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1.
Clin Transplant ; 37(8): e14903, 2023 08.
Article in English | MEDLINE | ID: mdl-36595343

ABSTRACT

INTRODUCTION: Many kidney transplant (KT) centers decline patients with a body mass index (BMI) ≥40 kg/m2 . This study's aim was to evaluate KT outcomes according to recipient BMI. METHODS: We performed a single-center, retrospective review of adult KTs comparing BMI ≥40 patients (n = 84, BMI = 42 ± 2 kg/m2 ) to a matched BMI < 40 cohort (n = 84, BMI = 28 ± 5 kg/m2 ). Patients were matched for age, gender, race, diabetes, and donor type. RESULTS: BMI ≥40 patients were on dialysis longer (5.2 ± 3.2 years vs. 4.1 ± 3.5 years, p = .03) and received lower kidney donor profile index (KDPI) kidneys (40 ± 25% vs. 53 ± 26%, p = .003). There were no significant differences in prevalence of delayed graft function, reoperations, readmissions, wound complications, patient survival, or renal function at 1 year. Long-term graft survival was higher for BMI ≥40 patients, including after adjusting for KDPI (BMI ≥40: aHR = 1.79, 95% CI = 1.09-2.9). BMI ≥40 patients had similar BMI change in the first year post-transplant (delta BMI: BMI ≥ 40 +.9 ± 3.3 vs. BMI < 40 +1.1 ± 3.2, p = .59). CONCLUSIONS: Overall outcomes after KT were comparable in BMI ≥40 patients compared to a matched cohort with lower BMI with improved long-term graft survival in obese patients. BMI-based exclusion criteria for KT should be reexamined in favor of a more individualized approach.


Subject(s)
Kidney Transplantation , Adult , Humans , Kidney Transplantation/adverse effects , Body Mass Index , Precision Medicine , Graft Survival , Risk Factors , Retrospective Studies
2.
Clin Transplant ; 36(5): e14599, 2022 05.
Article in English | MEDLINE | ID: mdl-35044001

ABSTRACT

The influence of African American (AA) recipient race on outcomes following simultaneous pancreas-kidney transplantation (SPKT) is uncertain. METHODS: From 11/01 to 2/19, we retrospectively studied 158 Caucasian (C) and 57 AA patients (pts) undergoing SPKT. RESULTS: The AA group had fewer patients on peritoneal dialysis (30% C vs. 14% AA), more patients with longer dialysis duration (28% C vs. 51% AA), more sensitized (PRA ≥20%) patients (6% C vs. 21% AA), and more patients with pretransplant C-peptide levels ≥2.0 ng/ml (11% C vs. 35% AA, all P < .05). With a mean 9.2 year follow-up, patient survival (65% C vs. 77% AA, P = .098) slightly favored the AA group, whereas kidney (55% C vs. 60% AA) and pancreas (48% C vs. 54% AA) graft survival rates (GSRs) were comparable. Death-censored kidney (71% C vs. 68% AA) and pancreas (both 62%) GSRs demonstrated that death with a functioning graft (DWFG) was more common in C vs. AA patients (23% C vs. 12% AA, P = .10). The incidence of death-censored dual graft loss (usually rejection) was 7% C versus 21% AA (P = .005). CONCLUSIONS: Following SPKT, AA patients are at a greater risk for dual immunological graft loss whereas C patients are at greater risk for DWFG.


Subject(s)
Kidney Transplantation , Pancreas Transplantation , Black or African American , Graft Rejection/epidemiology , Graft Survival , Humans , Pancreas , Retrospective Studies , Treatment Outcome
3.
Contact Dermatitis ; 85(6): 643-649, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34387868

