Search

Background: To compare the mechanical strength of antegrade versus retrograde lag screw fixation of anterior column acetabular fractures., Methods: Standardised anterior column fractures were created in synthetic pelvis models and stabilised by either antegrade (ANTE, n = 4) or retrograde (RETRO, n = 4) anterior column screw fixation. In a validated setup, a cyclic loading protocol was applied with increasing axial force (750 cycles, 250-750 N) followed by load to failure. Construct survival, energy absorbed, construct stiffness, and load to failure were assessed. Descriptive and opto-metric methods were used to describe the mode of failure., Results: All constructs failed with loads below 1500 N. With regard to energy absorbed until failure, the ANTE group resisted to 3.763 × 10 5  N*cycles (range 3.760 × 10 5 -3.763 × 10 5 ) and the RETRO group to 3.762 × 10 5  N*cycles (range 3.761 × 10 5 -3.765 × 10 5 ; p = 1.0). The load to failure was 1254 N (range 977-1299) in the ANTE group and 1234 N (range 1087-1456) in the RETRO group (p = 1.0). Construct stiffness with 250 N was not different between the two groups (ANTE 192 N/mm vs. RETRO 215 N/mm, p = 0.486). In all samples, the mode of failure was a transiliac fracture with screw breakout due to rotation of the pubic fragment around the axis of the screw with a range of rotational motion [ROM] during cyclic testing of 0.96° in one ANTE sample and 0.82° in one RETRO sample for 750 N, and ROM at failure of 2.53° in one ANTE sample and 2.23° in one RETRO sample. There was some plastic deformation of the screws in all cases but no breakage., Conclusions: In this in vitro mechanical study, antegrade screw fixation of an anterior column acetabular fracture was not different in construct survival, load to failure, stiffness, and mode of failure when compared to retrograde screw fixation., (© 2019. Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Short stem hip replacements may allow preservation of proximal bone stock and minimise soft tissue disruption, easing future revision surgery. However patient satisfaction with these implants must be determined before widespread use. We aimed to compare patient reported outcome measures (PROMs) between short and conventional stem hip replacements., Methods: A systematic review was conducted according to PRISMA guidelines for studies comparing short and conventional stem hip replacements with validated PROMs. Meta-analyses were performed for studies reporting Harris Hip and WOMAC scores. Study bias was assessed with the Cochrane Risk of Bias tool and Newcastle-Ottawa Scale., Results: 24 studies, incorporating 2593 total hip replacements were included for qualitative analysis. 17 studies were included in the meta-analyses. Of the 7 excluded, 1 study reported the Japanese Orthopaedic Association score and 2 others reported the Oxford Hip score. All three showed no difference between the stems. A meta-analysis of 17 studies reporting Harris hip scores showed no statistically significant difference between short and conventional stems (standard mean difference (SMD) -0.06, 95% CI -0.20-0.07, p  = 0.35). 6 studies reported WOMAC scores with higher scores indicating worse outcome. No difference was seen between the two groups (SMD 0.21, 95%CI, -0.01-0.42, p  = 0.06). 4 studies reported higher WOMAC scores as better. Once again, a meta-analysis showed no statistically significant difference between the stems (SMD 0.28, 95% CI -0.07-0.63, p  = 0.12)., Conclusions: Our systematic review showed no difference in PROMs between short and conventional stem total hip replacements. This is in keeping with previous evidence but is a more comprehensive analysis. Short stems may have an important role in younger individuals as they allow preservation of proximal femoral bone, minimal access surgery and are amenable to abnormal anatomy. The current literature is hindered by non-uniform methodologies and outcome assessments across studies. Further, standardised, high quality evidence is required before widespread changes in practice.

