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2.
Sci Adv ; 6(27)2020 07.
Article in English | MEDLINE | ID: mdl-32937447

ABSTRACT

Chromatin conformation regulates gene expression and thus, constant remodeling of chromatin structure is essential to guarantee proper cell function. To gain insight into the spatiotemporal organization of the genome, we use high-density photoactivated localization microscopy and deep learning to obtain temporally resolved super-resolution images of chromatin in living cells. In combination with high-resolution dense motion reconstruction, we find elongated ~45- to 90-nm-wide chromatin "blobs." A computational chromatin model suggests that these blobs are dynamically associating chromatin fragments in close physical and genomic proximity and adopt topologically associated domain-like interactions in the time-average limit. Experimentally, we found that chromatin exhibits a spatiotemporal correlation over ~4 µm in space and tens of seconds in time, while chromatin dynamics are correlated over ~6 µm and last 40 s. Notably, chromatin structure and dynamics are closely related, which may constitute a mechanism to grant access to regions with high local chromatin concentration.

3.
J Pediatr Urol ; 15(4): 385.e1-385.e6, 2019 Aug.
Article in English | MEDLINE | ID: mdl-31133505

ABSTRACT

INTRODUCTION: Vesicoureteral reflux (VUR) is a common pediatric urologic condition associated with urinary tract infection and pyelonephritis. It can be diagnosed via fluoroscopic voiding cystourethrogram (VCUG) and, more recently, contrast-enhanced voiding ultrasonography (ceVUS), which does not expose the patient to ionizing radiation. Voiding urosonography contrast agents used for the diagnosis of VUR have been widely available in Europe but were approved by the Food and Drug Administration for use in the United States only in 2016. OBJECTIVE: The objective was to optimize a protocol and compare the diagnostic performance of ceVUS to fluoroscopic VCUG in an academic medical center naïve to previous use of contrast-enhanced voiding urosonography. STUDY DESIGN: Thirty-nine patients referred for clinically indicated evaluation of VUR were enrolled between September 2016 and March 2017. Patients underwent contrast-enhanced ultrasonography with prediluted Lumason and under the same catheterization underwent fluoroscopic VCUG. Comparative grading was performed by pediatric radiologists on-site at the time of examination. RESULTS: Reflux was observed in 16 of 39 patients (20 of 64 renal units) ranging from grades 1 through 5. VCUG and ceVUS were concordant for detecting reflux in 10 of 39 patients (14 of 84 renal units) and excluding reflux in 23 of 39 patients (64 of 84 renal units) (Fig. 1). Using contrast enhanced voiding urosonography, 1 of 20 renal units had high-grade and 2 of 20 renal units had low-grade reflux that was not found on fluoroscopy. Using fluoroscopy, 1 of 20 renal units had high-grade and 2 of 20 renal units had low-grade reflux that had not been found on ceVUS. Two of 20 renal units were upgraded from low-grade on ceVUS to high-grade on fluoroscopy. This corresponds to a Cohen's kappa of 0.72 (confidence interval [CI] 0.54-0.91) or 'moderate.' DISCUSSION: During our investigation, we noted that there was a technical learning curve related to poor contrast mixing and the need to titrate the concentration of Lumason. However, over the course of the study, we were able to correct the technical aspects. Ultimately, our results showed good correlation between VCUG and Lumason ceVUS and only slightly less correlation than published studies by experienced centers. Future studies with voiding should allow for improved urethral visualization. CONCLUSION: While there is a considerable learning curve to the implementation of ceVUS for the diagnosis of pediatric VUR, these technical aspects can be corrected. Even a center previously naïve to contrast-enhanced ultrasound technology can, over a short period of time, demonstrate good correlation between VCUG and ceVUS in the diagnosis of VUR. Translation of ceVUS into clinical practice is an alternative to VCUG for diagnosis of reflux, is feasible, and can eliminate the radiation exposure associated with a VCUG.