ABSTRACT

BACKGROUND: In the 2010s an epidemic of allergic contact dermatitis to methylisothiazolinone (MI) occurred in Europe. European authorities banned the use of methylisothiazolinone in leave-on cosmetics in 2017 and limited its use in rinse-off products in 2018. OBJECTIVES: To investigate the sensitization rate to MI in Belgium between January 2014 and December 2019, and to assess cosensitizations to octylisothiazolinone (OIT) and benzisothiazolinone (BIT) in MI-sensitized patients. METHODS: A retrospective study of patch test results with MI, OIT, and BIT observed in patients attending five Belgian hospitals. RESULTS: Overall, 560 of 10 029 patients (5.58%) had a positive patch test reaction to MI, and its sensitization rate decreased from 7.9% in 2014 to 3.1% in 2019. Rinse-off cosmetics, paints, and detergents were the most prevalent sensitization sources in recent years. Simultaneous reactions readily occurred to OIT, and, surprisingly, and increasingly, also to BIT. CONCLUSIONS: Contact allergy to MI in Belgium has reached a pre-epidemic level, reflecting the impact of recent regulatory measures. Leave-on cosmetics, in contrast to rinse-off products, have almost disappeared as sensitization sources in Europe. Paints and detergents also remain problematic. The remarkably high number of patients (co)sensitized to BIT should be a focus of future research.


Subject(s)
Dermatitis, Allergic Contact/epidemiology , Dermatitis, Allergic Contact/etiology , Thiazoles/adverse effects , Adolescent , Adult , Aged , Belgium/epidemiology , Child , Child, Preschool , Cosmetics/adverse effects , Detergents/adverse effects , Female , Humans , Male , Middle Aged , Paint/adverse effects , Patch Tests , Retrospective Studies , Young Adult
4.
Subst Abus ; 42(4): 1040-1048, 2021.
Article in English | MEDLINE | ID: mdl-34236292

ABSTRACT

Background: With a drastic shortage of addiction medicine specialists-and an ever-growing number of patients with opioid use disorder (OUD)-there is a dire need for more clinicians to feel confident in prevention and management of OUD and obtain a DEA-X waiver to prescribe medications to treat OUD. Here we determine if it is feasible to certify 4th year medical students with DEA-X waiver training as a component of the PROUD (Prevent and Reduce Opioid Use Disorder) curriculum, and if PROUD enhanced preparedness for medical students to manage OUD as interns. Methods: We implemented a sequential mixed-methods IRB approved study to assess feasibility (completing all required components of DEA-X waiver training) and impact of PROUD (measured by knowledge growth, enhancement for residency, and utilization of training during internship). Students completed 11 hours of required OUD training. Quantitative data included pre-/post- knowledge and curriculum satisfaction assessments as well as long-term impact with follow up survey as interns. Qualitative data was collected by survey and semi-structured focus groups. Results: All 120 graduating medical students completed the required components of the curriculum. Knowledge improved on the Provider Clinical Support Services (12.9-17.3, p < 0.0001) and Brief Opioid Overdose Knowledge assessments (10.15-10.81, p < 0.0001). Course satisfaction was high: 90% recommended online modules; 85% recommended training overall. Six qualitative themes emerged: (1) curriculum content was practical, (2) online modules allowed flexibility, (3) in-person seminars ensured authenticity, (4) timing at the transition to residency was optimal, (5) curriculum enhanced awareness and confidence, and (6) training was applicable to future careers. At 3 months, 60% reported using their training during internship; 64% felt more prepared to treat OUD than peers. Conclusions: PROUD trained 4th year medical students in opioid stewardship. As interns, students felt ready to serve as change agents to prevent, diagnose, and treat OUD.


Subject(s)
Buprenorphine , Internship and Residency , Opioid-Related Disorders , Students, Medical , Analgesics, Opioid/therapeutic use , Buprenorphine/therapeutic use , Humans , Opiate Substitution Treatment , Opioid-Related Disorders/drug therapy
5.
J Med Internet Res ; 20(10): e284, 2018 10 30.
Article in English | MEDLINE | ID: mdl-30377147

