Ulnar Buttress Arthroplasty without Ulnar Stump Stabilization for Giant Cell Tumor of Distal Ulna.

Purpose Reconstruction and stabilization of ulnar stump after distal ulna tumor resection is still a matter of debate. We present the outcomes of ulnar buttress arthroplasty without stabilization of the ulna stump in giant cell tumor of bone (GCTB) of the distal ulna. Methods Evaluation of functional outcome was performed using Musculoskeletal Tumor Society 93 (MSTS93) score, Modified Mayo Wrist score (MMWS), and Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire. We also assessed the hand grip strength, range of motion at the wrist, and ulnar carpal translation. Results The study included 8 patients with Campanacci grade 3 GCTB of the distal ulna with a mean follow-up of 35.5 ± 9.1 months. The mean resection length was 7.7 ± 1.3 cm. The mean hand grip strength on the operated side was noted to be 90 ± 0.04% of the contralateral side. Mean MSTS93 score was 27.9 ± 1.25, mean MMWS was 86.9 ± 4.58%, and the mean DASH score was 4.9 ± 1.67, depicting a good to excellent functional outcome with low degree of disability. No radiocarpal instability, ulnar carpal translation, prominence, or instability of the proximal ulnar stump was noted in any patient. Conclusion Reconstruction of the distal radioulnar joint using iliac crest bone graft for ulnar buttress without stabilization of the ulnar stump after resection of the distal ulna is an effective reconstruction option with good functional outcome and preservation of good hand grip strength. Level of Evidence Level IV, Therapeutic study.

A Review on Alternative Methods to Experimental Animals in Biological Testing: Recent Advancement and Current Strategies.

With an increase in the progression of research and development in the medical field, the experimental use of animals for the efficacy and safety testing of pharmaceuticals is on rise. Every year, millions of animals are used for experimental testing during which these suffer from pain and are then eventually sacrificed. Besides bioethical issues, animal experimentation is associated with many disadvantages like high cost, the requirement of skilled manpower, approval, and is time-consuming. Therefore, attempts have been made by researchers to design and develop a number of alternative methods that could bypass animal experiments. These methods not only give accurate results but can also save lives of millions of animals annually. Research techniques, including computer and robotics together with molecular biology techniques, are applied to discover new methods to replace animal testing. Several alternative methods are discussed in this review. Some of these methods can predict the behavior of drugs accurately and are as reliable as in-vivo animal models. Furthermore, these alternative methods offer a variety of advantages over experimental animals. However, there is still a great need to discover and develop new, accurate, and reliable methods to replace experimental animals.

Development of a Citric-Acid-Modified Cellulose Adsorbent Derived from Moringa peregrina Leaf for Adsorptive Removal of Citalopram HBr in Aqueous Solutions.

A citric-acid-modified Moringa peregrina leaf substrate was prepared and studied as an effective adsorbent for the adsorptive removal of citalopram HBr (CTM). FTIR spectra were utilized to characterize the prepared solid. The effects of experimental variables on the percentage removal of citalopram HBr were investigated using response surface methodology. The optimum conditions selected for removal of CTM were 7 and 4 min, 0.17 g per 50 mL and 35 mg·L-1 for pH, contact time, adsorbent dose and initial concentration of CTM, respectively. Under the optimized experimental conditions, 82.59% CTM (35 mg·L-1) was removed. The Langmuir isotherm, Freundlich isotherm, pseudo second-order kinetic model and diffusion-chemisorption model explained the adsorption data successfully. The maximum adsorption capacity at 298 K was 8.58 mg·g-1. A thermodynamic study illustrated that CTM adsorption was spontaneous and endothermic in nature.

Leaving half the acetabulum in pelvic resections improves hip function. Is there a need to revisit conventional pelvic resections?