Subject(s)
Contrast Media , Cystography/methods , Fluoroscopy/methods , Ultrasonography/methods , Vesico-Ureteral Reflux/diagnostic imaging , Vesico-Ureteral Reflux/epidemiology , Academic Medical Centers , Adolescent , Age Distribution , Child , Child, Preschool , Female , Fluoroscopy/adverse effects , Follow-Up Studies , Humans , Incidence , Infant , Learning Curve , Male , Pyelonephritis/etiology , Pyelonephritis/prevention & control , Radiation Exposure/prevention & control , Radiography , Risk Assessment , Sex Distribution , United States , Urination/physiology , Urodynamics/physiology , Vesico-Ureteral Reflux/therapy
4.
Transplant Proc ; 50(10): 3516-3520, 2018 Dec.
Article in English | MEDLINE | ID: mdl-30577229

ABSTRACT

BACKGROUND: Exertional heatstroke is an extremely rare cause of fulminant hepatic failure. Maximal supportive care has failed to provide adequate survival in earlier studies. This is particularly true in cases accompanied by multiorgan failure. METHODS AND MATERIALS: Our prospectively collected transplant database was retrospectively reviewed to identify patients undergoing liver transplantation for heatstroke between January 1, 2012, and December 31, 2016. We report 3 consecutive cases of male patients with fulminant hepatic failure from exertional heatstroke. RESULTS: All patients developed multiorgan failure and required intubation, vasopressor support, and renal replacement therapy. All patients were listed urgently for liver transplantation and were supported with the molecular adsorbent recirculating system while awaiting transplantation. All patients underwent liver transplantation alone and are alive and well, with recovered renal function, normal liver allograft function, and no chronic sequelae of their multiorgan failure at more than one year. CONCLUSION: Extreme heatstroke leading to whole-body organ dysfunction and fulminant liver failure is a complex entity that may benefit from therapy using the Molecular Adsorbent Recirculating System while waiting for liver transplantation as a component of a multidisciplinary, multiorgan system approach.


Subject(s)
Fluid Therapy/methods , Heat Stroke/complications , Liver Transplantation/methods , Multiple Organ Failure/etiology , Adult , Fluid Therapy/instrumentation , Humans , Liver Failure, Acute/etiology , Liver Failure, Acute/surgery , Male , Multiple Organ Failure/surgery , Retrospective Studies , Young Adult
5.
Transplant Proc ; 50(10): 3689-3693, 2018 Dec.
Article in English | MEDLINE | ID: mdl-30577256

ABSTRACT

Despite the frequency of liver transplantation in alcoholic recipients, the burden of co-occurring psychosocial comorbidities remains poorly defined. METHODS: A survey study was conducted to examine demographic, substance use, mental health, and social support variables among liver transplant (LT) recipients with alcoholic liver disease (ALD) (LT-ALD: n  = 67). Survey completers (n = 67) were compared to a sample of liver transplant recipients without ALD (LT: n = 134). RESULTS: Survey participants (n  = 67) were predominately male, in their mid-fifties, and were retired or on disability. Alcohol consumption during the 6 months prior to transplant was reported by more than a third of participants. Alcohol consumption post-transplant was reported by 21.2% of respondents, with 4.5% of participants reporting "at-risk" levels of post-transplant alcohol use. Illicit drug use prior to transplant was reported by nearly half of participants (47.8%), and 16.4% reported illicit drug use post-transplant. Approximately half of the sample reported a history of cigarette smoking, and one-third of respondents (29.2%) reported current cigarette smoking. Participants frequently endorsed mental health symptoms consistent with moderate to severe depression (22.4%) and anxiety (17.9%). CONCLUSIONS: Despite relatively low rates of problematic alcohol use post-transplant, there is a significant burden of disability, substance use, and psychiatric symptomatology in this population.


Subject(s)
Liver Transplantation/psychology , Substance-Related Disorders/epidemiology , Adult , Comorbidity , Female , Humans , Male , Middle Aged , Social Support , Substance-Related Disorders/psychology
6.
Int J Infect Dis ; 67: 36-40, 2018 Feb.
Article in English | MEDLINE | ID: mdl-29183843

