The Management of Persistent Distal Occlusions after Mechanical Thrombectomy and Thrombolysis: An Inter- and Intrarater Agreement Study.

BACKGROUND AND PURPOSE: The best management of patients with persistent distal occlusion after mechanical thrombectomy with or without IV thrombolysis remains unknown. We sought to evaluate the variability and agreement in decision-making for persistent distal occlusions. MATERIALS AND METHODS: A portfolio of 60 cases was sent to clinicians with varying backgrounds and experience. Responders were asked whether they considered conservative management or rescue therapy (stent retriever, aspiration, or intra-arterial thrombolytics) a treatment option as well as their willingness to enroll patients in a randomized trial. Agreement was assessed using κ statistics. RESULTS: The electronic survey was answered by 31 physicians (8 vascular neurologists and 23 interventional neuroradiologists). Decisions for rescue therapies were more frequent (n = 1116/1860, 60%) than for conservative management (n = 744/1860, 40%; P < .001). Interrater agreement regarding the final management decision was "slight" (κ = 0.12; 95% CI, 0.09-0.14) and did not improve when subgroups of clinicians were studied according to background, experience, and specialty or when cases were grouped according to the level of occlusion. On delayed re-questioning, 23 of 29 respondents (79.3%) disagreed with themselves on at least 20% of cases. Respondents were willing to offer trial participation in 1295 of 1860 (69.6%) cases. CONCLUSIONS: Individuals did not agree regarding the best management of patients with persistent distal occlusion after mechanical thrombectomy and IV thrombolysis. There is sufficient uncertainty to justify a dedicated randomized trial.

NCCT Markers of Intracerebral Hemorrhage Expansion Using Revised Criteria: An External Validation of Their Predictive Accuracy.

BACKGROUND AND PURPOSE: Several NCCT expansion markers have been proposed to improve the prediction of hematoma expansion. We retrospectively evaluated the predictive accuracy of 9 expansion markers. MATERIALS AND METHODS: Patients admitted for intracerebral hemorrhage within 24 hours of last seen well were retrospectively included from April 2016 to April 2020. The primary outcome was revised hematoma expansion, defined as any of a ≥6-mL or ≥33% increase in intracerebral hemorrhage volume, a ≥ 1-mL increase in intraventricular hemorrhage volume, or de novo intraventricular hemorrhage. We assessed the predictive accuracy of expansion markers and determined their association with revised hematoma expansion. RESULTS: We included 124 patients, of whom 51 (41%) developed revised hematoma expansion. The sensitivity of each marker for the prediction of revised hematoma expansion ranged from 4% to 78%; the specificity, 37%-97%; the positive likelihood ratio, 0.41-7.16; and the negative likelihood ratio, 0.49-1.06. By means of univariable logistic regressions, 5 markers were significantly associated with revised hematoma expansion: black hole (OR = 8.66; 95% CI, 2.15-58.14; P = .007), hypodensity (OR = 3.18; 95% CI, 1.49-6.93; P = .003), blend (OR = 2.90; 95% CI, 1.08-8.38; P = .04), satellite (OR = 2.84; 95% CI, 1.29-6.61; P = .01), and Barras shape (OR = 2.41, 95% CI; 1.17-5.10; P = .02). In multivariable models, only the black hole marker remained independently associated with revised hematoma expansion (adjusted OR = 5.62; 95% CI, 1.23-40.23; P = .03). CONCLUSIONS: No single NCCT expansion marker had both high sensitivity and specificity for the prediction of revised hematoma expansion. Improved image-based analysis is needed to tackle limitations associated with current NCCT-based expansion markers.

Diagnostic and therapeutic approach to adult central nervous system vasculitis.