ABSTRACT

BACKGROUND: Despite their potential benefits, many electronic health (eHealth) innovations evaluated in major studies fail to integrate into organizational routines, and the implementation of these innovations remains problematic. OBJECTIVE: The purpose of this study was to describe health care professionals' self-identified perceived barriers and facilitators for the implementation of a Web-based portal to monitor asthmatic children as a substitution for routine outpatient care. Also, we assessed patients' (or their parents) satisfaction with this eHealth innovation. METHODS: Between April and November 2015, we recruited 76 health care professionals (from 14 hospitals). During a period of 6 months, participants received 3 questionnaires to identify factors that facilitated or impeded the use of this eHealth innovation. Questionnaires for patients (or parents) were completed after the 6-month virtual asthma clinic (VAC) implementation period. RESULTS: Major perceived barriers included concerns about the lack of structural financial reimbursement for Web-based monitoring, lack of integration of this eHealth innovation with electronic medical records, the burden of Web-based portal use on clinician workload, and altered patient-professional relationship (due to fewer face-to-face contacts). Major perceived facilitators included enthusiastic and active initiators, a positive attitude of professionals toward eHealth, the possibility to tailor care to individual patients ("personalized eHealth"), easily deliverable care according to current guidelines using the VAC, and long-term profit and efficiency. CONCLUSIONS: The implementation of Web-based disease monitoring and management in children is complex and dynamic and is influenced by multiple factors at the levels of the innovation itself, individual professionals, patients, social context, organizational context, and economic and political context. Understanding and defining the barriers and facilitators that influence the context is crucial for the successful implementation and sustainability of eHealth innovations.


Subject(s)
Asthma/therapy , Internet/trends , Telemedicine/methods , Ambulatory Care , Child , Female , Humans , Male , Middle Aged , Qualitative Research , Surveys and Questionnaires
6.
Clin Transplant ; 31(5)2017 05.
Article in English | MEDLINE | ID: mdl-28263408

ABSTRACT

Patients considering renal transplantation face an increasingly complex array of choices as a result of the revised kidney transplant allocation system. Decision aids have been shown to improve patient decision-making through the provision of detailed, relevant, individualized clinical data. A mobile iOS-based application (app) including animated patient education and individualized risk-adjusted outcomes following kidney transplants with varying donor characteristics and DSA waiting times was piloted in two large US transplant programs with a diverse group of renal transplant candidates (N = 81). The majority (86%) of patients felt that the app improved their knowledge and was culturally appropriate for their race/ethnicity (67%-85%). Patients scored significantly higher on transplant knowledge testing (9.1/20 to 13.8/20, P < .001) after viewing the app, including patients with low health literacy (8.0 to 13.0, P < .001). Overall knowledge of and interest in living and deceased donor kidney transplantation increased. This pilot project confirmed the benefit and cultural acceptability of this educational tool, and further refinement will explore how to better communicate the risks and benefits of nonstandard donors.


Subject(s)
Cell Phone/statistics & numerical data , Cultural Competency , Decision Making , Health Knowledge, Attitudes, Practice , Kidney Transplantation , Patient Education as Topic , Transplant Recipients/education , Adult , Aged , Female , Follow-Up Studies , Humans , Living Donors , Male , Middle Aged , Pilot Projects , Tissue and Organ Procurement , Young Adult
9.
Proc Natl Acad Sci U S A ; 109(19): 7457-62, 2012 May 08.
Article in English | MEDLINE | ID: mdl-22529385

ABSTRACT

Influenza A virus (IAV) enters host cells after attachment of its hemagglutinin (HA) to surface-exposed sialic acid. Sialylated N-linked glycans have been reported to be essential for IAV entry [Chu VC, Whittaker GR (2004) Proc Natl Acad Sci USA 102:18153-18158], thereby implicating the requirement for proteinaceous receptors in IAV entry. Here we show, using different N-acetylglucosaminyl transferase 1 (GnT1)-deficient cells, that N-linked sialosides can mediate, but are not required for, entry of IAV. Entry into GnT1-deficient cells was fully dependent on sialic acid. Although macropinocytic entry appeared to be affected by the absence of sialylated N-glycans, dynamin-dependent entry was not affected at all. However, binding of HA to GnT1-deficient cells and subsequent entry of IAV were reduced by the presence of serum, which could be reversed by back-transfection of a GnT1-encoding plasmid. The inhibitory effect of serum was significantly increased by inhibition of the viral receptor-destroying enzyme neuraminidase (NA). Our results indicate that decoy receptors on soluble serum factors compete with cell surface receptors for binding to HA in the absence of sialylated N-glycans at the cell surface. This competition is particularly disturbed by the additional presence of NA inhibitors, resulting in strongly reduced IAV entry. Our results indicate that the balance between HA and NA is important not only for virion release, but also for entry into cells.