ABSTRACT

BACKGROUND: HIV-associated neurocognitive disorders (HAND) are frequently occurring comorbidities in HIV-positive patients, diagnosed by means of a neuropsychological assessment (NPA). Due to the magnitude of the HIV-positive population in Sub-Saharan Africa, easy-to-use cognitive screening tools are essential. METHODS: This was a cross-sectional clinical trial involving 44 HIV-positive patients (on stable cART) and 73 HIV-negative controls completing an NPA, the International HIV Dementia Scale (IHDS), and a culturally appropriate cognitive screening tool, the Montreal Cognitive Assessment-Basic (MoCA-B). HAND were diagnosed by calculating Z-scores using internationally published normative data on NPA, as well as by using data from the HIV-negative group to validate the MoCA-B. RESULTS: One hundred and seventeen patients were included (25% male, median age 35 years, median 11 years of education). A moderate correlation was found between the MoCA-B and NPA total Z-score (Pearson's r=0.36, p=0.02). Area under the curve (AUC) values for MoCA-B and IHDS were 0.59 and 0.70, respectively. The prevalence of HAND in HIV-positive patients was 66% when calculating Z-scores using published normative data versus 48% when using the data from the present HIV-negative cohort. CONCLUSION: The MoCA-B appeared not to be a valid screening tool for HAND in this setting. The prevalence of HAND in this setting is high, but appeared overestimated when using published norms.


Subject(s)
AIDS Dementia Complex/diagnosis , Anti-HIV Agents/therapeutic use , Cognitive Dysfunction/diagnosis , HIV Infections/complications , Mental Status and Dementia Tests , AIDS Dementia Complex/psychology , Adult , Area Under Curve , Cognitive Dysfunction/etiology , Cross-Sectional Studies , Drug Therapy, Combination , Feasibility Studies , Female , HIV Infections/drug therapy , Humans , Male , Pilot Projects , Prevalence , Rural Population , South Africa
8.
J Neurovirol ; 23(1): 20-32, 2017 02.
Article in English | MEDLINE | ID: mdl-27718211

ABSTRACT

HIV-associated neurocognitive disorder (HAND) is a frequently occurring comorbidity of HIV infection. Evidence suggests this condition starts subclinical before a progression to a symptomatic stage. Blood oxygenated level dependent (BOLD) fMRI has shown to be a sensitive tool to detect abnormal brain function in an early stage and might therefore be useful to evaluate the effect of HIV infection on brain function. An extensive literature search was performed in June 2015. Eligibility criteria for included studies were as follows: (1) conducting with HIV-positive patients, (2) using BOLD fMRI, and (3) including a HIV-negative control group. A total of 19 studies were included in the review including 931 participants. Differences in activation between HIV-positive and -negative participants were found when testing multiple domains, i.e., attention, (working) memory, and especially executive functioning. Overall, HIV-positive patients showed hyperactivation in task-related brain regions despite equal performances as controls. Task performance was degraded only for the most complex tasks. A few studies investigated the effect of aging on fMRI, and most of them found no interaction with HIV infection. Only three studies evaluated the effect of combination antiretroviral therapy (cART) on functional data suggesting an increase in activation with the use of cART. fMRI is a sensitive instrument to detect subtle cognitive changes in HIV patients. Open questions remain regarding the effects of cART on fMRI and the effects of aging on fMRI.


Subject(s)
Cognitive Dysfunction/diagnostic imaging , HIV Infections/diagnostic imaging , Magnetic Resonance Imaging/methods , Adult , Antiretroviral Therapy, Highly Active , Antiviral Agents/therapeutic use , Brain/physiopathology , Brain Mapping , Case-Control Studies , Cognitive Dysfunction/complications , Cognitive Dysfunction/drug therapy , Cognitive Dysfunction/physiopathology , Executive Function/physiology , HIV Infections/complications , HIV Infections/drug therapy , HIV Infections/physiopathology , Humans , Memory, Short-Term/physiology , Neuropsychological Tests , Severity of Illness Index , Task Performance and Analysis
9.
BMJ Open ; 6(1): e009194, 2016 Jan 21.
Article in English | MEDLINE | ID: mdl-26801464