The clinical manifestations of central nervous system (CNS) vasculitis are highly variable. In the absence of a positive CNS biopsy, CNS vasculitis is particularly suspected when markers of both vascular disease and inflammation are present. To facilitate the clinical and therapeutic approach to this rare condition, CNS vasculitis can be classified according to the size of the involved vessels. Vascular imaging is used to identify medium vessel disease. Small vessel disease can only be diagnosed with a CNS biopsy. Medium vessel vasculitis usually presents with focal neurological signs, while small vessel vasculitis more often leads to cognitive deficits, altered level of consciousness and seizures. Markers of CNS inflammation include cerebrospinal fluid pleocytosis or elevated protein levels, and vessel wall, parenchymal or leptomeningeal enhancement. The broad range of differential diagnoses of CNS vasculitis can be narrowed based on the disease subtype. Common mimickers of medium vessel vasculitis include intracranial atherosclerosis and reversible cerebral vasoconstriction syndrome. The diagnostic workup aims to answer two questions: is the neurological presentation secondary to a vasculitic process, and if so, is the vasculitis primary (i.e., primary angiitis of the CNS) or secondary (e.g., to a systemic vasculitis, connective tissue disorder, infection, malignancy or drug use)? In primary angiitis of the CNS, glucocorticoids and cyclophosphamide are most often used for induction therapy, but rituximab may be an alternative. Based on the available evidence, all patients should receive maintenance immunosuppression. A multidisciplinary approach is necessary to ensure an accurate and timely diagnosis and to improve outcomes for patients with this potentially devastating condition.

[Cryptogenic stroke management : where are we ?] / Prise en charge de l'AVC cryptogénique : où en sommes-nous ?

Cryptogenic stroke is an old definition that designates an ischemic stroke with no identifiable cause. The term of the embolic stroke of undetermined source was then introduced to identify non-lacunar strokes in whom thromboembolism was the likely mechanism. This subgroup of cryptogenic strokes remains heterogeneous with many potential and possibly associated embolic causes. Covert atrial fibrillation is probably less often involved than initially expected, in contrast to intracranial and extracranial atherosclerosis. The cardiologist should be involved in the search of underlying causes of ischemic stroke by helping the neurologist to identify the most likely diagnosis. Further research is necessary to select populations that may benefit from more effective and individualized treatment.

DXA-based variables and osteoporotic fractures in Lebanese postmenopausal women.

INTRODUCTION: The aim of this study was to assess DXA-based variables (bone mineral density, bone mineral apparent density, compressive strength index of the femoral neck and trabecular bone score) in Lebanese postmenopausal women having presented a previous fracture. MATERIALS AND METHODS: One thousand Lebanese postmenopausal women between 45 and 89 years participated in this study. The women were recruited by advertisements offering bone mineral density measurements at a reduced cost. Subjects with previous history of radiotherapy or chemotherapy were excluded. Informed written consent was obtained from all the participants. RESULTS: Femoral neck compressive strength index (FN CSI) was significantly (P<0.001) associated with the presence of fracture using a simple logistic regression (odds ratio=0.51 [0.385-0.653]). When a multivariate logistic regression analysis was performed with the presence of fracture as a dependent variable and each of age, FN BMD and FN CSI as independent variables, only FN BMD (P=0.005) and FN CSI (P=0.004) were found to be associated with the presence of fracture. CONCLUSION: This study suggests that FN CSI is associated with history of osteoporotic fractures in postmenopausal women. The use of FN CSI in clinical practice may help to identify patients with high risk of fracture. LEVEL OF EVIDENCE: Epidemiological study, level IV.

Otitis media with effusion in Lebanese children: prevalence and pathogen susceptibility.

OBJECTIVE: To determine the prevalence and resistance profile of bacterial pathogens present in the middle ear of children with otitis media with effusion, and to report beta-lactamase-negative, ampicillin-resistant bacteria for the first time in Lebanese children. METHOD: We included 62 patients younger than 12 year (107 ears), who underwent myringotomy with tympanostomy tube placement for persistent otitis media with effusion. Bacteria were identified by Gram staining and biochemical tests, and antibiotic sensitivities tested by the disc diffusion method and via minimum inhibitory concentration (E-test). RESULTS: The commonest pathogen was Haemophilus influenzae (62 per cent), followed by Streptococcus pneumoniae (26 per cent). The H influenzae resistance profile was highest for amoxicillin (81.0 per cent) and lowest for cefotaxime (19.0 per cent). There was a high risk of developing H influenzae antibiotic resistance among children with a history of smoking exposure (p = 0.001), recurrent upper respiratory tract infection (p = 0.001) or previous antibiotic treatment (p = 0.005). Fifty-two per cent of H influenzae colonies were found to be beta-lactamase-negative and ampicillin-resistant. CONCLUSION: In these children with persistent otitis media with effusion, H influenzae was the most prevalent bacteria. It showed a high incidence of resistance to the antibiotics most commonly prescribed to treat acute otitis media.