Subject(s)
Influenza A Virus, H1N1 Subtype/metabolism , N-Acetylneuraminic Acid/metabolism , Polysaccharides/metabolism , Virus Internalization , Animals , CHO Cells , Cattle , Cell Line , Cricetinae , Cricetulus , Culture Media/metabolism , Culture Media/pharmacology , Dynamins/genetics , Dynamins/metabolism , Endocytosis , Fetal Blood/metabolism , HEK293 Cells , Hemagglutinin Glycoproteins, Influenza Virus/metabolism , Humans , Microscopy, Confocal , N-Acetylglucosaminyltransferases/genetics , N-Acetylglucosaminyltransferases/metabolism , Neuraminidase/metabolism , Protein Binding/drug effects , Serum/metabolism
10.
Contact Dermatitis ; 71(1): 41-8, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24815516

ABSTRACT

BACKGROUND: The rate of contact allergy and allergic contact dermatitis caused by methylisothiazolinone (MI) is dramatically increasing throughout Europe. OBJECTIVES: To report on methylchloroisothiazolinone (MCI)/MI and MI allergy in Belgium. PATIENTS AND METHODS: Between January 2010 and December 2012, the medical charts of 6599 patients of the Belgian Contact and Environmental Dermatitis Group were retrospectively reviewed for MCI/MI and MI sensitization by use of a standardized questionnaire. Available data on sensitization in 2081 patients tested in 2013 were also included. RESULTS: In 2012, the sensitization rate for MCI/MI had increased to 4.5% and that for MI to 6.0%; the latter showed a further increase to 7.2% in 2013. The people mainly affected were women with a median age of 49 years with hand and/or facial dermatitis, most often resulting from the use of cosmetics. Simultaneous reactions to octylisothiazolinone were observed. CONCLUSION: A dramatic increase in the rate of contact allergy caused by MI in cosmetics is occurring in Belgium. Notwithstanding the recent recommendation to discontinue the use of MI in leave-on cosmetics, safer use concentrations should also be determined for rinse-off products. Close monitoring of MI sensitization in the near future will be necessary, and the highest test concentrations reported for MI and MCI/MI should be included in the baseline series.


Subject(s)
Dermatitis, Allergic Contact/epidemiology , Preservatives, Pharmaceutical/adverse effects , Thiazoles/adverse effects , Adolescent , Adult , Aged , Aged, 80 and over , Belgium/epidemiology , Child , Child, Preschool , Cosmetics/adverse effects , Dermatitis, Allergic Contact/etiology , Dermatitis, Occupational/epidemiology , Dermatitis, Occupational/etiology , Female , Household Products/adverse effects , Humans , Male , Middle Aged , Retrospective Studies , Young Adult
11.
J Pediatr ; 163(2): 339-43, 2013 Aug.
Article in English | MEDLINE | ID: mdl-23490037

ABSTRACT

OBJECTIVE: To determine whether exposure to celebrity endorsement in television (TV) food advertising and a nonfood context would affect ad libitum intake of the endorsed product and a perceived alternative brand. STUDY DESIGN: A total of 181 children from the UK aged 8-11 years viewed 1 of the following embedded within a cartoon: (1) a commercial for Walker's Crisps (potato chips), featuring a long-standing celebrity endorser; (2) a commercial for a savory food; (3) TV footage of the same endorser in his well-known role as a TV presenter; or (4) a commercial for a nonfood item. Children's ad libitum intake of potato chips labeled "Walker's" and "supermarket brand" was measured using ANOVA. RESULTS: Children who viewed the endorsed commercial or the TV footage of the endorser outside of a food context consumed significantly more of the Walker's chips compared with children in other groups. These children did not reduce their intake of the supermarket brand product to compensate; thus, the endorser effect contributed to overconsumption. CONCLUSION: The influence of a celebrity endorser on food intake in children extends beyond his or her role in the specific endorsed food commercial, prompting increased consumption of the endorsed brand even when the endorser has been viewed in a nonfood context. Our data suggest that the ubiquitous nature of celebrity media presence may reinforce unhealthy eating practices in children, although research with other endorsers is needed.


