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Articles by Jérôme Kalifa in JoVE

 JoVE Clinical and Translational Medicine

High-Resolution endocardiale en epicardiale Optical Mapping in een Schaap Model van Stretch-Induced atriale fibrillatie


JoVE 3103 7/29/2011

Center for Arrhythmia Research. Internal Medicine, University of Michigan

Dit rapport geeft een gedetailleerde beschrijving van de methodologie en de resultaten van gelijktijdige endocardiale en epicardiale optische in kaart brengen van de elektrische prikkeling in de intacte linker atrium van een Langendorff-doorbloed schapen hart tijdens stretch-geïnduceerde atriumfibrilleren.

Other articles by Jérôme Kalifa on PubMed

Cochlear Implantation in a Child with CINCA Syndrome Who Also Has Wide Vestibular Aqueducts

Chronic infantile neurological cutaneous and articular (CINCA) syndrome is a severe auto-inflammatory disease, due to mutation of the CIAS1 gene. CINCA syndrome should be considered the most severe of a spectrum of three disorders all due to mutation of the CIAS1 gene. CINCA syndrome produces a triad of symptoms of neonatal onset: maculopapular urticarial rash, chronic meningitis, and chronic non-inflammatory arthropathy with recurrent fever. CINCA syndrome is also associated with sensory organ damage, especially progressive hearing loss and loss of vision. In this case report, we present the first case of cochlear implantation in a 13-year-old child with CINCA syndrome. Cochlear implantation was successful at rehabilitating the hearing loss with the child able to continue mainstream education, with her academic performance and speech discrimination both showing marked improvement. Anakinra (an interleukin 1 receptor antagonist) is now in widespread use to treat CINCA syndrome and is known to rapidly reverse the inflammatory features of CINCA syndrome. However, current evidence suggests that anakinra has limited effectiveness in reversing the sensorineural hearing loss seen in CINCA syndrome. We therefore propose that cochlear implantation is a viable treatment option in this rare yet severe auto-inflammatory disease, if the patient has failed to respond to anakinra. Owing to the unknown pathogenesis of the progressive hearing loss seen in CINCA syndrome and the limited effectiveness of anakinra in reversing the progressive hearing loss, we suggest that cochlear implantation is the modality of choice in rehabilitating severe-to-profound hearing loss not responsive to anakinra.

A Smart Micro-drill for Cochleostomy Formation: A Comparison of Cochlear Disturbances with Manual Drilling and a Human Trial

BACKGROUND: Cochleostomy formation is a key stage of the cochlear implantation procedure. Minimizing the trauma sustained by the cochlea during this step is thought to be a critical feature in hearing preservation cochlear implantation. The aim of this paper is firstly, to assess the cochlea disturbances during manual and robotic cochleostomy formation. Secondly, to determine whether the use of a smart micro-drill is feasible during human cochlear implantation. MATERIALS AND METHODS: The disturbances within the cochlea during cochleostomy formation were analysed in a porcine specimen by creating a third window cochleostomy, preserving the underlying endosteal membrane, on the anterior aspect of the basal turn of the cochlea. A laser vibrometer was aimed at this third window, to assess its movement while a traditional cochleostomy was performed. Six cochleostomies were performed in total, three manually and three with a smart micro-drill. The mean and peak membrane movement was calculated for both manual and smart micro-drill arms, to represent the disturbances sustained within cochlea during cochleostomy formation. The smart micro-drill was further used to perform live human robotic cochleostomies on three adult patients who met the National Institute of Health and Clinical Excellence criteria for undergoing cochlear implantation. RESULTS: In the porcine trial, the smart micro-drill preserved the endosteal membrane in all three cases. The velocity of movement of the endosteal membrane during manual cochleostomy is approximately 20 times higher on average and 100 times greater in peak velocity, than for robotic cochleostomy. The robot was safely utilized in theatre in all three cases and successfully created a bony cochleostomy while preserving the underlying endosteal membrane. CONCLUSIONS: Our experiments have revealed that controlling the force of drilling during cochleostomy formation and opening the endosteal membrane with a pick will minimize the trauma sustained by the cochlea by a factor of 20. Additionally, the smart micro-drill can safely perform a bony cochleostomy in humans under operative conditions and preserve the integrity of the underlying endosteal membrane.