Developmental dysplasia of the hip: is acetabular retroversion a crucial factor?

OBJECTIVE: The objective of this study was to investigate a possible relation between congenital hip dysplasia and acetabular retroversion and to explore the eventual influence of the latter in the surgical decision for periacetabular osteotomy. MATERIALS AND METHODS: We assessed the classical morphological characteristics of both hips, with an additional newly described retroversion index. The study was conducted in 174 patients with uni- or bilateral congenital hip dysplasia having undergone unilateral (153 patients) or bilateral (21 patients) periacetabular osteotomy when respectively one or both dysplastic hips remained symptomatic. RESULTS: In the group of operated hips (195 hips in total), 53% of the acetabuli were anteverted, 42% retroverted, and 5% neutral orientations. The group of nonoperated hips (153 hips) included 24% normal hips, 22% hips with normal coverage but retroverted, 35% dysplastic hips with anteverted or neutral orientation, and 19% dysplastic retroverted hips. Comparing the two hips in the subgroup of patients in whom the operated and nonoperated sides were both dysplastic failed to demonstrate statistically significant difference in the mean retroversion index. However, all the other variables measured were significantly different; with the operated side more dysplastic. Comparing the two hips in the other subgroups showed that acetabular retroversion was nearly always bilateral and symmetrical, even in presence of unilateral congenital dysplasia. DISCUSSION: Our data suggest that the presence of acetabular retroversion is probably independent of the congenital hip dysplasia and that this abnormality seems at best a secondary factor in the appearance of dysplastic hip symptoms. LEVEL OF EVIDENCE: Level IV, retrospective diagnostic study.

The spinal curvature irregularity index independently identifies vertebral fractures.

INTRODUCTION AND HYPOTHESIS: The spinal curvature irregularity index (SCII) is a quantitative measure of the irregularity of the spinal curvature. We evaluated the predictive ability of SCII to identify subjects with vertebral fractures (VF). METHODS: Vertebral heights were measured by quantitative vertebral morphometry in 461 Lebanese women 20-89 years of age and VFs were ascertained by the grade 1 Eastell method. SCII scores were log-transformed and expressed as Z-SCII, the number of standard deviations above or below the mean ln(SCII) of young patients without VF. Univariate and multivariate binary logistic regression models were used to identify clinical predictors of VF. RESULTS: Women with a higher SCII were more likely to have prevalent VF. A higher SCII was associated with a greater prevalence of VF within each category of femoral neck BMD (normal, osteopenia, osteoporosis). In univariate analysis, predictors of VF included Z-SCII (odds ratio, OR: 2.21, 95% CI: 1.80-2.71) and femoral neck T-score (OR: 1.35, 95% CI: 1.12-1.63). In multivariate analysis, predictors of VF were: Z-SCII (OR: 1.54, 95% CI: 1.02-2.32), femoral neck T-score (OR: 1.41, 95% CI: 1.11-1.78) and age(3) (OR: 1.40, 95% CI 1.10-1.82). At a cutoff SCII of 9.5%, the sensitivity and specificity of SCII for VF were 71 and 64% respectively, and higher SCII cutoffs identified VFs with greater specificity. CONCLUSION: The SCII is a robust, simple and independent indicator of the presence of VFs.

[Percutaneous fluoroscopic and arthroscopic controlled screw fixation of posterior facet fractures of the calcaneus]. / Réduction et vissage percutanés des fractures thalamiques du calcaneus sous contrôle arthroscopique et fluoroscopique.