ABSTRACT

OBJECTIVES: Prior research has shown that Dutch general practitioners (GPs) do not always offer HIV testing and the number of undiagnosed HIV patients remains high. We aimed to further investigate the frequency and reasons for (not) testing for HIV and the contribution of GPs to the diagnosis of HIV infections in the Netherlands. DESIGN: Observational study. SETTING: (1) Dutch primary care network of 42-45 sentinel practices where report forms during sexually transmitted infection (STI)-related consultations were routinely collected, 2008-2013. (2) Dutch observational cohort with medical data of HIV-positive patients in HIV care, 2008-2013. OUTCOME MEASURES: The proportion of STI-related consultations in patients from high-risk groups tested for HIV, with additional information requested from GPs on HIV testing preconsultation or postconsultation for whom HIV testing was indicated, but not performed. Next, information was collected on the profile of HIV-positive patients entering specialised HIV care following diagnosis by GPs. RESULTS: Initially, an HIV test was reported (360/907) in 40% of STI-related consultations in high-risk groups. Additionally, in 26% of consultations an HIV test had been performed in previous or follow-up consultations or at different STI-care facilities. The main reasons for not testing were perceived insignificant risk; 'too' recent risk according to GPs or the reluctance of patients. The initiative of the patient was a strong determinant for HIV testing. GPs diagnosed about one third of all newly found cases of HIV. Compared with STI clinics, HIV-positive patients diagnosed in general practice were more likely to be older, female, heterosexual male or sub-Saharan African. CONCLUSIONS: In one-third of the STI-related consultations of persons from high-risk groups, no HIV test was performed in primary care, which is lower than previously reported. Risk-based testing has intrinsic limitations and implementation of new additional strategies in primary care is warranted.


Subject(s)
General Practitioners , HIV Infections/diagnosis , Referral and Consultation , Female , Humans , Male , Medical Records/standards , Netherlands , Physician's Role , Risk-Taking , Surveys and Questionnaires , Unsafe Sex
10.
Transplant Proc ; 47(6): 1901-4, 2015.
Article in English | MEDLINE | ID: mdl-26293070

ABSTRACT

INTRODUCTION: We have aggressively used continuous veno-venous hemofiltration (CVVH) on high model for end-stage liver disease (MELD) score liver transplant patients with acute kidney injury and hypothesized that the addition of intraoperative CVVH therapy would improve overall outcomes. METHODS: We performed a retrospective review of all adult, single organ, liver transplant recipients requiring preoperative renal replacement therapy between January 1, 2011 and June 1, 2013. Intraoperative and perioperative records and laboratory values were collected and used to create a database of these patients. Patients were grouped according to whether or not they underwent CVVH at the time of liver transplantation. RESULTS: Twenty-one patients with new-onset renal failure requiring preoperative renal replacement therapy received a liver transplant alone. Fourteen received intraoperative CVVH and 7 patients did not. The average MELD score was similar between groups (34 for intraoperative CVVH vs 35; P = .8). Preoperative sodium and potassium were higher for the group receiving intraoperative CVVH, but still fell within normal ranges. Preoperative lactate levels were higher in the group that received intraoperative CVVH (4.7 vs 2.0 mmol/L; P = .01). Intraoperative CVVH did not decrease intraoperative transfusion requirements or intensive care unit (ICU) and hospital lengths of stay. Differences in reoperative rates did not reach statistical significance. All patients were weaned off renal replacement therapy. One-year patient survival rate was 86% for intraoperative CVVH versus 71% without. CONCLUSION: The judicious use of intraoperative CVVH therapy may permit patients with increasing severity of illness to achieve outcomes comparable with less ill patients.


Subject(s)
Acute Kidney Injury/therapy , Hemofiltration/methods , Intensive Care Units , Intraoperative Care/methods , Kidney Transplantation/methods , Acute Kidney Injury/mortality , Female , Humans , Male , Maryland/epidemiology , Middle Aged , Retrospective Studies , Survival Rate/trends
12.
J Microsc ; 254(3): 146-56, 2014 Jun.
Article in English | MEDLINE | ID: mdl-24684609