Reimplantation with a Conventional Length Electrode Following Residual Hearing Loss in Four Hybrid Implant Recipients

Hypothesis: Revision surgery using a newer-generation conventional length cochlear implant electrode will provide improved speech perception in patients that initially underwent hybrid electrode implantation and experienced post-operative loss of residual hearing and performance deterioration. CLINICAL PRESENTATION: We present four patients who experienced delayed post-operative hearing loss following implantation with the Nucleus Hybrid S8 device and underwent reimplantation with the Nucleus Freedom or Nucleus 5 device using the Contour Advance array. Pure-tone thresholds and speech perception data were retrospectively reviewed. INTERVENTION: Four subjects underwent reimplantation with the Nucleus Freedom or Nucleus 5 device after experiencing deteriorating performance related to delayed acoustic hearing loss. Comparison of pre-revision performance to the most recent post-revision performance demonstrated improved speech perception performance in all subjects following reimplantation. CONCLUSIONS: A small percent of patients will experience a significant loss of residual low-frequency hearing following hybrid implantation thereby becoming completely reliant on a shorter electrode for electrical stimulation. In the current series, reimplantation with a conventional length electrode provided improved speech perception performance in such patients. Revision surgery with a conventional length electrode should be considered in 'short electrode' recipients who experience performance deterioration following loss of residual hearing.

Cochlear Implantation in Children with Jervell and Lange-Nielsen Syndrome - a Cautionary Tale

OBJECTIVE AND IMPORTANCE: Jervell and Lange-Nielsen (JLN) syndrome is a rare cause of congenital profound hearing loss associated with a prolonged QT interval on the electrocardiogram. Children presenting for cochlear implantation with this condition may be asymptomatic but are at risk of sudden death. Screening and subsequent careful management is therefore required to ensure a successful outcome. We present our experience of cochlear implantation in children with JLN syndrome, including two who died unexpectedly, and suggest a protocol for management of such cases. CLINICAL PRESENTATION: Four cases of cochlear implantation in JLN syndrome are described. None had any previous cardiological family history. Two were diagnosed pre-operatively but, despite appropriate management under a cardiologist, died from cardiac arrest; the first in the perioperative period following reimplantation for infection, and the second unrelated to his cochlear implant surgery. The other two patients were diagnosed only subsequent to their implantation and continue to use their implants successfully. CONCLUSION: These cases highlight the variation in presentation of JLN syndrome, and the spectrum of disease severity that exists. Our protocol stresses the importance of careful assessment and counselling of parents by an experienced implant team.

The New Nucleus 5 Model Cochlear Implant: a New Surgical Technique and Early Clinical Results

OBJECTIVE: The Nucleus 5 or CI500 series cochlear implants are the new generation of Nucleus(®) cochlear implants. The receiver-stimulator package has a low profile without a pedestal projecting from the medial surface. This study aimed to demonstrate that the new design can facilitate a minimally invasive surgical approach, without the need for tie-down sutures and without a seat drilled for the receiver-stimulator package. METHODS: The surgical technique involved placing the device directly on the surface of the bone in a secure sub-periosteal pocket with a channel drilled for the lead. A well or ramped seat was not drilled and tie-down sutures were not used. Measurements were taken from the transmitting coil to the tragus and the coil to the lobule immediately after implantation, and serially thereafter to document implant position. RESULTS: To date, over 200 implants have been performed with the Nucleus 5 device. In all cases, healing was uneventful without major complications. Of 137 patients with at least 6-week follow-up data, 8% showed a measurement change of greater than 1 cm whereas only 4.4% demonstrated any clinically evident movement. None had any complications relating to migration and none required repositioning of the device. DISCUSSION: The new design can safely be inserted without drilling a well for the receiver-stimulator package. Some early post-operative movement of the package was observed which caused no clinical impact. This modified surgical technique reduces the risk of intracranial complications and reduces operating time.