We describe a new technique for reduction and percutaneous osteosynthesis of displaced posterior facet fractures of the calcaneus which appears to overcome the problems encountered with other percutaneous methods described for this type of surgery. The method relies on the use of traction which allows automatic reduction of the greater tubersosity. The patient is installed on an orthopedic traction table. Pin traction provides anatomic reduction of the posterior articular surface and restitution of Böhler's angle under fluoroscopic and arthroscopic control. We used this technique in thirteen patients with fifteen displaced posterior facet fractures of the calcaneum. Mean patient age was 50.4 Years. Mean follow-up was twenty Months. We did not have any cutaneous or infectious complications in this short series. In the majority of the cases, the overall functional and physical results were excellent or good. The mean Böhler's angle was 27 degrees, corresponding to 83% correction compared with the healthy side. These preliminary results are encouraging. We were able to restitute calcaneum anatomy, shorten hospital stay, and avoid all skin complications. Indications for this percutaneous technique could be widened. It is a valid alternative to open treatment of posterior facet fractures of the calcaneum.

Coracoclavicular joints. Reflections upon incidence, pathophysiology and etiology of the different forms.

Since the first description of the coracoclavicular joint in 1861, many papers have been published reporting its occurrence, anatomical description, and geographical distribution. However, there are as yet no published articles with a convincing explanation for the rather variable forms of this variant. In this study, we investigated the occurrence of the coracoclavicular joint in the current and medieval population of Toulouse city and propose, through biometric measures, an explanation for the different forms of this anatomical variant. A total of 2192 chest X-rays taken for various conditions at a receiving hospital and 392 specimens (784 scapulae and an equal number of clavicles) of the L'Isle-Jourdain Series were examined with this aim. When present in the osteologic collection, the sizes of the articular conoid process as well as the height of the corresponding coracoid and acromial processes were noted. A coracoclavicular joint was noted in 0.82% and in 1.78% of the individuals examined in the radiological and osteologic series, respectively. The conoid process varied in size and correlated with the disposition of each correspondent coracoacromial arch. Osteoarthritis was noted in some of these joints when there was discordance between the conoid process size and the architecture of the correspondent coracoacromial arch, suggesting impingement. Our findings support a genetic origin for this variant, and suggest that its occurrence is also probably influenced by environmental factors. Osteoarthritis of this joint may be responsible for shoulder pain.

[Effect of alendronate on periprosthetic bone loss after cemented primary total hip arthroplasty: a prospective randomized study]. / Action de l'Alendronate sur l'état osseux péri-prothétique après prothèse totale de hanche cimentée: étude prospective randomisée en double aveugle.

PURPOSE OF THE STUDY: Bone remodeling and osteolysis around total hip prostheses, with its inevitable corollary, prosthesis loosening, remains a difficult problem in orthopedic surgery. Alendronate (bisphosphonate) has proven its efficacy for the treatment of osteoporosis of the lumbar spine and femoral neck. A few in vitro studies have pointed out its inhibiting effect on particle-induced osteolysis. In vivo, one study has demonstrated its usefulness in preventing osteolysis around non-cemented total hip arthroplasties (THA). The purpose of this work was to study the efficacy of this agent for the prevention of changes in peri-prosthetic bone mineral density (BMD) after primary THA. MATERIAL AND METHODS: The study series included 38 patients with degenerative hip disease who underwent THA. The patients were randomized in double-blind fashion to two treatment arms: 10 alendronate and 600 mg calcium per day for 2 years (20 patients) or placebo and 600 mg calcium per day for 2 years (18 patients). Conventional x-rays and x-ray biphotonic absorptiometry (DPX) was performed on day four postop and at 3, 6, 12, and 24 months postop. The periprosthetic zones described by Grüen were used for analysis. RESULTS: DPX demonstrated a significant reduction in BMD in all patients included in the study. The bone loss was the same in both groups during the early postoperative period reaching maximum loss at 3 months. Differences were observed after this time. In the placebo group, bone loss reached a plateau at 6 months then BMD started to increase progressively, reaching 12.7% bone loss at 2 years follow-up (p<0.002). In the alendronate group, there was no plateau, BMD increased continuously starting from three months and reached 6.857% bone loss at 2 years (p<0.003). DISCUSSION: Administration of alendronate led to a significant reduction in peri-prosthetic bone loss at 2 years follow-up. These results are the first to our knowledge demonstrating the beneficial effect in vivo of alendronate on bone behavior around cemented THAs. CONCLUSION: This beneficial effect observed in vivo should be confirmed in further studies including a larger number of patients and longer follow-up. The action of alendronate could facilitate and even retard revision surgery by preserving bone stock.