BACKGROUND: Conventional periacetabular pelvic resections are associated with poor functional outcomes. Resections through surgical corridors beyond the conventional margins may be helpful in retaining greater function without compromising the oncological margins. METHODS: The study included a retrospective review of 82 cases of pelvic resections for pelvic tumors. Outcomes of acetabulum preservation (Group A) were compared with complete acetabular resection (Group B). Also, we compared outcomes of Type I + half resections (Group 1) with Type I + II resections (Group 2), and Type III + half resections (Group 3) with Type II + III resections (Group 4). RESULTS: Group A (n = 44) had significantly better functional outcome than Group B (n = 38) with average MSTS93 score 22.3 versus 20.1 and average HHS 91.3 versus 82.5 (p < 0.001). Group 1 (n = 14) and Group 2 (n = 12) had similar functional outcomes (mean MSTS93 score 22.07 vs. 21.58 [p = 0.597] and mean HHS 90.37 vs. 86.51 [p = 0.205]). Group 3 (n = 11) had significantly better functional outcome than Group 4 (n = 17), with mean MSTS93 score 22.8 versus 19.7 (p < 0.001) and mean HHS 92.3 versus 80.1 (p < 0.001). Oncological outcomes were similar among the groups. CONCLUSION: Transacetabular pelvic resections provide functional benefit over conventional resections without compromising oncological margins. There is a need to revisit and revise the pelvic resection planes.

Surgical phocomelia or phoco-reduction as a method of limb salvage for sarcomas of the upper limb: A suitable alternative to amputation.

BACKGROUND: Reconstruction following resection of sarcomas of the upper extremity with methods described in the prevalent literature may not be possible in few selected cases. We describe surgical phocomelia or phoco-reduction as a method of limb salvage in such cases of extensive sarcomas of the upper limb with its functional and oncological outcomes. METHODS: Evaluation of functional and oncological outcomes was performed for 11 patients who underwent surgical phocomelia or phoco-reduction for extensive sarcomas of the upper limb between 2010 and 2019. RESULTS: The mean follow-up period in the study was 27.8 months. Five patients required a segmental resection including the entire humerus while six patients underwent segmental resection around the elbow with a mean resection length of 21.5 cm. Mean Musculoskeletal Tumor Society 93 score was 22 depicting a good functional outcome. Mean handgrip strength on the operated side was 62% of the contralateral side with preservation of useful hand function. Meantime to humeroulnar union was 6.7 months. Radial nerve palsy and implant failure occurred in one patient each. No patient developed local recurrence while three patients died of metastasis. CONCLUSION: Surgical phocomelia is a prudent alternative to severely incapacitating amputations in situations where other reconstruction methods are not feasible.

Combating COVID-19: The role of drug repurposing and medicinal plants.

BACKGROUND: A novel corona virus-2 disease has spread to 213 countries and territories across the globe. The corona pandemic has claimed more than 548,934 deaths worldwide till the evening of 8th of July 2020 and the number of confirmed cases is increasing at an alarming rate. Therefore, there is an urgent need to find a treatment or a vaccine for COVID-19 at the earliest. The aim of this mini-review is to give an overview of identified repurposed anti-COVID-19 drugs which are currently under clinical trials. METHODS: A thorough literature survey was done to retrieve relevant information using various web based search engines such as Google, Google scholar, and various other electronic research databases such as PubMed, Medline, MeSh etc. The findings of the recently published articles, clinical trials, COVID-19 update by World Health Organization etc., and the opinion of the authors is summarized in this brief review. The antiviral medicinal plants were identified based on their use in Chinese/Indian indigenous systems of medicine, traditional use, published scientific phytochemical studies and/or their effectiveness against upper respiratory infections, severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS). RESULTS: The disease is just over six months old and effective prophylactic or therapeutic agents are yet to be developed for COVID-19. Thus, in the absence of an effective therapy, scientific community has rationally considered the drug repurposing approach for the development of anti COVID-19 drugs. Various studies and clinical trials involving antimalarial drugs, anti-HIV drugs, anti-hepatitis drugs, anti-parasitic drug, anti-inflammatory drugs, the combination of antimalarial and macrolide antibiotic and few other molecules identified through drug repurposing are currently underway to combat COVID-19. Due emphasis is also given to develop novel corona vaccines for the prophylaxis and to identify drugs for adjunct/supportive therapy. Several medicinal plants along with their major phytochemicals exhibiting antiviral activity are identified for further exploration. It is anticipated that these natural products might also play an important role in combating COVID-19. CONCLUSIONS: Use of drug repurposing strategy to develop anti COVID-19 drugs and exploring antiviral medicinal plants as adjunct or supportive therapy appears to be a viable option. Therefore, it is the need of the hour to work in parallel on different strategies such as genetic engineering, in silico approach, herbal remedies and drug repositioning to achieve the common goal of finding a safe and effective treatment for COVID-19 at the earliest.