ABSTRACT

Boron neutron capture therapy (BNCT) of cancer depends on the selective delivery of a sufficient number of boron-10 ((10)B) atoms to individual tumour cells. Cell killing results from the (10)B (n, α)(7) Li neutron capture and fission reactions that occur if a sufficient number of (10)B atoms are localized in the tumour cells. Intranuclear (10)B localization enhances the efficiency of cell killing via damage to the DNA. The net cellular content of (10)B atoms reflects both bound and free pools of boron in individual tumour cells. The assessment of these pools, delivered by a boron delivery agent, currently cannot be made at subcellular-scale resolution by clinically applicable techniques such as positron emission tomography and magnetic resonance imaging. In this study, a secondary ion mass spectrometry based imaging instrument, a CAMECA IMS 3f ion microscope, capable of 500 nm spatial resolution was employed. Cryogenically prepared cultured human T98G glioblastoma cells were evaluated for boron uptake and retention of two delivery agents. The first, L-p-boronophenylalanine (BPA), has been used clinically for BNCT of high-grade gliomas, recurrent tumours of the head and neck region and melanomas. The second, a boron analogue of an unnatural amino acid, 1-amino-3-borono-cyclopentanecarboxylic acid (cis-ABCPC), has been studied in rodent glioma and melanoma models by quantification of boron in the nucleus and cytoplasm of individual tumour cells. The bound and free pools of boron were assessed by exposure of cells to boron-free nutrient medium. Both BPA and cis-ABCPC delivered almost 70% of the pool of boron in the free or loosely bound form to the nucleus and cytoplasm of human glioblastoma cells. This free pool of boron could be easily mobilized out of the cell and was in some sort of equilibrium with extracellular boron. In the case of BPA, the intracellular free pool of boron also was affected by the presence of phenylalanine in the nutrient medium. This suggests that it might be advantageous if patients were placed on a low phenylalanine diet prior to the initiation of BNCT. Since BPA currently is used clinically for BNCT, our observations may have direct relevance to future clinical studies utilizing this agent and provides support for individualized treatment planning regimens rather than the use of fixed BPA infusion protocols.


Subject(s)
Boron/administration & dosage , Boron/metabolism , Cell Tracking/methods , Glioblastoma/metabolism , Isotopes , Microscopy, Confocal , Spectrometry, Mass, Secondary Ion/methods , Boron Compounds/administration & dosage , Boron Compounds/metabolism , Boron Neutron Capture Therapy , Calcium/metabolism , Cell Line, Tumor , Glioblastoma/radiotherapy , Humans , Intracellular Space/metabolism , Phenylalanine/administration & dosage , Phenylalanine/analogs & derivatives , Phenylalanine/metabolism , Potassium/metabolism , Sodium/metabolism , Time Factors
13.
Child Care Health Dev ; 40(6): 853-62, 2014 Nov.
Article in English | MEDLINE | ID: mdl-24117704

ABSTRACT

BACKGROUND: Positive family environments are crucial in promoting children's emotional and behavioural well-being, and may also buffer development of attention-deficit/hyperactivity disorder (ADHD). ADHD is highly heritable, but psychosocial factors in the family environment, particularly family cohesion and communication, may mediate genetic predispositions. The purpose of the current study is to examine the mediating influence of the adoptive family environment between pre-adoptive risk factors and youths' ADHD symptomatology at 14 years post adoption. METHODS: The data used in this study were obtained from the fourth wave of the California Long-Range Adoption Study (CLAS) (n = 449). Using structural equation modelling (SEM), family sense of coherence and family adaptability were tested as possible mediators between environmental and biological predictors and ADHD symptomatology. Predictors included birthweight, gender, age at adoption, adoption from foster care, transracial adoption status, ethnicity and having a previous diagnosis of ADHD. RESULTS: Results show that, while adoption from foster care is negatively associated with family functioning, higher family cohesion and adaptability mediate this influence on children's ADHD symptomatology. Older age of adoption directly predicts greater ADHD symptoms with no mediating influence of the family environment. CONCLUSIONS: The mediating influence of the family environment between children's risk factors and ADHD symptoms suggests that family intervention strategies may be helpful in improving adopted children's outcomes. Once children are adopted, targeting family communication patterns and dynamics may be an additional part of developing an evidence-based, post-adoption services toolkit.


Subject(s)
Adaptation, Psychological , Adoption , Attention Deficit Disorder with Hyperactivity/psychology , Child Behavior Disorders/psychology , Gene-Environment Interaction , Parent-Child Relations , Social Environment , Adolescent , Adoption/psychology , Adult , Attention Deficit Disorder with Hyperactivity/epidemiology , Child , Child Behavior Disorders/epidemiology , Child, Preschool , Evidence-Based Practice , Female , Humans , Infant , Male , Middle Aged , Parenting/psychology , Parents/psychology , Surveys and Questionnaires
14.
Am J Transplant ; 13(10): 2743-9, 2013 Oct.
Article in English | MEDLINE | ID: mdl-23915309