Age-associated changes in quantitative ultrasonometry (QUS) of the os calcis in Lebanese women-assessment of a Lebanese reference population.

OBJECTIVE: This study was aimed to assess age changes in quantitative ultrasonometry (QUS) in a large sample of Lebanese women to determine a Lebanese reference population. DESIGN: Cross-sectional study. SUBJECTS AND METHODS: Broadband ultrasound attenuation (BUA) and speed of sound (SOS) and the stiffness index (SI) of the os calcaneus was measured in 4,320 women with a mean age of 52.5 years (age range 20 to 79 years) using three identical Achilles Express (GE/Lunar) and one Achilles Plus (GE/Lunar) ultrasonometry devices. Women were randomly selected and asked to participate in a nationwide screening program using the media, conferences, telephone calls etc. Measurements were performed at Red Cross centers located all over the country. No inclusion or exclusion criteria were used. RESULTS: There was an overall decline of 19.2% for BUA, 3.1% for SOS and 30.3% for SI between late adolescence and old age. In premenopausal women, BUA decreased only slightly by 3%, while postmenopausal women showed a significant decline of 16.2%. In contrast, SOS continuously decreased from the age of 42; there was a decline of 0.8% from adolescence to the menopause; postmenopausal women showed a larger decline of 2.4%. The SI of premenopausal women decreased by 6%, while postmenopausal women showed a significantly larger decline of 24.3%. SI value for the female Lebanese young adult reference is 8% lower than that of the American and European women (92 SI units compared to 100). At the age of 42, SI value for the Lebanese women is 10.4% lower than the American women and 7.5% lower than the European women (86 SI units compared to 96 and 93, respectively). At the age of 75, SI values for the Lebanese women is 4.4% lower than the American women and the European women (65 SI units compared to 68). The decline in stiffness index for the Lebanese women between age 20 and 75 years is about 30.3% compared to 32% for the American or European reference curves. The rate of decrease for the Lebanese women was 0.2 SI units per year for the premenopausal period, and 0.7 SI units per year for the postmenopausal period. CONCLUSION: The age-related female, Lebanese reference curve was significantly different from the American and the European reference curves used by the manufacturer. Therefore, the use of our standardized reference data instead of the proposed US or European database reduces the risk of overestimating osteoporosis in the Lebanese population. The impact of our results on the prevalence of osteoporotic fracture in Lebanon has to be evaluated later on.

Osteoporosis: combination therapy for better or worse.

Osteoporosis is a condition that is associated with an increased susceptibility for fractures. In the past few years, several drugs have become available that can reduce the incidence of fractures in patients with osteoporosis. Since these drugs work through different cellular mechanisms, combining agents of different classes may have an additive or multiplicative effect on fracture risk reduction. Combination treatments that have been evaluated in clinical trials include bisphosphonates with estrogen, raloxifene or PTH/ bisphosphonates and PTH/ estrogen. In general, these trials have shown increases in bone mineral density over that observed with each agent alone. However, whether anti-fracture efficacy is improved, or worsened remains to be established. This article reviews the combination treatments that have been evaluated in clinical trials, with a discussion of the potential benefits and risks that those treatments entail. Integrating safety and cost issues will eventually determine whether those combinations will become the standard of care.