Recent Advances in the Development of Chemotherapeutic Agents for Malaria.

INTRODUCTION: Malaria, a devastating infectious parasitic disease, has been recognized by the World Health Organization (WHO) as a major public health problem worldwide. It is one of the leading causes of morbidity and mortality in developing countries. There are a number of antimalarial drugs available in the market to combat this deadly disease. The situation is further worsened due to the emergence of resistant strains of Plasmodium falciparum, which warrants the search for novel antimalarial drugs capable of acting at multiple targets to expand the current antimalarial drug arsenal for better therapeutic outcome. OBJECTIVES: This review aimed to provide the reader with the recent advances and progress made in the development of chemotherapeutic agents for malaria. METHODS: Literature review data on the chemistry and antimalarial activity of natural and synthetic heterocyclic compounds published in the last ten years were compiled by referring to various peerreviewed journal websites and medical search engines. RESULTS AND DISCUSSION: This review covers the recent advances and progress made in the treatment strategies, patent granted, synthetic approaches, mechanism of action with more emphasis on a Structure- activity Relationship (SAR) of potential chemotherapeutic agents as antimalarial agents which could pave the way for the development of more effective and potent antimalarial agents. This review might interest fellow researchers working on the development of novel antimalarial drug candidates with better therapeutic index. CONCLUSION: Based on the literature covered in the current review article and seeing the recent trends, authors are of the opinion that the multi-target conjugated hybrid approach is the best strategy to discover and develop effective antimalarial agents.

Design, synthesis, and biological evaluation of imidazopyridine-linked thiazolidinone as potential anticancer agents.

In this study, two series of imidazopyridine-linked thiazolidinone rings (5a-h and 6a-h) constituting 16 new compounds were synthesized and tested for their antiproliferative activity against a panel of three human cancer cell lines, that is, MCF-7 (human breast cancer), A549 (human lung cancer), and DU145 (human prostate cancer). Three compounds, 5h, 6f, and 6h, exhibited remarkable results against all three cell lines, but compound 6h was found to be the most active one against the breast cancer cell line. Among all the synthesized compounds, 6h displayed the highest antioxidant results. Furthermore, the potent compounds 5h, 6f, and 6h showed no signs of toxicity at doses ranging from 50 to 500 mg/kg of animal body weight. The biochemical parameters (SGOT and SGPT) of compound 6h nearly matched the control in hepatotoxicity studies. The molecular docking and MM-GBSADG binding studies are in agreement with the in vitro anticancer and antioxidant activity results. The most promising compound 6h was found to have the highest docking score and binding energy, and its absorption, distribution, metabolism, and excretion (ADME) parameters are in the acceptable range. Thus, it can be concluded that 6h, an imidazopyridine derivative endowed with a thiazolidinone ring system, has the potential to be developed as an anticancer agent.

Solid variant ABC of long tubular bones: A diagnostic conundrum for the radiologist.

Solid variant of aneurysmal bone cyst (sABC) is an extremely rare, reactive and non-neoplastic osseous lesion. On imaging it presents as a diaphyseal aggressive, eccentrically placed lytic and expansile lesion. However, differentiating this entity from the other possible malignant differentials is confounded by the histopathology mimicking several commoner lesions. We describe the distinctive MRI features of sABC of long bones from a series of four cases and briefly review the literature. We hope this review will educate all radiologists about this rare entity increasing their diagnostic confidence while formulating differentials for similar appearing lesions.