ABSTRACT

Procurement of a facial vascularized composite allograft (VCA) should allow concurrent procurement of all solid organs and ensure their integrity. Because full facial procurement is time-intensive, "simultaneous-start" procurement could entail VCA ischemia over 12 h. We procured a total face osteomyocutaneous VCA from a brain-dead donor. Bedside tracheostomy and facial mask impression were performed preoperative day 1. Solid organ recovery included heart, lungs, liver, kidneys, and pancreas. Facial dissection time was 12 h over 15 h to diminish ischemia while awaiting recipient preparation. Solid organ recovery began at 13.5 h, during midfacial osteotomies, and concluded immediately after facial explantation. Facial thoracic and abdominal teams worked concurrently. Estimated blood loss was 1300 mL, requiring five units of pRBC and two units FFP. Urine output, MAP, pH and PaO2 remained normal. All organs had good postoperative function. We propose an algorithm that allows "face first, concurrent completion" recovery of a complex facial VCA by planning multiple pathways to expedient recovery of vital organs in the event of clinical instability. Beginning the recipient operation earlier may reduce waiting time due to extensive recipient scarring causing difficult dissection.


Subject(s)
Algorithms , Brain Death , Face/surgery , Facial Transplantation/methods , Tissue Donors/supply & distribution , Tissue and Organ Procurement/methods , Adult , Anatomic Landmarks , Face/blood supply , Humans , Male , Young Adult
15.
Transplant Proc ; 45(5): 1931-3, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23769076

ABSTRACT

BACKGROUND: Although the LigaSure device is widely used, its use in liver transplantation, where compounding factors of portal hypertension, coagulopathy, and thrombocytopenia exist, is poorly described. METHODS: From October 1, 2011, to December 31, 2011, 6 patients underwent liver transplantation with recipient hepatectomy utilizing the LigaSure device. Outcomes using the device were compared with 6 contemporaneous patients in whom the device was not used. RESULTS: Patient demographics, preoperative laboratory values, and Model for End-Stage Liver Disease scores were not different. Recipient hepatectomy was performed, on average, 43 minutes faster using the LigaSure device (P = .02). Although total operative time and intraoperative blood product usage were lower when the LigaSure was used, these differences did not attain statistical significance. Duration of stay and recipient readmission rates were similar. CONCLUSIONS: LigaSure vessel sealing is an efficient method for recipient hepatectomy in liver transplantation. Vessel sealing of caval, portal, and other structures can be safely performed in the setting of end-stage liver disease.


Subject(s)
Hemostasis, Surgical , Hepatectomy/methods , Liver Transplantation , Female , Humans , Length of Stay , Ligation , Male , Middle Aged
16.
Ann Oncol ; 23(11): 2820-2827, 2012 Nov.
Article in English | MEDLINE | ID: mdl-22571859

ABSTRACT

BACKGROUND: Neoadjuvant therapy has been investigated for localized and locally advanced pancreatic ductal adenocarcinoma (PDAC) but no standard of care exists. Combination cetuximab/gemcitabine/radiotherapy demonstrates encouraging preclinical activity in PDAC. We investigated cetuximab with twice-weekly gemcitabine and intensity-modulated radiotherapy (IMRT) as neoadjuvant therapy in patients with localized or locally advanced PDAC. EXPERIMENTAL DESIGN: Treatment consisted of cetuximab load at 400 mg/m(2) followed by cetuximab 250 mg/m(2) weekly and gemcitabine 50 mg/m(2) twice-weekly given concurrently with IMRT to 54 Gy. Following therapy, patients were considered for resection. RESULTS: Thirty-seven patients were enrolled with 33 assessable for response. Ten patients (30%) manifested partial response and 20 (61%) manifested stable disease by RECIST. Twenty-five patients (76%) underwent resection, including 18/23 previously borderline and 3/6 previously unresectable tumors. Twenty-three (92%) of these had negative surgical margins. Pathology revealed that 24% of resected tumors had grade III/IV tumor kill, including two pathological complete responses (8%). Median survival was 24.3 months in resected patients. Outcome did not vary by epidermal growth factor receptor status. CONCLUSIONS: Neoadjuvant therapy with cetuximab/gemcitabine/IMRT is tolerable and active in PDAC. Margin-negative resection rates are high and some locally advanced tumors can be downstaged to allow for complete resection with encouraging survival. Pathological complete responses can occur. This combination warrants further investigation.