Obstetrical brachial plexus palsy. Prediction of outcome in upper root injuries.

Thirty obstetrical brachial plexus palsies involving the upper roots were retrospectively reviewed. There were 20 C5-C6 palsies and ten C5-C6-C7 palsies in which recovery of C7 occurred by the end of the first month. Recovery of elbow flexion at 3 months, C7 involvement and high birthweight were the best early predictors of outcome, but all were unreliable when used separately. In combination, recovery of elbow flexion and birthweight predicted the final outcome reasonably satisfactorily, particularly when elbow flexion at 9 months, and not 3 months was considered (risk of error = 13%). Brachial plexus reconstruction may therefore be justified when there was initial C7 involvement associated with increased birthweight and poor elbow flexion at 6-9 months.

Epidermal growth factor enhances cisplatin-induced apoptosis by a caspase 3 independent pathway.

PURPOSE: Activation of the epidermal growth factor (EGF) receptor has previously been shown to increase the sensitivity of cancer cells to DNA-damaging agents, including cisplatin, UV-B, and gamma-radiation. We now investigated the mechanisms by which EGF enhances the sensitivity of human ovarian cancer cells to cisplatin. RESULTS: The effect of EGF on cisplatin sensitivity could not be entirely explained by alterations in the cellular detoxification of cisplatin by glutathione or DNA repair of transcribed genes, as assessed by a plasmid reactivation assay. Furthermore, EGF did not affect the levels of several proteins that regulate apoptotic pathways, including bcl2, bclXL, bax and p53. Cisplatin treatment resulted in activation of caspase 3 and subsequent cleavage of specific substrates containing the DEVD (Asp-Glu-Val-Asp) amino acid sequence, including PARP (poly(ADP-ribose) polymerase). The EGF-mediated increase in cisplatin-induced apoptosis, however, did not result in increased caspase 3 activity. Moreover, apoptosis induced by cisplatin alone was completely inhibited by the caspase 3 inhibitor DEVD-CHO, whereas cell death induced by combined treatment with cisplatin and EGF was not prevented by inhibition of caspase 3. CONCLUSION: Our results suggest that, although cisplatin alone induces apoptosis by a caspase 3 dependent pathway, EGF enhances cisplatin-induced cell death by activating an apoptotic pathway that is independent of caspase 3.

Modulation of docetaxel-induced apoptosis and cell cycle arrest by all- trans retinoic acid in prostate cancer cells.

We report that all- trans retinoic acid (ATRA) enhanced the toxicity of docetaxel against DU145 and LNCaP prostate cancer cells, and that the nature of the interaction between ATRA and docetaxel was highly synergistic. Docetaxel-induced apoptotic cell death was associated with phosphorylation and hence inactivation of Bcl-2. ATRA enhanced docetaxel-induced apoptosis and combined treatment with ATRA and docetaxel resulted in down-regulation of Bcl-2. Docetaxel caused phosphorylation and hence inactivation of cdc2 kinase result ing in G2/M arrest. ATRA inhibited docetaxel-induced phosphorylation of cdc2 resulting in activation of cdc2 kinase and partial reversal of the G2/M arrest. ATRA also inhibited docetaxel-induced activation of MAPK indicating that the effects of docetaxel and ATRA on cdc2 phosphorylation are dependent on MAPK. We conclude that ATRA synergistically enhances docetaxel toxicity by down-regulating Bcl-2 expression and partially reverses the docetaxel-induced G2/M arrest by inhibiting docetaxel-induced cdc2 phosphorylation in a pathway that is dependent on MAPK.

Effect of c-Abl tyrosine kinase on the cellular response to paclitaxel-induced microtubule damage.