Subject(s)
Advertising , Eating/psychology , Famous Persons , Food Preferences/psychology , Hyperphagia/prevention & control , Hyperphagia/psychology , Sports , Television , Child , Female , Humans , Male
12.
Clin Drug Investig ; 43(4): 299-306, 2023 Apr.
Article in English | MEDLINE | ID: mdl-37012527

ABSTRACT

BACKGROUND: Tralokinumab, the first fully human monoclonal antibody that binds specifically to interleukin-13, was safe and effective for treating atopic dermatitis (AD) in clinical trials, but real-life experience is still limited. OBJECTIVES: The objective of this study was to evaluate the effectiveness and safety of tralokinumab in severe AD in a real-life multicenter prospective cohort. METHODS: Adult patients with severe AD were enrolled between January 2022 and July 2022 and received tralokinumab subcutaneously for 16 weeks. Objective and subjective scores were collected at baseline, weeks 6 and 16. Adverse events were reported throughout the study. RESULTS: Twenty-one patients were included. An improvement of at least 75% on the Eczema Area and Severity Index (EASI 75) was achieved in 66.7% of patients at week 16. The median objective and subjective scores at week 16 were significantly (p < 0.001) lower than those at baseline. Combination with cyclosporine was sometimes necessary at the beginning of treatment, and addition of upadacitinib was required for some patients with very severe disease during the treatment. The most frequent adverse events were flares of eczema (23.8%) and reactions at injection site (19.0%). No cases of conjunctivitis were reported. Four patients (19.0%) discontinued treatment. CONCLUSIONS: Tralokinumab is an effective first-line biotherapy for severe AD. However, therapeutic response may be progressive. Safety data were reassuring. Atopic dermatitis flares or reactions at the injection site may lead to discontinuation of treatment. A history of conjunctivitis on dupilumab is not a contraindication to the initiation of tralokinumab.


Subject(s)
Conjunctivitis , Dermatitis, Atopic , Eczema , Humans , Adult , Prospective Studies , Dermatitis, Atopic/diagnosis , Dermatitis, Atopic/drug therapy , Treatment Outcome , Injections, Subcutaneous , Double-Blind Method , Antibodies, Monoclonal/adverse effects , Severity of Illness Index , Conjunctivitis/chemically induced , Conjunctivitis/drug therapy , Eczema/chemically induced , Eczema/drug therapy
13.
J Am Coll Surg ; 234(4): 493-503, 2022 04 01.
Article in English | MEDLINE | ID: mdl-35290268

ABSTRACT

BACKGROUND: Allograft nephrectomy (AN) has been associated with considerable perioperative morbidity. We aimed to determine if preoperative angiographic kidney embolization (PAKE) to induce graft thrombosis before AN improves outcomes. STUDY DESIGN: We reviewed adult kidney transplant alone patients who underwent AN at a single center from 2002 to 2020 and compared perioperative outcomes for patients with and without PAKE. RESULTS: Eighty patients underwent AN, including 54 (67.5%) with PAKE before AN and 26 (32.5%) with AN alone. PAKE was associated with significantly reduced blood loss (PAKE: mean 266 ± 292 mL vs AN alone: 495 ± 689 mL; p = 0.04) and reduced transfusion requirements (PAKE: mean 0.5 ± 0.8 packed red blood cell units vs AN alone: 1.6 ± 2.6 units; p = 0.004) despite similar preoperative hemoglobin levels. Mean operating time (PAKE: 142 ± 43 minutes vs AN alone: 202 ± 111 minutes; p = 0.001) and length of hospital stay (PAKE: 4.3 ± 2.0 days vs AN alone: 9.3 ± 9.4 days; p = 0.0003) also favored PAKE, as did the surgical complication rate (PAKE: 6/54 [11%] vs AN alone: 9/26 [35%], p = 0.02). Long-term patient survival after AN was comparable in both groups. CONCLUSIONS: PAKE was associated with lower intraoperative blood loss, fewer transfusions, reduced operating time, shorter length of stay, and fewer surgical complications compared with AN alone at our center.