Background: Management of proximal humerus fractures is challenging, especially in elderly. Locking plating is a common surgical treatment option. The Proximal Humerus Internal Locking System (plate-A) has shown to lower complication rates compared to conventional plates, but is associated with impingement risk, which could be avoided using Peri-articular Proximal Humerus Plate (plate-B). Nevertheless, biomechanical performance and optimal screw configuration of plate-B is unknown. The aim of this study was to evaluate different screw configurations of plate-B and compare with plate-A using finite element analyses., Methods: Twenty-six proximal humerus models were osteotomised to create unstable three-part fractures, fixed with either of the two plates, and tested under three anatomical loading conditions using a previous established and validated finite element simulation framework. Various clinically relevant screw configurations were investigated for both plates and compared based on the predicted peri-implant bone strain, being a validated surrogate of cyclic cut-out failure., Findings: Besides increasing the number of screws, the placement of the posterior screws in combination with the calcar screw in the plate-B significantly decreased the predicted failure risk. Generally, plate-A had a lower predicted failure risk than plate-B., Interpretation: The posterior and calcar screws may be prioritized in plate-B. Compared to plate-A, the more distal positioning, less purchase in the posterior aspect and a smaller screw spread due to not fitting of the most distal calcar screw in most investigated subjects led to a significantly higher predicted failure risk for most plate-B configurations. The findings of the simulations study require clinical corroboration., Competing Interests: Declaration of Competing Interest The authors are not compensated and there are no other institutional subsidies, corporate affiliations, or funding sources supporting this work unless clearly documented and disclosed., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Introduction: Tibial plafond fractures (TPF) are complex injuries often resulting in poor outcomes. Combination of articular impaction, metaphysealcomminution and soft-tissue injury results in a significant treatment challenge. The aim of this study was to conduct a systematic review and meta-analysis to compare post-operative complications and functional outcomes of open reduction and internal fixation (ORIF) versus circular external fixation (CEF) for treatment of TPF., Methods: A comprehensive search of PubMed/MEDLINE, Embase, Scopus and Cochrane library was undertaken. All studies published in English language comparing ORIF with CEF for treatment of TPF were included., Results: 5 comparative studies with 239 fractures met the inclusion criteria. Meta-analysis showed no significant difference in rates of non-union, malunion, superficial infection, deep infection, and secondary arthrodesis between the two treatment groups. Significantly higher rate of unplanned metalwork removal (RR 5.68, 95% CI 1.13 to 28.55, p = 0.04) and lower rate of post-traumatic arthritis (RR 0.48, 95% CI 0.30 to 0.78, p = 0.003) were found in patients that underwent ORIF. 1 study showed significantly lower functional outcomes scores with CEF (p< 0.05), whereas 3 studies found comparable functional outcomes between the two treatment groups. Overall, there was a preference in treating more severe injuries with CEF., Conclusion: CEF and ORIF are both acceptable treatment options for surgical management of TPF, with comparable post-operative complication rates and functional outcomes. This study highlights paucity of high-quality evidence regarding the optimal fixation method for TPF., (Copyright © 2020. Published by Elsevier Ltd.)

We present three cases of proximal radioulnar translocation in adults. Although rare, it is most commonly seen in paediatric cases. There have been three previously documented cases in adults, all requiring surgery and associated with ulnohumeral dislocations. Two of our cases required operative intervention, whilst one was reduced closed and did not require stabilisation. Furthermore, we have for the first time shown that proximal radioulnar translocations can occur in isolation in adults without an ulnohumeral dislocation. LEVEL OF EVIDENCE: Level IV.

Aim: To compare the incidence of surgical site infection with different antibiotic regimes in elective total knee arthroplasty. We hypothesise that a single high dose of Teicoplanin and Gentamicin is as effective as other regimes., Methods: A retrospective study of prospectively collected data on a total of 4500 elective knee replacements over a 9-year period was conducted in a district general hospital. Data were collected on antibiotic regime, patient characteristics, infection (treatment, infective agents, sensitivities) and complications., Results: Five different antibiotic regimes that have been used in elective knee arthroplasty were identified in our institution. 40 patients in total were identified who had a deep infection. Rates of deep surgical site infection were not significantly different between the five groups (p = 0.83)., Conclusion: A single pre-operative dose of Teicoplanin and Gentamicin has similar efficacy of prophylaxis to other regimes for patients undergoing primary elective total knee replacements. We recommend the choice of prophylaxis regimen is made locally based on pathogen virulence, drug resistance and cost., (© 2018 Delhi Orthopedic Association. All rights reserved.)