DNA damage has been shown to activate c-Abl tyrosine kinase. We now report that, in addition to DNA damage, microtubule damage induced by paclitaxel results in activation of c-Abl kinase. In 3T3 cells, the presence of c-Abl kinase increased paclitaxel-induced cell death. In Abl-proficient cells, paclitaxel produced a marked and prolonged G2/M arrest which peaked at 24 h and a rapid and marked induction of p21(WAF1)which also peaked at 24 h. In Abl-deficient cells, the G2/M arrest induced by paclitaxel was less prominent and shorter in duration and the effect of paclitaxel on p21(WAF1)expression was reduced and delayed. Paclitaxel had no effect on p53 expression and MAPK phosphorylation. These findings indicate that, in 3T3 cells, c-Abl kinase facilitates cell death and regulates G2/M arrest in response to paclitaxel-induced microtubule damage in a pathway that is dependent on p21(WAF1)and independent of MAPK activity.

Middle turbinate medialization technique in functional endoscopic sinus surgery.

The middle turbinate is an important surgical landmark in functional endoscopic sinus surgery (FESS). Postoperatively, lateralization may obstruct the middle meatus, thereby increasing the risk of complications and recurrences. A new medialization technique using metallic clips between the head of the middle turbinate and the septum is described. The aim of this study is to evaluate the clip medialization technique applied in 56 cases of bilateral FESS. We think that this simple technique, with its low rate of complications, is an adequate and simple procedure for middle turbinate medialization. A good and accessible middle meatus was observed in 54 patients.

Hearing preservation mastoidectomy in otogenic meningitis secondary to an enlarged vestibular aqueduct. Case report.

In pyogenic meningitis resulting from a life-threatening ear infection, mastoidectomy is performed as part of the management of the disorder. A dilemma arises when the active ear is the only hearing ear. An active unsafe ear can lead to sensorineural hearing loss whereas ear surgery carries the risk of inner ear damage. We present the case of a 40-year-old woman admitted for severe purulent meningitis and sub-coma secondary to a left mastoiditis with mixed hearing loss on the left side and complete deafness on the right side. The study of this case shows that the intracranial complication was secondary to an abnormally enlarged left vestibular aqueduct. Because of the failure to control meningitis with medical treatment using highly specific antibiotherapy for two weeks, we proceeded with a left side mastoidectomy and closure of the external aperture of the vestibular aqueduct with a muscle graft. This surgery saved the patient's life, cured the meningitis and brought a recovery of a near normal hearing to the only hearing ear. Although demonstrating a rare etiology of intracranial complication, this case confirms that mastoidectomy, even on the only hearing ear, has to be done as early as possible to remove the source of infection, to prevent further intracranial complication, to arrest the progress of the ear disease and preserve or even recover almost normal hearing.

Induction of JNK and c-Abl signalling by cisplatin and oxaliplatin in mismatch repair-proficient and -deficient cells.

Loss of DNA mismatch repair has been observed in a variety of human cancers. Recent studies have shown that loss of DNA mismatch repair results in resistance to cisplatin but not oxaliplatin, suggesting that the mismatch repair proteins serve as a detector for cisplatin but not oxaliplatin adducts. To identify the signal transduction pathways with which the detector communicates, we investigated the effect of loss of DNA mismatch repair on activation of known damage-responsive pathways, and recently reported that cisplatin differentially activates c-Jun NH2-terminal kinase (JNK) and c-Abl in repair-proficient vs.-deficient cells. In the current study, we directly compared differential activation of these pathways by cisplatin vs. oxaliplatin. The results confirm that cisplatin activates JNK kinase 5.7 +/- 1.5 (s.d.)-fold more efficiently in DNA mismatch repair-proficient than repair-deficient cells, and that the c-Abl response to cisplatin is completely absent in DNA mismatch repair-deficient cells. In contrast, there was no detectable activation of the JNK or c-Abl kinases in DNA mismatch repair-proficient or -deficient cells exposed to oxaliplatin. The present study demonstrates that, despite the similarity of the adducts produced by cisplatin and oxaliplatin, they appear to be recognized by different detectors. The DNA mismatch repair system plays an important part in the recognition of cisplatin adducts, and activation of both the JNK and c-Abl kinases in response to cisplatin damage is dependent on the detector function of the DNA mismatch repair proteins. In contrast, this detector does not respond to oxaliplatin adducts.