Cochlear Implantation in a Patient with Sensori-neural Deafness Secondary to Charcot-Marie-Tooth Disease

Objective and importance Charcot-Marie-Tooth (CMT) disease is the most common hereditary motor and sensory neuropathy and can result in profound sensori-neural hearing loss with deficiency in speech perception out of proportion to that which would be expected if the loss was cochlear in origin. This study investigates whether the reintroduction of auditory synchrony by means of cochlear implantation will improve speech perception in those with dys-synchrony related to impairment of temporal processing abilities secondary to CMT. Clinical presentation A 67-year-old male presented with a gradual but significant decrease in his hearing as part of a slowly progressing demyelinating peripheral neuropathy. On open-set speech discrimination he scored 0%. Intervention A Med-el Flex(SOFT) cochlear implant (CI) was fully inserted into the left ear with no surgical complications. The CI speech processor was fitted 1 month post-implantation and standardized speech assessments conducted at 1 week, 3 months, 9 months, and 21 months following initial fitting, gave open-set speech discrimination scores of 0, 0, 53, and 54%, respectively. Conclusion This report demonstrates that cochlear implantation is an option to rehabilitate severe-to-profound hearing loss in adults with auditory dys-synchrony secondary to CMT disease. Progress post-implantation is likely to be slower than for the average CI user.

De Novo 7p Partial Trisomy Characterized by Subtelomeric FISH and Whole-genome Array in a Girl with Mental Retardation

ABSTRACT: Chromosome rearrangements involving telomeres have been established as one of the major causes of idiopathic mental retardation/developmental delay. This case of 7p partial trisomy syndrome in a 3-year-old female child presenting with developmental delay emphasizes the clinical relevance of cytogenetic diagnosis in the better management of genetic disorders. Application of subtelomeric FISH technique revealed the presence of interstitial telomeres and led to the ascertainment of partial trisomy for the distal 7p segment localized on the telomeric end of the short arm of chromosome 19. Whole-genome cytogenetic microarray-based analysis showed a mosaic 3.5 Mb gain at Xq21.1 besides the approximately 24.5 Mb gain corresponding to 7p15.3- > pter. The possible mechanisms of origin of the chromosomal rearrangement and the clinical relevance of trisomy for the genes lying in the critical regions are discussed.

Adrenomedullin And Nitric Oxide: Implications For The Etiology And Treatment Of Primary Brain Tumors

Gliomas, defined as tumors of glial origin, represent between 2-5 percent of all adult cancer and comprise the majority of the primary brain tumors. Infiltrating gliomas, with an incidence of more than 40percent of brain tumors, are the most common and destructive primary brain tumors for which conventional therapies have not significantly improved patient outcome. In fact, patients suffering from malignant gliomas have poor prognoses and the majority has local tumor recurrence after treatment. Tumor growth and spread of tumor cells depend basically upon angiogenesis and on functional abnormalities of tumor cells in the control of apoptosis, as they are paradigmatic for their intrinsic resistance to multiple pro-apoptotic stimuli. Therefore, promising strategies for treatment of brain cancer would be directed to appropriate neutralization of angiogenesis and sensibilization of cancer cells to undergo apoptosis. However, despite advances in this field, high-grade gliomas remain incurable with survival often measured in months. Therefore there is a need to discover new and more potent cocktails of drugs to target the key molecular pathways involved in glioma angiogenesis and apoptosis. This review deals with the effects of two groups of molecules closely linked to neural tissue, which have been implicated in brain cancer: nitric oxide and peptides of the adrenomedullin family. These molecules exert vasodilatory and proangiogenic actions. AM also has antiapoptotic functions at appropriate concentrations. The inhibition of these functions, in the case of cancer, may provide new pharmacological strategies in the treatment of this disease.

The Prevalence of Hyperuricemia in China: a Meta-analysis

The prevalence of hyperuricemia varied in different populations and it appeared to be increasing in the past decades. Recent studies suggest that hyperuricemia is an independent risk factor for cardiovascular disease. However, there has not yet been a systematic analysis of the prevalence of hyperuricemia in China.