Torus fractures of the distal radius are both a common pediatric forearm fracture and a common source of referral to orthopedic departments. Management of these injuries has moved away from traditional casting methods to using splints and softcasts., Aim: With the recent introduction of a virtual fracture clinic (VFC), we sought to improve our compliance with guidelines while ensuring all patients undergo review in the clinic., Methods: We audited the management of patients before and after the introduction of the VFC with new management protocols for torus fracture patients., Results: There was a 51% decrease in patients managed using plaster of Paris with 5% treated with a softcast and 59% using a splint., Outcome: Using the VFC can improve the management of patients with torus fractures and provide a cost-saving and a more positive experience for patients., (Copyright © 2019 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: Plain radiographs of the sternoclavicular joint (SCJ) are difficult to interpret, and a CT or MRI scan is the usual investigation of choice. At our hospital, we use digital SCJ tomograms as our first-line investigation for all SCJ pathologies. We wanted to ascertain whether this is a safe and appropriate first-line imaging investigation., Materials and Methods: We retrospectively reviewed every patient who had undergone an SCJ digital tomogram (DT) over a 4-year period. We cross-referenced each patient with their records to assess the reason for referral, result, requirement for further investigation, diagnosis and management., Results: We identified 132 SCJ tomograms over the study period. Twelve patients were referred from other hospitals with pre-existing imaging and were excluded. The reasons for radiological investigation in the remaining 120 patients were pain/lump without trauma (54.2%), pain/lump with trauma (30.8%) and post-operative review (15%). Of the 102 patients who had DT as their initial investigation, the most common diagnoses identified included osteoarthritis, normal SCJ, fracture and dislocation among others. Only 18 (17.6%) of these patients required further investigation with CT and/or MRI., Conclusion: Our study is the first to assess digital tomography in SCJ pathology. We have shown that digital tomograms are an accurate and economically beneficial investigation for SCJ pathology and propose that it should be used as a first-line imaging investigation.

Hamstrings identification and subsequent graft harvest can be made difficult by body habitus and variability in tendon anatomy. We describe a 'sentinel' blood vessel near the insertions of gracilis and semitendinosus to facilitate identification. A prospective study of 100 patients (100 knees) undergoing primary arthroscopic ACL reconstruction (via the anterior approach) with hamstrings graft was conducted. We searched for a 'sentinel' vessel and studied its position, orientation and perpendicular distance from the pes tendons. The 'sentinel' vessel was present in 98/100 knees. It passed from the superficial fascia to the periosteum at the pes insertion at a mean perpendicular distance of 8 mm from the upper border of the pes tendons. The 'sentinel' vessel was a consistent anatomical finding and served as a reliable guide in determining the pes insertion. Identifying this anatomical landmark allowed a small skin incision with limited wound dissection minimising risk of injury to the infra-patellar branch of the saphenous nerve.

Madelung's deformity of the wrist arises from premature closure of the medial and volar aspect of the distal radial physis. True Madelung deformities reveal the presence of a "Vickers" ligament which is a short, volar, radioulnar ligament. Clinically, patients report increasing deformity, pain, and poor range of motion. Radiological features include increased radial inclination, volar tilt of the distal radius, and a positive ulnar variance. Surgical intervention usually comprises either a "Vickers" ligament release and distal radius physiolysis or a radial dome osteotomy. In future, EOS Imaging could aid diagnosis by providing more detailed images of the deformity while minimizing radiation exposure. Furthermore, three-dimensional printing and computer-navigated deformity correction could revolutionize management by facilitating simulation training, expediting surgery, and reducing intraoperative error.

Smartphones have become a mainstream feature in medicine since the introduction of the Apple iPhone in 2007. Over the last decade they have taken on increasing prominence with multiple uses in daily practice. They have long been used for group messaging and accessing patient's electronic records while mobile. More recently, however, smartphones have allowed clinicians to improve patient assessment in clinic and manage follow-up appointments remotely. Furthermore they have been used to aid procedural tasks in surgery and provide a medium for simulation training for junior doctors. The role of smartphones in the future is predicted to increase exponentially and there will no doubt be countless further roles for them in the ever-expanding field of orthopaedics.

Tarsal coalitions represent a cohort of conditions characterized by bony, cartilaginous, or fibrous union of two or more tarsal bones. These disorders are often poorly understood by medical professionals, often leading to delays in diagnosis and treatment. They may be asymptomatic or cause hindfoot pain, stiffness, decreased range of motion, and foot deformities. Coalitions can be investigated by an ascending sequence of imaging including radiography, computed tomography, and magnetic resonance imaging. They may be managed conservatively with orthoses, activity modification, physiotherapy, anti-inflammatory medications, or definitive surgical intervention. To our knowledge, cuboid-lateral cuneiform coalition has not been reported in the orthopedic literature. We describe a 40-year-old woman with this condition who reported a 1-year history of left foot pain and stiffness. She was definitively diagnosed with magnetic resonance imaging and was managed conservatively with an aircast boot and hydrocortisone injection.