Subject(s)
Embolization, Therapeutic , Nephrectomy , Adult , Allografts , Blood Loss, Surgical/prevention & control , Humans , Kidney , Retrospective Studies , Treatment Outcome
14.
J Am Heart Assoc ; 11(19): e026198, 2022 10 04.
Article in English | MEDLINE | ID: mdl-36129031

ABSTRACT

Background Methohexital and propofol can both be used as sedation for direct current cardioversion (DCCV). However, there are limited data comparing these medications in this setting. We hypothesized that patients receiving methohexital for elective DCCV would be sedated more quickly, recover from sedation faster, and experience less adverse effects. Methods and Results This was a prospective, blinded randomized controlled trial conducted at a single academic medical center. Eligible participants were randomly assigned to receive either methohexital (0.5 mg/kg) or propofol (0.8 mg/kg) as a bolus for elective DCCV. The times from bolus of the medication to achieving a Ramsay Sedation Scale score of 5 to 6, first shock, eyes opening on command, and when the patient could state their age and name were obtained. The need for additional medication dosing, airway intervention, vital signs, and medication side effects were also recorded. Seventy patients who were randomized to receive methohexital (n=37) or propofol (n=33) were included for analysis. The average doses of methohexital and propofol were 0.51 mg/kg and 0.84 mg/kg, respectively. There were no significant differences between methohexital and propofol in the time from end of injection to loss of conscious (1.4±1.8 versus 1.1±0.5 minutes; P=0.33) or the time to first shock (1.7±1.9 versus 1.4±0.5 minutes; P=0.31). Time intervals were significantly lower for methohexital compared with propofol in the time to eyes opening on command (5.1±2.5 versus 7.8±3.7 minutes; P=0.0005) as well as at the time to the ability to answer simple questions of age and name (6.0±2.6 versus 8.6±4.0 minutes; P=0.001). The methohexital group experienced less hypotension (8.1% versus 42.4%; P<0.001) and less hypoxemia (0.0% versus 15.2%; P=0.005), had lower need for jaw thrust/chin lift (16.2% versus 42.4%; P=0.015), and had less pain on injection compared with propofol using the visual analog scale (7.2±9.7 versus 22.4±28.1; P=0.003). Conclusions In this model of fixed bolus dosing, methohexital was associated with faster recovery, more stable hemodynamics, and less hypoxemia after elective DCCV compared with propofol. It can be considered as a preferred agent for sedation for DCCV. Registration URL: https://www.clinicaltrials.gov/ct; Unique identifier: NCT04187196.


Subject(s)
Methohexital , Propofol , Electric Countershock/adverse effects , Humans , Hypoxia , Propofol/adverse effects , Prospective Studies
15.
Exp Clin Transplant ; 19(2): 104-109, 2021 02.
Article in English | MEDLINE | ID: mdl-31801449

ABSTRACT

OBJECTIVES: BK polyomavirus can infect healthy individuals; however, in renal transplant recipients, it can cause nephropathy, which can lead to renal allograftfailure. There are currently no effective antiviral agents against BK polyomavirus. Surveillance after kidney transplant for BK polyomavirus is the only means to prevent allograft failure. Transplant centers routinely screen for BK polyomavirus in either urine or blood. If BK polyomavirus replication occurs, itis usually detected first in urine, which is followed by detection in blood in a subset of cases. Screening for BK polyomavirus in urine has the potential for earlier detection of viralreactivation.However, not all patients with BK polyomavirus in urine will progress to BK viremia. Therefore, adding urine screening could increase the cost oftests without a clear clinical benefit. MATERIALS AND METHODS: We conducted an analysis of BK polyomavirus screening methods at 2 different centers and compared their clinical outcomes and efficiency of testing. RESULTS: We analyzed 209 patientswith BK polyomavirus reactivation after kidney transplant at 2 different institutions from 2008 to 2018. BK polyomavirus reactivation in blood was detected earlierifthe patient was screened by urine screening protocol. However, measurable clinical outcomes were similarin all groups with different screening methods. CONCLUSIONS: Although screening for BK polyomavirus in urine did detect viralreactivation earlier,there were no differences in graft or clinical outcomes when either the urine or blood screening method was used.