Exploring the Binding Mechanism of Ondansetron Hydrochloride to Serum Albumins: Spectroscopic Approach

The mechanism of interaction of ondansetron hydrochloride (OND) to serum albumins [bovine serum albumin (BSA) and human serum albumin (HSA)] was studied for the first time employing fluorimetric, circular dichroism, FTIR and UV-vis absorption techniques under the simulated physiological conditions. Fluorimetric results were utilized to investigate the binding and conformational characteristics of protein upon interaction with varying concentrations of the drug. Higher binding constant values revealed the strong interaction between the drug and protein while the number of binding sites close to unity indicated single class of binding site for OND in protein. Thermodynamic results revealed that both hydrogen bond and hydrophobic interactions played a major role in stabilizing drug-protein complex. Site marker competitive experiments indicated that the OND bound to albumins at subdomin II A (Sudlow's site I). Further, the binding distance between OND and serum albumin was calculated based on the Förster's theory of non-radioactive energy transfer and found to be 2.30 and 3.41 nm, respectively for OND-BSA and OND-HSA. The circular dichroism data revealed that the presence of OND decreased the α-helix content of serum albumins. 3D-fluorescence results also indicated the conformational changes in protein upon interaction with OND. Further, the effects of some cations have been investigated in the interaction of drug to protein.

Diabetes and Driving

Peripheral Blood MRNA Expression Patterns to Differentiate Hepatocellular Carcinoma from Other Hepatic Diseases

Peripheral blood genes expressions profiling (GeXP) have been convinced to be more specific for the diagnosis of cancer and other diseases, and the GeXP system provides an ideal method to analyze multiple genes expression in one normalized and equable system. We aim to differentiate hepatocellular carcinoma from other hepatic diseases based on peripheral blood and the GeXP system. Fifteen selected hepatic diseases related genes with two house-keeping genes for normalization were detected by the GeXP system. The diagnosis model was based on K nearest neighbor classifier and cross validation, and software based on MATLAB software was built for differential diagnosis of hepatic diseases. Eight hepatic related genes were demonstrated to show an obvious statistic difference in expressions while the K nearest neighbors classifier showed that the accuracy for normal controls, hepatitis B, liver cirrhosis, hepatocellular carcinoma and the Other group was separately 80.57 %, 78.17 %, 84.48 %, 73.24 % and 85.85 %. The set of validation has been carried out to assess the accuracy of Model Two and the accuracy was even higher than the set of building for the model, except for the hepatitis B (HBV) group. A sensitive and specific GeXP system of eight genes has been developed for the accurate differential diagnosis of hepatic disease.

Natural Mood Foods: The Actions of Polyphenols Against Psychiatric and Cognitive Disorders

OBJECTIVES: Polyphenols, natural compounds found in plant-based foods, possess special properties that can battle oxidative stress and stimulate the activation of molecules that aid in synaptic plasticity, a process that underlies cognitive function. Unlike many traditional treatments, polyphenols affect a broad range of mechanisms in the brain that can assist in the maintenance of cognitive and mental health, as well as the recovery from neurodegenerative diseases. Examining the molecular basis underlying the link between food intake and brain function has presented the exciting possibility of using diet as a viable method to battle cognitive and psychiatric disorders. METHODS: We will discuss the molecular systems that link polyphenols, the gut, and the brain, as well as introduce published human and animal studies demonstrating the effects of polyphenol consumption on brain plasticity and cognition. RESULTS: By influencing cellular energy metabolism and modulating the signaling pathways of molecules involved with brain plasticity, dietary factors - formerly recognized for just their effects on bodily systems - have emerged as affecters of the brain. CONCLUSION: Thus, the consumption of diets enriched with polyphenols may present the potential of dietary manipulation as a non-invasive, natural, and inexpensive therapeutic means to support a healthy brain.