Synthesis, Computational Studies and Anticonvulsant Activity of Novel Benzothiazole Coupled Sulfonamide Derivatives.

We report herein the synthesis of ¾ substituted benzene sulfonamides linked via phenyl ring to a benzothiazole moiety. The title compounds in the two series namely N-(4-(benzothiazole-2-yl) phenyl) 4- substituted benzene sulfonamides and N-(4-(benzothiazole-2-yl) phenyl) 3- substituted benzene sulfonamides were synthesized by condensing 2-(3/4-aminophenyl) benzothiazole with various substituted sulfonyl chlorides. The synthesized compounds were subjected to neurotoxicity screening, computational studies, and evaluation of their anticonvulsant potential. Amongst all the synthesized compounds, compound 9 emerged as the most potent anticonvulsant agent in maximal electroshock (MES) model (standard: phenytoin) in mice and showed three hydrogen bond interactions with the nicotinic acetylcholine ion gated receptors (PDB ID: 2BG9). Interestingly, compound 13 showed five hydrogen bond interactions with the target protein and thus excellent binding affinity upon computational analysis but was found to be neurotoxic.

A comprehensive review on Brigatinib - A wonder drug for targeted cancer therapy in non-small cell lung cancer.

The mortality rate in patients suffering from non-small cell lung cancer (NSCLC) is quite high. This type of cancer mainly occurs due to rearrangements in the anaplastic lymphoma kinase (ALK) gene which leads to form an oncogene of fused gene NPM-ALK. Brigatinib is recently approved by FDA in April 2017 as a potent tyrosine kinase inhibitor (TKI) for the NSCLC therapy. In the present scenario, it is no less than a wonder drug because it is indicated for the treatment of advanced stages of metastatic ALK positive NSCLC, a fatal disease to overcome the resistance of various other ALK inhibitors such as crizotinib, ceritinib and alectinib. In addition to ALK, it is also active against multiple types of kinases such as ROS1, Insulin like growth factor-1Receptor and EGFR. It can be synthesized by using N-[2-methoxy-4-[4-(dimethylamino) piperidin-1-yl] aniline] guanidine and 2,4,5-trichloropyrimidine respectively in two different ways. Its structure consists of mainly dimethylphosphine oxide group which is responsible for its pharmacological activity. It is active against various cell lines such as HCC78, H2228, H23, H358, H838, U937, HepG2 and Karpas- 299. Results of ALTA (ALK in Lung Cancer Trial of AP26113) phase ½ trial shows that 90 mg of brigatinib for 7 days and then 180 mg for next days is effective in the treatment of NSCLC. Brigatinib has been shown to have favorable risk benefit profile and is a safer drug than the available cytotoxic chemotherapeutic agents. In comparison to other FDA approved drugs for the same condition, it causes fewer minor adverse reactions which can be easily managed either by changing the dose or by providing good supportive care. This article is intended to provide readers with an overview of chemistry, pharmacokinetic, pharmacodynamic and safety profile of brigatinib, which addresses an unmet medical need.

Chemical composition and in-vitro antioxidant and antimicrobial activity of the essential oil of Citrus aurantifolia L. leaves grown in Eastern Oman.