Subject(s)
BK Virus , Kidney Transplantation , Polyomavirus Infections/diagnosis , BK Virus/isolation & purification , Humans , Kidney , Kidney Transplantation/adverse effects , Polyomavirus Infections/blood , Polyomavirus Infections/urine , Viremia/diagnosis , Virus Activation
17.
Contact Dermatitis ; 62(6): 349-54, 2010 Jun.
Article in English | MEDLINE | ID: mdl-20557341

ABSTRACT

BACKGROUND: Previously, a quantitative risk assessment suggested there was no risk of induction of fragrance allergy from minor residues of fragrance chemicals on washed fabrics. OBJECTIVE: To investigate whether there was any risk of the elicitation of contact allergy from fragrance chemical residues on fabric in individuals who were already sensitized. METHODS: Thirty-six subjects with a positive patch test to isoeugenol (n = 19) or hydroxyisohexyl 3-cyclohexene carboxaldehyde (n = 17) were recruited. Dose-response and fabric patch tests were performed, respectively, with filter paper and a cotton sample loaded with fragrance in ethanol-diethylphthalate (DEP) and applied in a Finn Chamber or a Hill Top Chamber. RESULTS: Only two subjects reacted to an isoeugenol patch test concentration of 0.01% (>20x the estimated likely skin exposure level), none reacted to lower concentrations. Of 36 subjects, 18 reacted to the fabric patch treated with ethanol-DEP vehicle alone and 20 to the fragrance-chemical-treated fabric patch. These were only minor non-specific skin reactions. They were also quite evenly distributed between the two fragrance chemical allergic groups. CONCLUSIONS: On the basis of the examples studied, fragrance chemical residues present on fabric do not appear to present a risk of the elicitation of immediate or delayed allergic skin reactions on individuals already sensitized.


Subject(s)
Dermatitis, Allergic Contact/etiology , Detergents/adverse effects , Hypersensitivity, Delayed/etiology , Perfume/adverse effects , Adult , Aged , Aldehydes/adverse effects , Aldehydes/analysis , Clothing , Cyclohexenes/adverse effects , Cyclohexenes/analysis , Detergents/chemistry , Eugenol/adverse effects , Eugenol/analogs & derivatives , Eugenol/analysis , Female , Humans , Male , Middle Aged , Perfume/analysis , Young Adult
18.
Neurobiol Aging ; 67: 10-20, 2018 07.
Article in English | MEDLINE | ID: mdl-29609077

ABSTRACT

The degeneration of basal forebrain cholinergic neurons (BFCNs) in Alzheimer's disease (AD) contributes to cognitive impairment. Nerve growth factor (NGF) secreted in the cerebral cortex is necessary for the phenotypic maintenance of BFCNs. AD is associated with disturbances in NGF metabolism, leading to reduced mature NGF levels and to an accumulation of its precursor, proNGF. We previously described that, in rats, this neurotrophic imbalance is sufficient to induce a loss of cortical cholinergic synapses. In the present study, we investigated whether this neurotrophic imbalance can produce an AD-like retrograde degeneration of BFCNs. Using a combination of retrograde labeling and quantitative cell imaging, we could demonstrate that inhibiting cortical proNGF maturation results in an atrophy of BFCNs, a downregulation of the NGF receptors p75 neurotrophin receptor and tropomyosin receptor kinase A, and a reduction in choline acetyltransferase protein expression. The transient increase in sortilin levels and the sustained colocalization with p75 neurotrophin receptor suggest a participation of proNGF in this degenerative process. This study demonstrates that impairments in the extracellular maturation of proNGF are sufficient to cause a somatodendritic retrograde degeneration of the BFCNs.


Subject(s)
Basal Forebrain/cytology , Cholinergic Neurons/pathology , Nerve Growth Factors/metabolism , Protein Precursors/metabolism , Adaptor Proteins, Vesicular Transport/metabolism , Alzheimer Disease/etiology , Alzheimer Disease/pathology , Animals , Atrophy/etiology , Choline O-Acetyltransferase/metabolism , Down-Regulation , Rats, Wistar , Receptor, Nerve Growth Factor/metabolism , Receptor, trkA/metabolism
19.
Transplantation ; 101(7): 1637-1644, 2017 07.
Article in English | MEDLINE | ID: mdl-28230641