Aims and Objectives: To determine the overall performance of an existing CAD algorithm with thin-section computed tomography (CT) in the detection of pulmonary nodules and to evaluate detection sensitivity at a varying range of nodule density, size, and location., Materials and Methods: A cross-sectional prospective study was conducted on 20 patients with 322 suspected nodules who underwent diagnostic chest imaging using 64-row multi-detector CT. The examinations were evaluated on reconstructed images of 1.4 mm thickness and 0.7 mm interval. Detection of pulmonary nodules, initially by a radiologist of 2 years experience (RAD) and later by CAD lung nodule software was assessed. Then, CAD nodule candidates were accepted or rejected accordingly. Detected nodules were classified based on their size, density, and location. The performance of the RAD and CAD system was compared with the gold standard that is true nodules confirmed by consensus of senior RAD and CAD together. The overall sensitivity and false-positive (FP) rate of CAD software was calculated., Observations and Results: Of the 322 suspected nodules, 221 were classified as true nodules on the consensus of senior RAD and CAD together. Of the true nodules, the RAD detected 206 (93.2%) and 202 (91.4%) by the CAD. CAD and RAD together picked up more number of nodules than either CAD or RAD alone. Overall sensitivity for nodule detection with the CAD program was 91.4%, and FP detection per patient was 5.5%. The CAD showed comparatively higher sensitivity for nodules of size 4-10 mm (93.4%) and nodules in hilar (100%) and central (96.5%) location when compared to RAD's performance., Conclusion: CAD performance was high in detecting pulmonary nodules including the small size and low-density nodules. CAD even with relatively high FP rate, assists and improves RAD's performance as a second reader, especially for nodules located in the central and hilar region and for small nodules by saving RADs time.

Teriparatide is a recombinant form of the biologically active component of Parathyroid hormone. It has been shown to increase bone mass and prevent fractures in osteoporotic bone. It is licensed by the Food and Drug Administration for the treatment of Osteoporosis. Over the last decade, a growing body of evidence has accumulated suggesting a role for Teriparatide in the management of fractures. Studies in both normal and delayed healing models have shown improvement in callus volume and mineralisation, bone mineral content, rate of successful union and strength at fracture sites. However most of these results have been derived from animal studies. The majority of this research on humans has comprised low level evidence, with few randomised controlled trials, many case reports and case series. Nevertheless, the results from these studies seem to support research from animal models. This has led to a growing number of clinicians using Teriparatide "off license" to treat fractures and non-unions in their patients. This review presents a critical appraisal of the current evidence supporting the use of Teriparatide for fracture healing, delayed unions and non unions and in the setting of osteoporotic fractures, the studies producing this evidence and their transferability to human beings.

A 73-year-old man presented to ENT clinic with a painless, smooth lump overlying his right cheek. Fine needle aspiration wrongly diagnosed necrotising malignancy with squamous differentiation. MRI showed a lesion overlying the right masseter, and positron emission tomography scanning incorrectly suggested this was a metabolically active lymph node. After surgical excision, immunohistochemical analysis showed this was in fact nodular fasciitis of the masseter. Nodular fasciitis is a rare, benign, proliferative lesion whose clinical and histological features make it difficult to distinguish from malignancies such as sarcoma. Immunohistochemical analysis for markers including vimentin and actin is crucial for diagnosis. Without this, misdiagnoses are common and patients are at risk of unnecessarily aggressive treatment. This case report summarises the epidemiological, aetiological and clinical features of nodular fasciitis, explores the pitfalls of investigation modalities and describes its management., (2015 BMJ Publishing Group Ltd.)