Research Addressing Follow-Up for Abnormal Cancer Screening Tests: NCI Portfolio Analyses

PURPOSE: The study's purposes were to identify the portfolio of grants awarded by the National Cancer Institute that addressed follow-up to abnormal screening tests for colon, breast and cervical cancer, document key research design characteristics, and discuss questions and issues for future practice and research.METHODS: A standardized form was used to audit grants funded from 2002 through 2011. Grant text was independently reviewed by two auditors; differences in reports were discussed until consensus was reached. The investigators then summarized findings in order to distill trends and issues.RESULTS: Twelve grants met inclusion criteria; 5, 4, 2 and 1 addressed follow-up of Pap tests, mammography, and colorectal tests and multiple screens respectively. Fifty percent were R01 awards, the majority of which applied group or individual RCT designs. One was a prospective cohort study. R21s typically emphasized qualitative methods and stressed behavioral epidemiology, measurement tool development and intervention planning; several listed aims related to determining prevalence. Definition of outcome measures was variable: e.g. completion of a follow-up test; time to follow-up; and steps until diagnosis. Four studies explicitly focused on ethnic/racial disparities; 5 on low income and underserved populations. Several emphasized measurement development. Three included cost analyses research questions. Most focused on individual level change, although changes in the broader multi-level context were proposed, but at times implicit, often viewed as process measures. A majority included aims related to understanding important mediator and moderator variables. Few explicated multilevel theories, although models reflected an ecological orientation.CONCLUSIONS: Future practice and research priorities include development of clear operational definitions of follow-up; conceptual and descriptive evaluations of how providers, patients, and organizations interact across the steps and interfaces of follow-up care; determination of priorities for multilevel intervention testing and improvement of measures, and application of appropriate and innovative study designs using multi-methods.This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261200800001E. Cancer Epidemiol Biomarkers Prev; 21(3); 1-9. ©2012 AACR.

Prospective Cohort Studies of Vitamin B6 Intake and Colorectal Cancer Incidence: Modification by Time?

BACKGROUND: Vitamin B6 may influence colorectal carcinogenesis through its role in one-carbon metabolism related DNA synthesis and methylation. However, observational studies have been inconclusive and no studies have investigated when in the natural history vitamin B6 intake may prevent colorectal cancer.METHOD: We followed 86,440 women in the Nurses' Health Study and 44,410 men in the Health Professionals Follow-up Study for up to 28 years. We assessed vitamin B6 intake every 4 years using validated food frequency questionnaires. We evaluated whether higher vitamin B6 intake in the remote past is strongly associated with a lower risk of colorectal cancer than intake in the recent past. Cox proportional hazards regression models were used to estimate multivariable relative risks (MV RRs, 95%CIs).RESULTS: Comparing top with bottom quintiles of total vitamin B6 intake, the mean plasma pyridoxal 5-phosphate (PLP, the active form of vitamin B6) levels were 98.3 pmol/mL and 38.9 pmol/mL in women and were 183.2 pmol/mL and 66.0 pmol/mL in men. Total vitamin B6 intake was significantly associated with an approximately 20-30% lower risk of colorectal cancer in age-adjusted results but these significant associations became attenuated and non-significant after adjustment for other colorectal cancer risk factors. Compared extreme quintiles of cumulative intake of total vitamin B6, the MV RRs (95%CIs) for colorectal cancer were 0.98 (0.80, 1.22; P trend = 0.79) in women and 0.98 (0.76, 1.26; P trend = 0.60) in men. For the same comparison, the MV RRs were 0.92 (0.73, 1.16) for total vitamin B6 intake 0-4 year before diagnosis, 0.99 (0.78, 1.26) for intake 4-8 year before diagnosis, 0.93 (0.71, 1.21) for intake 8-12 year before diagnosis, and 0.93 (0.69, 1.26) for intake 12-16 years before diagnosis. The corresponding MV RRs for men were 0.85 (0.63, 1.16), 0.98 (0.70, 1.37), 0.90 (0.63, 1.28), and 1.19 (0.78, 1.83), respectively. Additionally, results did not differ by cancer sub-site, sources of vitamin B6 (food or supplement), or intake of alcohol and folate.CONCLUSION: Although a small effect cannot be excluded, our results do not support a strong role of vitamin B6 intake in adulthood in colorectal carcinogenesis among middle-aged U.S. health professionals. Cancer Epidemiol Biomarkers Prev; 21(3); 1-9. ©2012 AACR.