ABSTRACT

BACKGROUND: The ongoing shortage of donor livers for transplantation and the increased use of marginal livers necessitate the development of accurate pretransplant tests of viability. Considering the importance energy status during transplantation, we aimed to correlate peritransplant energy cofactors to posttransplant outcome and subsequently model this in an ex vivo setting. METHODS: Sequential biopsies were taken from 19 donor livers postpreservation, as well as 30 minutes after portal venous reperfusion and hepatic arterial reperfusion and analyzed by liquid chromatography-mass spectrometry for energetic cofactors (adenosine triphosphate [ATP]/adenosine diphosphate [ADP]/adenosine monophosphate [AMP], nicotinamide adenine dinucleotide /NAD, nicotinamide adenine dinucleotide phosphate / nicotinamide adenine dinucleotide phosphate , flavin adenine dinucleotide , glutathione disulfide/glutathione). Energy status was correlated to posttransplant outcome. In addition, 4 discarded human donation after circulatory death livers were subjected to ex vivo reperfusion, modeling reperfusion injury and were similarly analyzed for energetic cofactors. RESULTS: A rapid shift toward higher energy adenine nucleotides was observed following clinical reperfusion, with a 2.45-, 3.17- and 2.12-fold increase in ATP:ADP, ATP:AMP and energy charge after portal venous reperfusion, respectively. Seven of the 19 grafts developed early allograft dysfunction. Correlation with peritransplant cofactors revealed a significant difference in EC between early allograft dysfunction and normal functioning grafts (0.09 vs 0.31, P < 0.05). In the simulated reperfusion model, a similar trend in adenine nucleotide changes was observed. CONCLUSIONS: A preserved energy status appears critical in the peritransplant period. Levels of adenine nucleotides change rapidly after reperfusion and ratios of ATP/ADP/AMP after reperfusion are significantly correlated to graft function. Using these markers as a viability test in combination with ex vivo reperfusion may provide a useful predictor of outcome that incorporates donor, preservation, and reperfusion factors.


Subject(s)
Adenine Nucleotides/metabolism , Energy Metabolism , Liver Transplantation/methods , Liver/surgery , Tissue Donors/supply & distribution , Adolescent , Adult , Aged , Biomarkers/metabolism , Biopsy , Cytokines/metabolism , Female , Humans , Inflammation Mediators/metabolism , Liver/metabolism , Liver/pathology , Liver Transplantation/adverse effects , Male , Middle Aged , Perfusion/adverse effects , Reperfusion Injury/etiology , Reperfusion Injury/metabolism , Retrospective Studies , Time Factors , Tissue Survival , Treatment Outcome , Young Adult
20.
J Parkinsons Dis ; 6(1): 231-7, 2016.
Article in English | MEDLINE | ID: mdl-26889635

ABSTRACT

BACKGROUND: Numerous large-scale studies have found diverse risk factors for Parkinson's disease (PD), including caffeine non-use, non-smoking, head injury, pesticide exposure, and family history. These studies assessed risk factors for PD overall; however, PD is a heterogeneous condition. One of the strongest identifiers of prognosis and disease subtype is the co-occurrence of rapid eye movement sleep behavior disorder (RBD).In previous studies, idiopathic RBD was associated with a different risk factor profile from PD and dementia with Lewy bodies, suggesting that the PD-RBD subtype may also have a different risk factor profile. OBJECTIVE: To define risk factors for PD in patients with or without associated RBD. METHODS: In a questionnaire, we assessed risk factors for PD, including demographic, medical, environmental, and lifestyle variables of 189 PD patients with or without associated polysomnography-confirmed RBD. The risk profile of patients with vs. without RBD was assessed with logistic regression, adjusting for age, sex, and disease duration. RESULTS: PD-RBD patients were more likely to have been a welder (OR = 3.11 (1.05-9.223), and to have been regular smokers (OR = 1.96 (1.04-3.68)). There were no differences in use of caffeine or alcohol, other occupations, pesticide exposure, rural living, or well water use. Patients with RBD had a higher prevalence of the combined family history of both dementia and parkinsonism (13.3% vs. 5.5% , OR = 3.28 (1.07-10.0). CONCLUSION: The RBD-specific subtype of PD may also have a different risk factor profile.


Subject(s)
Parkinson Disease/complications , REM Sleep Behavior Disorder/complications , Aged , Female , Humans , Male , Middle Aged , Risk Factors , Surveys and Questionnaires
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