OBJECTIVES: This study investigated the chemical composition and the antioxidant and antimicrobial activities of the essential oil isolated from the aerial parts of Citrus aurantifolia L. METHODS: Fresh Citrus aurantifolia L. leaves were collected from farms in Sur city, located in the Al-Sharqia (Eastern) region of the Sultanate of Oman, during June-July of 2015. The essential oil was isolated using hydrodistillation. Gas chromatography-mass spectrometry (GC-MS) was used to identify and quantify the chemical constituents of the oil. An in-vitro 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging method was used to determine the antioxidant activity of the isolated oil from the lime leaves while a disc diffusion method was used to evaluate the antibacterial activity against Gram-negative and Gram-positive bacteria. RESULTS: Thirty-three chemical compounds were identified, with d-limonene (63.35%) forming the major constituent. Other prominent constituents include 3,7-dimethyl-2,6-octadien-1-ol (7.07%), geraniol (6.23%), E-citral (4.35%), Z-citral (3.29%), and ß-ocimene (2.25%). The essential oil of Citrus aurantifolia L. leaves showed excellent antibacterial activity against Staphylococcus aureus and moderate activity against pathogenic Escherichia coli strains. The oil exhibited promising in-vitro antioxidant activity (IC50 value = 21.57 µg/mL) but showed moderate antibacterial activities. CONCLUSIONS: The essential oil from Omani lime leaves is characterized by a high d-limonene content, making it useful for food, pharmaceutical, and perfumery industries.

CT-guided percutaneous radiofrequency ablation of osteoid osteoma: Our experience in 87 patients.

PURPOSE: To evaluate the technical and clinical success of radiofrequency ablation of osteoid osteoma and analyze the factors responsible for clinical success. We also tried to investigate the role of follow-up computed tomography (CT) imaging. MATERIALS AND METHODS: This is a prospective study approved by the institute's ethics committee involving 87 patients with appendicular osteoid osteoma. CT-guided radio frequency ablation was performed using a bipolar ablation system. Patients were followed up over 15.4 (4-24) months for pain, and clinical success/failure was determined using established criteria. Patients with clinical failure were taken for repeat ablation. Follow-up CT was obtained at 6 months and correlated with clinical success. Procedural scans were later reviewed for technical success in a blinded manner and correlated with clinical success along with other imaging and patient characteristics. RESULTS: Mean pre-procedure visual analog scale (VAS) score was 7.0 ± 0.8. Primary success rate after single session was 86.2%(75/87 patients), and overall success rate after one/two sessions was 96.6%(84/87). No major complications were noted. Technical success rate was 89.7%(78/87). All 9 patients who had a suboptimal needle positioning had recurrence where as three patients had recurrence despite technical success. None of the imaging characteristics or history of prior intervention was significantly associated with clinical success. Follow-up CT showed advanced bone healing in 48 lesions, and was confined to the treatment success group. Alternately, minimal/absent bone healing was seen in all (12) patients of primary treatment failure and 27 patients with treatment success. CONCLUSIONS: CT-guided percutaneous radio frequency ablation is a safe and highly effective treatment for osteoid osteomas even in recurrent and residual cases. Technical success is the most important parameter affecting the outcome. Post radio frequency ablation CT findings have a good positive but a poor negative predictive value in prognostication.

Synthesis, Biological Evaluation and Pharmacokinetic Studies of Mefenamic Acid - N-Hydroxymethylsuccinimide Ester Prodrug as Safer NSAID.

BACKGROUND: Non steroidal anti-inflammatory drugs are the most widely prescribed drugs to manage pain and inflammatory conditions, but their long term use is associated with gastrointestinal toxicity. OBJECTIVES: The study aimed to synthesize an ester-based prodrug of a non steroidal anti-inflammatory agent, mefenamic acid in order to improve the therapeutic index vis a vis to overcome the side effects such as gastrointestinal irritation and bleeding associated with the use of mefenamic acid. METHODS: The ester prodrug (MA-NH) was prepared by condensing mefenamic acid with N-hydroxymethylsuccinimide in the presence of Phosphorus oxychloride. The pharmacokinetic profile, including stability and release of mefenamic acid and N-hydroxymethylsuccinimide from the ester prodrug (MA-NH) was studied by RP- HPLC in acidic medium (pH 1.2), basic medium (pH 7.4), 80 % v/v human plasma, 10 % w/v rat intestinal homogenate and 10 % w/v rat liver homogenate (pH 7.4). RESULTS: The chemical structure of the title compound was characterized by using modern spectroscopic techniques. The prodrug was found to be stable in acid medium, but it hydrolyzed and released sufficient quantities of the drug in alkaline medium. The prodrug produced lesser number of ulcers and showed improved analgesic and anti-inflammatory activity as compared to the parent drug. CONCLUSION: The results indicate that the synthesized prodrug (MA-NH) is better in terms of analgesic and antiinflammatory activities and with less GI toxicity than the parent drug.