Phenol Xenoestrogens and Mammographic Breast Density

Risk of Non-Hodgkin Lymphoma in Relation to Tricyclic Antidepressant Use

PURPOSE: We investigated the relationship between prior use of tricyclic antidepressants (TCA) and risk of non-Hodgkin lymphomas (NHL), both overall and for common subtypes of NHL; previous studies provided some evidence of an association with NHL, but did not assess the risk of specific subtypes of NHL, which have been shown to be etiologically diverse.METHODS: We conducted a population-based matched case-control study among members of Group Health (GH), an integrated healthcare delivery system. Cases included GH members diagnosed with NHL between 1980-2011 at age ≥25 with no record of a prior cancer or of certain autoimmune conditions, who had been enrolled for ≥2 years at the reference date (date of diagnosis). Eight controls were matched to each case on age, sex, enrollment on the reference date, and length of prior enrollment at GH. Information on prior TCA use, including dose, duration, recency, and type, was ascertained from automated pharmacy data. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) for NHL (and common subtypes) in relation to various patterns of TCA exposure using conditional logistic regression adjusted for confounders.RESULTS: We identified 2,768 cases and 22,127 matched controls. We did not observe an appreciably increased risk of NHL among persons who had filled ≥2 TCA prescriptions prior to the reference date compared to those who had filled none (OR: 1.1; 95% CI: 1.0-1.2). Overall risk of NHL was associated to at most a small degree with longer-term use (OR: 1.2; 95% CI: 1.0-1.4 for ≥10 prescriptions), high-dose use (OR: 1.1; 95% CI: 0.8-1.5 for ≥50 mg or equivalent), or use that began more than 5 years prior to reference date (OR: 1.0; 95% CI: 0.9-1.2). TCA use was generally not associated with most major NHL subtypes, though longer-term TCA use was associated with increased risk of chronic lymphocytic leukemia/small lymphocytic lymphoma (OR: 1.5; 95% CI: 1.1-2.0).CONCLUSIONS: We found little evidence that TCA use increases risk of NHL, overall or for specific common subtypes of NHL. Cancer Epidemiol Biomarkers Prev; 21(3); 1-9. ©2012 AACR.

Predictors of Cancer Survivors' Receptivity to Lifestyle Behavior Change Interventions

PURPOSE: To assess cancer survivors' interest in lifestyle behavior change interventions, and to identify predictors of interest.METHODS: Mailed surveys were sent to a stratified random sample of breast, colorectal, and prostate cancer survivors ascertained from the MD Anderson tumor registry and departmental databases. Surveys queried survivors about their diet, exercise, and smoking behaviors; symptoms; and their interest in interventions.RESULTS: Surveys were received from 1053 cancer survivors. Roughly half of the sample were very/extremely interested in programs to help them get in shape (45%), eat a healthy diet (54%), and control weight (49%), and 20% had no interest at all. Because they were highly intercorrelated we combined interest in diet/exercise/weight control into a single interest index. Interest was related to race/ethnicity (AA and Hispanics more interested than whites), age (p = .000, younger more interested), marital status (p = .000, divorced most interested, widowed least interested), education (p = .008, college-educated less interested than those with HS degree or some college/vocational training), and gender (p = .000; women more interested). Interest was not related to time from diagnosis, and there were no differences by cancer site after controlling for gender. BMI had a small but significant correlation with interest in programs (r = .19, p = .000; the correlation was higher in women [r = .24] than men [r = .18]). Symptom severity and interference, and feelings of distress and sadness, were positively correlated to interest (r = .07-.12, p = .000-.034); relationships were stronger among men than women. Among the 78 smokers, 51% were very/extremely interested in smoking cessation, while 20% were not at all interested. Demographic and disease-related predictors were not significantly related to interest in smoking cessation, but symptom severity and interference, and feelings of sadness were positively related to interest.CONCLUSION: Survivors' interest in lifestyle behavior change interventions varies with demographic variables, but also with symptom distress. Experiencing symptoms after cancer diagnosis is related to higher receptivity to intervention opportunities. Cancer Epidemiol Biomarkers Prev; 21(3); 1-9. ©2012 AACR.

Ruminant Fatty Acids and Prostate Cancer Risk in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study

Race and Risk of Large Bowel Polyps in Younger and Older Patients

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