 7 h and 2 h, respectively. All proved to be relatively stable in brain homogenate. Steric hindrance around the ester linkage of chlorambucil-tertiary butyl ester reduces its affinity to and rate of hydrolysis by plasma and liver esterases, and allows it to accumulate within the brain. Chlorambucil-tertiary butyl ester maintains high levels in brain despite rapidly declining plasma concentrations and, due to these favorable pharmacokinetics and to its intrinsic anticancer activity, it possess promising characteristics for the treatment of malignant brain tumors.

Electrocardiographic abnormalities in cerebrovascular accidents.

The electrocardiographic abnormalities found in 100 patients with acute cerebrovascular disease and previously normal hearts are described. The abnormalities were more often seen in patients with intracerebral and subarachnoid hemorrhages. The most common changes were Q-Tc Prolongation and ST segment and T wave abnormalities. The mechanisms of these electrocardiographic abnormalities appear to be multiple.

Brain and plasma pharmacokinetics and anticancer activities of cyclophosphamide and phosphoramide mustard in the rat.

By a sensitive and quantitative fluorometric assay, brain and plasma time-dependent concentration profiles were generated for phosphoramide mustard (PM) and active alkylating metabolites derived from cyclophosphamide (CPA) administration to rats. Whereas PM rapidly disappeared from plasma, with a monophasic half-life of 15.1 min, equimolar administration of CPA generated active metabolites in plasma that disappeared monoexponentially, with a composite half-life of 63 min. As a consequence, the time-dependent concentration integral of active alkylating metabolites derived from CPA administration, calculated between 5 min and infinity, was 3-fold that of PM. Pharmacokinetic parameters were calculated for each compound. The brain/plasma concentration-integral ratios of PM and active alkylating metabolites derived from CPA were 0.18 and 0.20, respectively. The cerebrovascular permeability-surface area product of PM was 7.5 x 10(-5) s-1, which is similar to that of other water-soluble anticancer agents that are restricted from entering the brain. The activities of a range of daily doses of PM and CPA were assessed against subcutaneous and intracerebral implants of Walker 256 carcinosarcoma tumor in rats. Inhibition of subcutaneous tumor growth by 50% was caused by CPA and PM doses of 6.6 and 12.0 mg/kg (daily for 5 consecutive days, starting 36 h after tumor implantation), respectively. However, administration of daily doses of up to 40 mg/kg did not significantly increase the survival of animals with intracerebral tumor implants. These studies indicate that active metabolites of CPA are restricted from entering the brain and that only subtherapeutic concentrations are achieved in brain tissue after systemic administration of CPA or PM.