Pharmacophore based virtual screening, synthesis and SAR of novel inhibitors of Mycobacterium sulfotransferase.

A planned 3D-pharmacophore mapping was carried out on the basis of chemical features associated with known Stf0 inhibitors. Four models (model 1-4) were obtained after GASP (Genetic Algorithm Similarity Program) refinement of seven models (D-1 to D-7) generated by using DISCOtech. The selected GASP model-1 has two hydrogen bond acceptor, two hydrogen bond donor and four hydrophobic points. This model was used for virtual screening (VS) of large public databases along with in house generated knowledge base database. VS followed by docking of selected compounds on Stf0 active site was carried and pose analysis done. Seven hits were identified after all the computational studies, of which 2 hits were synthesized along with their analogs and evaluated for antitubercular activity. IH-45 was found promising after in vitro assay.

99mTc-Methylene diphosphonate SPECT/CT as the one-stop imaging modality for the diagnosis of osteoid osteoma.

PURPOSE: The aim of this study was to evaluate the utility of Tc-methylene diphosphonate (Tc-MDP) single-photon emission tomography (SPECT)/computed tomography (CT) for the diagnosis of osteoid osteoma and compare the same with three-phase planar bone scintigraphy (BS) and CT alone. MATERIALS AND METHODS: Data of 31 patients (age: 20.6±13.2 years; male: 80.6%) who had undergone Tc-MDP BS with SPECT/CT for clinically and/or radiographically suspected osteoid osteoma were retrospectively evaluated. Planar BS images were analyzed by an experienced nuclear medicine physician. CT images were evaluated by an experienced radiologist. SPECT/CT images were evaluated by the nuclear medicine physician and radiologist in consensus. On the basis of the diagnostic confidence the interpreters used a scoring scale of 1-3, in which 1 is negative for osteoid osteoma, 2 is equivocal, and 3 is positive for osteoid osteoma. For the calculation of sensitivity, specificity, and predictive values for planar BS, CT, and SPECT/CT an interpretive score of 2 or higher was taken as positive for osteoid osteoma. Receiver operating characteristic curve analysis was performed and the area under the curve was calculated and compared. Histopathology and microbiology/clinical imaging follow-up was used as the reference standard. RESULTS: There were nine equivocal lesions on planar BS and five equivocal lesions on CT, but none on SPECT/CT. The sensitivity, specificity, and accuracy of SPECT/CT were all 100%; those of CT were 77.8, 92.3, and 83.8% and those of planar BS were 100, 38.4, and 74.1%, respectively. On comparison, the area under the curve of SPECT/CT was significantly larger than that of planar BS (1.00 vs. 0.761; P=0.005) and CT (1.00 vs. 0.872; P=0.044). However, no significant difference was seen between planar BS and CT (0.761 vs. 0.872; P=0.236). CONCLUSION: Tc-MDP SPECT/CT shows excellent diagnostic accuracy for osteoid osteoma and can be used as a one-stop imaging modality for the same. It is superior to planar BS and CT alone for the diagnosis of suspected osteoid osteoma.

Evaluation of online health information on clubfoot using the DISCERN tool.