Background: There is concern about potential interference of iodinated contrast used in contrast-enhanced computerized tomography (CECT) with radioiodine therapy in differentiated thyroid carcinoma (DTC). The aim of this study was to determine the effect of iodinated contrast on urinary iodine concentration (UIC) in patients having thyroidectomy compared with control groups without CECT and without thyroidectomy., Methods: This prospective control study consisted of 4 groups each comprising 32 patients. Group 1- DTC patients undergoing preoperative CECT, group 2- DTC patients not undergoing CECT, group 3- benign goiter patients undergoing preoperative CECT, and group 4- patients with non-thyroidal diseases undergoing preoperative CECT. Spot UIC before CECT, after surgery (5-7 d), and at follow-up (4-6 wk) were compared among the groups., Results: The median basal UIC levels were not significantly different between the four groups (232.2 versus 263.9 versus 268.2 versus 178.2 μg/L, respectively, P = 0.443). In contrast, groups having preoperative CECT had significantly higher UIC levels at discharge (924 versus 329 versus 776 versus 661 μg/L, respectively, P = 0.001). These differences became insignificant at follow-up (225 versus 252 versus 310 versus 275 μg/L, respectively, P = 0.505). Patients having follow-up UIC values above the conventional cut-off of clinically relevant iodine excess (>200 μg/L) also had significantly higher basal values than those having lower follow-up values (283.0 versus 181.7 μg/L; P = 0.037)., Conclusions: Irrespective of the fact whether a patient is thyroidectomized or not preoperative CECT using non-lipophilic contrast does not result in long-term iodine retention., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Maternal hypothyroidism affects postnatal lung structure. High prevalence of hypothyroxinemia (low T4, normal T3) in iodine-deficient pregnant women and associated risk for neuropsychological development along with high infant/neonatal mortality ascribed to respiratory distress prompted us to study the effects of maternal hypothyroxinemia on postnatal lung development. Female Sprague Dawley rats were given a low-iodine diet (LID) with 1% KClO(4) in drinking water for 10 days, to minimize thyroid hormone differences. Half of these rats were continued on iodine-deficient diet; ID (LID with 0.005% KClO(4)) for 3 mo, whereas the rest were switched to an iodine-sufficient diet; IS [LID + potassium iodide (10 μg iodine/20 g of diet + normal drinking water)]. Pups born to ID mothers were compared with age-matched pups from IS mothers at postnatal days 8 (P8) and 16 (P16) (n = 6-8/group). ID pups had normal circulating T3 but significantly low T4 levels (P < 0.05) and concomitantly approximately sixfold higher thyroid hormone receptor-β mRNA in alveolar epithelium. Lung histology revealed larger and irregularly shaped alveoli in ID pups relative to controls. Lung function was assessed at P16 using a double-chambered plethysmograph and observed reduced tidal volume, peak inspiratory and expiratory flow, and dynamic lung compliance in ID pups compared with IS pups. Significant lowering of surfactant protein (SP)-B and SP-C mRNA and protein found in ID pups at P16. ID pups had 16-fold lower matrix metalloproteinase-9 mRNA levels in their alveolar epithelium. In addition, mRNA levels of thyroid transcription factor-1 and SP-D were significantly higher (3-fold) compared with IS pups. At P16, significantly lower levels of SP-B and SP-C found in ID pups may be responsible for immature lung development and reduced lung compliance. Our data suggest that maternal hypothyroxinemia may result in the development of immature lungs that, through respiratory distress, could contribute to the observed high infant mortality in ID neonates.

Neurological deficits due to maternal and neonatal hypothyroxinemia under mild-moderate iodine deficiency are a major preventable health problem worldwide. The present study assesses the impact of hypothyroxinemia on postnatal neocortical development and also compares it to the known effects of severe hypothyroidism. Our results strongly suggest that even within elevated circulating triiodothyronine (T3) levels, hypothyroxinemia significantly impairs thyroid hormone responsiveness in developing rat neocortex. The significant compensatory alteration in deiodinase levels with unaltered monocarboxylate transporter 8 (MCT8) and thyroid hormone receptors (TRs), although found to be similar in hypothyroxinemic and hypothyroid condition, is more pronounced under later condition. The resultant downregulation of nuclear myelin binding protein (MBP) and mitochondrial transcripts Cytochrome oxidase III (Cox III) as well as significantly enhanced mitochondrial localization of Bax and reduced Bcl-2 and Bcl-xL accompanied by enhanced release of Cytochrome c and Smac with activation of caspase-3 indicates pronounced apoptosis leading to compromised cellular survival. The similarities of this responsiveness albeit with difference in degree under hypothyroidism and hypothyroxinemic state with adequate availability of T3 are suggestive of an independent role of thyroxine in neocortex development. Taken together, this study brings forth the neurophysiological aspects of hypothyroxinemia and underscores the importance of adequate iodine nutrition along with mandatory thyroxin monitoring during pregnancy and after birth., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Hypothyroidism during early mammalian brain development is associated with decreased expression of various mitochondrial encoded genes along with evidence for mitochondrial dysfunction. However, in-spite of the similarities between neurological disorders caused by perinatal hypothyroidism and those caused by various genetic mitochondrial defects we still do not know as to how thyroid hormone (TH) regulates mitochondrial transcription during development and whether this regulation by TH is nuclear mediated or through mitochondrial TH receptors? We here in rat cerebellum show that hypothyroidism causes reduction in expression of nuclear encoded genes controlling mitochondrial biogenesis like PGC-1alpha, NRF-1alpha and Tfam. Also, we for the first time demonstrate a mitochondrial localization of thyroid hormone receptor (mTR) isoform in developing brain capable of binding a TH response element (DR2) present in D-loop region of mitochondrial DNA. These results thus indicate an integrated nuclear-mitochondrial cross talk in regulation of mitochondrial transcription by TH during brain development., (Copyright 2010 Elsevier Inc. All rights reserved.)