Subject(s)
Adenocarcinoma/therapy , Antibodies, Monoclonal/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Deoxycytidine/analogs & derivatives , Pancreatic Neoplasms/therapy , Radiotherapy, Intensity-Modulated , Adult , Aged , Aged, 80 and over , Antibodies, Monoclonal/adverse effects , Antibodies, Monoclonal, Humanized , Antimetabolites, Antineoplastic/adverse effects , Antimetabolites, Antineoplastic/therapeutic use , Antineoplastic Agents/adverse effects , Antineoplastic Agents/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Cetuximab , Deoxycytidine/administration & dosage , Deoxycytidine/adverse effects , ErbB Receptors/biosynthesis , Female , Humans , Male , Middle Aged , Neoadjuvant Therapy/adverse effects , Radiotherapy, Intensity-Modulated/adverse effects , Treatment Outcome , Gemcitabine
17.
Am J Transplant ; 11(7): 1407-16, 2011 Jul.
Article in English | MEDLINE | ID: mdl-21668624

ABSTRACT

Vascularized composite allograft (VCA) transplantation (also referred to as composite tissue allotransplantation) has demonstrated clinical success in cases of hand, arm and face transplantation despite prior belief that skin provides an insurmountable barrier to allograft rejection. These overall good outcomes are facilitated by substantial immunosuppressive requirements in otherwise healthy patients, yet still demonstrate frequent rejection episodes. We developed a nonhuman primate model of facial segment allotransplantation to elucidate the unique pathophysiology and immunosuppressive requirements of VCA with addition of concomitant vascularized bone marrow (VBM). Heterotopically transplanted facial segment VCA with VBM treated only with tacrolimus and mycophenolate mofetil (MMF) demonstrated prolonged rejection-free survival, compared to VCA without VBM that demonstrated early rejection episodes and graft loss. While VCA with VBM demonstrated sporadic macrochimerism, acute and chronic rejection and graft loss occurred after discontinuation of immunosuppression. These data support an immunomodulatory role of VBM in VCA that reduces immunosuppressive requirements while providing improved outcomes.


Subject(s)
Bone Marrow/blood supply , Abdominal Wall/surgery , Animals , Bone Marrow/drug effects , Facial Transplantation/methods , Female , Graft Survival/drug effects , Immunosuppression Therapy , Immunosuppressive Agents/therapeutic use , Macaca fascicularis , Male , Mycophenolic Acid/analogs & derivatives , Mycophenolic Acid/therapeutic use , Tacrolimus/therapeutic use , Transplantation Chimera , Transplantation, Homologous
18.
J Radiol ; 92(2): 118-24, 2011 Feb.
Article in French | MEDLINE | ID: mdl-21352743

ABSTRACT

The purpose of this article is to review the technique of fetal chest ultrasound screening evaluation, the diagnostic work-up in the presence of fetal mediastinal shift and which ultrasound imaging features to look for. The first step in evaluating the fetal thorax is to confirm situs. Then, a median sagittal line is drawn from a four-chamber view to assist in spatial orientation followed by echotexture analysis of the structures of the thorax in the presence of mediastinal shift. We propose a systematic approach based on the direction of the mediastinal shift and echogenicity of the compressing hemithorax. When the hemithorax contralateral to the mediastinal shift is enlarged, which is the most frequent situation, diaphragmatic hernia and macrocystic congenital cystic adenomatoid malformation are the most likely etiologies when the mass is heterogeneous. Microcystic congenital cystic adenomatoid malformation, sometimes associated with sequestration, is the most frequent etiology when the mass is homogeneous. When the hemithorax ipsilateral to the mediastinal shift is small, which is less frequent, and the contralateral hemithorax is homogeneously isoechoic, then a diagnosis of lung hypoplasia-agenesis-aplasia should be considered.