The Internet has become a major source of health information on various aspects of clubfoot diagnosis and management. The World Wide Web becomes the first knowledge portal for a large number of anxious parents seeking information on clubfoot. Thus, a good quality webpage should provide necessary and comprehensive information on clubfoot so as to establish clarity in treatment options, compliance and bracing protocols. In contrast, modest quality information can induce bias and poor follow-up. We objectively evaluated online health information on clubfoot using the DISCERN tool. Using the universal search engine, Google, we conducted a Boolean search for the term 'clubfoot'. Only the first 50 sites providing health information on clubfoot were included in the study. We examined 334 links to include 50 of them. During analysis three websites were excluded because of duplication of content leaving 47 websites that were examined using the DISCERN tool. As per this tool, a score of less than 40% was graded as 'poor', 40-79% as 'fair' and at least 80% as 'good', whereas the overall quality was graded as 'low', 'moderate' and 'high' on similar standards. The overall quality of the publication was 'low' in 40% (19) websites, 'moderate' in 28% (13) and 'high' in 32% (15) of the websites we evaluated. Six (13%) of the publications showed good reliability; 25 (54%) showed fair reliability and 16 (33%) were unreliable. With regard to the quality of information on treatment choices, 44.7% (21) were 'good', 46.8% (22) were 'fair' and 8.5% (four) were 'poor'. We conclude that the quality of websites providing online health information on clubfoot needs significant improvement with emphasis on a universally acceptable template for disease information.

Accidentally falling instruments during orthopaedic surgery: time to wake up!

BACKGROUND: The aim of the study was to evaluate statistically the occurrence and causes of accidental fall of instruments and implants during orthopaedic procedures. METHODS: A prospective study was carried out over a period of 18 months. Total of 120 randomly chosen major orthopaedic surgeries were observed. The observer counted the number of times an instrument fell during surgery. The offending operating room personnel were identified. A note of the nature of instrument falling was made. RESULTS: A total of 120 surgeries were observed. There were 15 falls (38.5%) during elective surgeries and 24 (61.5%) during emergency (trauma) surgeries. Falls were classified as major and minor. There were a total of 39 falls with 11 major and 28 minor falls. Seven surgeries had two or more falls. In 26 instances (66.7%) the operating surgeon was responsible for the fall. In seven (17.9%) assisting surgeon and in three (7.7%) of the instances the scrub nurse was responsible for the fall of the instruments. Three falls (7.7%) were unaccountable. An average delay of 7.6 min was noted after the fall of the instrument or implant. CONCLUSIONS: Fall of instruments in the theatre is a common problem all over the world. It leads to increased operating time and extra resources and can hamper the end result of surgery. Our study is the first of its kind to evaluate the problem. Most falls occurred because of the operating surgeon. A course in instrument handling similar to one conducted by the theatre nurses may be helpful in preventing such falls.

Cardioprotection from ischemia-reperfusion injury due to Ras-GTPase inhibition is attenuated by glibenclamide in the globally ischemic heart.

The present study was designed to see if acute local inhibition of Ras-GTPase before or after ischemia (during perfusion) would produce protection against ischemia and reperfusion (I/R)-induced cardiac dysfunction. The effect of glibenclamide, an inhibitor of cardiac mitochondrial ATP-sensitive potassium (mitoK(ATP)) channels, on Ras-GTPase-mediated cardioprotection was also studied. A 40 min episode of global ischemia followed by a 30 min reperfusion in perfused rat hearts produced significantly impaired cardiac function, measured as left ventricular developed pressure (P(max)) and left ventricular end-diastolic pressure (LVEDP). Perfusion with Ras-GTPase inhibitor FPT III before I/R [FPT(pre)], significantly enhanced cardiac recovery in terms of left ventricular contractility. P(max) was significantly higher at the end of 30 min reperfusion in FPT(pre)-treated hearts compared to pre-conditioned hearts. However, the degree of improvement in left ventricular contractility was significantly less when FPT III was given only after ischemia during reperfusion [FPT(post)]. Combination treatment with FPT III and glibenclamide before I/R resulted in significant reduction of FPT III-mediated cardioprotection. These data suggest that activation of Ras-GTPase signaling pathways during ischemia are critical in the development of left ventricular dysfunction and that opening of mitoK(ATP) channels, at least in part, contributes to cardioprotection produced by Ras-GTPase inhibition.