Objective: The aim of the present study was to determine the impact of universal salt iodization (USI) on the prevalence of iodine deficiency in the population of an area previously known to have severe iodine deficiency in India., Design: In a cross-sectional survey, a total of 2860 subjects residing in fifty-three villages of four sub-districts of Gonda District were examined for goitre and urinary iodine concentration. Free thyroxine and thyroid-stimulating hormone levels were also measured. Salt samples from households were collected for estimation of iodine content., Results: A reduction in goitre prevalence was observed from 69 % reported in 1982 to 27.7 % assessed in 2007. However, 34 % of villages still had very high endemicity of goitre (goitre prevalence >30 %). Twenty-three per cent of households consumed a negligible amount (<5 ppm) and 56 % of households consumed an insufficient amount (5-15 ppm) of iodine from salt., Conclusions: Although there was an overall improvement in iodine nutrition as revealed by decreased goitre prevalence and increased median urinary iodine levels, there were several pockets of severe deficiency that require a more targeted approach. Poor coverage, the use of unpackaged crystal salt with inadequate iodine and the washing of salt before use by 90 % of rural households are the major causes of persisting iodine-deficiency disorders. This demonstrates lapses in USI implementation, lack of monitoring and the need to identify hot spots. We advocate strengthening the USI programme with a mass education component, the supply of adequately iodized salt and the implementation of complementary strategies for vulnerable groups, particularly neonates and lactating mothers.

N-(4-hydroxyphenyl)retinamide (4-HPR), a synthetic retinoid is under clinical evaluation as a therapeutic agent in a variety of cancers. Its mechanism(s) of action involves multiple overlapping pathways that still remain unclear. In glioma cells its mechanism of action is not well elucidated. Here, we show that 4-HPR and not all-trans retinoic acid and 9-cis retinoic acid effectively induce apoptosis in glioma cells. 4-HPR-induced apoptosis is associated with hydroperoxide production and loss of mitochondrial membrane potential (Delta Psi(m)). Ultrastructural changes further indicate 4-HPR-induced mitochondrial swelling, endoplasmic reticulum (ER) dilation as well as close proximity of mitochondria and ER. As suggested by dilated ER, 4-HPR treatment increased the free cytosolic Ca(2+) as well as mitochondrial Ca(2+). Chelation of extracellular Ca(2+) by EGTA did not prevent Ca(2+) elevation, thus suggesting involvement of intracellular calcium stores in the release. Buffering of intracellular calcium by BAPTA-AM did not prevent 4-HPR-induced apoptosis; however, blocking the release of Ca(2+) from ER by heparin inhibited apoptosis, indicating the role of depletion of Ca(2+) from ER stores in apoptosis. 4-HPR treatment also resulted in an increase in Bax levels along with its translocation to mitochondria that promote mitochondrial membrane permeabilization. 4-HPR-induced apoptosis was further associated with the release of cytochrome c and apoptosis-inducing factor (AIF) from mitochondria to cytosol and nucleus, respectively, along with caspase-3 and caspase-7 activation. However, AIF nuclear translocation, peripheral chromatin condensation and apoptosis were not completely prevented by general caspase inhibitors, thus suggesting involvement of a caspase-dependent and caspase-independent pathway in 4-HPR-induced apoptosis. Taken together, these results suggest the role of mitochondrial-mediated pathway and ER stress as a key event in 4-HPR-induced apoptosis in glioma cells.