Subject(s)
Mediastinum/abnormalities , Mediastinum/diagnostic imaging , Ultrasonography, Prenatal , Algorithms , Decision Trees , Female , Humans , Pregnancy , Thorax/abnormalities , Thorax/diagnostic imaging
19.
Am J Transplant ; 10(7): 1660-7, 2010 Jul.
Article in English | MEDLINE | ID: mdl-20455878

ABSTRACT

C4d+ antibody-mediated rejection following pancreas transplantation has not been well characterized. Therefore, we assessed the outcomes of 27 pancreas transplantation patients (28 biopsies), with both C4d staining and donor-specific antibodies (DSA) determined, from a cohort of 257 patients. The median follow-up was 50 (interquartile range [IQR] 8-118) months. Patients were categorized into 3 groups: group 1, patients with minimal or no C4d staining and no DSA (n = 13); group 2, patients with either DSA present but no C4d, diffuse C4d+ and no DSA or focal C4d+ and DSA (n = 6); group 3, patients with diffuse C4d+ staining and DSA (n = 9). Active septal inflammation, acinar inflammation and acinar cell injury/necrosis were significantly more abundant in group 3 than in group 2 (respective p-values: 0.009; 0.033; 0.025) and in group 1 (respective p-values: 0.034; 0.009; 0.002). The overall uncensored pancreas graft survival rate for groups 1, 2 and 3 were 53.3%, 66.7% and 34.6%, respectively (p = 0.044). In conclusion, recipients of pancreas transplants with no C4d or DSA had excellent long-term graft survival in comparison with patients with both C4d+ and DSA present. Hence, C4d should be used as an additional marker in combination with DSA in the evaluation of pancreas transplant biopsies.


Subject(s)
Complement C4b/analysis , Graft Rejection/pathology , Pancreas Transplantation/pathology , Peptide Fragments/analysis , Adult , Biopsy , Coloring Agents , Electronic Health Records , Female , Follow-Up Studies , Graft Rejection/blood , Graft Rejection/immunology , HLA Antigens/analysis , Histocompatibility Testing , Humans , Immunosuppressive Agents/therapeutic use , Inflammation/etiology , Inflammation/pathology , Male , Middle Aged , Pancreas Transplantation/immunology , Postoperative Complications/immunology , Postoperative Complications/pathology , Time Factors , Transplantation, Homologous/pathology , Treatment Outcome
20.
Ultrasound Obstet Gynecol ; 35(5): 560-5, 2010 May.
Article in English | MEDLINE | ID: mdl-20069658

ABSTRACT

OBJECTIVE: Congenital diarrhea is very rare, and postnatal diagnosis is often made once the condition has caused potentially lethal fluid loss and electrolyte disorders. Prenatal detection is important to improve the immediate neonatal prognosis. We aimed to describe the prenatal ultrasound and magnetic resonance (MRI) imaging findings in fetuses with congenital diarrhea. METHODS: The study reports the pre- and postnatal findings in four fetuses that presented with generalized bowel dilatation and polyhydramnios. We analyzed the fetal ultrasound and MRI examinations jointly, then compared our provisional diagnosis with the amniotic fluid biochemistry and subsequently with the neonatal stool characteristics. RESULTS: In each of the four cases an ultrasound examination between 22 and 30 weeks' gestation showed moderate generalized bowel dilatation and polyhydramnios suggesting intestinal obstruction. MRI examinations performed between 24 and 32 weeks' gestation confirmed that the dilatation was of gastrointestinal (GI) origin, with a signal indicating intraluminal water visible throughout the small bowel and colon. The expected hypersignal on T1-weighted sequences characteristic of physiological meconium was absent in the colon and rectum. This suggested that the meconium had been completely diluted and flushed out by the water content of the bowel. The constellation of MRI findings enabled a prenatal diagnosis of congenital diarrhea. The perinatal lab test findings revealed two cases of chloride diarrhea and two of sodium diarrhea. CONCLUSION: Congenital diarrhea may be misdiagnosed as intestinal obstruction on prenatal ultrasound but has characteristic findings on prenatal MRI enabling accurate diagnosis; this is important for optimal neonatal management.


Subject(s)
Amniotic Fluid/microbiology , Diarrhea/diagnosis , Fetal Diseases/diagnosis , Intestine, Small/abnormalities , Polyhydramnios/diagnosis , Prenatal Diagnosis/methods , Diarrhea/congenital , Diarrhea/embryology , Dilatation, Pathologic/congenital , Dilatation, Pathologic/diagnosis , Female , Gestational Age , Humans , Infant, Newborn , Intestine, Small/embryology , Magnetic Resonance Imaging , Male , Meconium/metabolism , Pregnancy
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